bluuebunny/crossref_metadata_2025 huggingface dataset:
Case–Control Study of Cutaneous Human Papillomaviruses in Squamous Cell Carcinoma of the Skin
Authors: Iannacone Michelle R. , Gheit Tarik , Waterboer Tim , Giuliano Anna R. , Messina Jane L. , Fenske Neil A. , Cherpelis Basil S. , Sondak Vernon K. , Roetzheim Richard G. , Michael Kristina M. , Tommasino Massimo , Pawlita Michael , Rollison Dana E.
Published: August 2012

Background: Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin.

Methods: To investigate the association between cutaneous HPV and SCC, a case–control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons.

Results: SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23–3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22–2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14–2.84), 17 (OR, 1.59; 95% CI, 1.02–2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04–4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (OR, 3.48; 95% CI, 1.27–9.59), 17 (OR, 3.36; 95% CI, 1.29–8.72), and 24 (OR, 3.79; 95% CI, 1.24–11.5).

Conclusion: Genus-beta HPV infections were associated with SCC in our study population.

Impact: Identifying the role of cutaneous HPV infection in SCC may lead to improved characterization of high-risk individuals and the development of novel prevention strategies. Cancer Epidemiol Biomarkers Prev; 21(8); 1303–13. ©2012 AACR.
Preoperative Serum Levels of Matrix Metalloproteinase-2 (MMP-2) and Survival of Breast Cancer among Korean Women
Authors: Song Nan , Sung Hyuna , Choi Ji-Yeob , Han Sohee , Jeon Sujee , Song Minkyo , Lee Yunhee , Park Chulbum , Park Sue K. , Lee Kyoung-Mu , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Lee Sang-Ah , Kang Daehee
Published: August 2012

Background: Matrix metalloproteinase-2 (MMP-2) has been thought of as a predictor of recurrence or metastasis risk or prognostic markers in cancer. We evaluated whether preoperative serum levels of MMP-2 work as a prognostic biomarker in breast cancer prognosis.

Methods: Preoperative serum levels of MMP-2 were measured with ELISA in 303 patients with histologically confirmed breast cancer. The median follow-up time for all patients was 4.24 years. The relationship of MMP-2 to survival was investigated using Cox proportional hazard regression model adjusted for the tumor–node–metastasis (TNM) stage and estrogen receptor (ER) status.

Results: In the multivariate analysis, disease-free survival (DFS) was worse among patients with the third tertile of MMP-2 level than with the first tertile of MMP-2 level [hazard ratio, 1.80; 95% confidence interval (CI), 1.04–3.11; P = 0.04]. However, when the patients were stratified by age, ER status, histologic grade, and nuclear grade, inverse correlation was shown between serum MMP-2 levels and prognostic factors, and the associations between MMP-2 and DFS were only significant among patients with poor prognostic factors (HR, 2.75; 95% CI, 1.32–5.73 in ER-negative; HR, 2.90; 95% CI, 1.42–5.92 in histologic grade III; and HR, 2.61; 95% CI, 1.26–5.39 in nuclear grade III).

Conclusions: Our results suggest that the preoperative serum levels of MMP-2 were associated with the survival in patients with breast cancer in ER-negative, higher histologic grade, or higher nuclear grade breast cancers.

Impact: Our results indicate that serum levels of MMP-2 may play a role as prognostic biomarker in breast cancer survival. Cancer Epidemiol Biomarkers Prev; 21(8); 1371–80. ©2012 AACR.
Genomic Methylation Changes Over Time in Peripheral Blood Mononuclear Cell DNA: Differences by Assay Type and Baseline Values
Authors: Wu Hui-Chen , Wang Qiao , Delgado-Cruzata Lissette , Santella Regina M. , Terry Mary Beth
Published: August 2012

Background: Lower levels of genomic DNA methylation in blood DNA has been associated with risk of different cancers and several cancer risk factors. To understand the use of genomic methylation measures as biomarkers of cancer risk, data are needed on within-individual changes over time.

Methods: Using information from 77 subjects with blood collected at 2 visits on average 8 years apart, we examined whether levels of DNA methylation change with time and if so, whether selected cancer risk factors predict these changes. We measured DNA methylation levels in peripheral blood mononuclear cells (PBMC) using three assays that have been used in epidemiologic studies: (i) luminometric methylation assay (LUMA)(ii) LINE-1 by pyrosequencing, and (iii) Sat2 by MethyLight.

Results: Close to a third of all individuals had large changes over time (≥10%) in LUMA with 19.5% increasing and 13.0% decreasing. For Sat2, two-thirds of individuals had large changes with 40% increasing and 26% decreasing over time. In contrast, only 3.9% of individuals had large changes in LINE-1 over time. The degree of change in PBMC DNA methylation was statistically significantly inversely associated with methylation levels at baseline; greater decreases were observed in individuals with higher baseline values for each assay.

Conclusions: These data, if replicated, suggest that changes in DNA methylation over time are highly associated with baseline values of the assay and vary by assay type.

