bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficits of Affect Mentalization in Patients with Drug Addiction: Theoretical and Clinical Aspects
Authors: Savov Svetoslav , Atanassov Nikola
Published: November 2012

Traditionally treated with wariness, drug addictions have provoked a serious interest in psychodynamically oriented clinicians in recent decades. This paper discusses the development of contemporary psychodynamic conceptualizations of addictions, focusing specifically on mentalization-based theories. The concept of mentalization refers to a complex form of self-regulation which includes attribution of psychological meaning to one’s own behavior and affective states, as well as those of the others. We hypothesize that drug-addicted patients have severe impairments in mentalizing, associated with developmental deficits, characteristic for the borderline personality disorder and psychosomatic conditions. Psychodynamic models of mentalization and their corresponding research operationalizations are reviewed, and implications for a contemporary understanding of drug addictions and psychotherapy are drawn. The authors propose that mentalization-oriented theories provide an adequate conceptualization, which is open to empirical testing and has clear and pragmatic guidelines for treatment.
Stability‐Indicating Validated HPLC Method for Analysis of Berberine Hydrochloride and Trimethoprim in Pharmaceutical Dosage Form
Authors: Wang Jing-Chun , Zhang Qi , Cai De-Fu
Published: November 2012

A stability‐indicating HPLC method was developed and validated for the determination of berberine hydrochloride and trimethoprim in pharmaceutical dosage form in the presence of degradation products. The proposed RP‐HPLC method utilizes an Agilent TC‐C18, 4.6 mm × 250 mm, 5 μm, column using a mobile phase consisting of acetonitrile‐50 mM potassium dihydrogen phosphate (30 : 70, v/v, pH adjusted to 3 with orthophosphoric acid) at a flow rate of 1.0 mL/min and UV detection at 271 nm. The linearity of berberine hydrochloride and trimethoprim was in the range of 2 to 60 μg/mL (r = 0.9996) and 1 to 30 μg/mL (r = 0.9995), respectively. Repeatability and intermediate precisions were also determined with percentage relative standard deviation (% RSD) less than 2.0%. The limits of detection were found to be 9.8 ng/mL for berberine hydrochloride and 2.5 ng/mL for trimethoprim. The mean recoveries for berberine hydrochloride and trimethoprim were 99.8 and 98.8%, respectively. The stability of the two drugs was determined under different conditions and the proposed method has shown effective separation for their degradation products. And the proposed assays method can thus be considered stability‐indicating.
The Dysregulation Profile Predicts Cannabis Use in the Offspring of Teenage Mothers
Authors: De Genna Natacha M. , Larkby Cynthia , Cornelius Marie D.
Published: November 2012

Background. Offspring of teenage mothers are at greater risk of early drug use. Research has identified a child behavior checklist (CBCL) profile for children with high levels of comorbid behavior problems, the dysregulation profile (DP), as another risk factor for drug use.Method. Teenage girls (12–18 years old; 71% African-American, 29% White) were recruited during pregnancy. Data were collected during pregnancy and when offspring were 6, 10, and 14 years old (). Mothers completed the CBCL when children were at ages 6 and 10, and children who scored 60 or higher on all 3 DP subscales (aggression, anxiety/depression, and attention problems) were categorized as dysregulated. At ages 10 and 14, the offspring (50% male, 50% female) reported on their cannabis use and completed the childhood depression inventory (CDI).Results. DP at age 6 and depressive symptoms at age 14 predicted recent cannabis use in the offspring. There was a significant interaction between race and pubertal timing such that White offspring who matured earlier were at greater risk of recent cannabis use.Conclusions. The results of this study suggest that it may be possible to identify a subset of children at risk of dual diagnosis as early as age 6.
Dual Targeting of EGFR and HER3 with MEHD7945A Overcomes Acquired Resistance to EGFR Inhibitors and Radiation
Authors: Huang Shyhmin , Li Chunrong , Armstrong Eric A. , Peet Chimera R. , Saker Jarob , Amler Lukas C. , Sliwkowski Mark X. , Harari Paul M.
Published: November 2012

EGF receptor (EGFR) inhibition is efficacious in cancer therapy, but initially sensitive tumors often develop resistance. In this study, we investigated the potential to overcome acquired resistance to EGFR inhibitors with MEHD7945A, a monoclonal antibody that dually targets EGFR and HER3 (ErbB3). In cancer cells resistant to cetuximab and erlotinib, we found that MEHD7945A, but not single target EGFR inhibitors, could inhibit tumor growth and cell-cycle progression in parallel with EGFR/HER3 signaling pathway modulation. MEHD7945A was more effective than a combination of cetuximab and anti-HER3 antibody at inhibiting both EGFR/HER3 signaling and tumor growth. In human tumor xenograft models, we confirmed the greater antitumor potency of MEHD7945A than cetuximab or erlotinib. MEHD7945A retained potent activity in tumors refractory to EGFR inhibitor alone. Furthermore, MEHD7945A also limited cross-resistance to radiation in EGFR inhibitor–resistant cells by modulating cell-cycle progression and repair processes that control apoptotic cell death. Taken together, our findings confirm an important role of compensatory HER3 signaling in the development of acquired resistance to EGFR inhibitors and offer preclinical proof-of-concept that MEHD7945A can effectively overcome EGFR inhibitor resistance. Cancer Res; 73(2); 824–33. ©2012 AACR.
1p36 Tumor Suppression—A Matter of Dosage?
Authors: Henrich Kai-Oliver , Schwab Manfred , Westermann Frank
Published: November 2012

