bluuebunny/crossref_metadata_2025 huggingface dataset:
Pipeline Embolization Device for treatment of high cervical and skull base carotid artery dissections: clinical case series
Authors: Brzezicki Grzegorz , Rivet Dennis J , Reavey-Cantwell John
Published: June 2015

Background

Most cervical dissections are treated with anticoagulation or antiplatelet agents with very good results; however, some patients may benefit from endovascular intervention. High cervical and skull base dissections are often more challenging to treat because of the distal location and tortuous anatomy. The Pipeline Embolization Device (PED) may be a reasonable treatment option for this indication.

Objectives

To report a case series of patients treated with the PED for high cervical and skull base dissections, focusing on their presentation, indications for treatment, dissection revascularization success, and pseudoaneurysm obliteration evaluated by imaging, and to review available pertinent literature.

Methods

We retrospectively reviewed all cases of high cervical and skull base dissections treated with a PED at our institution. Patient clinical characteristics, presentation, procedural and follow-up imaging, and clinical course were analyzed to evaluate for procedure complications, dissection revascularization success, pseudoaneurysm obliteration, and clinical outcome.

Results

This is a retrospective case series including 11 patients with 13 carotid dissections treated in our center. There were nine traumatic and four spontaneous dissections. The most common presentation was cerebrovascular accident/transient ischemic attack (CVA/TIA; 5 patients) and headache/face pain (4 patients). Eleven dissections were associated with pseudoaneurysms. Three patients failed medical management with anticoagulation, although flow-limiting stenosis was the main indication for endovascular intervention. Up to three PEDs per vessel were deployed. Angioplasty was used in 10 cases. Complete revascularization (<10% residual stenosis) was achieved in 91% of vessels and 50% of pseudoaneurysms were completely or near completely obliterated immediately after PED(s) deployment. Proximal iatrogenic dissection was the only intraoperative complication. Follow-up imaging was available for nine treated vessels and demonstrated patent PEDs without significant in-stent stenosis up to 9 months after intervention. 75% of pseudoaneurysms were completely obliterated at follow-up. One PED partially collapsed but had no neurological consequences. There were no new CVA/TIAs.

Conclusions

Our initial experience with treatment of high cervical and skull base dissections with the PED appears to show that this technique may be a safe and viable treatment option. However, long-term results are needed to fully evaluate the efficacy of such treatment.
CODE FAST: a quality improvement initiative to reduce door-to-needle times
Authors: Busby Leslie , Owada Kumiko , Dhungana Samish , Zimmermann Susan , Coppola Victoria , Ruban Rebecca , Horn Christopher , Rochestie Dustin , Khaldi Ahmad , Hormes Joseph T , Gupta Rishi
Published: June 2015

Background

Rapid delivery of IV tissue plasminogen activator (tPA) in qualifying patients leads to better clinical outcomes. The American Heart Association has reduced target door-to-needle (DTN) times from 60 to 45 min in the hopes of continued process improvements across institutions.

Objective

To start a quality improvement project called CODE FAST in order to reduce DTN times at our institution.

Materials and methods

We retrospectively reviewed data from our internally maintained database of patients treated with intravenous tPA before and after implementation of the CODE FAST protocol. We assessed demographic information, time of day and times of arrival to first image and delivery of tPA in patients from February 2014 to February 2015. Outcomes were assessed based on discharge to home. Univariate analysis was performed to assess for improvement in DTN times before and after implementation of the protocol.

Results

A total of 93 patients (41 pre-CODE FAST and 52 post-CODE FAST) received IV tPA during the study period. Patients were equally matched between the two groups except that in the pre-CODE FAST era patients receiving tPA were younger and more likely to be men. There was a substantial reduction in door-to-imaging time from a median of 16 to 8 min (p<0.0001) and DTN time with a reduction in the median from 62 to 25 min (p<0.0001). In logistic regression modeling, there was a trend towards more discharges to home in patients treated during the CODE FAST era.

