bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients
Authors: Carvalho Denise Maciel , Garcia Fernanda Gonçalves , Terra Ana Paula Sarreta , Lopes Tosta Ana Cristina , Silva Luciana de Almeida , Castellano Lúcio Roberto , Silva Teixeira David Nascimento
Published: December 2014

Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes.Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-αproduction by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-αproduction) when compared to DF patients.Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.
Protective Effect of Quercetin on Melphalan-Induced Oxidative Stress and Impaired Renal and Hepatic Functions in Rat
Authors: Olayinka Ebenezer Tunde , Ore Ayokanmi , Ola Olaniyi Solomon , Adeyemo Oluwatobi Adewumi
Published: December 2014

One major challenge with the use of anticancer agents is the phenomenon of drug-induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while quercetin (QCT) is an antioxidant. We investigated the protective role of quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160–170 g) were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%, and 188%, respectively (P<0.05). Similarly, plasma ALP, ALT, AST, andγ-GT activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%, respectively, relative to control. However, pre or cotreatment with QCT ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic acid and GSH and activities of glutathione-S-transferase, SOD, and catalase decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively, followed by increase in MDA content by 46.5% relative to control. Pre- and cotreatment with QCT reestablished the hepatic antioxidant status and lipid peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic toxicity in rats.
PDGFRα and β Play Critical Roles in Mediating Foxq1-Driven Breast Cancer Stemness and Chemoresistance
Authors: Meng Fanyan , Speyer Cecilia L. , Zhang Bin , Zhao Yongzhong , Chen Wei , Gorski David H. , Miller Fred R. , Wu Guojun
Published: December 2014

Many epithelial–mesenchymal transition (EMT)–promoting transcription factors have been implicated in tumorigenesis and metastasis as well as chemoresistance of cancer. However, the underlying mechanisms mediating these processes are unclear. Here, we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. Using an expression profiling assay, we identified Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets. We further show that PDGFRα and β can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β results in more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown of either PDGFRα or β alone. In addition, PDGFRβ is a more potent mediator of Foxq1-promoted stemness traits than PDGFRα. Finally, pharmacologic inhibition or gene silencing of PDGFRs sensitizes mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively implicate PDGFRs as critical mediators of breast cancer oncogenesis and chemoresistance driven by Foxq1, with potential implications for developing novel therapeutic combinations to treat breast cancer. Cancer Res; 75(3); 584–93. ©2014 AACR.
Host miR155 Promotes Tumor Growth through a Myeloid-Derived Suppressor Cell–Dependent Mechanism
Authors: Chen Siqi , Wang Long , Fan Jie , Ye Cong , Dominguez Donye , Zhang Yi , Curiel Tyler J. , Fang Deyu , Kuzel Timothy M. , Zhang Bin
Published: December 2014

miR155 is a regulator of immune cell development and function that is generally thought to be immunostimulatory. However, we report here that genetic ablation of miR155 renders mice resistant to chemical carcinogenesis and the growth of several transplanted tumors, suggesting that miR155 functions in immunosuppression and tumor promotion. Host miR155 deficiency promoted overall antitumor immunity despite the finding of defective responses of miR155-deficient dendritic cells and antitumor T cells. Further analysis of immune cell compartments revealed that miR155 regulated the accumulation of functional myeloid-derived suppressive cells (MDSC) in the tumor microenvironment. Specifically, miR155 mediated MDSC suppressor activity through at least two mechanisms, including SOCS1 repression and a reduced ability to license the generation of CD4+Foxp3+ regulatory T cells. Importantly, we demonstrated that miR155 expression was required for MDSC to facilitate tumor growth. Thus, our results revealed a contextual function for miR155 in antitumor immunity, with a role in MDSC support that appears to dominate in tumor-bearing hosts. Overall, the balance of these cellular effects appears to be a root determinant of whether miR155 promotes or inhibits tumor growth. Cancer Res; 75(3); 519–31. ©2014 AACR.
A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
Authors: Kendra Kari L. , Plummer Ruth , Salgia Ravi , O'Brien Mary E. R. , Paul Elaine M. , Suttle A. Benjamin , Compton Natalie , Xu Chun-Fang , Ottesen Lone H. , Villalona-Calero Miguel A.
Published: December 2014