A broad range of human malignancies is associated with nonrandom 1p36 deletions, suggesting the existence of tumor suppressors encoded in this region. Evidence for tumor-specific inactivation of 1p36 genes in the classic “two-hit” manner is scarce; however, many tumor suppressors do not require complete inactivation but contribute to tumorigenesis by partial impairment. We discuss recent data derived from both human tumors and functional cancer models indicating that the 1p36 genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development when reduced in dosage by genomic copy number loss or other mechanisms. We explore potential interactions among these candidates and propose a model where heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous downregulation of several dosage-dependent tumor suppressor genes. Cancer Res; 72(23); 6079–88. ©2012 AACR.
Why Your New Cancer Biomarker May Never Work: Recurrent Patterns and Remarkable Diversity in Biomarker Failures
Authors: Kern Scott E.
Published: November 2012

Less than 1% of published cancer biomarkers actually enter clinical practice. Although best practices for biomarker development are published, optimistic investigators may not appreciate the statistical near-certainty and diverse modes by which the other 99% (likely including your favorite new marker) do indeed fail. Here, patterns of failure were abstracted for classification from publications and an online database detailing marker failures. Failure patterns formed a hierarchical logical structure, or outline, of an emerging, deeply complex, and arguably fascinating science of biomarker failure. A new cancer biomarker under development is likely to have already encountered one or more of the following fatal features encountered by prior markers: lack of clinical significance, hidden structure in the source data, a technically inadequate assay, inappropriate statistical methods, unmanageable domination of the data by normal variation, implausibility, deficiencies in the studied population or in the investigator system, and its disproof or abandonment for cause by others. A greater recognition of the science of biomarker failure and its near-complete ubiquity is constructive and celebrates a seemingly perpetual richness of biologic, technical, and philosophical complexity, the full appreciation of which could improve the management of scarce research resources. Cancer Res; 72(23); 6097–101. ©2012 AACR.
Vegetarian Diets and the Incidence of Cancer in a Low-risk Population
Authors: Tantamango-Bartley Yessenia , Jaceldo-Siegl Karen , Fan Jing , Fraser Gary
Published: November 2012

Background: Cancer is the second leading cause of death in the United States. Dietary factors account for at least 30% of all cancers in Western countries. As people do not consume individual foods but rather combinations of them, the assessment of dietary patterns may offer valuable information when determining associations between diet and cancer risk.

Methods: We examined the association between dietary patterns (non-vegetarians, lacto, pesco, vegan, and semi-vegetarian) and the overall cancer incidence among 69,120 participants of the Adventist Health Study-2. Cancer cases were identified by matching to cancer registries. Cox proportional hazard regression analysis was conducted to estimate hazard ratios, with “attained age” as the time variable.

Results: A total of 2,939 incident cancer cases were identified. The multivariate HR of overall cancer risk among vegetarians compared with non-vegetarians was statistically significant [HR, 0.92; 95% confidence interval (CI), 0.85–0.99] for both genders combined. Also, a statistically significant association was found between vegetarian diet and cancers of the gastrointestinal tract (HR, 0.76; 95% CI, 0.63–0.90). When analyzing the association of specific vegetarian dietary patterns, vegan diets showed statistically significant protection for overall cancer incidence (HR, 0.84; 95% CI, 0.72–0.99) in both genders combined and for female-specific cancers (HR, 0.66; 95% CI, 0.47–0.92). Lacto-ovo-vegetarians appeared to be associated with decreased risk of cancers of the gastrointestinal system (HR, 0.75; 95% CI, 0.60–0.92).

Conclusion: Vegetarian diets seem to confer protection against cancer.

