bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L.
Authors: Brito Samara Alves , de Almeida Cynthia Layse Ferreira , de Santana Temístocles Italo , da Silva Oliveira Alisson Rodrigo , do Nascimento Figueiredo Jéssica Carla Bezerra , Souza Isis Torres , de Almeida Lécio Leone , da Silva Márcia Vanusa , Borges Augusto Santos , de Medeiros Jonathan Wagner , da Costa Silva Neto Jacinto , de Cássia Ribeiro Gonçalves Rita , Kitagawa Rodrigo Rezende , Sant′Ana Antônio Euzébio Goulart , Rolim Larissa Araújo , de Menezes Irwin Rose Alencar , da Silva Teresinha Gonçalves , Caldas Germana Freire Rocha , Wanderley Almir Gonçalves
Published: April 2018

Spondias mombin L. is used in folk medicine for the treatment of inflammation and gastrointestinal diseases. Our study investigated the antiulcer activity of S. mombin ethanolic extract (SmEE) and its majority compounds gallic acid (GA) and ellagic acid (EA). Phytochemical characterization was performed by HPLC. The SmEE was screened for in vitro antioxidant activities using phosphomolybdenum, ABTS, DPPH, and FRAP assays. The antiulcer activity of SmEE, GA, EA, or GA + EA was evaluated by gastric lesion models induced by absolute ethanol and indomethacin. Following this, it is capable of stimulating mucus production, antisecretory capacity, and the influence of −SH groups and NO in the effect of SmEE. Its healing activity was demonstrated by acetic acid‐induced chronic ulcer model. Anti‐Helicobacter pylori activity was assessed by determining the MIC of the SmEE (64–1024 μg/mL). The HPLC results identified the presence of gallic acid and ellagic acid in SmEE. The extract showed antioxidant activity in vitro. SmEE (50, 100, and 200 mg/kg) reduced the area of ulcerative lesions induced by ethanol in 23.8, 90.3, and 90.2%, respectively. In NSAID model, the SmEE induced protection of 36.8, 49.4, and 49.9%, respectively. GA (10 mg/kg) or EA (7 mg/kg) or the association of GA + EA (10 + 7 mg/kg) inhibited the ethanol‐induced lesions in 71.8, 70.9, and 94.9%, respectively, indicating synergistic action. SmEE (100 mg/kg) decreased acid secretion and H+ concentration in the gastric contents, increased levels of mucus, and showed to be dependent of −SH groups and NO on the protection of the gastric mucosa. In chronic ulcer model, SmEE reduced the gastric area lesion. SmEE showed anti‐H. pylori activity. In conclusion, our study showed that SmEE has antiulcerogenic activity. GA and EA are isolated gastric protectors and, when associated, acted synergistically to protect the gastric mucosa.
Acylcarnitine Profiles in Plasma and Tissues of Hyperglycemic NZO Mice Correlate with Metabolite Changes of Human Diabetes
Authors: Weiser Anna , Giesbertz Pieter , Daniel Hannelore , Spanier Britta
Published: April 2018

The New Zealand obese (NZO) mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM), obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC) and amino acid (AA) species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA-) derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA) including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs) further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM.
Function and Regulation of Protein Kinase D in Oxidative Stress: A Tale of Isoforms
Authors: Cobbaut Mathias , Van Lint Johan
Published: April 2018

Oxidative stress is a condition that arises when cells are faced with levels of reactive oxygen species (ROS) that destabilize the homeostatic redox balance. High levels of ROS can cause damage to macromolecules including DNA, lipids, and proteins, eventually resulting in cell death. Moderate levels of ROS however serve as signaling molecules that can drive and potentiate several cellular phenotypes. Increased levels of ROS are associated with a number of diseases including neurological disorders and cancer. In cancer, increased ROS levels can contribute to cancer cell survival and proliferation via the activation of several signaling pathways. One of the downstream effectors of increased ROS is the protein kinase D (PKD) family of kinases. In this review, we will discuss the regulation and function of this family of ROS‐activated kinases and describe their unique isoform‐specific features, in terms of both kinase regulation and signaling output.
Experimental Investigation on the Mechanical Characteristics and Deformation Behaviour of Fractured Rock‐Like Material with One Single Fissure under the Conventional Triaxial Compression
Authors: Xiao Taoli , Huang Mei , Cheng Cheng , He Yunlong
Published: April 2018

An experimental study was carried out on a rock‐like material specimen containing a single fissure to investigate its mechanical characteristics and deformation behaviour under triaxial compression. The mechanical characteristics, such as peak strength and residual strength, are discussed. The confining pressure had a distinct effect on the ductility characteristics of the specimen. “A distinct stress drop” occurred in the early stage of the stress‐strain curve when the length fissure was relatively long. The I‐crack, II‐crack, and III‐crack are all observed under triaxial compression, and the III‐crack is commonly observed under triaxial compression. Confining pressure plays an essential role in affecting the failure mode of the specimen. There are three kinds of failure modes in the triaxial compression experiment on a rock‐like material specimen with one single fissure: tensile‐shear comprehensive failure, “X”‐shaped shear failure, and shear failure along the fissure plane. These results are important and fundamental to understand the fracture mechanism of rock engineering.
Electroacupuncture Reduces Weight in Diet‐Induced Obese Rats via Hypothalamic Tsc1 Promoter Demethylation and Inhibition of the Activity of mTORC1 Signaling Pathway
Authors: Leng Jincheng , Xiong Feng , Yao Junpeng , Dai Xiahuan , Luo Yulei , Hu Maoqing , Zhang Lin , Li Ying
Published: April 2018

