bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Endoscopic Papillary Large Balloon Dilation for Removal of Large Bile Duct Stones in Advanced Age
Authors: Kim Kook Hyun , Kim Tae Nyeun
Published: October 2016

Objective. Bile duct stone-related adverse events can be detrimental in the elderly. However, little is known about clinical outcomes and adverse events following endoscopic papillary large balloon dilation (EPLBD) in the elderly. The aim of this study was to evaluate the safety and feasibility of EPLBD for the removal of CBD stones in patients aged ≥ 80 years.Methods. A total of 204 patients who underwent EPLBD from 2006 to 2012 were retrospectively reviewed. Patients were classified into two groups (148 patients < 80 years old, Group A; 56 patients ≥ 80 years old, Group B). Endoscopic findings, clinical outcomes, and adverse events in two groups were compared.Results. The number of underlying chronic diseases in Group B was significantly higher than in Group A (P=0.032). The rates of overall stone clearance were similar between two groups (P=0.145). No significant difference with regard to post-ERCP pancreatitis between two groups was observed (P=0.687). All episodes of pancreatitis had full recovery with conservative treatment. One major hemorrhage in Group A was successfully controlled endoscopically and one death caused by retroperitoneal perforation occurred in Group A.Conclusions. EPLBD appear to be safe and effective for CBD stone removal in patients aged ≥ 80 years.
Efficient Oxidative Removal of Organic Pollutants by Ordered Mesoporous Carbon-Supported Cobalt Phthalocyanine
Authors: Chen Yi , Gu Yan , Li Nan , Lu Wangyang , Chen Wenxing
Published: October 2016

Ordered mesoporous carbon (OMC) materials have received attention for use as supports in highly efficient catalytic systems because of their excellent properties. We used epoxy compound 2,3-epoxypropyl trimethylammonium chloride (EPTAC) to modify cobalt tetraaminophthalocyanine (CoTAPc) and obtained a novel catalyst (OMC-CoTAPc-EPTAC) based on OMC-bonded CoTAPc-EPTAC that could oxidize Acid Red 1 (AR1) dyes by hydrogen peroxide (H2O2) activation under neutral conditions. OMC enhanced the catalytic performance of OMC-CoTAPc-EPTAC, which resulted in the combined high catalytic activity and high stability. Because of its large surface area and tunable pore texture, OMC has high substrate accessibility, and the modification of the catalyst with EPTAC could promote adsorption of the target substrate into OMC, which achieved the aim of in situ catalytic oxidation with enrichment of the target substrate and improved the catalytic efficiency significantly. Electron paramagnetic resonance spin-trap experiments confirmed that the OMC-CoTAPc-EPTAC/H2O2system had a nonradical catalytic mechanism, and the high-valent cobalt-oxo intermediates and generated holes were speculated to act as dominant oxidation species for the catalytic degradation of AR1. These results demonstrated a new strategy for the elimination of low-concentration organic pollutants.
Total Hip Arthroplasty for Implant Rupture after Surgery for Atypical Subtrochanteric Femoral Fracture
Authors: Ozaki Yu , Baba Tomonori , Ochi Hironori , Homma Yasuhiro , Watari Taiji , Matsumoto Mikio , Kaneko Kazuo
Published: October 2016

Treatment methods for delayed union and nonunion of atypical femoral fracture are still controversial. Moreover, no treatment method has been established for implant rupture caused by delayed union and nonunion. We encountered a 74-year-old female in whom nonunion-induced implant rupture occurred after treatment of atypical subtrochanteric femoral fracture with internal fixation using a long femoral nail. It was unlikely that sufficient fixation could be obtained by repeating osteosynthesis alone. Moreover, the patient was elderly and early weight-bearing activity was essential for early recovery of ADL. Based on these reasons, we selected one-stage surgery with total hip arthroplasty and osteosynthesis with inverted condylar locking plate as salvage procedures. Bone union was achieved at 6 months after surgery. This case illustrated that osteosynthesis-combined one-staged total hip arthroplasty could be considered as one of the options for nonunion-induced implant rupture of atypical femoral subtrochanteric fracture.
Transient Decrease in Circulatory Testosterone and Homocysteine Precedes the Development of Metabolic Syndrome Features in Fructose-Fed Sprague Dawley Rats
Authors: Sakamuri Anil , Pitla Sujatha , Putcha Uday Kumar , Jayapal Sugeedha , Pothana Sailaja , Vadakattu Sai Santosh , Konapalli Nagabhushan Reddy , Sakamuri Siva Sankara Vara Prasad , Ibrahim Ahamed
Published: October 2016