Impact: These findings suggest that assays that change more over time may warrant consideration for studies that measure later life exposures. Cancer Epidemiol Biomarkers Prev; 21(8); 1314–8. ©2012 AACR.
Peripheral Blood Immune Cell Methylation Profiles Are Associated with Nonhematopoietic Cancers
Authors: Koestler Devin C. , Marsit Carmen J. , Christensen Brock C. , Accomando William , Langevin Scott M. , Houseman E. Andres , Nelson Heather H. , Karagas Margaret R. , Wiencke John K. , Kelsey Karl T.
Published: August 2012

Background: Blood leukocytes from patients with solid tumors exhibit complex and distinct cancer-associated patterns of DNA methylation. However, the biologic mechanisms underlying these patterns remain poorly understood. Because epigenetic biomarkers offer significant clinical potential for cancer detection, we sought to address a mechanistic gap in recently published works, hypothesizing that blood-based epigenetic variation may be due to shifts in leukocyte populations.

Methods: We identified differentially methylated regions (DMR) among leukocyte subtypes using epigenome-wide DNA methylation profiling of purified peripheral blood leukocyte subtypes from healthy donors. These leukocyte-tagging DMRs were then evaluated using epigenome-wide blood methylation data from three independent case-control studies of different cancers.

Results: A substantial proportion of the top 50 leukocyte DMRs were significantly differentially methylated among head and neck squamous cell carcinoma (HNSCC) cases and ovarian cancer cases compared with cancer-free controls (48 and 47 of 50, respectively). Methylation classes derived from leukocyte DMRs were significantly associated cancer case status (P < 0.001, P < 0.03, and P < 0.001) for all three cancer types: HNSCC, bladder cancer, and ovarian cancer, respectively and predicted cancer status with a high degree of accuracy (area under the curve [AUC] = 0.82, 0.83, and 0.67).

Conclusions: These results suggest that shifts in leukocyte subpopulations may account for a considerable proportion of variability in peripheral blood DNA methylation patterns of solid tumors.

Impact: This illustrates the potential use of DNA methylation profiles for identifying shifts in leukocyte populations representative of disease, and that such profiles may represent powerful new diagnostic tools, applicable to a range of solid tumors. Cancer Epidemiol Biomarkers Prev; 21(8); 1293–302. ©2012 AACR.
Combined PI3K/mTOR and MEK Inhibition Provides Broad Antitumor Activity in Faithful Murine Cancer Models
Authors: Roberts Patrick J. , Usary Jerry E. , Darr David B. , Dillon Patrick M. , Pfefferle Adam D. , Whittle Martin C. , Duncan James S. , Johnson Soren M. , Combest Austin J. , Jin Jian , Zamboni William C. , Johnson Gary L. , Perou Charles M. , Sharpless Norman E.
Published: August 2012

Purpose: Anticancer drug development is inefficient, but genetically engineered murine models (GEMM) and orthotopic, syngeneic transplants (OST) of cancer may offer advantages to in vitro and xenograft systems.

Experimental Design: We assessed the activity of 16 treatment regimens in a RAS-driven, Ink4a/Arf-deficient melanoma GEMM. In addition, we tested a subset of treatment regimens in three breast cancer models representing distinct breast cancer subtypes: claudin-low (T11 OST), basal-like (C3-TAg GEMM), and luminal B (MMTV-Neu GEMM).

Results: Like human RAS-mutant melanoma, the melanoma GEMM was refractory to chemotherapy and single-agent small molecule therapies. Combined treatment with AZD6244 [mitogen-activated protein–extracellular signal-regulated kinase kinase (MEK) inhibitor] and BEZ235 [dual phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor] was the only treatment regimen to exhibit significant antitumor activity, showed by marked tumor regression and improved survival. Given the surprising activity of the “AZD/BEZ” combination in the melanoma GEMM, we next tested this regimen in the “claudin-low” breast cancer model that shares gene expression features with melanoma. The AZD/BEZ regimen also exhibited significant activity in this model, leading us to testing in even more diverse GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly active in these distinct breast cancer models, showing equal or greater efficacy compared with any other regimen tested in studies of over 700 tumor-bearing mice. This regimen even exhibited activity in lapatinib-resistant HER2+ tumors.

Conclusion: These results show the use of credentialed murine models for large-scale efficacy testing of diverse anticancer regimens and predict that combinations of PI3K/mTOR and MEK inhibitors will show antitumor activity in a wide range of human malignancies. Clin Cancer Res; 18(19); 5290–303. ©2012 AACR.
Vitamin E Alters Inflammatory Gene Expression in Alcoholic Chronic Pancreatitis
Authors: Monteiro Thaís Helena , Silva Camila Siqueira , Cordeiro Simões Ambrosio Livia Maria , Zucoloto Sergio , Vannucchi Helio
Published: August 2012

Objective: To evaluate the effect of vitamin E supplementation on pancreatic gene expression of inflammatory markers in rats with alcoholic chronic pancreatitis. Methods: Wistar rats were divided into 3 groups: control (1), alcoholic chronic pancreatitis without (2) and with (3) vitamin E supplementation. Pancreatitis was induced by a liquid diet containing ethanol, cyclosporin A and cerulein. α-tocopherol content in plasma and liver and pancreas histopathology were analyzed. Gene expression of inflammatory biomarkers was analyzed by the quantitative real-time PCR technique. Results: The animals that received vitamin E supplementation had higher α-tocopherol amounts in plasma and liver. The pancreas in Group 1 showed normal histology, whereas in Groups 2 and 3, mild to moderate tissue destruction foci and mononuclear cell infiltration were detected. Real-time PCR analysis showed an increased expression of all genes in Groups 2 and 3 compared to Group 1. Vitamin E supplementation decreased the transcript number of 5 genes (α-SMA, COX-2, IL-6, MIP-3α and TNF-α) and increased the transcript number of 1 gene (Pap). Conclusion: Vitamin E supplementation had anti-inflammatory and beneficial effects on the pancreatic gene expression of some inflammatory biomarkers in rats with alcoholic chronic pancreatitis, confirming its participation in the inflammatory response mechanisms in the pancreas.
Risk and Cause of Interval Colorectal Cancer after Colonoscopic Polypectomy
Authors: Huang Yinglong , Gong Wei , Su Bingzhong , Zhi Fachao , Liu Side , Jiang Bo
Published: August 2012