This study was designed to evaluate the safety, pharmacokinetics, and clinical activity of pazopanib combined with paclitaxel to determine the recommended phase II dose in the first-line setting in patients with advanced solid tumors. Patients were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated regimen (MTR) of once daily pazopanib plus paclitaxel administered every 3 weeks at four dose levels (DL1-4). Safety, pharmacokinetics, pharmacogenetics, and disease assessments were performed. Twenty-eight patients received treatment. One patient at DL1 had dose-limiting toxicity (DLT) of elevated hepatic enzymes. After pazopanib discontinuation, liver enzyme concentrations remained high until a concurrent medication, simvastatin, was discontinued. This patient had the defective CYP2C8*3*3 genotype. At DL2, 1 patient had DLT of elevated hepatic enzymes with rash and 1 patient had DLT of rash. The MTR was paclitaxel 150 mg/m2 plus pazopanib 800 mg. The most common toxicities were alopecia, fatigue, hypertension, nausea, diarrhea, dysgeusia, neutropenia, myalgia, hair color changes, and peripheral neuropathy. Coadministration of pazopanib and paclitaxel resulted in a 38% increase in systemic exposure to paclitaxel, relative to administration of paclitaxel alone, at the MTR. Of the 28 patients treated with the combination, 10 achieved a partial response and 10 achieved stable disease of ≥12 weeks. Pazopanib 800 mg daily plus paclitaxel 150 mg/m2 every 3 weeks was the recommended phase II dose, with a manageable safety profile, and with clinical activity in both melanoma and non–small cell lung cancer that suggest further evaluation of this combination is warranted. Mol Cancer Ther; 14(2); 461–9. ©2014 AACR.
Glycogen Synthase Kinase 3β Sustains Invasion of Glioblastoma via the Focal Adhesion Kinase, Rac1, and c-Jun N-Terminal Kinase-Mediated Pathway
Authors: Chikano Yuri , Domoto Takahiro , Furuta Takuya , Sabit Hemragul , Kitano-Tamura Ayako , Pyko Ilya V. , Takino Takahisa , Sai Yoshimichi , Hayashi Yutaka , Sato Hiroshi , Miyamoto Ken-ichi , Nakada Mitsutoshi , Minamoto Toshinari
Published: December 2014

The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3β (GSK3β), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3β compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation. Here, we explore whether GSK3β also contributes to the highly invasive nature of glioblastoma. The effects of GSK3β inhibition on migration and invasion of glioblastoma cells were examined by wound-healing and Transwell assays, as well as in a mouse model of glioblastoma. We also investigated changes in cellular microarchitectures, cytoskeletal components, and proteins responsible for cell motility and invasion. Inhibition of GSK3β attenuated the migration and invasion of glioblastoma cells in vitro and that of tumor cells in a mouse model of glioblastoma. These effects were associated with suppression of the molecular axis involving focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase. Changes in cellular phenotypes responsible for cell motility and invasion were also observed, including decreased formation of lamellipodia and invadopodium-like microstructures and alterations in the subcellular localization, and activity of Rac1 and F-actin. These changes coincided with decreased expression of matrix metalloproteinases. Our results confirm the potential of GSK3β as an attractive therapeutic target against glioblastoma invasion, thus highlighting a second role in this tumor type in addition to its involvement in chemo- and radioresistance. Mol Cancer Ther; 14(2); 564–74. ©2014 AACR.
Wee-1 Kinase Inhibition Overcomes Cisplatin Resistance Associated with High-RiskTP53Mutations in Head and Neck Cancer through Mitotic Arrest Followed by Senescence
Authors: Osman Abdullah A. , Monroe Marcus M. , Ortega Alves Marcus V. , Patel Ameeta A. , Katsonis Panagiotis , Fitzgerald Alison L. , Neskey David M. , Frederick Mitchell J. , Woo Sang Hyeok , Caulin Carlos , Hsu Teng-Kuei , McDonald Thomas O. , Kimmel Marek , Meyn Raymond E. , Lichtarge Olivier , Myers Jeffrey N.
Published: December 2014

Although cisplatin has played a role in “standard-of-care” multimodality therapy for patients with advanced squamous cell carcinoma of the head and neck (HNSCC), the rate of treatment failure remains particularly high for patients receiving cisplatin whose tumors have mutations in the TP53 gene. We found that cisplatin treatment of HNSCC cells with mutant TP53 leads to arrest of cells in the G2 phase of the cell cycle, leading us to hypothesize that the wee-1 kinase inhibitor MK-1775 would abrogate the cisplatin-induced G2 block and thereby sensitize isogenic HNSCC cells with mutant TP53 or lacking p53 expression to cisplatin. We tested this hypothesis using clonogenic survival assays, flow cytometry, and in vivo tumor growth delay experiments with an orthotopic nude mouse model of oral tongue cancer. We also used a novel TP53 mutation classification scheme to identify which TP53 mutations are associated with limited tumor responses to cisplatin treatment. Clonogenic survival analyses indicate that nanomolar concentration of MK-1775 sensitizes HNSCC cells with high-risk mutant p53 to cisplatin. Consistent with its ability to chemosensitize, MK-1775 abrogated the cisplatin-induced G2 block in p53-defective cells leading to mitotic arrest associated with a senescence-like phenotype. Furthermore, MK-1775 enhanced the efficacy of cisplatin in vivo in tumors harboring TP53 mutations. These results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisplatin for the treatment of patients with TP53 mutant HNSCC. Mol Cancer Ther; 14(2); 608–19. ©2014 AACR.
Aural Fullness in M3ni2re's Disease
Authors: Levo Hilla , Kentala Erna , Rasku Jyrki , PyykkF Ilmari
Published: December 2014

