bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Platelet-Monocyte Interaction in Stable COPD in the Absence of Platelet Hyper-Reactivity
Authors: Aleva Floor E. , Temba Godfrey , de Mast Quirijn , Simons Sami O. , de Groot Philip G. , Heijdra Yvonne F. , van der Ven André J.A.M.
Published: October 2017

Background: Chronic obstructive pulmonary disease (COPD) is well known for its cardiovascular co-morbidities. Increased platelet-monocyte interaction is found in COPD and may reflect altered platelet function and a potential role for anti-platelet therapy. Objectives: The objectives were to investigate platelet-monocyte interaction, platelet activation and reactivity and plasmatic coagulation in stable COPD. Methods: Platelet-monocyte interaction and platelet activation were determined by flow cytometry in 30 stable COPD patients and 25 controls. Platelet activation was measured by binding of fibrinogen to the activated fibrinogen receptor and platelet P-selectin expression at baseline and after platelet stimulation with platelet agonists. Plasmatic coagulation was measured by D-dimer and thrombin generation. Results: Platelet-monocyte interaction was increased in stable COPD (median fluorescence intensity of platelet CD61 was 19.8 [IQR 14.0-33.2] vs. 10.0 [IQR 8.7-16.7], p = 0.002). In contrast, platelet activation and reactivity, reflected by fibrinogen binding and P-selectin expression, were the same in both groups. Plasma P-selectin and interleukin-6 were increased in COPD (p = 0.01 and p = 0.02, respectively), whereas soluble fibrinogen, D-dimer and thrombin generation were similar. Conclusions: Increased platelet-monocyte interaction was found in the absence of platelet hyper-reactivity and activation of plasmatic coagulation in stable COPD. Future clinical evaluation of the effects of different anti-platelet drugs in COPD is warranted, as anti-platelet therapy may interfere with platelet-monocyte interaction.
Early Outcome after Intracranial Hemorrhage Related to Non-Vitamin K Oral Anticoagulants
Authors: Frol Senta , Pretnar Oblak Janja
Published: October 2017

Background: Intracranial hemorrhage (ICH) is a serious, life-threatening, but fortunately rare complication of non-vitamin K oral anticoagulant (NOAC) therapy. There are limited data on NOAC-related ICH prognosis. Methods: All consecutive patients admitted to a single center due to acute NOAC-related ICH from September 2012 until the beginning of 2017 were included. Risk factors, type of NOAC, and location of ICH were evaluated. Risk for ischemic and bleeding events and clinical status upon admission and at discharge were evaluated using standard scales. Results: Thirty-four patients aged 77.8 ± 8.3 years with NOAC-related ICH were included. The main predisposing risk factors were age and arterial hypertension. The median CHA2DS2-VASc score was 3.4 and the median HAS-BLED score was 1.8. Eighteen patients were treated with rivaroxaban, 11 with dabigatran, and 5 with apixaban. Ten patients (29%) had a favorable outcome with a modified Rankin Scale score ≤2 and 13 patients (38%) died. The location of the ICH was mainly intraparenchymal and subdural. Conclusions: Our retrospective single-center study shows that the mortality rate with NOAC-related ICH is <40%, which makes it comparable to that with vitamin K antagonist-related ICH.
Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment
Authors: Ishimoto Utako , Kondo Shunsuke , Ohba Akihiro , Sasaki Mitsuhito , Sakamoto Yasunari , Morizane Chigusa , Ueno Hideki , Okusaka Takuji
Published: October 2017

Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. Methods: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Results: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Conclusions: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials.
The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study
Authors: Hooghiemstra Astrid M. , Bertens Anne Suzanne , Leeuwis Anna E. , Bron Esther E. , Bots Michiel L. , Brunner-La Rocca Hans-Peter , de Craen Anton J.M. , van der Geest Rob J. , Greving Jacoba P. , Kappelle L. Jaap , Niessen Wiro J. , van Oostenbrugge Robert J. , van Osch Matthias J.P. , de Roos Albert , van Rossum Albert C. , Biessels Geert Jan , van Buchem Mark A. , Daemen Mat J.A.P. , van der Flier Wiesje M. ,   on behalf of the Heart-Brain Connection Consortium
Published: October 2017

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.
Evaluation of the Predictive Value of the Serum Calcium-Magnesium Ratio for All-Cause and Cardiovascular Mortality in Incident Dialysis Patients
Authors: Sato Hiroyuki , Takeuchi Youichi , Matsuda Ken , Saito Ayako , Kagaya Saeko , Fukami Hirotaka , Ojima Yoshie , Nagasawa Tasuku
Published: October 2017

