bluuebunny/crossref_metadata_2025 huggingface dataset:
7-Day Nonbismuth-Containing Concomitant Therapy Achieves a High Eradication Rate forHelicobacter pyloriin Taiwan
Authors: Kao Sung-Shuo , Chen Wen-Chi , Hsu Ping-I , Lai Kwok-Hung , Yu Hsien-Chung , Cheng Hui-Hwa , Peng Nan-Jing , Lin Chiun-Ku , Chan Hoi-Hung , Tsai Wei-Lun , Wang Huay-Min , Tsai Tzung-Jiun , Lin Kung-Hung , Tsay Feng-Woei
Published: July 2012

Background.Ten-day concomitant therapy achieves a high eradication rate in Taiwan. Whether shortening the duration of concomitant therapy can still keep a high eradication rate remains unclear.Aim.To assess the eradication rate of 7-day pantoprazole-containing concomitant therapy in Taiwan and to investigate factors influencing the eradication outcome.Methods.From March 2008 to March 2012, 319H. pylori-infected patients receiving a 7-day pantoprazole-containing concomitant regimen (pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days) were included. Patients were asked to return at the second week to assess drug compliance and adverse effects. Repeated endoscopy or urea breath test was performed at 8 weeks after the end of eradication therapy.Results.The eradication rates according to intention-to-treat and per-protocol analyses were 93.7% (299/319) and 96.4% (297/308), respectively. Adverse events occurred in 13.2% (42/319) of the patients. The compliance rate was 98.4% (314/319). Multivariate analysis disclosed that poor compliance was the only independent factor influencing the efficacy of anti-H. pyloritherapy with an odds ratio of 0.073 (95% confidence interval, 0.011–0.483).Conclusion.7-day concomitant therapy achieved a very high eradication rate forH. pyloriinfection in Taiwan. Drug compliance was the only clinical factor influencing treatment efficacy.
The Faint Young Sun Paradox: A Simplified Thermodynamic Approach
Authors: Angulo-Brown F. , Rosales Marco A. , Barranco-Jiménez M. A.
Published: July 2012

Classical models of the Sun suggest that the energy output in the early stage of its evolution was 30 percent less than today. In this context, radiative balance alone between The Sun and the Earth was not sufficient to explain the early presence of liquid water on Earth’s surface. This difficulty is called the faint young Sun paradox. Many proposals have been published to solve this paradox. In the present work, we propose an oversimplified finite-time thermodynamic approach that describes the air convective cells in the Earth atmosphere. This model introduces two atmospheric modes of thermodynamic performance: a first mode consisting in the maximization of the power output of the convective cells (maximum power regime) and a second mode that consists in maximizing a functional representing a good trade-off between power output and entropy production (the ecological regime). Within the assumptions of this oversimplified model, we present different scenarios of albedo and greenhouse effects that seem realistic to preserve liquid water on the Earth in the early stage of formation.
Role of Peroxisome Proliferator-Activated Receptor-γin Vascular Inflammation
Authors: Ohshima Kousei , Mogi Masaki , Horiuchi Masatsugu
Published: July 2012

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γactivation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γactivation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γinvolvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.
Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies
Authors: McDaniel Jessica M. , Pinilla-Ibarz Javier , Epling-Burnette P. K.
Published: July 2012

The immunomodulatory agent, lenalidomide, is a structural analogue of thalidomide approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS) and multiple myeloma (MM). This agent is also currently under active investigation for the treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL), as well as in drug combinations for some solid tumors and mantle cell lymphoma (MCL). Although treatment with lenalidomide has translated into a significant extension in overall survival in MM and MDS and has superior safety and efficacy relative to thalidomide, the mechanism of action as it relates to immune modulation remains elusive. Based on preclinical models and clinical trials, lenalidomide, as well as other structural thalidomide derivatives, enhances the proliferative and functional capacity of T-lymphocytes and amplifies costimulatory signaling pathways that activate effector responses and suppress inflammation. This paper summarizes our current understanding of T- and natural killer (NK) cell pathways that are modified by lenalidomide in hematopoietic neoplasms to inform future decisions about potential combination therapies.
Oral Iron Prophylaxis in Pregnancy: Not Too Little and Not Too Much!
Authors: Milman Nils
Published: July 2012