Conclusions

We present a quality improvement project that has been overwhelmingly successful in reducing DTN time to <30 min. The template we present may be helpful to other institutions looking to reduce their DTN times and may also reduce costs as we note a trend towards more discharges to home.
Disease patterns and incidence of immune‐mediated disease in insured Swedish Nova Scotia Duck Tolling Retrievers
Authors: Bremer H. D. , Vilson Å. , Bonnett B. N. , Hansson‐Hamlin H.
Published: June 2015

In this study, morbidity in insured Nova Scotia Duck Tolling Retriever (NSDTR) dogs from Sweden was investigated and compared with all other breeds and other retriever breeds. In addition to describing common morbidities in NSDTRs, the hypotheses that NSDTRs are predisposed to lymphoma, immune‐mediated rheumatic disease (IMRD) and steroid‐responsive meningitis‐arteritis (SRMA) were tested. Included in the study were 445,336 dogs; of which, 2890 were NSDTRs that had been covered by veterinary insurance from the Agria Insurance Company (Stockholm, Sweden) at some point during the years 1995–2006. Incidences of various health problems were calculated using the number of veterinary visits as the numerator and the exact time at risk as the denominator. Overall, morbidity was higher in NSDTRs compared with all other breeds, but similar compared with other retriever breeds. The most common causes of veterinary visits in NSDTRs were injuries, gastrointestinal disease and locomotor disorders, with NSDTRs at increased risk of these compared with all other breeds. The incidences for IMRD, SRMA and lymphoma were significantly higher in NSDTRs than in all other dog breeds and all other retriever breeds. The study describes morbidity in NSDTRs, and identifies several disorders to which the breed is predisposed.
R.A. Daly’s early model of seafloor generation 40 years before the Vine–Matthews hypothesis: an outstanding theoretical achievement inspired by field work on St. Helena in 1921–1922
Authors: Letsch Dominik
Published: June 2015

Large-scale lateral mobility of the Earth’s lithosphere (mobilism) was a hotly debated issue in Earth Sciences during some two decades following publication of Wegener’s (1912) theory of continental displacement. The final acceptance of lithospheric mobility was brought about with the plate tectonics revolution during the late 1960s. Support for mobilism was rather popular in certain European countries during the 1920s, whereas the reactions in North America were mostly hostile. One of the very few influential mobilists in the New World was Reginald Aldworth Daly of Harvard University. The present paper discusses his model of continental displacement which is very remarkable in many aspects. We focus on the hitherto neglected fact that Daly proposed in the mid-1920s a mechanism to create oceanic crust which would have been totally consistent with the Vine–Matthews hypothesis of seafloor generation published in 1963. It is furthermore suggested that Daly’s geotectonic proposals were inspired by small-scale analogues of lava flows and multiple dike swarms he observed on Atlantic islands such as St. Helena and Ascension. His model to account for the construction of new oceanic crust is reminiscent of the models of Vine and Moores (1972) and Cann (1970) which eventually led to the “Penrose-definition” of ophiolites in 1972. As these scientists arrived at their conclusions absolutely independently of Daly, this episode is an instructive example of a multiple or repeated discovery in the Earth Sciences which renders it difficult to believe certain theories of science which assume scientific models to depend mostly on social factors.
RAP-PCR fingerprinting reveals time-dependent expression of development-related genes following differentiation process of Bacillus thuringiensis
Authors: Huang Tianpei , Yu Xiaomin , Gelbič Ivan , Guan Xiong
Published: June 2015

Gene expression profiles are important data to reveal the functions of genes putatively involved in crucial biological processes. RNA arbitrarily primed polymerase chain reaction (RAP-PCR) and specifically primed reverse transcription polymerase chain reaction (RT-PCR) were combined to screen differentially expressed genes following development of a commercial Bacillus thuringiensis subsp. kurstaki strain 8010 (serotype 3a3b). Six differentially expressed transcripts (RAP1 to RAP6) were obtained. RAP1 encoded a putative triple helix repeat-containing collagen or an exosporium protein H related to spore pathogenicity. RAP2 was homologous to a ClpX protease and an ATP-dependent protease La (LonB), which likely acted as virulence factors. RAP3 was homologous to a beta subunit of propionyl-CoA carboxylase required for the development of Myxococcus xanthus. RAP4 had homology to a quinone oxidoreductase involved in electron transport and ATP formation. RAP5 showed significant homology to a uridine kinase that mediates phosphorylation of uridine and azauridine. RAP6 shared high sequence identity with 3-methyl-2-oxobutanoate-hydroxymethyltransferase (also known as ketopantoate hydroxymethyltransferase or PanB) involved in the operation of the tricarboxylic acid cycle. The findings described here would help to elucidate the molecular mechanisms underlying the differentiation process of B. thuringiensis and unravel novel pathogenic genes.
Effects of charge on anisotropic conformally flat polytropes
Authors: Sharif M. , Sadiq Sobia
Published: June 2015

In this paper, we study the effects of electromagnetic field on conformally flat spherically symmetric anisotropic matter distribution satisfying two polytropic equations of state. We consider conformally flat condition and evaluate corresponding anisotropy, which is used to study polytropes for the charged compact object. Finally, we study stability of the resulting models using the Tolman mass. It is concluded that only one of the resulting models is physically viable.
NUMERICAL ESTIMATION OF DRUG DIFFUSION AT DERMAL REGIONS OF HUMAN BODY IN TRANSDERMAL DRUG DELIVERY SYSTEM
Authors: KHANDAY M. A. , RAFIQ AASMA
Published: June 2015

