bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA Interference Mediated Interleukin-1βSilencing in Inflamed Chondrocytes Decreases Target and Downstream Catabolic Responses
Authors: Ortved Kyla F. , Austin Bethany S. , Scimeca Michael S. , Nixon Alan J.
Published: March 2016

Posttraumatic activation of the catabolic cascade plays a major role in degradation of cartilage. Interleukin-1β(IL-1β), a primary instigator in the catabolic axis, is upregulated in chondrocytes following injury. IL-1βactivates key degradative enzymes, including MMPs and aggrecanases, and other proinflammatory mediators such as PGE2which contribute to ECM breakdown. Posttranscriptional silencing of IL-1βby RNA interference (RNAi) may drive a reduction in IL-1β. We hypothesized that transduction of chondrocytes using rAAV2 expressing a short hairpin RNAi motif targeting IL-1β(shIL-1β) would significantly decrease IL-1βexpression and, in turn, decrease expression of other catabolic enzymes. Chondrocyte cultures were transduced with rAAV2-tdT-shIL-1βin serum-free media. The fluorescent protein, tdTomato, was used to determine transduction efficiency via flow cytometry and fluorescent microscopy. Cells were stimulated with lipopolysaccharide (LPS) 48 hours following transduction. After 24-hour stimulation, supernatants were collected for cytokine analysis, and cells lysed for gene expression analysis. IL-1βknockdown led to significantly decreased expression ofIL-1β,TNF-α, andADAMTS5. PGE2synthesis was also significantly downregulated. Overall, effective silencing of IL-1βusing rAAV2 vector expressing a short hairpin IL-1βknockdown sequence was shown. Additionally, significant downstream effects were evident, including decreased expression ofTNF-αandADAMTS5. Targeted silencing of catabolic cytokines may provide a promising treatment avenue for osteoarthritic (OA) joints.
The Influence of Alcohol Consumption in Conjunction with Sex Hormone Deficiency on Ca/P Ratio in Rats
Authors: Lodi Karina Bortolin , Marchini Adriana Mathias Pereira da Silva , Santo Ana Maria do Espírito , Rode Sigmar de Mello , Marchini Leonardo , Rocha Rosilene Fernandes da
Published: March 2016

Deficiency of sex hormones and excessive alcohol consumption are factors that have been related to alterations in the pattern of bone mineralization and osteoporosis. The aim of this study was to evaluate possible alterations in the calcium/phosphorus (Ca/P) ratio in the femur of rats subjected to sex hormone deficiency and/or alcohol consumption.Methods. Female and male Wistar rats (n=108) were divided into ovariectomized (Ovx), orchiectomized (Orx), or sham-operated groups and subdivided according to diet: alcoholic diet (20% alcohol solution), isocaloric diet, andad libitumdiet. The diets were administered for 8 weeks. The Ca/P ratio in the femur was analyzed by energy dispersive micro-X-ray spectrometer (μEDX).Results. Consumption of alcohol reduced the Ca/P ratio in both females and males. The isocaloric diet reduced the Ca/P ratio in females. In groups with thead libitumdiet, the deficiency of sex hormones did not change the Ca/P ratio in females or males. However, the combination of sex hormone deficiency and alcoholic diet presented the lowest values for the Ca/P ratio in both females and males.Conclusions. There was a reduced Ca/P ratio in the femur of rats that consumed alcohol, which was exacerbated when combined with a deficiency of sex hormones.
Chemical Control for Host-Parasitoid Model within the Parasitism Season and Its Complex Dynamics
Authors: Wang Tao , Zhang Youtang
Published: March 2016

In the present paper, we develop a host-parasitoid model with Holling type II functional response function and chemical control, which can be applied at any time of each parasitism season or pest generation, and focus on addressing the importance of the timing of application pesticide during the parasitism season or pest generation in successful pest control. Firstly, the existence and stability of both the host and parasitoid populations extinction equilibrium and parasitoid-free equilibrium have been investigated. Secondly, the effects of key parameters on the threshold conditions have been discussed in more detail, which shows the importance of pesticide application times on the pest control. Thirdly, the complex dynamics including multiple attractors coexistence, chaotic behavior, and initial sensitivity have been studied by using numerical bifurcation analyses. Finally, the uncertainty and sensitivity of all the parameters on the solutions of both the host and parasitoid populations are investigated, which can help us to determine the key parameters in designing the pest control strategy. The present research can help us to further understand the importance of timings of pesticide application in the pest control and to improve the classical chemical control and to make management decisions.
miRNAs Participate in MS Pathological Processes and Its Therapeutic Response
Authors: Wu Ting , Chen Guangjie
Published: March 2016

