bluuebunny/crossref_metadata_2025 huggingface dataset:
Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response
Authors: Venturelli Massimo , Layec Gwenael , Trinity Joel , Hart Corey R. , Broxterman Ryan M. , Richardson Russell S.
Published: November 2016

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min−1·mmHg−1, respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min−1·mmHg−1, respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically.

NEW & NOTEWORTHY Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more useful clinically.
A Rare Tumor in the Cervical Sympathetic Trunk: Ganglioneuroblastoma
Authors: Erol Ozan , Koycu Alper , Aydin Erdinc
Published: November 2016

Ganglioneuroblastoma is a rare tumor with moderate malignancy, which is composed of mature ganglion cells and seen in sympathetic ganglia and adrenal medulla. The diagnosis is possible after cytological and immunohistochemical studies following a needle biopsy or surgical excision. There is no consensus regarding the need for chemo- or radiotherapy after surgery. In this case report, clinical behavior and diagnosis and treatment of the rare tumor cervical ganglioneuroblastoma were discussed.
Compressive Sensing of Multichannel EEG Signals via lq Norm and Schatten-p Norm Regularization
Authors: Zhu Jun , Chen Changwei , Su Shoubao , Chang Zinan
Published: November 2016

In Wireless Body Area Networks (WBAN) the energy consumption is dominated by sensing and communication. Recently, a simultaneous cosparsity and low-rank (SCLR) optimization model has shown the state-of-the-art performance in compressive sensing (CS) recovery of multichannel EEG signals. How to solve the resulting regularization problem, involving l0 norm and rank function which is known as an NP-hard problem, is critical to the recovery results. SCLR takes use of l1 norm and nuclear norm as a convex surrogate function for l0 norm and rank function. However, l1 norm and nuclear norm cannot well approximate the l0 norm and rank because there exist irreparable gaps between them. In this paper, an optimization model with lq norm and schatten-p norm is proposed to enforce cosparsity and low-rank property in the reconstructed multichannel EEG signals. An efficient iterative scheme is used to solve the resulting nonconvex optimization problem. Experimental results have demonstrated that the proposed algorithm can significantly outperform existing state-of-the-art CS methods for compressive sensing of multichannel EEG channels.
Role of B Cell Development Marker CD10 in Cancer Progression and Prognosis
Authors: Mishra Deepshikha , Singh Sunita , Narayan Gopeshwar
Published: November 2016

The human CD10 antigen is a single pass, type II transmembrane, 100 kD cell surface glycoprotein belonging to peptidase M13 family. Identified in common acute lymphoblastic leukemia as a cancer specific antigen, CD10 is a cell surface ectoenzyme widely expressed on different types of cells. Earlier, it was used only as a cell surface marker to identify and differentiate between haematological malignancies. Later, reported to be present in various malignancies, it is thought to play significant role in cancer development and progression. Regulated expression of CD10 is necessary for angiogenesis and so forth. However its expression level is found to be deregulated in different cancers. In some cancers, it acts as tumor suppressor and inhibits tumor progression whereas in others it has tumor promoting tendency. However, its role in tumorigenesis remains unclear. This review summarises structural features, functions, and probable role of CD10 in cancer development.
SPR Biosensing MUA/Poly-L-lysine Platform for the Detection of 2,4-Dinitrophenol as Small Molecule Model System
Authors: Daza Millone M. Antonieta , Ramirez Eduardo A. , Chain Cecilia Y. , Crivaro Andrea , Romanin David , Rumbo Martín , Docena Guillermo , Cocco Mauro D. , Pedano María L. , Fainstein Alejandro , Montoya Jorgelina , Vela María E. , Salvarezza R. C.
Published: November 2016

Surface Plasmon Resonance assays are being developed as alternative biodetection methods for a great number of pesticides and toxins. These substances typically have low molecular weight, making it necessary to perform competitive inhibition immunoassays. In most of the cases, the strategy is to immobilize a protein derivative of the analyte, which usually involves the appearance of nonspecific protein binding which limits the detection range of the assay. In this work we present results of a poly-L-lysine (Au-MUA-PLL) based sensor platform for quantitative determination of 2,4-dinitrophenol as model system for small molecular weight substances detection. The prepared sensor chip was characterized by means of Atomic Force Microscopy, Surface Plasmon Resonance, and Surface Enhanced Raman Spectroscopy. Experiments verified the absence of nonspecific protein adsorption to Au-MUA-PLL surfaces and the improvement of the competitive inhibition assays performance in comparison with single and mixed thiol self-assembled monolayers. The possibility of directly immobilizing 2,4-dinitrophenol to the poly-L-lysine containing platforms leads to an improvement in the detection of the soluble analyte by the competitive inhibition assay avoiding undesirable nonspecific protein adsorption. Therefore, Au-MUA-PLL surfaces constitute a suitable alternative for quantitative detection of small molecules when nonspecific adsorption cannot be avoided.
Assessment of Natural Radioactivity Levels and Radiation Hazards in Agricultural and Virgin Soil in the State of Kedah, North of Malaysia
Authors: Alzubaidi Ghazwa , Hamid Fauziah B. S. , Abdul Rahman I.
Published: November 2016