A mathematical model is proposed to study the amount of drug concentration at various regions of human dermal system. The model is based on the mechanism of transdermal drug delivery systems (TDDS) with appropriate boundary conditions. The analytical solution for such problems either does not exist or is too complicated to handle. In this paper, finite element and Crank–Nicholson methods were used to find the solution of the formulated model with greater accuracy.
Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration
Authors: Schall K. A. , Holoyda K. A. , Grant C. N. , Levin D. E. , Torres E. R. , Maxwell A. , Pollack H. A. , Moats R. A. , Frey M. R. , Darehzereshki A. , Al Alam D. , Lien C. , Grikscheit T. C.
Published: June 2015

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation.
Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity
Authors: Bender Shawn B. , Castorena-Gonzalez Jorge A. , Garro Mona , Reyes-Aldasoro Constantino C. , Sowers James R. , DeMarco Vincent G. , Martinez-Lemus Luis A.
Published: June 2015

Increased central vascular stiffening, assessed in vivo by determination of pulse wave velocity (PWV), is an independent predictor of cardiovascular event risk. Recent evidence demonstrates that accelerated aortic stiffening occurs in obesity; however, little is known regarding stiffening of other disease-relevant arteries or whether regional variation in arterial stiffening occurs in this setting. We addressed this gap in knowledge by assessing femoral PWV in vivo in conjunction with ex vivo analyses of femoral and coronary structure and function in a mouse model of Western diet (WD; high-fat/high-sugar)-induced obesity and insulin resistance. WD feeding resulted in increased femoral PWV in vivo. Ex vivo analysis of femoral arteries revealed a leftward shift in the strain-stress relationship, increased modulus of elasticity, and decreased compliance indicative of increased stiffness following WD feeding. Confocal and multiphoton fluorescence microscopy revealed increased femoral stiffness involving decreased elastin/collagen ratio in conjunction with increased femoral transforming growth factor-β (TGF-β) content in WD-fed mice. Further analysis of the femoral internal elastic lamina (IEL) revealed a significant reduction in the number and size of fenestrae with WD feeding. Coronary artery stiffness and structure was unchanged by WD feeding. Functionally, femoral, but not coronary, arteries exhibited endothelial dysfunction, whereas coronary arteries exhibited increased vasoconstrictor responsiveness not present in femoral arteries. Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding. Furthermore, our results suggest TGF-β signaling and IEL fenestrae remodeling as potential contributors to femoral artery stiffening in obesity.
Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?
Authors: Berger Marc Moritz , Macholz Franziska , Mairbäurl Heimo , Bärtsch Peter
Published: June 2015

Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed.
Hydroxamic Acid and Benzoic Acid–Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo
Authors: Yue Peibin , Lopez-Tapia Francisco , Paladino David , Li Yifei , Chen Chih-Hong , Namanja Andrew T. , Hilliard Tyvette , Chen Yuan , Tius Marcus A. , Turkson James
Published: June 2015

STAT3 offers an attractive target for cancer therapy, but small-molecule inhibitors with appealing pharmacologic properties have been elusive. Here, we report hydroxamic acid–based and benzoic acid–based inhibitors (SH5-07 and SH4-54, respectively) with robust bioactivity. Both inhibitors blocked STAT3 DNA-binding activity in vitro and in human glioma, breast, and prostate cancer cells and in v-Src–transformed murine fibroblasts. STAT3-dependent gene transcription was blocked along with Bcl-2, Bcl-xL, Mcl-1, cyclin D1, c-Myc, and survivin expression. Nuclear magnetic resonance analysis of STAT3-inhibitor complexes defined interactions with the SH2 and DNA-binding domains of STAT3. Ectopic expression of the SH2 domain in cells was sufficient to counter the STAT3-inhibitory effects of SH4-54. Neither compound appreciably affected STAT1 or STAT5 DNA-binding activities, STAT3-independent gene transcription, or activation of a panel of oncogenic kinases in malignant cells. Each compound decreased the proliferation and viability of glioma, breast, and prostate cancer cells and v-Src–transformed murine fibroblasts harboring constitutively active STAT3. Further, in mouse xenograft models of glioma and breast cancer, administration of SH5-07 or SH4-54 effectively inhibited tumor growth. Our results offer preclinical proof of concept for SH5-07 and SH4-54 as candidates for further development as cancer therapeutics. Cancer Res; 76(3); 652–63. ©2015 AACR.
The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test
Authors: Schiffman Mark , Boyle Sean , Raine-Bennett Tina , Katki Hormuzd A. , Gage Julia C. , Wentzensen Nicolas , Kornegay Janet R. , Apple Raymond , Aldrich Carrie , Erlich Henry A. , Tam Thanh , Befano Brian , Burk Robert D. , Castle Philip E.
Published: June 2015

Background: The cobas HPV Test (“cobas”; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology (“cotesting”), and (iii) primary HPV screening.