Multiple sclerosis is the most common autoimmune disease of the central nervous system. It is believed that the increased migration of autoreactive lymphocytes across the blood-brain barrier (BBB) may be responsible for axonal demyelination of neurons. In this review, we discuss microRNAs participating in the pathological processes of MS, including periphery inflammation, blood-brain barrier disruption, and CNS lesions, and in its therapeutic response, in order to find biomarkers of disease severity and to predict the response to therapy of the diseases.
Thermal Expansion Measurements in Fresh and Saline Ice Using Fiber Optic Strain Gauges and Multipoint Temperature Sensors Based on Bragg Gratings
Authors: Marchenko Aleksey , Lishman Ben , Wrangborg David , Thiel Torsten
Published: March 2016

This paper describes the use of Fiber Bragg Grating (FBG) sensors to investigate the thermomechanical properties of saline ice. FBG sensors allowed laboratory measurements of thermal expansion of ice samples with a range of different sizes and geometries. The high sampling frequency, accuracy, and resolution of the FBG sensors provide good quality data across a temperature range from 0°C to −20°C. Negative values of the effective coefficient of thermal expansion were observed in ice samples with salinities 6 ppt, 8 ppt, and 9.4 ppt. A model is formulated under which structural transformations in the ice, caused by temperature changes, can lead to brine transfer from closed pockets to permeable channels, and vice versa. This model is compared to experimental data. Further, in experiments with confined floating ice, heating as well as thermal expansion due to vertical migration of liquid brine, caused by under-ice water pressure, was observed.
Study of Large-Scale Aluminium-Doped Zinc Oxide Ceramic Targets Prepared by Slip Casting
Authors: Han Ling-yun , Shu Yong-chun
Published: March 2016

Aluminium-doped zinc oxide (AZO) ceramic green compacts at a size of 170 × 340 × 17 mm have been prepared by slip casting. An AZO slurry with good fluidity and viscosity was obtained when 1.2 wt% of dispersant was added, which indicates that the slurry prepared with micrometre particles is more suitable for slip casting. The densification and electrical properties of the AZO targets prepared by particles with different sizes were investigated after sintering from 1380 to 1460°C. The results showed that the relative density of the AZO target prepared with 45 nm particles could reach nearly 98% at 1380°C; the resistivity of the AZO target prepared with nanometre particles could be as low as 1.6 × 10−3 Ω·cm at 1400°C; and the average transmittance of the AZO film prepared with nanometre particles could reach a maximum value of 93.73% in the visible region at 250 W. In this study, the correlation between the density, resistivity, and grain growth of AZO ceramic green compacts was studied.
Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response duringLeishmania(Viannia)BraziliensisorLeishmania(Leishmania)AmazonensisInfection
Authors: Carvalho A. K. , Carvalho K. , Passero L. F. D. , Sousa M. G. T. , da Matta V. L. R. , Gomes C. M. C. , Corbett C. E. P. , Kallas G. E. , Silveira F. T. , Laurenti M. D.
Published: March 2016

Leishmania (L.) amazonensis(La) andL. (V.) braziliensis(Lb) are responsible for a large clinical and immunopathological spectrum in human disease; whileLamay be responsible for anergic disease,Lbinfection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by theseLeishmaniaspecies, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course ofLaandLbinfection in BALB/c mice. Our results demonstrated a high involvement of DCs inLainfection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely,Lbinfection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4+T-cells was observed inLbinfection. Interleukin- (IL-) 4- and IL-10-producing CD4+and CD8+T-cells were present in bothLaandLbinfection; however, interferon- (IFN-)γ-producing CD4+and CD8+T-cells were detected only inLbinfection. The results suggest that duringLbinfection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrastLainfection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.
Subjective Visual Vertical in PD Patients with Lateral Trunk Flexion
Authors: Gandor F. , Basta D. , Gruber D. , Poewe W. , Ebersbach G.
Published: March 2016

Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinson’s disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1–17.7],n=21, versus 0.8° [0.1–1.9],n=9;p<0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF.
Smoking Exposure and Survival of Patients with Esophagus Cancer: A Systematic Review and Meta-Analysis
Authors: Kuang Jun-jie , Jiang Zhi-min , Chen Yan-xian , Ye Wei-peng , Yang Qiong , Wang Hui-zhong , Xie De-rong
Published: March 2016

Smoking is a well-known major risk factor in development of esophageal cancer, but few studies have reported the association between smoking status and prognosis of these patients. We conduct the present study to summarize current evidence. A computerized search of the PubMed and EMBASE was performed up to April 30, 2015. Eight studies, containing 4,286 patients, were analyzed. In the grouping analysis, among esophageal squamous-cell carcinoma patients, current and former smokers, compared to those who have never smoked, seemed to have a poorer prognosis (HR = 1.41, 95% CI 1.22–1.64, and HR = 1.35, 95% CI 0.92–1.97, resp.). In the subgroup analysis, adverse effects on current smoker compared with never smoker were also observed in China and the other countries (HR = 1.5, 95% CI 1.18–1.92, and HR = 1.36, 95% CI 1.12–1.65, resp.). In the group that ever smoked, we could not get a similar result. No significantly increased risk was found in esophageal adenocarcinoma patients compared to the squamous-cell histology ones. In the smoking intensity analysis, heavy smoking was associated with poor survival in esophageal squamous-cell carcinoma. Our pooled results supported the existence of harmful effects of smoking on survival after esophagus cancer diagnosis.
Length Variation Effect of the Impulse Response Model of a Secondary Path in Embedded Control
Authors: Lee Young-Sup , Choi Yunseon , Kim Jeakwan
Published: March 2016