The activity concentrations of naturally occurring radionuclides226Ra,232Th, and40K were determined in 30 agricultural and virgin soil samples randomly collected from Kedah, north of Malaysia, at a fertile soil depth of 0–30 cm. Gamma-ray spectrometry was applied using high-purity germanium (HPGe) gamma-ray detector and a PC-based MCA. The mean radioactivity concentrations of226Ra,232Th, and40K were found to be 102.08 ± 3.96, 133.96 ± 2.92, and 325.87 ± 9.83 Bq kg−1, respectively, in agricultural soils and 65.24 ± 2.00, 83.39 ± 2.27, and 136.98 ± 9.76 Bq kg−1, respectively, in virgin soils. The radioactivity concentrations in agricultural soils are higher than those in virgin soils and compared with those reported in other countries. The mean values of radium equivalent activity (Raeq), absorbed dose ratesD(nGy h−1), annual effective dose equivalent, and external hazard index (Hex) are 458.785 Bq kg−1, 141.62 nGy h−1, and 0.169 mSv y−1, respectively, in agricultural soils and 214.293 Bq kg−1, 87.47 nGy h−1, and 0.106 mSv y−1, respectively, in virgin soils, with averageHexof 0.525. Results were discussed and compared with those reported in similar studies and with internationally recommended values.
The Outcome of Endoscopic Transethmosphenoid Optic Canal Decompression for Indirect Traumatic Optic Neuropathy with No-Light-Perception
Authors: Yu Bo , Ma Yingjie , Tu Yunhai , Wu Wencan
Published: November 2016

Purpose. To present the safety and effect of endoscopic transethmosphenoid optic canal decompression (ETOCD) for indirect traumatic optic neuropathy (ITON) patients with no-light-perception (NLP).Methods. A retrospective study performed on 96 patients (96 eyes) with NLP after ITON between June 1, 2010, and June 1, 2015, who underwent ETOCD, was reviewed. Visual outcome before and after treatment was taken into comparison.Results. The overall visual acuity improvement rate after surgery was 46.9%. The improvement rates of visual acuity of patients who received treatment within 3 days of injury, 3–7 days after injury, and later than 7 days were 63.6%, 42.9%, and 35.7%, respectively. Statistically significant difference was detected between the effective rates of within-3-day group and later-than-7-day group (χ2=5.772,P=0.016). The effective rate of atrophy group and nonatrophy group was 25.0% and 51.3%, respectively. The effective rate was significantly higher in nonatrophy group (χ2=4.417,P=0.036).Conclusion. For patients suffering from ITON with NLP, time to medical treatment within 3 days is an influential factor for visual prognosis. Optic nerve atrophy is an important predictor for visual prognosis. Treatment should still be recommended even for cases of delayed presentation to hospital.
Stroke as the Sole Manifestation of Takayasu Arteritis in a 15-Year-Old Boy with Latent Tuberculosis
Authors: Benjaminsen Espen , Reigstad Anne , Cengija Vanja , Lilleby Vibke , Carlsson Maria
Published: November 2016

Introduction. Takayasu arteritis is a rare disease affecting the aorta and its main branches, causing arterial claudication and end-organ ischemia, including stroke. The etiology is unknown but is believed to be autoimmune. An association between Takayasu arteritis and tuberculosis has been suggested, but the possible relation is unclear.Case Presentation. A 15-year-old Somali boy was diagnosed with latent tuberculosis. He had a lesion in the right lung, and both the tuberculin skin test by the Mantoux method and Quantiferon GOLD test turned out positive. After he suffered a cerebral infarct in the right hemisphere, childhood Takayasu arteritis was diagnosed. The diagnosis was based on diagnostic imaging showing a high-grade stenosis of the origin of the right common carotid artery, an occluded common carotid artery on the left side, a circumferential thickening of the vessel walls in the right and left common carotid artery, and laboratory findings with elevated C-reactive protein.Conclusion. Takayasu arteritis is an uncommon cause of stroke. It should however be kept in mind as a cause of cerebrovascular disease, especially in the young.
On Modelling and Comparative Study of LMS and RLS Algorithms for Synthesis of MSA
Authors: Hassan Ahmad Kamal , Affandi Adnan
Published: November 2016