Background. Increased fructose consumption is linked to the development of metabolic syndrome (MS). Here we investigated the time course of development of MS features in high-fructose-fed Sprague Dawley rats along with circulatory testosterone and homocysteine levels.Methods. Rats were divided into control and experimental groups and fed with diets containing 54.5% starch and fructose, respectively, for 4, 12, and 24 weeks. Plasma testosterone and homocysteine levels were measured along with insulin, glucose, and lipids. Body composition, insulin resistance, and hepatic lipids were measured.Results. Increase in hepatic triglyceride content was first observed in metabolic disturbance followed by hypertriglyceridemia and systemic insulin resistance in fructose-fed rats. Hepatic lipids were increased in time-dependent manner by fructose-feeding starting from 4 weeks, but circulatory triglyceride levels were increased after 12 weeks. Fasting insulin and Homeostatis Model Assessment of Insulin Resistance (HOMA-IR) were increased after 12 weeks of fructose-feeding. Decreased visceral adiposity, circulatory testosterone, and homocysteine levels were observed after 4 weeks of fructose-feeding, which were normalized at 12 and 24 weeks.Conclusions. We conclude that transient decrease in circulatory testosterone and homocysteine levels and increased hepatic triglyceride content are the earliest metabolic disturbances that preceded hypertriglyceridemia and insulin resistance in fructose-fed SD rats.
The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience
Authors: Dybko Jarosław , Jaźwiec Bożena , Haus Olga , Urbaniak-Kujda Donata , Kapelko-Słowik Katarzyna , Wróbel Tomasz , Lonc Tomasz , Sawicki Mateusz , Mędraś Ewa , Kaczmar-Dybko Agnieszka , Kuliczkowski Kazimierz
Published: October 2016

The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients.
Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment
Authors: Flores-Borja Fabian , Irshad Sheeba , Gordon Peter , Wong Felix , Sheriff Ibrahim , Tutt Andrew , Ng Tony
Published: October 2016

Our knowledge and understanding of the tumor microenvironment (TME) have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC). Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies.
Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection
Authors: Kahlfuss Sascha , Flieger Robert Rainer , Mankertz Annette , Yilmaz Kadir , Roepke Torsten Kai
Published: October 2016

Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.
Scrotal Apocrine Adenocarcinoma with Pagetoid Phenomenon and Inguinal Lymph Node Metastases
Authors: Zibis Aristeidis Hristos , Fyllos Apostolos Haralampos , Havaki Sophia , Sotiriou Sotirios , Kotakidis Georgios , Arvanitis Dimitrios Leonidas
Published: October 2016

We report a case of scrotal apocrine adenocarcinoma in a 72-year-old Caucasian male which was initially presented as a reddish superficial lesion which in time became an ulcerated nodule. The initial pathological examination showed an apocrine adenocarcinoma with pagetoid phenomenon. The tumor recurred after four months and then excision biopsy showed tumor with pagetoid phenomenon which reached all the surgical margins. Three months later an ulcerated nodule in the scrotum and greatly enlarged ipsilateral inguinal lymph nodes were noticed. The final pathological examination showed multiple separated malignant foci, some with overlying pagetoid phenomenon and inguinal lymph node metastases. Immunohistochemistry showed positivity for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), androgen receptors, and score 3+ for the Human Epidermal growth factor Receptor-2 (HER2). The aggressive behavior of the present tumor goes along with previous reports showing that HER2 high score cases exhibit a worse prognosis.
Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers
Authors: Cha Jung-Joon , Park Yangkyu , Yun Joho , Kim Hyeon Woo , Park Chang-Ju , Kang Giseok , Jung Minhyun , Pak Boryeong , Jin Suk-Won , Lee Jong-Hyun
Published: October 2016

Senescence of cardiac myocytes is frequently associated with heart diseases. To analyze senescence in cardiac myocytes, a number of biomarkers have been isolated. However, due to the complex nature of senescence, multiple markers are required for a single assay to accurately depict complex physiological changes associated with senescence. In single cells, changes in both cytoplasm and cell membrane during senescence can affect the changes in electrical impedance. Based on this phenomenon, we developed MEDoS, a novel microelectrochemical impedance spectroscopy for diagnosis of senescence, which allows us to precisely measure quantitative changes in electrical properties of aging cells. Using cardiac myocytes isolated from 3-, 6-, and 18-month-old isogenic zebrafish, we examined the efficacy of MEDoS and showed that MEDoS can identify discernible changes in electrical impedance. Taken together, our data demonstrated that electrical impedance in cells at different ages is distinct with quantitative values; these results were comparable with previously reported ones. Therefore, we propose that MEDoS be used as a new biomarker-independent methodology to obtain quantitative data on the biological senescence status of individual cells.
On a Numerical Radius Preserving Onto Isometry onL(X)
Authors: Kim Sun Kwang
Published: October 2016

We study a numerical radius preserving onto isometry onL(X). As a main result, whenXis a complex Banach space having both uniform smoothness and uniform convexity, we show that an onto isometryTonL(X)is numerical radius preserving if and only if there exists a scalarcTof modulus 1 such thatcTTis numerical range preserving. The examples of such spaces are Hilbert space andLpspaces for1<p<∞.
Liver Transplantation Utilizing Mixed Biologic and Synthetic Arterial Conduits
Authors: Chedid Marcio F. , Grezzana-Filho Tomaz J. M. , Chedid Aljamir D. , Hendges Luiz Pedro P. , Leipnitz Ian , Alvares-da-Silva Mario R. , Backes Ariane N. , Reis Matheus J. , Kruel Cleber Dario P. , Kruel Cleber R. P.
Published: October 2016