Subject. The study aimed to investigate the mechanism of electroacupuncture reducing weight via tuberous sclerosis complex 1 (Tsc1) promoter methylation, inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. Materials and Methods. Male Sprague‐Dawley rats were divided into chow‐fed group (chow group) or high‐fat diet group (HF group) for 14 weeks. The obesity rats in HF group were randomly divided into electroacupuncture group (EA group) and diet‐induced obesity (DIO) group, which received EA stimulation on bilateral ST25, RN12, SP6, and ST36 for 4 weeks or no further treatment, respectively. Methylation of the Tsc1 gene promoter and expression of agouti‐related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (PoMC) were detected at the 18th week. Results. At week 18, weight, body fat, and the body fat rate in DIO group were significantly higher than those of the chow and EA group. Compared with the chow group, the DIO group had increased methylation of the Tsc1 gene promoter and expression of mTORC1, AgRP, and NPY gene and decreased PoMC in the hypothalamus; after EA, methylation of the Tsc1 gene promoter, mRNA, and protein of the mTORC1 and expression of AgRP and NPY gene decreased and PoMC increased significantly. Conclusions. Our study could shed light on the potential pathway where EA exerts effects on the mechanism of EA treatment for obesity through the hypothalamic Tsc1 promoter demethylation and inhibition of the activity of mTORC1 signaling pathway.
FTOrs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents
Authors: Nascimento Gabrielle Araujo do , Leite Neiva , Furtado-Alle Lupe , Teixeira Mayza Dalcin , Souza Ricardo Lehtonen Rodrigues de , Milano Gerusa Eisfeld , Silva Larissa Rosa da , Pizzi Juliana , Lopes Wendell Arthur , Lopes Maria de Fátima Aguiar , Titski Ana Cláudia Kapp , Tureck Luciane Viater
Published: April 2018

Purpose. The rs9939609 SNP (T > A) inFTOgene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables.Methods. The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay.Results. The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise.Conclusions. In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise.
Variation of Contact Angles in Brine/CO2/Mica System considering Short-Term Geological CO2 Sequestration Condition
Authors: Jafari Mohammad , Jung Jongwon
Published: April 2018

Geological CO2 sequestration has been proposed as an effective solution to mitigate excessive human-emitted CO2 in atmosphere. Knowledge of immiscible two-phase flow of CO2-water/brine is necessary to evaluate the efficiency and safety of geological storage sites. Among forces dominating fluid flow, capillary pressure is highly important because of high uncertainty in measurement due to ambiguous wettability behavior of geomaterials. In particular, time-dependent wettability of geomaterials is of interest for predicting short-term performance of the storage site. After injection of CO2 into an aquifer, both the CO2 and water/brine in rocks pores are unsaturated and tend to dissolve into each other. Present study investigates the variation of contact angle on mica sheet using a captive bubble method at a wide range of pressures and salinities under unsaturated condition. Our results showed a general increase of contact angle with time. Comparison of unsaturated contact angle with previous results in the literature showed a wide span of wettability behavior, ranging from receding to advancing contact angle values reported in the literature. The observed decrease in wettability by time due to heterogeneity and pinning effect of triple line can jeopardize the safety of geological carbon sequestration projects in short-term after injection of CO2.
Induction of Apoptosis and Inhibition of Epithelial Mesenchymal Transition by α‐Mangostin in MG‐63 Cell Lines
Authors: Park Sung-Jin , Park Bong-Soo , Yu Su-Bin , Kang Hae-Mi , Kim Hye-Jin , Kim In-Ryoung
Published: April 2018

Osteosarcoma is the most common bone primary malignant tumor and nearly 30% of patients still die from osteosarcoma due to metastasis or recurrence. Thus, it is necessary to develop effective new chemotherapeutic agents for osteosarcoma treatment. α‐Mangostin is a xanthone derivative shown to have antioxidant and anticarcinogen properties. However, the molecular mechanisms underlying the antimetastatic effects of osteosarcoma remain unclear. In metastasis progression, epithelial mesenchymal transition (EMT) is a process that plays important roles in development, cell polarity, and increased invasion and migration. This study focused on the induction of apoptosis and inhibition of EMT process by α‐mangostin in human osteosarcoma cell line MG63. α‐Mangostin treatments on MG63 cells not only showed the several lines of evidence of apoptotic cell death but also inhibited cell migration, invasion, and EMT‐inducing transcription factor. In conclusion, we demonstrate that the α‐mangostin induces apoptosis via mitochondrial pathway and suppresses metastasis of osteosarcoma cells by inhibiting EMT.
Dynamic Safety Assessment in Nonlinear Hydropower Generation Systems
Authors: Li Shuang , Yang Yong , Xia Qing
Published: April 2018

