bluuebunny/crossref_metadata_2025 huggingface dataset:
Curing Effects on High‐Strength Concrete Properties
Authors: Wedatalla Afaf M. O. , Jia Yanmin , Ahmed Abubaker A. M.
Published: March 2019

This study was conducted to investigate the impact of hot and dry environments under different curing conditions on the properties of high‐strength concrete. The concrete samples were prepared at a room temperature of 20°C and cured under different curing conditions. Some specimens underwent standard curing from 24 h after casting until the day of testing. Some specimens underwent steam curing in a dry oven at 30°C and 50°C after casting until the day of testing. Other specimens were cured for 3, 7, 21, and 28 days in water and then placed in a dry oven at 30°C and 50°C and tested at the age of 28 days, except for the specimens that were cured for 28 days, which were tested at the age of 31 days, to study the effect of curing period on the strength of concrete exposed to dry and hot environments after moist curing. The effects of hot and dry environments on high‐strength concrete with different water/binder ratios (0.30, 0.35, and 0.40), using (30%) fly ash for all mixes, and (0%, 5%, and 10%) silica fume with the binder (450, 480, and 520 kg), respectively, were separately investigated, and the effects of curing under different conditions were evaluated by measuring the compressive strength, flexural strength, microhardness, and chloride diffusion and by assessing the concretes’ microstructure. The relationships between these properties were presented. A good agreement was noted between the concrete compressive strength and concrete properties at different temperatures, curing periods, and curing methods.
Protective Role of Nuclear Factor Erythroid-2-Related Factor 2 against Mechanical Trauma-Induced Apoptosis in a Vaginal Distension-Induced Stress Urinary Incontinence Mouse Model
Authors: Tang Jianming , Liu Cheng , Li Bingshu , Hong Shasha , Li Qiannan , Wang Linlin , Min Jie , Hu Ming , Li Yang , He Songming , Hong Li
Published: March 2019

Apoptosis and oxidative damage are involved in the pathogenesis and progression of stress urinary incontinence (SUI). Our previous results indicate that cell apoptosis and oxidative damage increase in a mouse model of mechanical injury-induced SUI and in fibroblasts treated with excessive mechanical strain. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a well-characterized global antioxidant gene inducer that can reduce oxidative damage and apoptosis. Therefore, we predicted that Nrf2 may have a protective role in mechanical trauma-induced SUI. To test this hypothesis, a mouse model of vaginal distension- (VD-) induced SUI was established. Leak point pressure (LPP); levels of apoptosis, apoptosis-related proteins, and peroxidation products; and the activities of antioxidative proteins in the anterior vaginal wall were measured in wild-type (Nfe2l2+/+) C57BL/6 mice and Nrf2-knockout mice (Nfe2l2-/-). The results showed that Nrf2 knockout aggravated VD-induced reduction in LPP, increase in cell apoptosis and peroxidation product levels, decrease in antioxidative protein activities, and alterations in apoptosis-related protein levels in the vaginal walls of mice. To further confirm the role of Nrf2 in mechanical trauma-induced apoptosis and SUI, VD was performed on mice overexpressing Nrf2 via in vivo transfection of LV-Nfe2l2. The results showed that Nrf2 overexpression significantly alleviated VD-induced abnormalities in the anterior vaginal wall. Taken together, our data suggested that Nrf2 is a potential protective factor in mechanical trauma-induced apoptosis in a mouse model of SUI. Antioxidative therapy may be a promising treatment for mechanical trauma-related SUI.
circSMARCA5 Functions as a Diagnostic and Prognostic Biomarker for Gastric Cancer
Authors: Cai Juan , Chen Zhiqiang , Zuo Xueliang
Published: March 2019

