bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetaldehyde accelerates HCV-induced impairment of innate immunity by suppressing methylation reactions in liver cells
Authors: Ganesan Murali , Zhang Jinjin , Bronich Tatiana , Poluektova Larisa I. , Donohue Terrence M. , Tuma Dean J. , Kharbanda Kusum K. , Osna Natalia A.
Published: August 2015

Alcohol exposure worsens the course and outcomes of hepatitis C virus (HCV) infection. Activation of protective antiviral genes is induced by IFN-α signaling, which is altered in liver cells by either HCV or ethanol exposure. However, the mechanisms of the combined effects of HCV and ethanol metabolism in IFN-α signaling modulation are not well elucidated. Here, we explored a possibility that ethanol metabolism potentiates HCV-mediated dysregulation of IFN-α signaling in liver cells via impairment of methylation reactions. HCV-infected Huh7.5 CYP2E1+ cells and human hepatocytes were exposed to acetaldehyde (Ach)-generating system (AGS) and stimulated with IFN-α to activate IFN-sensitive genes (ISG) via the Jak-STAT-1 pathway. We observed significant suppression of signaling events by Ach. Ach exposure decreased STAT-1 methylation via activation of protein phosphatase 2A and increased the protein inhibitor of activated STAT-1 (PIAS-1)-STAT-1 complex formation in both HCV+ and HCV− cells, preventing ISG activation. Treatment with a promethylating agent, betaine, attenuated all examined Ach-induced defects. Ethanol metabolism-induced changes in ISGs are methylation related and confirmed by in vivo studies on HCV+ transgenic mice. HCV- and Ach-induced impairment of IFN signaling temporarily increased HCV RNA levels followed by apoptosis of heavily infected cells. We concluded that Ach potentiates the suppressive effects of HCV on activation of ISGs attributable to methylation-dependent dysregulation of IFN-α signaling. A temporary increase in HCV RNA sensitizes the liver cells to Ach-induced apoptosis. Betaine reverses the inhibitory effects of Ach on IFN signaling and thus can be used for treatment of HCV+ alcohol-abusing patients.
Classification of functional bowel disorders by objective physiological criteria based on endoluminal image analysis
Authors: Malagelada Carolina , Drozdzal Michal , Seguí Santi , Mendez Sara , Vitrià Jordi , Radeva Petia , Santos Javier , Accarino Anna , Malagelada Juan-R , Azpiroz Fernando
Published: August 2015

We have previously developed an original method to evaluate small bowel motor function based on computer vision analysis of endoluminal images obtained by capsule endoscopy. Our aim was to demonstrate intestinal motor abnormalities in patients with functional bowel disorders by endoluminal vision analysis. Patients with functional bowel disorders ( n = 205) and healthy subjects ( n = 136) ingested the endoscopic capsule (Pillcam-SB2, Given-Imaging) after overnight fast and 45 min after gastric exit of the capsule a liquid meal (300 ml, 1 kcal/ml) was administered. Endoluminal image analysis was performed by computer vision and machine learning techniques to define the normal range and to identify clusters of abnormal function. After training the algorithm, we used 196 patients and 48 healthy subjects, completely naive, as test set. In the test set, 51 patients (26%) were detected outside the normal range ( P < 0.001 vs. 3 healthy subjects) and clustered into hypo- and hyperdynamic subgroups compared with healthy subjects. Patients with hypodynamic behavior ( n = 38) exhibited less luminal closure sequences (41 ± 2% of the recording time vs. 61 ± 2%; P < 0.001) and more static sequences (38 ± 3 vs. 20 ± 2%; P < 0.001); in contrast, patients with hyperdynamic behavior ( n = 13) had an increased proportion of luminal closure sequences (73 ± 4 vs. 61 ± 2%; P = 0.029) and more high-motion sequences (3 ± 1 vs. 0.5 ± 0.1%; P < 0.001). Applying an original methodology, we have developed a novel classification of functional gut disorders based on objective, physiological criteria of small bowel function.
Oncostatin M induces IL-33 expression in liver endothelial cells in mice and expands ST2+CD4+lymphocytes
Authors: Arshad Muhammad Imran , Guihard Pierre , Danger Yannic , Noel Gregory , Le Seyec Jacques , Boutet Marie-Astrid , Richards Carl D. , L'Helgoualc'h Annie , Genet Valentine , Lucas-Clerc Catherine , Gascan Hugues , Blanchard Frédéric , Piquet-Pellorce Claire , Samson Michel
Published: August 2015

