bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a Dialysis Access Coordinator on Preemptive Access Placement among Veterans: A Quality Improvement Initiative
Authors: Gale Randall C. , Kehoe Doreen , Lit Yiming Z. , Asch Steven M. , Kurella Tamura Manjula
Published: November 2016

Background and Objectives: Preemptive placement of permanent dialysis access is recommended in order to reduce the morbidity associated with central venous catheters. We assessed the effect of a dialysis access coordinator on preemptive access placement in veterans who are at high risk for end-stage renal disease (ESRD). Design, Setting, Participants, and Measurements: Pre-post evaluation of a dialysis access coordinator in the nephrology clinics of the Veterans Affairs Palo Alto. The access coordinator streamlined access referrals, prioritized surgical waiting lists and addressed patient barriers. We compared the frequency of preemptive access referral, surgery, and use for dialysis during the intervention period, July 1, 2013 to May 31, 2016, to a pre-intervention period, January 1, 2011 to December 31, 2013, among all patients with a predicted 1-year risk for ESRD ≥20%. Results: There were 156 patients in the historical cohort and 131 in the intervention cohort. The mean age was 69.9 ± 11.6 years and the mean estimated glomerular filtration rate was 14.5 ± 5.7 ml/min/1.73 m2. The intervention was associated with an 11.8% increase in access referral (p value = 0.03), and a 9.4% increase in completed access surgery (p value = 0.05). Increases in permanent access at the start of dialysis (15.2%), and functional permanent access at the start of dialysis (12.4%) did not reach statistical significance. Among patients who received access surgery, there was no significant difference in the prevalence of unused access. Conclusions: Implementation of an access coordinator was associated with a modest increase in preemptive access placement among patients who are at high risk for ESRD without increasing the prevalence of unused access.
Angiotensin-(1-7) Prevents Skeletal Muscle Atrophy Induced by Transforming Growth Factor Type Beta (TGF-β) via Mas Receptor Activation
Authors: Ábrigo Johanna , Simon Felipe , Cabrera Daniel , Cabello-Verrugio Claudio
Published: November 2016

Background: Transforming growth factor type beta 1 (TGF-β1) produces skeletal muscle atrophy. Angiotensin-(1-7) (Ang-(1-7)), through the Mas receptor, prevents the skeletal muscle atrophy induced by sepsis, immobilization, or angiotensin II (Ang-II). However, the effect of Ang-(1-7) on muscle wasting induced by TGF-β1 is unknown. Aim: To evaluate whether Ang-(1-7)/Mas receptor axis could prevent the skeletal muscle atrophy induced by TGF-β1. Methods: This study assessed the atrophic effect of TGF-β1 in C2C12 myotubes and mice in absence or presence of Ang-(1-7), and the receptor participation using A779, an antagonist of the Mas receptor. The levels of myosin heavy chain (MHC), polyubiquitination, and MuRF-1 were detected by western blot. Myotube diameter was also evaluated. In vivo analysis included the muscle strength, fibre diameter, MHC and MuRF-1 levels by western blot, and ROS levels by DCF probe detection. Results: The results showed that Ang-(1-7) prevented the increase in MuRF-1 and polyubiquitined protein levels, the decrease of MHC levels, the myotubes/fibre diameter diminution, and the increased production of reactive oxygen species (ROS) induced by TGF-β1. Utilizing A779 inhibited the anti-atrophic effect of Ang-(1-7). Conclusion: The preventive effect of Ang-(1-7) on skeletal muscle atrophy induced by TGF-β1 is produced through inhibition of ROS production and proteasomal degradation of MHC.
The Role Played by Adenosine in Modulating Reflex Sympathetic and Pressor Responses Evoked by Stimulation of TRPV1 in Muscle Afferents
Authors: Xing Jihong , Li Jianhua
Published: November 2016