Background. Circular RNAs have been implicated in various malignancies and can function as potential biomarkers for cancers. Reportedly, circSMARCA5 was downregulated in hepatocellular carcinoma and glioblastoma multiforme, but upregulated in prostate cancer. The functional roles and clinical significance of circSMARCA5 still remain unknown in the context of gastric cancer (GC). Methods. Expression levels of circSMARCA5 were detected by qRT-PCR. Clinical data including patient basic information, clinicopathological features, and survival data were obtained. The Kaplan-Meier methods, multivariate Cox regression models, and the receiver operating characteristic curve were used to assess the clinical significance of circSMARCA5 in GC. Cell proliferation assays and transwell assays were performed to elucidate the functional roles of circSMARCA5 in GC. Results. The circSMARCA5 level was decreased in GC tissues and cell lines. The low expression level of circSMARCA5 was correlated to poorer overall survival and disease-free survival. Low circSMARCA5 expression was revealed as an independent unfavorable predictive factor for GC. The results indicated that circSMARCA5 had a moderate ability for discrimination between GC patients and controls with an area under the curve of 0.806. Upregulation of circSMARCA5 dampened the proliferation, migration, and invasion of GC cells, whereas circSMARCA5 knockdown promoted GC progression. Discussion. Our results demonstrated that circSMARCA5 was decreased and exerted tumor-suppressive effects in GC. circSMARCA5 can function as a potential biomarker for GC prognosis and diagnosis.
Population Pharmacokinetics of Clozapine and Norclozapine and Switchability Assessment between Brands in Uruguayan Patients with Schizophrenia
Authors: Olmos Ismael , Ibarra Manuel , Vázquez Marta , Maldonado Cecilia , Fagiolino Pietro , Giachetto Gustavo
Published: March 2019

Clozapine (CZP) is an atypical antipsychotic agent commonly used in the treatment of schizophrenia. It is metabolized primarily by CYP1A2 enzyme, yielding a pharmacologically active metabolite, norclozapine (NCZP). Significant intra- and interindividual pharmacokinetic (PK) variability for CZP and NCZP has been observed in routine therapeutic drug monitoring. So the goal of this study was to evaluate the magnitude and variability of concentration exposure to CZP and its active metabolite NCZP on pharmacokinetic parameters in Uruguayan patients with schizophrenia with a focus on covariates such as cigarette smoking, age, sex, caffeine consumption, brands available of CZP, and comedication using population PK (PPK) modeling methodologies. Patients with a diagnosis of schizophrenia treated with brand-name CZP (Leponex®) for more than a year were included in the study. Then these patients were switched to the similar brand of CZP (Luverina®). Morning predose blood samples for determination of CZP and NCZP using a HPLC system equipped with a UV detector were withdrawn on both occasions at steady state and under the same comedication. Ninety-eight patients, 22 women and 76 men, took part in the study. Mean ± standard deviation for CZP and NCZP concentration was 421 ± 262 ng/mL and 275 ± 180 ng/mL, respectively. After covariate evaluation, only smoking status remained significant in CZP apparent clearance, inducing a mean increment of 32% but with no clinical impact. The results obtained with the two brands of CZP should ensure comparable efficacy and tolerability with the clinical use of either product. Smoking was significantly associated with a lower exposure to CZP due to higher clearance. The results obtained with the two brands commercialized in our country hint a bioequivalence scenario in the clinical setting.
Development and Validation of the Occupational Therapy Engagement Scale for Patients with Stroke
Authors: Wu Tzu-Yi , Lien Bella Ya-Hui , Lequerica Anthony H. , Lu Wen-Shian , Hsieh Ching-Lin
Published: March 2019

Background/Aim. Almost all interventions in occupational therapy require the active engagement of the patients. However, no scale has been specifically designed for assessing engagement in occupational therapy. The purposes of this study were to develop the occupational therapy engagement scale (OTES) and to examine its unidimensionality, reliability, and predictive validity. Methods. The OTES was developed through the review of similar scales, eight experts’ opinions, cognitive interviews, and pilot testing. The unidimensionality was verified with Rasch model fitting and principal component analysis. The Rasch reliability was also estimated. Pearson’s correlation coefficient (r) was used to validate the predictive validity by examining the association between the Rasch scores of the OTES and patients’ performance of activities of daily living (ADL). Results. A total of 253 patients with stroke were rated by 22 therapists using the OTES. The mean age of the patients was 62.3±13.2 years old, and 65.2% of the patients were male. The infit and outfit MNSQ of the 12 items of the OTES ranged from 0.62 to 1.34. The unexplained variance of the first dimension of the principal component analysis was 4.0%. The mean person reliability of the OTES was 0.88. Pearson’s r between the OTES and patients’ ADL performance was 0.37. Conclusions. The results of Rasch analysis supported that the items of the OTES were unidimensional. The OTES had sufficient person reliability and predictive validity in patients with stoke.
Bilateral Destructive Hip Disease from Untreated Juvenile Idiopathic Arthritis
Authors: Calafi Arash , Skaggs Alton W. , Shelton Trevor J. , Haus Brian M.
Published: March 2019