Impact: Vegan diet seems to confer lower risk for overall and female-specific cancer than other dietary patterns. The lacto-ovo-vegetarian diets seem to confer protection from cancers of the gastrointestinal tract. Cancer Epidemiol Biomarkers Prev; 22(2); 286–94. ©2012 AACR.
A Feasibility Study of the Intraductal Administration of Chemotherapy
Authors: Love Susan M. , Zhang Wei , Gordon Eva J. , Rao Jianyu , Yang Hongying , Li Junyao , Zhang Bailin , Wang Xiang , Chen Guoji , Zhang Baoning
Published: November 2012

Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5–9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a “chemical mastectomy”, where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery. Cancer Prev Res; 6(1); 51–58;. ©2012 AACR.
Association between CYP2C8 (rs1934951) Polymorphism and Bisphosphonate-Related Osteonecrosis of the Jaws in Patients on Bisphosphonate Therapy: A Meta-Analysis
Authors: Zhong Da-Ni , Wu Ji-Zhou , Li Guo-Jian
Published: November 2012

Aims: Bisphosphonate-related osteonecrosis of the jaws (BONJ) is a severe complication in patients on bisphosphonate therapy. The study was conducted to verify the association between CYP2C8 (rs1934951) polymorphism and BONJ predisposition. Methods: The relative epidemiologic studies were identified in PubMed and Embase to conduct a meta-analysis using STATA. Results: In the pooled analysis with multiple cancer types, patients carrying the CYP2C8 rs1934951 AA or AG genotype showed no significantly increased BONJ susceptibility compared with those carrying the wild GG genotype [dominant: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 0.67–6.29, p = 0.209; recessive: OR = 1.88, 95% CI = 0.23–15.6, p = 0.560; AG vs. GG: OR = 2.07, 95% CI = 0.80–5.32, p = 0.133, and AA vs. GG: OR = 1.34, 95% CI = 0.48–3.74, p = 0.578]. A significant association between AA and AG genotypes of CYP2C8 (rs1934951) and BONJ risk was found in the subgroup analysis of multiple myeloma (dominant: OR = 5.77, 95% CI = 1.21–27.63, p = 0.028; AG vs. GG: OR = 5.02, 95% CI = 2.06–12.23, p = 0.001, and AA vs. GG: OR = 16.23, 95% CI = 1.72–78.7, p = 0.015). Conclusion: The results indicated that AA and AG genotypes of CYP2C8 (rs1934951) might be predictors for multiple myeloma patients at high risk to develop BONJ.
Specific IgE Levels to Dermatophagoides pteronyssinus Are Associated with Meteorological Factors
Authors: Hervás D. , Pons J. , Milá J. , Matamoros N. , Hervás J.A. , García-Marcos L.
Published: November 2012

Background: Dermatophagoides pteronyssinus specific IgE (sIgE) measurement is a major diagnostic test for the detection of sensitization to that allergen. Methods: To investigate the effect of climate on the seasonal variations of D.pteronyssinus sIgE, we studied the tests performed in an insular population during a 10-year period. The association with meteorological factors was evaluated with multiple regression analyses. Results: Of 24,879 tests performed for D. pteronyssinus sIgE, 16,719 (67.2%) were D. pteronyssinus sIgE positive; 24.5% were tested for asthma and 46.07% for rhinitis. D. pteronyssinus sIgE levels showed a seasonal pattern with an annual peak in November. In the multivariate analyses solar radiation (r = –0.94) and relative humidity (r = 0.86) were independent factors associated with D. pteronyssinus sIgE levels. The resulting model could explain 93% (p < 0.001) of D. pteronyssinus sIgE variability. Conclusions: Our population showed a seasonal pattern of D. pteronyssinus sIgE explained by relative humidity and solar radiation.
Altered Reactivity of Tertiary Mesenteric Arteries following Acute Myocardial Ischemia
Authors: Han Young Soo , Brozovich Frank V.
Published: November 2012

Background: It is unknown if cardiac ischemia has any deleterious effect on the contractile properties of nonischemic, peripheral vascular beds. Thus, the objective of the present study was to determine whether acute myocardial ischemia results in peripheral vascular dysfunction. Methods and Results: This study characterized force maintenance and the sensitivity to acetylcholine (ACh)-mediated smooth muscle (SM) relaxation of tertiary (3rd) mesenteric arteries from Sprague-Dawley rats following 30 min of myocardial ischemia. Both the phosphorylation of nonmuscle (NM) light chain (LC) and SM-LCs as well as the expression of myosin phosphatase targeting subunit 1 (MYPT1) were also determined. Our data demonstrate that acute myocardial ischemia resulted in vascular dysfunction of 3rd mesenteric vessels, characterized by decreases in force maintenance, ACh- and cGMP-mediated SM relaxation, the phosphorylation of NM-LCs and SM-LCs, and MYPT1 expression. Ischemia was also associated with an increase in protein polyubiquitination, suggesting that during ischemia MYPT1 is targeted for degradation or proteolysis. Conclusion: Acute myocardial ischemia produces peripheral vascular dysfunction; the changes in LC phosphorylation and MYPT1 expression result in a decrease in both tone and the sensitivity to NO-mediated SM relaxation of the peripheral vasculature.
Histopathologic Insight into Saphenous Vein Bypass Graft Disease
Authors: Bikdeli Behnood , Hassantash Seyed-Ahmad , Pourabdollah Mihan , Kalantarian Shadi , Sadeghian Maryam , Afshar Haleh , Sabeti Shahram , Marzban Mehrab , Ahmadi Hossein , Mohammadi Foroozan
Published: November 2012