Arterial conduits are necessary in nearly 5% of all liver transplants and are usually constructed utilizing segments of donor iliac artery. However, available segments of donor iliac artery may not be lengthy enough or may not possess enough quality to enable its inclusion in the conduit. Although there are few reports of arterial conduits constructed solely utilizing prosthetic material, no previous reports of conduits composed of a segment of donor iliac artery and prosthetic material (mixed biologic and synthetic arterial conduits) were found in the medial literature to date. Two cases reporting successful outcomes after creation of mixed biologic and prosthetic arterial conduits are outlined in this report. Reason for creation of conduits was complete intimal dissection of the recipient’s hepatic artery in both cases. In both cases, available segments of donor iliac artery were not lengthy enough to bridge infrarenal aorta to porta hepatis. Both patients have patent conduits and normally functioning liver allografts, respectively, at 4 and 31 months after transplant. Mixed biologic and synthetic arterial conduits constitute a viable technical option and may offer potential advantages over fully prosthetic arterial conduits.
Apoptosis of Endothelial Cells by 13-HPODE Contributes to Impairment of Endothelial Barrier Integrity
Authors: Ryman Valerie E. , Packiriswamy Nandakumar , Sordillo Lorraine M.
Published: October 2016

Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis ofStreptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA) oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1) metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE), can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE), is abundantly produced during vascular activation. However, the relative contribution of specific LA-derived metabolites on impairment of mammary endothelial integrity is unknown. Our hypothesis was thatS. uberis-induced LA-derived 15-LOX-1 oxygenation products impair mammary endothelial barrier integrity by apoptosis. Exposure of bovine mammary endothelial cells (BMEC) toS. uberisdid not increase 15-LOX-1 LA metabolism. However,S. uberischallenge of bovine monocytes demonstrated that monocytes may be a significant source of both 13-HPODE and 13-HODE during mastitis. Exposure of BMEC to 13-HPODE, but not 13-HODE, significantly reduced endothelial barrier integrity and increased apoptosis. Changing oxidant status by coexposure to an antioxidant during 13-HPODE treatment prevented adverse effects of 13-HPODE, including amelioration of apoptosis. A better understanding of how the oxidant status of the vascular microenvironment impacts endothelial barrier properties could lead to more efficacious treatments forS. uberismastitis.
Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum
Authors: Hulbert Alicia , Jusue-Torres Ignacio , Stark Alejandro , Chen Chen , Rodgers Kristen , Lee Beverly , Griffin Candace , Yang Andrew , Huang Peng , Wrangle John , Belinsky Steven A. , Wang Tza-Huei , Yang Stephen C. , Baylin Stephen B. , Brock Malcolm V. , Herman James G.
Published: October 2016

Purpose: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer–specific gene panel to detect DNA methylation in sputum and plasma.

Experimental Design: This is a case–control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non–small cell lung cancer. Controls (n = 60) had non-cancer diagnoses. We detected promoter methylation using quantitative methylation-specific real-time PCR and methylation-on-beads for cancer-specific genes (SOX17, TAC1, HOXA7, CDO1, HOXA9, and ZFP42).

Results: DNA methylation was detected in plasma and sputum more frequently in people with cancer compared with controls (P < 0.001) for five of six genes. The sensitivity and specificity for lung cancer diagnosis using the best individual genes was 63% to 86% and 75% to 92% in sputum, respectively, and 65% to 76% and 74% to 84% in plasma, respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 98% and 71% using sputum and 93% and 62% using plasma. Area under the receiver operating curve for this panel was 0.89 [95% confidence interval (CI), 0.80–0.98] in sputum and 0.77 (95% CI, 0.68–0.86) in plasma. Independent blinded random forest prediction models combining gene methylation with clinical information correctly predicted lung cancer in 91% of subjects using sputum detection and 85% of subjects using plasma detection.

Conclusions: High diagnostic accuracy for early-stage lung cancer can be obtained using methylated promoter detection in sputum or plasma. Clin Cancer Res; 23(8); 1998–2005. ©2016 AACR.
Retroperitoneal Laparoscopic Nephrectomy Combined with Bench Surgery and Autotransplantation for Renal Cell Carcinoma in the Solitary Kidney or Tumor Involving Bilateral Kidneys: Experience at a Single Center and Technical Considerations
Authors: Ju Xiaobing , Li Pu , Shao Pengfei , Lv Qiang , Wang Zengjun , Qin Chao , Li Jie
Published: October 2016