This paper deals with analytical modelling of microstrip patch antenna (MSA) by means of artificial neural network (ANN) using least mean square (LMS) and recursive least square (RLS) algorithms. Our contribution in this work is twofold. We initially provide a tutorial-like exposition for the design aspects of MSA and for the analytical framework of the two algorithms while our second aim is to take advantage of high nonlinearity of MSA to compare the effectiveness of LMS and that of RLS algorithms. We investigate the two algorithms by using gradient decent optimization in the context of radial basis function (RBF) of ANN. The proposed analysis is based on both static and adaptive spread factor. We model the forward side or synthesis of MSA by means of worked examples and simulations. Contour plots, 3D depictions, and Tableau presentations provide a comprehensive comparison of the two algorithms. Our findings point to higher accuracies in approximation for synthesis of MSA using RLS algorithm as compared with that of LMS approach; however the computational complexity increases in the former case.
Checkpoint Proteins in Pediatric Brain and Extracranial Solid Tumors: Opportunities for Immunotherapy
Authors: Ring Eric K. , Markert James M. , Gillespie G. Yancey , Friedman Gregory K.
Published: November 2016

Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of all pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy, and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of long-term morbidities. Although these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described. When found on malignant cells or in the tumor microenvironment, they contribute to immune evasion and tumor escape. Agents designed to inhibit these proteins have demonstrated significant efficacy in human adult solid tumor studies. However, there is limited research focusing on immune checkpoint molecules and inhibitors in pediatric solid tumors. In this review, we examine the current knowledge on immune checkpoint proteins with an emphasis on cytotoxic T lymphocyte antigen-4 (CTLA-4); programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1); OX-2 membrane glycoprotein (CD200); and indoleamine 2,3-dioxygenase (IDO). We review T-cell signaling, the mechanisms of action of these checkpoint molecules, pediatric preclinical studies on checkpoint proteins and checkpoint blockade, pediatric checkpoint inhibitor clinical trials conducted to date, and future immunotherapy opportunities for childhood cancers. Clin Cancer Res; 23(2); 342–50. ©2016 AACR.
Randomized Trial to Compare Renal Function and Ductal Response between Indomethacin and Ibuprofen Treatment in Extremely Low Birth Weight Infants
Authors: Lin Yuh Jyh , Chen Chung Ming , Rehan Virender K. , Florens Adrian , Wu Shou Yien , Tsai Min Luen , Kuo Yung T. , Huang Fu Kuei , Yeh Tsu F.
Published: November 2016

Background: A head to head comparison study on renal function and ductal response between indomethacin and ibuprofen has rarely been conducted in extremely low birth weight (ELBW) infants. Objectives: The aim was to compare renal function and ductal response between indomethacin and ibuprofen in ELBW infants. Methods: We performed a double-blind randomized control trial to compare renal function and ductal response between indomethacin (0.2, 0.1, and 0.1 mg/kg i.v. every 24 h for 3 doses) and ibuprofen lysine (10, 5, and 5 mg/kg i.v. every 24 h for 3 doses) in ELBW infants with significant hemodynamic patent ductus arteriosus (cardiovascular dysfunction score >3 and LA/AO ratio ≥1.3). Results: A total of 144 infants were enrolled: 73 received indomethacin and 71 received ibuprofen lysine. Significant decreases in urine output were seen in 30 infants (41%) in the indomethacin group and 15 (21%) in the ibuprofen group (p = 0.02). The indomethacin group was associated with a significantly higher chance of persistent ductal response than the ibuprofen group (66 vs. 49%, p = 0.046), but with a lower glomerular filtration rate on day 1, higher serum creatinine on days 1, 2, and 7, and lower urinary prostaglandin on days 2-7. Both groups were comparable in mortality and in bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity morbidity. Conclusions: With the current dosage, ibuprofen had fewer renal side effects but was associated with a lower rate of persistent ductal closure in ELBW infants. The precise role of prostaglandin on renal tubular function in ELBW infants remains to be further investigated.
Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult
Authors: Yamamoto Mami , Yamamoto Kentaroh , Taketomi Hirotaka , Yamamoto Fumio , Yamamoto Hiroshi
Published: November 2016

