bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Management of Intracanal Rib Head Dislocation in Neurofibromatosis Type 1 Dystrophic Kyphoscoliosis: Report of Two Cases and Literature Review
Authors: Mataliotakis George I. , Bounakis Nikolaos , Garrido-Stratenwerth Enrique
Published: June 2016

There is still no consensus on the management of severe intracanal RH dislocation in neurofibromatosis type 1 dystrophic kyphoscoliosis. This study notes the early cord function impairment signs, reports a serious complication in a susceptible cord, identifies possible mechanisms of injury, and discusses the management of intracanal RH dislocation presented in the literature. First report is as follows: a 12-year-old female with cord compromise and preoperative neurology that underwent thoracotomy and anterior release. The RH was left in situ following a rib excision. During the posterior stage of the procedure she presented with complete loss of all IOM traces prior to any correction manoeuvres. The neurology recovered 72 h postop and the final correction and instrumented fusion were uneventfully completed 15 days postop. Second report is as follows: a 10-year-old male, whose only neurology was a provoked shock-like sensation to the lower limbs following direct pressure on the rib cage. He underwent an uneventful posterior RH excision and instrumented correction and posterior spinal fusion. In conclusion, any possible cord dysfunction sign should be sought during examination. Decompression of the spinal cord by resecting the impinging bony part, even in the absence of neurological symptoms, is advised before any attempt to release or correct the deformity.
Effect of Continuous Positive Airway Pressure on Airway Inflammation and Oxidative Stress in Patients with Obstructive Sleep Apnea
Authors: Tichanon Promsrisuk , Wilaiwan Khrisanapant , Sopida Santamit , Orapin Pasurivong , Watchara Boonsawat , Banjamas Intarapoka
Published: June 2016

Background. Airway inflammation and oxidative stress may be linked in obstructive sleep apnea (OSA) patients. We determined the effectiveness of continuous positive airway pressure (CPAP) therapy in reducing fractional exhaled nitric oxide (FeNO) and malondialdehyde (MDA) levels in OSA patients.Methods. Thirteen patients with OSA and 13 normal controls were recruited. FeNO and MDA levels were measured in the controls and in OSA patients before and after three months of CPAP therapy.Results. FeNO and MDA levels were higher in the patients compared to the age and gender matched controls (FeNO: 25.9 ± 5.0 versus 17.5 ± 5.9 ppb,P<0.001; MDA: 14.6 ± 7.8 versus 2.1 ± 0.3 μmol/L,P<0.001). FeNO and MDA levels were lower post-CPAP compared to pre-CPAP (FeNO: 25.9 ± 5.0 versus 17.0 ± 2.3 ppb,P<0.001; MDA: 14.6 ± 7.8 versus 10.0 ± 6.4 μmol/L,P<0.01). Apnea-hypopnea index (15.9 ± 6.6 versus 4.1 ± 2.1/h,P<0.001) and mean arterial pressure (P<0.01) decreased following CPAP treatment. Daytime mean SpO2(P<0.05) increased.Conclusion. Our study demonstrates that CPAP therapy yields clinical benefits by reducing upper airway inflammation and oxidative stress in OSA patients.
Traumatic Periprosthetic Acetabular Fracture Treated with One-Stage Exchange and Bone Reconstruction Using a Synthetic Bone Graft Substitute
Authors: Svacina Jan
Published: June 2016

A case of a traumatic periprosthetic acetabular fracture in an elderly patient, which was treated by one-stage hip exchange with implantation of an antiprotrusio cage and reconstruction of the acetabular bone loss with an injectable calcium sulphate/hydroxyapatite bone graft substitute, is reported. The paste-like bone graft substitute was injected through the holes of the antiprotrusio cage. After a setting time of 15 minutes, a low-profile cup was cemented onto the cage using polymethylmethacrylate and a new stem was inserted. The patient was encouraged to ambulate three days postoperatively weight-bearing as tolerated. At the one-year follow-up visit the patient was ambulatory and full weight-bearing without any walking aids. The follow-up radiographs demonstrated stable position and articulation of the revision hip arthroplasty with no signs of loosening of the antiprotrusio cage. However, the most interesting finding was that the bone graft substitute had remodelled to a great extent into bone. This calcium sulphate/hydroxyapatite composite shows high osteoconductive potential and can be used to regenerate bone stock in revision arthroplasty.
Analysis ofE. rutaecarpaAlkaloids ConstituentsIn VitroandIn Vivoby UPLC-Q-TOF-MS Combined with Diagnostic Fragment
Authors: Yang Shenshen , Tian Meng , Yuan Lei , Deng Haoyue , Wang Lei , Li Aizhu , Hou Zhiguo , Li Yubo , Zhang Yanjun
Published: June 2016