Background/Aim: Cardiovascular disease is the most serious cause of death in patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca) levels have been associated with poor outcome and cardiovascular mortality in patients on maintenance and initiation dialysis. As a more accurate marker is warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause and cardiovascular mortality that indicates vessel calcification. Methods: We recruited 378 consecutive patients with end-stage renal disease who started dialysis between January 2009 and December 2015 at the Japanese Red Cross Ishinomaki Hospital. We collected data of patients' demographic characteristics and comorbidities from their electronic medical records. We retrospectively examined the association of the serum Ca-Mg ratio with all-cause and cardiovascular mortality using the Cox proportional hazard model, and determined the value that predicted cardiovascular death using the receiver operating characteristic (ROC) curve. Results: Overall, 253 patients with serum Mg and Ca data were analyzed. The 3-year survival rate of this group was 0.70 (95% confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12 (95% CI 0.05-0.23), which was significantly higher than that of the other groups. The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037). Conclusion: A high Ca-Mg ratio was significantly associated with all-cause and cardiovascular mortality, and it was more accurate than serum Mg.
Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis
Authors: Torres Joana , Palmela Carolina , Gomes de Sena Pedro , Santos Maria Pia Costa , Gouveia Catarina , Oliveira Maria Helena , Henriques Ana Raquel , Rodrigues Cecília , Cravo Marília , Borralho Paula
Published: October 2017

Introduction: Microscopic colitis (MC) is a chronic inflammatory bowel disease with unclear etiology. Bile acid (BA) malabsorption has been described in MC patients. Farnesoid X receptor (FXR) is the main BA receptor; FXR-mediated mechanisms prevent the noxious effects of BA accumulation, preserving the integrity of the intestinal epithelial barrier and preventing intestinal inflammation. Aim: Our aim was to describe the expression of FXR in patients with MC. Methods: Archival formalin-fixed paraffin-embedded samples from the terminal ileum, right and left colon were obtained from patients with MC and matched controls. Immunohistochemistry was performed and nuclear FXR expression scored in a semi-quantitative way. Results: 169 formalin-fixed paraffin-embedded samples from 35 patients with MC and 31 controls were retrieved. There was a significant reduction of FXR expression in patients with MC versus controls both in the right colon (moderate-strong FXR expression: 21.1 vs. 64.3%; p = 0.003) and left colon (moderate-strong FXR expression: 8.3 vs. 38.7%; p = 0.027). No significant differences in FXR expression were observed in the ileum of patients with MC (moderate-strong FXR expression: 76.9 vs. 90.9%; p = 0.5). We found no difference in FXR expression between the two types of MC. No association between the degree of lymphocyte infiltration or the thickness of collagen band and FXR expression was found. Conclusions: Patients with MC present a significantly lower expression of FXR in the colon. This could render colonic epithelial cells more susceptible to the deleterious effects of BA, contributing to disease pathogenesis and symptoms in MC.
Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis
Authors: Ma Jie , Xuan Shu-Hong , Li Yan , Zhang Zhi-Ping , Li Xin-Hua
Published: October 2017

Background: The objective of the present study was to evaluate the role of the TGFβ/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship to NPC prognosis. Methods: NPC tissues collected from 66 NPC patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues. Immunohistochemical staining was performed to assess expression of transforming growth factor-β receptor I (TGFβRI), programmed cell death 4 (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to evaluate NPC patient overall survival (OS) and progression-free-survival (PFS). Cox regression analysis was used to estimate independent prognostic factors for NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an inhibitor of TGFβRI; expression of TGFβRI and PDCD4 in CNE2 cells was determined by western blotting. NPC tissues showed higher expression of TGFβRI and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05). Results: The results of Kaplan-Meier analysis showed that TGFβRI-positive patients and AP-1-positive patients had shorter OS and PFS than TGFβRI-negative patients and AP-1-negative patients; additionally, PDCD4-positive patients had higher OS and PFS than PDCD4-negative patients. Cox regression analysis revealed that advanced tumor stage, overexpression of TGFβRI and AP-1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in NPC patients. Compared with the control group, expression of TGFβRI decreased and that of PDCD4 increased significantly in CNE2 cells treated with the inhibitor (all P < 0.05). These findings indicate that the TGFβ/PDCD4/AP-1 pathway may be associated with NPC development and progression. Conclusion: High expression of TGFβRI and AP-1 and low expression of PDCD4 may be unfavorable prognostic factors for NPC.
The Emerging Roles of CIB1 in Cancer
Authors: Wang Xianwang , Peng Xiaochun , Zhang Xueqing , Xu Hanyi , Lu Chengbiao , Liu Lian , Song Jiaxing , Zhang Yingjie
Published: October 2017

Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer’s disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression.
Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production
Authors: Kong Lingbo , Wang Biao , Yang Xiaobin , Guo Hua , Zhang Ke , Zhu Ziqi , Liu Jijun , Hao Dingjun
Published: October 2017

Background/Aims: Osteoporosis is a metabolic bone disorder that tortures about millions of people worldwide. Recent study demonstrated agents derived from picrasma quassioides is a promising drug for targets multiple signaling pathways. However its potential in treatment of bone loss has not been fully understood. Methods: The bone marrow macrophages (BMMs) were cultured and induced with M-CSF and RANKL followed by picrasidine I (PI) treatment. Then the effects of PI on osteoclast formation were evaluated by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Moreover, effects of PI on bone resorption activity of mature osteoclast were studied through bone resorption pit counting and actin ring structure analysis. Further, the involved potential signaling pathways cross-talking were investigated by performed Western blotting and quantitative real-time PCR examination. Results: Results demonstrated PI strongly inhibited RANKL induced osteoclast formation from its precursors. Mechanistically, the inhibitory effect of PI on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and NFATc1. Moreover, PI markedly blocked the RANKL-induced osteoclastogenesis by attenuating MAPKs and NF-κB signaling pathways. In addition, PI decreased the ROS generation in osteoclast and osteoblast. Conclusion: Taken together our data demonstrate that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.
Ox-LDL-Induced MicroRNA-155 Promotes Autophagy in Human Endothelial Cells via Repressing the Rheb/ mTOR Pathway
Authors: Lv Jinlin , Yang Lixia , Guo Ruiwei , Shi Yankun , Zhang Ziwei , Ye Jinshan
Published: October 2017

Background/Aims: Autophagy, an evolutionary conserved biological process, is activated in cells to cope with various types of stress. MicroRNAs control several activities related to autophagy. However, the role of autophagy-related microRNAs during atherosclerosis is far from known. MicroRNA-155 was identified to be a crucial regulator of atherosclerosis. The objectives of the study were to analyze the effect of microRNA-155 on autophagic signaling and explore its mechanism in human endothelial cells under ox-LDL stress. Methods: The study included human endothelial cells surrogate EA.hy926 lines (EA.hy926 cells). The expression of microRNA-155 was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of microRNA-155 on endothelial autophagy was observed along with the expression levels of Rheb, LC3B, Beclin1, and P62/SQSTM1 by western blotting (WB) and immunofluorescence through microRNA-155 overexpression or inhibition. Bioinformatics analysis and Luciferase reporter assay were used to explore the target gene of microRNA-155. Cell viability and apoptosis were examined by 3-[4,5-dimethylthiazol-2-yl]-5- [3-carboxy-methoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium inner salt (MTS) assay and TdT-mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay. Results: MicroRNA-155 expression was significantly increased under ox-LDL stress. MicroRNA-155 increased autophagic activity, while inhibition of it alleviated ox-LDL-induced autophagy in EA.hy926 endothelial cells. In addition, dual-luciferase reporter assays showed that microRNA-155 suppressed Rheb transcription. MicroRNA-155 increased autophagic activity in EA.hy926 cells via inhibition of Rheb-mediated mTOR/P70S6kinase/4EBP signaling pathway. Furthermore, we demonstrated that microRNA-155 could regulate not only autophagy but also apoptosis in EA.hy926 cells. Conclusions: MicroRNA-155 works as a regulator of endothelial function under ox-LDL stress, making it a potential candidate for the novel therapeutic strategies against atherosclerotic diseases.
Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease
Authors: Kuo Ho-Chang , Wong Henry Sung-Ching , Chang Wei-Pin , Chen Ben-Kuen , Wu Mei-Shin , Yang Kuender D. , Hsieh Kai-Sheng , Hsu Yu-Wen , Liu Shih-Feng , Liu Xiao , Chang Wei-Chiao
Published: October 2017

Background—

Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant.

Methods and Results—

To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher’s exact
P
value 4.518×10
−
03
and 8.224×10
−
10
, respectively).