Objective: Aural fullness in M3ni2re's disease and the predisposing and consequential factors were investigated and possible consequences of aural fullness on participation activity were explored. Methods: 726 subjects of the Finnish M3ni2re Association replied to a questionnaire focusing on symptoms of M3ni2re's disease, sense of coherence, attitude, participation restriction, and general health-related quality of life (EQ-5D). In the analysis, the severity of the disease was controlled. Results: 68% of the subjects had aural fullness and in 37% it was moderate or strong. Aural fullness was rated as the worst problem by 4.4% of the subjects. Females reported more aural fullness than males. Tinnitus, hyperacusis and balance problems were significant predictors of aural fullness. Aural fullness was associated with reduced quality of life and complaints such as vertigo attacks, balance problems and hearing loss. Analysis based on participation restriction indicated that severe aural fullness leads to social isolation. Conclusions: Largely, psychological factors and personal traits modify problems experienced by aural fullness. Relaxation was the only statistically significant method that alleviated aural fullness. i 2014 S. Karger AG, Basel
SSEA-4+ CD34- Cells in the Adult Human Heart Show the Molecular Characteristics of a Novel Cardiomyocyte Progenitor Population
Authors: Sandstedt Joakim , Jonsson Marianne , Vukusic Kristina , Dellgren Göran , Lindahl Anders , Jeppsson Anders , Asp Julia
Published: December 2014

Stage-specific embryonic antigen (SSEA) expression is used to describe the differentiation state of an embryonic stem cell (ESC). In human ESCs, SSEA-3 and SSEA-4 are highly expressed in undifferentiated cells and downregulated upon differentiation. SSEA-4 has also been described as a marker for adult stem cells in various tissues, including human neonatal cardiac tissue. However, there is currently little data on the expression of SSEAs in human adult cardiac tissue. We obtained right and left atrial biopsies from patients undergoing cardiac surgery. These were dissociated, stained for SSEAs and other cardiac stem cell markers and analyzed by flow cytometry. Directly isolated cells expressed variable levels of SSEA-1, SSEA-3 and SSEA-4. The SSEA-1+ population was established as contaminating hematopoietic cells. The SSEA-4+ population, on the other hand, could be subdivided based on the endothelial progenitor marker CD34. The SSEA-4+ CD34- population in the right atrium had a high gene expression of both early (TBX5, NKX2.5) and late (TNNT2) cardiomyocyte markers. The SSEA-4+ CD34+ population, on the other hand, overlapped with previously described C-kit+ CD45- cardiac stem cells. Primary monolayer-cultured cells retained expression of SSEAs while the cardiomyogenic specification in the SSEA-4+ CD34- population was lost. In tissue sections, SSEA-4+ cells could be identified both within and outside the myocardium. Within the myocardium, some SSEA-4+ cells coexpressed cardiomyogenic markers. In conclusion, the results show that the adult human heart expresses SSEAs and that there is a subpopulation of SSEA-4+ CD34- cells that show features of a cardiomyocyte progenitor population.
Association between Single Nucleotide Polymorphisms in the OPRM1 Gene and Intraoperative Remifentanil Consumption in Northern Chinese Women
Authors: Liu Jing , Hu Dongxue , Jiang Yongdong , Xi Hongjie , Li Wenzhi
Published: December 2014

Background: Recent studies have suggested that some single nucleotide polymorphisms (SNPs) in the human -opioid receptor gene (OPRM1) affect the postoperative analgesic efficacy of opioids and their side effects. In this study, we assessed the association between SNPs in the OPRM1 gene and intraoperative remifentanil consumption as well as perioperative side effects during gynecological hysteroscopic surgery in women from Northern China. Methods: We analyzed 178 women undergoing gynecological hysteroscopic surgery. SNP genotyping was performed using the SNaPshot method. The state anxiety index (SAI) and pressure pain threshold (PPT) of all patients were assessed preoperatively. Monitored anesthesia care was maintained by the intravenous infusion of remifentanil. Intraoperative remifentanil usage and perioperative side effects were recorded. Statistical analyses were performed using SPSS software. Results: Patients carrying one or two copies of the minor allele (G allele) of rs558025 required significantly more intraoperative remifentanil than patients without the minor allele (p = 0.001, corrected p = 0.006). There were no significant associations between the six SNPs and various clinical characteristics. No significant associations between the six SNPs and PPT or SAI were found in our study. Conclusions: SNP rs558025 in the OPRM1 gene was associated with intraoperative remifentanil consumption during gynecological hysteroscopic surgery in our subjects. i 2014 S. Karger AG, Basel
Dilated, Arrhythmogenic Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy Due to the Emerin Splice-Site Mutation c.449 + 1G>A
Authors: Finsterer Josef , Stöllberger Claudia , Sehnal Ernst , Rehder Helga , Laccone Franco
Published: December 2014