Evodia rutaecarpa(Juss.) Benth. (Rutaceae) dried ripe fruit is used for dispelling colds, soothing liver, and analgesia. Pharmacological research has proved that alkaloids are the main active ingredients ofE. rutaecarpa. This study aimed to rapidly classify and identify the alkaloids constituents ofE. rutaecarpaby using UPLC-Q-TOF-MS coupled with diagnostic fragments. Furthermore, the effects of the material base ofE. rutaecarpabioactive ingredientsin vivowere examined such that the transitional components in the blood of rats intragastrically givenE. rutaecarpawere analyzed and identified. In this study, the type of alcohol extraction ofE. rutaecarpaand the corresponding blood sample were used for the analysis by UPLC-Q-TOF-MS in positive ion mode. After reviewing much of the literature and collected information on the fragments, we obtained some diagnostic fragments of the alkaloids. Combining the diagnostic fragments with the technology of UPLC-Q-TOF-MS, we identified the compounds ofE. rutaecarpaand blood samples and compared the ion fragment information with that of the alkaloids inE. rutaecarpa. A total of 17 alkaloids components and 6 blood components were identified. The proposed method was rapid, accurate, and sensitive. Therefore, this technique can reliably and practically analyze the chemical constituents in traditional Chinese medicine (TCM).
Iterative Deconvolution of PEA Measurements for Enhancing the Spatial Resolution of Charge Profile in Space Polymers
Authors: Arnaout Mohamad , Chahine Khaled , Baudoin Fulbert , Berquez Laurent , Payan Denis
Published: June 2016

This work aims to improve the PEA calibration technique through defining a well-conditioned transfer matrix. To this end, a numerical electroacoustic model that allows determining the output voltage of the piezoelectric sensor and the acoustic pressure is developed with the software COMSOL®. The proposed method recovers the charge distribution within the sample using an iterative deconvolution method that uses the transfer matrix obtained with the new calibration technique. The obtained results on theoretical and experimental signals show an improvement in the spatial resolution compared with the standard method usually used.
Optimal Synthesis of Horizontally Aligned Single-Walled Carbon Nanotubes and Their Biofunctionalization for Biosensing Applications
Authors: Jung Dawoon , Park Hyun Woo , Ma Gidong , Lee Chang Young , Kwon Taeyun , Han Jae-Hee
Published: June 2016

As an influential candidate for highly sensitive biomolecule sensor, which can capture disease related biomolecules, carbon nanotube is useful material due to its unique properties. To adopt as a sensing platform, it is strongly needed to find optimal refined synthetic condition. In order to find the optimal synthetic conditions of horizontally aligned CNT, we performed quantity control of the mixed gases of H2and CH4injected. We successfully find that the formation of amorphous-like carbon was critically affected by some gas condition such as the flow rate of injected gases and ratios of gas mixture. Moreover, it should be noted that our horizontally aligned carbon nanotube array platform developed would offer another potential in developing nanoscale light source, where light emission results from electron-hole carrier recombination.
Dry Matter Production, Nutrient Cycled and Removed, and Soil Fertility Changes in Yam-Based Cropping Systems with Herbaceous Legumes in the Guinea-Sudan Zone of Benin
Authors: Maliki Raphiou , Sinsin Brice , Floquet Anne , Cornet Denis , Malezieux Eric , Vernier Philippe
Published: June 2016

Traditional yam-based cropping systems (shifting cultivation, slash-and-burn, and short fallow) often result in deforestation and soil nutrient depletion. The objective of this study was to determine the impact of yam-based systems with herbaceous legumes on dry matter (DM) production (tubers, shoots), nutrients removed and recycled, and the soil fertility changes. We compared smallholders’ traditional systems (1-year fallow ofAndropogon gayanus-yam rotation, maize-yam rotation) with yam-based systems integrated herbaceous legumes (Aeschynomene histrix/maize intercropping-yam rotation,Mucuna pruriens/maize intercropping-yam rotation). The experiment was conducted during the 2002 and 2004 cropping seasons with 32 farmers, eight in each site. For each of them, a randomized complete block design with four treatments and four replicates was carried out using a partial nested model with five factors: Year, Replicate, Farmer, Site, and Treatment. Analysis of variance (ANOVA) using the general linear model (GLM) procedure was applied to the dry matter (DM) production (tubers, shoots), nutrient contribution to the systems, and soil properties at depths 0–10 and 10–20 cm. DM removed and recycled, total N, P, and K recycled or removed, and soil chemical properties (SOM, N, P, K, and pH water) were significantly improved on yam-based systems with legumes in comparison with traditional systems.
Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test
Authors: Lukman Nurhayati , Salim Gustiani , Kosasih Herman , Susanto Nugroho Harry , Parwati Ida , Fitri Silvita , Alisjahbana Bachti , Widjaja Susana , Williams Maya
Published: June 2016

Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73).
A Coproduction Community Based Approach to Reducing Smoking Prevalence in a Local Community Setting
Authors: McGeechan G. J. , Woodall D. , Anderson L. , Wilson L. , O’Neill G. , Newbury-Birch D.
Published: June 2016

Research highlights that asset-based community development where local residents become equal partners in service development may help promote health and well-being. This paper outlines baseline results of a coproduction evaluation of an asset-based approach to improving health and well-being within a small community through promoting tobacco control. Local residents were recruited and trained as community researchers to deliver a smoking prevalence survey within their local community and became local health champions, promoting health and well-being. The results of the survey will be used to inform health promotion activities within the community. The local smoking prevalence was higher than the regional and national averages. Half of the households surveyed had at least one smoker, and 63.1% of children lived in a smoking household. Nonsmokers reported higher well-being than smokers; however, the differences were not significant. Whilst the community has a high smoking prevalence, more than half of the smokers surveyed would consider quitting. Providing smoking cessation advice in GP surgeries may help reduce smoking prevalence in this community. Work in the area could be done to reduce children’s exposure to smoking in the home.
A New Local Modelling Approach Based on Predicted Errors for Near-Infrared Spectral Analysis
Authors: Chang Haitao , Zhu Lianqing , Lou Xiaoping , Meng Xiaochen , Guo Yangkuan , Wang Zhongyu
Published: June 2016

Over the last decade, near-infrared spectroscopy, together with the use of chemometrics models, has been widely employed as an analytical tool in several industries. However, most chemical processes or analytes are multivariate and nonlinear in nature. To solve this problem, local errors regression method is presented in order to build an accurate calibration model in this paper, where a calibration subset is selected by a new similarity criterion which takes the full information of spectra, chemical property, and predicted errors. After the selection of calibration subset, the partial least squares regression is applied to build calibration model. The performance of the proposed method is demonstrated through a near-infrared spectroscopy dataset of pharmaceutical tablets. Compared with other local strategies with different similarity criterions, it has been shown that the proposed local errors regression can result in a significant improvement in terms of both prediction ability and calculation speed.
Chaotic Vibration Prediction of a Free-Floating Flexible Redundant Space Manipulator
Authors: Wang Congqing , Wu Linfeng
Published: June 2016

The dynamic model of a planar free-floating flexible redundant space manipulator with three joints is derived by the assumed modes method, Lagrange principle, and momentum conservation. According to minimal joint torque’s optimization (MJTO), the state equations of the dynamic model for the free-floating redundant space manipulator are described. The PD control using the tracking position error and velocity error in the manipulator is introduced. Then, the chaotic dynamic behavior of the manipulator is analyzed by chaotic numerical methods, in which time series, phase plane portrait, Poincaré map, and Lyapunov exponents are used to analyze the chaotic behavior of the manipulator. Under certain conditions for the joint torque optimization and initial values, chaotic vibration motion of the space manipulator can be observed. The chaotic time series prediction scheme for the space manipulator is presented based on the theory of phase space reconstruction under Takens’ embedding theorem. The trajectories of phase space can be reconstructed in embedding space, which are equivalent to the original space manipulator in dynamics. The one-step prediction model for the chaotic time series and the chaotic vibration was established by using support vector regression (SVR) prediction model with RBF kernel function. It has been proved that the SVR prediction model has a good performance of prediction. The experimental results show the effectiveness of the presented method.
Prolactinoma: AMassiveEffect on Bone Mineral Density in a Young Patient
Authors: Sperling Scott , Bhatt Harikrashna
Published: June 2016

This case highlights a prolactinoma in a young male, and its impact on bone health. Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based onZ-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients. Furthermore it highlights the need for a thorough evaluation in such patients.
Müllerian Remnant Cyst as a Cause of Acute Abdomen in a Female Patient with Müllerian Agenesis: Radiologic and Pathologic Findings
Authors: Mohammed Mujtaba , Allen-Proctor Mary , Wojtowycz Andrij
Published: June 2016

We report a case of a 17-year-old female with Müllerian agenesis who presented with right sided abdominal pain clinically suspicious for acute appendicitis. Multimodality imaging workup revealed a heterogeneous cystic right upper quadrant mass with surrounding fluid and inflammatory changes. Surgical resection of this mass was performed and a histopathologic diagnosis of a hemorrhagic Müllerian remnant cyst was made, which to the best of our knowledge has never been described in a patient with Müllerian agenesis.
Gene Expression Music Algorithm‐Based Characterization of the Ewing Sarcoma Stem Cell Signature
Authors: Staege Martin Sebastian
Published: June 2016