Methods: To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+.

Results: Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the κ statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86–0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%–15.5% vs. 3.5%; 95% CI, 3.3–3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6–11.1 vs. 2.3%; 95% CI, 2.2–2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8–19.2 vs. 4.3%; 95% CI, 4.2–4.4).

Conclusion: The cobas and LA results show excellent agreement. The data support HPV16 typing.

Impact: HPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. Cancer Epidemiol Biomarkers Prev; 24(9); 1304–10. ©2015 AACR.

See related commentary by Del Mistro, p. 1302
A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis
Authors: Hanniford Doug , Zhong Judy , Koetz Lisa , Gaziel-Sovran Avital , Lackaye Daniel J. , Shang Shulian , Pavlick Anna , Shapiro Richard , Berman Russell , Darvishian Farbod , Shao Yongzhao , Osman Iman , Hernando Eva
Published: June 2015

Purpose: Brain metastasis is the major cause of mortality among patients with melanoma. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients.

Experimental Design: We performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n = 92, 119, and 45) with extensive clinical follow-up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis.

Results: Our analyses identified a 4-microRNA (miR-150-5p, miR-15b-5p, miR-16-5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from nonrecurrent and non–brain metastatic primary tumors (training cohort: C-index = 81.4%, validation cohort: C-index = 67.4%, independent cohort: C-index = 76.9%). Corresponding Kaplan–Meier curves of high- versus low-risk patients displayed a clear separation in brain metastasis-free and overall survival (training: P < 0.001; P < 0.001, validation: P = 0.033; P = 0.007, independent: P = 0.021; P = 0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150-5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45+ tumor-infiltrating lymphocytes.

Conclusions: A prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies. Clin Cancer Res; 21(21); 4903–12. ©2015 AACR.
Portal/Superior Mesenteric Vein Reconstruction during Pancreatic Resection Using a Cryopreserved Arterial Homograft
Authors: Mascoli Chiara , D''Ambra Marielda , Casadei Riccardo , Ricci Claudio , Taffurelli Giovanni , Ancetti Stefano , Stella Andrea , Minni Francesco , Freyrie Antonio
Published: June 2015

Background: Portal-superior mesenteric vein (PV/SMV) resection during pancreatic resection has been widely applied in clinical practice. Methods: From a prospective data base of pancreatic resections, patients undergoing PV/SMV resection and reconstruction with a cryopreserved arterial homograft were extracted with the aim of evaluating the safety, feasibility and reproducibility of the procedure. Data regarding patient demographics, preoperative staging, surgery, histopathology and postoperative outcomes were analyzed. Results: Five patients were extracted in the last year. Indications for this technique were type IV-V degree of vein involvement and a 3.5 cm median length of vein infiltration. Median operative and clamping times were satisfactory (385 and 27 min, respectively), postoperative outcomes were good and there was no graft infection, thrombosis or stenosis occurred postoperatively and during the follow-up period. Conclusion: The use of a cryopreserved arterial homograft for PV/SMV reconstruction after pancreatic resection seems to be a feasible, safe and easily reproducible surgical technique in high-volume specialized centers and can be added to the pool of surgical solutions in selected patients.
Diagnostic Value of Different Systematic Prostate Biopsy Methods in the Detection of Prostate Cancer with Ultrasonographic Hypoechoic Lesions - A Comparative Study
Authors: Xu Guang , Yao Minghua , Wu Jian , Guo Lehang , Feng Lijing , Wang Shuai , Zhao Lixia , Xu Huixiong , Wu Rong
Published: June 2015