An adequate supply of iron is essential for normal development of the fetus and newborn child. Iron deficiency and iron deficiency anemia (IDA) during pregnancy increase the risk of preterm birth and low birth weight. Iron is important for development of the fetal brain and cognitive abilities of the newborn. Children born to iron-deficient mothers will start their lives suffering from iron deficiency or even IDA. Oral iron prophylaxis to pregnant women improves iron status and prevents development of IDA. The Danish National Board of Health has since 1992 recommended prophylactic oral iron supplements to all pregnant women and the currently advocated dose is 40–50 mg ferrous iron taken between meals from 10 weeks gestation to delivery. However, 30–40 mg ferrous iron is probably an adequate dose in most affluent societies. In developed countries, individual iron prophylaxis guided by iron status (serum ferritin) has physiological advantages compared to general iron prophylaxis. In contrast, in most developing countries, general iron prophylaxis is indicated, and higher doses of oral iron, for example, 60 mg ferrous iron or even more should be recommended, according to the present iron status situation in the specific populations of women of fertile age and pregnant women.
Oral Lichenoid Contact Lesions to Mercury and Dental Amalgam—A Review
Authors: McParland Helen , Warnakulasuriya Saman
Published: July 2012

Human oral mucosa is subjected to many noxious stimuli. One of these substances, in those who have restorations, is dental amalgam which contains mercury. This paper focuses on the local toxic effects of amalgam and mercury from dental restorations. Components of amalgam may, in rare instances, cause local side effects or allergic reactions referred to as oral lichenoid lesions (OLLs). OLLs to amalgams are recognised as hypersensitivity reactions to low-level mercury exposure. The use of patch testing to identify those susceptible from OLL is explored, and recommendations for removing amalgam fillings, when indicated are outlined. We conclude that evidence does not show that exposure to mercury from amalgam restorations poses a serious health risk in humans, except for an exceedingly small number of hypersensitivity reactions that are discussed.
Supernumerary Teeth in Primary Dentition and Early Intervention: A Series of Case Reports
Authors: Bahadure Rakesh N. , Thosar Nilima , Jain Eesha S. , Kharabe Vidhi , Gaikwad Rahul
Published: July 2012

Supernumerary teeth are considered as one of the most significant dental anomalies during the primary and early mixed dentition stages. They are of great concern to the dentists and parents because of the eruption, occlusal, and esthetic problems they can cause. Supernumerary teeth occur more frequently in the permanent dentition but rarely in primary dentition. Mesiodens is the most common type of supernumerary teeth but rarely seen in lower arch. Early recognition and diagnosis of supernumerary teeth is important to prevent further complications in permanent dentition. Four cases of supernumerary teeth with mesiodens in upper and lower arch in primary dentition and their management have been discussed.
Porous Biodegradable Metals for Hard Tissue Scaffolds: A Review
Authors: Yusop A. H. , Bakir A. A. , Shaharom N. A. , Abdul Kadir M. R. , Hermawan H.
Published: July 2012

Scaffolds have been utilized in tissue regeneration to facilitate the formation and maturation of new tissues or organs where a balance between temporary mechanical support and mass transport (degradation and cell growth) is ideally achieved. Polymers have been widely chosen as tissue scaffolding material having a good combination of biodegradability, biocompatibility, and porous structure. Metals that can degrade in physiological environment, namely, biodegradable metals, are proposed as potential materials for hard tissue scaffolding where biodegradable polymers are often considered as having poor mechanical properties. Biodegradable metal scaffolds have showed interesting mechanical property that was close to that of human bone with tailored degradation behaviour. The current promising fabrication technique for making scaffolds, such as computation-aided solid free-form method, can be easily applied to metals. With further optimization in topologically ordered porosity design exploiting material property and fabrication technique, porous biodegradable metals could be the potential materials for making hard tissue scaffolds.
p16, Cyclin D1, and HIF-1αPredict Outcomes of Patients with Oropharyngeal Squamous Cell Carcinoma Treated with Definitive Intensity-Modulated Radiation Therapy
Authors: Rahimi Asal S. , Wilson David D. , Saylor Drew K. , Stelow Edward B. , Thomas Christopher Y. , Reibel James F. , Levine Paul A. , Shonka David C. , Jameson Mark J. , Read Paul W.
Published: July 2012

