bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Mode III Doubly Periodic Crack-Tip Field of Orthotropic Composite Materials
Authors: Zhao Wenbin , Li Chan , Zhang Xuexia , Xie Hailing , Yu Lujuan
Published: September 2013

The mechanical behavior near the doubly periodic crack tips for orthotropic composite materials plate subjected to antiplane shear loading is studied. This is done by complex function theory and conformal mapping of the Jacobi elliptic function with the help of boundary conditions. The analytical solution of the crack-tips stress intensity factor and the expression of stress fields are obtained. Numerical examples are given to analyze the impact of the different transverse spacing, longitudinal spacing, and the ratio of cracks periods on stress intensity factors. The results show that the crack-tip field increases with reducing either the transverse spacing or the longitudinal spacing. At the same time, the crack-tip field increases with the decrease of the ratio of cracks periods. This shows that the distribution form makes an important effect on the crack-tip field, but the crack density parameter is not the only cause.
Diffusion Models for Information Dissemination Dynamics in Wireless Complex Communication Networks
Authors: Cheng Shin-Ming , Karyotis Vasileios , Chen Pin-Yu , Chen Kwang-Cheng , Papavassiliou Symeon
Published: September 2013

Information dissemination has become one of the most important services of communication networks. Modeling the diffusion of information through such networks is crucial for our modern information societies. In this work, novel models, segregating between useful and malicious types of information, are introduced, in order to better study Information Dissemination Dynamics (IDD) in wireless complex communication networks, and eventually allow taking into account special network features in IDD. According to the proposed models, and inspired from epidemiology, we investigate the IDD in various complex network types through the use of the Susceptible-Infected (SI) paradigm for useful information dissemination and the Susceptible-Infected-Susceptible (SIS) paradigm for malicious information spreading. We provide analysis and simulation results for both types of diffused information, in order to identify performance and robustness potentials for each dissemination process with respect to the characteristics of the underlying complex networking infrastructures. We demonstrate that the proposed approach can generically characterize IDD in wireless complex networks and reveal salient features of dissemination dynamics in each network type, which could eventually aid in the design of more advanced, robust, and efficient networks and services.
Ultrasensitive Detection of Unknown Colon Cancer-Initiating Mutations Using the Example of the Adenomatous Polyposis Coli Gene
Authors: Gerecke Christian , Mascher Conny , Gottschalk Uwe , Kleuser Burkhard , Scholtka Bettina
Published: September 2013

Detection of cancer precursors contributes to cancer prevention, for example, in the case of colorectal cancer. To record more patients early, ultrasensitive methods are required for the purpose of noninvasive precursor detection in body fluids. Our aim was to develop a method for enrichment and detection of known as well as unknown driver mutations in the Adenomatous polyposis coli (APC) gene. By coupled wild-type blocking (WTB) PCR and high-resolution melting (HRM), referred to as WTB-HRM, a minimum detection limit of 0.01% mutant in excess wild-type was achieved according to as little as 1 pg mutated DNA in the assay. The technique was applied to 80 tissue samples from patients with colorectal cancer (n = 17), adenomas (n = 50), serrated lesions (n = 8), and normal mucosa (n = 5). Any kind of known and unknown APC mutations (deletions, insertions, and base exchanges) being situated inside the mutation cluster region was distinguishable from wild-type DNA. Furthermore, by WTB-HRM, nearly twice as many carcinomas and 1.5 times more precursor lesions were identified to be mutated in APC, as compared with direct sequencing. By analyzing 31 associated stool DNA specimens all but one of the APC mutations could be recovered. Transferability of the WTB-HRM method to other genes was proven using the example of KRAS mutation analysis. In summary, WTB-HRM is a new approach for ultrasensitive detection of cancer-initiating mutations. In this sense, it appears especially applicable for noninvasive detection of colon cancer precursors in body fluids with excess wild-type DNA like stool. Cancer Prev Res; 6(9); 898–907. ©2013 AACR.
Therapeutic Synergy between microRNA and siRNA in Ovarian Cancer Treatment
Authors: Nishimura Masato , Jung Eun-Jung , Shah Maitri Y. , Lu Chunhua , Spizzo Riccardo , Shimizu Masayoshi , Han Hee Dong , Ivan Cristina , Rossi Simona , Zhang Xinna , Nicoloso Milena S. , Wu Sherry Y. , Almeida Maria Ines , Bottsford-Miller Justin , Pecot Chad V. , Zand Behrouz , Matsuo Koji , Shahzad Mian M. , Jennings Nicholas B. , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , Sood Anil K. , Calin George A.
Published: September 2013

Development of improved RNA interference–based strategies is of utmost clinical importance. Although siRNA-mediated silencing of EphA2, an ovarian cancer oncogene, results in reduction of tumor growth, we present evidence that additional inhibition of EphA2 by a microRNA (miRNA) further “boosts” its antitumor effects. We identified miR-520d-3p as a tumor suppressor upstream of EphA2, whose expression correlated with favorable outcomes in two independent patient cohorts comprising 647 patients. Restoration of miR-520d-3p prominently decreased EphA2 protein levels, and suppressed tumor growth and migration/invasion both in vitro and in vivo. Dual inhibition of EphA2 in vivo using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes loaded with miR-520d-3p and EphA2 siRNA showed synergistic antitumor efficiency and greater therapeutic efficacy than either monotherapy alone. This synergy is at least in part due to miR-520d-3p targeting EphB2, another Eph receptor. Our data emphasize the feasibility of combined miRNA–siRNA therapy, and will have broad implications for innovative gene silencing therapies for cancer and other diseases.