The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth.
High Prevalence of Diastolic Dysfunction in Incident Patients on Peritoneal Dialysis: Association with Low Thyroid Hormones
Authors: Sánchez Virginia , Paniagua Ramón , Prado Maria del Carmen , Mora Carmen , Orihuela Oscar , Martínez-Baca Francisco , Pérez Estela Elizabeth , Calzada Claudia , Romero Renata , Avila Marcela
Published: November 2016

Background/Aims: Diastolic dysfunction (DD) and low levels of thyroid hormones (TH) are frequent found in chronic kidney disease; both are associated with all-cause and cardiovascular mortality. However, a link between them has not yet been established. The aim of this study was to analyze DD as a surrogate marker of fibrosis and its association with TH in incident patients on peritoneal dialysis (PD). Methods: A cross-sectional study with 183 incident patients on PD with preserved ejection fraction was performed. Clinical and demographic data were registered. Serum total and free (t/f) triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone levels were determined by RIA kits, albumin and high-sensitivity C-reactive protein by conventional assays. Transthoracic 2D echocardiogram was performed for evaluation of left ventricular (LV) mass and ejection fraction. DD was evaluated using pulsed-wave tissue Doppler imaging. Results: Patients were 43 ± 12, 42% with diabetes mellitus (DM). Some degree of DD was found in 62% of patients; 18% had grade I DD, 8% grade II DD and 36% grade III DD. Patients with grade III DD were more likely to have diabetes, older, high LV mass and low serum albumin, t/fT3 and tT4 levels. In logistic multivariate regression analysis, it was found that diabetes (B = -0.86, 95% CI 0.182-0.992, p < 0.05), hypertension (B = -0.95, 95% CI 0.184-0.817, p = 0.01) and tT3 (B = -1.94, 95% CI 0.023-0.876, p < 0.05) were associated with grade III DD. Conclusions: High prevalence of grade III DD was found in incident patients on PD. In addition to DM and hypertension, tT3 was found to be an independent risk factor for grade III DD and more studies are needed to understand the reasons as to why this association is present.
Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease
Authors: Liu Yuanyuan , Liao Shengtao , Quan Hongyu , Lin Yuhan , Li Jian , Yang Qingshan
Published: November 2016

Background/Aims: Development of effective therapeutic drugs for Parkinson's disease is in great need. During the progression of Parkinson's disease, Rho-associated protein kinase 2 (ROCK2) is activated to promote neurodegeneration. Hydrogen sulfide (H2S) has a neuroprotective effect during the neural injury of Parkinson's disease. However, the mechanisms that underlie the effects of ROCK2 and H2S remain ill-defined. In the current study, we addressed these questions. Methods: We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse subacute model of Parkinson's disease to study the effects of H2S on astrocytic activation in the mouse striatum, on the levels of tyrosine-hydroxylase (TH)-positive neuron loss, on the apomorphine-induced rotational behavior of the mice, and on the changes in ROCK2 and miR-135a-5p expression. Plasmid transfection was applied to modify miR-135a-5p levels in a neuronal cell line HCN-1A. Bioinformatics analysis was performed to predict the relationship between ROCK2 and miR-135a-5p in neuronal cells, and then was confirmed by luciferase reporter assay. Results: H2S alleviated MPTP-induced astrocytic activation in the mouse striatum, alleviated the increases in TH-positive neuron loss, and improved the apomorphine-induced rotational behavior of the mice. H2S significantly attenuated the increases in ROCK2 and the decreases in miR-135a-5p by MPTP. MiR-135a-5p targeted the 3'-UTR of ROCK2 mRNA to inhibit its translation in neuronal cells. Conclusion: MiR-135a-5p-regulated ROCK2 may play a role in the protective effects of hydrogen sulfide against Parkinson's disease.
MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer
Authors: Xie Tao , Huang Mengxi , Wang Ye , Wang Liya , Chen Cheng , Chu Xiaoyuan
Published: November 2016

Chemotherapy and targeted therapy are the main options for andvanced colorectal cancer (CRC). However, resistance to these therapies is a major challenge in the clinic. Understanding molecular mechanisms and developing effective strategies against the drug resistance are highly desired. Increasing evidence has revealed that microRNAs (miRNAs) are closely linked to drug resistance in CRC. The explosion of knowledge in this field has brought forward new predictive and therapeutic opportunities. In this review, we systemically summarize the roles of miRNAs as regulators, tissue or circulating biomarkers, and therapeutics in the CRC resistance to 5-fluorouracil (5-FU), oxaliplatin and anti-EGFR therapy. We also discuss the potential unsettled issues and future directions concerning these processes.
Caregivers burden in people in palliative care: an integrative literature review
Authors: Rezende Gabriela , Gomes Cristiane A. , Rugno Fernanda C. , Carvalho Renata C. , De Carlo Marysia M. R. P.
Published: November 2016

