bluuebunny/crossref_metadata_2025 huggingface dataset:
A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation
Authors: Toepfer Christopher N. , Sikkel Markus B. , Caorsi Valentina , Vydyanath Anupama , Torre Iratxe , Copeland O'Neal , Lyon Alexander R. , Marston Steven B. , Luther Pradeep K. , Macleod Kenneth T. , West Timothy G. , Ferenczi Michael A.
Published: May 2016

Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic “compensation” and congestive “decompensation.” Nothing is known about the ability of uninfarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drives progression of compensation. We hypothesized that enhanced cross-bridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared with noninfarcted controls. Isometric force during submaximal activations was raised >2.4-fold, while power was 2-fold greater. Electron and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae.
Biosynthesis of oxidized lipid mediators via lipoprotein-associated phospholipase A2hydrolysis of extracellular cardiolipin induces endothelial toxicity
Authors: Buland Justin R. , Wasserloos Karla J. , Tyurin Vladimir A. , Tyurina Yulia Y. , Amoscato Andrew A. , Mallampalli Rama K. , Chen Bill B. , Zhao Jing , Zhao Yutong , Ofori-Acquah Solomon , Kagan Valerian E. , Pitt Bruce R.
Published: May 2016

We (66) have previously described an NSAID-insensitive intramitochondrial biosynthetic pathway involving oxidation of the polyunsaturated mitochondrial phospholipid, cardiolipin (CL), followed by hydrolysis [by calcium-independent mitochondrial calcium-independent phospholipase A2-γ (iPLA2γ)] of oxidized CL (CLox), leading to the formation of lysoCL and oxygenated octadecadienoic metabolites. We now describe a model system utilizing oxidative lipidomics/mass spectrometry and bioassays on cultured bovine pulmonary artery endothelial cells (BPAECs) to assess the impact of CLox that we show, in vivo, can be released to the extracellular space and may be hydrolyzed by lipoprotein-associated PLA2(Lp-PLA2). Chemically oxidized liposomes containing bovine heart CL produced multiple oxygenated species. Addition of Lp-PLA2hydrolyzed CLox and produced (oxygenated) monolysoCL and dilysoCL and oxidized octadecadienoic metabolites including 9- and 13-hydroxyoctadecadienoic (HODE) acids. CLox caused BPAEC necrosis that was exacerbated by Lp-PLA2. Lower doses of nonlethal CLox increased permeability of BPAEC monolayers. This effect was exacerbated by Lp-PLA2and partially mimicked by authentic monolysoCL or 9- or 13-HODE. Control mice plasma contained virtually no detectable CLox; in contrast, 4 h after Pseudomonas aeruginosa ( P. aeruginosa) infection, 34 ± 8 mol% ( n = 6; P < 0.02) of circulating CL was oxidized. In addition, molar percentage of monolysoCL increased twofold after P. aeruginosa in a subgroup analyzed for these changes. Collectively, these studies suggest an important role for 1) oxidation of CL in proinflammatory environments and 2) possible hydrolysis of CLox in extracellular spaces producing lysoCL and oxidized octadecadienoic acid metabolites that may lead to impairment of pulmonary endothelial barrier function and necrosis.
Alveolar epithelial disintegrity in pulmonary fibrosis
Authors: Kulkarni Tejaswini , de Andrade Joao , Zhou Yong , Luckhardt Tracy , Thannickal Victor J.
Published: May 2016

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline in lung function, resulting in significant morbidity and mortality. Current concepts of the pathogenesis of IPF primarily center on dysregulated epithelial cell repair and altered epithelial-mesenchymal communication and extracellular matrix deposition following chronic exposure to cigarette smoke or environmental toxins. In recent years, increasing attention has been directed toward the role of the intercellular junctional complex in determining the specific properties of epithelia in pulmonary diseases. Additionally, recent genomewide association studies suggest that specific genetic variants predictive of epithelial cell dysfunction may confer susceptibility to the development of sporadic idiopathic pulmonary fibrosis. A number of genetic disorders linked to pulmonary fibrosis and familial interstitial pneumonias are associated with loss of epithelial integrity. However, the potential links between extrapulmonary clinical syndromes associated with defects in epithelial cells and the development of pulmonary fibrosis are not well understood. Here, we report a case of hereditary mucoepithelial dysplasia that presented with pulmonary fibrosis and emphysema on high-resolution computed tomography. This case illustrates a more generalizable concept of epithelial disintegrity in the development of fibrotic lung diseases, which is explored in greater detail in this review article.
Vascular endothelial-cadherin downregulation as a feature of endothelial transdifferentiation in monocrotaline-induced pulmonary hypertension
Authors: Nikitopoulou Ioanna , Orfanos Stylianos E. , Kotanidou Anastasia , Maltabe Violetta , Manitsopoulos Nikolaos , Karras Panagiotis , Kouklis Panos , Armaganidis Apostolos , Maniatis Nikolaos A.
Published: May 2016