Objective: To assess the feasibility of retroperitoneal laparoscopic nephrectomy combined with bench surgery and autotransplantation in treating complex renal tumor. Patients and Methods: Six patients with complex renal tumor were seen in our institution between 2010 and 2014. Three patients with bilateral renal cell carcinoma underwent retroperitoneal laparoscopic nephrectomy on both sides. Extracorporeal tumorectomy and renal reconstruction were performed on the side of the smaller tumor and then kidney autotransplantation was performed. The other 3 patients with tumor involving the solitary kidney underwent laparoscopic nephrectomy combined with bench surgery and autotransplantation. Result: The total time of the operation was 287 ± 25 min; warm ischemia time 3.1 ± 0.7 min; cold ischemia time 47 ± 8.1 min; and kidney autotransplantation required time 86 ± 8.6 min. Estimated blood loss was 232 ± 45.8 ml. Serum creatinine levels were 179 ± 44.7 µmol/l upon hospital discharge. Two patients received temporary hemodialysis. No patient needed further hemodialysis during follow-up. One patient died of multiple metastases 18 months after surgery. The other 5 patients survived without recurrence or metastasis during follow-up. Conclusions: Retroperitoneal laparoscopic radical nephrectomy combined with bench surgery and autotransplantation is a feasible choice for patients with complex renal cell carcinoma in bilateral kidneys and tumor involving the solitary kidney.
Risk Prediction Model for Progression of Age-Related Macular Degeneration
Authors: Shin Ko Un , Song Su Jeong , Bae Jeong Hun , Lee Mi Yeon
Published: October 2016

Aims: The aim of this paper was to develop a risk prediction model for the progression of age-related macular degeneration (AMD) in Koreans using systemic and environmental factors. Methods: The study sample included 10,890 individuals 50 years of age or older; 318 (2.92%) presented with early AMD findings in baseline examinations. Re-examinations were performed in 157 (49.37%) who were followed up for 4.4 years. The multivariate analysis of covariates included demographic and environmental factors. After using these data to develop a risk prediction model, the individual algorithm was made, and receiver operating characteristic curves were calculated to assess the predictive ability of the risk model for AMD progression. Results: The individual algorithm to predict the AMD progression risk based on systemic and ocular factors was as follows: Y = -9.565 + 1.709 (drusen locationcenter) + 0.795 (drusen locationparacentral) + 1.074 (both eyes) + 0.094 (drusen sizeintermediate) + 0.034 (drusen sizelarge) + 0.614 (drusen number10-20) + 2.278 (drusen number>20) + 0.577 (hyperpigmentation) + 0.725 (hypopigmentation) + 0.079 (male) - 0.025 (age) - 0.921 (SMKex) + 1.574 (SMKcurrent) + 0.363 (total protein) + 1.626 (globulin), where SMK means smoking status. The C statistics for the model was 0.84 (0.75-0.92) indicating a good predictive power. Conclusion: A comprehensive risk prediction model for AMD progression was made to calculate the individual AMD progression risk using personal systemic and environmental factors.
Ranolazine for Congenital Long-QT Syndrome Type III
Authors: Chorin Ehud , Hu Dan , Antzelevitch Charles , Hochstadt Aviram , Belardinelli Luiz , Zeltser David , Barajas-Martinez Hector , Rozovski Uri , Rosso Raphael , Adler Arnon , Benhorin Jesaia , Viskin Sami
Published: October 2016

Background—

The basic defect in long-QT syndrome type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential caused by mutations in the
SCN5A
gene. Most sodium channel blockers reduce the early (peak) and late components of the sodium current (
I
Na
and
I
NaL
), but ranolazine preferentially reduces
I
NaL
. We, therefore, evaluated the effects of ranolazine in LQT3 caused by the
D1790G
mutation in
SCN5A
.

Methods and Results—

We performed an experimental study of ranolazine in TSA201 cells expressing the
D1790G
mutation. We then performed a long-term clinical evaluation of ranolazine in LQT3 patients carrying the
D1790G
mutation. In the experimental study,
I
NaL
was significantly higher in
D1790G
than in wild-type channels expressed in the TSA201 cells. Ranolazine exerted a concentration-dependent block of
I
NaL
of the
SCN5A-D1790G
channel without reducing peak
I
Na
significantly. In the clinical study, among 8 patients with LQT3 and confirmed
D1790G
mutation, ranolazine had no effects on the sinus rate or QRS width but shortened the QTc from 509±41 to 451±26 ms, a mean decrease of 56±52 ms (10.6%;
P
=0.012). The QT-shortening effect of ranolazine remained effective throughout the entire study period of 22.8±12.8 months. Ranolazine reduced the QTc at all heart rates but less so during extreme nocturnal bradycardia. A type I Brugada ECG was never noticed.