This study presents theoretical and experimental investigation on the length variation effect of the impulse response function (IRF) for the secondary path model in active noise control using an embedded control board. A narrowband sweep noise was the disturbance for control in a duct with the length of 1800 mm. The IRF model incorporated into an adaptive feedforward filtered-x LMS (FxLMS) algorithm was then analyzed in the variation of its length in terms of the mean square error, computation complexity, stability requirement, and attenuation performance before and after control. The FxLMS algorithm with various IRF lengths was implemented in a dSPACE DS1104 embedded control board for the real-time control. Finally the most reasonable IRF length, considering the computation complexity and performance, can be determined through the systematic investigation. The results in this study can be used for practical active noise control systems.
Uncommon Complication of Uterine Artery Embolization: Expulsion of Infarcted Myoma and Uterine Sepsis
Authors: Martins Juliana G. , Gaudenti Dawn , Crespo Frank , Ganesh Dervi , Verma Usha
Published: March 2016

Uterine leiomyomas are the most common benign tumors in young females and leading cause of hysterectomy. Uterine artery embolization is a safe option for women who wish to retain their uterus. Several complications have been reported including expulsion and sepsis. MRI is a useful pretreatment tool to predict results and outcomes. We report a case of a 44-year-old female with a history of uterine fibroids with the largest one being intracavitary. Patient underwent uterine artery embolization that was complicated by endomyometritis that failed antibiotics, leading to sepsis and hysterectomy.
Direct Electrical Current Reduces Bacterial and Yeast Biofilm Formation
Authors: Ruiz-Ruigomez Maria , Badiola Jon , Schmidt-Malan Suzannah M. , Greenwood-Quaintance Kerryl , Karau Melissa J. , Brinkman Cassandra L. , Mandrekar Jayawant N. , Patel Robin
Published: March 2016

New strategies are needed for prevention of biofilm formation. We have previously shown that 24 hr of 2,000 µA of direct current (DC) reducesStaphylococcus epidermidisbiofilm formationin vitro. Herein, we examined the effect of a lower amount of DC exposure onS. epidermidis,Staphylococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Propionibacterium acnes, andCandida albicansbiofilm formation. 12 hr of 500 µA DC decreasedS. epidermidis,S. aureus,E. coli, andP. aeruginosabiofilm formation on Teflon discs by 2, 1, 1, and 2 log10cfu/cm2, respectively (p<0.05). Reductions inS. epidermidis,S. aureus, andE. colibiofilm formation were observed with as few as 12 hr of 200 µA DC (2, 2 and 0.4 log10 cfu/cm2, resp.); a 1 log10 cfu/cm2reduction inP. aeruginosabiofilm formation was observed at 36 hr. 24 hr of 500 µA DC decreasedC. albicansbiofilm formation on Teflon discs by 2 log10 cfu/cm2. No reduction inP. acnesbiofilm formation was observed. 1 and 2 log10 cfu/cm2reductions inE. coliandS. epidermidisbiofilm formation on titanium discs, respectively, were observed with 12 hr of exposure to 500 µA. Electrical current is a potential strategy to reduce biofilm formation on medical biomaterials.
HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors
Authors: Budina-Kolomets Anna , Webster Marie R. , Leu Julia I-Ju , Jennis Matthew , Krepler Clemens , Guerrini Anastasia , Kossenkov Andrew V. , Xu Wei , Karakousis Giorgos , Schuchter Lynn , Amaravadi Ravi K. , Wu Hong , Yin Xiangfan , Liu Qin , Lu Yiling , Mills Gordon B. , Xu Xiaowei , George Donna L. , Weeraratna Ashani T. , Murphy Maureen E.
Published: March 2016

The stress-inducible chaperone protein HSP70 (HSPA1) is implicated in melanoma development, and HSP70 inhibitors exert tumor-specific cytotoxic activity in cancer. In this study, we documented that a significant proportion of melanoma tumors express high levels of HSP70, particularly at advanced stages, and that phospho-FAK (PTK2) and BRAF are HSP70 client proteins. Treatment of melanoma cells with HSP70 inhibitors decreased levels of phospho-FAK along with impaired migration, invasion, and metastasis in vitro and in vivo. Moreover, the HSP70 inhibitor PET-16 reduced levels of mutant BRAF, synergized with the BRAF inhibitor PLX4032 in vitro, and enhanced the durability of response to BRAF inhibition in vivo. Collectively, these findings provide strong support for HSP70 inhibition as a therapeutic strategy in melanoma, especially as an adjuvant approach for overcoming the resistance to BRAF inhibitors frequently observed in melanoma patients. Cancer Res; 76(9); 2720–30. ©2016 AACR.
Neddylation Inhibition Activates the Extrinsic Apoptosis Pathway through ATF4–CHOP–DR5 Axis in Human Esophageal Cancer Cells
Authors: Chen Ping , Hu Tao , Liang Yupei , Li Pei , Chen Xiaoyu , Zhang Jingyang , Ma Yangcheng , Hao Qianyun , Wang Jinwu , Zhang Ping , Zhang Yanmei , Zhao Hu , Yang Shengli , Yu Jinha , Jeong Lak Shin , Qi Hui , Yang Meng , Hoffman Robert M. , Dong Ziming , Jia Lijun
Published: March 2016