Significance: This study addresses a new concept of RNA inhibition therapy by combining miRNA and siRNA in nanoliposomal particles to target oncogenic pathways altered in ovarian cancer. Combined targeting of the Eph pathway using EphA2-targeting siRNA and the tumor suppressor miR-520d-3p exhibits remarkable therapeutic synergy and enhanced tumor suppression in vitro and in vivo compared with either monotherapy alone. Cancer Discov; 3(11); 1302–15. ©2013 AACR.

See related commentary by Kasinski and Slack, p. 1220

This article is highlighted in the In This Issue feature, p. 1207
Genetic and Immunohistochemical Characterization of Epstein-Barr Virus-Associated Diffuse Large B-Cell Lymphoma
Authors: Al-Humood S. , AlQallaf A. , Al-Shemmari S. , Al-Faris L. , Al-Ayadhy B.
Published: September 2013

Epstein-Barr virus (EBV) has a pathogenic role in several lymphomas, including diffuse large B-cell lymphoma (DLBCL). EBV-associated genetic aberrations in DLBCL have not been fully characterized. The aim of this study was to investigate the prevalence of EBV infection in sporadic DLBCL cases in Kuwait and to evaluate their EBV status in relation to demographic data, the anatomical disease site, immunophenotypic features, particularly pertaining to the Choi's DLBCL prognostic classification, and chromosomal aberrations. Using immunohistochemistry (IHC), in situ hybridization (ISH), nested polymerase chain reaction (nPCR) and comparative genomic hybridization techniques, formalin-fixed paraffin-embedded blocks of archived DLBCL cases were included and evaluated in the study. EBV was detected in 6.9, 18.2 and 25% of the studied cases using IHC, ISH and nPCR, respectively, indicating that nPCR is more sensitive in detecting EBV than IHC and ISH. EBV- DLBCL cases showed BCL6 protein expression more frequently than EBV+ DLBCL cases. The reported prevalence of EBV+ DLBCL cases in this study is similar to that reported in the literature using ISH results and higher using nPCR results. There was a significant inverse correlation between BCL6 protein expression and the presence of EBV (p = 0.01).
Long-Term Outcome of Simultaneous or Staged Urinary Diversion and Kidney Transplantation
Authors: Teng Lichen , Wang Changxi , Li Jun
Published: September 2013

Objectives: We retrospectively analyzed the long-term outcomes of simultaneous or staged urinary diversion and kidney transplantation. Patients and Methods: Between June 2001 and December 2012, 4 patients with dysfunctional bladder resulting from spina bifida (n = 3) or bladder contraction following urologic tuberculosis (n = 1) underwent cadaveric kidney transplantation and urinary diversion simultaneously (n = 3) or 6 months post-transplantation (n = 1). Urinary diversion consisted of cutaneous ureterostomy in 1 patient and ileal conduits in 3 patients. All patients were followed prospectively. Results: All 4 patients received deceased donor transplants. Median follow-up was 110.5 months (range 50-120). At the last follow-up, serum creatinine levels ranged from 1.1 to 1.8 mg/dl. One patient with a functioning graft died of severe cirrhosis 105 months following transplantation. Graft function remained stable without any severe complications in 3 patients. Hematoma (Clavien-Dindo grade IIIa) and urinary leakage (grade II) occurred in 1 patient in the early postoperative period, but no surgical revision was required. Two patients developed cytomegalovirus pneumonia. Urinary tract infection was a common problem in all patients. Conclusions: For patients with lower urinary tract dysfunction, simultaneous kidney transplantation and urinary diversion with an ileal conduit may be a safe, feasible approach, with a satisfactory long-term outcome.
Predicting Residual Renal Function in Peritoneal Dialysis Patients Using an Estimated Glomerular Filtration Rate Based on Serum Creatinine Levels
Authors: Kang Seok Hui , Cho Kyu Hyang , Park Jong Won , Yoon Kyung Woo , Do Jun Young
Published: September 2013

Background: The aim of this study was to evaluate regression equations correcting estimated glomerular filtration rate (eGFR) and the clinical significance of the corrected eGFRs calculated using these equations. Patients and Methods: The authors determined how well corrected eGFR values calculated using regression equations predict residual renal function (RRF). Results: RRF values were correlated with all eGFR values of nonanuric patients of both genders. Peritoneal creatinine clearance values were not correlated with eGFRs in anuric patients of either gender. In males, eGFR biases ranged from -5.66 to -3.25, and in females, from -5.96 to -3.21. However, these biases decreased when eGFR values were transformed to corrected eGFR values. The area under the curve of the corrected eGFR values was acceptable for a diagnosis of RRF loss. Conclusion: Corrected eGFR values obtained using these methods may provide an alternative means of predicting RRF without 24-hour urine collection.
Clinical Features and Comprehensive Diagnosis of Autoimmune Pancreatitis in China
Authors: Wu Lili , Li Wen , Huang Xuefei , Wang Zikai
Published: September 2013