Interleukin (IL)-33 is crucially involved in liver pathology and drives hepatoprotective functions. However, the regulation of IL-33 by cytokines of the IL-6 family, including oncostatin M (OSM) and IL-6, is not well studied. The aim of the present study was to determine whether OSM mediates regulation of IL-33 expression in liver cells. Intramuscular administration in mice of an adenovirus encoding OSM (AdOSM) leads to increase in expression of OSM in muscles, liver, and serum of AdOSM-infected mice compared with control mice. The increase of circulating OSM markedly regulated mRNA of genes associated with blood vessel biology, chemotaxis, cellular death, induction of cell adhesion molecules, and the alarmin cytokine IL-33 in liver. Steady-state IL-33 mRNA was upregulated by OSM at an early phase (8 h) following AdOSM infection. At the protein level, the expression of IL-33 was significantly induced in liver endothelial cells [liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells] with a peak at 8 days post-AdOSM infection in mice. In addition, we found OSM-stimulated human microvascular endothelial HMEC-1 cells and human LSEC/TRP3 cells showed a significant increase in expression of IL-33 mRNA in a dose-dependent manner in cell culture. The OSM-mediated overexpression of IL-33 was associated with the activation/enrichment of CD4+ST2+cells in liver of AdOSM-infected mice compared with adenovirus encoding green fluorescent protein-treated control mice. In summary, these data suggest that the cytokine OSM regulates the IL-33 expression in liver endothelial cells in vivo and in HMEC-1/TRP3 cells in vitro and may specifically expand the target CD4+ST2+cells in liver.
Vorticity is a marker of right ventricular diastolic dysfunction
Authors: Fenster Brett E. , Browning James , Schroeder Joyce D. , Schafer Michal , Podgorski Chris A. , Smyser Jamie , Silveira Lori J. , Buckner J. Kern , Hertzberg Jean R.
Published: August 2015

Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559–3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27–44) vs. 9 (5–27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7–22) vs. 28 (15–31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A ( P < 0.05), and A-wave vorticity associated with both TV A and E/A ( P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH.
Chemerin promotes the proliferation and migration of vascular smooth muscle and increases mouse blood pressure
Authors: Kunimoto Hidemizu , Kazama Kyosuke , Takai Mizuho , Oda Mayuko , Okada Muneyoshi , Yamawaki Hideyuki
Published: August 2015

Blood chemerin concentration shows positive correlation not only with body mass index and serum triglyceride level but also with systolic blood pressure. While it seems likely that chemerin influences vascular smooth muscle cell (SMC) proliferation and migration, which are crucial to the development of hypertension, this remains to be clarified. In the present study, we investigated whether chemerin controls SMC proliferation and migration in vitro and also affects blood pressure in vivo. In vitro, chemerin significantly stimulated rat mesenteric arterial SMC proliferation and migration, as determined by a cell counting assay and Boyden chamber assay, respectively. The migratory effect of chemerin was confirmed in human aortic SMCs. Chemerin significantly increased ROS production in SMCs and phosphorylation of Akt (Ser473) and ERK, as measured by fluorescent staining and Western blot analysis, respectively. Various inhibitors (ROS inhibitor: N-acetyl-l-cysteine, phosphatidylinositol 3-kinase inhibitor: LY-294002, MAPKK inhibitor: PD-98059, NADPH oxidase inhibitor: gp91 ds-tat, and xanthine oxidase inhibitor: allopurinol) as well as chemokine-like receptor 1 small interfering RNA significantly inhibited chemerin-induced SMC proliferation and migration. Furthermore, chemerin-neutralizing antibody prevented carotid neointimal hyperplasia in the mouse ligation model. In vivo, chronic chemerin treatment (6 μg/kg, 6 wk) increased systolic blood pressure as well as phosphorylation of Akt and ERK in the mouse isolated aorta. In summary, we, for the first time, demonstrate that chemerin/chemokine-like receptor 1 stimulates SMC proliferation and migration via ROS-dependent phosphorylation of Akt/ERK, which may lead to vascular structural remodeling and an increase in systolic blood pressure.
Sympathoexcitation and arterial hypertension associated with obstructive sleep apnea and cyclic intermittent hypoxia
Authors: Weiss J. Woodrow , Tamisier Renaud , Liu Yuzhen
Published: August 2015

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction during sleep. These obstructive episodes are characterized by cyclic intermittent hypoxia (CIH), by sleep fragmentation, and by hemodynamic instability, and they result in sustained sympathoexcitation and elevated arterial pressure that persist during waking, after restoration of normoxia. Early studies established that 1) CIH, rather than sleep disruption, accounts for the increase in arterial pressure; 2) the increase in arterial pressure is a consequence of the sympathoactivation; and 3) arterial hypertension after CIH exposure requires an intact peripheral chemoreflex. More recently, however, evidence has accumulated that sympathoactivation and hypertension after CIH are also dependent on altered central sympathoregulation. Furthermore, although many molecular pathways are activated in both the carotid chemoreceptor and in the central nervous system by CIH exposure, two specific neuromodulators—endothelin-1 and angiotensin II—appear to play crucial roles in mediating the sympathetic and hemodynamic response to intermittent hypoxia.
Heparanase Enhances Tumor Growth and Chemoresistance by Promoting Autophagy
Authors: Shteingauz Anna , Boyango Ilanit , Naroditsky Inna , Hammond Edward , Gruber Maayan , Doweck Ilana , Ilan Neta , Vlodavsky Israel
Published: August 2015

Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity implicated in tumor inflammation, angiogenesis, and metastasis. Heparanase is secreted as a latent enzyme that is internalized and subjected to proteolytic processing and activation in lysosomes. Its role under normal conditions has yet to be understood. Here, we provide evidence that heparanase resides within autophagosomes, where studies in heparanase-deficient or transgenic mice established its contributions to autophagy. The protumorigenic properties of heparanase were found to be mediated, in part, by its proautophagic function, as demonstrated in tumor xenograft models of human cancer and through use of inhibitors of the lysosome (chloroquine) and heparanase (PG545), both alone and in combination. Notably, heparanase-overexpressing cells were more resistant to stress and chemotherapy in a manner associated with increased autophagy, effects that were reversed by chloroquine treatment. Collectively, our results establish a role for heparanase in modulating autophagy in normal and malignant cells, thereby conferring growth advantages under stress as well as resistance to chemotherapy. Cancer Res; 75(18); 3946–57. ©2015 AACR.
Osthole Inhibits Proliferation and Induces Catabolism in Rat Chondrocytes and Cartilage Tissue
Authors: Du Guoqing , Song Yi , Wei Lei , Li Linghui , Wang Xuezong , Xu Qinguang , Zhan Hongsheng , Cao Yuelong , Zheng Yuxin , Ding Daofang
Published: August 2015

Background/Aims: Cartilage destruction is thought to be the major mediator of osteoarthritis. Recent studies suggest that inhibition of subchrondral bone loss by anti-osteoporosis (OP) drug can protect cartilige erosion. Osthole, as a promising agent for treating osteoporosis, may show potential in treating osteoarthritis. The purpose of this study was to investigate whether Osthole affects the proliferation and catabolism of rat chondrocytes, and the degeneration of cartilage explants. Methods: Rat chondrocytes were treated with Osthole (0 μM, 6.25 μM, 12.5 μM, and 25 μM) with or without IL1-β (10ng/ml) for 24 hours. The expression levels of type II collagen and MMP13 were detected by western Blot. Marker genes for chondrocytes (A-can and Sox9), matrix metalloproteinases (MMPs), aggrecanases (ADAMTS5) and genes implicated in extracellular matrix catabolism were evaluated by qPCR. Cell proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and fluorescence activated cell sorter. Wnt7b/β-catenin signaling was also investigated. Cartilage explants from two-week old SD rats were cultured with IL-1β, Osthole and Osthole plus IL-1β for four days and glycosaminoglycan (GAG) synthesis was assessed with toluidine blue staining and Safranine O/Fast Green FCF staining, collagen type II expression was detected by immunofuorescence. Results: Osthole reduced expression of chondrocyte markers and increased expression of MMP13, ADAMTS5 and MMP9 in a dose-dependent manner. Catabolic gene expression levels were further improved by Osthole plus IL-1β. Osthole inhibited chondrocyte proliferation. GAG synthesis and type II collagen were decreased in both the IL-1β groups and the Osthole groups, and significantly reduced by Osthole plus IL-1β. Conclusions: Our data suggested that Osthole increases the catabolism of rat chondrocytes and cartilage explants, this effect might be mediated through inhibiting Wnt7b/β-catenin pathway.
A Randomized Comparative Study of Oral Corticosteroid Minipulse and Low-Dose Oral Methotrexate in the Treatment of Unstable Vitiligo
Authors: Singh Harsimer , Kumaran Muthu Sendhil , Bains Anupama , Parsad Davinder
Published: August 2015

Background: Despite continued progress towards elucidation of the biochemical, genetic and immunopathological pathways in vitiligo, a definitive cure remains elusive. The initial therapy must be directed to arrest disease progression. Oral minipulse therapy (OMP) with betamethasone/dexamethasone has been tried and shown to be an effective modality to arrest the disease progression in vitiligo. Objectives: Methotrexate (MTX) is a time-tested effective treatment extensively used in various autoimmune disorders with good efficacy, safety and tolerability on a long-term basis. We intended to compare the efficacy of MTX with that of OMP in patients with unstable vitiligo vulgaris. Patients and Methods: In a prospective randomized open label study, 52 patients with vitiligo were divided into two groups. Patients in group 1 received 10 mg methotrexate weekly. Group 2 patients received corticosteroid OMP which comprised tablets of dexamethasone 2.5 mg (5 tablets), taken on 2 consecutive days in a week (total weekly dose of 5 mg dexamethasone). Results: In the MTX group, among 25 patients analyzed, during the course of treatment for 24 weeks, overall 6 patients developed new vitiliginous lesions. In the OMP group, 7/25 patients developed new lesions. Statistical correlation between the two groups showed no significance in the number of patients who developed new lesions (increasing disease activity) in either of the groups. At the end of the study, it was demonstrated that patients in both groups had a similar reduction in the vitiligo disease activity score. Conclusion: Our study demonstrated that both drugs are equally effective in controlling the disease activity of vitiligo. MTX can be used in patients with active vitiligo, wherever corticosteroids are contraindicated.
Delirium Tremens Leads to Poor Outcomes for Acute Coronary Syndrome
Authors: Joy Parijat S. , Kumar Gagan
Published: August 2015