Background: To investigate the cause and risk of interval colorectal cancer (ICC) in patients undergoing surveillance colonoscopy within 5 years after colonoscopic polypectomy. Patients and Methods: We retrospectively analyzed data (endoscopy, pathology, demography) of patients who received surveillance colonoscopy within 5 years after colonoscopic polypectomy. Results: Among 1,794 patients undergoing surveillance colonoscopy within 5 years after colonoscopic polypectomy, 14 suffered from ICC. The mean follow-up time was 2.67 years and the incidence density of ICC was 2.9 cases per 1,000 person-years. 50% of ICCs were found in patients in whom adenomas had been incompletely removed by endoscopic therapy, 36% were missed cancers, and 14% were new cancers. Age >60 years (OR 2.97, 95% CI 2.31–3.82) was significantly associated with interval cancer on the surveillance colonoscopy as were advanced adenoma (OR 1.28, 95% CI 1.01–1.62), the presence of villous (HR 1.38, 95% CI 1.03–1.85) and high-grade dysplasia (OR 1.61, 95% CI 1.07–2.42). Conclusions: Among patients undergoing surveillance colonoscopy within 5 years after polypectomy, the incidence density of ICC was 2.9 cases per 1,000 person-years. The majority of interval cancers originated from incomplete resection of advanced adenomas and missed cancers, which can be prevented by improving endoscopic techniques and selecting an appropriate follow-up time interval.
Video Rating in Neurodegenerative Disease Clinical Trials: The Experience of PRION-1
Authors: Carswell Christopher , Rañopa Michael , Pal Suvankar , MacFarlane Rebecca , Siddique Durre , Thomas Dafydd , Webb Tom , Wroe Steve , Walker Sarah , Darbyshire Janet , Collinge John , Mead Simon , Rudge Peter
Published: August 2012

Background/Aims: Large clinical trials including patients with uncommon diseases involve assessors in different geographical locations, resulting in considerable inter-rater variability in assessment scores. As video recordings of examinations, which can be individually rated, may eliminate such variability, we measured the agreement between a single video rater and multiple examining physicians in the context of PRION-1, a clinical trial of the antimalarial drug quinacrine in human prion diseases. Methods: We analysed a 43-component neurocognitive assessment battery, on 101 patients with Creutzfeldt-Jakob disease, focusing on the correlation and agreement between examining physicians and a single video rater. Results: In total, 335 videos of examinations of 101 patients who were video-recorded over the 4-year trial period were assessed. For neurocognitive examination, inter-observer concordance was generally excellent. Highly visual neurological examination domains (e.g. finger-nose-finger assessment of ataxia) had good inter-rater correlation, whereas those dependent on non-visual clues (e.g. power or reflexes) correlated poorly. Some non-visual neurological domains were surprisingly concordant, such as limb muscle tone. Conclusion: Cognitive assessments and selected neurological domains can be practically and accurately recorded in a clinical trial using video rating. Video recording of examinations is a valuable addition to any trial provided appropriate selection of assessment instruments is used and rigorous training of assessors is undertaken.
Alterations in Plasma Amino Acid Levels in Alcoholic Chronic Pancreatitis in Japanese
Authors: Kawaguchi Yoshiaki , Ogawa Masami , Ito Hiroyuki , Mine Tetsuya
Published: August 2012

Aims: Our aim was to investigate plasma amino acid levels in chronic pancreatitis (CP) patients and examine their relationship with exocrine insufficiency. Methods: Thirty-nine patients with alcoholic CP and 20 healthy controls were examined. CP patients were divided into an exocrine normal group (n = 28) and an exocrine insufficiency group (n = 11). Selected clinical and laboratory values were compared among the three groups, and the effect of an elemental diet was observed in 6 patients of the exocrine insufficiency group. Results: Total amino acid concentration was significantly higher in the control group than in the exocrine normal group and exocrine insufficiency group (p = 0.032, p = 0.020). In the exocrine insufficiency group, significant reductions in the concentrations of serum histidine and methionine were found compared with the control group and exocrine normal group (histidine: p = 0.032, p = 0.045; methionine: p = 0.043, p = 0.049). In the exocrine normal group and exocrine insufficiency group, significant elevation in the concentration of serum glutamate was found compared with the control group (p = 0.036, p = 0.029). Elemental diet improved these amino acid concentrations. Conclusion: Patients with CP exhibit alterations in the levels of several amino acids, such as histidine, methionine, and glutamate. These amino acid deficiencies seem to correlate with exocrine insufficiency and be improved by an elemental diet.
Vascular Disturbances in Primary Aldosteronism: Clinical Evidence
Authors: Widimsky Jr. J. , Strauch B. , Petrák O. , Rosa J. , Somloova Z. , Zelinka T. , Holaj R.
Published: August 2012