Aim: To search for the key factors of autoimmune pancreatitis (AIP) in China and to improve the early identification of AIP in order to avoid misdiagnosing it as pancreatic carcinoma. Methods: Clinical, imaging, laboratory, and pathological data about AIP were collected and analyzed from 1996 to 2011 in The Chinese People's Liberation Army General Hospital. Results: A total of 33 patients (male 29, female 4) aged 35-76 years (52.3 ± 9.3 years) meeting the International Consensus Diagnostic Criteria for type 1 (n = 32) or type 2 (n = 1) AIP were included. With improved understanding of AIP, the misdiagnosis rate and unnecessary laparotomy rate was decreased from 95.7% (22/23) and 91.3% (21/23) before 2006, to 20.0% (2/10) (p = 0.001) and 0.0% (p = 0.001) respectively after 2006. The major symptoms were jaundice in (24/33, 72.7%) and abdominal pain (12/33, 36.4%). Half of the patients had other accompanied autoimmune disorders. Laboratory tests showed an elevated level of serum IgG in 9 out of 11 patients (81.8%) and an increased eosinophil count in 16 out of 33 patients (48.5%). The serum IgG4 levels were twice the upper limit of the normal value. CT scan showed a low-contrast margin characterized by a capsule-like rim in 24 of 32 patients (75.0%). Pathologic examinations showed fibrosis and infiltration of massive lymphocytes and plasma cells in the pancreas. Prednisone was given to the patients and proved to be quite effective for all of them (12/12, 100%). Conclusion: Type 1 AIP shows a sex predilection compared with type 2 AIP in China. In order to diagnose AIP exactly, a comprehensive strategy, especially including imaging and pathological examination, should be used. With growing awareness, fewer AIP patients with this diagnosis would be misdiagnosed and incorrectly treated.
Interplay between Parkin and p53 Governs a Physiological Homeostasis That Is Disrupted in Parkinson's Disease and Cerebral Cancer
Authors: Checler F. , Alves da Costa C.
Published: September 2013

Parkin is responsible for most autosomal juvenile recessive cases of Parkinson's disease (PD). Besides its well-characterized function as ubiquitin ligase, we previously established that parkin could repress p53 at the transcriptional level. Interestingly, p53 was recently shown to upregulate parkin, suggesting a feedback loop by which parkin and p53 interplay, thereby contributing to their physiological homeostasis. This equilibrium is disrupted in both PD and cerebral cancer. Thus, when parkin is mutated in PD, its transcriptional ability to repress p53 is abolished. Therefore, p53 elevation could likely contribute to the exacerbated cell death observed in PD-affected brains. Inversely, in brain-associated tumors linked to p53 mutations, the transcriptional control of parkin is reduced, and thereby, parkin expression is lowered. The reduction in parkin level could, in turn, contribute to an increase in the levels of transcriptionally inactive p53 that could explain, at least in part, the defect in cellular apoptotic commitment observed in cerebral cancer. Here, we discuss in detail the various studies demonstrating the importance of the functional interplay between parkin and p53 and its impairment by pathogenic mutations likely contributing to the etiology of PD and gliomas.
Mutations in the VEGFR3 Signaling Pathway Explain 36% of Familial Lymphedema
Authors: Mendola A. , Schlögel M.J. , Ghalamkarpour A. , Irrthum A. , Nguyen H.L. , Fastré E. , Bygum A. , van der Vleuten C. , Fagerberg C. , Baselga E. , Quere I. , Mulliken J.B. , Boon L.M. , Brouillard P. , Vikkula M. ,   The Lymphedema Research Group
Published: September 2013

Lymphedema is caused by dysfunction of lymphatic vessels, leading to disabling swelling that occurs mostly on the extremities. Lymphedema can be either primary (congenital) or secondary (acquired). Familial primary lymphedema commonly segregates in an autosomal dominant or recessive manner. It can also occur in combination with other clinical features. Nine mutated genes have been identified in different isolated or syndromic forms of lymphedema. However, the prevalence of primary lymphedema that can be explained by these genetic alterations is unknown. In this study, we investigated 7 of these putative genes. We screened 78 index patients from families with inherited lymphedema for mutations in FLT4, GJC2, FOXC2, SOX18, GATA2, CCBE1, and PTPN14. Altogether, we discovered 28 mutations explaining 36% of the cases. Additionally, 149 patients with sporadic primary lymphedema were screened for FLT4, FOXC2, SOX18,CCBE1, and PTPN14. Twelve mutations were found that explain 8% of the cases. Still unidentified is the genetic cause of primary lymphedema in 64% of patients with a family history and 92% of sporadic cases. Identification of those genes is important for understanding of etiopathogenesis, stratification of treatments and generation of disease models. Interestingly, most of the proteins that are encoded by the genes mutated in primary lymphedema seem to act in a single functional pathway involving VEGFR3 signaling. This underscores the important role this pathway plays in lymphatic development and function and suggests that the unknown genes also have a role.
Stress Impairs Synaptic Plasticity in Triple-Transgenic Alzheimer's Disease Mice: Rescue by Ryanodine
Authors: Grigoryan Gayane , Biella Gloria , Albani Diego , Forloni Gianluigi , Segal Menahem
Published: September 2013

