bluuebunny/crossref_metadata_2025 huggingface dataset:
NEW REACTION PATHWAYS OFPROPENE + BCl3DECOMPOSITION IN CHEMICAL VAPOR DEPOSITION PROCESS
Authors: YANG JIANHUA , SU KEHE , LIU YAN , WANG YANLI , ZENG QINGFENG , CHENG LAIFEI , ZHANG LITONG
Published: February 2012

More reaction pathways in the CVD process of preparing boron-carbides with BCl3-C3H6(propene)-H2precursors were examined in addition to the "lowest" path proposed by Jiang et al. in Theor Chem Acc127:519–538, 2010. The new pathways investigated in this work involve 81 new transition states and 79 new intermediates. Geometries of the species were optimized with the density functional theory at B3PW91/6-311G(d,p) level. Intrinsic reaction coordinates were analyzed to confirm the correct reaction linkages. Energy barriers and reaction energies were calculated with the accurate model chemistry method G3(MP2) after a non-dynamical electronic correlation detection using CASSCF method. Heat capacities and entropies were obtained with the statistical thermodynamics and fitted as a function of temperature. Gibbs free energies at 298.15 K and 1200 K were used to examine the reaction paths. It was found that some steps in the new paths at both 298.15 K and 1200 K are different from the "lowest" path obtained previously and the pathways for the new products CB and C2B were obtained.
EXPLORING THE MOLECULAR BASIS OF H5N1 HEMAGGLUTININ BINDING WITH CATECHINS IN GREEN TEA: A FLEXIBLE DOCKING AND MOLECULAR DYNAMICS STUDY
Authors: LIU JUNXING , YANG ZHIWEI , WANG SHUQIU , LIU LEI , CHEN GUANG , WANG LIN
Published: February 2012

The influenza A (H5N1) virus attracts a worldwide attention and calls for the urgent development of novel antiviral drugs. In this study, explicitly solvated flexible docking and molecular dynamics (MD) simulations were used to study the interactions between the H5N1 sub-type hemagglutinin (HA) and various catechin compounds, including EC ([–]-epicatechin), EGC ([–]-epigallocatechin), ECG ([–]-epicatechin gallate) and EGCG ([–]-epigallocatechin gallate). The four compounds have respective binding specificities and their interaction energies with HA decrease in the order of EGCG (-133.52) > ECG (-111.11) > EGC (-97.94) > EC (-83.39). Units in kcal mol-1. Residues IleA267, LysA269, ArgB68 and GluB78 play important roles during all the binding processes. EGCG has the best bioactivity and shows potential as a lead compound. Besides, the importance was clarified for the functional groups it was revealed that the C5′ hydroxyl and trihydroxybenzoic acid groups are crucial for the catechin inhibitory activities, especially the latter. Combined with the structural and property analyses, this work also proposed the way to effectively modify the functional groups of EGCG. The experimental efforts are expected in order to actualize the catechin derivatives as novel anti-influenza agents in the near future.
HÜCKEL TREATMENT OF PYRROLE AND PENTALENE AS A FUNCTION OF CYCLOPENTADIENYL USING LOCAL QUANTUM SIMILARITY INDEX (LQSI) AND THE TOPO-GEOMETRICAL SUPERPOSITION APPROACH (TGSA)
Authors: MORALES-BAYUELO ALEJANDRO , TORRES JUAN , VIVAS-REYES RICARDO
Published: February 2012

In this paper some of the characteristic of Hückel method, were exploited in order to obtain some important results, through a new technique with which it is possible to obtain non-degenerate characteristic values as in the case of pyrrole and allowing the expression of conjugated ring systems (Pentalene) as function of a system of diene monomer (Cyclopentadienyl). The local similarity index based on the Hirshfeld partitioning in the framework of conceptual Density Functional Theory (DFT), was introduced in the secular determinant of the Hückel method and was applied to Pyrrole molecule in order to express their orbital energies as a function of the orbital energy of Cyclopentadienyl, to express the energies of molecular orbitals of the Cyclopentadienyl as a function of Pentalene, resolved by the Hückel method and applied to Cyclopentadienyl, by means of six local similarity index: Overlap, Overlap-Interaction, Coulomb, Coulomb-Interaction, with their respective Euclidean distances, using the Topo-Geometrical Superposition Approach (TGSA) as a method of alignment, which allowed us to obtain good results in local similarity indices.