Gene Expression Music Algorithm (GEMusicA) is a method for the transformation of DNA microarray data into melodies that can be used for the characterization of differentially expressed genes. Using this method we compared gene expression profiles from endothelial cells (EC), hematopoietic stem cells, neuronal stem cells, embryonic stem cells (ESC), and mesenchymal stem cells (MSC) and defined a set of genes that can discriminate between the different stem cell types. We analyzed the behavior of public microarray data sets from Ewing sarcoma (“Ewing family tumors,” EFT) cell lines and biopsies in GEMusicA after prefiltering DNA microarray data for the probe sets from the stem cell signature. Our results demonstrate that individual Ewing sarcoma cell lines have a high similarity to ESC or EC. Ewing sarcoma cell lines with inhibited Ewing sarcoma breakpoint region 1‐Friend leukemia virus integration 1 (EWSR1‐FLI1) oncogene retained the similarity to ESC and EC. However, correlation coefficients between GEMusicA‐processed expression data between EFT and ESC decreased whereas correlation coefficients between EFT and EC as well as between EFT and MSC increased after knockdown of EWSR1‐FLI1. Our data support the concept of EFT being derived from cells with features of embryonic and endothelial cells.
Nonlocal Transport Processes and the Fractional Cattaneo-Vernotte Equation
Authors: Aguilar J. F. Gómez , Córdova-Fraga T. , Tórres-Jiménez J. , Escobar-Jiménez R. F. , Olivares-Peregrino V. H. , Guerrero-Ramírez G. V.
Published: June 2016

The Cattaneo-Vernotte equation is a generalization of the heat and particle diffusion equations; this mathematical model combines waves and diffusion with a finite velocity of propagation. In disordered systems the diffusion can be anomalous. In these kinds of systems, the mean-square displacement is proportional to a fractional power of time not equal to one. The anomalous diffusion concept is naturally obtained from diffusion equations using the fractional calculus approach. In this paper we present an alternative representation of the Cattaneo-Vernotte equation using the fractional calculus approach; the spatial-time derivatives of fractional order are approximated using the Caputo-type derivative in the range(0,2]. In this alternative representation we introduce the appropriate fractional dimensional parameters which characterize consistently the existence of the fractional space-time derivatives into the fractional Cattaneo-Vernotte equation. Finally, consider the Dirichlet conditions, the Fourier method was used to find the full solution of the fractional Cattaneo-Vernotte equation in analytic way, and Caputo and Riesz fractional derivatives are considered. The advantage of our representation appears according to the comparison between our model and models presented in the literature, which are not acceptable physically due to the dimensional incompatibility of the solutions. The classical cases are recovered when the fractional derivative exponents are equal to1.
Immunomodulatory Effects ofLactobacillus plantarumLp62 on Intestinal Epithelial and Mononuclear Cells
Authors: Ferreira dos Santos Thalis , Alves Melo Tauá , Almeida Milena Evangelista , Passos Rezende Rachel , Romano Carla Cristina
Published: June 2016

Probiotic lactic acid bacteria are known for their ability to modulate the immune system. They have been shown to inhibit inflammation in experiments with animal models, cell culture, and clinical trials. The objective of this study was to elucidate the anti-inflammatory potential ofLactobacillus plantarumLp62, isolated from cocoa fermentation, in a cell culture model. Lp62 inhibited IL-8 production bySalmonellaTyphi-stimulated HT-29 cells and prevented the adhesion of pathogens to these epithelial cells. The probiotic strain was able to modulate TNF-α, IL1-β, and IL-17 secretion by J774 macrophages. J774 activation was reduced by coincubation with Lp62. PBMC culture showed significantly higher levels of CD4+CD25+T lymphocytes following treatment with Lp62. Probiotics also induced increased IL-10 secretion by mononuclear cells.L. plantarumLp62 was able to inhibit inflammatory stimulation in epithelial cells and macrophages and activated a tolerogenic profile in mononuclear cells of healthy donors. These results indicate this strain for a possible application in the treatment or prevention of inflammatory diseases.
Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
Authors: Yan Ning , Wen Li , Peng Rui , Li Hongmei , Liu Handeng , Peng Huimin , Sun Yan , Wu Tianhui , Chen Lei , Duan Qingrui , Sun Yixuan , Zhou Qin , Wei Lijiang , Zhang Zheng
Published: June 2016

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.
Glutathione as a Biomarker in Parkinson’s Disease: Associations with Aging and Disease Severity
Authors: Mischley Laurie K. , Standish Leanna J. , Weiss Noel S. , Padowski Jeannie M. , Kavanagh Terrance J. , White Collin C. , Rosenfeld Michael E.
Published: June 2016