Objective: Cardiac involvement in X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) usually includes arrhythmias but not dilative cardiomyopathy (dCMP). Here, we report an X-EDMD patient with severe dCMP and life-threatening ventricular arrhythmias associated with other phenotypic features unusual for X-EDMD. Case Report: A 46-year-old patient with X-EDMD due to the known splice-site mutation c.449 + 1G>A in the emerin gene experienced palpitations for the first time at the age of 21 years, and a first syncope at the age of 23 years. He was started on phenprocoumon due to atrial fibrillation and systolic dysfunction. At the age of 28 years he received his first pacemaker. Echocardiography at the age of 36 years showed left ventricular dilatation, enlarged atria, myocardial thickening, 28% ejection fraction and diastolic dysfunction. dCMP was suspected. At the age of 38 years, a cardiac resynchronization therapy system was implanted, which was upgraded to an implantable cardioverter defibrillator (ICD) because of ventricular tachycardias (at the age of 42 years). During the following months, the ICD discharged 30 times due to ventricular tachycardias. In May 2013, he required recurrent cardio-pulmonary resuscitation because ventricular fibrillation occurred with no discharge of the ICD. He was listed for heart transplantation. He also had hypothyroidism, liver hemangiomas, thrombopenia, anemia and diverticulosis. Conclusions: X-EDMD may occur along with dCMP. An ICD may be ineffective for ventricular fibrillation in X-EDMD. X-EDMD may be associated with unusual, atypical phenotypic features.
Prevalence Analysis of de novo Hepatic Steatosis Following Pylorus-Preserving Pancreaticoduodenectomy
Authors: Yoo Dae-Gwang , Jung Bo-Hyun , Hwang Shin , Kim Song-Chul , Kim Ki-Hun , Lee Young-Joo , Ahn Chul-Soo , Moon Deok-Bog , Kim Kang-Mo , Ha Tae-Yong , Kang Sung-Hwa , Kim Nayoung
Published: December 2014

Background: Prevalence of hepatic steatosis following pylorus-preserving pancreaticoduodenectomy (PPPD) is high. This study intended to reveal the prevalence and patterns of de novo hepatic steatosis following PPPD. Methods: We investigated postoperative de novo hepatic steatosis following PPPD (n = 101) with a control group of bile duct resection (BDR) (n = 54). Results: At postoperative 1 year, hepatic steatosis occurred in 21 of 82 patients (25.6%) of PPPD group and in 2 of 47 patients (4.3%) of BDR group (p = 0.001). Thereafter, at 2 to 5 years, a high prevalence of hepatic steatosis persisted in the PPPD group, but no further occurrence developed in BDR group. Once steatosis developed, it persisted until the end of the study period or patient death. Five-year cumulative incidence of hepatic steatosis was 26.7% in the PPPD group and 3.7% in BDR group (p < 0.001). Univariate analyses showed that patient sex, age, body mass index, blood lipid profile, recurrence of tumor, and diabetes did not have significant influence on the development of hepatic steatosis following PPPD. Conclusions: De novo hepatic steatosis may develop in a not negligible proportion of patients undergone PPPD. Multicenter studies with a high number of patients are needed to elucidate its pathogenesis and to find effective treatment for pancreaticoduodenectomy-associated hepatic steatosis. i 2014 S. Karger AG, Basel
Anti-Neuronal Antibodies in Patients with Fragile X Syndrome: Is there a Role of Autoimmunity in Its Pathogenesis?
Authors: Lisik Małgorzata Zofia , Gutmajster Ewa , Sieroń Aleksander L.
Published: December 2014

Background: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and a strong association with autism. Objectives: In this study, the frequency of serum anti-neural antibodies was investigated in FXS patients who did and those who did not manifest autism spectrum disorders (ASD) in comparison to typically developing controls. Methods: The study involved 23 males (mean age, 19.78 ± 6.56 years) who harboured a full mutation in the FMR1 gene. The control group comprised 19 healthy students (mean age 24.63 ± 1.89 years). Serum anti-neuronal antibodies were analyzed using Western blotting. Results: Serum anti-neuronal antibodies were present in 10/23 (43.48%) FXS males. Conclusion: Serum anti-neuronal antibodies were found in a subgroup of FXS patients. Autistic symptoms in FXS may, in part, be caused by auto-immune factors. Further studies in larger patient and control groups are necessary to elucidate the aetiopathogenic role of anti-neuronal antibodies in FXS patients.
Prognostic Factors in Patients with Hepatocellular Carcinoma Refractory or Intolerant to Sorafenib
Authors: Okuyama Hiroyuki , Ikeda Masafumi , Kuwahara Akiko , Takahashi Hideaki , Ohno Izumi , Shimizu Satoshi , Mitsunaga Shuichi , Senda Shoichi , Okusaka Takuji
Published: December 2014

Objective: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. Methods: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. Results: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. Conclusions: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors. © 2014 S. Karger AG, Basel
The Evolving Use of Radioiodine Therapy in Differentiated Thyroid Cancer
Authors: Mayson Sarah E. , Yoo Don C. , Gopalakrishnan Geetha
Published: December 2014