This technique will permit the study of some molecular systems that differ in one atom in its molecular structure, resolving the Hückel method for the Pyrrole and Thiophene system without taking into account the considerations with its neighboring atoms. This proposed technique reduces the symmetry of fused ring systems which are Cyclopentadienyl derivatives, allowing to express the orbital energy of a diene dimmer (Pentalene) as a function of diene monomer systems, creating a tool of calculation to solve the problem of obtaining non-degenerate values in systems where the approximations in the Hückel method approximation provide degenerate values and providing a symmetry reduction technique.
Effects of leptin and obesity on the upper airway function
Authors: Polotsky Mikhael , Elsayed-Ahmed Ahmed S. , Pichard Luis , Harris Christopher C. , Smith Philip L. , Schneider Hartmut , Kirkness Jason P. , Polotsky Vsevolod , Schwartz Alan R.
Published: February 2012

Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that ( 1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that ( 2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob− /ob− mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (PN) to determine the passive expiratory critical pressure (PCRIT) and active responses to reductions in PN, including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the PN threshold at which IFL developed, maximum inspiratory airflow (Vimax), and genioglossus electromyographic (EMGGG) activity. Elevations in body weight were associated with progressive elevations in PCRIT (0.1 ± 0.02 cmH2O/g), independent of mouse strain. PCRIT was also elevated in ob− /ob− compared with BL6 mice (1.6 ± 0.1 cmH2O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and PN threshold and lower Vimax. Very obese ob− /ob− mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and PN threshold (from −0.8 ± 1.1 to −5.6 ± 0.8 cmH2O) and increase in Vimax (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive PCRIT in leptin-treated mice did not differ significantly from that seen in nontreated ob− /ob− mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.
Chemokines regulate small leucine-rich proteoglycans in the extracellular matrix of the pressure-overloaded right ventricle
Authors: Waehre Anne , Vistnes Maria , Sjaastad Ivar , Nygård Ståle , Husberg Cathrine , Lunde Ida Gjervold , Aukrust Pål , Yndestad Arne , Vinge Leif E. , Behmen Dina , Neukamm Christian , Brun Henrik , Thaulow Erik , Christensen Geir
Published: February 2012

Chemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. We have previously shown that the chemokine (C-X-C motif) ligand 13 (CXCL13) regulates small leucine-rich proteoglycans (SLRPs). We hypothesized that chemokines are upregulated in the pressure-overloaded RV, and that they regulate SLRPs. Mice with RV pressure overload following pulmonary banding (PB) had a significant increase in RV weight and an increase in liver weight after 1 wk. Microarray analysis (Affymetrix) of RV tissue from mice with PB revealed that CXCL10, CXCL6, chemokine (C-X3-C motif) ligand 1 (CX3CL1), chemokine (C-C motif) ligand 5 (CCL5), CXCL16, and CCL2 were the most upregulated chemokines. Stimulation of cardiac fibroblasts with these same chemokines showed that CXCL16 increased the expression of the four SLRPs: decorin, lumican, biglycan, and fibromodulin. CCL5 increased the same SLRPs, except decorin, whereas CX3CL1 increased the expression of decorin and lumican. CXCL16, CX3CL1, and CCL5 were also shown to increase the levels of glycosylated decorin and lumican in the medium after stimulation of fibroblasts. In the pressure-overloaded RV tissue, Western blotting revealed an increase in the total protein level of lumican and a glycosylated form of decorin with a higher molecular weight compared with control mice. Both mice with PB and patients with pulmonary stenosis had significantly increased circulating levels of CXCL16 compared with healthy controls measured by enzyme immunoassay. In conclusion, we have found that chemokines are upregulated in the pressure-overloaded RV and that CXCL16, CX3CL1, and CCL5 regulate expression and posttranslational modifications of SLRPs in cardiac fibroblasts. In the pressure-overloaded RV, protein levels of lumican were increased, and a glycosylated form of decorin with a high molecular weight appeared.
A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance
Authors: Jarvis S. S. , Florian J. P. , Curren M. J. , Pawelczyk J. A.
Published: February 2012

Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women ( P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min ( P < 0.05) and 21.8 vs. 45.0 min ( P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5–0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41–0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance.
Tumor Cell–Derived Angiopoietin-like Protein ANGPTL2 Is a Critical Driver of Metastasis
Authors: Endo Motoyoshi , Nakano Masahiro , Kadomatsu Tsuyoshi , Fukuhara Shigetomo , Kuroda Hiroaki , Mikami Shuji , Hato Tai , Aoi Jun , Horiguchi Haruki , Miyata Keishi , Odagiri Haruki , Masuda Tetsuro , Harada Masahiko , Horio Hirotoshi , Hishima Tsunekazu , Nomori Hiroaki , Ito Takaaki , Yamamoto Yutaka , Minami Takashi , Okada Seiji , Takahashi Takashi , Mochizuki Naoki , Iwase Hirotaka , Oike Yuichi
Published: February 2012

Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell–derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell–derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells–blunted metastasis and extended survival. Overall, our findings showed that tumor cell–derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process. Cancer Res; 72(7); 1784–94. ©2012 AACR.
Molecular Pathways: Pathogenesis and Clinical Implications of Microbiome Alteration in Esophagitis and Barrett Esophagus
Authors: Yang Liying , Francois Fritz , Pei Zhiheng
Published: February 2012

Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-κB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus. Clin Cancer Res; 18(8); 2138–44. ©2012 AACR.
Blastic Plasmacytoid Dendritic Cell Neoplasm: Cytopathologic Findings
Authors: Zheng Gang , Schmieg John , Guan Hui , Ali Syed Z.
Published: February 2012