Objectives: The mortality rate for patients with delirium tremens (DT) is 5%. As these patients present with elevated cardiac indices, coexisting DT in acute coronary syndrome (ACS) likely worsens outcomes. Our aim was to examine the outcomes of alcohol withdrawal syndrome (AWS) and DT in patients with ACS. Methods: We used the Nationwide Inpatient Sample (2000-2009) for our study. A multivariable logistic regression model was used to examine the independent association of AWS on inhospital mortality and a multivariable linear regression was used to examine the effect of AWS on inpatient length of stay (LOS). Results: An estimated 2,465,852 admissions with a primary diagnosis of ACS were analyzed. Of these, 4,499 patients had AWS and 3,460 patients had DT. Adjusting for age, gender, race, insurance, hospital characteristics, Charlson's comorbidity index, stent placement and year, the inhospital mortality was significant only for DT (OR 1.56; 95% CI 1.21-2.04). Inpatient LOS was 1.64 (95% CI 1.58-1.73) times higher in those with AWS and 2.33 (95% CI 2.22-2.43) times higher in DT when compared to nonalcoholics. Total hospital charges were higher for patients with AWS and DT when compared to nonalcoholics. Conclusions: Coexisting DT in ACS admissions is associated with increased mortality along with longer inpatient LOS and higher hospital costs.
All-trans-Retinoic Acid Modulates Nitric Oxide and Interleukin-17A Production by Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease
Authors: Behairi Nassima , Belkhelfa Mourad , Mesbah-Amroun Hamida , Rafa Hayet , Belarbi Soreya , Tazir Meriem , Touil-Boukoffa Chafia
Published: August 2015

Background: Alzheimer's disease (AD), the most common form of dementia in the elderly, is a neurodegenerative disorder associated with a complex pathophysiology. It is accepted that inflammation contributes to the pathogenesis of AD. All-trans-retinoic acid (ATRA) is a bioactive derivative of vitamin A that has shown immunomodulatory effects in many immune disorders. Objectives: In our study, we aimed to investigate in vitro immunomodulatory effects of ATRA on inducible nitric oxide synthase (iNOS) expression and interleukin-17A production during AD. Methods: Peripheral blood mononuclear cells (PBMCs) isolated from 30 Algerian AD patients and 14 age-matched nondemented controls were treated (or not) with ATRA. Production of NO and IL-17A in culture media was measured by the modified Griess method and enzyme-linked immunosorbent assay, respectively. Expression of iNOS in PBMCs was examined by fluorescence immunostaining. Results: Our results showed higher spontaneous in vitro production of NO related to overexpression of iNOS in AD patients compared to controls. Remarkably, ATRA treatment showed an important downregulatory effect on NO production and iNOS expression in patients. This effect was associated with a reduction in IL-17A production and increased IL-10 release. Conclusions: Taken together, our results indicate that ATRA exerts anti-inflammatory effects in AD. Furthermore, ATRA represents a promising tool for monitoring inflammatory responses associated with disease progression.
Localized Subcarinal Adenitis following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Authors: Sánchez-Font Albert , Álvarez Luis , Ledesma Gabriela , Curull Víctor
Published: August 2015

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for the diagnosis of mediastinal lymph nodes and masses. Its complications are rare and include hemorrhage, pneumothorax and infections such as mediastinitis. We report the case of a 51-year-old patient who presented with a localized subcarinal adenitis after EBUS-TBNA. Germs colonizing the oropharynx may have been dragged along by the echobronchoscope, inoculating the punctured mediastinal lymph node.
ITPA and SLC29A1 Genotyping for the Prediction of Ribavirin Dose Reduction in Anti-HCV Triple Therapy with Protease Inhibitors
Authors: Lombardi Andrea , Landonio Simona , Magni Carlo , Cheli Stefania , Mazzali Cristina , Mondelli Mario U. , Rizzardini Giuliano , Clementi Emilio , Falvella Felicia Stefania
Published: August 2015

Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs.
Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease
Authors: Wiseman Stewart J. , Doubal Fergus N. , Chappell Francesca M. , Valdés-Hernández Maria C. , Wang Xin , Rumley Ann , Lowe Gordon D.O. , Dennis Martin S. , Wardlaw Joanna M.
Published: August 2015

Background: The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. Methods: We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. Results: We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R2 0.289). Inflammatory biomarkers showed minor improvement over baseline (R2 0.291), but the other plasma biomarkers did not improve the baseline model. Conclusion: Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population.
Does CSE1L Overexpression Affect Distant Metastasis Development in Breast Cancer?
Authors: Yuksel Ulvi M. , Turker Ibrahim , Dilek Gulay , Dogan Lutfi , Gulcelik Mehmet A. , Oksuzoglu Berna
Published: August 2015