Primary aldosteronism (PA) is a common form of arterial hypertension with a high prevalence of cardiovascular complications. In patients with PA, complex mechanisms may lead to functional and/or structural abnormalities of the blood vessel wall. Clinical evidence indicates that patients with PA may have immune cell activation, increased oxidative stress, impaired endothelial function and vascular remodeling. Activation of fibroproliferation has been found in resistant arteries of patients with PA. Subjects with PA compared to essential hypertensives with similar blood pressure levels have increased intima-media thickness and arterial stiffness as measured by pulse wave velocity. These functional and morphological changes can be modified by an increased sodium intake. Vascular remodeling in PA may indicate a poor response to specific therapy with lower probability of cure and/or normalization of blood pressure. Early diagnosis of PA before blood vessel wall disturbances develop is of utmost importance.
The Cost of Asthma in Kuwait
Authors: Khadadah Mousa
Published: August 2012

Objective: To evaluate the direct costs of treating asthma in Kuwait. Materials and Methods: Population figures were obtained from the 2005 census and projected to 2008. Treatment profiles were obtained from the Asthma Insights and Reality for the Gulf and Near East (AIRGNE) study. Asthma prevalence and unit cost estimates were based on results from a Delphi technique. These estimates were applied to the total Kuwaiti population aged 5 years and over to obtain the number of people diagnosed with asthma. The estimates from the Delphi exercise and the AIRGNE results were used to determine the number of asthma patients managed in government facilities. Direct drug costs were provided by the Ministry of Health. Treatment costs (Kuwaiti dinars, KD) were also calculated using the Delphi exercise and the AIRGNE data. Results: The prevalence of asthma was estimated to be 15% of adults and 18% of children (93,923 adults; 70,158 children). Of these, 84,530 (90%) adults and 58,932 (84.0%) children were estimated to be using government healthcare facilities. Inpatient visits accounted for the largest portion of total direct costs (43%), followed by emergency room visits (29%), outpatient visits (21%) and medications (7%). The annual cost of treatment, excluding medications, was KD 29,946,776 (USD 107,076,063) for adults and KD 24,295,439 (USD 86,869,450) for children. Including medications, the total annual direct cost of asthma treatment was estimated to be over KD 58 million (USD 207 million). Conclusions: Asthma costs Kuwait a huge sum of money, though the estimates were conservative because only Kuwaiti nationals were included. Given the high medical expenditures associated with emergency room and inpatient visits, relative to lower medication costs, efforts should be focused on improving asthma control rather than reducing expenditure on procurement of medication.
Stat3 Contributes to Indoxyl Sulfate-Induced Inflammatory and Fibrotic Gene Expression and Cellular Senescence
Authors: Shimizu Hidehisa , Yisireyili Maimaiti , Nishijima Fuyuhiko , Niwa Toshimitsu
Published: August 2012

Background/Aim: Increased phosphorylation (activation) of signal transducer and activator of transcription 3 (Stat3) on tyrosine 705 leads to renal fibrosis. Indoxyl sulfate, a uremic toxin, induces renal fibrosis through expression of transforming growth factor-β1 (TGF-β1) in proximal tubular cells. The present study aimed to determine whether Stat3 is involved in indoxyl sulfate-induced dysfunction of proximal tubular cells. Methods: Localization of phosphorylated Stat3 in the kidneys of normal, subtotally nephrectomized, and AST-120-treated subtotally nephrectomized rats was examined by immunohistochemistry. The effect of indoxyl sulfate on phosphorylation of Stat3 and the role of Stat3 on indoxyl sulfate-induced cellular effects were examined using human proximal tubular cells (HK-2 cells). Results: Subtotally nephrectomized rats showed increased immunostaining of phosphorylated Stat3 in the renal tubules compared with normal rats. Administration of AST-120, which reduces serum level of indoxyl sulfate, to subtotally nephrectomized rats reduced the immunostaining of phosphorylated Stat3 in the renal tubules. Indoxyl sulfate induced phosphorylation of Stat3 in HK-2 cells. Stat3 small interfering RNA suppressed indoxyl sulfate-induced expression of an inflammation marker gene (monocyte chemotactic protein-1), fibrosis marker genes (TGF-β1, α-smooth muscle actin) and a subunit of nuclear factor-ĸB (p65), and attenuated a cellular senescence marker, senescence-associated β-galactosidase activity. Conclusions: Stat3 is involved in indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence in proximal tubular cells.
Long-term risk of vascular events after peripheral bypass surgery
Authors: Tangelder Marco J. D. , Lawson James A. , Moll Frans L. , Algra Ale , Van Hattum Eline S.
Published: August 2012