We report a novel case of a pediatric patient with bilateral hip destruction from untreated Juvenile idiopathic arthritis (JIA). She was presented at the age of 9 with hip pain associated with bilateral acetabular dysplasia and a dislocated left femoral head. Only 1.5 years later, the patient developed complete destruction of the left femoral head and dislocated right femoral head. The authors have not identified literature describing a similar case report of bilateral femoral head destruction resulting from Persistent Oligoarticular JIA. Pediatric patients presenting with rapidly evolving destructive process should be evaluated for rheumatologic, infectious, and spinal etiologies.
Recurrent Intestinal Obstruction after Radiation Therapy: A Case Report and Review of the Literature
Authors: Nguyen James , Jambhekar Amani , Nasrawi Ziyad , Gudavalli Prasad
Published: March 2019

Introduction. In patients who have undergone resection for rectal cancer after neoadjuvant radiotherapy, loop ileostomy is commonly performed with few serious complications. In rare cases, if this irradiated small bowel is strictured, reversal of the affected ileostomy can have dire consequences. We present a case of a 62-year-old male with recurrent intestinal obstruction after closure of his loop ileostomy. Case Report. RC is a 62-year-old male who initially presented with rectal cancer and underwent neoadjuvant chemoradiation prior to a laparoscopic low anterior resection with diverting loop ileostomy. He underwent elective reversal of his ileostomy and developed persistent postoperative obstruction. He underwent resection of the prior reversal site with normal-appearing dilated proximal bowel loops and collapsed distal bowel loops. He again developed an obstructive picture and underwent resection of the prior anastomosis with creation of an ileocolic anastomosis, after which he recovered well postoperatively. Conclusion. In patients who receive radiation adjuvant therapy for colon cancer, radiation-induced stricture should be considered as a cause of small bowel obstruction postoperative. In the setting of a longstanding ileostomy, evaluation of a defunctionalized distal ileum may be necessary to evaluate potential obstruction from radiation changes.
CPEO and Mitochondrial Myopathy in a Patient with DGUOK Compound Heterozygous Pathogenetic Variant and mtDNA Multiple Deletions
Authors: Montano V. , Simoncini C. , Calì Cassi L. , Legati A. , Siciliano G. , Mancuso M.
Published: March 2019

The classic features of deoxyguanosine kinase (DGUOK) deficiency are infantile onset hepatic failure with nystagmus and hypotonia; mitochondrial DNA studies on affected tissue reveal mitochondrial DNA depletion. Later, it has been shown that the mutations in the same gene may present with adult-onset mitochondrial myopathy and mitochondrial DNA multiple deletions in skeletal muscle. Here we report the case of a 42-year-old Italian woman presenting with a chronic progressive external ophthalmoplegia and myopathy with mtDNA multiple deletions and the compound heterozygous c.462T>A (p.Asn154Lys) and c.707+2T>G pathogenic variants in DGUOK.
Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture
Authors: Sun Xi , Guo Qi , Wei Wenhua , Robertson Stephen , Yuan Ying , Luo Xianghang
Published: March 2019