Background/Aims: Activation of metabolite-sensitive transient receptor potential vanilloid type 1 (TRPV1) receptors (capsaicin receptors) in afferent nerves of the hindlimb muscles of rats increases renal sympathetic nerve activity (RSNA) and blood pressure (BP) via a reflex mechanism. The purpose of this study was to examine the role of adenosine in modulating the reflex RSNA and BP responses to stimulation of TRPV1. Methods: RSNA and BP responses were recorded in rats. Immunofluorescence and patch-clamp methods were employed to examine the receptor mechanisms responsible for the effects of adenosine. Results: Adenosine, in the concentration of 100 µM, injected into the femoral artery had an inhibitory effect on the reflex RSNA and BP responses induced by capsaicin. Likewise, arterial injection of adenosine analogue CGS21680 (A2A subtype receptor agonist, 10 µM and100 µM) also attenuated the reflex responses. In addition, co-existence of A2A and TRPV1 was observed in the dorsal root ganglion neurons. The prior application of adenosine or CGS21680 inhibited the magnitude of capsaicin-induced currents in muscle sensory neurons. Conclusion: Adenosine contributes to muscle afferent TRPV1-engaged reflex sympathetic and pressor responses. It is likely that TRPV1 response is impaired as the levels of adenosine are increased in the hindlimb muscles under diseased conditions.
Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro
Authors: Huang Quanfang , Liang Chunhong , Wei Ling , Nie Jinlan , Lu Shengjuan , Lu Chunyuan , Zhuo Lang , Lu Zhongpeng , Lin Xing
Published: November 2016

Background/Aims: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.
Possible Noninvasive Biomarker of Eosinophilic Esophagitis: Clinical and Experimental Evidence
Authors: Venkateshaiah Sathisha Upparahalli , Manohar Murli , Verma Alok K. , Blecker Uwe , Mishra Anil
Published: November 2016

Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients. We show that CD274 expression on blood eosinophils and blood mRNA expression levels increase in the blood of EoE patients and decrease following treatment. These observations are consistent with the esophageal eosinophilia of before and after treatment in both examined patients. These two clinical and experimental analysis reports provide the possibility that the CD274 mRNA and CD274-expressing esinophil levels may be novel possible noninvasive biomarkers for EoE.
Factor XII as a Therapeutic Target in Thromboembolic and Inflammatory Diseases
Authors: Nickel Katrin F. , Long Andy T. , Fuchs Tobias A. , Butler Lynn M. , Renné Thomas
Published: November 2016

Coagulation factor XII (FXII, Hageman factor) is a plasma protease that in its active form (FXIIa) initiates the procoagulant and proinflammatory contact system. This name arises from FXII’s unique mechanism of activation that is induced by binding (contact) to negatively charged surfaces. Various substances have the capacity to trigger FXII contact-activation in vivo including mast cell–derived heparin, misfolded protein aggregates, collagen, nucleic acids, and polyphosphate. FXII deficiency is not associated with bleeding, and for decades, the factor was considered to be dispensable for coagulation in vivo. However, despite the fact that humans and animals with deficiency in FXII have a normal hemostatic capacity, animal models revealed a critical role of FXIIa-driven coagulation in thromboembolic diseases. In addition to its role in thrombosis, FXIIa contributes to inflammation through the activation of the inflammatory bradykinin-producing kallikrein-kinin system. Pharmacological inhibition of FXII/FXIIa interferes with thrombosis and inflammation in animal models. Thus, targeting the FXIIa-driven contact system seems to be a promising and safe therapeutic anticoagulation treatment strategy, with additional anti-inflammatory effects. Here, we discuss novel functions of FXIIa in cardiovascular thrombotic and inflammatory disorders.
Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse Remodeling
Authors: Kali Avinash , Cokic Ivan , Tang Richard , Dohnalkova Alice , Kovarik Libor , Yang Hsin-Jung , Kumar Andreas , Prato Frank S. , Wood John C. , Underhill David , Marbán Eduardo , Dharmakumar Rohan
Published: November 2016

Background—

Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI.

Methods and Results—

Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energy-dispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (
r
>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (
r
>0.5).

Conclusions—

Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process.
Chronic Kidney Disease Induces Inflammatory CD40
+
Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation
Authors: Yang Jiyeon , Fang Pu , Yu Daohai , Zhang Lixiao , Zhang Daqing , Jiang Xiaohua , Yang William Y. , Bottiglieri Teodoro , Kunapuli Satya P. , Yu Jun , Choi Eric T. , Ji Yong , Yang Xiaofeng , Wang Hong
Published: November 2016

Rationale:

Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold.

Objective:

We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD).