Increased pulmonary vascular resistance in pulmonary hypertension (PH) is caused by vasoconstriction and obstruction of small pulmonary arteries by proliferating vascular cells. In analogy to cancer, subsets of proliferating cells may be derived from endothelial cells transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within endothelial cells in PH, we injected rats with alkaloid monocrotaline to induce PH and measured lung tissue levels of endothelial-specific protein and critical differentiation marker vascular endothelial (VE)-cadherin. VE-cadherin expression by immonoblotting declined significantly 24 h and 15 days postinjection to rebound to baseline at 30 days. There was a concomitant increase in transcriptional repressors Snail and Slug, along with a reduction in VE-cadherin mRNA. Mesenchymal markers α-smooth muscle actin and vimentin were upregulated by immunohistochemistry and immunoblotting, and α-smooth muscle actin was colocalized with endothelial marker platelet endothelial cell adhesion molecule-1 by confocal microscopy. Apoptosis was limited in this model, especially in the 24-h time point. In addition, monocrotaline resulted in activation of protein kinase B/Akt, endothelial nitric oxide synthase (eNOS), nuclear factor (NF)-κB, and increased lung tissue nitrotyrosine staining. To understand the etiological relationship between nitrosative stress and VE-cadherin suppression, we incubated cultured rat lung endothelial cells with endothelin-1, a vasoconstrictor and pro-proliferative agent in pulmonary arterial hypertension. This resulted in activation of eNOS, NF-κB, and Akt, in addition to induction of Snail, downregulation of VE-cadherin, and synthesis of vimentin. These effects were blocked by eNOS inhibitor Nω-nitro-l-arginine methyl ester. We propose that transcriptional repression of VE-cadherin by nitrosative stress is involved in endothelial-mesenchymal transdifferentiation in experimental PH.
Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension
Authors: Nozik-Grayck Eva , Woods Crystal , Stearman Robert S. , Venkataraman Sujatha , Ferguson Bradley S. , Swain Kalin , Bowler Russell P. , Geraci Mark W. , Ihida-Stansbury Kaori , Stenmark Kurt R. , McKinsey Timothy A. , Domann Frederick E.
Published: May 2016

Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2′-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression.
Haplotype and diplotype analyses of variation inERCC5transcriptioncis-regulation in normal bronchial epithelial cells
Authors: Zhang Xiaolu , Crawford Erin L. , Blomquist Thomas M. , Khuder Sadik A. , Yeo Jiyoun , Levin Albert M. , Willey James C.
Published: May 2016

Excision repair cross-complementation group 5 ( ERCC5) gene plays an important role in nucleotide excision repair, and dysregulation of ERCC5 is associated with increased lung cancer risk. Haplotype and diplotype analyses were conducted in normal bronchial epithelial cells (NBEC) to better understand mechanisms responsible for interindividual variation in transcript abundance regulation of ERCC5. We determined genotypes at putative ERCC5 cis-regulatory SNPs ( cis-rSNP) rs751402 and rs2296147, and marker SNPs rs1047768 and rs17655. ERCC5 allele-specific transcript abundance was assessed by a recently developed targeted sequencing method. Syntenic relationships among alleles at rs751402, rs2296147, and rs1047768 were assessed by allele-specific PCR followed by Sanger sequencing. We then assessed association of ERCC5 allele-specific expression at rs1047768 with haplotype and diplotype structure at cis-rSNPs rs751402 and rs2296147. Genotype analysis revealed significantly ( P < 0.005) higher interindividual variation in allelic ratios in cDNA samples relative to matched gDNA samples at both rs1047768 and rs17655. By diplotype analysis, mean expression was higher at the rs1047768 alleles syntenic with rs2296147 T allele compared with rs2296147 C allele. Furthermore, mean expression was lower at rs17655 C allele, which is syntenic with G allele at a linked SNP rs873601 ( D′ = 0.95). These data support the conclusions that in NBEC, T allele at SNP rs2296147 upregulates ERCC5, variation at rs751402 does not alter ERCC5 regulation, and that C allele at SNP rs17655 downregulates ERCC5. Variation in ERCC5 transcript abundance associated with allelic variation at these SNPs could result in variation in NER function in NBEC and lung cancer risk.
Coronary artery disease susceptibility gene ADTRP regulates cell cycle progression, proliferation, and apoptosis by global gene expression regulation
Authors: Luo Chunyan , Wang Fan , Qin Subo , Chen Qiuyun , Wang Qing K.
Published: May 2016