Conclusions—

This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.
Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the
GPR98
Locus on 5q14.3
Authors: Guo Tingwei , Repetto Gabriela M. , McDonald McGinn Donna M. , Chung Jonathan H. , Nomaru Hiroko , Campbell Christopher L. , Blonska Anna , Bassett Anne S. , Chow Eva W.C. , Mlynarski Elisabeth E. , Swillen Ann , Vermeesch Joris , Devriendt Koen , Gothelf Doron , Carmel Miri , Michaelovsky Elena , Schneider Maude , Eliez Stephan , Antonarakis Stylianos E. , Coleman Karlene , Tomita-Mitchell Aoy , Mitchell Michael E. , Digilio M. Cristina , Dallapiccola Bruno , Marino Bruno , Philip Nicole , Busa Tiffany , Kushan-Wells Leila , Bearden Carrie E. , Piotrowicz Małgorzata , Hawuła Wanda , Roberts Amy E. , Tassone Flora , Simon Tony J. , van Duin Esther D.A. , van Amelsvoort Thérèse A. , Kates Wendy R. , Zackai Elaine , Johnston H. Richard , Cutler David J. , Agopian A.J. , Goldmuntz Elizabeth , Mitchell Laura E. , Wang Tao , Emanuel Beverly S. , Morrow Bernice E.
Published: October 2017

Background—

The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906) have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot (TOF), comprising the largest subset of severe congenital heart disease in the cohort.

Methods and Results—

To identify common genetic variants associated with TOF in individuals with 22q11.2DS, we performed a genome-wide association study using Affymetrix 6.0 array and imputed genotype data. In our cohort, TOF was significantly associated with a genotyped single-nucleotide polymorphism (rs12519770,
P
=2.98×10
−
8
) in an intron of the adhesion
GPR98
(G-protein–coupled receptor V1) gene on chromosome 5q14.3. There was also suggestive evidence of association between TOF and several additional single-nucleotide polymorphisms in this region. Some genome-wide significant loci in introns or noncoding regions could affect regulation of genes nearby or at a distance. On the basis of this possibility, we examined existing Hi-C chromatin conformation data to identify genes that might be under shared transcriptional regulation within the region on 5q14.3. There are 6 genes in a topologically associated domain of chromatin with
GPR98
, including
MEF2C
(Myocyte-specific enhancer factor 2C).
MEF2C
is the only gene that is known to affect heart development in mammals and might be of interest with respect to 22q11.2DS.

Conclusions—

In conclusion, common variants may contribute to TOF in 22q11.2DS and may function in cardiac outflow tract development.
Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left Atrial Deformation and Mechanics From a Large-Scale Asian Population
Authors: Liao Jo-Nan , Chao Tze-Fan , Kuo Jen-Yuan , Sung Kuo-Tzu , Tsai Jui-Peng , Lo Chi-In , Lai Yau-Huei , Su Cheng-Huang , Hung Chung-Lieh , Yeh Hung-I , Chen Shih-Ann
Published: October 2017

Background—

Left atrial (LA) function is tightly linked to several cardiovascular diseases and confers key prognostic information. Speckle tracking-based deformation as a feasible and sensitive LA mechanical assessment has proven its clinical significance beyond volume measures; however, the reference values remain largely unknown.

Methods and Results—

We studied 4042 participants undergoing annual cardiovascular survey. Among them, 2812 healthy participants (65% men; mean age, 47.4±9.9 years) were eligible for speckle tracking analysis. Peak atrial longitudinal systolic strain and strain rate (SR) at systolic (SRs), early diastolic (SRe), and late diastolic atrial contraction phases (SRa) were analyzed by dedicated software (EchoPAC, GE) and compared in terms of age, sex, and blood pressure. Overall, women demonstrated higher peak atrial longitudinal systolic strain (39.34±7.99% versus 37.95±7.96%; P<0.001) and showed age-dependent more pronounced peak atrial longitudinal systolic strain functional decay than those of men (P value for interaction, <0.05), with men showing higher SRs and SRa, although lower SRe (all P<0.001). Both increasing age and higher blood pressure were independently associated with deteriorated peak atrial longitudinal systolic strain, SRs, and SRe, although augmented LA SRa, even after accounting for baseline clinical covariates in multivariable models that incorporated LA volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or left ventricular E/e′ (all P<0.001).