Background: A possible contributing factor to the development of cognitive deficits in Alzheimer's disease (AD) patients involves the exposure to early life stress. Objective: We explored the impact of stress on synaptic plasticity (long-term potentiation, LTP) of 6-month-old triple-transgenic mice (3×Tg-AD). Methods: 3×Tg-AD and control (NonTg) mice were exposed to three stressors at the age of 2 and 4 months. Excitatory postsynaptic potentials were recorded in the stratum radiatum of the CA1 region of hippocampal slices, in a two-pathway paradigm. Results: Slices taken from 3×Tg-AD mice exhibited significant deficits in LTP compared with NonTg slices. Early stress led to a further decrease in LTP in these mice, while it did not affect NonTg mice. LTP in 3×Tg-AD and stressed 3×Tg-AD mice was rescued by pre-exposure to 0.2 µM ryanodine. In an attempt to find a molecular correlate for the effects of stress in the 3×Tg-AD mice, we found that stressed mice have an altered ratio of Aβ42/40 both in the cortex and hippocampus. Conclusions: Stress experiences in young adults may accelerate the cognitive loss in AD mice, adding another dimension to the plethora of factors that lead to AD.
Expression Levels and Significance of Nuclear Factor-κB and Epidermal Growth Factor Receptor in Hepatolithiasis Associated with Intrahepatic Cholangiocarcinoma
Authors: Zhou Quanbo , Gong Yuanfeng , Huang Feng , Lin Qing , Zeng Bing , Li Zhihua , Chen Rufu
Published: September 2013

Background: An increasing incidence of cholangiocarcinoma (CCA) and CCA mortality rates has been observed around the world. Patients with intrahepatic biliary stones have a 10% risk of developing CCA, and up to 70% of patients with histologically confirmed CCA have hepatolithiasis. Few previous studies have addressed the associations between the expression of nuclear factor (NF)-κB and epidermal growth factor receptor (EGFR) and clinicopathological prognosis in patients with hepatolithiasis-associated intrahepatic CCA. Aims: This study was designed to investigate the clinicopathological and prognostic significance of NF-κB and EGFR expression in hepatolithiasis-associated intrahepatic CCA and hepatolithiasis. Methods: A total of 90 liver specimens were immunohistochemically stained for NF-κB and EGFR expression, and the characteristics of 90 individual patients were retrospectively reviewed. Results: Differences in the positive rates of NF-κB and EGFR expression between the hepatolithiasis-associated intrahepatic CCA group, intrahepatic lithiasis group, and control group were found to be statistically significant. EGFR expression was closely associated with the degree of differentiation and depth of invasion (p < 0.05). The 1-, 3-, and 5-year overall survival rates were respectively 42.8, 21.0, and 10.3% in intrahepatic CCA groups. The survival rate of the EGFR-negative group was higher than in the EGFR-positive group (p < 0.01). Lymph node metastasis (HR 1.24, 95% CI 1.02-1.51) and EGFR positivity (HR 1.74, 95% CI 1.30-2.23) were associated with decreases in the survival rate. Conclusion: The expression of NF-κB may be an early step in intrahepatic cholangiocarcinogenesis. Overexpression of EGFR is associated with the degree of malignancy and with poor prognosis. NF-κB and EGFR may cooperate during intrahepatic cholangiocarcinogenesis and progression. Lymph node metastasis and EGFR positivity were associated with decreases in the survival rate.
Changes in Optical Coherence Tomography Findings in Acute Zonal Occult Outer Retinopathy
Authors: Makino Shinji , Tampo Hironobu
Published: September 2013

Purpose: To report a case of acute zonal occult outer retinopathy (AZOOR) in a 39-year-old woman. Methods: Images were obtained with fundus photography and optical coherence tomography (OCT). A multifocal electroretinogram (mfERG) was also obtained to evaluate retinal function. Results: The patient's right visual acuity was 0.8. Fundus photographs showed no specific abnormal findings. OCT showed attenuation of the photoreceptor inner segment/outer segment (IS/OS) line and the cone outer segment tip (COST) line in the right eye. The mfERG showed corresponding amplitude reductions. One month after the initial visit, her right visual acuity improved to 1.2. There was partial recovery of the IS/OS line; however, the COST line was still absent, and there was no apparent improvement in the mfERG responses. Conclusions: Our findings showed a discrepancy between the microstructural findings and visual function during recovery of AZOOR.
Cardiac Perforation From Implantable Cardioverter-Defibrillator Lead Placement
Authors: Hsu Jonathan C. , Varosy Paul D. , Bao Haikun , Dewland Thomas A. , Curtis Jeptha P. , Marcus Gregory M.
Published: September 2013

Background—

Cardiac perforation is a feared complication of implantable cardioverter-defibrillator (ICD) lead implantation because of the potential for significant morbidity and mortality. Predictors of perforation and the severity of associated adverse events have not been well studied. We sought to identify predictors of cardiac perforation from ICD lead implantation and subsequent outcomes.