Methods and Results:

We identified CD40 as a CKD-related monocyte activation gene using CKD-monocyte -mRNA array analysis and classified CD40 monocyte (CD40
+
CD14
+
) as a stronger inflammatory subset than the intermediate monocyte (CD14
++
CD16
+
) subset. We recruited 27 patients with CVD/CKD and 14 healthy subjects and found that CD40/CD40 classical/CD40 intermediate monocyte (CD40
+
CD14
+
/CD40
+
CD14
++
CD16
–
/CD40
+
CD14
++
CD16
+
), plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine levels were higher in CVD and further elevated in CVD+CKD. CD40 and CD40 intermediate subsets were positively correlated with plasma/cellular homocysteine levels, S-adenosylhomocysteine and S-adenosylmethionine but negatively correlated with estimated glomerular filtration rate. Hyperhomocysteinemia was established as a likely mediator for CKD-induced CD40 intermediate monocyte, and reduced S-adenosylhomocysteine/S-adenosylmethionine was established for CKD-induced CD40/CD40 intermediate monocyte. Soluble CD40 ligand, tumor necrosis factor (TNF)-α/interleukin (IL)-6/interferon (IFN)-γ levels were elevated in CVD/CKD. CKD serum/homocysteine/CD40L/increased TNF-α/IL-6/IFN-γ–induced CD40/CD40 intermediate monocyte in peripheral blood monocyte. Homocysteine and CKD serum-induced CD40 monocyte were prevented by neutralizing antibodies against CD40L/TNF-α/IL-6. DNA hypomethylation was found on nuclear factor-κB consensus element in CD40 promoter in white blood cells from patients with CKD with lower S-adenosylmethionine / S-adenosylhomocysteine ratios. Finally, homocysteine inhibited DNA methyltransferase-1 activity and promoted CD40 intermediate monocyte differentiation, which was reversed by folic acid in peripheral blood monocyte.

Conclusions:

CD40 monocyte is a novel inflammatory monocyte subset that appears to be a biomarker for CKD severity. Hyperhomocysteinemia mediates CD40 monocyte differentiation via soluble CD40 ligand induction and CD40 DNA hypomethylation in CKD.
The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis
Authors: Franklin Matthew , Wailoo Allan , Dayer Mark J. , Jones Simon , Prendergast Bernard , Baddour Larry M. , Lockhart Peter B. , Thornhill Martin H.
Published: November 2016

Background:

In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications.

Methods:

A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics.

Results:

AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 ($26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million ($7.3–$10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England.

Conclusions:

AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.
Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming
Authors: Mohamed Tamer M. A. , Stone Nicole R. , Berry Emily C. , Radzinsky Ethan , Huang Yu , Pratt Karishma , Ang Yen-Sin , Yu Pengzhi , Wang Haixia , Tang Shibing , Magnitsky Sergey , Ding Sheng , Ivey Kathryn N. , Srivastava Deepak
Published: November 2016

Background:

Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.

Methods:

We screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.

Results:

We found that a combination of the transforming growth factor-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; we observed beating cells as early as 1 week after reprogramming compared with 6 to 8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared with those exposed to only GMT. Human cardiac reprogramming was similarly enhanced on transforming growth factor-β and WNT inhibition and was achieved most efficiently with GMT plus myocardin.

Conclusions:

Transforming growth factor-β and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.
Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia
Authors: McLaughlin Kelsey , Baczyk Dora , Potts Audrey , Hladunewich Michelle , Parker John D. , Kingdom John C.P.
Published: November 2016

Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks’ gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased
PlGF-1
and
PlGF-2
transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability.
Premature Cardiac Aging in South Asian Compared to Afro‐Caribbean Subjects in a Community‐Based Screening Study
Authors: Shantsila Eduard , Shantsila Alena , Gill Paramjit S. , Lip Gregory Y.H.
Published: November 2016

Background

People of South Asian (SAs) and African Caribbean (AC) origin have increased cardiovascular morbidity, but underlying mechanisms are poorly understood. Aging is the key predictor of deterioration in diastolic function, which can be assessed by echocardiography using E/e′ ratio as a surrogate of left ventricular (LV) filling pressure. The study aimed to assess a possibility of premature cardiac aging in SA and AC subjects.

Methods and Results

We studied 4540 subjects: 2880 SA and 1660 AC subjects. All participants underwent detailed echocardiography, including LV ejection fraction, average septal‐lateral E/e′, and LV mass index (LVMI). When compared to ACs, SAs were younger, with lower mean LVMI, systolic blood pressure (BP), diastolic BP, and body mass index (BMI), as well as a lower prevalence of hypertension and smoking (
P
≤0.001 for all). In a multivariate linear regression model including age, sex, ethnicity, BP, heart rate, BMI, waist circumference, LVMI, history of smoking, hypertension, coronary artery disease, diabetes mellitus, medications, SA origin was independently associated with higher E/e′ (regression coefficient±standard error, −0.66±0.10;
P
<0.001, adjusted
R
2
for the model 0.21;
P
<0.001). Furthermore, SAs had significantly accelerated age‐dependent increase in E/e′ compared to ACs. On multivariable Cox regression analysis without adjustment for E/e′, SA ethnicity was independently predictive of mortality (
P
=0.04). After additional adjustment for E/e′, the ethnicity lost its significance value, whereas E/e′ was independently predictive of higher risk of death (
P
=0.008).