Conclusions—

Our findings suggest LA mechanical functional decays in association with increasing age and higher blood pressure, which seem to be compensated for by augmentation of atrial pump function. We have also provided age- and sex-stratified reference values for strain and SR based on a large-scale Asian population.
Statin Discontinuation, Reinitiation, and Persistence Patterns Among Medicare Beneficiaries After Myocardial Infarction
Authors: Booth John N. , Colantonio Lisandro D. , Chen Ligong , Rosenson Robert S. , Monda Keri L. , Safford Monika M. , Kilgore Meredith L. , Brown Todd M. , Taylor Benjamin , Dent Ricardo , Muntner Paul , Levitan Emily B.
Published: October 2017

Background—

Although the benefits of statins accrue over time, treatment discontinuation is common. Examining the patterns of statin discontinuation, reinitiation, and persistence after reinitiation among Medicare beneficiaries after hospital discharge for a myocardial infarction may help increase statin use in high-risk patients.

Methods and Results—

Medicare beneficiaries with a statin fill claim within 30 days after hospital discharge for myocardial infarction in 2007 to 2012 (n=158 795) were followed for 182 days post-discharge to identify discontinuation, defined as 60 continuous days without statins available. Reinitiation, defined by a statin fill, was identified in the 365 days post-discontinuation. High persistence was defined as proportion of days covered ≥80% with ≥1 day of statin supply 182 days after reinitiation. Follow-up ended on December 31, 2014. In the 182 days after myocardial infarction hospital discharge, 15.4% of beneficiaries discontinued statins. Of this group, 53.7% reinitiated statins. On reinitiation, 27.1% changed statin type, 6.9% up-titrated intensity, 14.4% down-titrated intensity, and 66.0% had the same statin and intensity. In the 182 days after reinitiation, 45.8% had high persistence. Moderate- and high- versus low-intensity statins were associated with a lower risk for statin discontinuation (moderate intensity: relative risk [RR], 0.93; 95% confidence interval [CI], 0.89–0.96; high-intensity: RR, 0.95; 95% CI, 0.91–0.99). High persistence was less common after reinitiating high- versus low-intensity statins (RR, 0.80; 95% CI, 0.75–0.86), but no association was present for those reinitiating a moderate- versus low-intensity statin (RR, 0.95; 95% CI, 0.90–1.01). Down-titrating versus reinitiating the same statin intensity (RR, 1.10; 95% CI, 1.05–1.16) and reinitiating a different versus the same statin (RR, 1.10; 95% CI, 1.06–1.14) were associated with high persistence after treatment reinitiation.

Conclusions—

Although many people who discontinue a statin reinitiate treatment, statin persistence after reinitiation was low. Reinitiating therapy with moderate-intensity statins, down-titration, and using a different statin may promote persistence.
Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells
Authors: Yang Libang , Gao Ling , Nickel Thomas , Yang Jing , Zhou Jingyi , Gilbertsen Adam , Geng Zhaohui , Johnson Caitlin , Young Bernice , Henke Craig , Gourley Glenn R. , Zhang Jianyi
Published: October 2017

Rationale:

The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood.

Objective:

To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs.

Methods and Results:

Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L
+
) medium or in standard (L
−
) medium. Compared with the L
−
medium, the L
+
medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for
NDRG
(
N-myc downstream regulated gene
). Proteomics, biomarker, and pathway analyses suggested that the L
+
medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L
+
-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues.

Conclusions:

These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.
Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Adults in the United States
Authors: Jackson Sandra L. , Cogswell Mary E. , Zhao Lixia , Terry Ana L. , Wang Chia-Yih , Wright Jacqueline , Coleman King Sallyann M. , Bowman Barbara , Chen Te-Ching , Merritt Robert , Loria Catherine M.
Published: October 2017

Background:

Higher levels of sodium and lower levels of potassium intake are associated with higher blood pressure. However, the shape and magnitude of these associations can vary by study participant characteristics or intake assessment method. Twenty-four–hour urinary excretion of sodium and potassium are unaffected by recall errors and represent all sources of intake, and were collected for the first time in a nationally representative US survey. Our objective was to assess the associations of blood pressure and hypertension with 24-hour urinary excretion of sodium and potassium among US adults.

Methods:

Cross-sectional data were obtained from 766 participants age 20 to 69 years with complete blood pressure and 24-hour urine collections in the 2014 National Health and Nutrition Examination Survey, a nationally representative survey of the US noninstitutionalized population. Usual 24-hour urinary electrolyte excretion (sodium, potassium, and their ratio) was estimated from ≤2 collections on nonconsecutive days, adjusting for day-to-day variability in excretion. Outcomes included systolic and diastolic blood pressure from the average of 3 measures and hypertension status, based on average blood pressure ≥140/90 and antihypertensive medication use.