Objectives: Vein graft disease is a major drawback of coronary artery bypass grafting. However, histopathologic studies of old human aortocoronary grafts are scarce. Methods: We screened patients undergoing redo coronary artery bypass grafting at three university hospitals and selected those with at least one excisable old vein graft. Native non-grafted saphenous veins were also obtained as controls. Clinical and angiographic data were separately documented. Results: We evaluated 117 segments from 29 veins. All but 4 old graft segments showed degrees of luminal narrowing and fibrointimal proliferation. Moreover, 61 segments demonstrated atherosclerotic plaques. Such plaques were typically concentric and, compared with other segments, more frequently represented necrosis, calcification and giant cells (p < 0.001 for all comparisons) and had a higher inflammatory cell count, predominantly of lymphocytic origin. Native saphenous veins frequently showed fibrosis, but no calcification or active inflammation. Angiographic findings showed moderate correlation with the histological degree of luminal stenosis (Spearman’s ρ = 0.564, p < 0.001). Conclusions: Human vein graft atherosclerosis and arterial atherosclerosis share many features; however, we found lymphocytes to be the dominant inflammatory cells within plaques. Conventional angiography underestimated the atherosclerosis burden in vein grafts. Improved understanding of disease pathophysiology could lead to the development of novel interventions that reduce costly and suboptimal repeat revascularizations.
Effective Induction Therapy with Subcutaneous Administration of Bortezomib for Newly Diagnosed POEMS Syndrome: A Case Report and a Review of the Literature
Authors: Zeng Ke , Yang Jin-rong , Li Jun , Wei Qing , Yang Yi-ming , Liu Ting , Niu Ting
Published: November 2012

POEMS syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Bortezomib is an important component of the chemotherapy regimen associated with multiple myeloma, and has been previously applied to POEMS syndrome. We present a 56-year-old Chinese man who was given subcutaneous administration of bortezomib as part of the BDex (bortezomib–dexamethasone) regimen for his POEMS syndrome. The peripheral neuropathy and laboratory-test results of the patient improved dramatically with 4 cycles of treatment, resulting in a complete response. In addition, the treatment was well tolerated and adequate peripheral blood hematopoietic stem cells were collected for an ensuing autologous stem cell transplant.
Microdialysis in Early Detection of Temporary Pancreatic Ischemia in a Porcine Model
Authors: Blind P.-J. , Kral J. , Wang W. , Kralova I. , Abrahamsson P. , Johansson G. , Winsö O.
Published: November 2012

Background: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. Aims: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. Methods: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (PtiO2) measurements. Results: PtiO2 decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. Conclusion: MD data were in concordance with changes in PtiO2, which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.
Laparoscopic Pyeloplasty: A Comparison between the Transperitoneal and Retroperitoneal Approach during the Learning Curve
Authors: Zhu Hongjian , Shen Cheng , Li Xuesong , Xiao Xuren , Chen Xianglong , Zhang Qingjiang , Wang Hua , He Zhisong , Zhou Liqun
Published: November 2012

Purpose: To compare the transperitoneal and the retroperitoneal approach in the laparoscopic management of pelviureteric junction (PUJ) obstruction, and to find out which approach is preferable during the learning curve period at two different urologic centers. Materials and Methods: We retrospectively evaluated 50 consecutive laparoscopic pyeloplasties performed by two urologists from different urologic centers during their learning curve period in laparoscopy. Each surgeon used a different approach: transperitoneal (group A) or retroperitoneal (group B). Timing for patient positioning, access to the operating field, ureter and PUJ isolation, PUJ suturing, total time of the surgery procedure and blood loss were recorded to compare the transperitoneal with the retroperitoneal approach. Intraoperative complications and perioperative morbidity were also reported. Results: 22 procedures were performed using the transperitoneal method (group A) and 28 using the retroperitoneal method (group B). Significant differences between groups A and B were observed in terms of time for access to the operating field (mean 25 and 15 min, respectively, p < 0.05), time for suturing the PUJ (mean 57 and 103 min, respectively, p < 0.001), and total operative time (mean 127 and 201 min, respectively, p < 0.002). No statistical differences were observed for any other parameters. Average follow-up was 10 and 11 months for groups A and B; no statistical differences were observed. Conclusions: We suggest that young urologists during the learning curve for laparoscopy should perform laparoscopic pyeloplasty using a transperitoneal route. In expert hands, both transperitoneal and retroperitoneal approaches are feasible, and the choice depends on personal preference.
Treatment of Anaemia with Erythropoiesis-Stimulating Agents in Patients with Chronic Kidney Disease Does Not Lower Mortality and May Increase Cardiovascular Risk: A Meta-Analysis
Authors: Vinhas J. , Barreto C. , Assunção J. , Parreira L. , Vaz A.
Published: November 2012