Emerging evidence demonstrates that microRNAs, as important endogenous posttranscriptional regulators, are essential for bone remodeling and regeneration. Undoubtedly, microRNA-based gene therapies show great potential to become novel approaches against bone-related diseases, including osteoporosis and associated fractures. The major obstacles for continued advancement of microRNA-based therapies in clinical application include their poorin vivostability, nonspecific biodistribution, and unwanted side effects. Appropriate chemical modifications and delivery vectors, which improve the biological performance and potency of microRNA-based drugs, hold the key to translating miRNA technologies into clinical practice. Thus, this review summarizes the current attempts and existing deficiencies of chemical modifications and delivery systems applied in microRNA-based therapies for osteoporosis and osteoporotic fractures to inform further explorations.
Study on the Process and Mechanism of Slope Failure Induced by Mining under Open Pit Slope: A Case Study from Yanqianshan Iron Mine, China
Authors: Hu Yingpeng , Ren Fengyu , Ding Hangxing , Fu Yu , Tan Baohui
Published: March 2019

Mining under an open pit slope results in the collapse and slide of the slope. In this paper, a combination of methods including Google Earth and field investigations is applied to investigate the process of eastern slope failure induced by underground mining in the Yanqianshan Iron Mine over five years. According to the observed ground deformation features, the geomorphic zone of the eastern slope can be divided into four regions (caved rock zone, cracking zone, toppling zone, and sliding zone). Break angles and fracture initiation angles at different times are counted separately. Based on the above work, the process of initiation and development of slope failure is studied. The analysis results show that the process of slope failure could be chronologically divided into three stages. First, a collapse pit, caused by the falling of the overlying strata above the goaf, appeared on the eastern slope. Then, the rock mass around the collapse pit slid into the pit to form a small landslide. Finally, because of mining disturbances and rock creep, a large landslide occurred on the northeastern phyllite slope. The control mechanisms of each failure stage are discussed separately. Finally, the RFPA3D code is employed to simulate the slope failure process under the influence of underground mining. The results are consistent with the field observations, which provided information on deformation failure and the mechanics of the slope that could not be directly observed in the field and deepened the mechanism analysis.
Strong Uniform Convergence Rates of Wavelet Density Estimators with Size-Biased Data
Authors: Guo Huijun , Kou Junke
Published: March 2019

This paper considers the strong uniform convergence of multivariate density estimators in Besov space Bp,qs(Rd) based on size-biased data. We provide convergence rates of wavelet estimators when the parametric μ is known or unknown, respectively. It turns out that the convergence rates coincide with that of Giné and Nickl’s (Uniform Limit Theorems for Wavelet Density Estimators, Ann. Probab., 37(4), 1605-1646, 2009), when the dimension d=1, p=q=∞, and ω(y)≡1.
Halloysite Nanotube-Reinforced Ion-Incorporated Hydroxyapatite-Chitosan Composite Coating on Ti-6Al-4 V Alloy for Implant Application
Authors: Chozhanathmisra Manickam , Pandian Kannaiyan , Govindaraj Dharman , Karthikeyan Palanisamy , Mitu Liviu , Rajavel Rangappan
Published: March 2019

To develop the corrosion resistance and improve the biological performance of a titanium implant (Ti6Al4V alloy), a series of mineral (M = Zn and Mg)-substituted hydroxyapatite (MHA), chitosan-MHA (CS-MHA), halloysite nanotube-MHA (HNT-MHA), and HNT-CS-MHA composite coatings were fabricated on the anodized titanium alloy by electrodeposition. The surface morphology and cross section of various coated composites were investigated by high-resolution scanning electron microscopy (HR-SEM). Furthermore, the functional groups and phase structure of the composite coatings were investigated by Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometry (XRD). Corrosion behaviors of the composite coatings were also investigated by polarization and impedance spectroscopy (EIS). Moreover, the cell-material interaction of the composite coating was observedin vitrowith human osteoblast MG63 cells for cell proliferation at 1, 4, and 7 days of incubation. Consequently, HNT-CS-MHA-Ti may have potential applications in the field of orthopedic and dental implants.
Optical Recording of Action Potentials in Human Induced Pluripotent Stem Cell-Derived Cardiac Single Cells and Monolayers Generated from Long QT Syndrome Type 1 Patients
Authors: Takaki Tadashi , Inagaki Azusa , Chonabayashi Kazuhisa , Inoue Keiji , Miki Kenji , Ohno Seiko , Makiyama Takeru , Horie Minoru , Yoshida Yoshinori
Published: March 2019