Purpose: Targeting the protein neddylation pathway has become an attractive anticancer strategy; however, the role of death receptor–mediated extrinsic apoptosis during treatment remained to be determined.

Experimental Design: The activation of extrinsic apoptosis and its role in MLN4924 treatment of human esophageal squamous cell carcinoma (ESCC) were evaluated both in vitro and in vivo. The expression of the components of extrinsic apoptotic pathway was determined by immunoblotting analysis and downregulated by siRNA silencing for mechanistic studies.

Results: Pharmaceutical or genetic inactivation of neddylation pathway induced death receptor 5 (DR5)–mediated apoptosis and led to the suppression of ESCC in murine models. Mechanistically, neddylation inhibition stabilized activating transcription factor 4 (ATF4), a Cullin-Ring E3 ubiquitin ligases (CRL) substrate. Transcription factor CHOP was subsequently transactivated by ATF4 and further induced the expression of DR5 to activate caspase-8 and induce extrinsic apoptosis. Moreover, the entire neddylation pathway was hyperactivated in ESCC and was negatively associated with patient overall survival.

Conclusions: Our findings highlight a critical role of ATF4–CHOP–DR5 axis-mediated extrinsic apoptosis in neddylation-targeted cancer therapy and support the clinical investigation of neddylation inhibitors (e.g., MLN4924) for the treatment of ESCC, a currently treatment-resistant disease with neddylation hyperactivation. Clin Cancer Res; 22(16); 4145–57. ©2016 AACR.
Differential Effects of PI3K and Dual PI3K/mTOR Inhibition in Rat Prolactin-Secreting Pituitary Tumors
Authors: Chanal Marie , Chevallier Pascale , Raverot Véronique , Fonteneau Guillaume , Lucia Kristin , Monteserin Garcia Jose Luis , Rachwan Alexa , Jouanneau Emmanuel , Trouillas Jacqueline , Honnorat Jérôme , Auger Carole , Theodoropoulou Marily , Raverot Gérald
Published: March 2016

Aggressive pituitary tumors are rare but difficult to manage, as there is no effective chemotherapy to restrict their growth and cause their shrinkage. Within these tumors, growth-promoting cascades, like the PI3K/mTOR pathway, appear to be activated. We tested the efficacy of two inhibitors of this pathway, NVP-BKM120 (Buparlisib; pan-PI3K) and NVP-BEZ235 (dual PI3K/mTOR), both in vitro on immortalized pituitary tumor cells (GH3) and on primary cell cultures of human pituitary tumors and in vivo on a rat model of prolactin (PRL) tumors (SMtTW3). In vitro, NVP-BEZ235 had a potent apoptotic and cytostatic effect that was characterized by decreased cyclin D/E and Cdk4/2 protein levels and subsequent accumulation of cells in G1. In vivo, the effect was transient, with a decrease in mitotic index and increase in apoptosis; long-term treatment had no significant inhibitory effect on tumor growth. In contrast, while NVP-BKM120 had little effect in vitro, it dramatically limited tumor growth in vivo. Increased Akt phosphorylation observed only in the NVP-BEZ235–treated tumors may explain the differential response to the two inhibitors. Primary cell cultures of human PRL pituitary tumors responded to NVP-BEZ235 with reduced cell viability and decreased hormone secretion, whereas NVP-BKM120 had little effect. Altogether, these results show a potential for PI3K inhibitors in the management of aggressive pituitary tumors. Mol Cancer Ther; 15(6); 1261–70. ©2016 AACR.
Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer
Authors: Mathur Priya S. , Gierut Jessica J. , Guzman Grace , Xie Hui , Xicola Rosa M. , Llor Xavier , Chastkofsky Michael I. , Perekatt Ansu O. , Tyner Angela L.
Published: March 2016