Study design: Integrative literature review. Objective: To summarize the main research findings and critically analyze the evidence on the burden of caregivers of people in Palliative Care. Method: Bibliographic search in the electronic databases: MEDLINE, LILACS, CINAHL and the virtual library SciELO, with crosses between the descriptors: “Caregivers”, “Palliative Care”, “Hospice Care”, “Terminal Care” and the keywords “Burden”, “Supportive Care”. Results: 23 articles were selected, having been published in journals between January 2004 and June 2014, categorized into three units of analysis: 1. the task of caring and the consequences to the life of the caregiver (N=7); 2. the caregiver burden before the approach of death (N=8); 3. programs and support services to caregivers (N=8). The articles indicate that the caregiver burden varies according to their experience of care task and the evolution of the cared person’s illness; the caregiver needs to be received on your needs and have access to reduce the burden and improve both caregiver’s quality life as the assisted one. However, scientific evidence is considered fragile, with levels 4 (65.2%) and 5 (21.8%) and only 13% of studies present evidence considered strong. Conclusion: The issue of burden of caregivers of people in palliative care is relevant for research and for clinical practice, but there is need for studies with better methodological quality and scientific evidence to support the care for this population
Home visits under the users’ perception of the family health strategy
Authors: Barbosa Débora C. M. , Mattos Augustus T. R. , Corrêa Márcio H. , Faria Mônica , Ribeiro Luciana C. , Santos Luciane L. , Ferreira Janise B. B. , Forster Aldaísa C.
Published: November 2016

Study design: Exploratory, descriptive and quantitative study. Objective: To characterize the home visit performed by community health workers through the perception of users. Methodology: a study with 364 registered users in four Health Units of a small municipality Family conducted between July and August 2009. Data were collected using a structured questionnaire administered in the home of the registered families. Results: Of the 364 respondents, half reported receiving home visit monthly, and the duration was approximately five minutes, not interfering in the daily 91% of respondents users. Most (77.2%) said the home visit partially meets their needs and only a third of visits made within the household. However, 75% of the users considered as good or excellent performance of community workers. Conclusions: Most users reported being partially satisfied with the home visit. Thus, there was satisfactory indicators relating to frequency, service needs, performance and position of agents in the home visit. However, its duration, localization and the topics discussed were aspects considered less satisfactory, justifying greater investment in this health action so that the Family Health Strategy fully taps their potential
Nicotine Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells
Authors: Wang Chen , Chen Han , Zhu Wei , Xu Yinchuan , Liu Mingfei , Zhu Lianlian , Yang Fan , Zhang Ling , Liu Xianbao , Zhong Zhiwei , Zhao Jing , Jiang Jun , Xiang Meixiang , Yu Hong , Hu Xinyang , Lu Hong , Wang Jian’an
Published: November 2016

Objective—

Cigarette smoking is an independent risk factor for atherosclerosis. Nicotine, the addictive component of cigarettes, induces mast cell (MC) release and contributes to atherogenesis. The purpose of this study was to determine whether nicotine accelerates atherosclerosis through MC-mediated mechanisms and whether MC stabilizer prevents this pathological process.

Approach and Results—

Nicotine administration increased the size of atherosclerotic lesions in apolipoprotein E–deficient (
Apoe
−/−
) mice fed a fat-enriched diet. This was accompanied by enhanced intraplaque macrophage content and lipid deposition but reduced collagen and smooth muscle cell contents. MC deficiency in
Apoe
−/−
mice (

Apoe
−/−
Kit
W-sh/W-sh

) diminished nicotine-induced atherosclerosis. Nicotine activated bone marrow–derived MCs in vitro, which was inhibited by a MC stabilizer disodium cromoglycate or a nonselective nicotinic acetylcholine receptor blocker mecamylamine. Further investigation revealed that α7 nicotinic acetylcholine receptor was a target for nicotine activation in MCs. Nicotine did not change atherosclerotic lesion size of

Apoe
−/−
Kit
W-sh/W-sh

mice reconstituted with MCs from

Apoe
−/−
α7nAChR

−/−
animals.

