bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Evaluation of the Effect of Short-Term Oral Vitamin D Supplementation on Peripheral Neuropathy in Type 2 Diabetes Mellitus
Authors: Shehab D. , Al-Jarallah Khaled , Abdella Nabila , Mojiminiyi Olusegun A. , Al Mohamedy Hisham
Published: February 2015

Objective: We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. Materials and Methods: This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy (DPN) and vitamin D [25(OH)D] deficiency. Patients were sequentially assigned to a treatment group (n = 57) and a placebo group (n = 55). DPN was assessed using a neuropathy symptom score (NSS), a neuropathy disability score (NDS) and a nerve conduction study (NCS). Vitamin D status was determined by measuring the serum total 25(OH)D concentration. Patients received either oral vitamin D3 capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. Results: Serum 25(OH)D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group (32.8 ± 23.7 vs. 1.1 ± 3.6, p < 0.0001). Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group (-1.49 ± 1.37 vs. -0.20 ± 0.59, p < 0.001). No improvement was observed for NDS and NCS between the 2 groups after treatment. Conclusion: Short-term oral vitamin D3 supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes.
Exome Sequencing Identification of EP300 Mutation in a Proband with Coloboma and Imperforate Anus: Possible Expansion of the Phenotypic Spectrum of Rubinstein-Taybi Syndrome
Authors: Masuda Koji , Akiyama Kazuhiro , Arakawa Michiko , Nishi Eriko , Kitazawa Noritaka , Higuchi Tsukasa , Katou Yuki , Shirahige Katsuhiko , Izumi Kosuke
Published: March 2015

Rubinstein-Taybi syndrome (RSTS) is a multisystem developmental disorder characterized by facial dysmorphisms, broad thumbs and halluces, growth retardation, and intellectual disability. In about 8% of RSTS cases, mutations are found in EP300. Previously, the EP300 mutation has been shown to cause the highly variable RSTS phenotype. Using exome sequencing, we identified a de novo EP300 frameshift mutation in a proband with coloboma, facial asymmetry and imperforate anus with minimal RSTS features. Previous molecular studies have demonstrated the importance of EP300 in oculogenesis, supporting the possibility that EP300 mutation may cause ocular coloboma. Since a wide phenotypic spectrum is well known in EP300-associated RSTS cases, the atypical phenotype identified in our proband may be an example of rare manifestations of RSTS.
Subclinical atherosclerosis in patients with rheumatoid arthritis
Authors: Ambrosino Pasquale , Lupoli Roberta , Di Minno Alessandro , Tasso Marco , Peluso Rosario , Di Minno Matteo Nicola Dario
Published: February 2015

We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of rheumatoid arthritis (RA) on common carotid artery intima-media thickness (CCAIMT) and on the prevalence of carotid plaques. Studies evaluating the relationship between RA and markers of cardiovascular (CV) risk (CCA-IMT and prevalence of carotid plaques) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. A total of 59 studies (4,317 RA patients and 3,606 controls) were included in the final analysis, 51 studies with data on CCA-IMT (52 data-sets on 3,600 RA patients and 3,020 controls) and 35 studies reporting on the prevalence of carotid plaques (2,859 RA patients and 2,303 controls). As compared to controls, RA patients showed a higher CCA-IMT (mean difference [MD]: 0.10 mm; 95 % confidence interval [CI]: 0.07, 0.12; p < 0.00001), and an increased prevalence of carotid plaques (odds ratio [OR]: 3.61; 95 %CI: 2.65, 4.93; p< 0.00001). Interestingly, when analysing studies on early RA, the difference in CCAIMT among RA patients and controls was even higher (MD: 0.21 mm; 95 %CI: 0.06, 0.35; p=0.006), and difference in the prevalence of carotid plaques was entirely confirmed (OR: 3.57; 95 %CI: 1.69, 7.51; p=0.0008). Meta-regression models showed that male gender and a more severe inflammatory status [as expressed by disease activity score in 28 joints (DAS28), C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR)] significantly impacted on CCA-IMT. In conclusion, RA appears significantly associated with subclinical atherosclerosis and CV risk. These findings can be useful to plan adequate prevention strategies and therapeutic approaches.
Role of High-Resolution Image Integration to Visualize Left Phrenic Nerve and Coronary Arteries During Epicardial Ventricular Tachycardia Ablation
Authors: Yamashita Seigo , Sacher Frédéric , Mahida Saagar , Berte Benjamin , Lim Han S. , Komatsu Yuki , Amraoui Sana , Denis Arnaud , Derval Nicolas , Laurent François , Montaudon Michel , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre , Cochet Hubert
Published: February 2015

Background—

Epicardial ventricular tachycardia (VT) ablation is associated with risks of coronary artery (CA) and phrenic nerve (PN) injury. We investigated the role of multidetector computed tomography in visualizing CA and PN during VT ablation.