Conclusions

Premature cardiac aging is evident in SAs and may contribute to high cardiovascular morbidity in this ethnic group, compared to ACs.
Stroke Thrombolysis in a Centralized and a Decentralized System (Helsinki and Telemedical Project for Integrative Stroke Care Network)
Authors: Hubert Gordian J. , Meretoja Atte , Audebert Heinrich J. , Tatlisumak Turgut , Zeman Florian , Boy Sandra , Haberl Roman L. , Kaste Markku , Müller-Barna Peter
Published: November 2016

Background and Purpose—

Intravenous thrombolysis with tissue-type plasminogen activator (tPA) for acute ischemic stroke is more effective when delivered early. Timely delivery is challenging particularly in rural areas with long distances. We compared delays and treatment rates of a large, decentralized telemedicine-based system and a well-organized, large, centralized single-hospital system.

Methods—

We analyzed the centralized system of the Helsinki University Central Hospital (Helsinki and Province of Uusimaa, Finland, 1.56 million inhabitants, 9096 km
2
) and the decentralized TeleStroke Unit network in a predominantly rural area (Telemedical Project for Integrative Stroke Care [TEMPiS], South-East Bavaria, Germany, 1.94 million inhabitants, 14 992 km
2
). All consecutive tPA treatments were prospectively registered. We compared tPA rates per total ischemic stroke admissions in the Helsinki and TEMPiS catchment areas. For delay comparisons, we excluded patients with basilar artery occlusions, in-hospital strokes, and those being treated after 270 minutes.

Results—

From January 1, 2011, to December 31, 2013, 912 patients received tPA in Helsinki University Central Hospital and 1779 in TEMPiS hospitals. Area-based tPA rates were equal (13.0% of 7017 ischemic strokes in the Helsinki University Central Hospital area versus 13.3% of 14 637 ischemic strokes in the TEMPiS area;
P
=0.078). Median prehospital delays were longer (88; interquartile range, 60–135 versus 65; 48–101 minutes;
P
<0.001) but in-hospital delays were shorter (18; interquartile range, 13–30 versus 39; 26–56 minutes;
P
<0.001) in Helsinki University Central Hospital compared with TEMPiS with no difference in overall delays (117; interquartile range, 81–168 versus 115; 87–155 minutes;
P
=0.45).

Conclusions—

A decentralized telestroke thrombolysis service can achieve similar treatment rates and time delays for a rural population as a centralized system can achieve for an urban population.
Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy
Authors: van Rooden Sanneke , van Opstal Anna M. , Labadie Gerda , Terwindt Gisela M. , Wermer Marieke J.H. , Webb Andrew G. , Middelkoop Huub A.M. , Greenberg Steven M. , van der Grond Jeroen , van Buchem Mark A.
Published: November 2016

Background and Purpose—

Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary cerebral hemorrhage with amyloidosis-Dutch type.

Methods—

Twenty-seven DNA-proven Dutch-type mutation carriers (15 symptomatic and 12 presymptomatic) (mean age of 45.9 years) and 33 controls (mean age of 45.6 years) were included. 7T and 3T MRI was performed, cerebral amyloid angiopathy and small-vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand and on the other, mutation status, adjusted for age, sex, and education.

Results—

In symptomatic patients, all established cerebral amyloid angiopathy MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities, and dilated perivascular spaces in centrum semiovale) were increased compared with controls (
P
<0.05). In presymptomatic subjects, the prevalence of microinfarcts and median volume of white matter hyperintensities were increased in comparison to controls (
P
<0.05). Symptomatic patients performed worse on all cognitive domains, whereas presymptomatic subjects did not show differences in comparison with controls (
P
<0.05).

Conclusions—

White matter hyperintensities and microinfarcts are more prevalent among presymptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages.
Impaired Collateral Flow Compensation During Chronic Cerebral Hypoperfusion in the Type 2 Diabetic Mice
Authors: Nishijima Yasuo , Akamatsu Yosuke , Yang Shih Yen , Lee Chih Cheng , Baran Utku , Song Shaozhen , Wang Ruikang K. , Tominaga Teiji , Liu Jialing
Published: November 2016

Background and Purpose—

The presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.