Objectives. Oxidative stress contributes to Parkinson’s disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross‐sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman’s rank‐order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient‐Reported Outcomes in PD (PRO‐PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age‐related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO‐PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.
Identification of Centella asiatica’s Effective Ingredients for Inducing the Neuronal Differentiation
Authors: Jiang Hui , Zheng Guoshuai , Lv Junwei , Chen Heyu , Lin Jinjin , Li Yiyang , Fan Guorong , Ding Xianting
Published: June 2016

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC‐MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination‐induced neurofilament expression, indicating the combination‐induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved.
Long-Term Follow-Up Evaluation of Renal Function in Patients with Chronic Kidney Disease Undergoing Cardiac Surgery
Authors: Santana-Santos Eduesley , Kamei Felipe Kenji Oshiro , Nascimento Tarcísia Karoline do , Abou Ismail Anas , Herbas Palomo Jurema da Silva , Silva Magro Marcia Cristina da , Ferreira Fátima Gil , de Oliveira Larissa Bertacchini , Baldacin Rodrigues Adriano Rogério , Galvão de Lima José Jayme
Published: June 2016

Background. Acute kidney injury (AKI) is a common complication of cardiac surgery but its long-term consequences, in patients with chronic kidney disease (CKD), are not known.Methods. We compared the long-term prognoses of CKD patients who developed (n=23) and did not develop (n=35) AKI during the period of hospitalization after undergoing coronary artery bypass graft (CABG). Fifty-eight patients who survived (69.6±8.4years old, 72% males, 83% Whites, 52% diabetics, baseline GFR:46±16 mL/min) were followed up for47.8±16.4months and treated for secondary prevention of events.Results. There were 6 deaths, 4 in the AKI+ and 2 in the AKI− group (Log-rank = 0.218), two attributed to CV causes. At the end of the study, renal function was similar in the two groups. One AKI− patient was started on dialysis. Only 4 patients had an increase in serum creatinine ≥ 0.5 mg/dL during follow-up.Conclusion. CKD patients developing AKI that survived the early perioperative period of coronary intervention present good renal and nonrenal long-term prognosis, compared to patients who did not develop AKI.
c-Myc Modulation and Acetylation Is a Key HDAC Inhibitor Target in Cancer
Authors: Nebbioso Angela , Carafa Vincenzo , Conte Mariarosaria , Tambaro Francesco Paolo , Abbondanza Ciro , Martens Joost , Nees Matthias , Benedetti Rosaria , Pallavicini Isabella , Minucci Saverio , Garcia-Manero Guillermo , Iovino Francesco , Lania Gabriella , Ingenito Concetta , Belsito Petrizzi Valeria , Stunnenberg Hendrik G. , Altucci Lucia
Published: June 2016

Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, the mechanism(s) underlying their tumor selectivity are poorly understood.

Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts and cell lines. MYC, the most prominently modulated, is preferentially altered in leukemia. Upon HDACi treatment, c-Myc is acetylated at lysine 323 and its expression decreases, leading to TRAIL activation and apoptosis. c-Myc binds to the TRAIL promoter on the proximal GC box through SP1 or MIZ1, impairing TRAIL activation. HDACi exposure triggers TRAIL expression, altering c-Myc-TRAIL binding. These events do not occur in normal cells. Excitingly, this inverse correlation between TRAIL and c-Myc is supported by HDACi treatment ex vivo of AML blasts and primary human breast cancer cells. The predictive value of c-Myc to HDACi responsiveness is confirmed in vivo in AML patients undergoing HDACi-based clinical trials.

Conclusions: Collectively, our findings identify a key role for c-Myc in TRAIL deregulation and as a biomarker of the anticancer action of HDACi in AML. The potential improved patient stratification could pave the way toward personalized therapies. Clin Cancer Res; 23(10); 2542–55. ©2016 AACR.
XPO1 Inhibition using Selinexor Synergizes with Chemotherapy in Acute Myeloid Leukemia by Targeting DNA Repair and Restoring Topoisomerase IIα to the Nucleus
Authors: Ranganathan Parvathi , Kashyap Trinayan , Yu Xueyan , Meng Xiaomei , Lai Tzung-Huei , McNeil Betina , Bhatnagar Bhavana , Shacham Sharon , Kauffman Michael , Dorrance Adrienne M. , Blum William , Sampath Deepa , Landesman Yosef , Garzon Ramiro
Published: June 2016

Purpose: Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore, we asked whether adding already established effective drugs such as topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML.

Experimental Design: The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML.

Results: Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared with each single therapy.