Disruption of the gene encoding Protein Tyrosine Kinase 6 (Ptk6) delayed differentiation and increased growth in the mouse intestine. However, Ptk6-null mice were also resistant to azoxymethane-induced colon tumorigenesis. To further explore functions of PTK6 in colon cancer, expression of epithelial and mesenchymal markers, as well as proliferation, migration, and xenograft tumor growth, was examined in human colon tumor cell lines with knockdown or overexpression of PTK6. PTK6 protein, transcript, and activation were also examined in a human colon tumor tissue array, using immunohistochemistry and qRT-PCR. Knockdown of PTK6 led to the epithelial–mesenchymal transition (EMT) in SW480 and HCT116 cells, whereas overexpression of PTK6 in SW620 cells restored an epithelial phenotype in a kinase-independent manner. PTK6 knockdown also increased xenograft tumor growth of SW480 cells, suggesting tumor suppressor functions. In clinical specimens, PTK6 expression was highest in normal differentiated epithelial cells and reduced in tumors. In contrast, overexpression of constitutively active PTK6 promoted STAT3 and ERK5 activation in colon cancer cells, and endogenous PTK6 promoted cell survival and oncogenic signaling in response to DNA-damaging treatments. These data indicate that PTK6 has complex, context-specific functions in colon cancer; PTK6 promotes the epithelial phenotype to antagonize the EMT in a kinase-independent manner, whereas activation of PTK6 promotes oncogenic signaling.

Implications: Understanding context-specific functions of PTK6 is important, because although it promotes cell survival and oncogenic signaling after DNA damage, expression of PTK6 in established tumors may maintain the epithelial phenotype, preventing tumor progression. Mol Cancer Res; 14(6); 563–73. ©2016 AACR.
Endothelial Cell-Immune Cell Interaction in IBD
Authors: Danese Silvio , Fiocchi Claudio
Published: March 2016

The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells.
Smoking and Diet: Impact on Disease Course?
Authors: Cosnes Jacques
Published: March 2016

Background: The impact of current smoking on inflammatory bowel disease (IBD) course has been studied extensively; smoking is deleterious in Crohn's disease (CD), and beneficial in ulcerative colitis (UC). Except for enteral nutrition, there are only limited data regarding the impact of diet on disease course. Key Messages: Current smoking worsens the course of CD, increasing the incidence of flares, the need for steroids, immunosuppressants and re-operations. Conversely, smoking cessation has a rapid beneficial effect on disease course, decreasing the risk of flares and of post-operative recurrences. From 3 months after the quit date, quitters have a disease course similar to that of never smokers. Achieving smoking cessation in CD is thus an important goal of therapy. On the contrary, smoking improves the course of UC and in particular, is associated with a decreased need for colectomy. Smoking cessation increases the risk of flare and the need for steroids or immunosuppressants. However, patients with UC should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious systemic effects of tobacco. Among dietary interventions, only exclusive enteral nutrition was shown to induce remission and achieve mucosal healing in some patients with CD. The beneficial effect of liquid-defined diet is observed whatever be the type of administration (orally or by tube), the type of diet regarding protein and fat content and resulting alterations in the gut microbiota. In UC, enteral nutrition has no effect. Finally, popularized restrictive diets in IBD as the specific-carbohydrate diet and the gluten-free diet have not been rigorously tested. In a small trial, a semi-vegetarian diet was shown to be effective in maintaining remission over 2 years in CD. Conclusions: Patients with IBD should not smoke and avoid passive smoking. Aside from the defined liquid diets, there is no rationale for advising particular diets.
ASCA, ANCA, ALCA and Many More: Are They Useful in the Diagnosis of Inflammatory Bowel Disease?
Authors: Zhou Guangxi , Song Yang , Yang Wenjing , Guo Yanmin , Fang Leilei , Chen Yamei , Liu Zhanju
Published: March 2016

Background: Inflammatory bowel disease (IBD) is characterized by excessive immune responses to altered intestinal microbiota in genetically susceptible individuals. The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Key Messages: Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. Importantly, serum antibodies against microbial antigens or auto-antigens have been used as biomarkers in predicting disease course, complications and responses to medications and surgery. Moreover, they have been demonstrated to be useful in distinguishing patients with Crohn's disease (CD) from those with ulcerative colitis (UC). Recently, a great number of new serum biomarkers (e.g., anti-glycoprotein 2, anti-granulocyte macrophage colony-stimulating factor, anti-neutrophil cytoplasmic antibody, anti-Saccharomyces cerevisiae antibody, anti-laminaribioside carbohydrate IgG antibody, anti-mannobioside carbohydrate IgG antibody, antibody to the outer membrane protein of Escherichia coli, anti-CBir1) have been found to be present in patients with IBD and are potentially used in the diagnosis and prediction. The presence of these antibodies in the sera is due to the disruption of intestinal mucosa barrier and they may reflect a possibly genetic loss of immunological tolerance toward microbiota-derived antigens. Due to their non-invasive, easily accessible, repetitive and economical characteristics, these biomarkers have been found to serve as precious supplementary means in the diagnosis and disease evaluation of IBD. Conclusions: Currently, the most important utility of serological biomarkers is to evaluate the aggressive risks of disease phenotype, complications or surgery requirement, predict prognosis of the disease and distinguish CD from UC. However, they have limited values in making initially definite diagnosis for IBD. Therefore, more effective biomarkers with high sensitivity and specificity need to be further explored in the future.
Oral or Topical 5-ASA in Ulcerative Colitis
Authors: Hanauer Stephen B.
Published: March 2016