Background/Aims: Interpretation of the results of earlier meta-analyses in chronic kidney disease (CKD) patients on the impact of anaemia treatment with erythropoiesis-stimulating agents (ESAs) on clinical outcomes has been hampered by the inclusion of small trials and trials of short duration. We re-evaluated the benefits and harms of treating anaemia, including only relevant clinical trials. Methods: We conducted a systematic review and meta-analysis of randomised controlled trials performed in adults with CKD which allocated patients to different doses of ESAs, and we compared the effect of these interventions on vascular access thrombosis, stroke, risk of end-stage renal disease (ESRD) and all-cause mortality. Additional inclusion criteria were studies with a duration of at least 1 year and enrolling more than 500 participants. Results: Five trials (7,902 participants) met the inclusion criteria and were included in the meta-analysis. The number of patients enrolled in each trial ranged from 596 to 4,038. The mean/median duration of follow-up ranged from 14 to 36 months. A higher haemoglobin target was associated with increased risk of vascular access thrombosis (RR 1.343; 95% CI 1.162–1.554; p = 0.0005) and stroke (RR 1.735; 95% CI 1.323–2.275; p = 0.0005), and no effect on risk of ESRD (RR 1.089; 95% CI 0.986–1.203; p = 0.094) or all-cause mortality (RR 1.148; 95% CI 0.977–1.350; p = 0.093). Conclusion: In CKD patients, treatment of anaemia with ESAs targeting a higher haemoglobin value does not lower mortality or reduce the risk of ESRD, and may increase cardiovascular risk.
Vascular Actions of Aldosterone
Authors: Briet Marie , Schiffrin Ernesto L.
Published: November 2012

Aldosterone exerts direct effects on the vascular system by inducing oxidative stress, inflammation, hypertrophic remodeling, fibrosis, and endothelial dysfunction. Aldosterone exerts its effects through genomic and nongenomic pathways in a mineralocorticoid receptor (MR)-dependent or independent manner. Other aldosterone receptors such as GPR30 have been identified. A tight relation exists between the aldosterone and angiotensin II pathways, as well as with the endothelin-1 system. There is a correlation between plasma levels of aldosterone and cardiovascular risk. Recently, an increasing body of evidence has underlined the importance of aldosterone in cardiovascular complications associated with the metabolic syndrome, such as arterial remodeling and endothelial dysfunction. Blockade of MR is an increasingly used evidence-based therapy for many forms of cardiovascular disease, including hypertension, heart failure, chronic kidney disease, and diabetes mellitus.
Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients with ST-Segment–Elevation Myocardial Infarction
Authors: Alexopoulos Dimitrios , Xanthopoulou Ioanna , Gkizas Vassilios , Kassimis George , Theodoropoulos Konstantinos C. , Makris George , Koutsogiannis Nikolaos , Damelou Anastasia , Tsigkas Grigorios , Davlouros Periklis , Hahalis George
Published: November 2012

Background—

Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel. Direct pharmacodynamic comparison between them has not yet been reported in ST-segment–elevation myocardial infarction patients.

Methods and Results—

In a prospective, single-center, single-blind study, 55 out of 117 (47%) screened consecutive ST-segment–elevation myocardial infarction patients undergoing primary percutaneous coronary intervention were randomized to either ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24 hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at hour 1, did not differ significantly between patients randomized to ticagrelor versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8–283.8 versus 231.3 PRU, 95% CI 205.3–257.4;
P
=0.2). PR did not differ at 2, 6, and 24 hours, although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI 12.3–38.9 versus 50.3 PRU, 95% CI 36.4–64.1;
P
=0.01). At hour 2, high on-treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and prasugrel, respectively, decreased significantly thereafter, whereas did not differ significantly between the 2 agents at all the time points of the study.

Conclusions—

In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action. Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment–elevation myocardial infarction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01463163.
Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis
Authors: Aldrovandi Annachiara , Cademartiri Filippo , Arduini Daniele , Lina Daniela , Ugo Fabrizio , Maffei Erica , Menozzi Alberto , Martini Chiara , Palumbo Alessandro , Bontardelli Federico , Gherli Tiziano , Ruffini Livia , Ardissino Diego
Published: November 2012

Background—

It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients.

Methods and Results—

Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (
P
=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm
2
versus 4.2±2.1 mm
2
;
P
=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2;
P
=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21;
P
=0.01).

Conclusions—

CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.
CXCR4 Antagonist AMD3100 Protects Blood–Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice
Authors: Huang Jun , Li Yaning , Tang Yaohui , Tang Guanghui , Yang Guo-Yuan , Wang Yongting
Published: November 2012

Background and Purpose—

Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia.