Methods and Results—

Ninety-five consecutive patients (86 men; age, 57±15) with VT underwent cardiac multidetector computed tomography. The PN detection rate and anatomic variability were analyzed. In 49 patients undergoing epicardial mapping, real-time multidetector computed tomographic integration was used to display CAs/PN locations in 3-dimensional mapping systems. Elimination of local abnormal ventricular activities (LAVAs) was used as ablation end point. The distribution of CAs/PN with respect to LAVA was analyzed and compared between VT etiologies. Multidetector computed tomography detected PN in 81 patients (85%). Epicardial LAVAs were observed in 44 of 49 patients (15 ischemic cardiomyopathy, 15 nonischemic cardiomyopathy, and 14 arrhythmogenic right ventricular cardiomyopathy) with a mean of 35±37 LAVA points/patient. LAVAs were located within 1 cm from CAs and PN in 35 (80%) and 18 (37%) patients, respectively. The prevalence of LAVA adjacent to CAs was higher in nonischemic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy than in ischemic cardiomyopathy (100% versus 86% versus 53%;
P
<0.01). The prevalence of LAVAs adjacent to PN was higher in nonischemic cardiomyopathy than in ischemic cardiomyopathy (93% versus 27%;
P
<0.001). Epicardial ablation was performed in 37 patients (76%). Epicardial LAVAs could not be eliminated because of the proximity to CAs or PN in 8 patients (18%).

Conclusions—

The epicardial electrophysiological VT substrate is often close to CAs and PN in patients with nonischemic cardiomyopathy. High-resolution image integration is potentially useful to minimize risks of PN and CA injury during epicardial VT ablation.
Catheter-Based Renal Denervation Reduces Atrial Nerve Sprouting and Complexity of Atrial Fibrillation in Goats
Authors: Linz Dominik , van Hunnik Arne , Hohl Mathias , Mahfoud Felix , Wolf Milan , Neuberger Hans-Ruprecht , Casadei Barbara , Reilly Svetlana N. , Verheule Sander , Böhm Michael , Schotten Ulrich
Published: February 2015

Background—

Atrial fibrillation (AF) leads to structural and neural remodeling in the atrium, which enhances AF complexity and perpetuation. Renal denervation (RDN) can reduce renal and whole-body sympathetic activity. Aim of this study was to determine the effect of sympathetic nervous system modulation by RDN on atrial arrhythmogenesis.

Methods and Result—

Eighteen goats were instrumented with an atrial endocardial pacemaker lead and a burst pacemaker. Percutaneous catheter-based RDN was performed in 8 goats (RDN-AF). Ten goats undergoing a sham procedure served as control (SHAM-AF). AF was induced and maintained by burst pacing for 6 weeks. High-resolution mapping was used to record epicardial conduction patterns of the right and left atrium. RDN reduced tyrosine hydroxylase-positive sympathetic nerve staining and resulted in lower transcardiac norepinephrine levels. This was associated with reduced expression of nerve growth factor-β, indicating less atrial nerve sprouting. Atrial endomysial fibrosis content was lower and myocyte diameter was smaller in RDN-AF. Median conduction velocity was higher (75±9 versus 65±10 cm/s,
P
=0.02), and AF cycle length was shorter in RDN-AF compared with SHAM-AF. Left atrial AF complexity (4.8±0.8 fibrillation waves/AF cycle length versus 8.5±0.8 waves/AF cycle length,
P
=0.001) and incidence of breakthroughs (2.0±0.3 versus 4.3±0.5 waves/AF cycle length,
P
=0.059) were lower in RDN-AF compared with SHAM-AF. Blood pressure was normal and not significantly different between the groups.

Conclusions—

RDN reduces atrial sympathetic nerve sprouting, structural alterations, and AF complexity in goats with persistent AF, independent of changes in blood pressure.
Epicardial Catheter Ablation of Ventricular Tachycardia in No Entry Left Ventricle
Authors: Soejima Kyoko , Nogami Akihiko , Sekiguchi Yukio , Harada Tomoo , Satomi Kazuhiro , Hirose Takeshi , Ueda Akiko , Miwa Yousuke , Sato Toshiaki , Nishio Satoru , Shirai Yasuhiro , Kowase Shinya , Murakoshi Nobuyuki , Kunugi Shinobu , Murata Hiroshige , Nitta Takashi , Aonuma Kazutaka , Yoshino Hideaki
Published: February 2015

Background—

In patients with mechanical aortic and mitral valves and left ventricular tachycardia, catheter ablation may be prevented by limited access to the left ventricle.

Methods and Results—

In our series of 6 patients, 2 patients underwent direct surgical ablation and 4 underwent epicardial catheter ablation via a pericardial window. All patients had abnormal low voltage areas with fractionated or delayed isolated potentials on the apical epicardium. Most of the ventricular tachycardias were targeted by pace mapping. Sites with a good pace match or abnormal electrograms were ablated using an irrigated radiofrequency ablation catheter. A microscopic pathological evaluation of the resected tissue from 2 of the open-heart ablation patients revealed dense fibrosis on the epicardium compared with the endocardium, supporting the feasibility of an epicardial ablation for the ventricular tachycardia.