Methods—

We examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in
db/+
and
db/db
mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.

Results—

After unilateral CCAO,
db/db
mice exhibited diminished leptomeningeal collateral flow compensation compared with
db
/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO.
db/db
mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with
db/+
mice.

Conclusions—

Type 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.
Cyclooxygenase-2-Derived Prostaglandins Mediate Cerebral Microcirculation in a Juvenile Ischemic Rat Model
Authors: Leger Pierre-Louis , Pansiot Julien , Besson Valerie , Palmier Bruno , Renolleau Sylvain , Baud Olivier , Cauli Bruno , Charriaut-Marlangue Christiane
Published: November 2016

Background and Purpose—

We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply.

Methods—

Fourteen-day-old rats were subjected to ischemia–reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F
1α
was measured using ELISA. COX-1 and COX-2 and prostaglandin terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction and immunofluorescence. Microvascular blood flow indexes (artery diameter and capillaries number) were measured using sidestream dark-field videomicroscopy in PBS- and 7-NI-treated ischemic rats in the absence or presence of the COX-2 inhibitor NS-398 (5 mg/kg). Cell death was measured with the TUNEL (terminal transferase dUTP nick end labeling) assay and cleaved-caspase-3 immunostaining.

Results—

Six-keto-prostaglandin F
1α
and COX-2, associated with a prostaglandin E synthase, were significantly increased in PBS- and 7-NI-treated animals 15 minutes and 1 hour after ischemia–reperfusion, respectively. In contrast and as compared with PBS, 7-NI significantly decreased prostacyclin synthase and cytosolic prostaglandins E synthase mRNA. Selective COX-2 inhibition significantly decreased blood flow indexes and significantly reversed the effects of 7-NI, including the number of TUNEL
+
- and cleaved-caspase-3
+
-nuclei.

Conclusions—

These results show that the juvenile rat brains mostly respond to ischemia by a COX-2-dependent prostaglandins production and suggest that the transcriptional responses observed under 7-NI facilitate and reorient COX-2-dependent prostaglandins production.
20-Hydroxyeicosatetraenoic Acid as a Predictor of Neurological Deterioration in Acute Minor Ischemic Stroke
Authors: Yi Xingyang , Han Zhao , Zhou Qiang , Lin Jing , Liu Ping
Published: November 2016

Background and Purpose—

The relationship between high plasma 20-hydroxyeicosatetraenoic acid (20-HETE) levels and neurological deterioration (ND) has not been investigated in patients with acute minor ischemic stroke.

Method—

We conducted a prospective, multicenter observational study in patients with acute minor ischemic stroke. Plasma levels of 20-HETE were measured at admission in all patients. The primary end point of the study was ND within 10 days after admission. The degree of disability was assessed using modified Rankin scale at 3 months after admission.

Results—

A total of 322 patients were enrolled, of which 85 patients (26.4%) developed ND. Mean 20-HETE level was 1687±158 pmol/L. On multivariate analyses, high level (>1675 pmol/L) of 20-HETE was an independent predictor of ND (third and fourth quartiles). Neurological deterioration was associated with a higher risk of poor outcome (modified Rankin scale scores 3–6) at 3 months.

Conclusions—

ND is fairly common in acute minor ischemic stroke and is associated with poor prognosis. Elevated plasma level of 20-HETE may be a predictor for ND in acute minor ischemic stroke.
Influencing Human Affective Responses to Dynamic Virtual Environments
Authors: Moghimi Mohammadhossein , Stone Robert , Rotshtein Pia , Cooke Neil
Published: November 2016

Detecting and measuring emotional responses while interacting with virtual reality (VR), and assessing and interpreting their impacts on human engagement and “immersion,” are both academically and technologically challenging. While many researchers have, in the past, focused on the affective evaluation of passive environments, such as listening to music or the observation of videos and imagery, virtual realities and related interactive environments have been used in only a small number of research studies as a mean of presenting emotional stimuli. This article reports the first stage (focusing on participants' subjective responses) of a range of experimental investigations supporting the evaluation of emotional responses within a virtual environment, according to a three-dimensional (Valence, Arousal, and Dominance) model of affects, developed in the 1970s and 1980s. To populate this three-dimensional model with participants' emotional responses, an “affective VR,” capable of manipulating users' emotions, has been designed and subjectively evaluated. The VR takes the form of a dynamic “speedboat” simulation, elements (controllable VR parameters) of which were assessed and selected based on a 35-respondent online survey, coupled with the implementation of an affective power approximation algorithm. A further 68 participants took part in a series of trials, interacting with a number of VR variations, while subjectively rating their emotional responses. The experimental results provide an early level of confidence that this particular affective VR is capable of manipulating individuals' emotional experiences, through the control of its internal parameters. Moreover, the approximation technique proved to be fairly reliable in predicting users' potential emotional responses, in various affective VR settings, prior to actual experiences. Finally, the analysis suggested that the emotional response of the users, with different gender and gaming experiences, could vary, when presented with the same affective VR situation.
Qurʾān and Sunna or the Madhhabs?: A Salafi Polemic Against Islamic Legal Tradition
Authors: Hamdeh Emad
Published: November 2016