Methods—

Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.

Results—

Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (
P
<0.05). Brain edema–induced change of water content, IgG protein leakage, Evans blue extravasation, occludin, and ZO-1 expression in ipsilateral hemisphere were alleviated by acute treatment of AMD3100. MPO expression and activity revealed that AMD3100 profoundly reduced the number of MPO-positive cells in the ischemic region (
P
<0.05). It also attenuated proinflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ; their mRNA and protein levels changed accordingly compared with the controls (
P
<0.05).

Conclusions—

CXCR4 antagonist AMD3100 significantly suppressed inflammatory response and reduced blood–brain barrier disruption after MCAO. AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte migration and infiltration, in addition to reducing proinflammatory cytokine expression in the ischemic region.
Postal and Face-to-Face Administration of Stroke Outcome Measures
Authors: Sutton Christopher J. , Watkins Caroline L. , Cook Neil , Leathley Michael J. , McAdam Joanna , Dey Paola
Published: November 2012

Background and Purpose—

Different modes of administration are used to collect stroke outcomes, even within the same study, potentially leading to different results. We investigated the effect of administration mode (postal questionnaire; face-to-face interview) on self-reports of activities of daily living and mood.

Methods—

The study was nested within a poststroke motivational interviewing trial. Activities of daily living (Barthel; Nottingham Extended) and mood (General Health Questionnaire; Yale) were collected at 3 and 12 months via postal questionnaire. Participants were approached to respond again via face-to-face interview. Paired
t
tests (McNemar test) and intraclass correlation coefficients (Cohen κ) were used, with 95% CI, to compare scores (items).

Results—

Forty-four participants consented. Only Barthel scores were significantly different; they were 1.0 (95% CI, 0.5–1.6) higher face-to-face. The intraclass correlation coefficient for the Barthel was 0.90; for the other scales it was between 0.83 and 0.87. The Yale κ was 0.72.

Conclusions—

Modes of administration might be used interchangeably, albeit in conjunction with corrections for the Barthel.
Correlation of Large Artery Intracranial Occlusive Disease With Carotid Intima-Media Thickness and Presence of Carotid Plaque
Authors: Leng Xin Yi , Chen Xiang Yan , Chook Ping , Xiong Li , Lin Wen Hua , Liu Jing Yi , Tomlinson Brian , Thomas G. Neil , Lam Tai Hing , Lam Karen S.L. , Cheung Bernard M.Y. , Wong Ka Sing
Published: November 2012

Background and Purpose—

Large artery intracranial occlusive disease (LAICOD) is a predominant cause of ischemic stroke in China. Carotid intima-media thickness (CIMT) and presence of carotid plaque are also related to subsequent ischemic stroke. However, the correlation between these and LAICOD is less clear.

Methods—

This was a community-based cross-sectional study. All subjects underwent carotid duplex ultrasonography and transcranial Doppler. Mean CIMT value of bilateral common carotid arteries was used. Plaque was defined as a focal CIMT of >1.5 mm. LAICOD in transcranial Doppler was defined by peak systolic velocity and age, and presence of turbulence or musical sound was also considered.

Results—

For the 537 subjects studied (mean age, 54.7±10.1 years; 46.9% males), mean CIMT was 0.74±0.12 mm, with the 75th percentile of 0.80 mm. CIMT ≥1.0 mm was identified in 13 subjects (2.4%). Plaques were detected in 79 subjects (14.7%). Compared with those without LAICOD, the 48 subjects (8.9%) with LAICOD had greater CIMTs (0.77±0.09 versus 0.73±0.12 mm;
P
=0.044), more with CIMT of higher quartiles (
P
=0.007), and more with carotid plaques (25.0% versus 13.7%;
P
=0.035). However, after adjusting for confounding factors, CIMT and presence of carotid plaque were not significantly associated with LAICOD.

Conclusions—

The results suggest that CIMT and presence of carotid plaque probably are not independently correlated with LAICOD in Chinese community residents, which supported the existence of pathologic and pathophysiologic differences in atherogenesis of intra- and extracranial arteries.
Militant Abolitionism: Douglass, Emerson, and the Rise of the Anti-Slave
Authors: Gougeon Len
Published: November 2012

This essay, relying on a wealth of original sources, reveals for the first time the dynamic and personal relationship that evolved between Fredrick Douglass and Ralph Waldo Emerson from 1844 until the onset of the Civil War as they mounted a militant campaign against the heinous institution of slavery.
Mesoscale Energy Spectra of Moist Baroclinic Waves
Authors: Waite Michael L. , Snyder Chris
Published: November 2012