We evaluated a panel of 8 immunohistochemical biomarkers as predictors of clinical response to definitive intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma (OPSCC). 106 patients with OPSCC were treated to a total dose of 66–70 Gy and retrospectively analyzed for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). All tumors had p16 immunohistochemical staining, and 101 tumors also had epidermal growth factor receptor (EGFR) staining. 53% of the patients had sufficient archived pathologic specimens for incorporation into a tissue microarray for immunohistochemical analysis for cyclophilin B, cyclin D1, p21, hypoxia-inducible factor-1α(HIF-1α), carbonic anhydrase, and major vault protein. Median followup was 27.2 months. 66% of the tumors were p16 positive, and 34% were p16 negative. On univariate analysis, the following correlations were statistically significant: p16 positive staining with higher LRC (P=0.005) and longer DFS (P<0.001); cyclin D1 positive staining with lower LRC (P=0.033) and shorter DFS (P=0.002); HIF-1αpositive staining with shorter DFS (P=0.039). On multivariate analysis, p16 was the only significant independent predictor of DFS (P=0.023). After immunohistochemical examination of a panel of 8 biomarkers, our study could only verify p16 as an independent prognostic factor in OPSCC.
The Influence of Na and Ti on theIn VitroDegradation and Bioactivity in 58S Sol-Gel Bioactive Glass
Authors: Ni Shirong , Du Ruilin , Ni Siyu
Published: July 2012

The aim of this study was to investigate the effect of Na and Ti on thein vitrodegradation and bioactivity in the 58S bioactive glass. The degradation was evaluated through the activation energy of Si ion release from bioactive glasses and the weight loss of bioactive glasses in Tris-HCl buffer solution. Thein vitrobioactivity of the bioactive glasses was investigated by analysis of apatite-formation ability in the simulated body fluid (SBF). The results showed that Na in the 58S glass accelerated the dissolution rate of the glass, whereas Ti in the 58S glass slowed down the rate of glass solubility. Bioactivity tests showed that Na in glass increased the apatite-forming ability in SBF. In contrast, Ti in glass retards the apatite formation at the initial stage of SBF soaking but does not affect the growth of apatite after long periods of soaking.
Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port
Authors: Sugarbaker Paul H. , Bijelic Lana
Published: July 2012

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.
Comparison of the Effects on Rib Fracture between the Traditional Japanese Medicine Jidabokuippo and Nonsteroidal Anti-Inflammatory Drugs: A Randomized Controlled Trial
Authors: Nakae Hajime , Yokoi Aya , Kodama Hiroyuki , Horikawa Akira
Published: July 2012

Jidabokuippo is a traditional Japanese medicine used for contusion-induced swelling and pain. This open multicenter randomized study was designed to compare the efficacies of jidabokuippo and nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rib fracture by analyzing the treatment duration. Our study involved 170 rib fracture patients capable of oral ingestion divided randomly into 2 groups: the jidabokuippo and NSAID groups. We compared the duration of treatment and healthcare expenditure between these 2 groups. Medication was continued in both groups until the visual analogue scale score decreased to less than 50% of the pretreatment score. We excluded the patients in whom medication was prematurely discontinued. We analyzed 81 patients belonging to the jidabokuippo and NSAIDs groups. No significant intergroup differences were observed in age, gender, severity (injury severity score), and presence/absence of underlying disease. The treatment duration was significantly shorter in the jidabokuippo group than in the NSAIDs group (P=0.0003). Healthcare expenditure was significantly lower in the jidabokuippo group than in the NSAIDs group (P<0.0001). Our results suggest that compared to NSAIDs, jidabokuippo can shorten the duration of treatment in patients with rib fracture and is a promising analgesic agent based on the medical economic viewpoint.
Cervical Cytopathology in a Population of HIV-Positive and HIV-Negative Women
Authors: de Lemos Patrícia Abreu Pinheiro , García-Zapata Marco Túlio Antonio , Tavares Suelene Brito do Nascimento
Published: July 2012

The association between abnormal cervical cytology and HIV infection status in women was evaluated to correlate with CD4 cell count and viral load in HIV-positive patients with the presence of low-grade (LSIL) and high-grade squamous intraepithelial lesion (HSIL). Cervical samples were collected at the Tropical Disease Hospital, Maternal and Child Healthcare Hospital and at theNascer CidadãoMaternity Hospital in Goiânia, Goiás, Brazil. An Ayre’s spatula was used to collect samples from the ectocervix and a cytology brush to collect samples from the endocervix. Of a total of 237 women, 125 were HIV positive and 112 were HIV negative. Abnormal cytology (; 8.9%) was more common in the HIV positive group (; 12.1%) compared to the HIV-negative group (; 5.4%) (). Cytological abnormalities were not found to be associated with immunosuppression, defined as CD4 count < 200 cells/mm3. A higher frequency was found between higher viral loads (>10,000/mm3) and the presence of abnormal cytology. Pregnant women, irrespective of whether they were HIV positive or negative, were less likely to have lesions compared to the nonpregnant women in the same groups. The higher frequency of abnormal findings in Papanicolaou cytology in HIV-positive women with higher viral loads suggests the association between preinvasive cervical lesions and human immunodeficiency.
PCA-1/ALKBH3 Contributes to Pancreatic Cancer by Supporting Apoptotic Resistance and Angiogenesis
Authors: Yamato Ichiro , Sho Masayuki , Shimada Keiji , Hotta Kiyohiko , Ueda Yuko , Yasuda Satoshi , Shigi Naoko , Konishi Noboru , Tsujikawa Kazutake , Nakajima Yoshiyuki
Published: July 2012