The incidence of differentiated thyroid cancer has increased worldwide over the last three decades, but thyroid cancer-related mortality remains stable. Until recently, the standard treatment for most thyroid cancers has been near-total thyroidectomy followed by radioiodine remnant ablation. Observational data support lower recurrence rates and improved survival after radioiodine ablation in patients with high-risk cancers; however, a similar benefit has not been established for all patients with thyroid cancer. Risk stratification should be used to identify patients who are likely to benefit from radioiodine ablation and guide therapeutic decisions. For most patients who need radioiodine remnant ablation, preparation for therapy with recombinant human thyroid-stimulating hormone stimulation is as effective as thyroid hormone withdrawal. Lower therapeutic doses of radioiodine are recommended for the majority of thyroid remnant ablations. Higher doses are reserved for advanced disease at initial diagnosis, local recurrences that cannot be treated with surgery alone, and distant metastatic disease. © 2014 S. Karger AG, Basel
A 25-Year-Old Woman with Type 2 Diabetes and Liver Disease
Authors: Junker Anders Ellekær , Gluud Lise Lotte , Pedersen Jens , Langhoff Jill Levin , Holst Jens Juul , Knop Filip Krag , Vilsbøll Tina
Published: December 2014

A 25-year-old female nurse was referred to our diabetes outpatient clinic with poorly controlled type 2 diabetes, obesity and elevated liver function tests (LFTs). Following a liver biopsy she was diagnosed with non-alcoholic steatohepatitis (NASH) and liver fibrosis. Treatment with subcutaneous injections of the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was initiated. After 46 weeks of treatment the patient had lost 16 kg, glycemic control was excellent and LFTs had normalized. Repeat liver biopsy and ultrasound showed reduction in hepatic fat content and inflammatory cells. The biopsy no longer fulfilled the criteria for NASH. The liver biopsies did not express hepatic GLP-1Rs using quantitative polymerase chain reaction. Our case suggests that liraglutide may benefit patients with NASH.
Cystic Lymphangioma of the Chest Wall: A Case Report
Authors: Yokoigawa Norio , Okuno Masashi , Kwon A.-H.
Published: December 2014

Cystic lymphangioma is a congenital cystic malformation that occurs mostly in children. While it is mainly found in the cervix, cases in the chest wall are very rare. We report a case of cystic lymphangioma found in the chest wall of a 2-month-old girl. The patient was noted to have a tumor in the left chest wall at birth. Since it gradually increased in size, the patient was referred to our department. Transillumination and ultrasonography showed a cystic lesion in the left chest. Surgical resection was performed in one step. Histopathological examination showed a cystic lymphangioma.
Very Late-Onset Friedreich Ataxia with Laryngeal Dystonia
Authors: Rota Silvia , Marchina Eleonora , Todeschini Alice , Nanetti Lorenzo , Rinaldi Fabrizio , Vanotti Alessandra , Mariotti Caterina , Padovani Alessandro , Filosto Massimiliano
Published: December 2014

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia, cerebellar, pyramidal and dorsal column involvement, visual defects, scoliosis, pes cavus and cardiomyopathy. It is caused by a homozygous guanine-adenine-adenine (GAA) trinucleotide repeat expansion in intron 1 of the frataxin gene (FXN) on chromosome 9q13-q21.1. Onset is usually in the first or second decade of life; however, late-onset cases of Freidreich ataxia (LOFA), after the age of 25 years, and very late-onset cases of Freidreich ataxia (VLOFA), after the age of 40 years, have been reported. VLOFA is quite rare and usually presents a milder progression of the disease. We report the case of a 64-year-old woman affected with VLOFA whose first symptoms (balance and gait disturbances) occurred at the age of 44 years. At the age of 62 years, she started complaining of a slowly progressive dysphonia showing the clinical aspects of laryngeal dystonia. Molecular analysis showed a 210- and 230-trinucleotide GAA repeat expansion in the two alleles of the FXN gene. Laryngeal dystonia has been reported only in very few cases of ataxia syndrome and never before in FRDA patients. It may represent a rare clinical manifestation of VLOFA thus confirming the high variability of the clinical spectrum of FRDA.
Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data
Authors: Gröner Albrecht , Jian Ye , Inna Pendrak , Solomon Cristina
Published: December 2014

Fibrinogen concentrate use as a haemostatic agent has been increasingly explored. This study evaluates spontaneous reports of potential adverse drug reactions (ADRs) that occurred during postmarketing pharmacovigilance of Haemocomplettan P/RiaSTAP, and reviews published safety data. This descriptive study analysed postmarketing safety reports recorded in the CSL Behring pharmacovigilance database from January 1986 to December 2013. A literature review of clinical studies published during the same period was performed. Commercial data indicated that 2,611,294 g of fibrinogen concentrate were distributed over the pharmacovigilance period, main-contribonding to 652,824 standard doses of 4 g each, across a range of clinical settings and indications. A total of 383 ADRs in 106 cases were reported (approximately 1 per 24,600 g or 6,200 standard doses). Events of special interest included possible hypersensitivity reactions in 20 cases (1 per 130,600 g or 32,600 doses), possible thromboembolic events in 28 cases (1 per 93,300 g or 23,300 doses), and suspected virus transmission in 21 cases (1 per 124,300 g or 31,000 doses). One virus transmission case could not be analysed due to insufficient data; for all other cases, a causal relationship was assessed as unlikely due to negative polymerase chain reaction tests and/or alternative explanations. The published literature revealed a similar safety profile. In conclusion, underreporting of ADRs is a known limitation of pharmacovigilance. However, the present assessment indicates that fibrinogen concentrate is administered across a range of indications, with few ADRs and a low thromboembolic event rate. Overall, fibrinogen concentrate showed a promising safety profile.