The role of moist processes in the development of the mesoscale kinetic energy spectrum is investigated with numerical simulations of idealized moist baroclinic waves. Dry baroclinic waves yield upper-tropospheric kinetic energy spectra that resemble a −3 power law. Decomposition into horizontally rotational and divergent kinetic energy shows that the divergent energy has a much shallower spectrum, but its amplitude is too small to yield a characteristic kink in the total spectrum, which is dominated by the rotational part. The inclusion of moist processes energizes the mesoscale. In the upper troposphere, the effect is mainly in the divergent part of the kinetic energy; the spectral slope remains shallow (around −) as in the dry case, but the amplitude increases with increasing humidity. The divergence field in physical space is consistent with inertia–gravity waves being generated in regions of latent heating and propagating throughout the baroclinic wave. Buoyancy flux spectra are used to diagnose the scale at which moist forcing—via buoyant production from latent heating—injects kinetic energy. There is significant input of kinetic energy in the mesoscale, with a peak at scales of around 800 km and a plateau at smaller scales. If the latent heating is artificially set to zero at some time, the enhanced divergent kinetic energy decays over several days toward the level obtained in the dry simulation. The effect of moist forcing of mesoscale kinetic energy presents a challenge for theories of the mesoscale spectrum based on the idealization of a turbulent inertial subrange.
Time Scales of the Trade Wind Boundary Layer Adjustment
Authors: Bellon Gilles , Stevens Bjorn
Published: November 2012

The adjustment of the trade wind atmospheric boundary layer to an abrupt sea surface warming is investigated using a large-eddy simulation (LES) and two simple bulk models: a mixed-layer model (MLM), and a model based on the mixing-line hypothesis (XLM). The near-surface temperature adjusts in a few hours, faster than can be expected from the characteristic time scales associated with the physical processes at play. The near-surface humidity adjusts more slowly, with a time scale of about a day, and it exhibits an initial decrease before increasing to its equilibrium value. An analysis of the MLM suggests that the initial tendency of humidity and temperature results from the difference in Bowen ratios between the equilibrium and the perturbation. An analysis of the three linear modes of the XLM shows that the fastest-decaying mode adjusts the subcloud-layer buoyancy, with a constructive interaction of all of the physical processes. The second-fastest-decaying mode is an adjustment of the boundary layer thermodynamical structure and the slowest mode adjusts the boundary layer depth. Approximate analytical expressions of the time scales characterizing these linear modes are derived both for the MLM and the XLM. The MLM exhibits no scale separation between the fastest and second-fastest time scales and a scale separation between these and the slowest time scale only in the case of a shallow well-mixed boundary layer. The XLM exhibits a scale separation between the buoyancy adjustment of the subcloud layer and the overall thermodynamic adjustment, while conserving the scale separation with the slower adjustment of the boundary layer depth.
Global Observations of Ocean-Bottom Subinertial Current Dissipation
Authors: Wright Corwin J. , Scott Robert B. , Furnival Darran , Ailliot Pierre , Vermet Franck
Published: November 2012

Quadratic bottom boundary layer drag is a potentially significant source of energy dissipation in the deep ocean. This study presents a new estimate of the energy dissipated by this process, using results from the world’s largest archive of ocean current meter time series and focusing strongly upon the potential uncertainties in this calculation. Two methods are used, one based on a simple division of the World Ocean into a series of regular grids and the other based on a more sophisticated analysis using a hierarchical clustering mechanism assisted by estimates from the Hybrid Coordinate Ocean Model (HYCOM) model. From these analyses, the authors estimate a globally integrated bottom boundary layer dissipation of 0.65 ± 0.15 (statistical uncertainty) ± 0.15 (methodological uncertainty) TW.
Ship-Mounted Real-Time Surface Observational System on board Indian Vessels for Validation and Refinement of Model Forcing Fields*
Authors: Harikumar R. , Balakrishnan Nair T. M. , Bhat G. S. , Nayak Shailesh , Reddem Venkat Shesu , Shenoi S. S. C.
Published: November 2012

A network of ship-mounted real-time Automatic Weather Stations integrated with Indian geosynchronous satellites [Indian National Satellites (INSATs)] 3A and 3C, named Indian National Centre for Ocean Information Services Real-Time Automatic Weather Stations (I-RAWS), is established. The purpose of I-RAWS is to measure the surface meteorological–ocean parameters and transmit the data in real time in order to validate and refine the forcing parameters (obtained from different meteorological agencies) of the Indian Ocean Forecasting System (INDOFOS). Preliminary validation and intercomparison of analyzed products obtained from the National Centre for Medium Range Weather Forecasting and the European Centre for Medium-Range Weather Forecasts using the data collected from I-RAWS were carried out. This I-RAWS was mounted on board oceanographic research vessel Sagar Nidhi during a cruise across three oceanic regimes, namely, the tropical Indian Ocean, the extratropical Indian Ocean, and the Southern Ocean. The results obtained from such a validation and intercomparison, and its implications with special reference to the usage of atmospheric model data for forcing ocean model, are discussed in detail. It is noticed that the performance of analysis products from both atmospheric models is similar and good; however, European Centre for Medium-Range Weather Forecasts air temperature over the extratropical Indian Ocean and wind speed in the Southern Ocean are marginally better.
Structure and properties of the polyurethane and polyurethane foam synthesized from castor oil polyols
Authors: Stirna Uldis , Lazdiņa Brigita , Vilsone Dzintra , Lopez Maria J , Vargas-Garcia María del Carmen , Suárez-Estrella Francisca , Moreno Joaquin
Published: November 2012