The ADTRP gene encodes the androgen-dependent TFPI-regulating protein and is a susceptibility gene for contrary artery disease (CAD). We performed global gene expression profiling for ADTRP knock-down using microarrays in human HepG2 cells. Follow-up real-time RT-PCR analysis demonstrated that ADTRP knock-down regulates a diverse set of genes, including upregulation of seven histone genes, downregulation of multiple cell cycle genes ( CCND1, CDK4, and CDKN1A), and upregulation of apoptosis genes ( CASP7 and PDCD2) in HepG2 cells and endothelial cells. Consistently, ADTRP increases the number of S phase cells during cell cycle, promotes cell proliferation, and inhibits apoptosis. Our study provides novel insights into the function of ADTRP and biological pathways involving ADTRP, which may be involved in the pathogenesis of CAD.
Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity
Authors: Tarale Prashant , Chakrabarti Tapan , Sivanesan Saravanadevi , Naoghare Pravin , Bafana Amit , Krishnamurthi Kannan
Published: May 2016

Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson’s disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson’s disease is characterized by theα-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression ofα-synuclein.α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis.α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson’s disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson’s disease.
The Spectrum and Clinical Impact of Epigenetic Modifier Mutations in Myeloma
Authors: Pawlyn Charlotte , Kaiser Martin F. , Heuck Christoph , Melchor Lorenzo , Wardell Christopher P. , Murison Alex , Chavan Shweta S. , Johnson David C. , Begum Dil B. , Dahir Nasrin M. , Proszek Paula Z. , Cairns David A. , Boyle Eileen M. , Jones John R. , Cook Gordon , Drayson Mark T. , Owen Roger G. , Gregory Walter M. , Jackson Graham H. , Barlogie Bart , Davies Faith E. , Walker Brian A. , Morgan Gareth J.
Published: May 2016

Purpose: Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike other B-cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been reported previously. We sought to address this using the results from whole-exome sequencing in the context of a large prospective clinical trial of newly diagnosed patients and targeted sequencing in a cohort of previously treated patients for comparison.

Experimental Design: Whole-exome sequencing analysis of 463 presenting myeloma cases entered in the UK NCRI Myeloma XI study and targeted sequencing analysis of 156 previously treated cases from the University of Arkansas for Medical Sciences (Little Rock, AR). We correlated the presence of mutations with clinical outcome from diagnosis and compared the mutations found at diagnosis with later stages of disease.

Results: In diagnostic myeloma patient samples, we identify significant mutations in genes encoding the histone 1 linker protein, previously identified in other B-cell malignancies. Our data suggest an adverse prognostic impact from the presence of lesions in genes encoding DNA methylation modifiers and the histone demethylase KDM6A/UTX. The frequency of mutations in epigenetic modifiers appears to increase following treatment most notably in genes encoding histone methyltransferases and DNA methylation modifiers.

Conclusions: Numerous mutations identified raise the possibility of targeted treatment strategies for patients either at diagnosis or relapse supporting the use of sequencing-based diagnostics in myeloma to help guide therapy as more epigenetic targeted agents become available. Clin Cancer Res; 22(23); 5783–94. ©2016 AACR.
Submaximal Exercise Systolic Blood Pressure and Heart Rate at 20 Years of Follow‐up: Correlates in the Framingham Heart Study
Authors: Spartano Nicole L. , Lyass Asya , Larson Martin G. , Lewis Gregory D. , Vasan Ramachandran S.
Published: May 2016

Background

Beyond their resting values, exercise responses in blood pressure (
BP
) and heart rate (
HR
) may add prognostic information for cardiovascular disease (
CVD
). In cross‐sectional studies, exercise
BP
and
HR
responses correlate with
CVD
risk factors; however, it is unclear which factors influence longitudinal changes in exercise responses over time, which is important for our understanding of the development of
CVD
.

Methods and Results

We assessed
BP
and
HR
responses to low‐level exercise tests (6‐minute Bruce protocol) in 1231 Framingham Offspring participants (55% women) who underwent a routine treadmill test in 1979–1983 (baseline; mean age 39±8 years) that was repeated in 1998–2001 (follow‐up; mean age 58±8 years). Adjusting for baseline exercise responses, we related the follow‐up exercise responses to baseline
CVD
risk factors and to their changes between examinations. Compared with men, women had greater rise in exercise systolic (S)
BP
and
HR
at 20‐year follow‐up (both
P
<0.005). Baseline blood lipid levels, resting
SBP
and
HR
, and smoking status were associated with greater exercise
SBP
at follow‐up (all
P
<0.05). Weight gain across examinations was associated with higher exercise
SBP
and
HR
at follow‐up (both
P
<0.0001). Smoking cessation was associated with a 53% reduced risk of attaining the highest quartile of exercise
SBP
(≥180 mm Hg) at follow‐up (
P
<0.05).