Conclusions—

Ranolazine blocks
I
NaL
in experimental models of LQT3 harboring the
SCN5A-D1790G
mutation and shortened the QT interval of LQT3 patients.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
; Unique identifier: NCT01728025.
Studying Dynamic Myofiber Aggregate Reorientation in Dilated Cardiomyopathy Using In Vivo Magnetic Resonance Diffusion Tensor Imaging
Authors: von Deuster Constantin , Sammut Eva , Asner Liya , Nordsletten David , Lamata Pablo , Stoeck Christian T. , Kozerke Sebastian , Razavi Reza
Published: October 2016

Background—

The objective of this study is to assess the dynamic alterations of myocardial microstructure and strain between diastole and systole in patients with dilated cardiomyopathy relative to healthy controls using the magnetic resonance diffusion tensor imaging, myocardial tagging, and biomechanical modeling.

Methods and Results—

Dual heart-phase diffusion tensor imaging was successfully performed in 9 patients and 9 controls. Tagging data were acquired for the diffusion tensor strain correction and cardiac motion analysis. Mean diffusivity, fractional anisotropy, and myocyte aggregate orientations were compared between both cohorts. Cardiac function was assessed by left ventricular ejection fraction, torsion, and strain. Computational modeling was used to study the impact of cardiac shape on fiber reorientation and how fiber orientations affect strain. In patients with dilated cardiomyopathy, a more longitudinal orientation of diastolic myofiber aggregates was measured compared with controls. Although a significant steepening of helix angles (HAs) during contraction was found in the controls, consistent change in HAs during contraction was absent in patients. Left ventricular ejection fraction, cardiac torsion, and strain were significantly lower in the patients compared with controls. Computational modeling revealed that the dilated heart results in reduced HA changes compared with a normal heart. Reduced torsion was found to be exacerbated by steeper HAs.

Conclusions—

Diffusion tensor imaging revealed reduced reorientation of myofiber aggregates during cardiac contraction in patients with dilated cardiomyopathy relative to controls. Left ventricular remodeling seems to be an important factor in the changes to myocyte orientation. Steeper HAs are coupled with a worsening in strain and torsion. Overall, the findings provide new insights into the structural alterations in patients with dilated cardiomyopathy.
SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Is Essential for Cardiac Function by Regulating Junctional Membrane Complex Activity
Authors: Quick Ann P. , Wang Qiongling , Philippen Leonne E. , Barreto-Torres Giselle , Chiang David Y. , Beavers David , Wang Guoliang , Khalid Maha , Reynolds Julia O. , Campbell Hannah M. , Showell Jordan , McCauley Mark D. , Scholten Arjen , Wehrens Xander H.T.
Published: October 2016

Rationale:

Junctional membrane complexes (JMCs) in myocytes are critical microdomains, in which excitation–contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein SPEG (striated muscle preferentially expressed protein kinase) remains unclear.

Objective:

To determine the role of SPEG in healthy and failing adult hearts.

Methods and Results:

Proteomic analysis of immunoprecipitated JMC proteins ryanodine receptor type 2 and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine–threonine kinase SPEG as the only novel binding partner for both proteins. Real-time polymerase chain reaction revealed the downregulation of
SPEG
mRNA levels in failing human hearts. A novel cardiac myocyte-specific
Speg
conditional knockout (MCM-
Speg
fl/fl
) model revealed that adult-onset SPEG deficiency results in heart failure (HF). Calcium (Ca
2+
) and transverse-tubule imaging of ventricular myocytes from MCM-
Speg
fl/fl
mice post HF revealed both increased sarcoplasmic reticulum Ca
2+
spark frequency and disrupted JMC integrity. Additional studies revealed that transverse-tubule disruption precedes the development of HF development in MCM-
Speg
fl/fl
mice. Although total JPH2 levels were unaltered, JPH2 phosphorylation levels were found to be reduced in MCM-
Speg
fl/fl
mice, suggesting that loss of SPEG phosphorylation of JPH2 led to transverse-tubule disruption, a precursor of HF development in SPEG-deficient mice.

Conclusions:

The novel JMC protein SPEG is downregulated in human failing hearts. Acute loss of SPEG in mouse hearts causes JPH2 dephosphorylation and transverse-tubule loss associated with downstream Ca
2+
mishandling leading to HF. Our study suggests that SPEG could be a novel target for the treatment of HF.
Aspirin for Primary Cardiovascular Risk Prevention and Beyond in Diabetes Mellitus
Authors: Capodanno Davide , Angiolillo Dominick J.
Published: October 2016

Daily administration of low-dose aspirin has proved to be beneficial in preventing recurrent cardiovascular events. However, the role of aspirin for primary prevention in patients with no overt cardiovascular disease is more controversial. In fact, in lower risk patients, the modest benefit in reducing serious vascular events can be offset by the increased risk of bleeding, including intracranial and gastrointestinal hemorrhage. Diabetes mellitus has been associated with a substantially increased risk of both first and recurrent atherothrombotic events, which makes aspirin therapy of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in diabetes mellitus, this article reviews the literature on the topic of aspirin for primary prevention in general, and in subjects with diabetes mellitus in particular, to culminate with arguments pro and con and a practical risk-based algorithm for aspirin initiation in daily practice.
Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10‐Year Follow‐up of the Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Anderson John J.B. , Kruszka Bridget , Delaney Joseph A.C. , He Ka , Burke Gregory L. , Alonso Alvaro , Bild Diane E. , Budoff Matthew , Michos Erin D.
Published: October 2016

Background

Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (
CVD
) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (
CAC
).