Aminosalicylates (5-ASAs) are foundational therapies for patients with mild-moderate active ulcerative colitis (UC) and to maintain remissions. A variety of oral and topical formulations have been evaluated in both active and quiescent disease in both extensive and distal UC. This review summarizes data on pharmacokinetics and applications of oral and topical 5-ASA therapies in active and quiescent, extensive colitis and distal disease, both as monotherapies and in combination and reviews dosing and dosing intervals for oral 5-ASA in both active disease and to maintain remissions.
Methotrexate for Inflammatory Bowel Diseases - New Developments
Authors: Herfarth Hans H.
Published: March 2016

Methotrexate (MTX) is an established therapy for patients with steroid-dependent Crohn's disease (CD). MTX is also frequently used in combination with anti-TNF agents to suppress anti-drug antibody formation. It has been suggested in the past that MTX lacks any clinical effectiveness in patients with ulcerative colitis (UC); however, newer data at least partially contradict this assumption. The following review will discuss recent data for the use of MTX in CD, UC and in combination with anti-TNF agents.
Mucosal Healing - How Deep Is Enough?
Authors: Iacucci Marietta , Ghosh Subrata
Published: March 2016

Mucosal healing has emerged as an important outcome measure of treatment in inflammatory bowel disease (IBD). It is increasingly incorporated in the outcome measures of clinical trials along with patient reported outcomes and used in clinical practice as a therapeutic target or goal. The exact definition of mucosal healing continues to evolve and several scoring systems have been developed, some of which require further validation. Considerable inter-observer variation may also exist in interpretation of mucosal appearance in IBD. Novel endoscopic techniques demonstrate that even in patients who have achieved mucosal healing by conventional criteria, subtle inflammation may continue to persist. Whether mucosal healing needs to incorporate or reflect histological healing is a topic of intense debate and further studies. In addition, surrogate markers of mucosal healing, such as fecal calprotectin, may serve as a therapeutic target, but there is debate about whether normalization of fecal calprotectin always reflects mucosal healing. Patients with mucosal healing may also continue to have clinical symptoms reflecting visceral hypersensitivity.
High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease
Authors: Kapoor Sarika , Rodriguez Daniel , Mitchell Katharyn , Wüthrich Rudolf P.
Published: March 2016

Background/Aims: The PCK rat model of polycystic kidney disease is characterized by the progressive development of renal medullary cysts. Here, we evaluated the suitability of high resolution ultrasonography (HRU) to assess the kidney and cyst volume in PCK rats, testing three different ultrasound image analysis methods, and correlating them with kidneys weights and histological examinations. Methods: After inducing anesthesia, PCK rats (n=18) were subjected to HRU to visualize the kidneys, to perform numeric and volumetric measurements of the kidney and any cysts observed, and to generate 3-dimensional images of the cysts within the kidney parenchyma. Results: HRU provided superior information in comparison to microscopic analysis of stained kidney sections. HRU-based kidney volumes correlated strongly with kidney weights (R2=0.809; P<0.0001). Conclusion: HRU represents a useful diagnostic tool for kidney and cyst volume measurements in PCK rats. Sequential HRU examinations may be useful to study the effect of drugs on cyst growth without the need to euthanize experimental animals.
An (Anti)-Inflammatory Microbiota: Defining the Role in Inflammatory Bowel Disease?
Authors: Burman S. , Hoedt E.C. , Pottenger S. , Mohd-Najman N.-S. , Ó Cuív P. , Morrison Mark
Published: March 2016

While it is now accepted that the gut microbiota contribute to the genotype-environment-lifestyle interactions triggering inflammatory bowel disease (IBD) episodes, efforts to identify the pathogen(s) that cause these diseases have met with limited success. The advent of culture-independent techniques for characterizing the structure and/or function of microbial communities (hereafter referred to as metagenomics) has provided new insights into the events associated with the onset, remission and recurrence of IBD. A large number of observational and/or case-control studies of IBD patients have confirmed substantive changes in gut bacterial profiles (dysbiosis) associated with disease. These types of studies have been augmented by new profiling approaches that support the identification of more ‘colitogenic' bacteria from numerically predominant taxa. Evidence of alterations in lesser abundant taxa such as the methanogenic archaea, to favor types that are more immunogenic, has also been forthcoming. Several recent longitudinal studies of patients with Crohn's disease have produced additional insights, including evidence for the role of ‘anti-inflammatory' microbiota in providing a protective effect and/or promoting remission. In summation, the implications of dysbiosis and restoration of a ‘healthy microbiota' in IBD patients requires definition beyond a taxonomic assessment of the changes in the gut microbiota during disease course. The available evidence does suggest that specific members of the gut microbiota can contribute either pro- or anti-inflammatory effects, and their ecological fitness in the large bowel affects the onset and recurrence of IBD. While metagenomics and related approaches offer the potential to provide novel and important insights into these microbiota and thereby the pathophysiology of IBD, we also need to better understand factors affecting the ecological fitness of these microbes, if new treatment of IBD patients are to be delivered.
Methods for Measuring Lung Volumes: Is There a Better One?
Authors: Tantucci Claudio , Bottone Damiano , Borghesi Andrea , Guerini Michele , Quadri Federico , Pini Laura
Published: March 2016