Conclusion

An adverse
CVD
risk factor profile in young adults and its worsening over time were associated with higher
SBP
and
HR
responses to low‐level exercise in midlife. Maintaining or adopting a healthy risk factor profile may favorably impact the exercise responses over time.
Excessively High Hydration Volume May Not Be Associated With Decreased Risk of Contrast‐Induced Acute Kidney Injury After Percutaneous Coronary Intervention in Patients With Renal Insufficiency
Authors: Liu Yong , Li Hualong , Chen Shiqun , Chen Jiyan , Tan Ning , Zhou Yingling , Liu Yuanhui , Ye Piao , Ran Peng , Duan Chongyang , Chen Pingyan
Published: May 2016

Background

No well‐defined protocols currently exist regarding the optimal rate and duration of normal saline administration to prevent contrast‐induced acute kidney injury (
CI
‐
AKI
) in patients with renal insufficiency.

Methods and Results

Hydration volume ratios (hydration volume/weight;
HV
/W) were calculated in 1406 patients with renal insufficiency (estimated glomerular filtration rate [
eGFR
], <90 mL/min per 1.73 m
2
) undergoing percutaneous coronary intervention (
PCI
) with routine speed hydration (1 or 0.5 mL/kg per hour). We investigated the relationship between hydration volume, risk of
CI
‐
AKI
(increase in serum creatinine ≥0.5 mg/dL or 25% within 48–72 hours), and prognosis. Mean follow‐up duration was 2.85±0.88 years. Individuals with higher
HV
/W were more likely to develop
CI
‐
AKI
(quartiles: Q1, Q2, Q3, and Q4: 4.3%, 6.6%, 10.9%, and 15.0%, respectively;
P
<0.001). After adjusting 12 confounders, including age, sex,
eGFR
, anemia, emergent
PCI
, diabetes mellitus, chronic heart failure, diuretics, contrast volume, lesions, smoking status, and number of stents, multivariate analysis showed that a higher
HV
/W ratio was not associated with a decreased
CI
‐
AKI
risk (Q2 vs Q1: adjusted odds ratio [
OR
], 1.13; Q3 vs Q1: adjusted
OR
, 1.51; Q4 vs Q1: adjusted
OR
, 1.87; all
P
>0.05) and even increased
CI
‐
AKI
risk (
HV
/W >25 mL/kg: adjusted
OR
, 2.11; 95%
CI
, 1.24–3.59;
P
=0.006). Additionally, higher
HV
/W was significantly associated with an increased risk of death (Q4 vs Q1: adjusted hazard ratio, 3.44; 95%
CI
, 1.20–9.88;
P
=0.022).

Conclusions

Excessively high hydration volume at routine speed might be associated with increased risk of
CI
‐
AKI
and death post‐
PCI
in patients with renal insufficiency.
Class origin and sibling similarities in long-term income
Authors: Andrade Stefan Bastholm
Published: May 2016

Sibling correlations have gained increasing prominence in inequality studies as a measurement of the total impact of family background on individual outcomes. Whilst previous studies have tended to use traditional socio-economic measures such as parent’s income or education, this paper introduces an analytical class approach to sibling studies by analysing how much of the influence that siblings share in their long-term income results from class origin. Data are from Statistics Denmark and consist of 290,399 individuals born between 1963 and 1973. Models are estimated which – in addition to parents’ education and income – include modifications of the Erikson–Goldthorpe–Portocarero schemes ranging from 3 to 15 classes and Grusky’s micro-class scheme of 72 classes. The results show that although class adds to explanations of the family influence on children’s income, most of the sibling similarities are not explained by parental education, income or class. Depending on gender, the class schemes explain between 8 and 13 per cent of the sibling similarities and 15 to 20 per cent when parents’ income and educations are also included. Models with different class schemes demonstrate that elaborated versions of the EGP class scheme add little to the explanation of similarities between brothers, sisters and mixed siblings.
Cohort differences in intergenerational income transmission in Finland
Authors: Sirniö Outi , Kauppinen Timo M , Martikainen Pekka
Published: May 2016

