bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum Dot-Loaded Liposomes to Evaluate the Behavior of Drug Carriers after Oral Administration
Authors: Tahara Kohei , Fujimoto Shiho , Fujii Fumihiko , Tozuka Yuichi , Jin Takashi , Takeuchi Hirofumi
Published: July 2013

We have developed submicron-sized liposomes modified with a mucoadhesive polymer to enhance peptide drug absorption after oral administration. Liposomal behavior in the gastrointestinal tract is a critical factor for effective peptide drug delivery. The purpose of this study was to prepare quantum dot- (QD-) loaded submicron-sized liposomes and examine liposomal behavior in the body after oral administration using in vivo fluorescence imaging. Two types of CdSe/CdZnS QDs with different surface properties were used: hydrophobic (unmodified) QDs and hydrophilic QDs with glutathione (GSH) surface modifications. QD- and GSH-QD-loaded liposomes were prepared by a thin film hydration method. Transmission electron microscopy revealed that QDs were embedded in the liposomal lipid bilayer. Conversely, GSH-QDs were present in the inner aqueous phase. Some of the GSH-QDs were electrostatically associated with the lipid membrane of stearylamine-bearing cationic liposomes. QD-loaded liposomes were detected in Caco-2 cells after exposure to the liposomes, and these liposomes were not toxic to the Caco-2 cells. Furthermore, we evaluated the in vivo bioadhesion and intestinal penetration of orally administered QD-loaded liposomes by observing the intestinal segment using confocal laser scanning microscopy.
Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst ofHelicobacter pylori-Stimulated Neutrophil
Authors: Bonacorsi Cibele , da Fonseca Luiz Marcos , Raddi Maria Stella Gonçalves , Kitagawa Rodrigo Rezende , Vilegas Wagner
Published: July 2013

Ten Brazilian medicinal plants used to treat gastritis and ulcers were carefully selected on the basis of ethnopharmacological importance and antiulcerogenic activity previously described. The antioxidant activity of the methanolic extracts was determined in analysis conditions that simulate a real biological activity on inhibition of the oxidative burst induced in neutrophils usingHelicobacter pylorias activator, by a luminol-amplified chemiluminescence assay. The extracts, at low concentration (5 μg/mL), exhibited a large variation in inhibitory effects ofH. pylori-induced oxidative burst ranging from 48% inhibition to inactive, but all extracts, excludingByrsonima intermedia, had inhibitory activity over 80% at the concentration of 100 μg/mL. The total suppressive antioxidant capacity measured as the effective concentration, which represents the extract concentration producing 50% inhibition of the chemiluminescence induced byH. pylori, varies from 27.2 to 56.8 μg/mL and was in the following order:Qualea parviflora > Qualea multiflora > Alchornea triplinervia > Qualea grandiflora > Anacardium humile > Davilla elliptica > Mouriri pusa > Byrsonima basiloba > Alchornea glandulosa > Byrsonima intermedia. The main groups of compounds in tested extracts are presented. Differences in the phytochemical profile, quantitatively and qualitatively, of these plants can explain and justify their protective effect on the gastric mucosa caused by the neutrophil-generated ROS that occurs whenH. pyloridisplays its evasion mechanisms.
Effect of Minicutting Length and Leaf Area Reduction on Growth and Nutritional Status of Eucalypt Propagules
Authors: Santana Reynaldo Campos , Fernandes Sula Janaina Oliveira , Titon Miranda , Xavier Aloisio , de Souza Priscila Fernandes , Barros Filho Nairam Felix
Published: July 2013

Significant improvements to the technique of minicuttingEucalyptusclones have been reported in the literature. However, despite these recent efforts, studies addressing the proper size of minicuttings and the reduction of leaf area have not been well explored. Thus, the present study had the objective of evaluating the effects of the length of the minicuttings and the leaf area reduction on the growth and nutritional condition ofEucalyptus urophylladuring propagation. The experiment was conducted for 90 days in the Plantar Reforestation Co. Nursery in the municipality of Curvelo, MG, using a randomized block design with 4 replicates in a4×2×2factorial arrangement. The effects of 4 lengths of minicuttings (4, 6, 8, and 10 cm), 2 levels of leaf area reductions (0 and 50%), and 2 commercial clones were studied. The length of the minicuttings and the reduction of leaf area did not affect the nutritional status of the leaves, nor did the length affect the quality of the plants at the age of 90 days. The results indicate that it is unnecessary to reduce the leaf area forEucalyptuspropagation.
A Comparison between Use of Spray and Freeze Drying Techniques for Preparation of Solid Self-Microemulsifying Formulation of Valsartan andIn VitroandIn VivoEvaluation
Authors: Singh Sanjay Kumar , Vuddanda Parameswara Rao , Singh Sanjay , Srivastava Anand Kumar
Published: July 2013

The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug inin vitroandin vivoconditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.
A Proposed Stochastic Finite Difference Approach Based on Homogenous Chaos Expansion
Authors: Galal O. H.
Published: July 2013