Results:

After multivariable adjustment, each 1000-mg difference in usual 24-hour sodium excretion was directly associated with systolic (4.58 mm Hg; 95% confidence interval [CI], 2.64–6.51) and diastolic (2.25 mm Hg; 95% CI, 0.83–3.67) blood pressures. Each 1000-mg difference in potassium excretion was inversely associated with systolic blood pressure (–3.72 mm Hg; 95% CI, –6.01 to –1.42). Each 0.5 U difference in sodium-to-potassium ratio was directly associated with systolic blood pressure (1.72 mm Hg; 95% CI, 0.76–2.68). Hypertension was linearly associated with progressively higher sodium and lower potassium excretion; in comparison with the lowest quartile of excretion, the adjusted odds of hypertension for the highest quartile was 4.22 (95% CI, 1.36–13.15) for sodium, and 0.38 (95% CI, 0.17–0.87) for potassium (
P
<0.01 for trends).

Conclusions:

These cross-sectional results show a strong dose-response association between urinary sodium excretion and blood pressure, and an inverse association between urinary potassium excretion and blood pressure, in a nationally representative sample of US adults.
Combined Salt and Caloric Restrictions: Potential Adverse Outcomes
Authors: Homma Tsuyoshi , Homma Mika , Huang Yuefei , Mayurasakorn Korapat , Rodi Nurul Mahamad , Hamid Anis Amalina Abdul , Hurwitz Shelley , Yao Tham , Adler Gail K. , Pojoga Luminita H. , Williams Gordon H. , Romero Jose R.
Published: October 2017

Background

We hypothesized that caloric restriction (
CR
) and salt restriction (ResS) would have similar effects on reducing cardiovascular risk markers and that combining
CR
and ResS would be synergistic in modulating these markers.

Methods and Results

To test our hypothesis, rats were randomized into 2 groups: ad libitum liberal salt diet (ad libitum/high‐sodium, 1.6% sodium) or ResS diet (ad libitum/ResS, 0.03% sodium).
CR
was initiated in half of the rats in each group by reducing caloric intake to 60% while maintaining sodium intake constant (
CR
/high‐sodium, 2.7% sodium or
CR
/ResS, 0.05% sodium) for 4 weeks.
CR
in rats on a high‐sodium diet improved metabolic parameters, renal transforming growth factor‐β and collagen‐1α1 and increased plasma adiponectin and renal visfatin and
NAD
+
protein levels. Although
CR
produced some beneficial cardiovascular effects (increased sodium excretion and reduced blood pressure), it also was associated with potentially adverse cardiovascular effects. Adrenal zona glomerulosa cell responsiveness and aldosterone levels and activation were inappropriately increased for the volume state of the rodent. Like
CR
on
HS
,
CR
on a ResS diet also produced relative increased zona glomerulosa responsiveness and an increased blood pressure with no improvement in metabolic parameters.

Conclusions

These results suggest that combining
CR
and ResS may decrease the beneficial effects of each alone. Furthermore,
CR
, regardless of dietary salt intake, inappropriately activates aldosterone production. Thus, caution should be used in combining ResS and
CR
because the combination may lead to increased cardiovascular risk.
Prevalence and Outcomes of Left‐Sided Valvular Heart Disease Associated With Chronic Kidney Disease
Authors: Samad Zainab , Sivak Joseph A. , Phelan Matthew , Schulte Phillip J. , Patel Uptal , Velazquez Eric J.
Published: October 2017

Background

Chronic kidney disease (
CKD
) is an adverse prognostic marker for valve intervention patients; however, the prevalence and related outcomes of valvular heart disease in
CKD
patients is unknown.

Methods and Results

Included patients underwent echocardiography (1999–2013), had serum creatinine values within 6 months before index echocardiogram, and had no history of valve surgery. CKD was defined as diagnosis based on the
International Classification of Diseases, Ninth Revision
or an estimated glomerular filtration rate <60 mL/min per 1.73 m
2
. Qualitative assessment determined left heart stenotic and regurgitant valve lesions. Cox models assessed
CKD
and aortic stenosis (
AS
) interaction for subsequent mortality; analyses were repeated for mitral regurgitation (
MR
). Among 78 059 patients, 23 727 (30%) had
CKD
; of these, 1326 were on hemodialysis. CKD patients were older; female; had a higher prevalence of hypertension, hyperlipidemia, diabetes, history of coronary artery bypass grafting/percutaneous coronary intervention, atrial fibrillation, and heart failure ≥mild AS; and ≥mild MR (all
P
<0.001). Five‐year survival estimates of mild, moderate, and severe
AS
for
CKD
patients were 40%, 34%, and 42%, respectively, and 69%, 54%, and 67% for non‐CKD patients. Five‐year survival estimates of mild, moderate, and severe
MR
for
CKD
patients were 51%, 38%, and 37%, respectively, and 75%, 66%, and 65% for non‐CKD patients. Significant interaction occurred among
CKD
,
AS
/
MR
severity, and mortality in adjusted analyses; the
CKD
hazard ratio increased from 1.8 (non‐
AS
patients) to 2.0 (severe
AS
) and from 1.7 (non‐
MR
patients) to 2.6 (severe
MR
).