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematopoietic neoplasm, which in the past was also known variously as blastic NK cell lymphoma, agranular CD4+ natural killer cell leukemia, and CD4+/CD56+ hematodermic neoplasm. BPDCN is now believed to arise from plasmacytoid dendritic cells, but its exact etiology is still unknown. We report here on the cerebrospinal fluid (CSF) cytology of a BPDCN, a hypercellular specimen comprised of malignant, singly dispersed cells with scant to moderate amounts of pale blue, agranular cytoplasm, and uniform round to oval nuclei, fine chromatin, prominent nucleoli, occasional cytoplasmic microvacuoles, and pseudopodia. Neither mitoses nor karyorrhexis were identified. Flow cytometry of the CSF demonstrated that the malignant cells expressed bright CD45, HLA-DR and CD33, dim CD4, heterogeneous CD56, and partial CD123. The importance of clinical, histopathological, and phenotypic correlation is emphasized. Clinical and histopathological correlation and a literature review are also presented. The poor clinical outcome makes it important to accurately report this rare tumor in a CSF specimen.
Metastatic Squamous Cell Carcinoma in Cerebrospinal Fluid: Why a Rare Diagnosis on Cytology?
Authors: Ren Shuyue , Huang Yajue , Shah Pallav , Manucha Varsha
Published: February 2012

Background: Squamous cell carcinoma metastatic to cerebrospinal fluid (CSF) is a rare diagnosis on cytology, and thereby more challenging in comparison to an adenocarcinoma metastatic to CSF. We recently encountered a case of metastatic squamous cell carcinoma in CSF. The primary site was unknown. A review of the literature was performed to understand why this is a rare diagnosis in cytology. Case: A 56-year-old male was diagnosed with a keratinizing squamous cell carcinoma involving multiple lymph nodes in the neck. On extensive clinical and radiologic evaluation, a primary could not be identified. Subsequently, the patient presented with sudden loss of vision (in the right eye), nausea and vomiting. MRIs of the lumbar spine and optic nerve were suggestive of leptomeningeal and perineural seeding, respectively. Cytologic evaluation of CSF revealed a few atypical, round hyperchromatic cells which were confirmed as epithelial cells through immunocytochemistry for a broad-spectrum keratin. The diagnosis of metastatic carcinoma consistent with squamous cell carcinoma was rendered. Conclusion: Definitive diagnosis of metastatic squamous cell carcinoma is challenging unless clinical evidence is present. Besides other factors, the mode of spread to CSF may be responsible for this less common diagnosis.
Multicentric Extranodal Rosai Dorfman Disease – A Cytological Diagnosis, with Histological Corroboration
Authors: Majumdar Kaushik , Tyagi Ila , Saran Ravindra K. , Kumar Sushil , Gondal Ranjana
Published: February 2012

Background: Rosai Dorfman disease (RDD) typically presents with massive bilateral cervical lymphadenopathy, a viral-like prodrome, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Other lymph nodes may be less commonly involved. Extranodal RDD is quite rare, and orbital disease accounts for only 10% of the extranodal sites of involvement. Multicentric disease has also been described, which is usually accompanied by lymphadenopathy either initially or later in the disease course. Case: We report an extremely rare extranodal multicentric disease in a diabetic patient, presenting with bilateral orbital involvement, causing ocular motility restriction, which was diagnosed on aspiration cytology of the orbital mass. This was followed in quick succession by new mass lesions in the lower back and infratemporal fossa. On extensive work-up, no lymphadenopathy was detected. The patient responded well to surgical debulking of the orbital lesions and systemic steroids. Conclusion: Fine needle aspiration cytology can be effectively applied for early diagnosis of multicentric extranodal RDD. Surgical debulking in such cases may be supplemented by systemic steroids.
Fine-Needle Cytology and Flow Cytometry Assessment of Reactive and Lymphoproliferative Processes of the Breast
Authors: Vigliar Elena , Cozzolino Immacolata , Fernandez Laura Virginia Sosa , Di Pietto Leda , Riccardi Albina , Picardi Marco , Pane Fabrizio , Vetrani Antonio , Troncone Giancarlo , Zeppa Pio
Published: February 2012