Conclusions: Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of patients with AML that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC–dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. Clin Cancer Res; 22(24); 6142–52. ©2016 AACR.
An Aggressive Subtype of Stage I Lung Adenocarcinoma with Molecular and Prognostic Characteristics Typical of Advanced Lung Cancers
Authors: Dama Elisa , Melocchi Valentina , Dezi Fabio , Pirroni Stefania , Carletti Rose Mary , Brambilla Daniela , Bertalot Giovanni , Casiraghi Monica , Maisonneuve Patrick , Barberis Massimo , Viale Giuseppe , Vecchi Manuela , Spaggiari Lorenzo , Bianchi Fabrizio , Di Fiore Pier Paolo
Published: June 2016

Purpose: The National Lung Cancer Screening Trial has confirmed that lung cancer mortality can be reduced if tumors are diagnosed early, that is, at stage I. However, a substantial fraction of stage I lung cancer patients still develop metastatic disease within 5 years from surgery. Prognostic biomarkers are therefore needed to identify patients at risk of an adverse outcome, who might benefit from multimodality treatment.

Experimental Design: We extensively validated a 10-gene prognostic signature in a cohort of 507 lung adenocarcinoma patients using formalin-fixed paraffin-embedded samples. Furthermore, we performed an integrated analysis of gene expression, methylation, somatic mutations, copy number variations, and proteomic profiles on an independent cohort of 468 patients from The Cancer Genome Atlas (TCGA).

Results: Stage I lung cancer patients (N = 351) identified as high-risk by the 10-gene signature displayed a 4-fold increased risk of death [HR = 3.98; 95% confidence interval (CI), 1.73–9.14], with a 3-year overall survival of 84.2% (95% CI, 78.7–89.7) compared with 95.6% (92.4–98.8) in low-risk patients. The analysis of TCGA cohort revealed that the 10-gene signature identifies a subgroup of stage I lung adenocarcinomas displaying distinct molecular characteristics and associated with aggressive behavior and poor outcome.

Conclusions: We validated a 10-gene prognostic signature capable of identifying a molecular subtype of stage I lung adenocarcinoma with characteristics remarkably similar to those of advanced lung cancer. We propose that our signature might aid the identification of stage I patients who would benefit from multimodality treatment. Clin Cancer Res; 23(1); 62–72. ©2016 AACR.
Mitochondrial Sirtuin 3 and Renal Diseases
Authors: Perico Luca , Morigi Marina , Benigni Ariela
Published: June 2016

Mitochondria are dynamic organelles whose functions are tightly regulated at multiple levels to maintain proper cellular homeostasis. Mitochondrial Sirtuin 3 (SIRT3), which belongs to an evolutionary conserved family of NAD+-dependent deacetylases, is a key regulator of the mitochondrial respiratory chain, ATP production, and fatty acid β-oxidation, and it exerts an antioxidant activity. Changes in SIRT3 expression are critical in the pathophysiology of several diseases, such as metabolic syndrome, diabetes, cancer, and aging. In experimental acute kidney injury (AKI), impairment of renal function and development of tubular injury are associated with SIRT3 reduction and mitochondrial dysfunction in proximal tubuli. SIRT3-deficient mice are more susceptible to AKI and die. Pharmacological manipulations able to increase SIRT3 preserve mitochondrial integrity, markedly limit renal injury, and accelerate functional recovery. This review highlights all the selective rescue mechanisms that point to the key role of SIRT3 as a new therapeutic target for curing renal diseases.
Dietary Inflammatory Index and Risk of Multiple Sclerosis in a Case-Control Study from Iran
Authors: Shivappa Nitin , Hebert James R. , Behrooz Maryam , Rashidkhani Bahram
Published: June 2016

Background: Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS). Objectives: In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran. Methods: This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate ORs adjusted for age, energy, sex, body mass index, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's milk in the first 2 years of life. Results: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used both as a continuous variable (ORcontinuous 1.66; 95% CI 1.19-2.31; 1 unit increase corresponding to ≈15% of its range in the current study) and a categorical variable (ORDII (>1.43 vs.≤1.43) 2.68; 95% CI 1.15-6.26). Conclusions: These results indicate that a pro-inflammatory diet is associated with increased risk of MS.
Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer
Authors: Lima Maíra Assis , dos Santos Liliane , Turri José Antonio , Nonogaki Suely , Buim Marcilei , Lima Joema Felipe , de Jesus Viana Pinheiro João , Bueno de Toledo Osório Cynthia Aparecida , Soares Fernando Augusto , Freitas Vanessa Morais
Published: June 2016

Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.
Genetic Risk Evaluation in Wet Age-Related Macular Degeneration Treatment Response
Authors: Chaudhary Varun , Brent Michael , Lam Wai-Ching , Devenyi Robert , Teichman Joshua , Mak Michael , Barbosa Joshua , Kaur Harneel , Carter Ronald , Farrokhyar Forough
Published: June 2016