Major social changes such as occupational restructuring, educational expansion and increasing income inequality are likely to significantly influence the intergenerational transmission of income. The aim in this article is to investigate this question in an analysis of the transmission of low and high income in Finland in five birth cohorts born between 1956 and 1978. The focus is on the contribution of parental social class and personal educational level to this association. The analyses are based on a longitudinal register-based data set that is a representative 11-per-cent sample of the Finnish population. The level of intergenerational income transmission among those with a low- and a high-income parental background is stable among men, and is increasing slightly among women. Simultaneously, the role of achieved education as a mechanism strengthens slightly upon entry to the lowest income level, and declines upon entry to the highest level. These results indicate that despite the increasing income inequality, intergenerational transmission remains rather stable, but the mediating role of educational qualifications may have changed. Occupational restructuring seems to have no clear influence on the process.
Transcranial Doppler Emboli Identifies Asymptomatic Carotid Patients at High Stroke Risk: Why This Technique Should be Used More Widely
Authors: Spence J. David
Published: May 2016

With modern intensive medical therapy, the annual risk of ipsilateral stroke in asymptomatic carotid stenosis (ACS) is now ∼0.5%. Therefore, even the relative low risks reported from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) trial do not justify routine intervention in most (90%) of the patients with ACS. It is therefore necessary to identify the ∼10% to15% of patients with ACS who have a stroke risk high enough to justify intervention. Transcranial Doppler (TCD) embolus detection has been shown in 2 prospective studies (one with 468 patients and the other with 467 patients) to identify patients at high risk and distinguish them from those who would be better served by medical therapy. There is no valid reason why carotid intervention should be carried out in ACS without first identifying that the patient’s risk of stroke is higher than the risk of intervention. The best validated way to do this is by TCD embolus detection, and the cost of TCD equipment and training is approximately the same as the cost of 2 carotid stenting procedures in the United States. This procedure should be used more widely.
Femoral Artery Ultrasound Examination
Authors: Lucatelli Pierleone , Fagnani Corrado , Tarnoki Adam Domonkos , Tarnoki David Laszlo , Stazi Maria Antonietta , Salemi Miriam , Cirelli Carlo , Sacconi Beatrice , d’Adamo Alessandro , Fanelli Fabrizio , Catalano Carlo , Pucci Giacomo , Schillaci Giuseppe , Baracchini Claudio , Medda Emanuela
Published: May 2016

We compared intima–media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment.
Illicit Tactics as Substitutes
Authors: Kuo Didi , Teorell Jan
Published: May 2016

What is the relationship between ballot reforms and electoral malpractice? This article contributes to the growing comparative politics literature on the causes of election fraud in democratizing countries using the case of the 19th-century United States. We examine the adoption of the Australian ballot and disenfranchisement laws, and estimate their effects on multiple types of election fraud. Using a new measure of fraud in elections to the House of Representatives from 1860 to 1930, we find that the Australian ballot and disenfranchisement measures reduced vote-buying and voter intimidation. However, we further find that the Australian ballot had an “iatrogenic effect” of increasing registration and ballot fraud. Voting secrecy therefore led to substitution of one illicit electoral tactic for another.
“I Am More Than What I Look Alike”
Authors: Liang Jia “Grace” , Peters-Hawkins April L.
Published: May 2016

Purpose: Little research exists that examines the leadership experiences of Asian American women in public schools. This study sought to understand the meanings Asian American women school administrators have constructed out of their professional lives given the intersection of gender, race-ethnicity, and leadership. Research Method/Approach: Data collection primarily relied on semistructured in-depth interviews and informal observations with 11 building-level administrators in two demographically contrasting states in the United States. Data were analyzed through constant comparative methods, using three iterations of initial codes/surface content analysis, pattern variables development, and application to data set. Findings: The Asian American women’s paths to leadership were to a large degree emergent and personal. The women embraced a lifetime mission as to make a difference on their students’ lives and uplift the social groups embodied in their identities. They struggled with gender, racial-ethnic, and cultural discrimination. Critiques and resistance to racism were often tempered, particularly in their professional lives, as evident in their careful usage of agentic behavior and balanced communal practices. Their agency to fully assume leadership and fight against the oppressive system was a cooperant process of survival, the “I have to,” and resistance, the “I want to and can.” Conclusion: By centering on the lived experiences of Asian American women, this study adds a new intersectionality, positionality, and voice to the established knowledge about women of color and educational leadership.
Designing a smart electrically heated sleeping bag to improve wearers’ feet thermal comfort while sleeping in a cold ambient environment
Authors: Zhang Chengjiao , Ren Chongguang , Li Ying , Song Wenfang , Xu Pengjun , Wang Faming
Published: May 2016