Conclusions—

Epicardial catheter ablation of ventricular tachycardia is a potentially useful therapy in patients who have mechanical aortic and mitral valves.
Quantification of the Transmural Dynamics of Atrial Fibrillation by Simultaneous Endocardial and Epicardial Optical Mapping in an Acute Sheep Model
Authors: Gutbrod Sarah R. , Walton Richard , Gilbert Stephen , Meillet Valentin , Jaïs Pierre , Hocini Mélèze , Haïssaguerre Michel , Dubois Rémi , Bernus Olivier , Efimov Igor R.
Published: February 2015

Background—

Therapy strategies for atrial fibrillation based on electric characterization are becoming viable personalized medicine approaches to treat a notoriously difficult disease. In light of these approaches that rely on high-density surface mapping, this study aims to evaluate the presence of 3-dimensional electric substrate variations within the transmural wall during acute episodes of atrial fibrillation.

Methods and Results—

Optical signals were simultaneously acquired from the epicardial and endocardial tissue during acute fibrillation in ovine isolated left atria. Dominant frequency, regularity index, propagation angles, and phase dynamics were assessed and correlated across imaging planes to gauge the synchrony of the activation patterns compared with paced rhythms. Static frequency parameters were well correlated spatially between the endocardium and the epicardium (dominant frequency, 0.79±0.06 and regularity index, 0.93±0.009). However, dynamic tracking of propagation vectors and phase singularity trajectories revealed discordant activity across the transmural wall. The absolute value of the difference in the number, spatial stability, and temporal stability of phase singularities between the epicardial and the endocardial planes was significantly >0 with a median difference of 1.0, 9.27%, and 19.75%, respectively. The number of wavefronts with respect to time was significantly less correlated and the difference in propagation angle was significantly larger in fibrillation compared with paced rhythms.

Conclusions—

Atrial fibrillation substrates are dynamic 3-dimensional structures with a range of discordance between the epicardial and the endocardial tissue. The results of this study suggest that transmural propagation may play a role in atrial fibrillation maintenance mechanisms.
Three-Year Outcomes Associated With Embolic Protection in Saphenous Vein Graft Intervention
Authors: Brennan J. Matthew , Al-Hejily Wesam , Dai David , Shaw Richard E. , Trilesskaya Marina , Rao Sunil V. , Brilakis Emmanouil S. , Anstrom Kevin J. , Messenger John C. , Peterson Eric D. , Douglas Pamela S. , Sketch Michael H.
Published: February 2015

Background—

Information is limited on contemporary use and outcomes of embolic protection devices (EPDs) in saphenous vein graft interventions.

Methods and Results—

We formed a longitudinal cohort (2005–2009; n=49 325) by linking National Cardiovascular Data Registry CathPCI Registry to Medicare claims to examine the association between EPD use and both procedural and long-term outcomes among seniors (65+ years), adjusting for clinical factors using propensity and instrumental variable methodologies. Prespecified high-risk subgroups included acute coronary syndrome and de novo or graft body lesions. EPDs were used in 21.2% of saphenous vein grafts (median age, 75; 23% women) and were more common in acute coronary syndrome (versus non–acute coronary syndrome; 22% versus 19%), de novo (versus restenotic; 22% versus 14%), and graft body lesions (versus aortic and distal anastomosis; 24% versus 20% versus 8%, respectively). EPDs were associated with a slightly higher incidence of procedural complications, including no reflow (3.9% versus 2.8%;
P
<0.001), vessel dissection (1.3% versus 1.1%;
P
=0.05), perforation (0.7% versus 0.4%;
P
=0.001), and periprocedural myocardial infarction (2.8% versus 1.8%;
P
<0.001). By 3 years, death, myocardial infarction, and repeat revascularization occurred in 25%, 15%, and 30% of cases, respectively. EPD use was associated with a similar adjusted risk of death (propensity score–matched hazard ratio, 0.96; 95% confidence interval, 0.91–1.02), myocardial infarction (propensity score–matched hazard ratio, 1.00; 95% confidence interval, 0.93–1.09), and repeat revascularization (propensity score–matched hazard ratio, 1.02; 95% confidence interval, 0.96–1.08) in the overall cohort and high-risk subgroups.

Conclusions—

In this contemporary cohort, EPDs were used more commonly among patients with high-risk clinical indications, yet there was no evidence of improved acute- or long-term outcomes. Further prospective studies are needed to support routine EPD use.
Doppler-Derived Intracoronary Physiology Indices Predict the Occurrence of Microvascular Injury and Microvascular Perfusion Deficits After Angiographically Successful Primary Percutaneous Coronary Intervention
Authors: Teunissen Paul F.A. , de Waard Guus A. , Hollander Maurits R. , Robbers Lourens F.H.J. , Danad Ibrahim , Biesbroek P. Stefan , Amier Raquel P. , Echavarría-Pinto Mauro , Quirós Alicia , Broyd Christopher , Heymans Martijn W. , Nijveldt Robin , Lammertsma Adriaan A. , Raijmakers Pieter G. , Allaart Cornelis P. , Lemkes Jorrit S. , Appelman Yolande E. , Marques Koen M. , Bronzwaer Jean G.F. , Horrevoets Anton J.G. , van Rossum Albert C. , Escaned Javier , Beek Aernout M. , Knaapen Paul , van Royen Niels
Published: February 2015

Background—

A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET).