Objective: The breast may be affected by reactive and lymphoproliferative processes such as primary (PBL) or secondary (SBL) lymphoma, reactive intramammary lymph nodes and sclerosing lobulitis; imaging may be not specific and surgical treatment not indicated. We report an experience with fine-needle cytology (FNAC) combined with flow cytometry (FC) and immunocytochemistry (ICC) in the diagnosis of these processes. Study Design: Thirty-seven cases comprising intramammary lymph nodes (n = 15), sclerosing lobulitis (n = 2), PBL (n = 11) and SBL (n = 9) are reported. FNAC was used to prepare traditional smears, conventional ICC or FC. Cytological diagnoses were compared to the imaging data, checked by histology or follow-up and statistically evaluated. Results: Imaging was not conclusive in most PBL, SBL, sclerosing lobulitis and some intramammary lymph nodes. FNAC combined with FC and ICC provided a definitive diagnosis of intramammary lymph node, sclerosing lobulitis, PBL and SBL in 18 cases with indication of the specific subtype in 10 cases. Statistical analysis showed 90% sensitivity, 100% specificity, 100% positive predictive value and 89% negative predictive value. Conclusions: FNAC combined with FC and ICC is a helpful procedure for the diagnosis of reactive and lymphoproliferative processes of the breast. It may prevent unnecessary biopsy and speed up therapeutic procedures.
Isolated Renal Zygomycosis: Novel Diagnostic and Prognostic Criteria with Experience of a Tertiary Care Center
Authors: Chipde Saurabh S. , Ranjan Priyadarshi , Lal Hira , Singh Vivek , Naval Ram , Marak Rungmei S. , Prakash Anand , Bhadoria Dharmendra , Sharma R.K. , Kapoor Rohit , Pradhan Manas Ranjan , Singh Manmeet , Kumar Jatinder , Ansari Mohammad S. , Mandhani Anil , Srivastava Aneesh , Kapoor Rakesh
Published: February 2012

Background: Isolated renal zygomycosis is a life-threatening infection and difficult to diagnose ante mortem due to varied presentations. Most reports in the literature are case reports. We are presenting our experience of 10 patients. Materials and Methods: Retrospective data of 10 consecutive patients with primary renal zygomycosis, including 2 post-transplant patients, in our tertiary care center was analyzed. Epidemiological characteristics, predisposing conditions, clinical presentation, diagnostic findings and treatment outcomes were recorded. Characteristic radiological findings were recorded. Localized disease was managed by supportive treatment or percutaneous drainage and extensive disease with unilateral or bilateral nephrectomy. Renal involvement was confirmed in all patients by histopathology. Results: The mean age of presentation was 35 years. Five patients who had bilateral renal involvement presented with oliguric acute renal failure, hematuria and abdominal pain. Three had unilateral renal disease and presented with flank pain and fever. The two post-transplant patients presented with fever and graft dysfunction. Even after aggressive treatment 5 patients died, accounting for a mortality rate of 50%. Conclusion: Isolated renal zygomycosis can be diagnosed with typical radiological findings, combined with clinical, laboratory and histopathological features. This study describes the newer ante mortem radiological diagnostic criteria and prognostic predictors of the disease.
Clinical Course of Plasmacytoid Urothelial Carcinoma of the Upper Urinary Tract: A Case Report
Authors: Keck Bastian , Giedl Johannes , Kunath Frank , Goebell Peter Juergen , Engehausen Dirk Gerhard , Hartmann Arndt , Wullich Bernd
Published: February 2012

Plasmacytoid urothelial carcinoma of the bladder represents a rare and aggressive variant of urothelial carcinoma, which is usually diagnosed at an advanced pathologic stage. Until now, no reports exist on this rare tumor type in the upper urinary tract. Herein, we present the first report on the clinical course of a metastatic plasmacytoid urothelial carcinoma of the renal pelvis and show its unfavorable outcome despite multimodal therapy.
Cytomorphological Analysis of Uterine Cervical Pap Smears in Relation to Human Papillomavirus Infection in Indonesian Women
Authors: Rachmadi Lisnawati , Jordanova Ekaterina S. , Kolkman-Uljee Sandra , van der Linden-Narain Ingrid , Purwoto Gatot , Siregar Budiningsih , Fleuren Gert Jan , Cornain Santoso , Veselic Maud
Published: February 2012

Objective: Cervical cancer is the number one cause of cancer-associated death in Indonesian women (30/100,000 annually), where no screening program is present. The Papanicolaou test is widely accepted as an effective screening method for cervical neoplasia detection and often shows certain cytological features associated with human papillomavirus (HPV) infection. Especially in developing countries, cytological investigation is still the method of choice as compared to the frequent use of HPV DNA testing in western countries. Study Design: In the present study, we investigated the validity of the use of cytomorphological changes as a marker for HPV infection. A total of 140 smears collected in three different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV DNA testing was performed using INNO-LiPA assays. Results and Conclusions: We found a highly significant association of classical koilocytosis, multinucleated cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei, moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using classical and nonclassical cytomorphological parameters we found an overall sensitivity of 42% and a specificity of 90%. The combination of classical and nonclassical parameters led to a higher sensitivity of HPV positivity prediction. These results are of importance for cytologists in developing countries as molecular HPV testing still poses a major financial, logistic and expertise problem.
Intracerebral Infections as a Complication of Deep Brain Stimulation
Authors: Blomstedt Patric , Bjartmarz Hjalmar
Published: February 2012