In this study, a novel smart electrically heated sleeping bag was developed by incorporating a proportional–integral–derivative heating control system into a traditional sleeping bag. The smart sleeping bag was aimed to maintain human feet temperature within the thermoneutral range (i.e. 25.0–34.0℃) by automatically adjusting the heat power to the feet region based on real-time human toe temperatures. Subsequently, the performance of the newly developed smart sleeping bag in improving human thermal comfort was investigated by human trials. Eight female subjects underwent two 8-hour sleep trials, that is, the smart sleeping bag with power turned on (SleepingbagHT) and the smart sleeping bag with power turned off (SleepingbagCON). All trials were performed at an air temperature of 6.1 ± 0.5℃ (i.e. the EN 13537 defined comfort temperature for females), relative humidity of 80 ± 5% and air velocity of 0.4 ± 0.1 m/s. It was found that SleepingbagHT could maintain both the foot and toe temperatures within the thermal neutral range as well as keep the local-, and whole-body thermal and comfort sensations in thermal neutral state throughout the 8-hour cold exposure. In contrast, linearly decreasing foot and toe temperatures and aggravated local-, and whole-body thermal and comfort sensations were detected in SleepingbagCON within a 4.5-hour cold exposure. It could thus be concluded that the smart electrical heating sleeping bag was able to provide wearers an 8-hour comfortable sleep in the studied cold environment.
Market expansion, state intervention and wage differentials between economic sectors in urban China: A multilevel analysis
Authors: Liu Ye , Xu Wei , Shen Jianfa , Wang Guixin
Published: May 2016

The rising earnings inequality in China has sparked a heated debate on the socioeconomic outcomes of market transformation. While a large body of literature has focussed on the temporal trend of wage inequality during the reform period, much less attention has been devoted to the structural causes of regional variations in sectoral wage differentials. Using a micro-data sample from the 2005 one percent population sample survey and multilevel methods, this article examines the geographic variability of wage differentials between economic sectors in urban China, with a particular focus on the combination effects of market expansion and state intervention. The results indicate that sectoral wage differentials vary substantially across regions, and that market expansion interacts with state intervention to reconfigure earnings outcomes. Specifically, prefectures located in the interior region tend to exhibit a large wage premium for the state sectors, while prefectures located in the coastal region tend to display a wage advantage of the foreign-invested sector. The wage gap between the state and non-state sectors is smaller in areas with diversified ownership; openness to foreign investment increases the relative wages of foreign-invested-sector employees; stringent government regulation of industries increases the wage gap between the state monopoly sector and the non-monopoly sector; and strong redistributive power increases the wage premium for the public service sector over other sectors. Our findings suggest the necessity to take into account contextually constituted and locally specific wage-setting mechanisms when studying China’s wage inequality.
Wittgenstein, Tolstoy, and the “Apocalyptic View”
Authors: Lovibond Sabina
Published: May 2016

Some aspects of Wittgenstein’s thought are considered in the light of a remark he makes about the “apocalyptic” view of the world. The influence of Tolstoy on Wittgenstein is discussed and elaborated with reference to the idea of a “form of life” as a locus of order, and also to that of “exceptionality” in an unfolding course of events—the latter setting up a connection with the “apocalyptic” theme. This imaginative backdrop remains discernible in Wittgenstein’s later philosophy, which draws upon it to perhaps unexpected effect in achieving a dialectical balance between the motifs of order and breakdown.
Are Rural Costs of Living Lower? Evidence from a Big Mac Index Approach
Authors: Loveridge Scott , Paredes Dusan
Published: May 2016

Rural leaders can point to low housing costs as a reason that their area should be competitive for business attraction. To what extent do rural housing costs offset transportation and other locational disadvantages in cost structures? The United States lacks information to systematically answer the question. We adapt a strategy employed by The Economist in exploring purchasing power parity: the Big Mac index. We gather information on Big Mac prices with a random sample of restaurants across the contiguous United States. We find that core metro counties exhibit slightly higher Big Mac prices than other counties, but that differences across the balance of the rural–urban continuum code are not significant, implying that costs in a metroadjacent county are not different than areas that are much more rural. We show that some groups of states exhibit lower prices, especially in the southeast. Furthermore, we test for the presence of spatial monopoly and find that distance to other MacDonald’s restaurants has some influence on price. Stores at a greater distance from their competitors tend to charge more, ceteris paribus. We also show our results are consistent with other localized estimates of living costs. Our general findings could help rural decision makers determine whether their area truly holds cost advantages for firms looking to relocate.
The catastrophe of neo-liberalism
Authors: Foster Roger
Published: May 2016