This paper focuses on the stability problems in a hydropower station. To enable this study, we consider a nonlinear hydropower generation system for the load rejection transient process based on an existing hydropower station. Herein we identify four critical variables of the generation system. Then, we carry out the dynamic safety assessment based on the Fisher discriminant method. The dynamic safety level of the system is determined, and the evolution behavior in the transient process is also performed. The result demonstrates that the hydropower generation system in this study case can operate safely, which is in a good agreement with the corresponding theory and actual engineering. Thus, the framework of dynamic safety assessment aiming at transient processes will not only provide the guidance for safe operation, but also supply the design standard for hydropower stations.
Effect of Yin‐Xing‐Tong‐Zhi Tablets on Improving Vascular Cognitive Impairment No Dementia
Authors: Pan Weidong , Zhu Wei , Gao Qi , Liao Weilong , Gao Penglin , Liu Te
Published: April 2018

Objective. Observe the effect of the Chinese herbal extracts, Yin‐Xing‐Tong‐Zhi, in tablet form, on improving vascular cognitive impairment no dementia (VCIND). Methods. Sixty‐eight patients with VCIND were divided randomly into treatment and placebo groups with oral administration of Yin‐Xing‐Tong‐Zhi tablets (YXTZTs) or placebo, respectively, for 24 weeks. Alzheimer’s Disease Assessment Scale‐Cognitive (ADAS‐Cog) subscale score, MMSE score, Clinician’s Interview‐Based Impression of Change Plus Caregiver Input (CIBIC‐Plus) score, expression of interleukin‐ (IL‐) 6, IL‐8, and tumor necrosis factor‐ (TNF‐) α in serum, and variation of blood‐lipid levels were evaluated at different time points. Results. At weeks 12 and 24, the scores for the ADAS‐Cog, CIBIC‐Plus, and MMSE of the treatment group were significantly lower than those of the control group (P < 0.05). All clinical scales at week 24 of the control group were significantly different from those before treatment (P < 0.05). Expression of IL‐6, IL‐8, and TNF‐α in the two groups was reduced significantly with variation of the clinical scales of cognitive impairment. Conclusion. YXTZTs may delay the development of cognitive impairment in VCIND patients by modulating expression of VCIND‐associated proinflammatory factors.
Amino Acids, Mineral Nutrients, and Efficacy of Vermicompost and Seafood and Municipal Solid Wastes Composts
Authors: Abbey Lord , Annan Nana , Asiedu Samuel Kwaku , Esan Ebenezer Oluwaseun , Iheshiulo Ekene Mark-Anthony
Published: April 2018

Growing medium amino acids and mineral nutrients stimulate rhizosphere activities and plant growth. A greenhouse experiment was performed to compare amino acid and mineral nutrient profiles of seafood waste compost (SFWC) and municipal solid waste compost (MSWC) and vermicompost (VC). Their efficacies were also tested on onion (Allium cepa L. “Sweet Utah”). The control was Promix-BX™ alone. The MSWC, SFWC, and VC were composed of total of 36.4, 48.3, and 67.5 mg amino acids/100 g dry weight, respectively. Glutamic acid, aspartic acid, and glycine were the highest while methionine, histamine, and cysteine were the least in all the amendments. The VC had the highest Ca content but the least P and K contents. SFWC had the highest content of P and K and most of the determined micronutrients. The MSWC had significantly (P<0.05) the highest N and leaf chlorophyll contents followed by the VC. The MSWC significantly (P<0.05) increased anthocyanin content while the control recorded the least. The maximum quantum yield of photosystem II (Fv/Fm) and the potential photosynthetic capacity (Fv/Fo) were least in the VC treated plants. Dry matter was not affected by the type of amendment. Overall, plant growth was improved by the MSWC. Future research should investigate effect on secondary metabolites.
Boundedness and Continuity of Several Integral Operators with Rough Kernels inWFβSn-1on Triebel-Lizorkin Spaces
Authors: Liu Feng
Published: April 2018

A systematic treatment is given of singular integrals and Marcinkiewicz integrals associated with surfaces generated by polynomial compound mappings as well as related maximal functions with rough kernels inWFβ(Sn-1), which relates to the Grafakos-Stefanov function class. Certain boundedness and continuity for these operators on Triebel-Lizorkin spaces and Besov spaces are proved by applying some criterions of bounds and continuity for several operators on the above function spaces.
Study on the REV Size of Fractured Rock in the Non-Darcy Flow Based on the Dual-Porosity Model
Authors: Wang Yuan , Niu Yu-long , Feng Qiang
Published: April 2018