This paper proposes a stochastic finite difference approach, based on homogenous chaos expansion (SFDHC). The said approach can handle time dependent nonlinear as well as linear systems with deterministic or stochastic initial and boundary conditions. In this approach, included stochastic parameters are modeled as second-order stochastic processes and are expanded using Karhunen-Loève expansion, while the response function is approximated using homogenous chaos expansion. Galerkin projection is used in converting the original stochastic partial differential equation (PDE) into a set of coupled deterministic partial differential equations and then solved using finite difference method. Two well-known equations were used for efficiency validation of the method proposed. First one being the linear diffusion equation with stochastic parameter and the second is the nonlinear Burger's equation with stochastic parameter and stochastic initial and boundary conditions. In both of these examples, the probability distribution function of the response manifested close conformity to the results obtained from Monte Carlo simulation with optimized computational cost.
Improvement of Medium Chain Fatty Acid Content and Antimicrobial Activity of Coconut Oil via Solid-State Fermentation Using a MalaysianGeotrichum candidum
Authors: Khoramnia Anahita , Ebrahimpour Afshin , Ghanbari Raheleh , Ajdari Zahra , Lai Oi-Ming
Published: July 2013

Coconut oil is a rich source of beneficial medium chain fatty acids (MCFAs) particularly lauric acid. In this study, the oil was modified into a value-added product using direct modification of substrate through fermentation (DIMOSFER) method. A coconut-based and coconut-oil-added solid-state cultivation using a Malaysian lipolyticGeotrichum candidumwas used to convert the coconut oil into MCFAs-rich oil. Chemical characteristics of the modified coconut oils (MCOs) considering total medium chain glyceride esters were compared to those of the normal coconut oil using ELSD-RP-HPLC. Optimum amount of coconut oil hydrolysis was achieved at 29% moisture content and 10.14% oil content after 9 days of incubation, where the quantitative amounts of the modified coconut oil and MCFA were 0.330 mL/g of solid media (76.5% bioconversion) and 0.175 mL/g of solid media (53% of the MCO), respectively. MCOs demonstrated improved antibacterial activity mostly due to the presence of free lauric acid. The highest MCFAs-rich coconut oil revealed as much as 90% and 80% antibacterial activities againstStaphylococcus aureusandEscherichia coli, respectively. The results of the study showed that DIMOSFER by a local lipolyticG. candidumcan be used to produce MCFAs as natural, effective, and safe antimicrobial agent. The produced MCOs and MCFAs could be further applied in food and pharmaceutical industries.
Dual Targeting of Wild-Type and Mutant p53 by Small Molecule RITA Results in the Inhibition of N-Myc and Key Survival Oncogenes and Kills Neuroblastoma Cells In Vivo and In Vitro
Authors: Burmakin Mikhail , Shi Yao , Hedström Elisabeth , Kogner Per , Selivanova Galina
Published: July 2013

Purpose: Restoration of the p53 function in tumors is a promising therapeutic strategy due to the high potential of p53 as tumor suppressor and the fact that established tumors depend on p53 inactivation for their survival. Here, we addressed the question whether small molecule RITA can reactivate p53 in neuroblastoma and suppress the growth of neuroblastoma cells in vitro and in vivo.

Experimental Design: The ability of RITA to inhibit growth and to induce apoptosis was shown in seven neuroblastoma cell lines. Mechanistic studies were carried out to determine the p53 dependence and the molecular mechanism of RITA-induced apoptosis in neuroblastoma, using cell viability assays, RNAi silencing, co-immunoprecipitation, qPCR, and Western blotting analysis. In vivo experiments were conducted to study the effect of RITA on human neuroblastoma xenografts in mice.

Results: RITA induced p53-dependent apoptosis in a set of seven neuroblastoma cell lines, carrying wild-type or mutant p53; it activated p53 and triggered the expression of proapoptotic p53 target genes. Importantly, p53 activated by RITA inhibited several key oncogenes that are high-priority targets for pharmacologic anticancer strategies in neuroblastoma, including N-Myc, Aurora kinase, Mcl-1, Bcl-2, Wip-1, MDM2, and MDMX. Moreover, RITA had a strong antitumor effect in vivo.

Conclusions: Reactivation of wild-type and mutant p53 resulting in the induction of proapoptotic factors along with ablation of key oncogenes by compounds such as RITA may be a highly effective strategy to treat neuroblastoma. Clin Cancer Res; 19(18); 5092–103. ©2013 AACR.
Tumor-Specific T-cell Help Is Associated with Improved Survival in Melanoma
Authors: Woods Katherine , Cebon Jonathan
Published: July 2013

Despite success with immune checkpoint inhibitors, clinical benefit from cancer vaccines remains elusive. Combined targeting of melanoma-specific CD4+ and CD8+ T-lymphocyte epitopes was associated with improved survival compared with targeting either alone, or when a nonspecific helper epitope was used. We discuss the potential role of antigen-specific CD4 help. Clin Cancer Res; 19(15); 4021–3. ©2013 AACR.
AIM2, an IFN-Inducible Cytosolic DNA Sensor, in the Development of Benign Prostate Hyperplasia and Prostate Cancer
Authors: Ponomareva Larissa , Liu Hongzhu , Duan Xin , Dickerson Eric , Shen Hui , Panchanathan Ravichandran , Choubey Divaker
Published: July 2013