Objective: To evaluate the pharmacogenetic relationship between CFH haplotypes and single nucleotide polymorphisms (SNPs) with response to ranibizumab treatment for neovascular age-related macular degeneration (nAMD). Patients and Methods: This was a prospective cohort study involving 70 treatment-naive nAMD patients. Patients were genotyped for CFH haplotypes and SNPs in the C3, ARMS2, and mtDNA genes. Visual acuity and central macular thickness were assessed at baseline and during 6 monthly follow-up visits. Multivariate logistic regression was used to determine the association between genotypes and a gain of ≥15 letters at the 6-month endpoint after adjusting for potential confounders. Results:CFH haplotypes were associated with a gain of ≥15 letters at the 6-month endpoint (p = 0.046). Patients expressing protective haplotypes were more likely to achieve a gain of ≥15 letters relative to the greatly increased risk haplotypes [OR 6.58 (95% CI: 1.37, 31.59)]. Conclusion:CFH is implicated in nAMD patient treatment response to ranibizumab.
Proposed New Sub-Grouping for Intermediate-Stage Hepatocellular Carcinoma Using Albumin-Bilirubin Grade
Authors: Hiraoka Atsushi , Kumada Takashi , Nouso Kazuhiro , Tsuji Kunihiko , Itobayashi Ei , Hirooka Masashi , Kariyama Kazuya , Ishikawa Toru , Tada Toshifumi , Toyoda Hidenori , Kawasaki Hideki , Hiasa Yoichi , Michitaka Kojiro
Published: June 2016

Aim: We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for evaluation of the prognosis of intermediate-stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer criteria stage B, BCLC-B). Patients and Methods: We enrolled 754 naïve BCLC-B patients (multiple tumors) and retrospectively analyzed their clinical features [surgical resection (hepatectomy), n = 170; radiofrequency ablation (RFA), n = 110; percutaneous ethanol injection, n = 7; transcatheter arterial chemoembolization, n = 396; others, n = 25; best supportive care, n = 46]. Four sub-groups were defined for the Modified Intermediate Stage of Liver Cancer (MICAN) criteria as follows: B1 (ALBI-1/within up-to-7 criteria), B2 (ALBI-2/within up-to-7 criteria), B3 (ALBI-1 and ALBI-2/multiple and beyond up-to-7 criteria), and B4 (ALBI-3/any). Results: The median survival time of patients classified as B1 (n = 94), B2 (n = 175), B3 (n = 452), and B4 (n = 33) was 65.1, 48.1, 29.6, and 14.6 months, respectively (p < 0.01 for each). Those in B1 treated with hepatectomy and RFA comprised 67.0%, while that ratio was 51.4% in B2, 28.3% in B3, and 12.1% in B4. Conclusion: The MICAN criteria based on ALBI grade are simple and useful for prediction of prognosis and therapy decision-making in the heterogeneous population of BCLC-B patients.
Paradoxical Reductions in Serum Anti-p53 Autoantibody Levels by Chemotherapy in Unresectable Colorectal Cancer: An Observational Study
Authors: Nozawa Hiroaki , Ishihara Soichiro , Kawai Kazushige , Murono Koji , Yasuda Koji , Otani Kensuke , Nishikawa Takeshi , Tanaka Toshiaki , Kiyomatsu Tomomichi , Hata Keisuke , Watanabe Toshiaki
Published: June 2016

Objective: The anti-p53 autoantibody is an emerging tumor marker that is commonly produced in response to p53 mutations. The usefulness of this antibody has been suggested in screening for and the monitoring of recurrence in colorectal cancer; however, its significance as a marker during chemotherapy remains largely unknown. Methods: We measured serum anti-p53 antibody levels in patients with unresectable colorectal cancer who underwent first-line systemic chemotherapy. Tumor responses were evaluated by computed tomography. We determined whether temporal changes in this antibody during therapy are associated with radiological responses. Results: Of the 83 patients in our study, 29 (35%) had elevated serum anti-p53 antibody levels before chemotherapy. Among these, antibody levels decreased in all 14 responders. In contrast, among those patients with elevated pretherapeutic serum anti-p53 antibody levels, 89% showed a paradoxical decrease in antibody levels and exhibited disease progression after chemotherapy. Moreover, serum anti-p53 antibody levels before and after chemotherapy were not associated with survival. Conclusion: These results suggest that serum anti-p53 antibody levels are of limited value in the evaluation of responses to palliative chemotherapy in patients with colorectal cancer.
T2 Fluid-Attenuated Inversion Recovery Imaging of Uveal Melanomas and Other Ocular Pathology
Authors: Damento Gena M. , Koeller Kelly K. , Salomão Diva R. , Pulido Jose S.
Published: June 2016