Conclusions—

Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.
Zebrafish Model for Functional Screening of Flow-Responsive Genes
Authors: Serbanovic-Canic Jovana , de Luca Amalia , Warboys Christina , Ferreira Pedro F. , Luong Le A. , Hsiao Sarah , Gauci Ismael , Mahmoud Marwa , Feng Shuang , Souilhol Celine , Bowden Neil , Ashton John-Paul , Walczak Henning , Firmin David , Krams Rob , Mason Justin C. , Haskard Dorian O. , Sherwin Spencer , Ridger Victoria , Chico Timothy J.A. , Evans Paul C.
Published: November 2016

Objective—

Atherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries.

Approach and Results—

First, we demonstrated that flow regulates EC apoptosis in developing zebrafish vasculature. Specifically, suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) enhanced that rate of EC apoptosis (≈10%) compared with controls exposed to flow (≈1%). A panel of candidate regulators of apoptosis were identified by transcriptome profiling of ECs from high and low shear stress regions of the porcine aorta. Genes that displayed the greatest differential expression and possessed 1 to 2 zebrafish orthologues were screened for the regulation of apoptosis in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. A phenotypic change was observed in 4 genes; p53-related protein (
PERP
) and programmed cell death 2–like protein functioned as positive regulators of apoptosis, whereas angiopoietin-like 4 and cadherin 13 were negative regulators. The regulation of
perp
,
cdh13
,
angptl4
, and
pdcd2l
by shear stress and the effects of
perp
and
cdh13
on EC apoptosis were confirmed by studies of cultured EC exposed to flow.

Conclusions—

We conclude that a zebrafish model of flow manipulation coupled to gene knockdown can be used for functional screening of mechanosensitive genes in vascular ECs, thus providing potential therapeutic targets to prevent or treat endothelial injury at atheroprone sites.
Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging
Authors: Kim Jiwon , Di Franco Antonino , Seoane Tania , Srinivasan Aparna , Kampaktsis Polydoros N. , Geevarghese Alexi , Goldburg Samantha R. , Khan Saadat A. , Szulc Massimiliano , Ratcliffe Mark B. , Levine Robert A. , Morgan Ashley E. , Maddula Pooja , Rozenstrauch Meenakshi , Shah Tara , Devereux Richard B. , Weinsaft Jonathan W.
Published: November 2016

Background—

Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown.

Methods and Results—

The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all
P
≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both
P
<0.01), without difference in corresponding anterior defects (
P
=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both
P
<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes;
P
<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0;
P
<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9;
P
<0.001|2.7±1.0 versus 3.1±1.0;
P
<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (
P
<0.001) and was associated with each parameter independent of age or medication regimen.

Conclusions—

Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction.
Lifelong Physical Activity Regardless of Dose Is Not Associated With Myocardial Fibrosis
Authors: Abdullah Shuaib M. , Barkley Kyler W. , Bhella Paul S. , Hastings Jeffrey L. , Matulevicius Susan , Fujimoto Naoki , Shibata Shigeki , Carrick-Ranson Graeme , Palmer M. Dean , Gandhi Nainesh , DeFina Laura F. , Levine Benjamin D.
Published: November 2016

Background—

Recent reports have suggested that long-term, intensive physical training may be associated with adverse cardiovascular effects, including the development of myocardial fibrosis. However, the dose–response association of different levels of lifelong physical activity on myocardial fibrosis has not been evaluated.

Methods and Results—

Seniors free of major chronic illnesses were recruited from predefined populations based on the consistent documentation of stable physical activity over >25 years and were classified into 4 groups by the number of sessions/week of aerobic activities ≥30 minutes: sedentary (group 1), <2 sessions; casual (group 2), 2 to 3 sessions; committed (group 3), 4 to 5 sessions; and Masters athletes (group 4), 6 to 7 sessions plus regular competitions. All subjects underwent cardiopulmonary exercise testing and cardiac magnetic resonance imaging, including late gadolinium enhancement assessment of fibrosis. Ninety-two subjects (mean age 69 years, 27% women) were enrolled. No significant differences in age or sex were seen between groups. Median peak oxygen uptake was 25, 26, 32, and 40 mL/kg/min for groups 1, 2, 3, and 4, respectively. Cardiac magnetic resonance imaging demonstrated increasing left ventricular end-diastolic volumes, end-systolic volumes, stroke volumes, and masses with increasing doses of lifelong physical activity. One subject in group 2 had late gadolinium enhancement in a noncoronary distribution, and no subjects in groups 3 and 4 had evidence of late gadolinium enhancement.