The Albanian scholar Muḥammad Nāṣir al-Dīn al-Albānī (d. 1999) established a unique type of Salafism, a movement whose adherents follow a puritanical model of Muslim creed, exegesis, and conduct that is critical of madhhab Traditionalism. In this article I present an annotated translation of an audio lecture in which Albānī attempted to defend Salafism against its anti-madhhab image. I shed light on the religious and social climate that played a critical role in triggering Albānī’s disdain for Traditionalism and led him to discredit madhhab Traditionalist fiqh and replace it with his own interpretation of the jurisprudential requirements of Islamic scripture. Among the arguments I make is that Albānī’s claim to follow only the Qurʾān and Sunna is a rhetorical strategy designed to present Salafism as the absolute truth and distinguish it from being categorized as another madhhab or religious movement.
Conflicting Russian Orthodox and European Secular Values and Their Reflection in Russian Law
Authors: Belov Sergei Aleksandrovich
Published: November 2016

This article focuses on the widely discussed apparent contradictions between traditional Russian Orthodox values and modern secular European values as these contradictions can be observed in the Russian legal system. On the one hand, the 1993 Russian Constitution—in particular, the provisions declaring the highest values of human rights—requires observance of secular European values. On the other hand, the ideas of the ‘Russian way’ (osobyi put’ Rossii) and cultural specificity are very influential in Russian politics and society today. This article examines how this value dualism appears in legal documents, which can be seen when the Russian legislative, executive, or judicial branch reaches a decision in which they seem to be guided by Orthodox dogma. Although examples are to be found by monitoring Russian media, the Internet, and most importantly via online databases of Russian judicial decisions, I argue that these instances are not significant enough to enable one to draw a broad conclusion. In fact, they are quite rare and non-systematic. Arguably, factors other than religious motives can be seen as the grounds in which these decisions are rooted. Nonetheless, a tendency toward strengthening the influence of Orthodoxy on the Russian ‘law in books’ and ‘law in action’ is obvious. One result likely will be a sharpening of the divide between Orthodox and secular European values in the Russian legal system in the future.
A Comparative Perspective on the Concept of Ownership in Russian Law: From the Svod Zakonov to the 1994 Civil Code
Authors: Raff Murray , Taitslin Anna
Published: November 2016

The modern European unitary conception of ownership emerged from the dissolution of feudalism and achievement of a deeper understanding of Roman law to become an ideal of property law in the European Civil-Law tradition. Prior to its dissolution European feudalism represented hierarchies of legal tenure in land, such as the division of land ownership between dominus directus (direct owner) and dominus utilis (beneficial owner) and overlapping hierarchies of social class descending from monarchy and aristocracy to bonded serfdom. Support for the resolution of divided land ownership and victory for the unitary concept of ownership was found in the Roman law tradition. The dissolution of feudal hierarchies took different historical courses in the legal traditions that we now identify as the French, German, Common-Law and Russian legal systems and with great local variation even within those emergent traditions. The unitary concept of ownership is found today in the French and German Civil Codes and is for practical purposes reflected in the prevalence of the common-law tenure of freehold. In Russia the systemized digest of the laws of the Russian Empire, the Svod Zakonov of 1832, provided no civil-law notion of divided ownership or perpetual rights. In the Soviet era exclusive state ownership of land and the means of production was also viewed as unitary, which raised serious questions about how state agencies and enterprises could engage in transactions with their assets and products. Venediktov’s celebrated doctrine of the right of operative management, codified in the Civil Code of the rsfr of 1964, provided legal recognition of de facto proprietary rights for state enterprises. This introduced a form of divided ownership ‘on the ground’ despite the dogma of unitary state ownership. This reality further manifested itself in widespread division of ownership between land and buildings. The Civil Code of the Russian Federation of 1994 retained and even extended some of these solutions that relied on split or divided ownership. This might have been a pragmatic way forward in the early 1990s, however twenty years later the demands of a modern sophisticated legal system require a policy trajectory back toward a modern European unitary conception of ownership. The Russian Civil Code thus should be extended in this direction.
The Importance of Critical Layer in Differentiating Developing from Nondeveloping Easterly Waves
Authors: Asaadi Ali , Brunet Gilbert , Yau M. K.
Published: November 2016