Methods and Results—

We studied 440 251 first-time ICD recipients in the ICD Registry implanted between January 2006 and September 2011. Using hierarchical multivariable logistic regression adjusting for patient, implanting physician, and hospital characteristics, we examined the predictors of perforation and the association of perforation with other major complications, length of stay, and in-hospital mortality. Cardiac perforation occurred in 625 patients (0.14%). After multivariable adjustment, older age, female sex, left bundle branch block, worsened heart failure class, higher left ventricular ejection fraction, and non–single-chamber ICD implant were associated with a greater odds of perforation. Conversely, atrial fibrillation, diabetes mellitus, previous cardiac bypass surgery, and higher implanter procedural volume were associated with a lower odds of perforation (all
P
<0.05). After adjustment, ICD recipients with perforation had greater odds of other associated major complications (odds ratio, 27.5; 95% confidence interval, 19.9–38.0;
P
<0.0001), postprocedural hospital stays >3 days (odds ratio, 16.3; 95% confidence interval, 13.7–19.4;
P
<0.0001), and in-hospital death (odds ratio, 17.7; 95% confidence interval, 12.2–25.6;
P
<0.0001).

Conclusions—

In a large population of ICD recipients, specific patient and implanter characteristics predicted cardiac perforation risk. Cardiac perforation was associated with a substantially increased risk of other major complications, prolonged hospital stays, and death.
High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy
Authors: Mora Samia , Glynn Robert J. , Ridker Paul M
Published: September 2013

Background—

Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy.

Methods and Results—

In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman
r
=0.69,
P
<0.0001) than with HDL-C (
r
=0.55,
P
<0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all
P
<0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor–adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63–0.98], 0.75 [0.62–0.92], and 0.81 [0.67–0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57–0.93,
P
=0.01) than HDL-C (0.82, 0.63–1.08,
P
=0.16) or apoA-I (0.86, 0.67–1.10,
P
=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53–0.97,
P
=0.03) after additionally adjusting for HDL-C. In risk factor–adjusted models, HDL size showed no significant association with CVD.

Conclusions—

In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00239681.
Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci
Authors: Kelly Tanika N. , Takeuchi Fumihiko , Tabara Yasuharu , Edwards Todd L. , Kim Young Jin , Chen Peng , Li Huaixing , Wu Ying , Yang Chi-Fan , Zhang Yonghong , Gu Dongfeng , Katsuya Tomohiro , Ohkubo Takayoshi , Gao Yu-Tang , Go Min Jin , Teo Yik Ying , Lu Ling , Lee Nanette R. , Chang Li-Ching , Peng Hao , Zhao Qi , Nakashima Eitaro , Kita Yoshikuni , Shu Xiao-Ou , Kim Nam Hee , Tai E. Shyong , Wang Yiqin , Adair Linda S. , Chen Chien-Hsiun , Zhang Shihiu , Li Changwei , Nabika Toru , Umemura Satoshi , Cai Qiuyin , Cho Yoon Shin , Wong Tien Yin , Zhu Jingwen , Wu Jer-Yuarn , Gao Xin , Hixson James E. , Cai Hui , Lee Juyoung , Cheng Ching-Yu , Rao Dabeeru C. , Xiang Yong-Bing , Cho Myeong-Chan , Han Bok-Ghee , Wang Aili , Tsai Fuu-Jen , Mohlke Karen , Lin Xu , Ikram Mohammad Kamran , Lee Jong-Young , Zheng Wei , Tetsuro Miki , Kato Norihiro , He Jiang
Published: September 2013

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a
P
<5.0×10
–8
in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected
P
<1.4×10
–3
. No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at
ATP2B1
(
P
=7.5×10
–15
), rs2681492 at
ATP2B1
(
P
=3.4×10
–7
), rs11191593 at
NT5C2
(1.1×10
–6
), rs3824755 at
CYP17A1
(
P
=1.2×10
–6
), and rs13149993 at
FGF5
(
P
=2.4×10
–4
). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and
P
<0.05), including rs319690 at
MAP4
(
P
=0.014) and rs1173771 at
NPR3
(
P
=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at
ATP2B1
(
P
=1.2×10
–5
) and rs11191593 at
NT5C2
(
P
=1.1×10
–3
), with suggestive evidence of replication among an additional 2 variants including rs3824755 at
CYP17A1
(
P
=6.1×10
–3
) and rs2681492 at
ATP2B1
(
P
=9.0×10
–3
). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.
Amyloid-β Peptides Activate α
1
-Adrenergic Cardiovascular Receptors
Authors: Haase Nadine , Herse Florian , Spallek Bastian , Haase Hannelore , Morano Ingo , Qadri Fatimunnisa , Szijártó István A. , Rohm Ilonka , Yilmaz Atilla , Warrington Junie P. , Ryan Michael J. , Gollasch Maik , Müller Dominik N. , Dechend Ralf , Wallukat Gerd
Published: September 2013