Background: Intracerebral infections after deep brain stimulation (DBS) are rare. The published material is limited to 2 case reports. A review of 20 publications of 3,818 patients focusing on complications of DBS did not reveal one single case. For that reason, we decided to present our own experience of 4 patients with this complication. Objectives: To analyze and present our material regarding intracerebral infections after DBS. Methods: Four patients with intracerebral infection after DBS were retrospectively analyzed. Results: The 4 patients exhibited signs of intracerebral infection 2–14 days after DBS for Parkinson’s disease. CT and MRI verified signs of possible cerebral involvement. In 3 patients, positive cultures were obtained from the extracted electrodes. All patients recovered completely following treatment with antibiotics and removal of the implanted hardware. Two of the patients were later re-implanted. Conclusions: Intracerebral infection is a rare complication of DBS. It does, however, occur occasionally and should be taken into consideration when evaluating the risks of DBS.
Analysis of Squash Smear Cytology of Ependymomas
Authors: Manasa P. Lakshmi , Uppin Megha S. , Sundaram C.
Published: February 2012

Background: Ependymomas constitute 8–10 and 1–3% of central nervous system tumors in children and adults, respectively. Though intraoperative squash smear cytology is well documented, grading is rarely described. Objectives: (1) To assess cytomorphology and grade ependymomas in squash smears. (2) To compare utility of hematoxylin and eosin (H&E) and toluidine blue (TB) staining. Study Design: Ependymomas diagnosed from 2004 to 2010 were retrieved from pathology records. Intraoperative squash smears stained with TB and H&E were studied. Results: Histological sections of 29 ependymomas were graded according to WHO 2007 classification. There were 3 myxopapillary (grade I), 13 grade II, and 13 grade III (anaplastic) ependymomas. Perivascular pseudorosettes were seen in 23 smears, and 11 showed rosettes. Less cohesive cells at the periphery of fragments with unipolar cytoplasmic processes were seen in all smears. The background was fibrillary in all except in myxopapillary ependymoma. Metachromatic material was seen in myxopapillary ependymoma around vessels and in globi. The nucleus was round with stippled chromatin and 1–2 small nucleoli could be seen. All smears of grade III ependymomas showed pleomorphism, mitoses, microvascular proliferation and necrosis. Conclusion: Ependymomas can be diagnosed and graded reliably by squash smear. Myxoid stroma was better appreciated by TB staining. TB and H&E complement each other in squash smears for cytomorphology.
Dental Caries Experience in a Hungarian Police Student Population
Authors: Faragó I. , Nagy G. , Márton S. , Túry F. , Szabó E. , Hopcraft M. , Madléna M.
Published: February 2012

The aim of this study was to assess the caries experience of Hungarian police students and to evaluate its relationship with nutrition, oral hygiene habits, behavioural and social factors. This representative cross-sectional epidemiological survey was conducted in a dental office of the Miskolc Law Enforcement Secondary School in Hungary in 2008. Altogether 792 Hungarian police student volunteers (male/female ratio was 90.3/9.7%, age: 20.4 ± 1.3 years, mean ± SD) participated in the study. Caries experience was measured using World Health Organization criteria and a validated questionnaire was used to collect social and oral health behaviour data. The DMFT number was 10.3 ± 5.7 (mean ± SD). Significant relationships were found between the DMFT value and the education of fathers, frequency of dental attendance, and use of dental floss (p < 0.05). D and T components of caries prevalence showed significant relationships with the frequency of dental attendance, while from the components the FT value showed statistically significant relationships with the education of fathers and the MT component with the use of dental floss (p < 0.05). Based on the results of this survey, strategies aiming at effective caries-preventive programmes should be established in police student populations ensuring the official basic requirements on their health condition and suitability for subsequent service. The published information can be used as a base for new strategies, and allows the evaluation of the effects of a carefully planned and implemented health care system.
Parental Smoking in Childhood and Brachial Artery Flow-Mediated Dilatation in Young Adults
Authors: Juonala Markus , Magnussen Costan G. , Venn Alison , Gall Seana , Kähönen Mika , Laitinen Tomi , Taittonen Leena , Lehtimäki Terho , Jokinen Eero , Sun Cong , Viikari Jorma S.A. , Dwyer Terence , Raitakari Olli T.
Published: February 2012

Objective—

Passive smoking has been associated with increased cardiovascular morbidity. The present study aimed to examine the long-term effects of childhood exposure to tobacco smoke on endothelium-dependent vasodilation in adults.

Methods and Results—

The analyses were based on 2171 participants in the population-based Cardiovascular Risk in Young Finns (N=2067) and Childhood Determinants of Adult Health (N=104) studies who had measures of conventional risk factors (lipids, blood pressure, adiposity, socioeconomic status) and self-reported parental smoking status when aged 3 to 18 years at baseline. They were re-examined 19 to 27 years later when aged 28 to 45 years. Brachial artery flow-mediated dilatation was measured at follow-up with ultrasound. In analyses adjusting for age, sex, and childhood risk factors, flow-mediated dilatation was reduced among participants who had parents that smoked in youth compared to those whose parents did not smoke (Young Finns: 9.2±0.1% (mean±SEM) versus 8.6±0.1%,
P
=0.001; Childhood Determinants of Adult Health: 7.4±0.6% versus 4.9±0.9%,
P
=0.04). These effects remained after adjustment for adult risk factors including own smoking status (Young Finns,
P
=0.003; Childhood Determinants of Adult Health,
P
=0.03).