Conclusions

Prevalence of at least mild
AS
and
MR
is substantially higher and is associated with significantly lower survival among patients with versus without
CKD
. There is significant interaction among
CKD
,
AS
/
MR
severity, and mortality, with increasingly worse outcomes for
CKD
patients with increasing
AS
/
MR
severity.
Impact of Hemodialysis on Procedural Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusion: Insights From the Japanese Multicenter Registry
Authors: Nakachi Tatsuya , Kohsaka Shun , Yamane Masahisa , Muramatsu Toshiya , Okamura Atsunori , Kashima Yoshifumi , Matsuno Shunsuke , Sakurada Masami , Kijima Mikihiko , Tanabe Masaki , Habara Maoto
Published: October 2017

Background

Among patients treated with percutaneous coronary intervention for chronic total occlusion (
CTO
‐
PCI
), patients on long‐term hemodialysis are at significantly high risk for cardiovascular mortality and morbidity. However, clinical or angiographic predictors that might aid in better patient selection remain unclear. We aimed to assess the acute impact of hemodialysis in patients who underwent
CTO
‐
PCI
.

Methods and Results

The Retrograde Summit registry is a multicenter, prospective registry of patients undergoing
CTO
‐
PCI
at 65 Japanese centers. Patient characteristics and procedural outcomes of 4749 patients were analyzed, according to the presence (n=313) or absence (n=4436) of baseline hemodialysis. A prediction model for technical failure among hemodialysis patients was also developed. The technical success rate of
CTO
‐
PCI
was significantly lower in hemodialysis than in nonhemodialysis patients (78.0% versus 89.1%,
P
<0.001). The rates of in‐hospital major adverse cardiac and cerebrovascular events were similar between the 2 groups (1.6% versus 0.9%,
P
=0.24). Irrespective of clinical/angiographic characteristics or previously developed scoring systems, hemodialysis independently predicted technical failure for
CTO
‐
PCI
. Among hemodialysis patients, predictors of technical failure were blunt stump (odds ratio 2.45, 95% confidence interval, 1.15–5.21,
P
=0.021), severe lesion calcification (odds ratio 2.50, 95% confidence interval, 1.19–5.24,
P
=0.015), and absence of diabetes mellitus (odds ratio 3.15, 95% confidence interval, 1.49–6.64,
P
=0.003). In hemodialysis patients without these predictors, the technical success rate was 96.2%.

Conclusions

Hemodialysis is significantly associated with technical failure. Contemporary
CTO
‐
PCI
seems feasible and safe in selected hemodialysis patients.
Understanding Violence, Strategising Protection
Authors: Guhathakurta Meghna
Published: October 2017

Northern Rakhine State in Myanmar is inhabited by a majority Arakanese Muslim population and a minority Rakhine Buddhist population, in a state that is largely Buddhist and authoritarian. The recent history of exclusionary citizenship policies and consequent military operations against Arakanese Muslims, often called Rohingyas, have led them to flee Myanmar and take shelter in Bangladesh. In this study, I examine and review the stereotypes of each of these groups, implicated in the exclusionary nationalist policies of the Myanmar state, and the general hostility expressed towards the refugees by the host community in Bangladesh, with a view to understanding the multi-layered spaces of violence in which they live. The aim of this study is to elucidate protection mechanisms against such violence from the perspectives of refugees themselves. This is done through practices and observations noted by the author while engendering participatory processes among Rohingya refugees as part of a project being implemented by the organisation, Research Initiatives Bangladesh (RIB).
Protection Rackets and Party Machines
Authors: Martin Nicolas , Michelutti Lucia
Published: October 2017