Close links have been noted between chronic inflammation of the prostate and the development of human prostatic diseases such as benign prostate hyperplasia (BPH) and prostate cancer. However, the molecular mechanisms that contribute to prostatic inflammation remain largely unexplored. Recent studies have indicated that the IFN-inducible AIM2 protein is a cytosolic DNA sensor in macrophages and keratinocytes. Upon sensing DNA, AIM2 recruits the adaptor ASC and pro-CASP1 to assemble the AIM2 inflammasome. Activation of the AIM2 inflammasome cleaves pro-interleukin (IL)-1β and pro-IL-18 and promotes the secretion of IL-1β and IL-18 proinflammatory cytokines. Given that human prostatic infections are associated with chronic inflammation, the development of BPH is associated with an accumulation of senescent cells with a proinflammatory phenotype, and the development of prostate cancer is associated with the loss of IFN signaling, the role of AIM2 in mediating the formation of prostatic diseases was investigated. It was determined that IFNs (α, β, or γ) induced AIM2 expression in human prostate epithelial cells and cytosolic DNA activated the AIM2 inflammasome. Steady-state levels of the AIM2 mRNA were higher in BPH than in normal prostate tissue. However, the levels of AIM2 mRNA were significantly lower in clinical tumor specimens. Accordingly, constitutive levels of AIM2 mRNA and protein were lower in a subset of prostate cancer cells as compared with BPH cells. Further, the cytosolic DNA activated the AIM2 inflammasome in the androgen receptor—negative PC3 prostate cancer cell line, suggesting that AIM2-mediated events are independent of androgen receptor status.

Implications: The AIM2 inflammasome has a fundamental role in the generation of human prostatic diseases. Mol Cancer Res; 11(10); 1193–202. ©2013 AACR.
Expression of Cytochrome P450 2A5 in a C57BL/6J Mouse Model of Nonalcoholic Fatty Liver Disease
Authors: Li Rui , Guo Guifang , Cao Yuzhen , Wang Yuanyuan , Liu Fangping , Zhang Xiuying
Published: July 2013

Cytochrome P450 2A5 (CYP2A5) expression is induced during the hepatotoxicity caused by various hepatotoxins and hepatitis. However, CYP2A5 expression during nonalcoholic fatty liver disease (NAFLD) is still unknown. In this study, serum biochemical parameters and liver histopathological analyses found that NAFLD had developed in C57BL/6J mice via administration of a high-fat diet continuously for 8 weeks. Subsequently, CYP2A5 expression was probed in the mice diagnosed with NAFLD that were treated with or without pyrazole, the inducer of chemical liver injury. It is shown that hepatic CYP2A5 mRNA, protein expression and coumarin 7-hydroxylase activity are enhanced with high-fat feed, and that pyrazole is able to further increase CYP2A5 expression and activity in mice with NAFLD. These results revealed that CYP2A5 is elevated during NAFLD and suggested that pyrazole and NAFLD act synergistically to induce the expression of CYP2A5 via an unclear mechanism.
Heart Surgery Stems Increased Nutritional Risk, Expressed during the Course of Stationary Rehabilitation
Authors: Boban M. , Persic V. , Miletic B. , Kovacicek K. , Madzar Z.
Published: July 2013

Background: Cardiovascular diseases are a vast global health burden. Despite common prevalence, current knowledge and investigations concerning nutritional aspects are limited. Characteristics and dynamics of nutritional risk are not entirely known for most of the entities, disease stages or treatment-induced fluctuations. This study assessed the effects of heart surgery on unintentional weight loss and nutritional risk using the NRS-2002. Methods: A noninterventional study that included patients scheduled for rehabilitation 1-6 months after heart surgery was performed. Evaluation included routine cardiovascular diagnostics and review of medical histories. Documented baseline weight was available for >85% of the patients. Nutritional risk screening was performed with the standardized NRS-2002 questionnaire. Results: A total of 145 patients were involved, with a mean age of 65.3 ± 11.5 years in a range of 23-84 years. The male to female ratio was 121:24 (83.4%:16.6%), respectively. Coronary artery bypass graft surgery (CABG) was performed in 89 patients (61.4%), valvular surgery (VS) in 34 (23.4%) and combined operations (CABG + VS) in 22 (15.2%). Percentage weight loss history was 11.1 ± 3.4% in a range of 0-20.1%, while NRS-2002 was 4.77 ± 1.05 in a range of 1-6. Increased nutritional risk (NRS-2002 ≥3) was found in nearly all patients. Combined ischemic and valvular etiology displayed the highest values of NRS-2002 (5.0 ± 1.2). Patient age and creatinine showed significant correlations with NRS-2002 (Rho = 0.521, p < 0.001 and Rho = 0.335, p < 0.001, respectively). Conclusion: Increased nutritional risk was found to be frequently prevalent in patients scheduled for rehabilitation after heart surgery. Risk was found to be in relation with underlying coronary artery disease as well as with the age of patients and parameters of renal function. Routine application of nutritional risk screening appears to be a valuable clinical tool for detecting this relevant comorbidity, particularly since no connection was found with traditional anthropometrics.
Successful Everolimus Treatment in a Patient with Advanced Pancreatic Neuroendocrine Tumor Who Developed Everolimus-Induced Interstitial Lung Disease on Two Occasions: A Case Report
Authors: Nakayama Yusuke , Ikeda Masafumi , Kojima Motohiro , Goto Koichi , Hara Miyuki , Okuyama Hiroyuki , Takahashi Hideaki , Ohno Izumi , Shimizu Satoshi , Mitsunaga Shuichi , Okusaka Takuji
Published: July 2013