Institution to which work should be attributed: CSL Behring, Marburg, Germany.
Venous thromboembolism diagnosis: unresolved issues
Authors: Le Gal Grégoire , Bounameaux Henri , Righini Marc
Published: December 2014

Recent advances in the management of patients with suspected VTE have both improved diagnostic accuracy and made management algorithms safer, easier to use and well standardised. These diagnostic algorithms are mainly based on the assessment of clinical pretest probability, D-dimer measurement and imaging tests, mainly represented by compression ultrasound (CUS) for suspected DVT and computed tomography pulmonary angiography (CTPA) or lung ventilationperfusion scan for pulmonary embolism. These diagnostic algorithms allow a safe and cost-effective diagnosis for most patients with suspected VTE. In this review, we focus on the challenge of diagnosing VTE in special patient populations, such as elderly patients, pregnant women, or patients with a prior VTE. Some additional challenges are arising that might require adjustments to current diagnostic strategies, such as the reduced clinical suspicion threshold, resulting in a lower proportion of VTE among suspected patients; the overdiagnosis and overtreatment of VTE, especially regarding calf deep-vein thrombosis (DVT) and subsegmental pulmonary embolism (SSPE).
The Rule of Law and Poverty Eradication in Africa
Authors: Mbaku John Mukum
Published: December 2014

Africa’s struggle against mass poverty and deprivation is examined using a constitutional political economy approach. It is argued that the failure of many African countries to deal effectively with poverty is due to the fact that since independence, these countries have not been able to engage in democratic constitution making to provide themselves with institutional arrangements that guarantee the rule of law. Such institutions must adequately constrain civil servants and political elites, enhance peaceful coexistence, and provide an enabling environment for the creation of wealth. The process to reconstruct and reconstitute African states has been on going since decolonization. The Arab awakening, which began in North Africa, and the pro-democracy demonstrations of the mid-1980s and early-1990s, are a continuation of this effort to secure the laws and institutions that enhance the creation of wealth and provide an enabling environment for the eventual eradication of poverty. Unless the African countries provide themselves with institutional arrangements that guarantee the rule of law, poverty will remain pervasive.
Rejecting Continuity and Rupture
Authors: Willott Chris
Published: December 2014

Patronage and financial corruption are rife in the contemporary Nigerian state and have gained widespread social acceptance, indicating a belief that it is legitimate to appropriate state resources for personal gain. In this paper I concentrate on the historical antecedents of this state of affairs. Focusing on the Igbo-speaking south-east of the country, I argue that an understanding of contemporary Nigeria must be based on a syncretic analysis: that is, a combination of influences from pre-colonial, colonial and post-colonial eras. Despite this, the colonial era should not be downplayed as an influence, as some have sought to argue. In particular, I argue that the imposition of warrant chiefs in previously acephalous communities with participatory governance engendered a belief that government did not belong to local people.
Africa – Asia Relations through the Prism of Television Drama
Authors: Bodomo Adams , Chabal Eun-Sook
Published: December 2014

Even though many African and Asian countries share a common history of European colonialism and thus a model of economic development shaped within the aegis of center-periphery analysis, many Asian countries have been able to ride through the burden of center-periphery economics and built more successful political economies than most African countries. This state of affairs has often led many African analysts to point to Asian success stories like China and South Korea for comparative analysis and often see these Asian countries as models of socio-economic and socio-cultural success to emulate. In particular, Africans in the Diaspora, especially Africans in China, tend to compare very frequently the socio-economic and socio-cultural conditions of their host countries with those of their source countries. This paper outlines and discusses how a group of Africans living in Hong Kong and other parts of Asia see Korea and Korean culture through the prism of Korean television dramas, which constitute a popular cultural phenomenon among Hong Kong/Asian youths. Through qualitative and quantitative survey methods, participant-observation, and questionnaire surveys, the paper reports on how African community members of Hong Kong and others think of Koreans. We show that Africans draw a lot of comparisons between Korean and African ways of conceptualizing the world.
Portuguese Settlement of the Chaul/Korlai area and the Formation of Korlai Creole Portuguese
Authors: Clancy Clements J.
Published: December 2014

A perspective is offered on the social and historical developments surrounding the formation of Korlai Creole Portuguese (kcp), a creole language spoken in the village of Korlai, located around 150 kms south of Mumbai. I argue that lower-caste Hindus who were enslaved by the Portuguese in the Chaul-Korlai area were instrumental in the creation of kcp. I claim that kcp formed by 1530 and that it has been maintained up to the present day due in large part to the isolation of its speakers because of their religion, their caste and their occupation.
French Guianese Creole
Authors: Jennings William , Pfänder Stefan
Published: December 2014