The PCA-1/ALKBH3 gene implicated in DNA repair is expressed in several human malignancies but its precise contributions to cancer remain mainly unknown. In this study, we have determined its functions and clinical importance in pancreatic cancer. PCA-1/ALKBH3 functions in proliferation, apoptosis and angiogenesis were evaluated in human pancreatic cancer cells in vitro and in vivo. Further, PCA-1/ALKBH3 expression in 116 patients with pancreatic cancer was evaluated by immunohistochemistry. siRNA-mediated silencing of PCA-1/ALKBH3 expression induced apoptosis and suppressed cell proliferation. Conversely, overexpression of PCA-1/ALKBH3 increased anchorage-independent growth and invasiveness. In addition, PCA-1/ALKBH3 silencing downregulated VEGF expression and inhibited angiogenesis in vivo. Furthermore, immunohistochemical analysis showed that PCA-1/ALKBH3 expression was abundant in pancreatic cancer tissues, where it correlated with advanced tumor status, pathological stage and VEGF intensity. Importantly, patients with low positivity of PCA-1/ALKBH3 expression had improved postoperative prognosis compared with those with high positivity. Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer with potential utility as a therapeutic target in this fatal disease. Cancer Res; 72(18); 4829–39. ©2012 AACR.
Activation of Robo1 Signaling of Breast Cancer Cells by Slit2 from Stromal Fibroblast Restrains Tumorigenesis via Blocking PI3K/Akt/β-Catenin Pathway
Authors: Chang Po-Hao , Hwang-Verslues Wendy W. , Chang Yi-Cheng , Chen Chun-Chin , Hsiao Michael , Jeng Yung-Ming , Chang King-Jen , Lee Eva Y.-H.P. , Shew Jin-Yuh , Lee Wen-Hwa
Published: July 2012

Tumor microenvironment plays a critical role in regulating tumor progression by secreting factors that mediate cancer cell growth. Stromal fibroblasts can promote tumor growth through paracrine factors; however, restraint of malignant carcinoma progression by the microenvironment also has been observed. The mechanisms that underlie this paradox remain unknown. Here, we report that the tumorigenic potential of breast cancer cells is determined by an interaction between the Robo1 receptor and its ligand Slit2, which is secreted by stromal fibroblasts. The presence of an active Slit2/Robo1 signal blocks the translocation of β-catenin into nucleus, leading to downregulation of c-myc and cyclin D1 via the phosphoinositide 3-kinase (PI3K)/Akt pathway. Clinically, high Robo1 expression in the breast cancer cells correlates with increased survival in patients with breast cancer, and low Slit2 expression in the stromal fibroblasts is associated with lymph node metastasis. Together, our findings explain how a specific tumor microenvironment can restrain a given type of cancer cell from progression and show that both stromal fibroblasts and tumor cell heterogeneity affect breast cancer outcomes. Cancer Res; 72(18); 4652–61. ©2012 AACR.
Changing the Tumor Microenvironment: New Strategies for Immunotherapy
Authors: Berraondo Pedro , Umansky Viktor , Melero Ignacio
Published: July 2012

Solid tumors are composed of malignant cells surrounded by a tumor-conditioned stroma that contains extracellular matrix and a variety of nonmalignant populations, including myeloid cells, lymphocytes, fibroblasts, and endothelial cells. These stromal elements form a local immunoregulatory network that must be overcome to achieve eradication of established tumors by immunotherapy. On March 21–22, 2012, a symposium was held in Pamplona, Spain, to share the recent advances regarding the molecules and cells that create and sustain this immune-hostile tumor microenvironment. Excellent targets for immunotherapeutic intervention were identified, and a number of therapeutic strategies under translation from mouse to human were presented. Cancer Res; 72(20); 5159–64. ©2012 AACR.
Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer
Authors: Julien Sylvia , Merino-Trigo Ana , Lacroix Ludovic , Pocard Marc , Goéré Diane , Mariani Pascale , Landron Sophie , Bigot Ludovic , Nemati Fariba , Dartigues Peggy , Weiswald Louis-Bastien , Lantuas Denis , Morgand Loïc , Pham Emmanuel , Gonin Patrick , Dangles-Marie Virginie , Job Bastien , Dessen Philippe , Bruno Alain , Pierré Alain , De Thé Hugues , Soliman Hany , Nunes Manoel , Lardier Guillaume , Calvet Loreley , Demers Brigitte , Prévost Grégoire , Vrignaud Patricia , Roman-Roman Sergio , Duchamp Olivier , Berthet Cyril
Published: July 2012

Purpose: Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and advanced preclinical models. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer (CRC) models.