Chemotherapy-associated interstitial lung disease (ILD) is often fatal, and the chemotherapeutic regimen generally cannot be resumed. ILD associated with the mammalian target of rapamycin (mTOR) inhibitor everolimus has many features distinct from chemotherapy-associated ILD. We present the case of a 58-year-old woman with an advanced pancreatic neuroendocrine tumor with liver metastases, in whom everolimus treatment was maintained and resulted in a partial response despite two occurrences of everolimus-induced ILD during a 31-month treatment period until disease progression. Physicians treating with everolimus should monitor patients closely for ILD and should apply appropriate management strategies to optimize the possibility of maintaining everolimus therapy.
Gemcitabine and Docetaxel for Metastatic Soft Tissue Sarcoma - a Single Center Experience
Authors: Schmitt Thomas , Kosely Florentina , Wuchter Patrick , Schmier Johann-Wilhelm , Ho Anthony D. , Egerer Gerlinde
Published: July 2013

Background: Prognosis and survival for patients with metastatic soft tissue sarcoma (STS) are dismal. Standard first-line systemic chemotherapy is anthracycline-based. Gemcitabine/docetaxel (GD) is a therapeutic option in the second-line setting. Here we present the data of our single center retrospective analysis, using GD in locally advanced or metastatic disease. Patients and Methods: Between 2005 and 2012, a total of 34 patients were identified. The majority of tumors were located in the extremities (19/34, 56%) and abdomen/retroperitoneum (10/34, 29%). Most frequent histologies included leiomyosarcoma (13/34, 38%), liposarcoma (7/34, 21%), and pleomorphic sarcoma (6/34, 18%). Results: Objective response to treatment by RECIST criteria after 3 cycles was low with 6% partial responses (PR, 2/34), 65% stable disease (SD, 22/34), and 29% progressive disease (PD, 10/34). Progression-free survival at 3 and 6 months was 77 and 62%, respectively. Patients with a clinical benefit (defined as PR or SD after the 3rd treatment cycle) had a significantly prolonged median progression-free and overall survival with 8.6 months (p < 0.0001; hazard ratio (HR) 33.1) and 22.4 months (p < 0.0001; HR 12.9), respectively. Most common toxicities included hand-foot syndrome, edema, pancytopenia, febrile neutropenia, and mucositis. Conclusion: Overall, we conclude that GD is an active second-line regimen in metastatic STS, with manageable side effects.
Primary Intracranial Small Cell Carcinoma: A Case Report and Review of the Literature
Authors: Zhang Sheng , Cai Qian , Fan Li , Zhang Ruiguang , Zhao Yingchao , Wu Gang , Dong Xiaorong
Published: July 2013

Background: Extrapulmonary small cell carcinoma is a distinct clinicopathological entity accounting for only 2.5-4% of small cell carcinomas. Here we present a case of primary intracranial small cell carcinoma. Case Report: A 69-year-old woman with an isolated brain lesion presented with progressive headaches, confusion, nausea, and vomiting. A magnetic resonance imaging scan of the brain revealed a 4 × 3 × 5-cm solitary cystic tumor in the right frontoparietal lobe, accompanied by a midline shift. The mass was resected and pathologically proven to be a small cell carcinoma. The patient was given adjuvant radiotherapy but refused any chemotherapy. At the 12-month follow-up the patient was alive and well. Conclusion: Primary intracranial small cell carcinoma presenting as an isolated lesion is extremely rare. While there are no standard treatment guidelines for these patients, the authors believe multimodality treatment including tumorectomy and postoperative radiotherapy should be recommended.
Interactions between Human Immunodeficiency Virus Type 1 and Polymorphonuclear Neutrophils
Authors: Casulli Sarah , Elbim Carole
Published: July 2013

Polymorphonuclear neutrophils (PMN) are the most abundant circulating leukocytes. They represent a first line of innate immunity against a large panel of microbial pathogens, pending development of specific immune responses. The role of PMN in human immunodeficiency virus type 1 (HIV-1) disease has mainly been investigated from the point of view of the increased susceptibility of HIV-1-infected patients to bacterial and fungal infections. However, it is now clear that the relationship between PMN and HIV-1 is far more complex. This review examines both the beneficial and the detrimental effects of PMN during HIV infection.
Cancer Patients and Advance Directives: A Survey of Patients in a Hematology and Oncology Outpatient Clinic
Authors: Hubert Elisabeth , Schulte Nadine , Belle Sebastian , Gerhardt Axel , Merx Kirsten , Hofmann Wolf-Karsten , Stein Alexander , Burkholder Iris , Hofheinz Ralf-Dieter , Kripp Melanie
Published: July 2013