Conclusions—

A lifelong history of consistent physical activity, regardless of dose ranging from sedentary to competitive marathon running, was not associated with the development of focal myocardial fibrosis.
Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease
Authors: Jones W. Schuyler , Baumgartner Iris , Hiatt William R. , Heizer Gretchen , Conte Michael S. , White Christopher J. , Berger Jeffrey S. , Held Peter , Katona Brian G. , Mahaffey Kenneth W. , Norgren Lars , Blomster Juuso , Millegård Marcus , Reist Craig , Patel Manesh R. , Fowkes F. Gerry R.
Published: November 2016

Background:

In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.

Methods:

The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.

Results:

Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98–1.23,
P
=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08–1.55,
P
=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86–6.25,
P
<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88–1.15;
P
=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86–1.15;
P
=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78–1.36;
P
=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83–1.59;
P
=0.41). The median duration of follow-up was ≈30 months.

Conclusions:

After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01732822.
Aimed Inquiry and Positive Theology in Sefer Maʿayan ha-Ḥokhmah
Authors: Porat Oded
Published: November 2016

This article discusses the anonymous early kabbalistic work Sefer Maʿayan ha-Ḥokhmah (The Book of the Fountain of Wisdom), one of the pivotal works of ʿIyyun literature. The first part deals with the book’s historical and literary aspects. The second part interprets a specific formulation in light of the basic ideas of the book itself, presenting the twofold pattern as a mystical type and as a grounding for linguistic-theological theory. The third part discusses the term “positive theology” in the theosophical and religious dimension, from the phenomenological perspective of extrovertive mysticism, and as a linguistic structure that provides the layer of signs as a stable basis for the restrained progress of Tongue. Acquiring the source as hidden but attendant by its constant grounding as a part of linguistic progression, uses the bifocal sight of binary extrovertive mysticism to denote the twofold structure of each being and each part of speech.
New Perspectives on the Significance of the Scrolls for the New Testament and Early Christian Literature
Authors: Brooke George J.
Published: November 2016

This article places the contributions of the thematic volume in the larger research context where the Dead Sea Scrolls and early Christian source texts have been juxtaposed and compared with each other. Whereas earlier scholarship was keen on identifying direct links and dependencies or, alternatively, underlining dissimilarities between the Scrolls’ Judaean priestly movement and the Galilean non-elite Jesus movement and its diaspora follow-up, this thematic volume represents more nuanced attempts to contextualise the similarities and differences in appropriate ways and find new ways of thinking that illuminate both textual corpora.
Initiation and the Ritual Purification from Sin: Between Qumran and the Apostolic Tradition
Authors: Furstenberg Yair
Published: November 2016

Second Temple Judaism witnessed the rise of a new approach to sin impurity. While in the Hebrew Bible sin impurity was associated with improper actions, and there was no formula to dissipate it, this form of impurity underwent a process of reification during the Second Temple period and was consequently identified with specific objects and people, such as idols, gentiles and “outsiders” in general. Consequently, the distinction between moral and ritual impurity was blurred, and practices for the disposal of bodily impurity were gradually applied to carriers of sin impurity. Arguably, both Qumran sectarians and Christians shared this Second Temple tendency, and it shaped their common ritual language. In this article, I examine the gradual development of initiation as a locus of purification from sin impurity in various Qumran texts and in the Christian Apostolic Tradition. The two corpora share the challenge of expelling the impure presence of sin through concrete ritual patterns of bodily purification. Although they seem to differ in their choice of ritual resources, in both cases the principles of gradual bodily purification merge with the language of exorcism to create a separate purification procedure in addition to the initial rite of initiation.
Hydrolysis probe-based PCR for detection of Pratylenchus crenatus, P. neglectus and P. penetrans
Authors: Oliveira Claudio M.G. , Blok Vivian , Neilson Roy , Mróz Tomasz , Roberts David
Published: November 2016

Molecular detection of pest and pathogens relies on rapid and dependable methods for their identification as well as an assessment of their abundance. This study describes the development and evaluation of a diagnostic method for detection ofPratylenchus crenatus,P. penetransandP. neglectus, based on a hydrolysis probe qPCR assay. Primer/probe sets were designed targeting the ITS-1 rDNA. In order to assess the specificity, primer/probe sets were tested with samples of non-targetPratylenchusspecies andRadopholus similis. Experiments using dilutions of purified plasmid standards tested the sensitivity of the hydrolysis assay against detection of DNA extracted from individual nematodes. Target DNA was detected in soil samples collected from potato fields and this indicated thatP. crenatus,P. neglectusandP. penetransare widely distributed in Scotland, frequently co-existing in mixed populations, withP. crenatusmore prevalent than eitherP. neglectusorP. penetrans.
Male-biased litter sex ratio in the southernmost Iberian population of edible dormouse: a strategy against isolation?
Authors: Ferrandiz-Rovira Mariona , Freixas Lídia , Torre Ignasi , Míguez Sílvia , Arrizabalaga Antoni
Published: November 2016