Background:CSE1L (chromosome segregation 1-like) is the human homologue to the yeast gene CSE1, and is related to invasion and metastasis in cancer progression. The aim of this study was to investigate the potential role of CSE1L expression in distant metastasis of breast cancer. Patients and Methods: A total of 71 breast cancer patients were included in this study. Clinical characteristics and CSE1L status were evaluated. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded archival breast tumor tissue. The results of CSE1L staining were analyzed according to the percentage of immunoreactive cells. Results: 34 patients had distant metastasis and 37 did not. The mean age of the patients was 50.5 ± 12.1 years. Age, tumor size, and hormone receptor status were similar in patients with distant metastasis and in those without. A statistically significant relationship was found between nuclear CSE1L expression and distant metastasis of breast cancer. Lymph node metastasis and nuclear grade were other factors affecting distant metastasis. Conclusion: There is a relationship between nuclear CSE1L overexpression and distant metastasis in breast cancer. CSE1L status may therefore become a valuable prognostic tool in the future.
Association Between Comorbidities and Outcomes in Heart Failure Patients With and Without an Implantable Cardioverter‐Defibrillator for Primary Prevention
Authors: Khazanie Prateeti , Hellkamp Anne S. , Fonarow Gregg C. , Bhatt Deepak L. , Masoudi Frederick A. , Anstrom Kevin J. , Heidenreich Paul A. , Yancy Clyde W. , Curtis Lesley H. , Hernandez Adrian F. , Peterson Eric D. , Al‐Khatib Sana M.
Published: August 2015

Background

Implantable cardioverter‐defibrillator (
ICD
) therapy is associated with improved outcomes in patients with heart failure (
HF
), but whether this association holds among older patients with multiple comorbid illnesses and worse
HF
burden remains unclear.

Methods and Results

Using the National Cardiovascular Data Registry's
ICD
Registry and the Get With The Guidelines–Heart Failure (
GWTG
‐
HF
) registry linked with Medicare claims, we examined outcomes associated with primary‐prevention
ICD
versus no
ICD
among
HF
patients aged ≥65 years in clinical practice. We included patients with an ejection fraction ≤35% who received (
ICD
Registry) and who did not receive (
GWTG
‐
HF
) an
ICD
. Compared with patients with an
ICD
, patients in the non‐
ICD
group were older and more likely to be female and white. In matched cohorts, the 3‐year adjusted mortality rate was lower in the
ICD
group versus the non‐
ICD
group (46.7% versus 55.8%; adjusted hazard ratio [
HR
] 0.76; 95%
CI
0.69 to 0.83). There was no associated difference in all‐cause readmission (
HR
0.99; 95%
CI
0.92 to 1.08) but a lower risk of
HF
readmission (
HR
0.88; 95%
CI
0.80 to 0.97). When compared with no ICD,
ICD
s were also associated with better survival in patients with ≤3 comorbidities (
HR
0.77; 95%
CI
0.69 to 0.87) and >3 comorbidities (
HR
0.77; 95%
CI
0.64 to 0.93) and in patients with no hospitalization for
HF
(
HR
0.75; 95%
CI
0.65 to 0.86) and at least 1 prior
HF
hospitalization (
HR
0.69; 95%
CI
0.58 to 0.82). In subgroup analyses, there were no interactions between
ICD
and mortality risk for comorbidity burden (
P
=0.95) and for prior
HF
hospitalization (
P
=0.46).

Conclusion

Among older
HF
patients,
ICD
s for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior
HF
hospitalization.
Remote Ischemic Conditioning Alters Methylation and Expression of Cell Cycle Genes in Aneurysmal Subarachnoid Hemorrhage
Authors: Nikkola Elina , Laiwalla Azim , Ko Arthur , Alvarez Marcus , Connolly Mark , Ooi Yinn Cher , Hsu William , Bui Alex , Pajukanta Päivi , Gonzalez Nestor R.
Published: August 2015

Background and Purpose—

Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC.

Methods—

Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein–protein interactions.

Results—

We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (
P
<3.8×10
−4
) and inflammatory responses (
P
<1.4×10
−4
). The cell cycle pathway genes form a significant protein–protein interaction network of tightly coexpressed genes (
P
<0.00001).

Conclusions—

Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.
Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID?
Authors: Chaturvedi Seemant , Turan Tanya N. , Lynn Michael J. , Derdeyn Colin P. , Fiorella David , Janis L. Scott , Chimowitz Marc I.
Published: August 2015

Background and Purpose—

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses.

Methods—

Using proportional hazards regression, we compared the SAMMPRIS primary end point between SAMMPRIS medical patients and WASID patients meeting the same qualifying criteria adjusted for confounding baseline characteristics.