Alzheimer disease features amyloid-β (Aβ) peptide deposition in brain and blood vessels and is associated with hypertension. Aβ peptide can cause vasoconstriction and endothelial dysfunction. We observed that Aβ peptides exert a chronotropic effect in neonatal cardiomyocytes, similar to α
1
-adrenergic receptor autoantibodies that we described earlier. Recently, it was shown that α
1
-adrenergic receptor could impair blood–brain flow. We hypothesized that Aβ peptides might elicit a signal transduction pathway in vascular cells, induced by α
1
-adrenergic receptor activation. Aβ (25–35) and Aβ (10–35) induced a positive chronotropic effect in the cardiac contraction assay (28.75±1.15 and 29.40±0.98 bpm), which was attenuated by α
1
-adrenergic receptor blockers (urapidil, 1.53±1.17 bpm; prazosin, 0.30±0.96 bpm). Both Aβ peptides induced an intracellular calcium release in vascular smooth muscle cells. Chronotropic activity and calcium response elicited by Aβ (25–35) were blocked with peptides corresponding to the first extracellular loop of the α
1
-adrenergic receptor. We observed an induction of extracellular-regulated kinase 1/2 phosphorylation by Aβ (25–35) in Chinese hamster ovary cells overexpressing α
1
-adrenergic receptor, vascular smooth muscle cells, and cardiomyocytes. We generated an activation-state–sensitive α
1
-adrenergic receptor antibody and visualized activation of the α
1
-adrenergic receptor by Aβ peptide. Aβ (25–35) induced vasoconstriction of mouse aortic rings and in coronary arteries in Langendorff-perfused rat hearts that resulted in decreased coronary flow. Both effects could be reversed by α
1
-adrenergic receptor blockade. Our data are relevant to the association between Alzheimer disease and hypertension. They may explain impairment of vascular responses by Aβ and could have therapeutic implications.
Longitudinal Trajectories of Arterial Stiffness and the Role of Blood Pressure
Authors: AlGhatrif Majd , Strait James B. , Morrell Chris H. , Canepa Marco , Wright Jeanette , Elango Palchamy , Scuteri Angelo , Najjar Samer S. , Ferrucci Luigi , Lakatta Edward G.
Published: September 2013

Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is an established independent cardiovascular risk factor. Little information is available on the pattern and determinants of the longitudinal change in PWV with aging. Such information is crucial to elucidating mechanisms underlying arterial stiffness and the design of interventions to retard it. Between 1988 and 2013, we collected 2 to 9 serial measures of PWV in 354 men and 423 women of the Baltimore Longitudinal Study of Aging, who were 21 to 94 years of age and free of clinically significant cardiovascular disease. Rates of PWV increase accelerated with advancing age in men more than women, leading to sex differences in PWV after the age of 50 years. In both sexes, not only systolic blood pressure (SBP) ≥140 mm Hg but also SBP of 120 to 139 mm Hg was associated with steeper rates of PWV increase compared with SBP<120 mm Hg. Furthermore, there was a dose-dependent effect of SBP in men with marked acceleration in PWV rate of increase with age at SBP ≥140 mm Hg compared with SBP of 120 to 139 mm Hg. Except for waist circumference in women, no other traditional cardiovascular risk factors predicted longitudinal PWV increase. In conclusion, the steeper longitudinal increase of PWV in men than women led to the sex difference that expanded with advancing age. Age and SBP are the main longitudinal determinants of PWV, and the effect of SBP on PWV trajectories exists even in the prehypertensive range.
Natural History of Small Unruptured Anterior Circulation Aneurysms
Authors: Güresir Erdem , Vatter Hartmut , Schuss Patrick , Platz Johannes , Konczalla Jürgen , de Rochement Richard Du Mesnil , Berkefeld Joachim , Seifert Volker
Published: September 2013

Background and Purpose—

The natural history of small unruptured intracranial aneurysms of the anterior circulation in the European population is unclear. Therefore, the management of unruptured intracranial aneurysms <7 mm in the anterior circulation is controversial.

Methods—

Between June 1999 and June 2012, 384 unruptured intracranial aneurysms of the anterior circulation <7 mm in diameter underwent conservative treatment and regular annual follow-up in our institution. Patient- and aneurysm-specific information, as well as information on aneurysm enlargement and rupture, was entered into a prospectively conducted database.

Results—

The mean follow-up duration was 48.5±37 months. Three aneurysms enlarged during the follow-up period and were treated by surgical clipping. Three aneurysms were ruptured during the follow-up period. The overall annual incidence of subarachnoid hemorrhage was 0.2% during the follow-up. In the multivariate Cox proportional hazard regression analysis, hypertension (
P
<0.001; hazard ratio, 2.6; 95% confidence interval, 2.1–3.3) and <50 years of age (
P
=0.04; hazard ratio, 1.3; 95% confidence interval, 1.01–1.7) were significant independent predictors of aneurysm rupture.

Conclusions—

The present data indicate that the annual incidence of subarachnoid hemorrhage associated with small anterior circulation unruptured intracranial aneurysms is low in this single-institution prospective cohort study. The natural course varies according to arterial hypertension and patient age.
Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke
Authors: Ankolekar Sandeep , Fuller Michael , Cross Ian , Renton Cheryl , Cox Patrick , Sprigg Nikola , Siriwardena A. Niroshan , Bath Philip M.
Published: September 2013

Background and Purpose—

The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed.