Methods and Results

We studied 5448 adults free of clinically diagnosed
CVD
(52% female; aged 45–84 years) from the Multi‐Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline
CAC
was measured by computed tomography, and
CAC
measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline
CAC
, the relative risk (
RR
) of developing incident
CAC
over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79–1.14), 1.02 (0.85–1.23), 0.86 (0.69–1.05), and 0.73 (0.57–0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident
CAC
(
RR
=1.22 [1.07–1.39]). No relation was found between baseline calcium intake and 10‐year changes in log‐transformed
CAC
among those participants with baseline
CAC
>0.

Conclusions

High total calcium intake was associated with a decreased risk of incident atherosclerosis over long‐term follow‐up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident
CAC
.
Effects of a Health‐Partner Intervention on Cardiovascular Risk
Authors: Al Mheid Ibhar , Kelli Heval Mohamed , Ko Yi‐An , Hammadah Muhammad , Ahmed Hina , Hayek Salim , Vaccarino Viola , Ziegler Thomas R. , Gibson Greg , Lampl Michelle , Alexander R. Wayne , Brigham Ken , Martin Greg S. , Quyyumi Arshed A.
Published: October 2016

Background

Lifestyle modifications are first‐line measures for cardiovascular disease prevention. Whether lifestyle intervention also preserves cardiovascular health is less clear. Our study examined the role of a Health Partner–administered lifestyle intervention on metrics of ideal cardiovascular health.

Methods and Results

A total of 711 university employees (48±11 years; 66% women, 72% Caucasian/22.5% African Americans) enrolled in a program that promoted healthier lifestyles at Emory University (Atlanta, GA). Anthropometric, laboratory, and physical activity measurements were performed at baseline and at 6 months, 1 year, and 2 years of follow‐up. Results were utilized by the Health Partner to generate a personalized plan aimed at meeting ideal health metrics. Compared to baseline, at each of the 6‐month, 1‐year, and 2‐year follow‐up visits, systolic blood pressure was lower by 3.6, 4.6, and 3.3 mm Hg (
P
<0.001), total cholesterol decreased by 5.3, 6.5, and 6.4 mg/dL (
P
<0.001), body mass index declined by 0.33, 0.45, and 0.38 kg/m
2
(
P
<0.001), and the percentage of smokers decreased by 1.3%, 3.5%, and 3.5% (
P
<0.01), respectively. Changes were greater in those with greater abnormalities at baseline. Finally, the American Heart Association “Life's Simple 7” ideal cardiovascular health score increased by 0.28, 0.40, and 0.33 at 6 month, 1 year, and 2 years, respectively, compared to baseline visit.

Conclusions

A personalized, goal‐directed Health Partner intervention significantly improved the cardiometabolic risk profile and metrics of cardiovascular health. These effects were evident at 6 months following enrollment and were sustained for 2 years. Whether the Health Partner intervention improves long‐term morbidity and mortality and is cost‐effective needs further investigation.
Association Between Endogenous Testosterone and Cerebrovascular Disease in the ARIC Study (Atherosclerosis Risk in Communities)
Authors: Srinath Reshmi , Gottesman Rebecca F. , Hill Golden Sherita , Carson Kathryn A. , Dobs Adrian
Published: October 2016

Background and Purpose—

Epidemiological studies in men suggest a relationship between endogenous testosterone and ischemic vascular events. We hypothesized that low testosterone is independently associated with ischemic stroke and ischemic brain changes.

Methods—

In 1558 male participants (mean [SD] age, 63.1 [5.6] years; body mass index, 28.2 [4.3] kg/m
2
) from visit 4 (1996–1998) of the ARIC study (Atherosclerosis Risk in Communities) without cardiovascular disease, stroke, and previous testosterone therapy, we measured plasma total testosterone by liquid chromatography mass spectrometry using morning samples and divided levels into tertiles (median [25th–75th percentile], 377.6 [288.4–480.1] ng/dL). General linear models, for cross-sectional analyses, and proportional hazards regression, for time-to-event analysis, examined the association of testosterone with participant characteristics and incident stroke through 2011. Linear and logistic regression models examined the association of testosterone with percentage white matter hyperintensities and prevalent infarcts in participants (n=257) who underwent brain magnetic resonance imaging at visit 5 (2011–2013). Analyses were adjusted for age, race, and ARIC center, body mass index, waist circumference, smoking status, diabetes mellitus, hypertension, low-density lipoprotein, and high-density lipoprotein.

Results—

Lower testosterone was significantly associated with higher body mass index, greater waist circumference, diabetes mellitus, hypertension, lower high-density lipoprotein, and never smoking. After adjustment, no association of testosterone with incident stroke was found (hazard ratios [95% confidence intervals] for tertile 1 or 3 versus 2, 1.47 [0.83–2.61], 1.15 [0.62–2.14]; median follow-up, 14.1 years), nor with percentage white matter hyperintensities, cortical infarcts, or subcortical infarcts.