Conclusion—

Parental smoking in youth is associated with reduced flow-mediated dilatation in young adulthood measured over 20 years later. These findings suggest that passive exposure to cigarette smoke among children might cause irreversible impairment in endothelium-dependent vasodilation.
Interleukin-1 Assembles a Proangiogenic Signaling Module Consisting of Caveolin-1, Tumor Necrosis Factor Receptor–Associated Factor 6, p38–Mitogen-Activated Protein Kinase (MAPK), and MAPK-Activated Protein Kinase 2 in Endothelial Cells
Authors: Jagielska Joanna , Kapopara Piyushkumar R. , Salguero Gustavo , Scherr Michaela , Schütt Harald , Grote Karsten , Schieffer Bernhard , Bavendiek Udo
Published: February 2012

Objective—

Interleukin-1β (IL-1β) is a major cytokine linking inflammation and angiogenesis in pathological vascular processes, such as atherosclerosis and tumor neoangiogenesis. However, signaling pathways mediating IL-1β-induced proangiogenic processes in endothelial cells (ECs) have barely been elucidated yet. Therefore, the present study investigated IL-1β-induced proangiogenic signaling in ECs.

Methods and Results—

IL-1β potently induced tube formation and migration of ECs. This was associated with and dependent on activation of p38–mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase 2 (MK2) as determined by pharmacological inhibition and gene silencing. Furthermore, silencing of the adaptor protein tumor necrosis factor receptor–associated factor 6 (TRAF6) (lentiviral short hairpin RNA) inhibited these IL-1β-induced processes. Moreover, IL-1β promoted translocation of TRAF6 to insoluble cellular fractions (containing membrane rafts/caveolae) and interaction of TRAF6 with caveolin-1. Accordingly, cellular cholesterol depletion (cyclodextrin) and silencing of caveolin-1 (small interfering RNA) inhibited IL-1β-induced activation of p38-MAPK and MK2, as well as IL-1β-induced tube formation and migration. Finally, silencing of TRAF6 and MK2 deficiency inhibited IL-1β-induced microvessel outgrowth in murine aortic rings ex vivo, and deficiency of MK2 or caveolin-1 significantly reduced IL-1β-induced angiogenesis in mice in vivo (Matrigel plug assay).

Conclusion—

IL-1β assembles a proangiogenic signaling module consisting of caveolin-1, TRAF6, p38-MAPK, and MK2 in ECs, representing a potential target to intervene into angiogenesis-dependent processes and diseases.
Transgenic Expression and Genetic Variation of Lmf1 Affect LPL Activity in Mice and Humans
Authors: Hosseini Maryam , Ehrhardt Nicole , Weissglas-Volkov Daphna , Lai Ching-Mei , Mao Hui Z. , Liao Jo-Ling , Nikkola Elina , Bensadoun André , Taskinen Marja-Riitta , Doolittle Mark H. , Pajukanta Päivi , Péterfy Miklós
Published: February 2012

Objective—

Lipoprotein lipase (LPL) is a principal enzyme in lipoprotein metabolism, tissue lipid utilization, and energy metabolism. LPL is synthesized by parenchymal cells in adipose, heart, and muscle tissues followed by secretion to extracellular sites, where lipolyic function is exerted. The catalytic activity of LPL is attained during posttranslational maturation, which involves glycosylation, folding, and subunit assembly within the endoplasmic reticulum. A lipase-chaperone, lipase maturation factor 1 (Lmf1), has recently emerged as a critical factor in this process. Previous studies demonstrated that loss-of-function mutations of Lmf1 result in diminished lipase activity and severe hypertriglyceridemia in mice and human subjects. The objective of this study is to investigate whether, beyond its role as a required factor in lipase maturation, variation in Lmf1 expression is sufficient to modulate LPL activity in vivo.

Methods and Results—

To assess the effects of Lmf1 overexpression in adipose and muscle tissues, we generated aP2-Lmf1 and Mck-Lmf1 transgenic mice. Characterization of relevant tissues revealed increased LPL activity in both mouse strains. In the omental and subcutaneous adipose depots, Lmf1 overexpression was associated with increased LPL specific activity without changes in LPL mass. In contrast, increased LPL activity was due to elevated LPL protein level in heart and gonadal adipose tissue. To extend these studies to humans, we detected association between
LMF1
gene variants and postheparin LPL activity in a dyslipidemic cohort.

Conclusion—

Our results suggest that variation in Lmf1 expression is a posttranslational determinant of LPL activity.
Left Atrial Diverticula in Patients Referred for Radiofrequency Ablation of Atrial Fibrillation
Authors: Peng Li-Qing , Yu Jian-Qun , Yang Zhi-Gang , Wu Dan , Xu Jian-Jun , Chu Zhi-Gang , Li Xue-Ming , Chen Dong-Dong , Luo Yi , Shao Heng , Tang Si-Shi , Chen Jing
Published: February 2012

Background—

The anatomic features of left atrial diverticula (LAD) are still unclear in patients with atrial fibrillation (AF). The purpose of this study was to evaluate the prevalence and morphological characteristics of LAD in patients referred for radiofrequency transcatheter ablation of AF with dual-source computed tomography.