This article hypothesizes that French Guianese Creole (fgc) had a markedly different formative period compared to other French lexifier creoles, a linguistically diverse slave population with a strong Bantu component and, in the French Caribbean, much lower or no Arawak and Portuguese linguistic influence.The historical and linguistic description of the early years of fgc shows, though, that the founder population of fgc was dominated numerically and socially by speakers of Gbe languages, and had almost no speakers of Bantu languages. Furthermore, speakers of Arawak pidgin and Portuguese were both present when the colony began in Cayenne.
French on the Island of Bourbon (Réunion)
Authors: Bollée Annegret
Published: December 2014

France first laid claim to the uninhabited Island of Bourbon in 1640 (the name was changed into La Réunion in 1848), but permanent settlement and colonisation did not start until 1665. The present study zooms in on the first 50 years of the French colony and examines the intricacies of who spoke which language to whom on the basis of sociodemographic data concerning colonial households in the société d’habitation (‘homestead society’). Interethnic marriages were frequent in the first years; many of the first French settlers had Malagasy spouses and servants, others married young women from India. Malagasy can be shown to have left an imprint on the variety of French spoken during the early years of the colony. It is assumed that the colonists and their slaves spoke varieties which can be classified as approximative French, sharing several features with other varieties of overseas French. These early approximative varieties of French became the basis from which Réunion Creole developed in the société de plantation (‘plantation society’) in the years after 1725.
A new species of Scytodes from Algeria (Araneae: Scytodidae), with a review of the species from the Maghreb
Authors: KEER JOHAN VAN , BOSMANS ROBERT
Published: December 2014

Four spitting spider species in the genus Scytodes are recorded from the Maghreb: Scytodes annulipes Simon, 1907, stat. n. (elevated to species rank), S. major Simon, 1885, S. velutina Heineken & Lowe, 1832 and Scytodes seppoi Bosmans & Van Keer, sp. n. The male and female of the latter are described and illustrated. No recent records of the commonly cited S. thoracica (Latreille, 1804) can be provided, so earlier citations are considered to be erroneous. Images, illustrations and new distribution data of the other three known species in the Maghreb are given.
The first fossil spider (Araneae: Palpimanoidea) from the Lower Jurassic (Grimmen, Germany)
Authors: SELDEN PAUL A. , DUNLOP JASON A.
Published: December 2014

The first Lower Jurassic (Lias) spider is described as Seppo koponeni n. gen. & n. sp. from a single female specimen from Grimmen, Germany. It most likely belongs to the Palpimanoidea, on account of the presence of cheliceral peg teeth and other features consistent with palpimanoid families, though its familial placement is uncertain. Its presence in the region at that time concurs with ideas about the more widespread presence of palpimanoids across the world in the early Mesozoic, before the break-up of Pangaea.
Two new species of the Polysphincta genus-group (Hymenoptera: Ichneumonidae: Pimplinae) reared from their spider (Araneae) hosts in Europe
Authors: FRITZÉN NICLAS R.
Published: December 2014

Flacopimpla barathrica sp. n. and Zatypota flamma sp. n., belonging to the Polysphincta genus-group, are described, the former from Fennoscandia and the latter from Hungary. Like other species of this group for which the natural history is known, the new species are koinobiont ectoparasitoids of spiders. They have been reared from the theridiid spiders Thymoites bellissimus (L. Koch) and Parasteatoda sp. Archer respectively. The host records support the hypothesis of Flacopimpla being parasitoids of the spider family Theridiidae. The results also indicate that F. barathrica sp. n. has a very narrow host range consisting of a single species in Fennoscandia. The genus Flacopimpla was previously only known from the New World, and F. barathrica sp. n. is thus the first species of its genus in the Palaearctic. It is also the first troglophilic species of the Polysphincta genus-group. Zatypota albicoxa (Walker) is reported as new to Hungary.
The Birmingham Urban Climate Laboratory: An Open Meteorological Test Bed and Challenges of the Smart City
Authors: Chapman Lee , Muller Catherine L. , Young Duick T. , Warren Elliott L. , Grimmond C. S. B. , Cai Xiao-Ming , Ferranti Emma J. S.
Published: December 2014