Recently Asaadi et al. found that an easterly wave (EW) train over the Atlantic and eastern Pacific is oriented in a southeast–northwest direction because of the observed tilt in the easterly jet. This tilt results in only one out of four (~25%) waves to be located at the cyclonic critical layer south of the jet axis in a comoving frame, and they subsequently developed into named storms. Asaadi et al. suggested a geometrical view for developing disturbances, which is the coexistence of a nonlinear critical layer and a region of weak meridional potential vorticity (PV) gradient over several days. Asaadi et al. focused on the developing waves and did not investigate the nondeveloping ones.

To determine whether the nondeveloping EWs are not associated with a critical layer, a simple objective tracking technique is used to identify EWs. Composite views of the large-scale structure and characteristics of nondeveloping EWs show that ~91% of nondeveloping waves are not located on a critical layer, while the remaining ~9% indicate characteristics similar to the developing waves. Examination of the composite Okubo–Weiss parameter indicates that the nondeveloping waves are characterized by larger negative values, implying that they are dominated by deformation, unlike developing waves, which tend to be more immune from the deformation.
Scotellaro poeta eclettico (e poco contadino)
Authors: Giovannetti Paolo
Published: November 2016

Il saggio illustra i rapporti fra la poesia di Rocco Scotellaro e le principali tradizioni della poesia italiana novecentesca. Pur in presenza di un corpus testuale eterogeneo, non privo di notevoli discontinuità, il suo nucleo forte, affidato alle liriche di È fatto giorno (1954), rivela un profilo stilistico meno ingenuo (meno immediatamente popolare) di quanto solitamente si creda. Certe sprezzature sintattiche non sono estranee alla prosa ‘modernista’ degli anni Trenta, e anche le frequenti scelte metriche sospese, claudicanti, sembrano essere il frutto di una ricerca, esemplarmente incardinata sulla figura dell’ellissi. Ne è prova il fatto che Scotellaro non realizza pressoché mai una poesia in senso pieno narrativa: la sua è un’esperienza che si muove quasi senza residui all’interno del genere lirico, anche se – beninteso – è sempre attenta a mettere in rapporto fra loro l’ io isolato del locutore e il noi di una comunità che al soggetto possa conferire un senso. Da questo punto di vista, allora, non stupiscono alcune tangenze con la produzione poetica di Amelia Rosselli, che dal popolare ‘concettualizzato’ di Scotellaro ha certo appreso molto.
Briganti e brigantaggio in Levi e Scotellaro: La memoria intermedia
Authors: Marmo Marcella
Published: November 2016

Il saggio svolge una lettura delle pagine di Levi e Scotellaro che richiamano il brigantaggio postunitario con metodologia che, da aggiornate tematiche storiografiche e dalla letteratura sui due scrittori, va all’analisi testuale. Significativi sviluppi storiografici mettono in luce le complessità del conflitto legittimista che insanguinò ampi territori meridionali lungo l’unificazione nazionale, affiancando alle vie già battute sulla questione sociale una rinnovata attenzione agli aspetti di guerra civile, ricorrenti nelle fonti coeve, di cui è interessante studiare la memoria sociale rintracciabile lungo la storia italiana. La memoria intermedia restituita da Levi risulta ricca, nell’affiancare voci paesane frastagliate sull’antica tragica vicenda, alla personale propensione interpretativa relativista, che fa del Cristo si è fermato a Eboli un’originale prova fuori disciplina del campo antropologico writing culture. I lunghi interventi d’autore restituiscono peraltro al contesto politico resistenziale-azionista il discorso astraente sul brigantaggio come guerra contadina antistatalista. Un deposito memoriale diverso viene nel dopoguerra nella celebre poesia di Scotellaro Sempre nuova è l’alba, che include un richiamo simbolico all’antico brigante solitario e perdente, da lasciare ormai al passato. L’evocazione di enigmatica bellezza è particolarmente significativa nel far precedere, alla chiusura ottimista, le tensioni tra incertezze politiche e inquietudini esistenziali, che segnano a tutto tondo la figura di Scotellaro.
Scotellaro, Mario Colombi Guidotti e “Il Raccoglitore” di Parma
Authors: Briganti Paolo
Published: November 2016