Patients with peripheral arterial disease (PAD) are at high risk of major ischaemic events. Long-term data of all major ischaemic events in PAD patients are scarce and outdated, especially for patients with severe PAD requiring bypass surgery. Our objective was to define their longterm prognosis and develop a prediction model which quantifies this risk up to a decade after surgery. We conducted a retrospective cohort study in patients from the Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study; a multicentre randomised trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery. The primary outcome was the composite event of nonfatal myocardial infarction, non-fatal ischaemic stroke, major amputation, and vascular death. Cumulative risks were assessed by Kaplan-Meier analysis and independent determinants by multivariable Cox regression models. From 1995 until 2009, 482 patients were followed for a median period of 7.8 years. Follow-up was complete in 94%. Overall 60% of patients experienced a primary outcome event, of which the majority was a vascular death (30%), followed by major amputations (12%). The primary cause of vascular death was a cardiovascular event (29%), whereas the minority was due to complications directly related to PAD (6%). Within five years after bypass surgery vascular death occurred in about a quarter of patients and within 10 years in nearly half of patients. This was double the rate as for non-vascular death. The primary outcome event occurred in over a third and over half of patients in 5 and 10 years after bypass surgery, respectively. From four independent determinants for the primary outcome event: age, diabetes, critical limb ischaemia, and prior vascular interventions, we developed a risk chart, which systematically classifies the 10-year risks of the primary outcome event, ranging from 25% to 85%. This study provided a detailed insight in the course of PAD long after peripheral bypass surgery and enables individual risk assessment of major fatal and non-fatal ischaemic events by means of cumulative incidences and a risk chart.
Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel
Authors: Emmerechts Jan , De Vooght Vanessa , Haenen Steven , Loyen Serena , Van kerckhoven Soetkin , Hemmeryckx Bianca , Vanoirbeek Jeroen A. J. , Hoet Peter H. , Nemery Ben , Hoylaerts Marc F.
Published: August 2012

Epidemiological studies indicate that elderly persons are particularly susceptible to the cardiovascular health complications of air pollution, but pathophysiological mechanisms behind the increased susceptibility remain unclear. Therefore, we investigated how continuous traffic-related air pollution exposure affects haemostasis parameters in young and old mice. Young (10 weeks) and old (20 months) mice were placed in an urban roadside tunnel or in a clean environment for 25 or 26 days and markers of inflammation and endothelial cells or blood platelet activation were measured, respectively. Plasma microvesicles and pro/ anticoagulant factors were analysed, and thrombin generation analysis was performed. Despite elevated macrophage carbon load, tunnel mice showed no overt pulmonary or systemic inflammation, yet manifested reduced pulmonary thrombomudulin expression and elevated endothelial von Willebrand factor (VWF) expression in lung capillaries. In young mice, soluble P-selectin (sP-sel) increased with exposure and correlated with soluble E-selectin and VWF. Baseline plasma factor VIII (FVIII), sP-sel and VWF were higher in old mice, but did not pronouncedly increase further with exposure. Traffic-related air pollution markedly raised red blood cell and blood platelet numbers in young and old mice and procoagulant blood platelet-derived microvesicle numbers in old animals. Changes in coagulation factors and thrombin generation were mild or absent. Hence, continuous traffic-related air pollution did not trigger overt lung inflammation, yet modified pulmonary endothelial cell function and enhanced platelet activity. In old mice, subchronic exposure to polluted air raised platelet numbers, VWF, sP-sel and microvesicles to the highest values presently recorded, collectively substantiating a further elevation of thrombogenicity, already high at old age.
Effects of intracoronary delivery of allogenic bone marrow-derived stem cells expressing heme oxygenase-1 on myocardial reperfusion injury
Authors: Tendera Michal , Cybulski Wieslaw , Zuba-Surma Ewa K. , Szade Krzysztof , Florczyk Urszula , Kozakowska Magdalena , Szymula Agnieszka , Krzych Lukasz , Paslawska Urszula , Paslawski Robert , Milewski Krzysztof , Buszman Piotr P. , Nabialek Edyta , Kuczmik Waclaw , Janiszewski Adrian , Dziegiel Piotr , Buszman Pawel E. , Józkowicz Alicja , Wojakowski Wojciech , Dulak Jozef
Published: August 2012

Heme oxygenase-1 (HO-1) decreases apoptosis, inflammation and oxidative stress. The aim of the study was to investigate the effects of intracoronary infusion of allogenic bone marrow cells (BMC) overexpressing HO-1 in the porcine model of myocardial infarction (MI). MI was produced by balloon occlusion of a coronary artery. BMC were transduced with adenoviruses encoding for HO-1 (HO-1 BMC) or GFP (GFP-BMC) genes. Prior to reperfusion animals received HO-1 BMC, control BMC (unmodified or GFP-BMC) or placebo. Left ventricular (LV) ejection fraction (EF), shortening fraction (SF), end-systolic and enddiastolic diameters (EDD, ESD) were assessed by echocardiography before, 30 minutes (min) and 14 days after reperfusion. BMC significantly improved LVEF and SF early (30 min) after reperfusion as well as after 14 days. Early after reperfusion HO-1 BMC were significantly more effective than control BMC, but after 14 days, there were no differences. There were no effect of cells on LV remodelling and diastolic function. Both HO-1 BMC and control BMC significantly reduced the infarct size vs. placebo (17.2 ± 2.7 and 18.8 ± 2.5, respectively, vs. 27.5 ± 5.1, p= 0.02) in histomorphometry. HO-1-positive donor BMC were detected in the infarct border area in pigs receiving HO-1-cells. No significant differences in expression of inflammatory genes (SDF-1, TNF-α, IL-6, miR21, miR29a and miR133a) in the myocardium were found. In conclusion, intracoronary delivery of allogeneic BMC immediately prior to reperfusion improved the LVEF and reduced the infarct size. HO-1 BMC were not superior to control cells after 14 days, however, produced faster recovery of LVEF. Transplanted cells survived in the peri-infarct zone.
Clinical scores to predict recurrence risk of venous thromboembolism
Authors: Eichinger Sabine , Kyrle Paul
Published: August 2012