Control over means of violence and protection emerge as crucial in much research on corruption in non-South Asian contexts. In the Indian context, however, we still know little about the systems of organised violence that sustain the entanglement of crime, capital and democratic politics. This timely comparative ethnographic piece explores two different manifestations of what our informants identify as “Mafia Raj” (“rule by mafia”) across North India (Uttar Pradesh and Punjab). Drawing on analytical concepts developed in the literature on bossism and “mafias”, we explore protection and racketeering as central statecraft repertoires of muscular styles of governance in the region. We show how a predatory economy together with structures of inter- and intra-party political competition generate the demand for and the imposition of unofficial and illegal protection and shape different manifestations of Mafia Raj. In doing so, the paper aims to contribute to debates on the relationship between states and illegalities in and beyond South Asia.
Gramsci, No Longer a Communist?
Authors: Peretti Luca
Published: October 2017

In his last three books, Franco Lo Piparo (a philosopher of language who teaches in Palermo) presents fresh and contested interpretations of the last part of Gramsci’s life. In his view, the Sardinian thinker was distancing himself from the Communist world, not just from the Soviet Union. In the first part of the review-essay I will introduce the three books; in the second part I will then highlight some passages in the books that present Gramsci as a non-Communist thinker; in the final part, I will discuss the comparative analysis of Wittgenstein and Gramsci that the author traces in his last book. I believe that while this can open up new avenues, it is ultimately based on unconvincing and/or vague arguments.
The Xianggu Mushroom Industry in Xixia County, Henan: A Case Study (西峡香菇产业的个案研究)
Authors: Liu (刘昶) Chang , Bao (包诗卿) Shiqing , Pei (裴丹青) Danqing
Published: October 2017

The xianggu (shiitake) mushroom industry in Xixia county, Henan, emerged and initially experienced rapid growth during the reform and opening up period. It has benefited from both the rapid expansion of the food consumption market in China and the guidance and support of the local government. After thirty years of sustained expansion, the growth of the mushroom market began to slow down and competition within the industry became fierce. Facing rich and powerful mushroom dealers, individual mushroom farmers have had to bear the brunt of market fluctuations. To break the predicament of farmers’ suffering from low prices (because of the bumper harvest paradox) and to help farmers protect their interests and gain a fair share of the industry’s profits, and thus to achieve sustained and healthy development of the mushroom industry, important institutional innovations are needed.

西峡县香菇产业在改革开放时期经历了从零开始的飞速增长，这既得益于食品消费市场的迅速扩张，也得益于地方政府的引导和扶持。在经历了三十年的持续扩张后，香菇市场增速开始放缓，业内竞争压力凸显。面对财大气粗的菇行，势孤力单的个体菇农首当其冲,受到市场的挤压。要破解菇贱伤农的困局，帮助菇农保护自己的利益和分享产业的利润，并实现香菇产业的健康持续发展，就需要在产业组织和制度上进行创新。 (This article is in English.)
From “Involution” to “Capitalization”: The “New Agriculture” and the “New Peasant”—A Case Study of Tobacco Growers in a Chinese Township (从“过密化”到“资本化”：“新农业”与“新农民”——以湖北省恩施市烟叶种植农户为例的讨论)
Authors: Jiao (焦长权) Changquan , Chen (陈莹骄) Yingjiao
Published: October 2017

With the acceleration of the urbanization process and the transformation of the population structure, China’s small peasant economy is breaking away from involutionary growth. At the same time, capital investment in family farms is increasing, leading to the capitalization of family farms and the rise of “new agriculture.” Based on a case study of tobacco growers in a Chinese township, this article demonstrates how capital investment contributes to specialization and scale production in tobacco production and how a capitalized family farm operates, depending mainly on family labor and partly on rented land. As a typical new agriculture, tobacco production achieves the dual intensification of both capital and labor and manages to get out from the involution trap. This article argues that the capitalized family farm is not only a new type of economic subject but that it also shapes a new type of social subject. As the “new peasant,” the holder of a capitalized family farm is a member of a social elite in villages and serves as the crucial social force in the transformation of village society.

伴随城市化的快速发展和农村人口结构的转型，中国的小农经济正逐渐摆脱“过密化”陷阱。同时，农业生产中的资本投入日益增长，家庭农场日益“资本化”，“新农业”获得了空前的发展。文章以中国恩施地区烟叶生产为例，阐述了资本投入对烟叶专业化、规模化生产的关键作用，分析了资本化家庭农场的经营方式：其主要依赖家庭劳动力（少部分季节性雇佣劳动力），并通过土地流转实现适度规模经营。烟叶生产是一种典型的“新农业”，它在家庭农场中实现了资本和劳动的“双密集”，摆脱了“过密化”陷阱。作者认为，资本化的家庭农场不仅形成了一种“新农业”（新型经济主体），更塑造了一群“新农民”（新型社会主体），他们是村庄中的精英群体，对村庄社会转型具有重要意义。 (This article is in English.)