Background: Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. Objectives: It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive ‘a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. Results: The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. Conclusion: In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction.
Genotype and Phenotype Characteristics in 22 Patients with Vitamin D-Dependent Rickets Type I
Authors: Tahir Sophia , Demirbilek Hüseyin , Ozbek Mehmet Nuri , Baran Riza Taner , Tanriverdi Sibel , Hussain Khalid
Published: March 2016

Background and Aims: Vitamin D-dependent rickets type I (VDDR1) is an autosomal recessive disorder caused by mutations in the 25-hydroxyvitamin D 1-alpha-hydroxylase gene (CYP27B1). Mutations in CYP27B1 disrupt or lead to a total loss of the 1-α-hydroxylase activity and require treatment with physiological doses of calcitriol. Patients and Methods: A genetic analysis of the CYP27B1 gene was conducted in 22 Turkish patients with VDDR1 from 13 families. Presenting characteristics, biochemical features, treatment, and results from the genetic analysis are described. Results: A splice donor site mutation c.195 + 2T>G was found in 10 patients. The novel missense p.192K>E (c.574A>G) mutation was detected in 5 patients, and a novel missense p.197G>D (c.590G>A) mutation was found in 4 patients. A previously reported 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) in exon 8 was detected in 1 patient, and 1 patient was a compound heterozygote for the novel p.192K>E and the previously described 1319-1325dupCCCACCC mutations. A novel single base pair deletion, c.171_171delG, leading to a frameshift, was found in 1 patient. Conclusions: We identified 3 novel and 2 previously described mutations in the CYP27B1 gene. A marked phenotypical diversity was observed between families that carried identical mutations, suggesting phenotypical heterogeneity.
O emprego da fotografia como método de análise da transformação da paisagem - o caso de Anchieta
Authors: Goltara Giovani Bonadiman , Mendonça Eneida Maria Souza
Published: March 2016

A imagem fotográfica, desde o início de sua utilização, é aceita pelo censo comum, e em parte, também, pelo meio técnico-científico, como imagem da realidade. Contudo, seu processo criativo é pautado em ações que podem gerar ambiguidades. Este artigo vincula-se à pesquisa sobre a transformação da paisagem contemporânea, focada no município de Anchieta como nova fronteira metropolitana ao sul da Grande Vitória, Espírito Santo, no sudeste do Brasil e tem como objetivo avaliar o potencial da utilização da fotografia nos estudos relacionados à paisagem. A metodologia envolveu revisão bibliográfica acerca do emprego da fotografia como expressão da realidade e sua utilização em trabalhos técnico-científicos. Através de identificação de fotografias de Anchieta em comparação com estudos históricos e de evolução da ocupação do município, concluiu-se que, embora sejam sujeitas a questões relacionadas à veracidade ou confiabilidade, as fotografias são capazes de remontar a história da transformação da paisagem de forma eficaz.
Espaços livres e morfologia urbana: discussões sobre influências na qualidade climática e sustentabilidade urbana a partir de estudos em cidades no estado de Alagoas – Brasil
Authors: Barbirato Gianna Melo , Torres Simone Carnaúba , Barbosa Ricardo Victor Rodrigues
Published: March 2016

O presente artigo traz reflexões sobre morfologia urbana, espaços livres e sua relação com a adequação climática e a sustentabilidade urbana, a partir da análise de mapas climáticos e cenários urbanos com o auxílio de simulações computacionais realizadas nas cidades de Maceió e Arapiraca, no Estado de Alagoas. Esses estudos revelam que os padrões de ocupação urbana determinados pelos atuais instrumentos de legislação urbanística não são capazes de potencializar o aproveitamento de condicionantes ambientais no meio urbano. Este artigo destaca, também, a necessidade de revisão e refinamento destes para o alcance da adequação ambiental de espaços, enfatizando a possibilidade do estímulo ao adensamento construtivo fundamentado na capacidade de carga do sistema urbano.
Another Look at p.ifao ii 31 (𝔓98)
Authors: Málik Peter
Published: March 2016

The article provides a fresh edition and analysis of p.ifao inv. 237b (𝔓98), supposedly the earliest manuscript of the Book of Revelation. The new edition includes corrections to Hagedorn’s 1992 edition, an updated transcription (including two previously undeciphered lines of text), and a colour image of the papyrus. The text of the papyrus is then inspected and classified based on the manner of transmission and the textual quality it reflects.
Phylogenetic insights into the Anomopoda, mainly derived from a comparative study of trunk limb 1
Authors: Dumont Henri J.
Published: March 2016