For the problem of whether the representative elementary volume (REV) obtained in the Darcy flow is also applicable to the case of the non-Darcy flow, the study on the REV size within the non-Darcy flow is proposed tentatively. The concept of the REV in the non-Darcy flow is based on the definition of the REV. According to the determination of the REV in the Darcy flow, the intrinsic permeability k and non-Darcy coefficient β are used simultaneously for the determination of the REV in the non-Darcy flow. The pore pressure cohesive element (PPCE) is developed with the subroutine in ABAQUS. Then the simulation method of the Darcy and non-Darcy flow in the fractured rock mass is built using the PPCE. The proposed plan is examined through the comparison with existing research results. It is validated that this technic is efficient and accurate in simulating the Darcy and non-Darcy flow in the fractured rock mass. Combined with fracture networks generated by Monte Carlo Simulation technique, the PPCE is applied to the study on the REV size. Both conditions of the Darcy and non-Darcy flow are simulated for comparison. The simulation results of this model show that the REV of the non-Darcy flow is inconsistent with the REV of the Darcy flow, and the REV of the non-Darcy flow is more significant than the REV of the Darcy flow. The intrinsic permeability k tensors obtained in the Darcy flow and the non-Darcy flow are basically the same.
Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
Authors: Díaz Adriana Graciela , de Lima Andrea Paes , Garibaldi Paula , Rubio Maria de los Milagros , García Florencia , Kral Marta , Bruno Oscar D.
Published: April 2018

Insulinomas are pancreatic neuroendocrine tumors (pNET), usually benign. Akt/p27kip1 is an intracellular pathway overexpressed in many pNET. There are no data regarding its expression in human insulinomas. We aimed to investigate the expression of Akt and p27kip1 in 24 human insulinomas and to compare them to their expression in normal surrounding islets. Staining was performed on embedded paraffin tissue using polyclonal antibodies against total Akt, p-Akt, p27kip1, and pp27kip1. p-Akt was the predominant form in insulinomas; they presented lower Akt and p-Akt expression than normal islets in 83.3% and 87.5% of tumors, respectively. p27kip1 and pp27kip1 were mainly cytoplasmic in both insulinomas and normal tissue. Cytoplasmic pp27kip1 staining was higher in insulinomas and surprisingly nearly half of the insulinomas also presented nuclear p27kip1 (p=0.029). No differences were observed in the subcellular localization of p27kip1 and activation of Akt between benign and malignant insulinomas. The low expression of Akt seen in insulinomas might explain the usual benign behavior of this type of pNET. Cytoplasmic p27kip1 in both insulinomas and normal islet cells could reflect the low rate of replication of beta cells, while nuclear p27kip1 would seem to indicate stabilization and nuclear anchoring of the cyclin D-Cdk4 complex. Our data seem to suggest that the Akt pathway is not involved in human insulinoma tumorigenesis.
Drug Induced Sleep Endoscopy Identification of Adenoid Regrowth in Pediatric Obstructive Sleep Apnea
Authors: Zalzal Habib G. , Carr Michele , Nanda Nainika , Coutras Steven
Published: April 2018

Objective. To establish the incidence and possible contributing factors leading to adenoid regrowth in children with pediatric sleep apnea using drug induced sleep endoscopy (DISE). Methods. Children treated for obstructive sleep apnea following previous adenoidectomy were evaluated using DISE. Adenoid regrowth was scored by the same attending physician using a 5-point grading scale. Age, sex, body mass index (BMI) percent for age, polysomnogram results, initial adenoid size before adenoidectomy, and postoperative complications were evaluated. Results. Fifty-six patients (age range 22 months to 16 years) met inclusion criteria. Twenty-five children (44.6%) had Grade 2 adenoid or larger. Mean age at the time of DISE was 7.11 years, with an average of 1.75 years since initial adenoidectomy. Mean preadenoidectomy size based on intraoperative nasopharyngeal mirror assessment was Grade 2.55 (95% CI 2.30–2.79). Adenoid size at time of sleep endoscopy was Grade 1.64 (95% CI 1.30–1.98). Characteristics associated with adenoid regrowth were higher body mass index for age percentile at time of endoscopy (P<0.05), initial adenoid size (P<0.01), and time between initial adenoidectomy and endoscopy (P=0.05). Conclusions. Body mass index for age percentile, initial adenoid size, and time between initial adenoidectomy and drug induced sleep endoscopy correlate with regrowth in childhood obstructive sleep apnea.
Gundelia tournefortii Antidiabetic Efficacy: Chemical Composition and GLUT4 Translocation
Authors: Kadan Sleman , Sasson Yoel , Saad Bashar , Zaid Hilal
Published: April 2018