Objective: To assess if a less extended biopsy in the transperineal approach is sufficient for detection of prostate cancer (PC) in patients with hypoechoic lesions. Methods: This was a prospective study of 167 consecutive patients with prostate hypoechoic lesion and who underwent transperineal ultrasound (TPUS)-guided 12-core and hypoechoic lesion core biopsy between January 2012 and February 2013. Results: PC was detected in 64.1% (107/167) of patients. The PC detection rate of the 12-core prostate biopsy scheme was the highest, but when including the hypoechoic lesion core, there was no difference between the 6- and 12-core schemes (all p > 0.05), irrespective of prostate volume or prostate-specific antigen levels (all p > 0.05). Conclusions: A more limited biopsy scheme could be sufficient for the detection of PC if the hypoechoic lesion is sampled.
The Effects of 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone on Pressure Overload-Induced Cardiac Remodeling in Rats and the Endothelial Mechanisms Based on PGI2
Authors: Huang Jianchun , Tang Xiaojun , Liang Xingmei , Wen Qingwei , Zhang Shijun , Xuan Feifei , Jian Jie , Lin Xing , Huang Renbin
Published: June 2015

Aim: The primary objective of this study was to study the effects of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on pressure overload-induced cardiac remodeling in rats, as well as the endothelial mechanisms based on PGI2. Methods: Six weeks following surgery, rats were divided randomly into the following groups: a sham group, a model group, an MHBFC 12 mg/kg/day group (MHBFC 12), an indomethacin 2 mg/kg/day group (Indo 2), and an Indo 2+ MHBFC 12 group. The MS 4000 organism signal system was used to record the rats' hemodynamic indices. Additionally, the heart weight was determined, and the cardiac remodeling index was calculated. HE and Masson's stains were utilized to perform histological analyses; the immunofluorescence was used to observe the microvessel density of myocardial tissue; the colorimetric method was used to determine the hydroxyproline content of cardiac tissue; the ELISA method was used to measure the plasma PGI2 content; and transmission electron microscopy was used to observe the ultrastructure of the myocardium. Results: A hyperdynamic circulation state, cardiac remodeling, decreased microvessel density and decreased plasma PGI2 content were each observed in the model group compared with the sham group, in which any changes in the above parameters were effectively reversed by MHBFC. Single-use Indo administration resulted in the progression of these pathophysiological changes; however, MHBFC prevented the worsening of these parameters. Conclusion: MHBFC significantly reverses pressure overload-induced cardiac remodeling, and its mechanism may partially contribute to the amelioration of endothelial cell function and the augmentation of PGI2 synthesis and secretion.
Urinary Trypsin Inhibitor Attenuates Acute Lung Injury by Improving Endothelial Progenitor Cells Functions
Authors: Guo Weixin , Li Zhihong , Xie Xiaoyun , Qin Tiehe , Wu Yan , Li Zhou , Chai Jing , Yi Frank , Tan Tao , Zhu Hua , Wang Shouhong
Published: June 2015

Background: Urinary Trypsin Inhibitor (UTI) is involved in various aspects of tissue repair, regeneration and development. However, the potential role of UTI in protection against acute lung injury (ALI) remains largely unknown. In the present study, we demonstrated that UTI treatment could ameliorate ALI induced by oleic acid (OA) treatment in rabbit model. Methods: Intravenous application of UTI (10000 U/kg/d) significantly improved the pathologies associated with OA-induced ALI. The lungs were stained with hematoxylin and eosin to scored the lung injury. Peripheral blood mononuclear cells were isolated by density gradient centrifugation with Ficoll-Plaque Plus. The proliferation and ability of tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. Results: Consistent with pathological scores, UTI treatment significantly reduced wet/dry ratio of OA injured lungs. A quantification of capillary density revealed that UTI treatment led to about 2 fold increase over uninjured control and about 1.5 fold increase over PBS treatment. The capacity for tube formation of EPCs on ECM gel was significantly reduced in the ALI group and recovered with UTI treatment. Quantification of western blot bands was summarized and showed that UTI treatment activates Akt/eNOS signaling. NO production could contribute to the improvement of EPCs function by UTI treatment. Conclusions: UTI-induced phosphorylation/activation of eNOS and Akt, increases the intracellular level of NO, thereby improving tube formation and proliferation function of EPCs. EPCs function is crucial for re-endothelialization after denuding injuries of arteries.
Outcomes of Neoadjuvant Chemotherapy without Radiation for Rectal Cancer
Authors: Matsumoto Takuya , Hasegawa Suguru , Zaima Masazumi , Inoue Naoya , Sakai Yoshiharu
Published: June 2015