Methods—

We performed a randomized controlled trial with screening, consent, randomization, and treatment performed by paramedics prior to hospitalization. Patients with probable ultra-acute stroke (<4 hours) and systolic blood pressure (SBP) >140 mm Hg were randomized to transdermal glyceryl trinitrate (GTN; 5 mg/24 hours) or none (blinding under gauze dressing) for 7 days with the first dose given by paramedics. The primary outcome was SBP at 2 hours.

Results—

Of a planned 80 patients, 41 (25 GTN, 16 no GTN) were enrolled >22 months with median age [interquartile range] 79 [16] years; men 22 (54%); SBP 168 [46]; final diagnosis: stroke 33 (80%) and transient ischemic attack 3 (7%). Time to randomization was 55 [75] minutes. After treatment with GTN versus no GTN, SBP at 2 hours was 153 [31] versus 174 [27] mm Hg, respectively, with difference −18 [30] mm Hg (
P
=0.030). GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [3] point (
P
=0.040). The rates of death, 4 (16%) versus 6 (38%;
P
=0.15), and serious adverse events, 14 (56%) versus 10 (63%;
P
=0.75), did not differ between GTN and no GTN.

Conclusions—

Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial. GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke. A larger trial is needed to assess whether GTN improves functional outcome.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com/ISRCTN66434824/66434824
. Unique identifier: 66434824.
Determinants of Cerebral Lesions in Endocarditis on Systematic Cerebral Magnetic Resonance Imaging
Authors: Iung Bernard , Tubiana Sarah , Klein Isabelle , Messika-Zeitoun David , Brochet Eric , Lepage Laurent , Al-Attar Nawwar , Ruimy Raymond , Leport Catherine , Wolff Michel , Duval Xavier
Published: September 2013

Background and Purpose—

Cerebral lesions are frequent complications of infective endocarditis (IE) and have a prognostic impact. Cerebral MRI identifies lesions in a high number of patients. However, their determinants have not been identified. The aim of the study was to define the determinants of cerebral lesions in patients with IE undergoing systematic cerebral MRI.

Methods—

Determinants of ischemic lesions and of microbleeds were prospectively analyzed in 120 patients with left-sided IE, using systematic cerebral MRI.

Results—

Median age was 60 years (interquartile range 51–72); IE occurred on a prosthetic valve in 37 patients (30.8%) and was due to
Streptococci
in 47 patients and
Staphylococci
in 36; 15 (12.5%) had neurological symptoms. MRI detected ischemic lesions in 64 patients (53.3%; territorial lesions in 32 and small lesions in 57) and microbleeds in 72 (60.0%). In multivariate analysis, ischemic lesions were associated with vegetation length (odds ratio 1.10/mm; 95% confidence interval 1.03–1.16;
P
=0.003) and
Staphylococcus aureus
IE (odds ratio 2.65; 95% confidence interval 1.01–6.96;
P
=0.05). A vegetation length >4 mm identified ischemic lesions with a sensitivity of 74.6% and a specificity of 51.5%. Microbleeds were associated with prosthetic IE (odds ratio 8.01; 95% confidence interval 2.58–24.90;
P
=0.0003) and not with prior anticoagulant therapy (
P
=0.67).

Conclusions—

Systematic cerebral MRI frequently detects ischemic lesions and microbleeds during acute IE. The high sensitivity of MRI shows that each millimeter increase in vegetation length is associated with a 10% increase in the rate of ischemic lesions. Conversely, microbleeds are associated only with prosthetic IE in this study.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00144885.
Good Outcome Rate of 35% in IV-tPA–Treated Patients With Computed Tomography Angiography Confirmed Severe Anterior Circulation Occlusive Stroke
Authors: González R. Gilberto , Furie Karen L. , Goldmacher Gregory V. , Smith Wade S. , Kamalian Shervin , Payabvash Seyedmehdi , Harris Gordon J. , Halpern Elkan F. , Koroshetz Walter J. , Camargo Erica C.S. , Dillon William P. , Lev Michael H.
Published: September 2013

Background and Purpose—

To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke.

Methods—

Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed.

Results—

Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (
P
<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%;
P
=0.031). The number needed to treat was 7 (95% confidence interval, 3–60).

Conclusions—

IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.
Distribution of National Institutes of Health Stroke Scale in the Cincinnati/Northern Kentucky Stroke Study
Authors: Reeves Mathew , Khoury Jane , Alwell Kathleen , Moomaw Charles , Flaherty Matthew , Woo Daniel , Khatri Pooja , Adeoye Opeolu , Ferioli Simona , Kissela Brett , Kleindorfer Dawn
Published: September 2013

Background and Purpose—

Little is known about the distribution of National Institutes of Health Stroke Scale (NIHSS) scores from patients with ischemic stroke sampled from population-based studies. We describe the distribution of NIHSS in ischemic stroke cases from the Cincinnati/Northern Kentucky Stroke Study.

Methods—

Within a biracial population of 1.3 million, all strokes among area residents in 2005 were ascertained by screening discharge records at local hospitals and outpatient clinics. A sampling scheme was developed to ascertain additional cases presenting to physician offices and nursing homes, not identified through the other sources. All confirmed ischemic stroke cases underwent chart abstraction, and a retrospective NIHSS (rNIHSS) score (range, 0–42) was generated on the basis of initial physician examination findings.