In the present in vitro study, we tested the chemical composition, cytotoxicity and antidiabetic activity of two distinct extracts of wild Artichoke‐like vegetable, Gundelia tournefortii: methanol and hexane. GC/MS phytochemical analysis of G. tournefortii methanol and hexane extracts revealed 39 compounds reported here for the first time in G. tournefortii out of the 45 detected compounds. Only Stigmasterol was present in both extracts. The efficacy of G. tournefortii extracts in enhancing glucose transporter 4 (GLUT4) translocation to the plasma membrane (PM) was tested in L6 muscle cells stably expressing myc‐tagged GLUT4 (L6‐GLUT4myc) using cell‐ELISA test. Results obtained here indicate that methanol and hexane extracts were safe up to 250 μg/ml as measured with MTT and the LDH leakage assays. The methanol extract was the most efficient in GLUT4 translocation enhancement. It increased GLUT4 translocation at 63 μg/ml 1.5‐ and 2‐fold relative to the control in the absence and presence of insulin, respectively. These findings indicate that G. tournefortii possesses antidiabetic activity in part by enhancing GLUT4 translocation to the PM in skeletal muscle.
Factors Influencing Compliance and Health Seeking Behaviour for Hypertension in Mukono and Buikwe in Uganda: A Qualitative Study
Authors: Musinguzi Geofrey , Anthierens Sibyl , Nuwaha Fred , Van Geertruyden Jean-Pierre , Wanyenze Rhoda K. , Bastiaens Hilde
Published: April 2018

Background and Methods. Hypertension is a global public health challenge and a leading risk factor for cardiovascular morbidity and mortality. Hypertension control rates are low worldwide, and delay in seeking care is associated with increased mortality. Methods. In a qualitative study, known hypertensive patients were interviewed to explore factors influencing compliance and health seeking behaviour (HSB). Data was analyzed following a semantic thematic analysis approach. Results. Patients sought various channels of care for their hypertension. Self-medication and access to antihypertensive drugs with or without prescription were common as well as use of herbal remedies. Regular monitoring of blood pressure was not a common practice. Factors influencing HSB were related to health systems and the patient socioeconomic and structural environment. The main system issues were related to availability and attitudes of staff and shortage of supplies and medicines. The patient factors were related to awareness, perceived severity, perceived effectiveness of therapy, adverse effects, and perceived fears of lifelong dependence on medicines. The patient socioeconomic status played a role as did the marketing of traditional medicine. Conclusion. Patients seek varied channels of care for their hypertension. Strategies to address the multifactorial dimensions that affect HSB are needed to improve hypertension control in this population.
Prevalence of Diabetes Mellitus and Its Risk Factors among Individuals Aged 15 Years and Above in Mizan-Aman Town, Southwest Ethiopia, 2016: A Cross Sectional Study
Authors: Aynalem Shiferaw Birhanu , Zeleke Ayalew Jejaw
Published: April 2018

Introduction. Diabetes mellitus (DM), which is related to cardiovascular disease, is one of the main global health problems. In Ethiopia, information about this disease is known to be scarce. Objective. To assess the prevalence of diabetes mellitus and its risk factors among individuals aged 15 years and above. Methods. A community-based cross sectional study was carried out from January 01 to March 30, 2016 in Mizan-Aman town, southwest Ethiopia. A multistage sampling technique was used to select study participants. The World Health Organization (WHO) stepwise approach for noncommunicable disease surveillance was deployed to collect data. Total cholesterol and triglyceride level measurements were done using the HumaStar 80 chemistry analyzer. Glucose meter was used to check fasting venous blood glucose level. Descriptive and logistic regression analyses were used. Results. A total of 402 participants were included in the study. The prevalence of DM was found to be 6.5% (26 out of 402). Of which, the proportion of previously undiagnosed diabetes mellitus was 88.5%. The prevalence of prediabetes was also found to be 15.9%. The waist circumference (WC), body mass index, smoking habit, hypertension, and total cholesterol level were significantly associated with diabetes mellitus. Conclusion. In this study, higher prevalence of diabetes mellitus was observed than the IDFA-projected estimate of DM for Ethiopia. Modifiable associated risk factors were also identified. Therefore, targeting the prevention strategy to such modifiable risk factors might reduce the prevalence of diabetes mellitus and screening of DM particularly in those individuals having high WC, history of smoking habit, and hypertension needs attention.
Vision-Threatening Behcet’s Disease: Severity of Ocular Involvement Predictors
Authors: Hussein Mohammed A. , Eissa Iman M. , Dahab Ahmed A.
Published: April 2018

Purpose. To examine and spot systemic findings commonly associated with a serious form of ocular Behcet’s disease. This could potentially help ophthalmologists categorize their patients based on future risk and plan treatment accordingly. Subjects and Methods. The data of 249 patients with Behcet’s disease were examined thoroughly. Correlations between systemic and ocular findings were recorded. Patients were further subgrouped by the authors as having a vision-threatening form of the disease or not. Regression analysis was done to spot predictors for a vision-threatening form of the disease. Results. The presence of systemic vasculitis and oral and genital ulcers in a patient with Behcet’s disease was found to be associated with a milder form of ocular affection or none at all and vice versa. Certain correlations between findings were also found. Conclusion. Certain findings in Behcet’s disease may act as predictors for the severity of ocular affection. Directing our attention to these factors by the internist and ophthalmologist can help plan the frequency of follow-up as well as the aggressiveness of treatment in patients with Behcet’s disease.
Inhibition of the Wnt/β-Catenin Pathway Overcomes Resistance to Enzalutamide in Castration-Resistant Prostate Cancer
Authors: Zhang Zhuangzhuang , Cheng Lijun , Li Jie , Farah Elia , Atallah Nadia M. , Pascuzzi Pete E. , Gupta Sanjay , Liu Xiaoqi
Published: April 2018