Methods and Results—

Dual-source computed tomography images were obtained in 214 patients referred for AF catheter ablation and 214 sex- and age-matched control subjects. Images were analyzed to determine the prevalence and morphological characteristics of LAD and their relationship with adjacent pulmonary veins and left atrial appendage. In AF patients 77 (36.0%) (95% confidence interval, 29.6–42.4%) had 90 LAD, whereas in control subjects 70 (32.7%) (95% confidence interval, 26.4–39.0%) had 81 LAD (
P
=0.551). In patients with AF, LAD locations were right anterosuperior (47.8%), left anterosuperior (8.9%), left lateral (32.2%), interatrial septum (4.4%), right inferior (5.6%), and posterosuperior (1.1%) walls, respectively. The mean size of LAD was 5.3±2.9×5.6±3.3 mm. The wall of the LAD was much thinner than that of adjacent left atrium (0.89±0.46 versus 2.39±0.83 mm). Most LAD were located close to a pulmonary vein or atrial appendage ostium, with a mean distance of 8.7–13.1 mm.

Conclusions—

LAD are common, with a prevalence of 36.0% in patients with AF, which is not statistically greater than that in patients without AF. Thin-walled LAD are more commonly located on the superior anterior wall of left atrium and close to common ablation sites.
A New Method for Cardiac Computed Tomography Regional Function Assessment
Authors: Pourmorteza Amir , Schuleri Karl H. , Herzka Daniel A. , Lardo Albert C. , McVeigh Elliot R.
Published: February 2012

Background—

Quantitative assessment of regional myocardial function has important diagnostic implications in cardiac disease. Recent advances in CT imaging technology have allowed fine anatomic structures, such as endocardial trabeculae, to be resolved and potentially used as fiducial markers for tracking local wall deformations. We developed a method to detect and track such features on the endocardium to extract a metric that reflects local myocardial contraction.

Methods and Results—

First-pass CT images and contrast-enhanced cardiovascular magnetic resonance images were acquired in 8 infarcted and 3 healthy pigs. We tracked the left ventricle wall motion by segmenting the blood from myocardium and calculating trajectories of the endocardial features seen on the blood cast. The relative motions of these surface features were used to represent the local contraction of the endocardial surface with a metric we call Stretch Quantifier of Endocardial Engraved Zones (SQUEEZ). The average SQUEEZ value and the rate of change in SQUEEZ were calculated for both infarcted and healthy myocardial regions. SQUEEZ showed a significant difference between infarct and remote regions (
P
<0.0001). No significant difference was observed between normal myocardium (noninfarcted hearts) and remote regions (
P
=0.8).

Conclusions—

We present a new quantitative method for measuring regional cardiac function from high-resolution volumetric CT images, which can be acquired during angiography and myocardial perfusion scans. Quantified measures of regional cardiac mechanics in normal and abnormally contracting regions in infarcted hearts were shown to correspond well with noninfarcted and infarcted regions as detected by delayed enhancement cardiovascular magnetic resonance images.
Ranolazine Improves Cardiac Diastolic Dysfunction Through Modulation of Myofilament Calcium Sensitivity
Authors: Lovelock Joshua D. , Monasky Michelle M. , Jeong Euy-Myoung , Lardin Harvey A. , Liu Hong , Patel Bindiya G. , Taglieri Domenico M. , Gu Lianzhi , Kumar Praveen , Pokhrel Narayan , Zeng Dewan , Belardinelli Luiz , Sorescu Dan , Solaro R. John , Dudley Samuel C.
Published: February 2012

Rationale:

Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late inward sodium current (I
Na
), reducing the net cytosolic Ca
2+
efflux.

Objective:

Oxidative stress in the DOCA-salt model may increase late I
Na
, resulting in diastolic dysfunction amenable to treatment with ranolazine.

Methods and Results:

Echocardiography detected evidence of diastolic dysfunction in hypertensive mice that improved after treatment with ranolazine (E/E′:sham, 31.9±2.8, sham+ranolazine, 30.2±1.9, DOCA-salt, 41.8±2.6, and DOCA-salt+ranolazine, 31.9±2.6;
P
=0.018). The end-diastolic pressure-volume relationship slope was elevated in DOCA-salt mice, improving to sham levels with treatment (sham, 0.16±0.01 versus sham+ranolazine, 0.18±0.01 versus DOCA-salt, 0.23±0.2 versus DOCA-salt+ranolazine, 0.17±0.0 1 mm Hg/L;
P
<0.005). DOCA-salt myocytes demonstrated impaired relaxation, τ, improving with ranolazine (DOCA-salt, 0.18±0.02, DOCA-salt+ranolazine, 0.13±0.01, sham, 0.11±0.01, sham+ranolazine, 0.09±0.02 seconds;
P
=0.0004). Neither late I
Na
nor the Ca
2+
transients were different from sham myocytes. Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca
2+
with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca
2+
response and cross-bridge kinetics.