Methods and Results—

Sixty patients with ST-segment–elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure–flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure–velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H
2
15
O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H
2
15
O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure–velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second;
P
=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg;
P
=0.015). Multivariable analysis showed HMR to independently predict MVI (
P
=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second;
P
=0.04).

Conclusions—

Doppler-flow–derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR3164.
Percutaneous Fetal Cardiac Catheterization Technique for Stenting the Foramen Ovale in a Midgestation Lamb Model
Authors: Edwards Andrew , Veldman Alex , Nitsos Ilias , Chan Yuen , Brew Nadine , Teoh Mark , Menahem Samuel , Schranz Dietmar , Wong Flora Y.
Published: February 2015

Background—

Intact or highly restricted intra-atrial septum can be reliably diagnosed in the human fetus as early as 22 to 24 weeks of gestation. Fetal interventions targeting the atrial septum have used a direct approach through the atrial wall. Here, we report stenting of the foramen ovale with a large, open-cell stent via percutaneous access through the fetal hepatic vein in a sheep model.

Methods and Results—

In 5 fetal sheep of 109 to 111 days of gestation (term, 147 days), the fetal hepatic vein was punctured percutaneously under ultrasound guidance and a 13.3-cm 14-gauge intravenous catheter was inserted. After catheterization of the inferior vena cava, right atrium, foramen ovale, and left atrium with a guidewire and 1.8F to 2.6F tapered catheter, a self-expandable, 8×12-mm flexible open-cell stent was positioned in an unrestricted foramen ovale. Flow and fetal well-being were documented for 45 minutes after the procedure. Access to the left atrium was achieved in all 5 animals and all survived. In 4 animals, the stent was successfully positioned in the foramen ovale. One fetus was born at term and euthanized on day 3: postmortem examination confirmed the patency of the stent. The other 3 fetuses were well after being monitored by ultrasound for 45 minutes. In 1 animal, the stent dislodged immediately after release obstructing the mitral valve. This fetus developed ascites and was euthanized after 4 days.

Conclusions—

It is feasible to safely advance a large diameter, self-expandable, open-cell design stent into the fetal atrial septum via a percutaneous access route through the fetal hepatic vein.
Sex Is Associated With Differences in Individual Trajectories of Change in Social Health After Implantable Cardioverter-Defibrillator
Authors: Lauck Sandra B. , Sawatzky Richard , Johnson Joy L. , Humphries Karin , Bennett Matthew T. , Chakrabarti Santabhanu , Kerr Charles R. , Tung Stanley , Yeung-Lai-Wah John A. , Ratner Pamela A.
Published: February 2015

Background—

Social health is a dimension of quality of life, and refers to people’s involvement in, and satisfaction with social roles, responsibilities, and activities. The implantable cardioverter-defibrillator is associated with changes in overall quality of life, but little is known about sex differences in individual trajectories of change in social health.

Methods and Results—

We prospectively measured changes in 3 subscales of the SF-36v2 generic health questionnaire (role physical, role emotional, and social functioning), 2 Patient-Reported Outcomes Measurement Information System short forms (satisfaction with participation in social roles and satisfaction with participation in discretionary social activities), and the Florida Patient Acceptance Survey before and at 1, 2, and 6 months after implantation. Individual growth models of temporal change were estimated. The scores of the 6 indicators improved with time. The unconditional model demonstrated significant (fixed effects:
P
<0.05; covariance parameters:
P
<0.10) residual variability in the individual trajectories. In the conditional model, men and women differed significantly in their rates of change in the scores of 3 of the 6 measures. Although men’s mean scores exceeded women’s mean scores on all indicators at baseline (range of relative mean difference: 11.0% to 17.8%), the rate of women’s change resulted in a reversal in relative standing at 6 months after implantation, with the mean scores of women exceeding the men’s by 4.5% to 5.6%.

Conclusions—

Men and women differed in their trajectories of change in social health, both in terms of their starting points (ie, baseline scores) and their rates of change.
Characteristics and Outcomes of Women Veterans Undergoing Cardiac Catheterization in the Veterans Affairs Healthcare System
Authors: Davis Melinda B. , Maddox Thomas M. , Langner Paula , Plomondon Mary E. , Rumsfeld John S. , Duvernoy Claire S.
Published: February 2015

Background—

The number of women veterans is increasing, yet little is known about their cardiovascular risk factors, coronary anatomy, cardiac treatments, and outcomes after cardiac catheterization. Prior studies have shown that nonveteran women have more risk factors, receive less aggressive treatment, and have worse outcomes, despite having less obstructive coronary artery disease than men. Whether these differences exist among women veterans in the veterans affairs healthcare system is unknown.

Methods and Results—

Data on 85 936 veterans (3181 women) undergoing initial cardiac catheterization between October 1, 2007, and September 30, 2012, were examined using the national veterans affairs Clinical Assessment Reporting and Tracking (CART) Program. Sex differences in demographics, indications, coronary anatomy, cardiac treatments, and outcomes were analyzed. Women veterans were younger (56.9 versus 63.0 years,
P
<0.0001) with fewer traditional cardiovascular risk factors, but with more obesity, depression, and posttraumatic stress disorder than men. Women had lower rates of obstructive coronary artery disease than men (22.6% versus 53.3%). Rates of procedural complications were similar in both genders. Adjusted outcomes at 1 year showed women had lower mortality (hazard ratio, 0.74; confidence interval, 0.60–0.92) and less all-cause rehospitalization (hazard ratio, 0.87; confidence interval, 0.82–0.93), but no difference in rates of unplanned percutaneous coronary intervention.