Experimental Design: From the 85 unsupervised surgical colorectal samples collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinoses and 14 metastases. Histologic and molecular characterization of patient tumors, first and late passages on mice includes the sequence of key genes involved in CRC (i.e., APC, KRAS, TP53), aCGH, and transcriptomic analysis.

Results: This comprehensive characterization shows that our collection recapitulates the clinical situation about the histopathology and molecular diversity of CRC. Moreover, patient tumors and corresponding models are clustering together allowing comparison studies between clinical and preclinical data. Hence, we conducted pharmacologic monotherapy studies with standard of care for CRC (5-fluorouracil, oxaliplatin, irinotecan, and cetuximab). Through this extensive in vivo analysis, we have shown the loss of human stroma cells after engraftment, observed a metastatic phenotype in some models, and finally compared the molecular profile with the drug sensitivity of each tumor model. Through an experimental cetuximab phase II trial, we confirmed the key role of KRAS mutation in cetuximab resistance.

Conclusions: This new collection could bring benefit to evaluate novel targeted therapeutic strategies and to better understand the basis for sensitivity or resistance of tumors from individual patients. Clin Cancer Res; 18(19); 5314–28. ©2012 AACR.
CpG Island Methylator Phenotype–Positive Tumors in the Absence ofMLH1Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis
Authors: Fu Tao , Pappou Emmanouil P. , Guzzetta Angela A. , Jeschke Jana , Kwak Ruby , Dave Pujan , Hooker Craig M. , Morgan Richard , Baylin Stephen B. , Iacobuzio-Donahue Christine A. , Wolfgang Christopher L. , Ahuja Nita
Published: July 2012

Purpose: Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis.

Experimental Design: Demographics, tumor characteristics, and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation, and CpG island methylator phenotype (CIMP) status was conducted. A Cox proportional hazard model was built to predict survival.

Results: CIMP+ was detected in 27 of 99 (27.3%) duodenal adenocarcinomas and was associated with MSI (P = 0.011) and MLH1 methylation (P < 0.001), but not with KRAS mutations (P = 0.114), as compared with CIMP− tumors. No BRAF V600E mutation was detected. Among the CIMP+ tumors, 15 (55.6%) were CIMP+/MLH1-unmethylated (MLH1-U). Kaplan–Meier analysis showed that tumors classified by CIMP, CIMP/MLH1 methylation status, or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), whereas CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value in both OS (P < 0.001) and TTR (P = 0.023). Patients with CIMP+/MLH1-U tumors had the worst OS and TTR.

Conclusions: Our results showed existence of CIMP in duodenal adenocarcinomas. The combination of CIMP+/MLH1-U seems to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI, or CIMP development. Clin Cancer Res; 18(17); 4743–52. ©2012 AACR.
Cilostazol-Based Triple Antiplatelet Therapy Compared to Dual Antiplatelet Therapy in Patients with Coronary Stent Implantation: A Meta-Analysis of 5,821 Patients
Authors: Geng Deng-feng , Liu Mo , Jin Dong-mei , Wu Wei , Deng Jing , Wang Jing-feng
Published: July 2012

Background: Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. Methods: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. Results: Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. Conclusion: Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.
A Meta-Analysis of Randomized Controlled Trials Appraising the Efficacy and Safety of Cilostazol after Coronary Artery Stent Implantation
Authors: Jang Jae-Sik , Jin Han-Young , Seo Jeong-Sook , Yang Tae-Hyun , Kim Dae-Kyeong , Kim Dong-Soo , Kim Dong-Kie , Seol Sang-Hoon , Kim Doo-Il , Cho Kyoung-Im , Kim Bo-Hyun , Park Yong Hyun , Je Hyung-Gon , Jeong Young-Hoon , Kim Won-Jang , Lee Jong-Young , Lee Seung-Whan
Published: July 2012