Due troppo rapidi destini esistenziali con un minimo incrocio in extremis, carico di promesse letterarie, appena delibate. Si parla qui dell’incipiente amicizia fra Rocco Scotellaro e Mario Colombi Guidotti: due giovani letterati trentenni, entrambi di brevissima vita, quasi polarmente diversi, non solo geograficamente – uno del Sud (Tricarico), l’altro del Nord (Parma) – ma anche per estrazione sociale, inclinazioni politiche, propensioni letterarie. Eppure, nell’arco di appena un mese (dall’incontro a metà novembre ’53 all’improvvisa scomparsa di Scotellaro il 15 dicembre), i due stavano già costruendo un fecondo rapporto di collaborazione: Mario aveva già pubblicato infatti, il 10 dicembre, su “Il Raccoglitore” (la pagina culturale da lui diretta), Cena, una bella poesia di Rocco, ideologicamente programmatica (testo che commentiamo, ripresentandolo in quella stessa prima redazione); poi però, al critico di Parma, restò soltanto lo spazio immediato d’un sincero e accorato ricordo il 7 gennaio ’54 e, quasi alla fine di quell’anno, l’occasione d’una recensione, lucidamente spassionata, a È fatto giorno, la raccolta postuma del poeta lucano. Di lì a poco infine, il 15 gennaio ’55, anche Colombi Guidotti avrebbe tragicamente perso la vita.
Cristo si è fermato a Eboli alla luce della tecnica narratologica
Authors: de Miguel y Canuto Juan Carlos
Published: November 2016

Queste pagine cercano di rispondere a un insieme di domande circa l’opera Cristo si è fermato a Eboli, presa in considerazione in quanto testo letterario. Si tratta, fra le altre, di domande quali: in quale modo sono assemblati i (disparati) materiali che lo compongono? Quali sono le tecniche narrative adoperate? Qual è il rapporto fra narratore-protagonista e autore? Quale ruolo ha l’autore nel testo? È un ruolo unitario? L’opera è un romanzo? Come agisce la commistione di generi? Come cresce il libro? Nelle risposte si cerca di aprire nuovi spiragli alla critica leviana.
Le memorie ingarbugliate. Tensioni autobiografiche nell’Uva puttanella e in Contadini del Sud di Scotellaro
Authors: Marchese Lorenzo
Published: November 2016

L’intervento s’inserisce nel dibattito sull’autobiografismo di Scotellaro nelle sue due maggiori opere in prosa, arrivateci incomplete e non pronte per la pubblicazione: Contadini del Sud e, soprattutto, L’uva puttanella, che Scotellaro definiva in fase di preparazione un “romanzo”. Se Contadini del Sud, nelle parti disponibili oggi, sembra anticipare alcuni esiti dell’attuale non-fiction per via dell’uso disinvolto del materiale documentario, del risalto dato alle testimonianze e alle ricognizioni sul campo, della creazione di veri e propri “personaggi” a tutto tondo che si esprimono direttamente sulla pagina, L’uva puttanella ha caratteristiche che ne sottolineano invece l’inattualità e insieme la natura di memoir ancora, alla morte di Scotellaro, incerto sulla direzione da prendere. Vengono proposte alcune ricognizioni testuali intorno all’ Uva puttanella, al fine di ricostruire la sua natura autobiografica sospesa fra autoapologia politica (il testo fu iniziato durante la prigionia di Scotellaro) ed espressione poetica, ricordo familiare e apertura in forma di micro-racconti di alcuni abitanti del paese. Non si ricompongono le tensioni narrative di una prosa ellittica per scelta, che tende al frammento di realtà da una parte e al lirismo dall’altra: è ciò che sembra dimostrare la conclusione della Parte prima, di cui si propone una nuova lettura.
Passaggio alla città
Authors: Sparagna Ambrogio
Published: November 2016

L'articolo è la testimonianza di come l'esperienza e la poesia di Scotellaro abbiano inciso sull'attività di un musicista ed etnomusicologo. In particolare, viene evidenziato il fascino della cultura orale nel suo variegato sistema di segni e come nella rielaborazione musicale di alcuni testi scotellariani sia stata determinante la conservazione del timbro originale, policromatico e di sicura appartenenza contadina. L'opera di Scotellaro è vista ancora attuale e antidoto alla crisi presente.