Induced pluripotent stem cells (iPSCs) from type 1 long QT (LQT1) patients can differentiate into cardiomyocytes (CMs) including ventricular cells to recapitulate the disease phenotype. Although optical recordings using membrane potential dyes to monitor action potentials (APs) were reported, no study has investigated the disease phenotypes of cardiac channelopathy in association with the cardiac subtype at the single-cell level. We induced iPSC-CMs from three control and three LQT1 patients. Single-cell analysis using a fast-responding dye confirmed that ventricular cells were the dominant subtype (control-iPSC-CMs: 98%, 88%, 91%; LQT1-iPSC-CMs: 95%, 79%, 92%). In addition, LQT1-iPSC-ventricular cells displayed an increased frequency of early afterdepolarizations (pvalue=0.031). Cardiomyocyte monolayers constituted mostly of ventricular cells derived from LQT1-iPSCs showed prolonged AP duration (APD) (pvalue=0.000096). High-throughput assays using cardiomyocyte monolayers in 96-well plates demonstrated that IKr inhibitors prolonged APDs in both control- and LQT1-iPSC-CM monolayers. We confirmed that the optical recordings of APs in single cells and monolayers derived from control- and LQT1-iPSC-CMs can be used to assess arrhythmogenicity, supporting the feasibility of membrane potential dye-based high-throughput screening to study ventricular arrhythmias caused by genetic channelopathy or cardiotoxic drugs.
Ruxolitinib for Therapy of Graft-versus-Host Disease
Authors: Neumann Thomas , Schneidewind Laila , Weigel Martin , Plis Andrzej , Vaizian Rem , Schmidt Christian A. , Krüger William
Published: March 2019

Objective. Steroid-resistant graft-versus-host disease (GvHD) is a major challenge after allogeneic stem cell transplantation and associated with significant morbidity and mortality. There is no therapeutic standard defined beyond calcineurin inhibitors (CNI) and steroids. Furthermore, some patients may have contraindications against CNI or high-dose steroids. Efficacy of ruxolitinib against GvHD has been described recently. Methods. Ruxolitinib was used for treatment of acute or chronic GvHD in eight patients. The patients either needed intensification of therapy or had contraindications against use of CNI or high-dose steroids. Results. Supplementation of therapy in acute GvHD with severe diarrhea with ruxolitinib was unsuccessful. All these patients died from acute GvHD. Introduction of ruxolitinib into therapy and relapse prophylaxis in other patients was successful in 4/4 cases (CR=3, PR=1). Indications for ruxolitinib were contraindications against CNI due to aHUS in two cases and the need for steroid sparing in two other cases. None of these patients suffered from diarrhea at the initiation of ruxolitinib. Conclusion. Ruxolitinib was effective for therapy of acute and chronic GvHD in higher lines in patients without severe diarrhea. Ruxolitinib could replace successfully CNI and high-dose steroids. Further investigations are necessary to define the position of ruxolitinib in GvHD-therapy.
Earthquake‐Induced Domino‐Type Progressive Collapse in Regular, Semiregular, and Irregular Bridges
Authors: Seyedkhoei Amir , Akbari Reza , Maalek Shahrokh
Published: March 2019