Background: In 2009, Germany enacted a new law supporting advance directives that led to heated discussions in the media and the public. 3 years after the law passed, we surveyed patients with malignant diseases with regards to their views on advance directives. Patients and Methods: Between September 2011 and July 2012 an anonymous survey on advance directives was conducted among 617 patients at the hematology and oncology outpatient department of the University Hospital Mannheim, using a standardized questionnaire developed for this investigation. Results: Of the 503 patients who returned the questionnaire, 31% (n = 157) indicated having an advance directive. Of these 157, 54% (n = 85) completed the advance directive after 2009. 56% (282 out of 503) desired more information on advance directives. Of these, 71% (201 out of 282) wanted their general physician and 45% (128 out of 282) their specialist, to provide more information about this issue. Of the 339 patients without an advance directive, 47% (n = 158) stated that they had ‘not worried about that yet'. Conclusion: Although the percentage of patients with advance directives has increased since the legislative amendment, more information is still required by patients. It is recommended that physicians should discuss advance directives more frequently with their patients.
Fatigue in the General Population of Colombia - Normative Values for the Multidimensional Fatigue Inventory MFI-20
Authors: Hinz Andreas , Barboza Carolyn Finck , Barradas Susana , Körner Annett , Beierlein Volker , Singer Susanne
Published: July 2013

Background: Fatigue is a frequent symptom in cancer patients. In Europe and Northern America fatigue questionnaires were developed and tested, but their generalizability to other cultural contexts is largely unknown. The aim of this study is to provide normative values for the Multidimensional Fatigue Inventory (MFI-20) based on a representative sample of the general population in Colombia and to test psychometric properties. Methods: 1,500 individuals completed a questionnaire that contained the MFI-20, as well as other questionnaires, and questions on sociodemographic variables and chronic diseases. Results: The mean values of the scales were marginally higher than those for 2 European samples. The mean value of the total score was 44.3 ± 14.1. Women were affected by fatigue more than men, and there was an almost linear age trend, with higher mean scores for older subjects. People with chronic diseases were affected by fatigue more than people without chronic conditions. The best psychometric properties were obtained for the total scale (sum score) of the MFI-20. Conclusion: The normative values presented here can help us to assess the individual burden of fatigue in a Latin American context. Psychometric properties of the MFI-20 in Colombia are similar to those obtained in Europe.
Exploration of the Role of Radiotherapy in the Management of Early Glottic Cancer with Complete Carotid Artery Occlusion
Authors: Mourad Waleed F. , Hu Kenneth S. , Shourbaji Rania A. , Dolan James , Blakaj Dukagjin M. , Shasha Daniel , Harrison Louis B.
Published: July 2013

Background: The aim of this study was to compare intensity-modulated radiation therapy (IMRT) vs. 2D and 3D radiotherapy (RT) in the treatment of T1 glottic squamous cell carcinoma in an effort to highlight the advantages of IMRT in this particular clinical situation. Case Report: We present the case of an 82-year-old female patient with T1 left true vocal cord squamous cell carcinoma and complete occlusion of the left carotid artery resulting in multiple strokes. The patient underwent definitive RT with 63 Gy (28 × 2.25 Gy). 3 plans were generated: 2D RT, 3D RT, and IMRT. The right carotid artery (Rt.CA) mean dose was 865, 2,065, and 4,268 cGy for IMRT, 3D RT, and 2D RT, respectively. The inferior pharyngeal constrictor (IPC) mean dose was 5,341, 6,456, and 6,451 cGy for IMRT, 3D RT, and 2D RT, respectively. IMRT provided the best homogeneity but at a higher cost and with prolonged treatment time. Conclusion: IMRT provided the finest planning target volume coverage with minimal Rt.CA and IPC doses. IMRT is recommended in certain clinical scenarios which are not manageable with other techniques.
Primary Dermal Melanoma in a Patient with a History of Multiple Malignancies: A Case Report with Molecular Characterization
Authors: Sini Germana , Colombino Maria , Lissia Amelia , Maxia Sara , Gulino Marcello , Paliogiannis Panagiotis , Palomba Grazia , Palmieri Giuseppe , Cossu Antonio , Rubino Corrado
Published: July 2013

Introduction: Primary dermal melanoma (PDM) is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachronous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis), came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80-100 vs. 5-20%, respectively).
TRUC or the Need for a New Microbial Classification
Authors: Raoult Didier
Published: July 2013

Microbes were defined in the 19th century by L. Pasteur. Prokaryotes and eukaryotes, which are divided into two worlds of microbes, were introduced by E. Chatton in 1925. R. Woese divided this world into three domains based on ribosomal analysis (Bacteria, Archaea, and Eukarya). The discovery of Mimivirus and other Megavirales, that are microbes, led to divide the microbiological world into four branches. I introduced the name TRUC (Things Resisting Uncompleted Classifications) to accommodate the division in four of the currently known microbiological world.
Platelets and matrix metalloproteinases
Authors: Seizer Peter , May Andreas E.
Published: July 2013

Matrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a variety of pathophysiologies by modulating cell migration, tissue degradation and inflammation. Platelet-associated MMP activity appears to play a major role in these processes. First, platelets can concentrate leukocyte-derived MMP activity to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct receptor interaction or/and by paracrine pathways. Third, platelets synthesise and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1-MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and their inhibitors.
Genetics of Thoracic Aortic Aneurysm
Authors: Gillis Elisabeth , Van Laer Lut , Loeys Bart L.
Published: July 2013