Aim: The efficacy of neoadjuvant chemotherapy without radiation (NAC) in the treatment of rectal cancer remains unclear. This retrospective study was aimed at determining the pathological complete response rate and short-term outcomes of NAC in patients with locally advanced rectal cancer. Patients and Methods: We collected data on 159 consecutive patients treated for rectal cancer (cT3/cT4a, cN+, and cM0 status) at five tertiary referral hospitals between 2005 and 2010. Pathological complete response (pCR) and safety were assessed as the main outcomes in 124 eligible patients comprising 15 who received NAC (NAC group) and 109 who received no neoadjuvant chemotherapy (non-NAC group). Results: In the NAC group, 2 patients (13.3%) achieved a pCR (95% confidence interval: 1.7-40.5%) and 3 patients (20%) experienced grade 3/4 adverse events. No significant differences were found between the NAC and non-NAC groups in terms of short-term outcomes, including R0 proportion (100 vs. 96.3%, p = 0.45) and postoperative grade 3/4 complications (13.3 vs. 18.4%, p = 0.63). Conclusions: Neoadjuvant systemic chemotherapy without radiation appears to be safe, without worsening short-term outcomes, in patients with locally advanced rectal cancer. A further study is needed to verify these findings in larger samples.
Peritoneal-Pleural Leaks Demonstrated by CT Peritoneography
Authors: Xu Tian , Xie Jingyuan , Wang Weiming , Ren Hong , Chen Nan
Published: June 2015

Introduction: Acute hydrothorax is an uncommon complication of peritoneal dialysis (PD). Currently, there is no specific diagnostic method. Although it is not a life-threatening complication, hydrothorax often requires interrupting or quitting PD. Misdiagnosis often leads to more serious consequences. Case Presentation: A 49-year-old woman (height 163 cm, weight 58 kg, BMI 21.82), who started PD 3 months previously, suddenly presented with acute dyspnea and a right pleural effusion. Blood routine examination, serum albumin and a series of laboratory tests were immediately performed. Except for the serum creatinine, all of the other tests were within normal range. Thoracentesis was performed to obtain pleural fluid specimens; there was also no evidence of a tumor or inflammation. Congestive heart failure, infection and hypoalbuminemia were excluded as well. Because PD-associated pleural leakage was suspected, computerized tomography (CT) peritoneography was performed next. The first CT scan showed that the CT value of pleural effusion was 6 Hounsfield units (HU). On the evening of the same day, 100 ml ionic contrast medium was mixed with 2 l dialysate and infused into the peritoneal cavity. The next morning, a CT scan was performed again. The CT value of pleural effusion at the same site increased to 40 HU. At the end, pleural leakage was clearly diagnosed. Subsequently, she received temporary hemodialysis and a small dose of automated PD. After 3 months, she successfully returned to PD without any recurrence of hydrothorax. Conclusion: Although similar case reports are not rare, this report provided a simple and effective method for diagnosing pleural leakage. Furthermore, noninvasive treatment of pleural effusion will also get a satisfactory outcome.
Refractory Abdominal Pain in a Hemodialysis Patient
Authors: Qian Ying , Chen Xiao-nong , Shi Hao , Xie Jing-yuan , Chen Nan
Published: June 2015

Nonocclusive mesenteric ischemia (NOMI) is a rare disorder. Failure of an early diagnosis may cause progressive intestinal ischemia, leading to abdominal pain, sepsis, and death. Patients with end-stage renal disease are among the highest risk populations for developing this lethal complication. The key to a correct diagnosis at an early stage is a high index of suspicion in predisposed patients. In our case, we present a 62-year-old female undergoing maintenance hemodialysis for 8 years; she complained of abdominal pain after hemodialysis in the last 3 months; NOMI was suspected after a CT angiography. She partially recovered after multiple clinical interventions such as decreased ultrafiltration, an increased dose of low molecular-weight heparin and the use of vasoactive drugs. In conclusion, NOMI can be reversible if it is diagnosed as early as possible and after the necessary diagnostic measurements are initiated.
Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study
Authors: Rudkowska Iwona , Pérusse Louis , Bellis Claire , Blangero John , Després Jean-Pierre , Bouchard Claude , Vohl Marie-Claude
Published: June 2015

Background/Aim: Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective was to examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies. Methods: SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects. Results: The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p < 10-5, including SNPs in the following genes: ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, and SUSD4. Conclusions: This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.
High Expressions of Lgr5 and ALDH1 in Primary Epithelial Ovarian Cancer Correlate with Advanced Tumor Stage and Grade as well as Poor Prognosis of the Patients
Authors: Sun Yanan , Jia Xiaopeng , Wu Xiaohua
Published: June 2015