Results—

The unadjusted comparison of the SAMMPRIS primary end point showed a significantly higher risk for WASID patients (
P
=0.009, logrank test) with 12 month Kaplan–Meier estimates of 21.9% in WASID and 12.6% in SAMMPRIS and hazard ratio 1.9 (95% confidence interval =1.2–3.0). The analyses identified the following confounding factors that varied between the studies and that conferred a higher risk: lack of statin use at enrollment (hazard ratio =1.8, 95% confidence interval =1.1–2.9,
P
=0.027) that was more prevalent among WASID patients (39% versus 14%,
P
<0.0001) and prior infarcts in the territory of the symptomatic vessel (hazard ratio =1.8, 95% confidence interval =1.1–2.9,
P
=0.023) that was more prevalent among SAMMPRIS patients (34% versus 22%,
P
=0.015).The hazard ratio for WASID versus SAMMPRIS adjusted for these 2 characteristics was 1.9 (95% confidence interval =1.1–3.2).

Conclusions—

After adjustment for confounding baseline characteristics, WASID patients had an almost 2-fold higher risk of the SAMMPRIS primary end point, which supports the hypothesis that the lower rate of the primary end point in the medical arm of SAMMPRIS compared with WASID patients was as a result of the aggressive medical management used in SAMMPRIS.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00576693.
Patients With Ischemic Stroke and Incident Atrial Fibrillation
Authors: Fauchier Laurent , Clementy Nicolas , Pelade Christele , Collignon Cecile , Nicolle Emmanuelle , Lip Gregory Y.H.
Published: August 2015

Background and Purpose—

A substantial part of ischemic strokes is attributed to atrial fibrillation (AF). We hypothesized that patients with ischemic stroke without prior diagnosed AF were at higher risk of having a subsequent diagnosis of AF, and this was associated with multiple risk factors.

Methods—

This French longitudinal cohort study was based on the national database covering hospital care from 2008 to 2012 for the entire population.

Results—

Of 65 807 patients with ischemic stroke in 2009, 48 992 did not have AF at baseline. A total of 4828 of these patients were diagnosed as having AF during a follow-up of 15±15 months (incidence rate 7.9 per 100 person-years). By comparison, the yearly rate of new-onset AF for the 826 416 patients with a cardiac hospitalization was 5.9%. CHADS
2
(congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack) and CHA
2
DS
2
-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack [doubled], vascular disease, age 65–75 years, and sex category [female]) scores were both associated with the risk of new-onset AF during follow-up (CHADS
2
: hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.66–1.75; CHA
2
DS
2
-VASc: HR 1.45, 95% CI 1.42–1.48). The c statistics were 0.700 (95% CI 0.696–0.706) for CHADS
2
and 0.706 (95% CI 0.702–0.710) with CHA
2
DS
2
-VASc (
P
=0.003 for comparison of the 2 scores). Independent predictors of subsequent diagnosis of AF were age 65 to 74 years (HR 2.29, 95% CI 2.06–2.54), age ≥75 years (HR 3.31, 95% CI 3.02–3.64), hypertension (HR 1.22, 95% CI 1.13–1.32), heart failure (HR 2.56, 95% CI 2.41–2.72), and vascular disease (HR 1.10, 95% CI 1.04–1.17).

Conclusions—

Ischemic stroke was associated with a substantially increased risk of incident AF, particularly among individuals with higher CHADS
2
or CHA
2
DS
2
-VASc scores. These risk scores seem to be simple tools for identifying patients at higher risk of incident AF after ischemic stroke.
Decentralization and Primary Education Service Delivery
Authors: Venkataraman M. , Keno Eyob
Published: August 2015

Ethiopia’s post 1991 decentralization drive is fairly a recent phenomenon borne out of the realization that devolution of political powers to constituent units would be the best alternative in ensuring development. The move, which was also inevitable given the history of a little over two decades of authoritarian rule in the country, was deepened culminating in the launching of District Level Decentralization Programme (dldp) in 2001 in order to enhance the scope and quality of the delivery of social services to the grass root level communities. This article aims to assess the extent of service delivery with education sector as its focus taking the case of two selected Woredas from Oromo Nationality Zone of Amhara National Regional State and find out constraints if any on the provision of the same. Using primary data collected from sampled population of the two Woredas, the article analyzes how far Ethiopia’s decentralization drive has produced the desired results in terms of performance of the woredas in service delivery and thereby benefiting the concerned community people at large. The findings of the study reveal that although there have been significant improvements made in extending educational service delivery in the two woredas, the quality of it is constrained in view of existing challenges such as lack of adequate financial support, trained manpower, increasing rate of teacher attrition, lack of adequate participation by the community and planning and these have to be tackled with in order that meaningful devolution of powers at the grass root level is assured.
Leadership of University Women for Development in the Democratic Republic of Congo
Authors: Luhahi Jacqueline Nembe Songu
Published: August 2015