Aortic aneurysm, including both abdominal aortic aneurysm and thoracic aortic aneurysm, is the cause of death of 1% to 2% of the Western population. This review focuses only on thoracic aortic aneurysms and dissections. During the past decade, the genetic contribution to the pathogenesis of thoracic aortic aneurysms and dissections has revealed perturbed extracellular matrix signaling cascade interactions and deficient intracellular components of the smooth muscle contractile apparatus as the key mechanisms. Based on the study of different Marfan mouse models and the discovery of several novel thoracic aortic aneurysm genes, the involvement of the transforming growth factor-β signaling pathway has opened unexpected new avenues. Overall, these discoveries have 3 important consequences. First, the pathogenesis of thoracic aortic aneurysms and dissections is better understood, although some controversy still exists. Second, the management strategies for the medical and surgical treatment of thoracic aortic aneurysms and dissections are becoming increasingly gene-tailored. Third, the pathogenetic insights have delivered new treatment options that are currently being investigated in large clinical trials.
Intervention for Recoarctation in the Single Ventricle Reconstruction Trial
Authors: Hill Kevin D. , Rhodes John F. , Aiyagari Ranjit , Baker G. Hamilton , Bergersen Lisa , Chai Paul J. , Fleming Gregory A. , Fudge J. Curt , Gillespie Matthew J. , Gray Robert G. , Hirsch Russel , Lee Kyong-Jin , Li Jennifer S. , Ohye Richard G. , Oster Matthew E. , Pasquali Sara K. , Pelech Andrew N. , Radtke Wolfgang A.K. , Takao Cheryl M. , Vincent Julie A. , Hornik Christoph P.
Published: July 2013

Background—

Recoarctation after the Norwood procedure increases risk for mortality. The Single Ventricle Reconstruction (SVR) trial randomized subjects with a single right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt or a right ventricle–pulmonary artery shunt. We sought to determine the incidence of recoarctation, risk factors, and outcomes in the SVR trial.

Methods and Results—

Recoarctation was defined by intervention, either catheter based or surgical. Univariate analysis and multivariable Cox proportional hazard models were performed with adjustment for center. Of the 549 SVR subjects, 97 (18%) underwent 131 interventions (92 balloon aortoplasty, 39 surgical) for recoarctation at a median age of 4.9 months (range, 1.1–10.5 months). Intervention typically occurred at pre–stage II catheterization (n=71, 54%) or at stage II surgery (n=38, 29%). In multivariable analysis, recoarctation was associated with the shunt type in place at the end of the Norwood procedure (hazard ratio, 2.0 for right ventricle–pulmonary artery shunt versus modified Blalock-Taussig shunt;
P
=0.02), and Norwood discharge peak echo-Doppler arch gradient (hazard ratio, 1.07 per 1 mm Hg;
P
<0.01). Subjects with recoarctation demonstrated comorbidities at pre–stage II evaluation, including higher pulmonary arterial pressures (15.4±3.0 versus 14.5±3.5 mm Hg;
P
=0.05), higher pulmonary vascular resistance (2.6±1.6 versus 2.0±1.0 Wood units·m
2
;
P
=0.04), and increased echocardiographic volumes (end-diastolic volume, 126±39 versus 112±33 mL/BSA
1.3
, where BSA is body surface area;
P
=0.02). There was no difference in 12-month postrandomization transplantation-free survival between those with and without recoarctation (
P
=0.14).

Conclusions—

Recoarctation is common after Norwood and contributes to pre–stage II comorbidities. Although with intervention there is no associated increase in 1-year transplantation/mortality, further evaluation is warranted to evaluate the effects of associated morbidities.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00115934.
On Ebū al-Fazl Mūsā bin Haci Huseyn Iznikī’s Translation of Tha‘labī’s Qiṣaṣ al-Anbiyā
Authors: Bayraktar Nesrin
Published: July 2013

This article focuses on Iznikī’s translation of Tha‘labī’s Qiṣaṣ al-Anbiyā’ as a valuable gateway to our understanding of features of Old Anatolian Turkish. Comprising of two volumes, the manuscript is incomplete, with a missing second volume. There are two extant copies (Yozgat and Şazeli) of the first volume of the manuscript. An examination of the two copies reveals that both copies contain characteristic morphological and phonetic features of 15th century Old Anatolian Turkish. The manuscript embodies informative information concerning lexical and morphological features of Turkish of the era as well as transitional forms of Turkish. Syntactically, however, the texts carries resemblance to Arabic syntax, attributable to Iznikī’s profound command of Arabic and Persian and the original language of Tha‘labī’s work.
When Two Leviathans Clash: Free Movement of Persons in ECOWAS and the Ghana Investment Act of 1994
Authors: Kufuor Kofi Oteng
Published: July 2013

Abstract

The Economic Community of West African States transformed itself into a supranational order in 1993. A supranational treaty entails a surrender of sovereignty by the members to the organs of the treaty. This has led to a trading dilemma in Ghana as its citizens are no longer protected from competition from national of parties to the new order.
Resurgence of the Traditional Justice System in Postcolonial Benin (Nigeria) Society
Authors: Idumwonyi Itohan Mercy , Ikhidero Solomon Ijeweimen
Published: July 2013