Objectives: To evaluate the impact of cilostazol on the angiographic and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) with stents and treated with aspirin and thienopyridine. Methods: A total of 11 randomized controlled trials including 8,525 patients comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included in the analysis. The primary end points were in-segment late loss and angiographic restenosis at angiographic follow-up. Secondary end points included mortality, stent thrombosis, target lesion revascularization (TLR) and major adverse cardiac events (MACE). Results: Triple antiplatelet therapy was associated with a significant reduction in late loss [weighted mean difference 0.14, 95% confidence interval (CI) 0.08–0.20; p < 0.001] and angiographic restenosis [odds ratio (OR) 0.58, 95% CI 0.48–0.71; p < 0.001]. Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.56, 95% CI 0.41–0.77; p < 0.001) and MACE (OR 0.72, 95% CI 0.60–0.86; p < 0.001) with no differences in mortality (p = 0.29), stent thrombosis (p = 0.60) or bleeding episodes (p = 0.77). Conclusions: Cilostazol in addition to dual antiplatelet therapy appears to be effective in reducing the risk of restenosis and repeat revascularization after PCI without any significant benefits for mortality or stent thrombosis.
Increased Shedding of Microvesicles from Intimal Smooth Muscle Cells in Athero-Prone Areas of the Human Aorta: Implications for Understanding of the Predisease Stage
Authors: Bobryshev Yuri V. , Killingsworth Murray C. , Orekhov Alexander N.
Published: July 2012

Objective: This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage. Methods: Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta. Results: The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001). Conclusion: The present study supports the concept that alterations of the arterial intima occur at the predisease stage.
Expression Profiling of Breast Tumors Based on Human Epidermal Growth Factor Receptor 2 Status Defines Migration-Related Genes
Authors: Cuadros M. , Cano C. , López F.J. , López-Castro R. , Concha A.
Published: July 2012

Objective: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative breast cancer tumors remain unclear. The aim of this study was to identify a gene expression profile for breast tumors based on their HER2 status. Methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, other genes located on 17q12 and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomic profiling to shed light on the molecular knowledge of HER2-positive breast tumors.
A Novel Transdermal Fomulation of 18β-Glycyrrhetic Acid with Lysine for Improving Bioavailability and Efficacy
Authors: Li S. , Qiu Y.Q. , Zhang S.H. , Gao Y.H.
Published: July 2012

The aim of this study was to develop a novel topical liposomal system entrapping 18β-glycyrrhetic acid (GA) for the treatment of chronic allergic dermatitis. A novel liposomal system with molar ratios of GA to lysine from 1:1 to 1:3 was prepared by high-pressure homogenization. The liposomes at the optimized molar ratio of GA to lysine of 1:2 significantly improved GA loading (1.2%) and penetration in vitro. Liposomal gels containing GA 0.3, 0.6 and 0.9% were prepared to investigate the dosage effect on transdermal delivery and anti-inflammatory activity. In vivo pharmacokinetic studies were carried out by nonocclusive application of GA liposomal gels to ICR mouse ears. GA concentrations in skin and plasma increased proportionally with dose over the dose range of 0.3–0.9%. A 2,4-dinitrofluorobenzene-induced contact dermatitis mouse model was made up to evaluate the pharmacodynamics of GA liposomal gels. The liposomal gel with GA 0.9% showed a stronger anti-inflammatory activity than triamcinolone acetonide and econazole nitrate cream, while few side effects were observed in the present model. The topical administration of gel containing novel elastic liposomes of GA was safe and effective in the treatment of chronic allergic dermatitis.
Cone Beam CT Evaluation of Maxillary Sinus Septa Prevalence, Height, Location and Morphology in Children and an Adult Population
Authors: Orhan Kaan , Kusakci Seker Basak , Aksoy Seçil , Bayindir Hakan , Berberoğlu Atilla , Seker Emre
Published: July 2012