The P1 in a clade formed by the radopods and daphniid-like families of the anomopods nicely reflects the evolution that has occurred in the order. The Gondwanotrichidae are the only family that has a remnant of an exopodite, but in several other families an exopodite seta is still preserved. The primitive Gondwanothrix has a total of 20 setae on its surface, a number that decreases in the 11 families considered to a minimum of 9 in Moina salina Daday, 1888. Radopods plus Daphniid families are housed in a new suborder, the Mixopoda. The three daphniid families themselves belong in the new infraorder Verripoda. The P1 of the Radopoda has a basal inflexion and a gnathobase; the Verripoda have lost both. Even in the most advanced Mixopoda, the P1 still shows evidence of at least four endite segments. This is no longer the case in the Bosminidae and Ilyocryptidae, which also have ejector hooks in the apical instead of the basal position on the limb. The building blocks of the limb in the latter families are not identifiable. Both families appear old and probably merit to be classified as suborders.
In Deep Water: Towards a Greater Commitment for Human Rights in Sea Operations Coordinated by Frontex?
Authors: Vara Juan Santos , Sánchez-Tabernero Soledad R.
Published: March 2016

Frontex and the eu Member States have been criticised for not carrying out sea surveillance operations coordinated by the Agency in full compliance with human rights obligations. While Frontex and the Member States are clearly obliged to respect human rights when carrying out maritime surveillance operations within their territorial waters and contiguous zone, the question is much more complex on the high seas and especially in the territorial waters of a third country. Therefore, the most problematic question in Frontex operations is the extraterritorial application of human rights obligations of the eu and its Member States. The aim of this paper is to determine to what extent Regulation 656/2014 has introduced a clear regulation of the interception and rescue operations coordinated by Frontex while at the same time fully respecting fundamental rights and, in particular, the principle of non-refoulement.
“ʼTis but the chance of War”: Fortune and Opportunity in Shakespeare’s Troilus and Cressida
Authors: Ansaldo Marina
Published: March 2016

The study of the representation of the interrelated notions of Fortune and Occasio in Shakespeare’s Troilus and Cressida has been largely neglected by critics. This is particularly surprising because this play, where all that takes place is nothing “but the chance of war,” and characters’ efforts and expectations are often contradicted by the turns of events, seems to invite us to meditate upon what determines a successful outcome. This article shows that considering the concepts of Fortune and Occasion, and the imagery traditionally associated with them, can provide original critical perspectives on this play. The manner in which the characters refer to Fortune/Occasio reveals the extent to which each of them is willing and capable of exercising agency. Sheer opportunism and brute force are what is required to win in the world of the play, where valor, honor and chivalry have become obsolete vestiges of a lost mythical past.
Structure and Performance in a Violent Extremist Network
Authors: Kenney Michael , Coulthart Stephen , Wright Dominick
Published: March 2016

This study combines network science and ethnography to explore how al-Muhajiroun, a banned Islamist network, continued its high-risk activism despite being targeted for disruption by British authorities. We analyze news reports, interviews, and field notes using social network analysis and qualitative content analysis to test hypotheses pertaining to network structure and performance. Our analysis suggests that the activist network’s structural properties had important implications for its performance during three separate time periods. What began as a centralized, scale-free-like, small-world network centered on a charismatic leader evolved into a more decentralized “small-world-like” network featuring clusters of local activists connected through multiple bridges. This structure allowed the activist network to engage in contentious politics even as its environment became increasingly hostile. We conclude by discussing the implications of al-Muhajiroun’s small-world solution for scholars and policy makers.
Burnout, depressive symptoms, job demands and satisfaction with life: discriminant validity and explained variance
Authors: Thuynsma Cara , de Beer Leon T
Published: March 2016

Burnout is considered an occupational health concern. The burnout–depression overlap is an important area of research as the foundations of burnout and its diagnostic value have come under increasing scrutiny, calling for burnout to not be classified as an independent disorder but rather as a subtype of depression. Furthermore, as burnout is defined as a work-specific syndrome, workplace factors have been argued to be the major indicators of burnout. Recent research however, calls this into question. This study seeks to establish the overlap between burnout and depressive symptoms and to determine if burnout is in fact a multi-domain phenomenon. A cross-sectional research design was used, a convenience sample of educators from the Gauteng province of South Africa was collected ( N = 399). Confirmatory factor analysis was applied in a structural equation modelling framework. Discriminant validity analysis was conducted by investigating the average variance extracted and the shared variance between constructs. Finally, relative weight analysis was conducted to ascertain the unique contribution explained by the work-specific and general life domain factors. Results showed that burnout could be distinguished from depressive symptoms. Job demands, depressive symptoms, and satisfaction with life all explained significant amounts of variance in the burnout construct. Relative weight analysis revealed that emotional load and depressive symptoms explained equal amounts of variance in burnout, but that the aggregated work-specific factors explained the most variance in burnout. This study indicates that burnout is a multi-domain phenomenon and not isolated to the domain of work. Further research is needed in this regard.