Conclusions—

After controlling for atherosclerotic risk factors, there was no association between endogenous testosterone and incident clinical stroke or ischemic brain changes in community-dwelling men.
Hepatocyte Growth Factor Is Positively Associated With Risk of Stroke
Authors: Bell Elizabeth J. , Larson Nicholas B. , Decker Paul A. , Pankow James S. , Tsai Michael Y. , Hanson Naomi Q. , Wassel Christina L. , Longstreth W.T. , Bielinski Suzette J.
Published: October 2016

Background and Purpose—

Hepatocyte growth factor (HGF) is positively associated with ischemic and hemorrhagic stroke risk factors. However, understanding the relation between HGF and stroke is in its infancy. Therefore, we sought to examine the association of circulating HGF with incident stroke using data from the MESA (Multi-Ethnic Study of Atherosclerosis). We hypothesized that circulating HGF would be positively associated with an increased risk of stroke.

Methods—

Participants aged 45 to 84 years (n=6711) had HGF measured between 2000 and 2002 and were followed for incident stroke through 2013 (n=233). Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals for incident stroke. A secondary analysis stratified results by adjudicated stroke type (n=183 ischemic; n=39 hemorrhagic; n=11 other).

Results—

After adjustment for potential confounding variables, risk of stroke was 17% higher with each standard deviation increase in HGF (hazard ratio, 1.17; 95% confidence interval, 1.03–1.34). This association was mainly driven by ischemic stroke and did not change on exclusion of cardioembolic strokes, although the number of excluded cases was small. The few hemorrhagic and other types of stroke were not associated with HGF.

Conclusions—

Circulating HGF was positively associated with the incidence of stroke in a diverse, population-based cohort of men and women from the United States. Our findings support the hypothesis that circulating HGF is a marker of endothelial damage and suggest that HGF may have utility as a prognostic marker of stroke risk.
Takotsubo-Like Myocardial Dysfunction in Ischemic Stroke
Authors: Jung Jin-Man , Kim Jae-Gyum , Kim Jung Bin , Cho Kyung-Hee , Yu Sungwook , Oh Kyungmi , Kim Yong-Hyun , Choi Jeong-Yoon , Seo Woo-Keun
Published: October 2016

Background and Purpose—

We investigated clinical and radiological characteristics of ischemic stroke patients with Takotsubo-like myocardial dysfunction.

Methods—

From multicenter stroke registry database, ischemic stroke patients who underwent transthoracic echocardiography were found. Among these, patients were classified if they had specific ventricular regional wall motion abnormalities discording with coronary artery distribution, such as apical (typical pattern) or nonapical ballooning (atypical pattern), considered as echocardiographic findings of Takotsubo cardiomyopathy. Patients with ischemic heart disease history, myocarditis, or pheochromocytoma were excluded. We compared patients with Takotsubo-like myocardial dysfunction with those without and further performed systematic literature review on those with Takotsubo cardiomyopathy.

Results—

This study included 23 patients (0.42%). The mean age was 70.7±13.9 years, with predominance of women (73.9%) and typical pattern of Takotsubo-like myocardial dysfunction (91.3%). They were associated with short-term poor functional outcomes, including high mortality, neurological deterioration, and functional status at discharge, compared with those without (39.1% versus 2.4%, 47.8% versus 7.4%; and median [interquartile range], 5 [5–6] versus 3 [2–4]; all
P
<0.001). They had a higher inflammatory marker level and lower triglyceride level. Ischemic lesions were more commonly found in the right anterior circulation with specific dominant regions being the insula and peri-insular areas. In addition, a trend toward a remarkable mortality rate and higher prevalence of insular involvement was observed in the propensity-score matching, subgroup fulfilling the strict Takotsubo cardiomyopath criteria, and was as reported in literature review.

Conclusion—

Stroke patients with Takotsubo-like myocardial dysfunction may differ from those without in clinical outcomes, laboratory findings, and radiological features.
Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
Authors: Qin Xianhui , Li Jianping , Spence J. David , Zhang Yan , Li Youbao , Wang Xiaobin , Wang Binyan , Sun Ningling , Chen Fang , Guo Jingxuan , Yin Delu , Sun Liming , Tang Genfu , He Mingli , Fu Jia , Cai Yefeng , Shi Xiuli , Ye Ping , Chen Hong , Zhao Shuiping , Chen Mao , Gao Chuanyu , Kong Xiangqing , Hou Fan Fan , Huang Yining , Huo Yong
Published: October 2016

Background and Purpose—

We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial.

Methods—

A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke.

Results—

The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18–1.97;
P
=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril–folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56–0.84;
P
<0.001; number needed to treat, 78; 95% confidence interval, 52–158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril–folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75–1.30;
P
=0.982). The effect was greater among participants with elevated total cholesterol (
P
for interaction=0.024).