Conclusions—

Women veterans undergoing catheterization are younger, have more obesity, depression, and posttraumatic stress disorder, less obstructive coronary artery disease, and similar long-term outcomes, compared with men. These findings suggest a significant portion of women veterans may have chest pain not attributable to obstructive coronary artery disease. Further research into possible causes, such as endothelial dysfunction or concurrent psychological comorbidities, is needed.
ADAMTS-7 Inhibits Re-endothelialization of Injured Arteries and Promotes Vascular Remodeling Through Cleavage of Thrombospondin-1
Authors: Kessler Thorsten , Zhang Lu , Liu Ziyi , Yin Xiaoke , Huang Yaqian , Wang Yingbao , Fu Yi , Mayr Manuel , Ge Qing , Xu Qingbo , Zhu Yi , Wang Xian ,   German Mouse Clinic Consortium, Schmidt Kjestine , de Wit Cor , Erdmann Jeanette , Schunkert Heribert , Aherrahrou Zouhair , Kong Wei
Published: February 2015

Background—

ADAMTS-7, a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, was recently identified to be significantly associated genomewide with coronary artery disease. However, the mechanisms that link ADAMTS-7 and coronary artery disease risk remain elusive. We have previously demonstrated that ADAMTS-7 promotes vascular smooth muscle cell migration and postinjury neointima formation via degradation of a matrix protein cartilage oligomeric matrix protein. Because delayed endothelium repair renders neointima and atherosclerosis plaque formation after vessel injury, we examined whether ADAMTS-7 also inhibits re-endothelialization.

Methods and Results—

Wire injury of the carotid artery and Evans blue staining were performed in
Adamts7
–/–
and wild-type mice. Adamts-7 deficiency greatly promoted re-endothelialization at 3, 5, and 7 days after injury. Consequently, Adamts-7 deficiency substantially ameliorated neointima formation in mice at days 14 and 28 after injury in comparison with the wild type. In vitro studies further indicated that ADAMTS-7 inhibited both endothelial cell proliferation and migration. Surprisingly, cartilage oligomeric matrix protein deficiency did not affect endothelial cell proliferation/migration and re-endothelialization in mice. In a further examination of other potential vascular substrates of ADAMTS-7, a label-free liquid chromatography-tandem mass spectrometry secretome analysis revealed thrombospondin-1 as a potential ADAMTS-7 target. The subsequent studies showed that ADAMTS-7 was directly associated with thrombospondin-1 by its C terminus and degraded thrombospondin-1 in vivo and in vitro. The inhibitory effect of ADAMTS-7 on postinjury endothelium recovery was circumvented in
Tsp1
–/–
mice.

Conclusions—

Our study revealed a novel mechanism by which ADAMTS-7 affects neointima formation. Thus, ADAMTS-7 is a promising treatment target for postinjury vascular intima hyperplasia.
Brainstem Hypoxia Contributes to the Development of Hypertension in the Spontaneously Hypertensive Rat
Authors: Marina Nephtali , Ang Richard , Machhada Asif , Kasymov Vitaliy , Karagiannis Anastassios , Hosford Patrick S. , Mosienko Valentina , Teschemacher Anja G. , Vihko Pirkko , Paton Julian F. R. , Kasparov Sergey , Gourine Alexander V.
Published: February 2015

Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O
2
sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal P
O
2
in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower P
O
2
of brainstem parenchyma may be associated with higher levels of ambient ATP and
l
-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure.
Design, Characterization, and First-In-Human Study of the Vascular Actions of a Novel Biased Apelin Receptor Agonist
Authors: Brame Aimee L. , Maguire Janet J. , Yang Peiran , Dyson Alex , Torella Rubben , Cheriyan Joseph , Singer Mervyn , Glen Robert C. , Wilkinson Ian B. , Davenport Anthony P.
Published: February 2015