My article provides a systematic interpretation of the transformation of capitalist society in the neo-liberal era as a form of what Karl Polanyi called ‘cultural catastrophe’. I substantiate this claim by drawing upon Erich Fromm’s theory of social character. Fromm’s notion of social character, I argue, offers a plausible, psychodynamic explanation of the processes of social change and the eventual class composition of neo-liberal society. I argue, further, that Fromm allows us to understand the psychosocial basis of the process that Polanyi calls cultural catastrophe. This requires an elucidation of the major social forces of financialization and emancipation which, I argue, proved to be important formative factors in the emergence of neo-liberal society. The cultural catastrophe of neo-liberalism concerns the working class, whose prevailing social character has become misaligned with the new expectations and requirements of neo-liberal society.
Scientific and Regulatory Policy Committee Points to Consider Review
Authors: Halpern Wendy G. , Ameri Mehrdad , Bowman Christopher J. , Elwell Michael R. , Mirsky Michael L. , Oliver Julian , Regan Karen S. , Remick Amera K. , Sutherland Vicki L. , Thompson Kary E. , Tremblay Claudine , Yoshida Midori , Tomlinson Lindsay
Published: May 2016

Standard components of nonclinical toxicity testing for novel pharmaceuticals include clinical and anatomic pathology, as well as separate evaluation of effects on reproduction and development to inform clinical development and labeling. General study designs in regulatory guidances do not specifically mandate use of pathology or reproductive end points across all study types; thus, inclusion and use of these end points are variable. The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) formed a Working Group to assess the current guidelines and practices on the use of reproductive, anatomic pathology, and clinical pathology end points in general, reproductive, and developmental toxicology studies. The Working Group constructed a survey sent to pathologists and reproductive toxicologists, and responses from participating organizations were collected through the STP for evaluation by the Working Group. The regulatory context, relevant survey results, and collective experience of the Working Group are discussed and provide the basis of each assessment by study type. Overall, the current practice of including specific end points on a case-by-case basis is considered appropriate. Points to consider are summarized for inclusion of reproductive end points in general toxicity studies and for the informed use of pathology end points in reproductive and developmental toxicity studies.
Tracking Epidermal Nerve Fiber Changes in Asian Macaques
Authors: Mangus Lisa M. , Dorsey Jamie L. , Weinberg Rachel L. , Ebenezer Gigi J. , Hauer Peter , Laast Victoria A. , Mankowski Joseph L.
Published: May 2016

Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus–associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.
Cardiac resynchronization therapy for ischemic myopathy
Authors: Ikeda Shinichiro , Yoshida Hideo , Yunoki Keiji , Hisamochi Kunikazu
Published: May 2016

We performed coronary artery grafting, mitral valve plasty, and tricuspid plasty in a 75-year-old man who had double-vessel coronary disease and moderate mitral and tricuspid insufficiency. Preoperative transthoracic echocardiography revealed an ejection fraction of 34% and dyssynchronous wall motion of the septum and free wall. We placed pacing leads on the right ventricular outlet and posterior left ventricular wall for cardiac resynchronization therapy. The dyssynchrony disappeared postoperatively and the New York Heart Association functional class improved from IV to I.
Using Mindfulness-Based Strengths Practices with gifted populations
Authors: Sharp Jennifer E , Niemiec Ryan M , Lawrence Christopher
Published: May 2016

Mindfulness and character strengths are synergistic tools that work together to cultivate well-being. Mindfulness-Based Strengths Practice (MBSP) combines the research and practice of these constructs to enhance well-being, meaning, and engagement. In this article, research supporting how mindfulness and character strengths may benefit the gifted population is explored. Particular attention is devoted to exploring practical implications for the integration of mindfulness and character strengths together and the application to support gifted students and their teachers/parents. MBSP provides a promising avenue for addressing some of the unique challenges inherent in working with gifted students.
Does depth of the frontal sinus affect near-infrared spectroscopy measurement?
Authors: Holmgaard Frederik , Vedel Anne G , Langkilde Annika , Nilsson Jens C , Ravn Hanne Berg
Published: May 2016

Near-infrared spectroscopy (NIRS) is a non-invasive method that reflects real-time cerebral oxygenation (rSO2) by the use of two adhesive optodes placed on the forehead of the patient. Frontal sinuses vary anatomically and a large frontal sinus might compromise the NIRS signal since the NIRS optodes are placed at the skin surface superficial to the underlying frontal sinus. The aim of this case-series was to elucidate whether there is a difference in the obligate changes in rSO2 during cardiac surgery between patients with a small as opposed to a large anterior-posterior distance of the frontal sinus based on magnetic resonance imaging. Two matched groups with small (n = 5) vs. large (n = 5) frontal sinus (3.2 vs. 18.1 millimeters) in this case-series showed no difference in obligate changes of rSO2 (p = 0.54).
Assessment of arterial stiffness in patients with venous thromboembolism: Separate or continuous circuits?
Authors: Aykan Ahmet Çağrı , Hatem Engin , Kalaycıoğlu Ezgi , Gökdeniz Tayyar , Karabay Can Yucel
Published: May 2016

Objectives

The aim of this study is to evaluate the association of venous thromboembolism with arterial stiffness by cardio-ankle vascular index method.