Conclusions:

Diastolic dysfunction could be reversed by ranolazine, probably resulting from a direct effect on myofilaments, indicating that cardiac oxidative stress may mediate diastolic dysfunction through altering the contractile apparatus.
CIP, a Cardiac Isl1-Interacting Protein, Represses Cardiomyocyte Hypertrophy
Authors: Huang Zhan-Peng , Young Seok Hee , Zhou Bin , Chen Jinghai , Chen Jian-Fu , Tao Yazhong , Pu William T. , Wang Da-Zhi
Published: February 2012

Rationale:

Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well-established, the molecular events that inhibit or repress cardiac hypertrophy are less known.

Objective:

To identify and investigate novel regulators that modulate cardiac hypertrophy.

Methods and Results:

Here, we report the identification, characterization, and functional examination of a novel cardiac Isl1-interacting protein (CIP). CIP was identified from a bioinformatic search for novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear protein without recognizable motifs. Northern blotting, in situ hybridization, and reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes of developing and adult hearts. Yeast two-hybrid screening identified Isl1, a LIM/homeodomain transcription factor essential for the specification of cardiac progenitor cells in the second heart field, as a cofactor of CIP. CIP directly interacted with Isl1, and we mapped the domains of these two proteins, which mediate their interaction. We show that CIP represses the transcriptional activity of Isl1 in the activation of the myocyte enhancer factor 2C. The expression of CIP was dramatically reduced in hypertrophic cardiomyocytes. Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy.

Conclusions:

Our studies therefore identify CIP as a novel regulator of cardiac hypertrophy.
Pseudocontinuous Arterial Spin Labeling Quantifies Relative Cerebral Blood Flow in Acute Stroke
Authors: Hernandez Daymara A. , Bokkers Reinoud P.H. , Mirasol Raymond V. , Luby Marie , Henning Erica C. , Merino José G. , Warach Steven , Latour Lawrence L.
Published: February 2012

Background and Purpose—

The aim of this study was to test whether arterial spin labeling (ASL) can detect significant differences in relative cerebral blood flow (rCBF) in the core, mismatch, and reverse-mismatch regions, and whether rCBF values measured by ASL in those areas differ from values obtained using dynamic susceptibility contrast (DSC) MRI.

Methods—

Acute stroke patients were imaged with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (ASL and DSC) MRI. An expert reader segmented the ischemic lesion on DWI and the DSC time-to-peak (TTP) maps. Three regions were defined: core (DWI+, TTP+), mismatch (DWI−, TTP+), and reverse-mismatch (DWI+, TTP−). For both ASL and DSC, rCBF maps were created with commercially available software, and the ratio was calculated as the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere. Values obtained from core, mismatch, and reverse-mismatch were used for paired comparison.

Results—

Twenty-eight patients were included in the study. The mean age was 65.6 (16.9) years, with a median baseline National Institutes of Health Stroke Scale score of 10 (interquartile range, 4–17). Median time from last known normal to MRI was 5.7 hours (interquartile range, 2.9–22.6). Mean rCBF ratios were significantly higher in the mismatch 0.53 (0.23) versus the core 0.39 (0.33) and reverse-mismatch 0.68 (0.49) versus the core 0.38 (0.35). Differences in rCBF measured with DSC and ASL were not significant.

Conclusions—

ASL allows for the measurement of rCBF in the core and mismatch regions. Values in the mismatch were significantly higher than in the core, suggesting there is potential salvageable tissue.
Telomere Length and Risk of Stroke in Chinese
Authors: Ding Hu , Chen Chen , Shaffer John R. , Liu Lei , Xu Yujun , Wang Xiaojing , Hui Rutai , Wang Dao Wen
Published: February 2012

Background and Purpose—

Accumulating evidence suggests that telomere length is a maker for biological aging of the cardiovascular system. Whether stroke is associated with accelerated biological aging as measured by telomere length has not been conclusively demonstrated. Our aim was to determine whether mean leukocyte telomere length is a predictor for the development of stroke.

Methods—

The relative telomere length of leukocytes was determined by quantitative polymerase chain reaction in 1309 stroke patients and 1309 age- and sex-matched control subjects as well as 858 stroke patients followed prospectively for 5 years. For each measure, the study sample was divided into quartiles. The associations between the telomere length and risk of stroke as well as poststroke adverse outcomes were determined.

Results—

Mean telomere length was significantly shorter in stroke patients than in control subjects. Shorter telomere length levels were directly associated with a higher risk of stroke in the case/control sample. As compared with the fourth (longest) quartile, the odd ratios [OR] (and 95% confidence intervals [CI]) for ischemic stroke risk were as follows: third quartile, 1.37 (1.04–1.82); second quartile, 1.53 (1.17–2.02); and first quartile, 2.12 (1.62–2.77). Follow-up of the patients from the prospective cohort also showed that shorter telomere length levels were associated with mortality from all causes but not with recurrence of stroke.

Conclusions—

Shorter telomere length was associated with ischemic stroke and was a strong predictor of poststroke death.