Enzalutamide is a second-generation nonsteroidal antiandrogen clinically approved for the treatment of castration-resistant prostate cancer (CRPC), yet resistance to endocrine therapy has limited its success in this setting. Although the androgen receptor (AR) has been associated with therapy failure, the mechanisms underlying this failure have not been elucidated. Bioinformatics analysis predicted that activation of the Wnt/β-catenin pathway and its interaction with AR play a major role in acquisition of enzalutamide resistance. To validate the finding, we show upregulation of β-catenin and AR in enzalutamide-resistant cells, partially due to reduction of β-TrCP–mediated ubiquitination. Although activation of the Wnt/β-catenin pathway in enzalutamide-sensitive cells led to drug resistance, combination of β-catenin inhibitor ICG001 with enzalutamide inhibited expression of stem-like markers, cell proliferation, and tumor growth synergistically in various models. Analysis of clinical datasets revealed a molecule pattern shift in different stages of prostate cancer, where we detected a significant correlation between AR and β-catenin expression. These data identify activation of the Wnt/β-catenin pathway as a major mechanism contributing to enzalutamide resistance and demonstrate the potential to stratify patients with high risk of said resistance.

Significance: Wnt/β-catenin inhibition resensitizes prostate cancer cells to enzalutamide. Cancer Res; 78(12); 3147–62. ©2018 AACR.
Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo
Authors: Kaid Carolini , Goulart Ernesto , Caires-Júnior Luiz C. , Araujo Bruno H.S. , Soares-Schanoski Alessandra , Bueno Heloisa M.S. , Telles-Silva Kayque A. , Astray Renato M. , Assoni Amanda F. , Júnior Antônio F.R. , Ventini Daniella C. , Puglia Ana L.P. , Gomes Roselane P. , Zatz Mayana , Okamoto Oswaldo K.
Published: April 2018

Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells during early development. Here, we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKVBR) against human breast, prostate, colorectal, and embryonal CNS tumor cell lines, we verified a selective infection of CNS tumor cells followed by massive tumor cell death. ZIKVBR was more efficient in destroying embryonal CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKVBR in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis, and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level with activated Wnt signaling were more susceptible to the oncolytic effects of ZIKVBR. Furthermore, modulation of Wnt signaling pathway significantly affected ZIKVBR-induced tumor cell death and viral shedding. Altogether, these preclinical findings indicate that ZIKVBR could be an efficient agent to treat aggressive forms of embryonal CNS tumors and could provide mechanistic insights regarding its oncolytic effects.

Significance: Brazilian Zika virus strain kills aggressive metastatic forms of human CNS tumors and could be a potential oncolytic agent for cancer therapy. Cancer Res; 78(12); 3363–74. ©2018 AACR.
MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors
Authors: Walter Vonn , Du Ying , Danilova Ludmila , Hayward Michele C. , Hayes D. Neil
Published: April 2018

Integrated analyses of multiple genomic datatypes are now common in cancer profiling studies. Such data present opportunities for numerous computational experiments, yet analytic pipelines are limited. Tools such as the cBioPortal and Regulome Explorer, although useful, are not easy to access programmatically or to implement locally. Here, we introduce the MVisAGe R package, which allows users to quantify gene-level associations between two genomic datatypes to investigate the effect of genomic alterations (e.g., DNA copy number changes on gene expression). Visualizing Pearson/Spearman correlation coefficients according to the genomic positions of the underlying genes provides a powerful yet novel tool for conducting exploratory analyses. We demonstrate its utility by analyzing three publicly available cancer datasets. Our approach highlights canonical oncogenes in chr11q13 that displayed the strongest associations between expression and copy number, including CCND1 and CTTN, genes not identified by copy number analysis in the primary reports. We demonstrate highly concordant usage of shared oncogenes on chr3q, yet strikingly diverse oncogene usage on chr11q as a function of HPV infection status. Regions of chr19 that display remarkable associations between methylation and gene expression were identified, as were previously unreported miRNA–gene expression associations that may contribute to the epithelial-to-mesenchymal transition.

Significance: This study presents an important bioinformatics tool that will enable integrated analyses of multiple genomic datatypes. Cancer Res; 78(12); 3375–85. ©2018 AACR.
21-Gene Recurrence Score Assay Predicts Benefit of Post-Mastectomy Radiotherapy in T1-2 N1 Breast Cancer
Authors: Goodman Chelain R. , Seagle Brandon-Luke L. , Kocherginsky Masha , Donnelly Eric D. , Shahabi Shohreh , Strauss Jonathan B.
Published: April 2018

Purpose: Post-mastectomy radiotherapy (PMRT) yields improvements in both locoregional control and overall survival (OS) for women with T1-2 N1 breast cancer. The value of PMRT in this population has been questioned given advances in systemic therapy. The 21-gene recurrence score (RS) assay was evaluated as a predictor of OS among women with T1-2 N1 breast cancer who received or did not receive PMRT.