Results—

There were 2233 ischemic stroke cases identified during the 12-month study. The overall median rNIHSS score was 3 (interquartile range, 1–7). Median rNIHSS score was 3, 7, and 1, respectively, for stroke cases ascertained through the admitted, in-hospital, and out-of-hospital sources. Median rNIHSS was significantly higher in subjects ≥80 years compared with younger cases (4 versus 3).

Conclusions—

More than half of all ischemic stroke cases have mild symptom severity on initial presentation (ie, rNIHSS≤3). Monitoring trends in NIHSS represents a legitimate target for population-based surveillance efforts.
The Labor Question in America: Economic Democracy in the Gilded Age, Rosanne Currarino, Champaign, IL.: University of Illinois Press, 2011
Authors: Gourevitch Alex
Published: September 2013

Abstract

It is said we live in a second Gilded Age, which makes our understanding of the first all the more relevant. Rosanne Currarino’sThe Labor Question in Americamakes the bold claim that, far from being a period of defeat for the Left, the original Gilded Age saw an expansion of democratic citizenship. A group of economists, social reformers and labour organisers transformed our understanding of political participation from the earlier, producerist to a more modern, consumerist ideal of social inclusion and collective agency. However, on her own telling, Currarino’s ‘expansion’ comes across more as a ‘substitution’. Some workers gained in wages what they lost in control of the means of production. Though Currarino fairly identifies the utopian aspirations underlying the demand for higher levels of consumption, her narrative relies on an overly rigid distinction between production and consumption, missing out on the way in which consumption came to be defined in ways that assumed the workplace would be a site of submission. Finally,The Labor Questionfails to include, as parts of its narrative, the extraordinary violence that marked struggles over the labour question. In this context, the shift from ‘producerist’ emphases on worker control to ‘consumerist’ views of economic citizenship look more like an ideological displacement than they do a progressive expansion of democracy.
This Land is Ours Now: Social Mobilization and the Meanings of Land in Brazil, Wendy Wolford, Durham, NC.: Duke University Press, 2010
Authors: Vergara-Camus Leandro
Published: September 2013

Abstract

In this review, I highlight the valuable contributions of Wendy Wolford’s latest book, which rest on her extensive understanding of the diversity of the Brazilian countryside and her acute ability to weave together the impact that land-tenure patterns, labour regimes and regional cultures have had upon settlers of the Landless Rural Workers’ Movement. It also assesses the central claim of the book which suggests that the MST is often unable to retain its membership because the leadership reproduces an understanding of peasant agriculture that is specific to the South of Brazil. The review argues that Wolford’s main argument falls foul of four shortcomings related to her methodology, her understanding of the MST’s ideology, her choice of not including the process of encampment and the MST’s commitment to radical social change in her analysis, and finally her problematic interpretation of the relationship between the grassroots membership and the leadership of the movement.
Seasons of Self-Delusion: Opium, Capitalism and the Financial Markets
Authors: Banaji Jairus
Published: September 2013

Abstract

To grasp current trends within capitalism without abandoning the framework of Marx’sCapitalwe need to return to the category of ‘fictitious capital’ and make it central to our explanations. Based on the 2012 Isaac and Tamara Deutscher Memorial Lecture, this essay combines reflections on Marx’s account of ‘fictitious capital’; an investigation of the role of bills of exchange; and an analysis of the recent turmoil in British and US banking. It looks at the way the opium trade, financed through the London bill market, integrated a constellation of interests in the City with the labour of peasant households in India as parts of a unified accumulation process. Opium was vital to the fortunes of British capitalism for most of the nineteenth century. The merchant banks that were the mainstay of Britain’s form of capitalism were also the key element in the re-emergence of global finance in the postwar period. The concluding part of the paper deals with the current banking crisis and follows Hilferding in arguing that by providing liquidity to the markets for fictitious capital, speculation plays a crucial role in sustaining profitability for the bigger capitals.
Urban Marxism and the Post-colonial Question: Henri Lefebvre and ‘Colonisation’
Authors: Kipfer Stefan , Goonewardena Kanishka
Published: September 2013

Abstract

The post-colonial has often functioned as a code word for a form of French post-theory. In more recent efforts to reconstruct linkages between metropolitan Marxism and counter-colonialism, the post-colonial refers to an open-ended research field for investigating the present weight of colonial histories. But even in these reformulations, post-colonial research presents formidable challenges to Euro-American urban Marxism. In this context, this paper redirects Henri Lefebvre’s work to analyse post-colonial situations. It traces in particular the notion of ‘colonisation’ as it develops from his critique of everyday life (which signalled an extension of his critique of alienation) to his work on the state (where the notion reappears in discussions of theories of imperialism). We argue that Lefebvre’s notion of ‘colonisation’ (which refers to multi-scalar strategies for organising territorial relations of domination) presents a promising opening to understanding the ‘colonial’ aspects of urbanisation today. Still, for this promise to be realised, Lefebvre’s notion must be refracted through dialectical-humanist counter-colonial traditions.