Venous thromboembolism (VTE) is a common and chronic disease with a considerable risk of recurrence. Patients with unprovoked (in the absence of a transient risk factor) VTE have a recurrence risk as high as 30% within five years after cessation of anticoagulation. Depending on patient selection the case-fatality rate of recurrence ranges between 3.6%-10%. Thus, indefinite anticoagulation treatment should be considered in these patients. However, anticoagulation confers a considerable risk of bleeding (fatal bleedings 0.1%–0.5%/year). It is therefore of utmost clinical importance to identify those patients, who will not benefit from indefinite anticoagulation, i.e. patients, in whom the bleeding risk during anticoagulant treatment is higher than the risk of recurrence. Several attempts to discriminate patients with a high from those with a low risk of recurrence including screening for acquired and inherited thrombotic risk factors or measurement of coagulation activation markers have either failed (thrombophilia screening) or were of moderate success (stratification according to D-dimer only). A novel approach for assessing risk of recurrent VTE consists of linking clinical patient characteristics with laboratory testing. Several such scoring models which can be used to assess the risk of recurrent VTE have been developed and await prospective validation before they can be applied in daily routine care. The aim of this report is to describe currently available scoring systems in more detail.
Ces3/TGH Deficiency Improves Dyslipidemia and Reduces Atherosclerosis in
Ldlr
−/−
Mice
Authors: Lian Jihong , Quiroga Ariel D. , Li Lena , Lehner Richard
Published: August 2012

Rationale:

Carboxylesterase 3/triacylglycerol hydrolase (TGH) has been shown to participate in hepatic very low-density lipoprotein (VLDL) assembly. Deficiency of TGH in mice lowers plasma lipids and atherogenic lipoproteins without inducing hepatic steatosis.

Objective:

To investigate the contribution of TGH to atherosclerotic lesion development in mice that lack low-density lipoprotein receptor (LDLR).

Methods and Results:

Mice deficient in LDL receptor (
Ldlr

−/−

) and mice lacking both TGH and LDLR (
Tgh

−/−

/Ldlr

−/−

) were fed with a Western-type diet for 12 weeks. Analysis of
Tgh

−/−

/Ldlr

−/−

plasma showed an atheroprotective lipoprotein profile with decreased cholesterol in the VLDL and the LDL fractions, concomitant with elevated high-density lipoprotein cholesterol. Significantly reduced plasma apolipoprotein B levels were also observed in
Tgh

−/−

/Ldlr

−/−

mice. Consequently,
Tgh

−/−

/Ldlr

−/−

mice presented with a significant reduction (54%,
P
<0.01) of the high-fat, high-cholesterol dieteninduced atherosclerotic plaques when compared with
Tgh

+/+

/Ldlr

−/−

mice in the cross-sectional aortic root analysis. TGH deficiency did not further increase liver steatosis despite lowering plasma lipids, mainly due to reduced hepatic lipogenesis. The ameliorated dyslipidemia in Tgh

−/−

/Ldlr

−/−

mice was accompanied with significantly improved insulin sensitivity.

Conclusions:

Inhibition of TGH activity ameliorates atherosclerosis development and improves insulin sensitivity in
Ldlr

−/−

mice.
Detection of Paroxysmal Atrial Fibrillation by 30-Day Event Monitoring in Cryptogenic Ischemic Stroke
Authors: Flint Alexander C. , Banki Nader M. , Ren Xiushui , Rao Vivek A. , Go Alan S.
Published: August 2012

Background and Purpose—

Patients with cryptogenic ischemic stroke may have undetected paroxysmal atrial fibrillation (PAF). We established the Stroke and Monitoring for PAF in Real Time (SMART) Registry to determine the yield of 30-day outpatient PAF monitoring in cryptogenic ischemic stroke.

Methods—

The SMART Registry was a 3-year, prospective multicenter registry of 239 patients with cryptogenic ischemic stroke undergoing 30-day outpatient autotriggered PAF detection in Kaiser Permanente Northern California.

Results—

In intention-to-monitor analysis, PAF was detected in 29 of 239 patients (12.1%; 95% CI, 8.6%–16.9%). After retrospective chart review was performed, a new diagnosis of PAF was confirmed in 26 of 236 patients (11.0%; 95% CI, 7.6%–15.7%). The majority of detected PAF events were asymptomatic; only 6 of 98 recorded PAF events (6.1%) were patient-triggered or associated with symptoms.