Objective: The purpose of this study was to determine the prevalence, height, location and morphology of maxillary sinus septa in dentate, partially dentate and edentulous adults as well as in mixed dentition children using cone beam computed tomography (CBCT) for maxillary sinus surgical interventions. Subjects and Methods: Five hundred and fifty-four sides in the CBCT scans of 272 patients (30 children and 242 adults) were retrospectively analyzed. The prevalence, location and morphology were assessed in axial, sagittal, cross-sectional and panoramic 3-dimensional images. The height of septa was measured with the angle between the direction of the septum and median palatine suture. The differences among age, localization and measurements were statistically analyzed. Results: The prevalence of maxillary sinus segments with septa was 58%. There were a total of 13 (3.2%) septa of completely edentulous (CE), 198 (53.9%) septa of edentate and 14 (3.8%) septa of the mixed dentition maxillary segments. The location of septa observed in all study groups demonstrated a greater prevalence (69.1%) in the middle region than in the anterior and posterior regions. No statistically significant differences were observed with regard to gender or age, for septum height (p > 0.05). However, maxillary sinus septa are higher in partially edentulous patients than edentate and CE ones (p < 0.05). Conclusion: Septa of various heights and courses developed in all parts of the maxillary sinus, therefore to prevent possible complications during sinus surgery, extensive evaluation with an appropriate radiographic technique was indispensable.
Newly Isolated and Characterized Bacteria with Great Application Potential for Decomposition of Lignocellulosic Biomass
Authors: Maki Miranda L. , Idrees Amna , Leung Kam Tin , Qin Wensheng
Published: July 2012

This study focuses on the isolation and characterization of bacteria from municipal waste and peat to determine those bacteria with good potential for modification and decomposition of lignocellulosic biomass for industrial application. Twenty cellulase-producing bacteria belonging to four major phyla – Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes – were found when screened on carboxymethyl cellulose-containing agar. Six isolates also exhibited activities towards filter paper as the sole carbon source in salt media, while 12 exhibited activities towards xylan when screened on xylan-containing plates. Moreover, 5 isolates survived in and increased the absorbance of 1% black liquor in salt media by an average of 2.07-fold after 21 days of incubation. Similarly, these 5 isolates increased the absorbance of 0.1% pure lignin at 280 nm in salt media, indicating modification of lignin. Additionally, the Fourier transform infrared spectroscopy analysis of 1% barley straw treated for 21 days with these 5 strains showed a preference for consumption of hemicelluloses over lignin; however, a change in lignin was observed. A Bacillus strain (55S5) and a Pseudomonas strain (AS1) displayed the greatest potential for lignocellulose decomposition due to a variety of cellulase activities, as well as xylanase activity and modification of lignin. Several of these isolates have good potential for industrial use in the degradation of lignocellulosic biomass.
Observational Study Mortality in Treated Primary Aldosteronism
Authors: Reincke Martin , Fischer Evelyn , Gerum Sabine , Merkle Katrin , Schulz Sebastian , Pallauf Anna , Quinkler Marcus , Hanslik Gregor , Lang Katharina , Hahner Stefanie , Allolio Bruno , Meisinger Christa , Holle Rolf , Beuschlein Felix , Bidlingmaier Martin , Endres Stephan
Published: July 2012

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (
P
value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03–1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04–12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07–6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17–0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls;
P
<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.
The Persistent Cold-Air Pool Study
Authors: Lareau Neil P. , Crosman Erik , Whiteman C. David , Horel John D. , Hoch Sebastian W. , Brown William O. J. , Horst Thomas W.
Published: July 2012

The Persistent Cold-Air Pool Study (PCAPS) was conducted in Utah's Salt Lake valley from 1 December 2010 to 7 February 2011. The field campaign's primary goal was to improve understanding of the physical processes governing the evolution of multiday cold-air pools (CAPs) that are common in mountain basins during the winter. Meteorological instrumentation deployed throughout the Salt Lake valley provided observations of the processes contributing to the formation, maintenance, and destruction of 10 persistent CAP episodes. The close proximity of PCAPS field sites to residences and the University of Utah campus allowed many undergraduate and graduate students to participate in the study.

Ongoing research, supported by the National Science Foundation, is using the PCAPS dataset to examine CAP evolution. Preliminary analyses reveal that variations in CAP thermodynamic structure are attributable to a multitude of physical processes affecting local static stability: for example, synoptic-scale processes impact changes in temperatures and cloudiness aloft while variations in boundary layer forcing modulate the lower levels of CAPs. During episodes of strong winds, complex interactions between the synoptic and mesoscale f lows, local thermodynamic structure, and terrain lead to both partial and complete removal of CAPs. In addition, the strength and duration of CAP events affect the local concentrations of pollutants such as PM2.5.
World Meteorological Organization Assessment of the Purported World Record 58°C Temperature Extreme at El Azizia, Libya (13 September 1922)
Authors: El Fadli Khalid I. , Cerveny Randall S. , Burt Christopher C. , Eden Philip , Parker David , Brunet Manola , Peterson Thomas C. , Mordacchini Gianpaolo , Pelino Vinicio , Bessemoulin Pierre , Stella José Luis , Driouech Fatima , Wahab M. M Abdel , Pace Matthew B.
Published: July 2012