As perceived protectors of the Congolese cultures figuratively and realistically and agents of positive economic and social changes, the role and the place of the Congolese women in general in the development schemes cannot be denied. However, intellectual debates about what the Congolese society at large expects the Congolese university women to contribute to the discourses about development and its various models have not been systematically studied. While, for instance, the discourse about the parity between women and men in the workplace is being promoted by the government, the studies on gender in higher education is still in its infancy. This study investigates women’s role within the context of the evolution of educational systems and their values since the Belgian administration. It examines educational policies in relationship to the models of development that both colonial and post-colonial administrations formulated and implemented. Although the study is essentially a reflection, putting an emphasis on conceptualization and theories, it is also supported by historical and cultural arguments and propositions. It is argued that the Congolese university women have ‘citizenry responsibility’ and ‘university education and engagement’ to propose new leadership role in development. Using historical-structuralist perspectives as developed in social sciences at large, I analyze further the issue of the nature of the relationship between the place and the role of university and that of leadership and development. I raise the issue of whether or not the Congolese university women’s leadership matters in the search for developmental models in the Congo.
Regime Change and Foreign Policy
Authors: Dossi Simone
Published: August 2015

Regime change and foreign policy adjustments have been closely intertwined in Myanmar’s recent experience. Since 2011, domestic political transition has been paralleled by changes in the country’s foreign policy posture, with Naypyitaw reconsidering its dependence on Beijing while seeking rapprochement with Washington. Taking Myanmar as a case study, this essay aims to address the theoretical issue of how regime change influences the foreign policy of a country. The first two sections draw on Foreign Policy Analysis and Comparative Politics to develop an analytical framework for the study of foreign policy choices during regime change. The focus is on how transitional politics interacts with external influence, against the background of loosened distinctions between the domestic and international levels. The last two sections test the analytical framework against the ups and downs of Myanmar’s economic cooperation with China. Two decisions of the Myanmar government are analysed: the 2011 decision to suspend cooperation on the Myitsone dam, and the 2012 decision to continue cooperation on the Letpadaung mine. While apparently contradictory, Naypyitaw’s behaviour on these two occasions helps to unravel the dilemmas that foreign policy decision-makers face at times of political transition.
Litsea udayanii (Lauraceae): A new species from the southern Western Ghats, India
Authors: Jose Robi Aloor , Thengumpallil Satheesh George , THUSHAR Tushar K.V.
Published: August 2015

Litsea udayanii, a new species of Lauraceae from the Anamalai phytogeographical zone of southern Western Ghats is described and illustrated here. The new species resembles L. cubeba in its clustered inflorescence and L. beddomei in fruits. Litsea udayanii differs from L. cubeba by its coriaceous leaves, 12 staminodes in the female flowers, ellipsoid fruits, and an enlarged and cup-shaped perianth tube; it differs from L. beddomei by its elliptic-oblong leaves with cuneate to rounded base and abaxially prominent tertiary veins, and by its clustered inflorescence. In contrast, L. cubeba is characterized by chartaceous leaves, 8–9 staminodes in the female flowers, subglobose fruits, and a small and flattened perianth tube and L. beddomei is distinguished by linear-oblong leaves with acute to attenuate base and abaxially inconspicuous tertiary veins, and by inflorescences arranged on 1–5 cm long brachyblasts.
Compsocommosis new genus, with a new species in Vietnam, and Transfer of Mictocommosis to Archipini (Lepidoptera: Tortricidae: Tortricinae: Archipini)
Authors: HEPPNER JOHN B. , BAE YANG-SEOP
Published: August 2015

Compsocommosis, n. gen. (Tortricidae: Tortricinae: Archipini), is described, with one new species from Vietnam, Compsocommosis vietnamensis Heppner & Bae, n. sp. The new genus is related to the Asian genus Mictocommosis, and both are placed in the tribe Archipini.
New species and records of Burmagomphus Williamson, 1907 (Odonata, Gomphidae) from China
Authors: ZHANG HAO-MIAO , KOSTERIN OLEG E. , CAI QING-HUA
Published: August 2015

Four new species of Burmagomphus Williamson, 1907 are described from Southwestern China: B. apricus sp. nov. from Xishuangbanna National Nature Reserve, Menglun Town, Xishuangbanna Dai Autonomous Prefecture, Yunnan Province; B. magnus sp. nov. from Huayudong, Nanxi Town, Hekou County, Hani-Yi Autonomous Prefecture of Honghe, Yunnan Province, B. dentatus sp. nov. from Zhangjiang River in Xiaoqikong scenic spot, altitude 400 m, Libo County, Guizhou Province, and B. latescens sp. nov. from Sifangjing, Mengding Town, Gengma County, Lincang City, Yunnan Province. New records of Burmagomphus spp. in China are provided, with B. asahinai and B. williamsoni williamsoni for the first time reported from China. A revised checklist of Burmagomhus spp. of China is provided which includes 14 species. A doubtful record of B. arboreus and relations of the newly described species are discussed. All types are deposited in the Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan City, Hubei Province, China.
Three new species of the genus Trachelas (Araneae: Trachelidae) from an oak forest inside the Mesoamerican biodiversity hotspot in Mexico
Authors: RIVERA-QUIROZ F. ANDRÉS , ALVAREZ-PADILLA FERNANDO
Published: August 2015