Abstract

Rules and norms of behaviour are common features in human society. This is confirmed by human being’s desire for protection, fairness and mutual respect from fellow humans in their social groups. Recognized authorities whose sanctions are respected help to ensure fairness and mutual respect for each other. For the traditional Benin (African) society, the issue of law and justice is the joint concern of the deities, ancestors and the human members within the society. The aim of this paper, is to examine (i) the relevance of traditional justice system in postcolonial Benin (African) society; and (ii) the unwavering respect for traditional values which the Benin (African) people have maintained even in a postcolonial era; and argue that the continual preference for traditional methods of obtaining justice by the people of Benin (Africa) are not unconnected with the inherent limitations of the received English legal system within an African terrain. As insiders, we propose a harmonization of a ‘euro-afro-centric judicial system, for we believe that this would be beneficial and progressive for us as a people in quest for justice in a postcolonial Benin (African) society.
The ICC Addresses Non-Cooperation By States Parties: The Malawi Decision
Authors: Magliveras Konstantinos , Naldi Gino
Published: July 2013

Abstract

This article examines the decision, issued by the Pre-Trial Chamber I of the ICC on 12 December 2011, concerning the failure of the Republic of Malawi to comply with the requests of co-operation that the ICC has extended to contracting parties in relation to the arrest and surrender of the indicted Sudanese President al-Bashir. Faced with blatant defiance by African States Parties, as well as a hostile African Union, the ICC has of late no longer restricted its reaction simply to informing the UN Security Council and the Assembly of States Parties of instances of non co-operation, but has also, for the first time, justified why it has found specific states to have violated their Rome Statute obligations by hosting al-Bashir on official visits to their territories.
An Appraisal of the Night Masquerade Festival and Discrimination against Women in Nigeria from an International Human Rights Law Perspective
Authors: Okeowo Demola
Published: July 2013

Abstract

The Night Masquerade is one of several cultural practices that are well rooted within the Yoruba people in the south-western part of Nigeria. The masquerade is believed to be an adult male member of the society. This person traditionally walks about the town nakedly in the company of numerous other adult male members of the society, performing rituals and appeasing the gods. Generally, women are forbidden from viewing this masquerade and any woman who violates this rule shall be put to death to appease the gods. Over the years, this cultural practice has generated heated arguments and concern, especially from human rights activists and feminists. The paper will argue that any cultural practice that promotes discrimination on the basis of sex and that in fact leads to unnecessary restriction of movement and wanton loss of lives is repugnant to natural justice, equity and good conscience.
The International Law Principle of Permanent Sovereignty over Natural Resources as an Instrument for Development: The Case of Zimbabwean Diamonds
Authors: Chekera Yolanda T. , Nmehielle Vincent O.
Published: July 2013

Abstract

Extensive research has shown that revenue from the exploitation of natural resources can sustain development. Conversely, development research literature has shown that many developing countries have failed to use the natural resources to improve and sustain good living for their citizens. In most cases, those in political offices have squandered the resources and benefits that have accrued from the country’s natural endowments. This article explores how the international law principle of permanent sovereignty over natural resources (PSNR) could be used as a vehicle for development, particularly looking at the case of Zimbabwean diamonds. While the principle could be an instrument for development, this article argues that legislation governing mining in Zimbabwe is not facilitative of a people-centred interpretation of the principle. Mining legislation vests the custodial right over the country’s mineral resources in the President. This creates an opportunity for abuse, as it limits the extent to which the people, as beneficiaries of the principle, can lay claim to the content of the principle. It also effectively limits any say the people may have on how revenue from the sale of diamonds is utilised, and how they would want to benefit from the resource. The article concludes that there is a need for legislative reform that speaks to development that is people-centred without which the majority of the people will keep sinking into the doldrums of extreme poverty, despite the country’s resource endowment. The hope is that the new Zimbabwean constitution will provide the impetus in this regard.
Revisiting Securities Regulation in the Aftermath of the Global Financial Crisis: Disclosure – Panacea or Pandora’s Box?
Authors: Solaiman S.M.
Published: July 2013

The United States introduced federal securities regulation by adopting the Disclosure-Based Regulation (DBR) in 1933 resembling the doctrine of caveat venditor (DCV) as a substitute for the doctrine of caveat emptor (DCE) in the securities market. The overarching objective of the DBR was to protect investors by enabling them to make ‘informed decisions’. Although the change aimed to protect investors, the causes of the GFC suggest that the DCV exists only in theory, while issuers of securities are still enjoying the benefits of the DCE in practice. Financial innovations that intend to camouflage the risks inherent in the complex derivative products should be strictly regulated through a merit regulation which should be applied to only public offers, and the DBR should still remain in force for other securities. It concludes that the DBR has now emerged as more a ‘Pandora’s box’ than a panacea.
On Re-invigorating the Australia-China Free Trade Agreement Negotiation Process
Authors: Ling He Ling
Published: July 2013

Driven by both economic and geopolitical imperatives, negotiation of the Australia-China Free Trade Agreement (ACFTA) has been slow and difficult. The negotiation process has reached an impasse since the latest round took place in March 2012. Major reasons for this include difficulties encountered in negotiating on agriculture, services, investment, and government procurement contracts and surrounding populist resistance from both Australian and Chinese domestic constituencies. Following more than eight years of negotiations and establishment of closer trade related ties, there is a lot at stake for both countries in the outcome of these discussions. This paper examines these issues and of the way forward towards a workable negotiation process.
Edraianthus canescens (Campanulaceae), a new species from the Central Balkan peninsula
Authors: LAKUŠIĆ DMITAR , NIKETIĆ MARJAN , RAKIĆ TAMARA , STEVANOVIĆ VLADIMIR
Published: July 2013