Experimental Design: An observational cohort study was performed on women with T1-2 N1 estrogen receptor–positive breast cancer from the National Cancer Database (NCDB) and, as a validation cohort, from the surveillance, epidemiology, and end results (SEER) registry who underwent mastectomy and were evaluated for RS. Multivariable parametric accelerated failure time models were used to estimate associations of RS and PMRT with OS using propensity score-adjusted matched cohorts.

Results: In both the NCDB (N = 7,332) and SEER (N = 3,087) cohorts, there was a significant interaction of RS and PMRT with OS (P = 0.009 and P = 0.03, respectively). PMRT was associated with longer OS in women with a low RS [NCDB: time ratio (TR) = 1.70; 95% CI (confidence interval), 1.30–2.22; P < 0.001; SEER: TR = 1.85; 95% CI, 1.33–2.57; P < 0.001], but not in women with an intermediate RS (NCDB: TR = 0.89; 95% CI, 0.69–1.14; P = 0.35; SEER: TR = 0.84; 95% CI, 0.62–1.14; P = 0.26), or a high RS (NCDB: TR = 1.10; 95% CI, 0.91–1.34; P = 0.33; SEER: TR = 0.79; 95% CI, 0.50–1.23; P = 0.28).

Conclusions: Longer survival associated with PMRT was limited to women with a low RS. PMRT may confer the greatest OS benefit for patients at the lowest risk of distant recurrence. These results caution against omission of PMRT among women with low RS. Clin Cancer Res; 24(16); 3878–87. ©2018 AACR.
The Concentration of Iodine in Perigastric Adipose Tissue: A Novel Index for the Assessment of Serosal Invasion in Patients with Gastric Cancer after Neoadjuvant Chemotherapy
Authors: Yang Li , Li Yong , Shi Gao-feng , Zhou Tao , Tan Bi-bo
Published: April 2018

Objective: This study aims to explore the association between iodine concentration (IC) in perigastric adipose tissue (PAT), quantified by dual-energy computed tomography (DECT) and serosal invasion (SI) in patients with gastric cancer post-neoadjuvant chemotherapy (NAC). Methods: Forty-three patients with T4-staged gastric cancer were enrolled. IC and standardized IC in PAT (ICPAT and SICPAT) were quantified by DECT pre and post NAC. A postoperative pathologic examination was performed to stage gastric cancer. Results: After NAC, a total of 43 participants were assigned to group A with 13 patients and group B with 30 patients according to the results of the postoperative pathologic examination. The accuracy of conventional CT in identifying SI was 74.42%. Differences of variations between pre- and post- NAC ICPAT, SICPAT, ∆ICPAT, and ∆SICPAT were observed respectively (p < 0.05). Intragroup ICPAT and SICPAT also changed significantly after NAC (p < 0.05). The area under the ROC curve was 0.929, with the threshold of ∆SICPAT reaching 0.095. The sensitivity, specificity, and accuracy of SICPAT in identifying post-NAC SI were 92.30, 86.70, and 88.37% respectively. Moreover, the 2 measurements in the same patient maintain a high level of consistency. Conclusion: These results showed that SICPAT is a reliable index for identifying post-NAC SI.
Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study
Authors: Yacoub Mona-Rita , Ramirez Giuseppe A. , Berti Alvise , Mercurio Giuseppe , Breda Daniela , Saporiti Nicoletta , Burastero Samuele , Dagna Lorenzo , Colombo Giselda
Published: April 2018

Introduction: Diamine oxidase (DAO) catabolizes and inactivates histamine, a key player in a wide range of invalidating conditions, such as migraine and chronic spontaneous urticaria (CSU). The highest expression of DAO occurs in the gastrointestinal tract, possibly to control the burden of histamine intake from food. Methods: Here, we tested the hypothesis that a 30-day oral supplementation with DAO (1 capsule b.i.d., 15 min before a meal) could reduce the severity of CSU as estimated by the 7-Day Urticaria Activity Score (UAS-7). The study was designed as a double-blind, placebo-controlled, crossover investigation of 22 patients with CSU incompletely controlled by first-line antihistamine therapy. Results: Twenty patients completed the study. Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo). The degree of UAS-7 improvement was inversely correlated with the levels of basal DAO (p = 0.019). Patients receiving DAO supplementation were able to slightly reduce their daily antihistamine dose (p = 0.049). Conclusion: These data suggest that DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.
Gamma Knife Stereotactic Radiosurgery for the Treatment of Brain Metastases from Primary Tumors of the Urinary Bladder
Authors: Taylor James M. , McTyre Emory R. , Tatter Stephen B. , Laxton Adrian W. , Munley Michael T. , Chan Michael D. , Cramer Christina K.
Published: April 2018