Polyols were synthesized from castor oil with diethanolamine and triethanolamine at the molar ratios from 1:1 M to 1:3 M with the total hydroxyl value and amino value in the range from 291 to 512 mg KOH/g. Bio-based rigid polyurethane foams with good mechanical properties, a high closed-cell content and the renewable content in the range from 25.0 to 35.6 wt% were obtained. Polyurethane coatings’ tensile strength and modulus of elasticity are higher for the samples obtained from castor oil/diethanolamine polyols, but the highest elongation at break is for the polyurethane from castor oil/triethanolamine polyols. In the temperature range from 150°C to 350°C, the polyurethanes from castor oil/triethanolamine have lower weight losses than the polyurethane from castor oil/diethanolamine polyols. The presence of polyethylene glycol enhances the degradability of the bio-based polyurethane foams in the presence of fungi.
Foams based on poly(ethylene terephthalate) nanocomposites with enhanced thermal stability
Authors: Scamardella Anna Maria , Vietri Umberto , Sorrentino Luigi , Lavorgna Marino , Amendola Eugenio
Published: November 2012

Novel poly(ethylene terephthalate) nanocomposites have been developed, incorporating commercial bottle grade polyester and modified organoclay, which exhibit enhanced thermal and dynamic-mechanical properties and improved foaming behavior. A benefit arising from the use of an organoclay is that this class of material is generally able to withstand the high processing temperatures of engineering polymers, such as poly(ethylene terephthalate), and not undergo decomposition. This offers a great advantage over the use of organic modifiers, whose volatile by-products are known to promote thermal degradation of the polymer matrix under such conditions.

In this work, a novel organoclay was obtained via intercalation of bis-(hydroxyethyl terephthalate) in sodium montmorillonite layers and then used to prepare poly(ethylene terephthalate)-clay nanocomposites via melt compounding by using a twin-screw extruder. Thermogravimetric analysis indicated that the onset decomposition temperatures of poly(ethylene terephthalate) nanocomposites incorporating this organoclay were higher than those of controls based on commercial organoclays. However, the inclusion of this new nanofiller also led to a drastic decrease of melt viscosity, which in turn suppressed foaming. In order to compensate for the effects of the viscosity reduction, pyromellitic dianhydride was used in the reactive extrusion process of poly(ethylene terephthalate) nanocomposites. Rheological analysis showed a strong improvement in viscosity of these poly(ethylene terephthalate)/pyromellitic dianhydride/organoclay nanocomposites, to levels of the same order of magnitude as reference commercial foaming grade poly(ethylene terephthalate), or higher. Samples were foamed using carbon dioxide as physical blowing agent in a batch foaming process. Comparison of sample morphology, performed by scanning electron microscopic analysis, indicated very good results in some samples in terms of cellular morphology and foam density.
Native and cross-linked modified Dioscorea trifida (cush-cush yam) starches as bio-matrices for edible films
Authors: Pérez Elevina , Segovia Xiomara , Tapia María Soledad , Schroeder Mily
Published: November 2012

Native and modified starches from non-conventional sources could be used as raw materials that represent appropriate bio-matrices to support diverse bioactive substances when formulating composite edible films or foams. In order to be used as raw materials, the starch and the starch-based films or foams obtained have to be characterized. The goals of this study were first, to isolate the starch from the edible portion of Dioscorea trifida, a sub-utilized agricultural commodity of the Venezuelan Amazons; second, to modify by cross-linking the native starch already isolated with sodium trimetaphosphate; third, to produce edible films with both the native and modified starches; and finally to characterize both while comparing their functional properties and proposing them to be utilized to produce foams . The bio-matrices represented by native and modified starches were used to formulate films with 5% of D. trifida starch and 1.5% glycerol. A native D. trifida starch with high purity was obtained, as well as a cross-linked modified starch with a 0.002% of degree of substitution. Significant statistical differences in the film thickness, color profile, deformation, and stress to puncture were found in both types of films. The modified starch-based films exhibited higher width and opalescence than those formed with native starch. The water vapor permeability, water retention, and water solubility differed also between both bio-matrices. The results suggested, in spite of these differences, that both of them could be proposed for gasification in order to obtain foams.