[Pyr
1
]apelin-13 is an endogenous vasodilator and inotrope but is downregulated in pulmonary hypertension and heart failure, making the apelin receptor an attractive therapeutic target. Agonists acting at the same G-protein–coupled receptor can be engineered to stabilize different conformational states and function as biased ligands, selectively stimulating either G-protein or β-arrestin pathways. We used molecular dynamics simulations of apelin/receptor interactions to design cyclic analogues and identified MM07 as a biased agonist. In β-arrestin and internalization assays (G-protein–independent), MM07 was 2 orders of magnitude less potent than [Pyr
1
]apelin-13. In a G-protein–dependent saphenous vein contraction assay, both peptides had comparable potency (pD
2
:[Pyr
1
]apelin-13 9.93±0.24; MM07 9.54±0.42) and maximum responses with a resulting bias for MM07 of ≈350- to 1300-fold for the G-protein pathway. In rats, systemic infusions of MM07 (10-100nmol) caused a dose-dependent increase in cardiac output that was significantly greater than the response to [Pyr
1
]apelin-13. Similarly, in human volunteers, MM07 produced a significant dose-dependent increase in forearm blood flow with a maximum dilatation double that is seen with [Pyr
1
]apelin-13. Additionally, repeated doses of MM07 produced reproducible increases in forearm blood flow. These responses are consistent with a more efficacious action of the biased agonist. In human hand vein, both peptides reversed an established norepinephrine constrictor response and significantly increased venous flow. Our results suggest that MM07 acting as a biased agonist at the apelin receptor can preferentially stimulate the G-protein pathway, which could translate to improved efficacy in the clinic by selectively stimulating vasodilatation and inotropic actions but avoiding activating detrimental β-arrestin–dependent pathways.
Implantable Cardioverter‐Defibrillator Therapy in Patients With Ventricular Fibrillation out of Hospital Cardiac Arrest Secondary to Acute Coronary Syndrome
Authors: Madhavan Malini , Friedman Paul A. , Lennon Ryan J. , Prasad Abhiram , White Roger D. , Sriram Chenni S. , Gulati Rajiv , Gersh Bernard J.
Published: February 2015

Background

Survivors of ventricular fibrillation out of hospital cardiac arrest (
VF
‐
OHCA
) due to a potentially reversible cause such as acute myocardial infarction (MI) or ischemia are considered to be at low risk of recurrent arrhythmia. Implantable cardioverter defibrillators (
ICD
) are not routinely recommended in such patients. However, the outcome of these patients in the era of rapid coronary revascularization and
ICD
therapy is not known.

Methods and Results

We examined the outcome of 114 consecutive survivors of
VF OHCA
due to acute
MI
or ischemia in Olmsted County,
MN
from 1990 to 2011. An
ICD
was implanted in 45/114 patients.
ICD
recipients had lower
EF
[median (
IQR
) 38 (26 to 54) versus 48 (35 to 58) %,
P
=0.04]. During a median (
IQR
) follow‐up of 9.9 (4.4 to 14.6) years,
ICD
implantation was associated with reduced cardiac mortality (
HR
0.24 [0.07 to 0.88],
P
=0.031) and a trend towards reduced all‐cause mortality (
HR
0.56 [0.30 to 1.02],
P
=0.059) after adjusting for the first principal component. One or more appropriate
ICD
therapies were delivered in 19/45, with half of the patients receiving therapy within 1 year. Patients with
EF
≤35% at discharge continued to be at long‐term risk for
ICD
therapy compared with those with
EF
>35% who were at increased risk predominantly in the first 8 months.
EF
and revascularization were not significantly associated with
ICD
therapy in the multivariable analysis.

Conclusions

Patients with
VF
‐
OHCA
in the setting of acute
MI
or myocardial ischemia remain at high risk of recurrent ventricular arrhythmias, particularly if
EF
≤35%. This suggests that
ICD
implantation may be reasonable if
EF
≤35%.
Naturalizing Sharīʿa: Foundationalist Ambiguities in Modern Islamic Apologetics
Authors: March Andrew F.
Published: February 2015

This essay discusses an important feature of much modern Islamic writing on law, politics and morality. The feature in question is the claim that Islamic law and human nature (fiṭra) are in perfect harmony, that Islam is the “natural religion” (dīn al-fiṭra), and thus that the demands of Islamic law are easy and painless for ordinary human moral capacities. My discussion proceeds through a close reading of the Moroccan independence leader and religious scholar ʿAllāl al-Fāsī (d. 1974). I discuss the ambiguities within Fāsī’s theory and suggest that the natural religion doctrine might be better understood less as a reduction of Islamic law to “natural law” and more as an apologetic effort to defend the realism and feasibility of Islamic law. In the hands of reformers like Fāsī, this project is beset with unresolved ambiguities around the constraining quality of revealed law in practice and the moral validity of non-Islamic political and ethical systems.
The International Law Association’s Legal Principles on Climate Change and Climate Liability Under Public International Law
Authors: Schwarte Christoph , Frank Will
Published: February 2015

In April 2014, the International Law Association (ila) adopted draft articles on the existing legal principles relating to climate change. Developed by leading legal scholars, these draft articles with commentaries formulate potential guidance to states in their joint efforts to tackle climate change and negotiate a new international agreement. The ila finds that the general principles of public international and international environmental law apply to climate change. States are under a ‘due diligence’ obligation to ensure that ghg emissions under their jurisdiction or control do not cause damage in other states or areas beyond national jurisdiction. States that violate the duty of prevention can be held liable. However, there are different obligations and rights for industrialised and developing countries. The ila’s Legal Principles Relating to Climate Change clarify and develop the relevant criteria. Overall, they mark a paradigm shift in favour of ‘victim states’ that are particularly exposed to the negative effects of climate change. As a result, the traditional beneficiaries of international charity have become creditors with legal rights.
Mediated versus Cumulative Environmental Damage and the International Law Association’s Legal Principles on Climate Change
Authors: Zahar Alexander
Published: February 2015