Conclusions—

-Approximately 1 in every 9 patients with cryptogenic ischemic stroke was found to have new PAF within 30 days. Routine monitoring in this population should be strongly considered.
Documenting Climate Models and Their Simulations
Authors: Guilyardi Eric , Balaji V. , Lawrence Bryan , Callaghan Sarah , Deluca Cecelia , Denvil Sébastien , Lautenschlager Michael , Morgan Mark , Murphy Sylvia , Taylor Karl E.
Published: August 2012

The results of climate models are of increasing and widespread importance. No longer is climate model output of sole interest to climate scientists and researchers in the climate change impacts and adaptation fields. Now nonspecialists such as government officials, policy makers, and the general public all have an increasing need to access climate model output and understand its implications. For this host of users, accurate and complete metadata (i.e., information about how and why the data were produced) is required to document the climate modeling results. Here we describe a pilot community initiative to collect and make available documentation of climate models and their simulations. In an initial application, a metadata repository is being established to provide information of this kind for a major internationally coordinated modeling activity known as CMIP5 (Coupled Model Intercomparison Project, Phase 5). It is expected that for a wide range of stakeholders, this and similar community-managed metadata repositories will spur development of analysis tools that facilitate discovery and exploitation of Earth system simulations.
Happiness and Feeling Connected
Authors: Zelenski John M. , Nisbet Elizabeth K.
Published: August 2012

Subjective connection with nature, or nature relatedness, is similar to other environmental worldview measures in predicting sustainable attitudes and behaviors, yet is unique in predicting happiness. In two studies, the authors assessed the overlap between nature relatedness and other subjective connections (e.g., with friends or country) and examined these connections as a possible confound in explaining the link between nature relatedness and happiness. Study 1 adapted a measure of general connectedness and administered it to student ( n = 331) and community ( n = 415) samples along with multiple nature relatedness and happiness indicators. Study 2 examined more established measures of subjective connections in another community sample ( n = 204). General connectedness predicted happiness well, yet nature relatedness remained a significant distinct predictor of many happiness indicators, even after controlling for other connections. Results support the notion that nature relatedness could be a path to human happiness and environmental sustainability, though confirming this causal direction requires additional research.
Blaming the Government for Environmental Problems
Authors: Kentmen Cin Cigdem
Published: August 2012

Although the determinants of trust in governments have received significant attention in the literature on political trust, there has been no attention paid to whether environmental concerns affect governmental trust. Yet, if individuals are worried about local and global environmental degradation, they may think that the government has failed in providing them with the best living conditions. Hence, it is plausible to expect local and global environmental concerns and trust in government to be inversely correlated. Using 2005 data from 24 countries, this hypothesis is tested against competing theories of civic participation, interpersonal trust, and economic considerations to explain individual trust in government. Multilevel models that specify the impact of individual- and national-level factors provide evidence that global environmental concerns do actually matter.
Twin Cities: Territorial and Relational Geographies of ‘Worldly’ Manchester
Authors: Jayne Mark , Hubbard Philip , Bell David
Published: August 2012

This paper contributes to recent interest in city twinning by urban theorists. It begins with a review of writing from across the social sciences which describes the institutional context and content of twinning programmes, as well as work which theorises how care and hospitality are key elements of twinning practices. Ethnographic research is then presented from the City of Manchester (UK) in order to consider the ways in which twinning is constituted through circuits, networks and webs of co-operation and competition involved in the transfer of policy and knowledge which can be strategic, uneven and at times ambivalent. In doing so, it is argued that the conflicts, tensions and contradictions bound up with twinning have much to offer theoretical and empirical understanding of territorial and relational urban politics. The paper concludes with theoretical, methodological and policy relevant insights.
An Alternative Approach to Addressing Selection Into and Out of Social Settings
Authors: Sharkey Patrick
Published: August 2012

This article develops a method to estimate the impact of change in a particular social setting, the residential neighborhood, that is designed to address nonrandom selection into a neighborhood and nonrandom selection out of a neighborhood. Utilizing matching to confront selection into neighborhood environments and instrumental variables to confront selection out of changing neighborhoods, the method is applied to assess the effect of a decline in neighborhood concentrated disadvantage on the economic fortunes of African American children living within changing neighborhoods. Substantive findings indicate that a decline in neighborhood concentrated disadvantage during childhood leads to increases in adult earnings and income, but has no effects on educational attainment or other social outcomes.
Making Use of “Benford’s Law” for the Randomized Response Technique
Authors: Diekmann Andreas
Published: August 2012

In this article, “Benford’s law” is applied to the “randomized response technique” (RRT) to increase the validity of answers to sensitive questions. Using the Newcomb–Benford distribution as a randomizing device has several advantages. It is easy to explain and follow the procedure, as no physical device such as a coin or a dice is necessary and the method guarantees full anonymity. As is well known, the price for the anonymity of the RRT is a decrease in the efficiency of the estimator. However, because of the subjective overestimation of certain numbers (Benford illusion), the conflict between the variance of the estimates and the degree of anonymity is less pronounced compared to other RRT methods. The suggested RRT variant has the potential to improve the efficiency of the estimator. Moreover, the assumption is that this method works well with self-administered questionnaires.
Intelligent instrumentation for identification of scales in petroleum pipelines in situ
Authors: Christidis Konstantinos , Gunarathne Gunti PP , Peteineri Kalliopi
Published: August 2012

This paper presents a microcomputer-based method that can be used to categorize mineral deposits in petroleum pipelines using ultrasonic measurements. The system was developed for use in the field in order to avoid expensive and time-consuming procedures. The identification of mineral deposits is based on an intelligent method using a multi-layer perceptron neural network consisting of three layers of neurons. The artificial neural network was trained to identify six different materials (calcium carbonate, wax, marble, barium sulphate, strontium sulphate and steel) and implemented using a microcontroller.
Effects of Environmentally Relevant Mixtures of Persistent Organic Pollutants on the Developmental Neurobiology in Rats
Authors: Gill Santokh , Bowers Wayne J. , Nakai Jamie S. , Yagminas Al , Mueller Rudi , Pulido Olga
Published: August 2012