The Birmingham Urban Climate Laboratory (BUCL) is a near-real-time, high-resolution urban meteorological network (UMN) of automatic weather stations and inexpensive, nonstandard air temperature sensors. The network has recently been implemented with an initial focus on monitoring urban heat, infrastructure, and health applications. A number of UMNs exist worldwide; however, BUCL is novel in its density, the low-cost nature of the sensors, and the use of proprietary Wi-Fi networks. This paper provides an overview of the logistical aspects of implementing a UMN test bed at such a density, including selecting appropriate urban sites; testing and calibrating low-cost, nonstandard equipment; implementing strict quality-assurance/quality-control mechanisms (including metadata); and utilizing preexisting Wi-Fi networks to transmit data. Also included are visualizations of data collected by the network, including data from the July 2013 U.K. heatwave as well as highlighting potential applications. The paper is an open invitation to use the facility as a test bed for evaluating models and/or other nonstandard observation techniques such as those generated via crowdsourcing techniques.
The Deep Convective Clouds and Chemistry (DC3) Field Campaign
Authors: Barth Mary C. , Cantrell Christopher A. , Brune William H. , Rutledge Steven A. , Crawford James H. , Huntrieser Heidi , Carey Lawrence D. , MacGorman Donald , Weisman Morris , Pickering Kenneth E. , Bruning Eric , Anderson Bruce , Apel Eric , Biggerstaff Michael , Campos Teresa , Campuzano-Jost Pedro , Cohen Ronald , Crounse John , Day Douglas A. , Diskin Glenn , Flocke Frank , Fried Alan , Garland Charity , Heikes Brian , Honomichl Shawn , Hornbrook Rebecca , Huey L. Gregory , Jimenez Jose L. , Lang Timothy , Lichtenstern Michael , Mikoviny Tomas , Nault Benjamin , O’Sullivan Daniel , Pan Laura L. , Peischl Jeff , Pollack Ilana , Richter Dirk , Riemer Daniel , Ryerson Thomas , Schlager Hans , St. Clair Jason , Walega James , Weibring Petter , Weinheimer Andrew , Wennberg Paul , Wisthaler Armin , Wooldridge Paul J. , Ziegler Conrad
Published: December 2014

The Deep Convective Clouds and Chemistry (DC3) field experiment produced an exceptional dataset on thunderstorms, including their dynamical, physical, and electrical structures and their impact on the chemical composition of the troposphere. The field experiment gathered detailed information on the chemical composition of the inflow and outflow regions of midlatitude thunderstorms in northeast Colorado, west Texas to central Oklahoma, and northern Alabama. A unique aspect of the DC3 strategy was to locate and sample the convective outflow a day after active convection in order to measure the chemical transformations within the upper-tropospheric convective plume. These data are being analyzed to investigate transport and dynamics of the storms, scavenging of soluble trace gases and aerosols, production of nitrogen oxides by lightning, relationships between lightning flash rates and storm parameters, chemistry in the upper troposphere that is affected by the convection, and related source characterization of the three sampling regions. DC3 also documented biomass-burning plumes and the interactions of these plumes with deep convection.
The LatMix Summer Campaign: Submesoscale Stirring in the Upper Ocean
Authors: Shcherbina Andrey Y. , Sundermeyer Miles A. , Kunze Eric , D’Asaro Eric , Badin Gualtiero , Birch Daniel , Brunner-Suzuki Anne-Marie E. G. , Callies Jörn , Kuebel Cervantes Brandy T. , Claret Mariona , Concannon Brian , Early Jeffrey , Ferrari Raffaele , Goodman Louis , Harcourt Ramsey R. , Klymak Jody M. , Lee Craig M. , Lelong M.-Pascale , Levine Murray D. , Lien Ren-Chieh , Mahadevan Amala , McWilliams James C. , Molemaker M. Jeroen , Mukherjee Sonaljit , Nash Jonathan D. , Özgökmen Tamay , Pierce Stephen D. , Ramachandran Sanjiv , Samelson Roger M. , Sanford Thomas B. , Shearman R. Kipp , Skyllingstad Eric D. , Smith K. Shafer , Tandon Amit , Taylor John R. , Terray Eugene A. , Thomas Leif N. , Ledwell James R.
Published: December 2014

Lateral stirring is a basic oceanographic phenomenon affecting the distribution of physical, chemical, and biological fields. Eddy stirring at scales on the order of 100 km (the mesoscale) is fairly well understood and explicitly represented in modern eddy-resolving numerical models of global ocean circulation. The same cannot be said for smaller-scale stirring processes. Here, the authors describe a major oceanographic field experiment aimed at observing and understanding the processes responsible for stirring at scales of 0.1–10 km. Stirring processes of varying intensity were studied in the Sargasso Sea eddy field approximately 250 km southeast of Cape Hatteras. Lateral variability of water-mass properties, the distribution of microscale turbulence, and the evolution of several patches of inert dye were studied with an array of shipboard, autonomous, and airborne instruments. Observations were made at two sites, characterized by weak and moderate background mesoscale straining, to contrast different regimes of lateral stirring. Analyses to date suggest that, in both cases, the lateral dispersion of natural and deliberately released tracers was O(1) m2 s–1 as found elsewhere, which is faster than might be expected from traditional shear dispersion by persistent mesoscale flow and linear internal waves. These findings point to the possible importance of kilometer-scale stirring by submesoscale eddies and nonlinear internal-wave processes or the need to modify the traditional shear-dispersion paradigm to include higher-order effects. A unique aspect of the Scalable Lateral Mixing and Coherent Turbulence (LatMix) field experiment is the combination of direct measurements of dye dispersion with the concurrent multiscale hydrographic and turbulence observations, enabling evaluation of the underlying mechanisms responsible for the observed dispersion at a new level.