The content of international climate change law is being subjected to investigation and critical analysis after twenty years of international policy on climate change. The ila’s Legal Principles Relating to Climate Change are a contribution to this discussion. The ila has put forth a ‘principle of prevention’ as being not just relevant to, but at the very foundation of, climate change law—in particular mitigation law. In their article in this issue of the journal, Schwarte and Frank focus on the ila’s reliance on the prevention principle, endorsing the ila’s approach in this respect. However, as I argue in this comment, the principle of prevention is neither applicable nor of relevance to the problem of climate change, and thus cannot be an element of climate change mitigation law. I also question the ila’s utilization of another legal principle—the precautionary principle—as a basis for the development of an international law of adaptation.
The Role of the unfccc Regime in Ensuring Effective Adaptation in Developing Countries: Lessons from Bangladesh
Authors: Doelle Meinhard , Evans Steven , Puthucherril Tony George
Published: February 2015

The goal of this article is to explore climate change adaptation efforts in Bangladesh within the context of the unfccc’s current efforts to assist developing countries such as Bangladesh with adaptation, and to offer recommendations for negotiators of the future climate regime.
Taxonomy of 'Euconnus complex'. Part III. Morphology of Euconnus subgenus Napochus and revision of the Australian species (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: February 2015

Morphological structures of the type species of Euconnus (Napochus) are described and illustrated, and compared with those of Euconnus s. str. Napochus is maintained as a subgenus of Euconnus, and its revised diagnosis is given. Australian species of Napochus are revised: E. palmwoodianus Franz and E. pisoniae Franz are redescribed, and E. setiphallus sp. n., E. yadhaigana sp. n., E. microlaminatus sp. n, E. feeneyi sp. n. (with a subspecies E. feeneyi parallelilaminatus ssp. n.) are described. An unusual variability in body size and proportions of body parts found in E. feeneyi is analyzed and discussed.
New species of Omalodes and redefinition of the tribe Omalodini (Coleoptera: Histeridae: Histerinae)
Authors: LEIVAS FERNANDO W. T. , DEGALLIER NICOLAS , ALMEIDA LÚCIA M.
Published: February 2015

A new species of Omalodini, Omalodes atacamanus sp. nov., is described from Chile. A redefinition of Omalodini is proposed and an identification key to the genera is provided. The new species can be distinguished from other species of Omalodes mainly by all tibiae having a row of setae on outer submarginal region. Omalodini sensu nov. is herein restricted to a lineage of Ebonius Lewis, 1885 and Omalodes Dejean, 1833. The tribe has known distribution across Latin America with some species reaching the southern USA.
Clouds Over Half the Sky
Authors: Mohanty Manoranjan
Published: February 2015

This article addresses the question of why despite the enormous success achieved by China in economic growth there are significant indicators showing relatively adverse life situations for women in many respects. A falling proportion of women in the population, unfavourable employment situation, disparity in wages, inadequate representation of women in political leadership are some of the indicators of the negative fallout of the Chinese growth story even as women too have benefited from the substantial improvement of Chinese people’s livelihood conditions during the recent decades. Based on field visits to Wuxi over a thirty-year period and using macro data we argue that the Chinese experience raises serious questions about the pattern of economic growth that has been adopted by the Chinese leadership and advanced globally in recent years.
Weathering unrest
Authors: Yeeles Adam
Published: February 2015

Over the last several years research has examined anew the potential for climate change to induce political conflict and potentiate social unrest. Several explanations for the relationship between weather and social unrest have been proposed, including the idea that temperature, acting through a physiological response mechanism, gives rise to collective aggression. This proposition first appeared in the aftermath of the 1960s US riots, which occurred primarily in the heat of summer, and has re-emerged within the contemporary literature on conflict and climate, in addition to explanations rooted in political economic processes. Building on both bodies of work, this article utilizes a case-crossover time-series design to explore the relationship between meteorological factors derived from high resolution spatial data of temperature and precipitation and social disturbances occurring in 50 major cities in Africa and Asia between 1960 and 2006. Poisson regression and generalized additive modeling are utilized to model linear and non-linear effects, respectively. A significant, but qualified, association between heat and urban social disturbances is found. The general relationship is non-linear, with peak levels of unrest occurring in the upper 20s (°C). The relationship between temperature and social unrest within individual cities is linear. In addition, there are differential effects of heat on lethal versus non-lethal episodes of unrest. The non-linear response to temperature is much more pronounced among lethal events than it is among non-lethal episodes. The conclusion taken from this research is that heat is associated with urban social conflict, but generally does not trigger episodes and instead acts to supplement aggression while other factors govern the primary timing of social unrest.
Effective cryopreservation of golden Syrian hamster embryos by open pulled straw vitrification
Authors: Fan Z , Meng Q , Bunch TD , White KL , Wang Z
Published: February 2015