We report the developmental neuropathology for rat pups at postnatal day (PND) 37 and PND 77 and the molecular biomarkers for PND 35, 75, and 350 after perinatal exposure to a reconstituted mixture of persistent organochlorine pollutants (POPs) based on the blood profiles of people living in the Great Lake Basin. The developmental neuropathology included routine histopathology evaluation, quantification of cell proliferation and death in the subventricular zone, linear morphometric measurements, and transcriptional analysis. No histopathological, structural, or stereological changes were observed in animals treated with the POPs or Aroclor 1254, on PND 37 or PND 77. While no transcriptional changes were found in Arcolor-treated animals, significant transcriptional changes were observed on PND 350 in female offspring perinatally exposed to 0.13 mg/kg of the POP mixture. Markers of the cholinergic system including acetylcholinesterase and the muscarinic receptors (subtypes M1–M5) were downregulated 2- to 6-fold. In addition, structural genes including neurofilaments (NFLs) and microtubule-associated protein (MAP-2) were downregulated at least 2-fold or greater. Our results support that in utero and lactational exposure to the chemical mixture of POPs lead to developmental changes in adult rat brains.
Histopathological Assessment in Glossectomy
Authors: Cristalli Giovanni , Mercante Giuseppe , Covello Renato , Sperduti Isabella , Cristalli Maria Paola , Spriano Giuseppe
Published: August 2012

Objectives

The aim of the study was to gather information on outcomes and effect sizes of 2 surgical methods of glossectomy by using a grade system and an objective measure of artifacts in micrometers (µm). The collected data would be used to plan a definitive study.

Study Design

Pilot study.

Setting

Tertiary referral center.

Material and Methods

Nineteen patients affected with tongue cancer were consecutively enrolled in a pilot study and treated by partial glossectomy. Eleven patients (57.89%) of group A were treated with monopolar electrocautery, while 8 patients (42.10%) of group B were treated with Harmonic Focus Curved Shears. Specimens were examined by a pathologist blinded to the surgical procedure, using a 4‐grade system for margin artifact assessment (margin fragmentation, cautery/crush artifact, extravascular blood clot, capillary congestion) and for measuring artifact depth.

Results

Artifact depth was more relevant in group A (765,633 µm) than in group B (473,939 µm). The difference between groups was significant at the 95% confidence interval (P <. 0001). Margin fragmentation and capillary congestion compared between the 2 groups were of no significance. There were less cautery/crush artifacts and extravascular blood clots observed in the harmonic shears group.

Conclusion

When used to perform a partial glossectomy, Harmonic Focus Curved Shears produce less cautery/crush artifact and a smaller artifact depth compared with monopolar cautery.
Long-Term Outcomes of Young Adults Exposed to Maltreatment
Authors: Smith Carolyn A. , Park Aely , Ireland Timothy O. , Elwyn Laura , Thornberry Terence P.
Published: August 2012

This study investigates whether positive educational experiences in midadolescence mitigate the impact of exposure to substantiated maltreatment and reduces young adult antisocial behavior. While there is theoretical and empirical support for the mediating or moderating role of educational experiences on maltreatment and antisocial outcomes, few prospective studies exist. In this exploratory study, data are from the Rochester Youth Development Study (RYDS), a longitudinal panel study of 1,000 adolescents. The original sample included 73% males, and 85% African American or Hispanic youth of whom about 20% were maltreated. Measures in this study are from a combination of interview data and official records collected through age 23. Outcomes include self-reported crime and violence, arrest, and partner violence perpetration. Educational variables include midadolescent self-report of high school graduation, educational aspiration, college expectation, school commitment, teacher attachment, self-reported grades, school GPA, attendance, and an additive index of all school assets. Multivariate path analysis controlled for gender, race/ethnicity, poverty, and early antisocial behavior. Path analysis examined whether educational experiences mediated the impact of maltreatment on antisocial outcomes. Although maltreatment was significantly predictive of criminal and violent behaviors, it only was weakly associated with educational experiences. The impact of maltreatment on arrest was weakly mediated (reduced) by educational GPA and by high school graduation. The additive index also mediated the impact of maltreatment on crime and violence. Maltreatment’s impact on partner violence was also weakly mediated by school GPA. Interaction terms were used to test for moderation: only one significant effect was found: school GPA protects maltreated youth from perpetration of partner violence as young adults. Although there are few significant effects in a number of models, the research is consistent with a focus on promoting school achievement and completion among urban youth in general, in conjunction with addressing earlier antisocial behavior problems.
State Political Culture, Higher Education Spending Indicators, and Undergraduate Graduation Outcomes
Authors: Heck Ronald H. , Lam Wendy S. , Thomas Scott L.
Published: August 2012

Issues concerning higher education today (e.g., rising costs, declining public trust, changing state economics) have created new demands for postsecondary institutions to demonstrate their productivity. We examine whether differences in states’ political cultures (i.e., underlying traditions, values, and public policy choices) are reflected in variability between state finance policy indicators and institutional variables that explain undergraduate graduation rates. To test our proposed model, we use longitudinal data on state indicators and institutional variables that explain differences in graduation rates compiled over an 11-year period. Our findings suggest that differences in political culture represent mediating factors between states’ economic contexts and higher education appropriations, which help explain variation in their graduation rates over time.