Edraianthus canescens is described as a new species from the central part of the Balkan Peninsula (eastern Dinaric Alps of western Serbia). It is a calcicolous stenoendemic of the Ovčarsko-Kablarska gorge of the river West Morava. Its population size is estimated to be less than 2000 mature individuals occupying less than 1 km2. The new species inhabits south-facing exposed rocky crevices, rarely screes, on calcareous bedrock, at elevations between 300 and 750 m. The closest relatives are taxa distributed in the central Balkans from the Balkan-Apennine E. graminifolius complex.
A new mute species of the genus Nemobius Serville (Orthoptera, Gryllidae, Nemobiinae) discovered in colluvial, stony debris in the Iberian Peninsula: A biological, phenological and biometric study
Authors: BARRANCO PABLO , GILGADO JOSÉ D. , ORTUÑO VICENTE M.
Published: July 2013

Sampling of a Mesovoid Shallow Substratum (MSS) of a scree in the Guadarrama mountains (Madrid, Spain) revealed a population of crickets of the genus Nemobius Serville. A detailed morphological study revealed that the cricket was a new species, Nemobius interstitialis sp. nov., which is principally characterized by the absence of a tympanum in the outer margin of the foreleg tibiae and a peculiar design of venation of the forewing of the male. Sampling of this environment over 1 year using surface and MSS pitfall traps, set at a depth of one meter, allowed study of population dynamics. A pop-ulation maximum is attained in August. Abiotic (temperature and humidity) and biotic (accompanying fauna) data are giv-en to contextualize the habitat of this new species.
A new species of the pagurid hermit crab genus Lophopagurus McLaughlin, 1981 (Crustacea: Decapoda: Anomura) from French Polynesia, and additional record of L. indonesiensis McLaughlin, 1997 from the Philippines
Authors: KOMAI TOMOYUKI , RAHAYU DWI LISTYO
Published: July 2013

Two species of the pagurid hermit crab genus Lophopagurus McLaughlin, 1981 are reported herein. Lophopagurus (Lophopagurus) minimus n. sp., described on the basis of two females from Tuamotu Archipelago, French Polynesia, appears closest to L. (L.) nanus (Henderson, 1888), but is easily distinguished from the latter by the different shape of the ocular peduncles and the less developed armature of the right cheliped. A single female from the Bohol Sea, the Philippines, is identified with L. (Australeremus) indonesiensis McLaughlin, 1997, a species for which possible synonymy with L. (A.) triserratus has been suggested. The newly collected specimen confirms the validity of the species and represents its second record since the original description.
The Making of an Extreme Event: Putting the Pieces Together
Authors: Dole Randall , Hoerling Martin , Kumar Arun , Eischeid Jon , Perlwitz Judith , Quan Xiao-Wei , Kiladis George , Webb Robert , Murray Donald , Chen Mingyue , Wolter Klaus , Zhang Tao
Published: July 2013

We examine how physical factors spanning climate and weather contributed to record warmth over the central and eastern United States in March 2012, when daily temperature anomalies at many locations exceeded 20°C. Over this region, approximately 1°C warming in March temperatures has occurred since 1901. This long-term regional warming is an order of magnitude smaller than temperature anomalies observed during the event, indicating that most of the extreme warmth must be explained by other factors. Several lines of evidence strongly implicate natural variations as the primary cause for the extreme event. The 2012 temperature anomalies had a close analog in an exceptionally warm U.S. March occurring over 100 years earlier, providing observational evidence that an extreme event similar to March 2012 could be produced through natural variability alone. Coupled model forecasts and simulations forced by observed sea surface temperatures (SSTs) show that forcing from anomalous SSTs increased the probability of extreme warm temperatures in March 2012 above that anticipated from the long-term warming trend. In addition, forcing associated with a strong Madden–Julian oscillation further increased the probability for extreme U.S. warmth and provided important additional predictive information on the timing and spatial pattern of temperature anomalies. The results indicate that the superposition of a strong natural variation similar to March 1910 on longterm warming of the magnitude observed would be sufficient to account for the record warm March 2012 U.S. temperatures. We conclude that the extreme warmth over the central and eastern United States in March 2012 resulted primarily from natural climate and weather variability— a substantial fraction of which was predictable.
The 2012 Organizations and the Natural Environment Division Annual Dissertation Award Competition
Authors: Weber James
Published: July 2013

The Organizations and the Natural Environment (ONE) Division of the Academy of Management, like many divisions, has an annual dissertation competition to recognize and honor emerging and exemplary work in the field. This special research forum provides an opportunity for the finalists of this competition, doctoral students or recently doctored faculty members, to present and discuss their work that will undoubtedly shape research in the ONE field for decades. Some of the dissertation abstracts and commentaries authored by the award finalists appear later. This overview to the forum provides a synopsis of the administrative process of the dissertation award competition and a few reflective thoughts from the committee chair.