Litter sex ratio is a key component of parental fitness due to its impact on lifetime reproductive success. Multiple causes may lay at the origin of sex ratio variation among species and populations, such as maternal condition, local resource competition, presence of helpers, habitat quality or inbreeding levels. Whereas variation in sex allocation between species is relatively well understood, it is still unclear how and why litter sex allocation differs within species. Here, we present an analysis of litter sex ratio variation in two populations of edible dormice (Glis glis) over nine years of study. Populations are situated in the Montnegre and Montseny massifs in Catalonia (NE Iberian Peninsula). The Montnegre population is nowadays an isolated population located at the southernmost range edge of the species in the Iberian Peninsula. Litter sex ratio was male-biased in Montnegre but balanced in Montseny, whereas both populations showed a balanced adult sex ratio. We suggest that this differential sex allocation investment in Montnegre, may be a strategy to overcome isolation effects in this massif, as males are the dispersing sex in this and other rodent species.
The Impact of Contingency Fees on Collective Antitrust Actions: Experiments from Lithuania and Poland
Authors: Juška Žygimantas
Published: November 2016

Contingency-fee agreements are one—if not the only—tool that can be used to ensure that small-stakes collective antitrust actions are heard, yet they are subject to strong resistance from the European Union. There is a concern that contingency fees could lead to abuses of the system or conflicts of interest, as has been seen in the United States. Contrary to eu policy, two proactive member states—Lithuania and Poland—have introduced the possibility of using contingency fees in group litigation in order to facilitate group actions. Despite having a lot of potential, this paper will demonstrate that the introduction alone of contingency fees will not facilitate the compensation objective that is embedded in the Directive on damages actions. In addition, it will show that the safeguard policy against frivolous litigation is sufficient to limit the possibilities for litigation abuses, but it is ineffective for monitoring the individual behavior of group representatives.
The Requirements and Limits of the Codification of Administrative Procedures in Slovenia According to European Trends
Authors: Kovač Polonca
Published: November 2016

In regulating administrative procedures, legislators at the national and European levels should devote special attention to the codification of procedural rights in administrative relations that are recognized as European principles of good administration. Furthermore, there is a normative issue to be addressed between a more or less centralized general codification, with common minimum standards applying in any kind of administrative relation, and the admissibility of special procedural rules adapted to the specifics of individual administrative areas. A comparative analysis of the Slovenian General Administrative Procedure Act and eu standards regarding principles of administrative procedures is conducted in order to identify the role of principles, such as the right to be heard, the right of access to information, and the right to legal protection, on the national level. An additional analysis of the case law of the Slovenian Constitutional Court shows that the general codification of respective procedural rights is indispensable in pursuing the principle of the equal protection of rights. The Slovenian case can serve as a model for other, especially Eastern European, countries. The author argues that there is a need for general codification, which should not be overly detailed, but which should still serve the basic objectives of administrative procedures, namely ensuring substantive rights and the most important legal interests of the parties, in addition to guaranteeing effective protection of the public interest. At the same time, special rules should be allowed as exceptions in order to regulate sector-specific aspects, while nonetheless ensuring that such rules remain in compliance with European and constitutional procedural principles.
Mechanisms Controlling the Downstream Poleward Deflection of Midlatitude Storm Tracks
Authors: Tamarin Talia , Kaspi Yohai
Published: November 2016

The Atlantic and Pacific storm tracks in the Northern Hemisphere are characterized by a downstream poleward deflection, which has important consequences for the distribution of heat, wind, and precipitation in the midlatitudes. In this study, the spatial structure of the storm tracks is examined by tracking transient cyclones in an idealized GCM with a localized ocean heat flux. The localized atmospheric response is decomposed in terms of a time- and zonal-mean background flow, a stationary wave, and a transient eddy field. The Lagrangian tracks are used to construct cyclone composites and perform a spatially varying PV budget. Three distinct mechanisms that contribute to the poleward tilt emerge: transient nonlinear advection, latent heat release, and stationary advection. The downstream evolution of the PV composites shows the different role played by the stationary wave in each region. In the region where the tilt is maximized, all three mechanisms contribute to the poleward propagation of the low-level PV anomaly associated with the cyclone. Upstream of that region, the stationary wave is opposing the former two, and the poleward tendency is therefore reduced. Finally, through repeated experiments with enhanced strength of the heating source, it is shown that the poleward deflection of the storms enhances when the amplitude of the stationary wave increases.