Three new species of the spider genus Trachelas L. Koch, 1872 are described and included in the speciosus group based on the following features: embolus as a separate sclerite from the tegulum with no basal coils, legs with a conspicuous fringe of long trichobothria and narrow copulatory ducts coiled irregularly. The new species described are: T. crassus sp. n., T. ductonuda sp. n. and T. odoreus sp. n. A total of 46 specimens were collected in an oak forest near Pico de Orizaba Volcano, Mexico. Most individuals were collected on low vegetation using beating trays and direct collecting at night. Additional images are available at www.unamfcaracnolab.com.
Climate Variability and Change since 850 CE: An Ensemble Approach with the Community Earth System Model
Authors: Otto-Bliesner Bette L. , Brady Esther C. , Fasullo John , Jahn Alexandra , Landrum Laura , Stevenson Samantha , Rosenbloom Nan , Mai Andrew , Strand Gary
Published: August 2015

The climate of the past millennium provides a baseline for understanding the background of natural climate variability upon which current anthropogenic changes are superimposed. As this period also contains high data density from proxy sources (e.g., ice cores, stalagmites, corals, tree rings, and sediments), it provides a unique opportunity for understanding both global and regional-scale climate responses to natural forcing. Toward that end, an ensemble of simulations with the Community Earth System Model (CESM) for the period 850–2005 (the CESM Last Millennium Ensemble, or CESM-LME) is now available to the community. This ensemble includes simulations forced with the transient evolution of solar intensity, volcanic emissions, greenhouse gases, aerosols, land-use conditions, and orbital parameters, both together and individually. The CESM-LME thus allows for evaluation of the relative contributions of external forcing and internal variability to changes evident in the paleoclimate data record, as well as providing a longer-term perspective for understanding events in the modern instrumental period. It also constitutes a dynamically consistent framework within which to diagnose mechanisms of regional variability. Results demonstrate an important influence of internal variability on regional responses of the climate system during the past millennium. All the forcings, particularly large volcanic eruptions, are found to be regionally influential during the preindustrial period, while anthropogenic greenhouse gas and aerosol changes dominate the forced variability of the mid- to late twentieth century.
Characterization of Northern Hemisphere Snow Water Equivalent Datasets, 1981–2010
Authors: Mudryk L. R. , Derksen C. , Kushner P. J. , Brown R.
Published: August 2015

Five, daily, gridded, Northern Hemisphere snow water equivalent (SWE) datasets are analyzed over the 1981–2010 period in order to quantify the spatial and temporal consistency of satellite retrievals, land surface assimilation systems, physical snow models, and reanalyses. While the climatologies of total Northern Hemisphere snow water mass (SWM) vary among the datasets by as much as 50%, their interannual variability and daily anomalies are comparable, showing moderate to good temporal correlations (between 0.60 and 0.85) on both interannual and intraseasonal time scales. Wintertime trends of total Northern Hemisphere SWM are consistently negative over the 1981–2010 period among the five datasets but vary in strength by a factor of 2–3. Examining spatial patterns of SWE indicates that the datasets are most consistent with one another over boreal forest regions compared to Arctic and alpine regions. Additionally, the datasets derived using relatively recent reanalyses are strongly correlated with one another and show better correlations with the satellite product [the European Space Agency (ESA)’s Global Snow Monitoring for Climate Research (GlobSnow)] than do those using older reanalyses. Finally, a comparison of eight reanalysis datasets over the 2001–10 period shows that land surface model differences control the majority of spread in the climatological value of SWM, while meteorological forcing differences control the majority of the spread in temporal correlations of SWM anomalies.
Maintenance and Broadening of the Ocean’s Salinity Distribution by the Water Cycle
Authors: Zika Jan D. , Skliris Nikolaos , Nurser A. J. George , Josey Simon A. , Mudryk Lawrence , Laliberté Frédéric , Marsh Robert
Published: August 2015

The global water cycle leaves an imprint on ocean salinity through evaporation and precipitation. It has been proposed that observed changes in salinity can be used to infer changes in the water cycle. Here salinity is characterized by the distribution of water masses in salinity coordinates. Only mixing and sources and sinks of freshwater and salt can modify this distribution. Mixing acts to collapse the distribution, making saline waters fresher and fresh waters more saline. Hence, in steady state, there must be net precipitation over fresh waters and net evaporation over saline waters. A simple model is developed to describe the relationship between the breadth of the distribution, the water cycle, and mixing—the latter being characterized by an e-folding time scale. In both observations and a state-of-the-art ocean model, the water cycle maintains a salinity distribution in steady state with a mixing time scale of the order of 50 yr. The same simple model predicts the response of the salinity distribution to a change in the water cycle. This study suggests that observations of changes in ocean salinity could be used to infer changes in the hydrological cycle.