Background: The aim of our study was to investigate the clinical role of aldehyde dehydrogenase 1 (ALDH1) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) expressions in epithelial ovarian cancer (EOC) and their prognostic significance. Methods: One hundred primary EOC samples were obtained for immunohistochemical analysis of ALDH1 and Lgr5 expressions. Correlation analysis was performed between ALDH1 or Lgr5 and clinical factors. Results: High expression of ALDH1 and Lgr5 was identified in 71 and 55 cases of EOC tissues, respectively. The ALDH1 and Lgr5 expressions in EOC tissues were significantly higher as compared to the normal ovaries and benign ovarian tumors. High expression of ALDH1 and Lgr5 was strongly correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stages, higher tumor grades, and poor overall survival of the patients. Conclusions: Lgr5 and ALDH1 were highly expressed in EOC tissues, and correlated with different FIGO operation-pathological stages and tumor grades, clinical outcome, and with each other. The combined use of ALDH1 and Lgr5 might be useful for the diagnosis and prognosis prediction of EOC patients.
Intensive Perioperative Simvastatin Treatment Protects from Chronic Kidney Allograft Injury
Authors: Palin Niina K. , Savikko Johanna , Rintala Jukka M. , Koskinen Petri K.
Published: June 2015

Background/Aims: Ischemia-reperfusion injury (IRI) and innate immune response augment adaptive immunity and may also trigger repair processes that lead to uncontrolled fibrosis and atherosclerosis as seen in chronic allograft injury. Simvastatin has been shown to protect from renal IRI in several experimental studies. The aim of this study was to examine the effect of donor simvastatin pretreatment and early initiation of recipient simvastatin treatment on chronic kidney allograft injury. Methods: A rat renal transplantation model was used. Simvastatin was administered perorally for donor (5 mg/kg) and/or for recipient (2 mg/kg) 2 hours before transplantation and/or as daily treatment starting on the first postoperative day (2 mg/kg/day). The study included 5 groups: (1) no simvastatin, (2) donor pretreatment, (3) daily recipient treatment, (4) donor pretreatment + daily recipient treatment and (5) donor pretreatment + recipient pretreatment + daily recipient treatment. The grafts were recovered at day 90 for histopathological and immunohistochemical analysis. Kidney function was followed weekly with serum creatinine, and 24-hour urine protein was measured 60 and 90 days after transplantation. Results: We found that donor and recipient simvastatin pretreatment combined with daily recipient treatment reduced graft inflammation and chronic allograft injury. Treatment using only statins started after transplantation reduced inflammation to some extent, but did not affect chronic kidney allograft injury. Pretreatment using only donor statins impaired graft function and increased proteinuria. Conclusion: Our data suggest that perioperative recipient statin treatment reduces inflammation and may protect the graft in the long term.
Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis
Authors: Gul Utku Ozlem , Akbay Karatay Eylem , Erdal Harun , Arhan Mehmet , Onal Ibrahim Koral , Ibis Mehmet , Ekinci Ozgur , Yilmaz Demirtas Canan , Unal Selahattin
Published: June 2015

Objective: This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and Methods: Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis. Results: Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor β1 (TGF-β1) and the activites of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-β1. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration. Conclusions: Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.
Nucleoside Diphosphate Kinase B–Activated Intermediate Conductance Potassium Channels Are Critical for Neointima Formation in Mouse Carotid Arteries
Authors: Zhou Xiao-Bo , Feng Yu-Xi , Sun Qiang , Lukowski Robert , Qiu Yi , Spiger Katharina , Li Zhai , Ruth Peter , Korth Michael , Skolnik Edward Y. , Borggrefe Martin , Dobrev Dobromir , Wieland Thomas
Published: June 2015

Objective—

Vascular smooth muscle cells (VSMC) proliferation is a hallmark of atherosclerosis and vascular restenosis. The intermediate conductance Ca
2+
-activated K
+
(SK4) channel is required for pathological VSMC proliferation. In T lymphocytes, nucleoside diphosphate kinase B (NDPKB) has been implicated in SK4 channel activation. We thus investigated the role of NDPKB in the regulation of SK4 currents (I
SK4
) in proliferating VSMC and neointima formation.

Approach and Results—

Function and expression of SK4 channels in VSMC from injured mouse carotid arteries were assessed by patch-clamping and real-time polymerase chain reaction. I
SK4
was detectable in VSMC from injured but not from uninjured arteries correlating with the occurrence of the proliferative phenotype. Direct application of NDPKB to the membrane of inside-out patches increased I
SK4
, whereas NDPKB did not alter currents in VSMC obtained from injured vessels of SK4-deficient mice. The NDPKB-induced increase in I
SK4
was prevented by protein histidine phosphatase 1, but not an inactive protein histidine phosphatase 1 mutant indicating that I
SK4
is regulated via histidine phosphorylation in proliferating VSMC; moreover, genetic NDPKB ablation reduced I
SK4
by 50% suggesting a constitutive activation of I
SK4
in proliferating VSMC. In line, neointima formation after wire injury of the carotid artery was substantially reduced in mice deficient in SK4 channels or NDPKB.