Background/Aims: This study describes patterns of intraocular lesions on T2 fluid-attenuated inversion recovery (FLAIR) imaging, exploring a prospective role of FLAIR imaging sequence in diagnosis and treatment. Methods: A retrospective study of orbital magnetic resonance imaging (MRI) studies from the years 2000 to 2015 was performed. MRI sequences included: pre-contrast T1-weighted, T2-weighted, T2 FLAIR, and postcontrast T1 and T2 imaging gadolinium, which were evaluated by a neuroradiologist. Two cases of melanoma were correlated to their pathology. Results: Twenty-four patients with intraocular pathology were evaluated. All lesions, regardless of pigmentation, revealed previously described melanotic patterns on T1- and T2-weighted images; 80% of 10 melanomas localized were hyperintense on T2 FLAIR, which better delineated lesion margins. All of the four inflammatory pathologies on T2 FLAIR were hyperintense, as were 80% of the amelanotic neoplasms. Pathology of two large uveal melanomas paralleled the findings seen on T2 FLAIR. Conclusions: T2 FLAIR appears beneficial in the demarcation of pigmented ocular lesions and may aid in determining protein content or previous treatment. Data also promote previous assertions that blood flow impacts intensity of lesions on T2 FLAIR. Further research is warranted.
Simvastatin Treatment Upregulates Anti-Fibrotic Bone Morphogenetic Protein-7 Expression at Rat Cardiac Allograft Rejection
Authors: Holmström Emil J. , Lemström Karl B. , Tuuminen Raimo
Published: June 2016

Background: Bone morphogenetic protein (BMP)-7 mediates ischemic tolerance and anti-fibrotic effects in various organs such as kidney and heart. Recently, reno- and podocyte-protective effects of a potent HMG-CoA reductase inhibitor, pitavastatin, were accompanied by BMP-7 upregulation. Methods: Here, we investigated the effect of simvastatin treatment on BMP-7 expression in major MHC-mismatched rat cardiac allografts subjected to ischemia-reperfusion injury and adaptive immune activation at 10 days. Results: We localized Smad2 activity and Reca-1+ fibroblast specific protein-1+ immunoreactivity, suggesting endothelial-to-mesenchymal transition, at fibrotic borderline of cardiac allografts at 10 days. Simvastatin donor and recipient combination treatment significantly upregulated cardiac allograft BMP-7 expression when compared to nontreated controls at 10 days. Conclusion: The beneficial effect of statin treatment on cardiac allograft may in part be mediated through the upregulation of BMP-7.
Cost of economic fluctuations after the Plano Real
Authors: Barros Júnior Fernando Antônio de , Pinho Neto Valdemar Rodrigues de
Published: June 2016

Neste artigo, calculamos o custo das ﬂutuações econômicas no Brasil. Utilizamos dados trimestrais do consumo real entre o início do Plano Real e o terceiro trimestre de 2013 e computamos o custo das ﬂutuações permitindo diferentes formas paramétricas para o processo estocástico da série. EstimamosqueocustodasﬂutuaçõeseconômicasnoBrasiléaproximadamente6,48%do consumo per capita utilizando a melhor das especiﬁcações para o processo estocástico do consumo
Structural breaks in the cattle price series in the State of São Paulo, Brazil
Authors: Shikida Cláudio , Paiva Guilherme Leite , Araújo Junior Ari Francisco
Published: June 2016

O objetivo deste artigo é analisar a existência de quebras estruturais na série do preço do boi gordo (porarroba)no estado de São Paulo entre 1954 e 2012. Devido às especiﬁcidades do preço do boi gordo (sazonalidade e ciclos) e também à importância da bovinocultura na agropecuária brasileira, a série foi anteriormente utilizada para discussão e estudo de testes econométricos, como análise de raiz unitária sazonal, modelos de transferência e cointegração. Neste trabalho, testam-se se quebras estruturais apresentam origem em determinados eventos históricos, inclusive intervenções governamentais. A principal metodologia utilizada para identiﬁcação e estimação das quebras é a desenvolvida por Bai & Perron (1998, 2003). Os resultados sugerem que as intervenções governamentais, especialmente os planos de estabilização, levaram a mudanças signiﬁcativas no comportamento do preço do boi gordo
The Dynamics of the Brazilian Current Account with Rule of Thumb Consumers
Authors: Oliveira Lucio Hellery Holanda , Carrasco-Gutierrez Carlos Enrique
Published: June 2016

O modelo intertemporal tradicional da conta corrente assume que todos os indivíduos seguem a teoria da renda permanente. A inovação propostanestetrabalhoéincorporaraomodeloclássicodadinâmicadaconta corrente a ideia de que uma parte dos consumidores apresenta comportamento do tipo rule of thumb. São estimadas a parcela da renda agregada que segue o comportamento rule of thumb e o coeﬁciente de formação de hábitos. Usando os dados de conta corrente para a economia brasileira,os resultados conﬁrmam alguns fatos estilizados apresentados na literatura assim como algumas proposições básicas testáveis do modelo intertemporal da conta corrente