Method

We included 52 patients with a documented lower extremity venous thromboembolism within the last six months and 52 healthy subjects to this cross sectional observational study.

Results

Cardio-ankle vascular index (8.58 ± 1.60 versus 7.05 ± 1.44, p < 0.001, respectively) and systolic blood pressure (128.02 ± 7.13 mmHg versus 123.94 ± 8.12 mmHg, p = 0.008, respectively) were significantly higher among patients with venous thromboembolism than controls. Cardio-ankle vascular index was an independent predictor of venous thromboembolism in multivariate logistic regression analysis (p < 0.001, odds ratio = 1.864, 95% confidence interval = 1.370–2.536). Cardio-ankle vascular index value > 7.8 had a sensitivity of 82.7% and a specificity of 80.8% for predicting venous thromboembolism (area under curve = 0.789, 95% confidence interval = 0.698–0.863, p < 0.001) in receiver operating characteristic curve analysis.

Conclusion

We found that arterial stiffness was increased in patients with venous thromboembolism which highlights the fact that arterial and venous circulation is in continuum and an insult may affect both of these circuits.
Effects of d-amphetamine upon psychosocial stress responses
Authors: Childs Emma , Bershad Anya K , de Wit Harriet
Published: May 2016

Psychostimulant drugs alter the salience of stimuli in both laboratory animals and humans. In animals, stimulants increase rates of responding to conditioned incentive stimuli, and in humans, amphetamine increases positive ratings of emotional images. However, the effects of stimulants on real-life emotional events have not been studied in humans. In this study, we examined the effect of d-amphetamine on responses to acute psychosocial stress using a public speaking task. Healthy volunteers ( N=56) participated in two experimental sessions, one with a psychosocial stressor (the Trier Social Stress Test) and one with a non-stressful control task. They were randomly assigned to receive d-amphetamine (5 mg n=18, 10 mg n=20) or placebo ( n=18) on both sessions under double blind conditions. Salivary cortisol, subjective mood, and vital signs were measured at regular intervals during the session. Subjects also provided cognitive appraisals of the tasks before and after their performances. Amphetamine produced its expected mood and physiological effects, and the Trier Social Stress Test produced its expected effects on cortisol and mood. Although neither dose of amphetamine altered cardiovascular or hormonal responses to stress, amphetamine (10 mg) increased participants’ pre-task appraisals of how challenging the task would be, and it increased post-task ratings of self-efficacy. Paradoxically, it also increased ratings of how stressful the task was, and prolonged aversive emotional responses. These findings suggest that amphetamine differentially affects stress response components: it may increase participants’ appraisals of self-efficacy without dampening the direct emotional or physiological responses to the stress.
Functional and morphological alterations associated with working memory dysfunction in patients with generalized anxiety disorder
Authors: Moon Chung-Man , Jeong Gwang-Woo
Published: May 2016

Background

Generalized anxiety disorder (GAD) has been related to functional brain activities and structural brain abnormalities.

Purpose

To investigate the neural mechanism on working memory dysfunction in patients with GAD in terms of the combined functional and morphological brain abnormalities.

Material and Methods

Patients with GAD and healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted (T1W) magnetic resonance imaging (MRI) and functional MRI (fMRI). In this study, fMRI and voxel-based morphometry (VBM) were used for assessing the differential brain activation patterns, as well as for comparing the morphological alterations between the two groups.

Results

In response to the neutral distractors, the patients showed significantly lower activities in the regions of the fusiform gyrus (FuG), superior parietal gyrus (SPG), precuneus (PCu), superior occipital gyrus (SOG), lingual gyrus (LiG), cuneus (Cun), calcarine cortex (CaC), parahippocampal gyrus (PHG) and cerebellar cortex (Cb) compared to the controls. In response to the anxiety-inducing distractors, the patients showed significantly higher activity in the hippocampus and lower activities in the regions of the dorsolateral prefrontal cortex (DLPFC), FuG, SPG, PCu, SOG, and Cb. Also, the patients showed a significant reduction of the white matter volumes in the DLPFC, anterior limb of the internal capsule (ALIC) and midbrain.

Conclusion

This study provides the first evidence for the association between the morphometric alterations and functional deficit in the working memory processing with the neutral and anxiety-inducing distractors in GAD patients. These findings would be helpful to understand the neural mechanisms on working memory impairment in connection with GAD symptoms.