Conclusions—

NDPKB to SK4 signaling is required for neointima formation. Constitutive activation of SK4 by NDPKB in proliferating VSMC suggests that targeting this interaction via, for example, activation of protein histidine phosphatase 1 may provide clinically meaningful effects in vasculoproliferative diseases such as atherosclerosis and post angioplasty restenosis.
High-Density Lipoproteins Reduce Endothelial-to-Mesenchymal Transition
Authors: Spillmann Frank , Miteva Kapka , Pieske Burkert , Tschöpe Carsten , Van Linthout Sophie
Published: June 2015

Objective—

Endothelial-to-mesenchymal transition is an inflammation-induced process by which endothelial cells can transdifferentiate into fibroblasts. Based on the endothelial-protective and antifibrotic effects of high-density lipoproteins (HDL), we aimed to investigate whether HDL can reduce endothelial-to-mesenchymal transition.

Approach and Results—

Therefore, human aortic endothelial cells were stimulated with the profibrotic factor transforming growth factor (TGF)-β1 in the presence or absence of HDL. Their impact on the transition of endothelial cells to mesenchymal-like cells was analyzed. Phase contrast microscopy demonstrated that HDL abrogated the TGF-β1–induced spindle-shape morphology in human aortic endothelial cells. Furthermore, HDL decreased the TGF-β1–mediated induction of α-smooth muscle actin expression and concomitant loss in endothelial cadherin expression, as shown by immunofluorescence staining and flow cytometry. In addition, HDL decreased the TGF-β1–induced collagen deposition in human aortic endothelial cells involving the scavenger receptor class B, type 1 and downstream phosphatidyl inositol-3-kinase following the findings that the HDL-mediated reduction was abrogated by scavenger receptor class B, type 1 siRNA knockdown and phosphatidyl inositol-3-kinase inhibition, respectively. The HDL-mediated reduction in endothelial-to-mesenchymal transition was associated with an induction of the inhibitory Smad, Smad 7.

Conclusions—

We provide the first in vitro evidence that the endothelial-protective and antifibrotic effects of HDL include the reduction in endothelial-to-mesenchymal transition.
Meta‐Analysis of Intracranial Hemorrhage in Acute Coronary Syndromes: Incidence, Predictors, and Clinical Outcomes
Authors: Mahaffey Kenneth W. , Hager Rebecca , Wojdyla Daniel , White Harvey D. , Armstrong Paul W. , Alexander John H. , Tricoci Pierluigi , Lopes Renato D. , Ohman E. Magnus , Roe Matthew T. , Harrington Robert A. , Wallentin Lars
Published: June 2015

Background

Little is known about the incidence, predictors, or outcomes of intracranial hemorrhage (
ICH
) in patients with non–
ST
‐segment elevation acute coronary syndromes (
NSTE ACS
). We aimed to determine the incidence and timing of
ICH
, characterize the location of
ICH
, and identify independent baseline predictors of
ICH
in
NSTE ACS
patients.

Methods and Results

We pooled patient‐level data from 4 contemporary antithrombotic therapy trials. Multivariable modeling identified independent predictors of
ICH
.
ICH
s were adjudicated by a clinical events committee. Of 37 815 patients, 135 (0.4%) had an
ICH
. The median (25th, 75th percentiles) follow‐up was 332 (184, 434) days but differed across trials. Locations of
ICH
were intracerebral (50%), subdural (31%), subarachnoid (18.5%), and intraventricular (11%). Independent predictors of
ICH
were older age (
HR
per 10 years, 1.61; 95%
CI
, 1.35 to 1.91); prior stroke/transient ischemic attack;
HR
, 1.95; 95%
CI
, 1.14 to 3.35), higher systolic blood pressure;
HR
per 10 mm Hg increase, 1.09; 95%
CI
, 1.01 to 1.18), and larger number of antithrombotic agents (
HR
per each additional agent, 2.06; 95%
CI
, 1.49 to 2.84). Of all
ICH
s, 45 (33%) were fatal.

Conclusions

In patients with
NSTE ACS
enrolled in recent clinical trials of antithrombotic therapies,
ICH
was uncommon. Patients with older age, prior transient ischemic attack/stroke, higher systolic blood pressure, or larger number of antithrombotic agents were at increased risk. One‐third of patients with
ICH
died. These data may be useful to trialists and data and safety monitoring committees for trial conduct and monitoring.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov/
. Unique identifiers: TRACER: NCT00527943, PLATO: NCT00391872, APPRAISE‐2: NCT00831441, TRILOGY ACS: NCT00699998.