Conclusions—

Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00794885.
Neurorestorative Responses to Delayed Human Mesenchymal Stromal Cells Treatment of Stroke in Type 2 Diabetic Rats
Authors: Yan Tao , Venkat Poornima , Chopp Michael , Zacharek Alex , Ning Ruizhuo , Roberts Cynthia , Zhang Yi , Lu Mei , Chen Jieli
Published: October 2016

Background and Purpose—

Comorbidity of diabetes mellitus and stroke results in worse functional outcome, poor long-term recovery, and extensive vascular damage. We investigated the neurorestorative effects and mechanisms of stroke treatment with human bone marrow–derived mesenchymal stromal cells (hMSCs) in type 2 diabetes mellitus (T2DM) rats.

Methods—

Adult male Wistar rats were induced with T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5×10
6
) at 3 days after MCAo.

Results—

In T2DM rats, hMSCs administered at 3 days after MCAo significantly improves neurological function without affecting blood glucose, infarct volume, and incidence of brain hemorrhage in comparison to T2DM-MCAo PBS-treated rats. Delayed hMSC treatment of T2DM stroke significantly improves blood–brain barrier integrity, increases vascular and arterial density and cerebral vascular perfusion, and promotes neuroblast cell migration and white matter remodeling as indicated by increased doublecortin, axon, myelin, and neurofilament density, respectively. Delayed hMSC treatment significantly increases platelet-derived growth factor expression in the ischemic brain, decreases proinflammatory M1 macrophage and increases anti-inflammatory M2 macrophage compared to PBS-treated T2DM-MCAo rats. In vitro data show that hMSCs increase subventricular zone explant cell migration and primary cortical neuron neurite outgrowth, whereas inhibition of platelet-derived growth factor decreases hMSC-induced subventricular zone cell migration and axonal outgrowth.

Conclusions—

In T2DM stroke rats, delayed hMSC treatment significantly improves neurological functional outcome and increases neurorestorative effects and M2 macrophage polarization. Increasing brain platelet-derived growth factor expression may contribute to hMSC-induced neurorestoration.
Characterization of Tetraselmis verrucosa f. rubens (Chlorodendrophyceae) strains from coastal lagoons of Western Greece using a multivariate approach
Authors: CHANTZISTROUNTSIOU XANTHI , TZOVENIS IOANNIS , PARMAKELIS ARISTEIDIS , ECONOMOU-AMILLI ATHENA
Published: October 2016

Strains of Tetraselmis, a genus with systematic and biotechnological interest and one of the most prominent genera in marine phytoplankton, were studied. Five strains of T. verrucosa f. rubens, a taxon first documented in coastal lagoons of Greece, are examined herein under a multivariate approach i.e. in relation to their morphological variability under light and transmission electron microscopy (LM and TEM, respectively), and taking into account certain molecular and biochemical attributes as taxonomic markers, including the plastid-encoded rbcL and nuclear-encoded 18S rRNA gene sequences, and the fatty acid profile. The molecular markers were used to verify the phylogenetic position of the strains within the genus Tetraselmis and the class Chlorodendrophyceae. For that purpose, the original Tetraselmis verrucosa f. rubens isolate (CCAP strain 66/6) was included in the analysis. The molecular data are in agreement with the classification based on morphology. The five strains grouped firmly together and formed a monophyletic group with the original T. verrucosa f. rubens isolate. Lipid analysis of the strains was performed using the FAME (Fatty Acid Methyl-Ester) method and the resulting profile might be used as an additional taxonomic marker.
Allopatric color forms of Scaphidium morimotoi Löbl, 1982 (Coleoptera, Staphylinidae, Scaphidiinae) endemic to the Amami Islands, the Ryukyus, Japan
Authors: OGAWA RYO , MATSUO SUSUMU , HOSHINA HIDETO , MAETO KAORU
Published: October 2016

The shining fungus beetle, Scaphidium amamiense Hoshina & Morimoto, 1999 is synonymized with S. morimotoi Löbl, 1982, based on a review of morphological characters and molecular analysis. This species is endemic to the Amami Islands, the Ryukyus, Japan. An almost completely melanic form (morimotoi in strict) is known only on the island Yoro-shima, where the ordinary form with reddish fasciae on the elytra (previously called amamiense) is absent. The present study suggests that the melanic form on the small island has been fixed by random genetic drift.
A review of the genus Spiropagurus Stimpson, 1858 (Crustacea: Decapoda: Paguridae) from the China seas
Authors: HAN YUAN-YUAN , AN JIAN-MEI , SHA ZHONG-LI
Published: October 2016

Three species of the genus Spiropagurus Stimpson, 1858, are reported in the present paper, including a new species, S. monospinosus sp. nov. This new species is easily recognized by the carpus of the cheliped bearing only one row of spines, whereas two rows are present in the other two species from the China seas. A key to all the species of Spiropagurus is provided.