On 13 September 1922, a temperature of 58°C (136.4°F) was purportedly recorded at El Azizia (approximately 40 km south-southwest of Tripoli) in what is now modern-day Libya. That temperature record of 58°C has been cited by numerous world-record sources as the highest recorded temperature for the planet. During 2010–11, a World Meteorological Organization (WMO) Commission of Climatology (CCl) special international panel of meteorological experts conducted an in-depth investigation of this record temperature for the WMO World Archive of Weather and Climate Extremes (http://wmo.asu.edu/). This committee identified five major concerns with the 1922 El Azizia temperature extreme record, specifically 1) potentially problematical instrumentation, 2) a probable new and inexperienced observer at the time of observation, 3) unrepresentative microclimate of the observation site, 4) poor correspondence of the extreme to other locations, and 5) poor comparison to subsequent temperature values recorded at the site. Based on these concerns, the WMO World Archive of Weather and Climate Extremes rejected this temperature extreme of 58°C as the highest temperature officially recorded on the planet. The WMO assessment is that the highest recorded surface temperature of 56.7°C (134°F) was measured on 10 July 1913 at Greenland Ranch (Death Valley), California.
The ε4 Allele of the APOE Gene Is Associated With More Severe Peripheral Neuropathy in Type 2 Diabetic Patients
Authors: Monastiriotis C. , Papanas N. , Trypsianis G. , Karanikola K. , Veletza S. , Maltezos E.
Published: July 2012

We examined the association between the ∊4 allele of the apolipoprotein E gene and severity of peripheral neuropathy in 234 patients with type 2 diabetes mellitus (T2DM). Based on the Neuropathy Disability Score (NDS), patients were divided into group A (NDS ≤6: mild or no neuropathy) and group B (NDS >6: severe neuropathy). In each group, patients were further divided into ∊4 carriers and non-∊4 carriers. In multivariate analysis, a more than 5-fold increased risk of severe neuropathy was associated with ∊4 carrier status (adjusted odds ratio [aOR]: 5.26, 95% confidence interval [CI]: 2.24-12.31, P = .0001). The other significant risk factors for severe neuropathy included male gender (aOR: 2.08, 95% CI: 1.05-4.14, P = .036), diabetes duration (aOR: 1.05, 95% CI: 1.00-1.09, P = .039), and hemoglobin A1c (aOR: 1.32, 95% CI: 1.05-1.66, P = .020). In conclusion, the ∊4 carrier status appears to be associated with severe peripheral neuropathy in T2DM.
Historical Invariance in Delinquency Causation
Authors: Johnson Matthew C. , Morris Robert G. , Menard Scott
Published: July 2012

To date, research on multigenerational aspects of delinquency has been devoted to transmission from parents to offspring, largely ignoring long-term invariance of criminological theories. This study uses multigenerational data from the most recent waves of the National Youth Survey Family Study to test a general model of delinquency across two samples of adolescents of similar ages, separated by more than 25 years. Original respondents were compared with their adolescent offspring using identical models based on a partial general strain approach. Direct and indirect effects of strains on delinquency were generally consistent across generations. The discussion of the findings centers on general theoretical and methodological issues associated with a relatively unexplored avenue for understanding crime and delinquency.
‘With a Heavy Heart’: Ethics, Emotions and Rationality in Norwegian Immigration Administration
Authors: Eggebø Helga
Published: July 2012

This article analyses decision-making processes concerning applications for family immigration to Norway by giving an account of the dilemmas and challenges faced by the employees of the Norwegian immigration administration. I argue that these civil servants negotiate two somewhat different ethical principles where the foundation for ethical conduct is either emotion or reason. The article investigates the ethical potential of bureaucracy and aims to contribute to sociological debates about ethics, emotion and rationality.
‘They’re Gonna Think it Now’: Narratives of Shame in the Sexual Health Experiences of Young People
Authors: Fallon Debbie
Published: July 2012

This article explores how shame operated for a group of young females who accessed emergency contraception (EC) following either contraceptive failure or unprotected sex. Accessing EC invoked anticipated judgements and feelings of shame that made them feel out of place – even in youth friendly environments, and this compelled many of them to avoid seeking much needed support. The article explores this issue, highlighting how the complex relationships that young people have with adults around them is often overlooked, and particularly the idea that they may be ‘shamers’ who unwitting evoke feelings of shame, troubling the notion that it is poor relationships that drive young people to avoid communicating with parents about sexual health matters. This has implications for healthcare practice, not least because current approaches suggest that the involvement of parents and the development of a better rapport with service providers may be the key to reducing teenage pregnancy rates.