Background/Aims: Brain metastases from bladder cancer are rare and published outcomes data are sparse. To date, no institutions have reported a series of patients with brain metastases from bladder cancer treated with stereotactic radiosurgery (SRS). Our aim was to identify patients with brain metastases from bladder primaries treated with SRS with or without surgical resection and report the clinical outcomes. Methods: Patients meeting eligibility criteria at our institution between 2000 and 2017 were included. The clinical variables of interest, including overall survival (OS), local recurrence, V12, distant brain failure (DBF), and initial brain metastases velocity, were calculated. Cox proportional hazards analysis was performed to identify predictors of time-to-event outcomes. Results: A total of 14 patients were included. The median OS from the time of treatment was 2.1 months. Factors predictive of OS include intracranial resection (HR 0.21, p = 0.03). The cumulative incidence of local failure was 21% at 6 months and 30% at 12 months. The cumulative incidence of DBF at 6 and 12 months was 23 and 31%, respectively. Conclusions: The prognosis in this patient population remains guarded. Factors associated with improved survival include intracranial resection. Future, prospective work is needed to further define optimal management.
Effectiveness of Wound-Edge Protectors for Preventing Surgical Site Infections after Open Surgery for Colorectal Disease: A Prospective Cohort Study with Two Parallel Study Groups
Authors: Kobayashi Hirotoshi , Uetake Hiroyuki , Yasuno Masamichi , Sugihara Kenichi
Published: April 2018

Background: Standard procedures to reduce the surgical site infection (SSI) rate after colorectal surgery have not been established. A prospective cohort study with 2 parallel study groups was performed to clarify the SSI rate after open surgery with and without a wound-edge protector (WEP) for colorectal disease. Methods: A total of 102 patients who underwent elective open surgery for colorectal disease between October 2012 and August 2014 were randomly assigned to a WEP group and a WEP (–) group. The primary endpoint was the SSI rate in both groups. Results: Fifty-one patients were assigned to the WEP group and 51 to the WEP (–) group. Two patients were excluded from this study. The rate of SSI with and without a WEP was 16 and 36% respectively (p = 0.021). Older age (p = 0.0073) and no WEP (p = 0.021) were risk factors for SSI after open surgery for colorectal diseases on univariate analysis. On multivariate analysis, both older age (p = 0.016) and no WEP (p = 0.012) were independent risk factors for SSI. Conclusion: The present randomized, phase II trial found an SSI rate of 16% with use of a WEP. The SSI rate was lower in the WEP group than in the WEP (–) group. A WEP may reduce the SSI rate after open surgery for colorectal disease in Japanese patients.
Motorized Spiral Enteroscopy for Occult Bleeding
Authors: Mans Laura , Arvanitakis Marianna , Neuhaus Horst , Devière Jacques
Published: April 2018

Small-bowel disorders remain a diagnostic and therapeutic challenge due to intestinal length. Their management was revolutionized by the emergence of deep enteroscopy. In comparison with video capsule endoscopy, deep enteroscopy allows diagnostic and therapeutic interventions. Spiral enteroscopy (Spirus Medical Endo-Ease Overtube) achieves progression by gentle push and manual clockwise rotation inducing pleating of the small bowel on the endoscope. It has the advantage of shorter examination time and more stability during withdrawal but requires two operators. The Novel Motorized Spiral Enteroscope (Olympus Corp.) incorporates a user-controlled motor contained in the handle of the endoscope. This would offer the possibility to accelerate the procedure, facilitate insertion, and simplify the technique with a single operator.
Accidental Insertion of a Peritoneal Dialysis Catheter in the Urinary Bladder
Authors: Riar Shivraj , Abdulhadi Mohammed , Day Christine , Prasad Bhanu
Published: April 2018

Percutaneous insertion of a peritoneal dialysis (PD) catheter has inherent risks of complications, more so if done “blind” (without fluoroscopy and ultrasound guidance). Despite the perceived disadvantages, there are very few reported cases of mechanical complications after PD catheter insertion. We present an 81-year-old man who underwent percutaneous insertion of dual-cuffed coiled Tenckhoff PD catheter under local anesthesia by a trained nephrologist. The procedure was uneventful, and the patient was discharged 45 min later in a stable state. A day later, he noticed a decline in the urine output. A week later at a scheduled clinic visit, upon unclamping the PD catheter, there was a sudden gush of amber colored fluid. A diagnostic CT scan confirmed the presence of PD catheter entering the abdominal cavity inferior to the umbilicus and the distal end coiled in the urinary bladder. This case illustrates the need for prophylactic Foley catheterization in individuals at high risk for a distended bladder either as a consequence of a mechanical obstruction from an enlarged prostate or due to a neurogenic bladder while undergoing “blind” percutaneous placement.
The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1
Authors: Radtke Arlo , Hennig Finja , Ikogho Raphael , Hammel Johannes , Anheuser Petra , Wülfing Christian , Belge Gazanfer , Dieckmann Klaus-Peter
Published: April 2018

Background: Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment. Patients and Methods: Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days. Three had additional tests done within 24 h after surgery. Measurement results were analysed using descriptive statistical methods. Results: Serum levels dropped to 2.62, 1.27, and 0.47% of the preoperative level within 1, 2, and 3 days, respectively. The computed half-life amounts to 3.7–7 h. The velocity of decay is significantly associated with tumour size. Conclusions: Serum-levels of miR-371a-3p have a short half-life of less than 12 h. The rapid decay after treatment represents a valuable feature confirming the usefulness of miR-371a-3p as a valuable serum biomarker of GCT.