Golden Syrian hamster embryos are difficult to cryopreserve due to their high sensitivity to cryoprotectants and in vitro handling. The objective of this study is to develop a robust open pulled straw (OPS) vitrification technique for cryopreserving hamster embryos at various developmental stages. We first systematically tested the concentrations of cryoprotectants and the exposure times of two-cell embryos to various vitrification solutions. We identified pretreatment of two-cell embryos with 10% (v/v) ethylene glycol (EG) + 10% (v/v) dimethylsulfoxide (DMSO) for 30 s followed by exposure in the vitrification solution, EDFS30 (containing 15% EG + 15% DMSO), for 30 s before plunging into liquid nitrogen (two-step exposure method) as the optimal OPS vitrification protocol. We then investigated the resourcefulness of this protocol for vitrifying hamster embryos at different developmental stages. The results showed that high blastocyst rates from embryos vitrified at two-cell, four-cell, eight-cell, or morula stage (62%, 78%, 80%, or 72%, respectively), but not those verified at pronuclear (0%) or blastocyst stage (24%; P < 0.05), were achieved by this protocol. When embryos vitrified at the two-cell stage were recovered and then directly transferred to recipient females, 29% of them developed to term, a development rate not significantly different ( P > 0.05) from the 40% birth rate of the unvitrified controls. In conclusion, we have developed an effective two-step OPS vitrification protocol for hamster embryos.
Local catholicity: The bodies and places where Jesus is (found)
Authors: Inscore Essick John , Medley Mark S.
Published: February 2015

Inspired by Stanley Hauerwas and building on the lives and writings of Wendell Berry and William Carlos Williams, this article argues that locality and catholicity incorporate one another and must account for one another if Jesus is to be made visible in the world. A locally catholic vision of the church emphasizes the visible, gathered church as a “placed people,” which holds in appropriate tension the local and the catholic without retreating to isolated places or escaping to a disembodied universal conception of the church. Intercessory prayer and the fellowship hall windows of Highland Baptist Church, Louisville, Kentucky are offered as two examples of how local catholicity is attentive to the faith lived locally and to the broader Christian tradition.
Why tolerance and voluntaryism are bad ideas: Stanley Hauerwas’s summons to Baptists and other “enlightened” Christians
Authors: Wood Ralph C.
Published: February 2015

I here argue that, among Stanley Hauerwas’ many other salutary influences on Baptists, not the least of them is his pointing us beyond tolerance and voluntaryism as Christian virtues. I show how he has helped us discern that the church will be tolerated by an increasingly dominating nation-state only if we Christians behave as the state demands, especially in moral matters, and that we must thus learn how to live in a non-tolerant manner. I also argue that Hauerwas’ case against a strictly voluntarist idea of Christian faith helps us to reclaim the Church’s original understanding of baptism as the act whereby, even among us who advocate believers’ baptism, we are incorporated into the Body of Christ. It is not something we voluntarily choose but rather the gift that we non-voluntarily receive.
Set free from freedom: Stanley Hauerwas among Baptist politics
Authors: Newman Elizabeth
Published: February 2015

Our dominant political culture understands freedom primarily as the individual’s right to choose. Such freedom, typically described as purely procedural, elevates the good of the nation state over that of the church. In fact, such freedom makes the church invisible since the only imaginable politics is that of the state. Following Stanley Hauerwas, I argue that seeing the church itself as a polis, a politics, enables Baptists and other Christians to practice an alternative freedom—one grounded in an ecclesial way of life made possible by the Triune God. In conclusion, I suggest that saying the ancient creeds is one way to remember more fully this alternative freedom.
Detection of fiber effects on skin health of the human foot
Authors: Laing Raechel M , Wilson Cheryl A , Dunn Linda A , Niven Brian E
Published: February 2015

The objective of this investigation was to better understand the effects of foot coverings differing in fiber content on the health of the skin on the foot. A longitudinal controlled parallel design wear trial was carried out over 8 weeks: four sock types differing in fiber/yarn closely matched for fiber diameter (100% acrylic, 100% wool (24.5 µm), 100% cotton, 100% wool (20.5 µm)), manufactured such that only fiber type differed, were worn by 16 men. The effects on transepidermal water loss, stratum corneum hydration, pH, skin temperature were examined. Variability in effects among the participants was evident. Each person was his own control, with change expressed as a percentage from baseline. Fabric structural properties and selected performance properties were measured on fabrics of the same fiber/structure as of the socks. Improvement in skin health at the heel, in particular, was evident. Wool socks were associated with more cases of improved skin health (e.g. reduced percentage changes in transepidermal water loss and increased stratum corneum hydration). Results from two indicators of skin health considered together provided stronger evidence of effects than one alone.
Improving Research Participant Ethics
Authors: Barber Larissa K. , Bailey Sarah F. , Bagsby Patricia G.
Published: February 2015

The undergraduate psychology curriculum often does not address guidelines for acceptable participant behavior. This two-part study tested the efficacy of a recently developed online learning module on ethical perceptions, knowledge, and behavior. In the preliminary quasi-experiment, students who viewed the module did not have higher end-of-semester ethical perceptions than a control group, although the experimental group demonstrated increased ethical knowledge and behavior than the control group. Study 2 replicated these findings with a pretest–posttest experimental design at another university. These findings lend support for the module increasing ethical knowledge and behavior, although not necessarily perceptions. However, exploratory analyses suggested that ethical perceptions appear to increase across all research participants through experience.