Progressive collapse is a persistent spread and enlargement of initial local failure of structures characterized by inconsistency between the initial failure and its resulting extensive collapse. Although, great contributions have been made towards the progressive collapse of building structures, comparably small attention has been paid to bridge structures. In this study, the procedure of progressive collapse of bridges with concrete prestressed voided slab under earthquakes and effects of other parameters on propagation of collapse of regular, semiregular, and irregular bridges are investigated. At first, a bridge specimen, which its shake table test results were provided by previous researchers, was modeled and verified using the applied element method. Then, the progressive collapse of the box girder bridge was investigated. In the next step, progressive collapse process of the same bridge with posttensioned voided slab under earthquakes was studied using nonlinear time history analysis. Irregularities of the piers were analyzed parametrically. The results show that domino‐type progressive collapse happens in bridges with voided slab after the initial failure of the deck at the seating of bridge abutment. Also, it is concluded that, type of the deck, height of the piers, and ground slope have a great effect on the progressive collapse procedure of both regular and irregular bridges with voided slab deck.
Positive Correlation between Activated CypA/CD147 Signaling and MMP-9 Expression in Mice Inflammatory Periapical Lesion
Authors: Wang Yan-qing , Zhang Jie , Zhu Ling-xin , Yu Jing-jing , Liu Ming-wen , Zhu Shen-ting , Liu Guo-jing , Peng Bin
Published: March 2019

Aim. Cyclophilin A (CypA)/CD147 signaling plays critical roles in the regulation of inflammation and bone metabolism. This study aimed to investigate the participation of CypA/CD147 in mice periapical lesions progression and its relationship with bone resorption.Methodology. Periapical lesions were induced by pulp exposure in the first lower molars of 40 C57BL/6J mice. The mice were sacrificed on days 0, 7, 14, 21, 28, 35, 42, and 49. Mandibles were harvested for X-ray imaging, microcomputed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. Western blot was employed to further detect the related molecular signaling pathways in LPS-stimulated RAW 264.7 cells treated with CypA inhibitor.Results. The volume and area of the periapical lesions increased from day 0 to day 35 and remained comparably stable until day 49. Immunohistochemistry demonstrated that the CypA expression levels also increased from day 0 to day 35 and decreased until day 49, similar to CD147 expression (R2= 0.4423, P < 0.05), osteoclast number (R2= 0.5101, P < 0.01), and the expression of osteoclastogenesis-related matrix metalloproteinase 9 (MMP-9) (R2= 0.4715, P < 0.05). Serial sections further confirmed the colocalization of CypA and CD147 on osteoclasts with immunohistochemistry. And the distribution of CypA-positive or CD147-positive cells was positively correlated with the dynamics of MMP-9-positive cells by using immunofluorescence analysis. Furthermore, CD147 and MMP-9 expression in RAW 264.7 cells were both downregulated with CypA inhibitor treatment (P < 0.05).Conclusions. The present study reveals the positive correlation of CypA/CD147 signaling and osteoclast-related MMP-9 expression in mice inflammatory periapical lesions progression. Therefore, intervention of CypA/CD147 signaling could probably provide a potential therapeutic target for attenuating inflammatory bone resorption.
Investigation of Miscanthus and Sunflower Stalk Fiber‐Reinforced Composites for Insulation Applications
Authors: Eschenhagen Arne , Raj Magdalena , Rodrigo Natalia , Zamora Alejandro , Labonne Laurent , Evon Philippe , Welemane Hélène
Published: March 2019

The development of materials based on renewable and low‐cost resources is today’s crucial interest for civil engineering. This work intends to investigate two new vegetable fibers as composite reinforcement for insulation application in the building industry. Miscanthus and sunflower stalk have mainly been selected for their high fiber content, low water content after harvesting, and availability. These criteria lead to good structural properties and allow a reduction in production and transportation costs. This study aims at demonstrating the feasibility to produce cohesive panels from these lignocellulosic fibers and their related interesting mechanical and thermal properties according to various natural binders.
Radiomics of Multiparametric MRI for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer: A Multicenter Study
Authors: Liu Zhenyu , Li Zhuolin , Qu Jinrong , Zhang Renzhi , Zhou Xuezhi , Li Longfei , Sun Kai , Tang Zhenchao , Jiang Hui , Li Hailiang , Xiong Qianqian , Ding Yingying , Zhao Xinming , Wang Kun , Liu Zaiyi , Tian Jie
Published: March 2019

Purpose:

We evaluated the performance of the newly proposed radiomics of multiparametric MRI (RMM), developed and validated based on a multicenter dataset adopting a radiomic strategy, for pretreatment prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer.

Experimental Design:

A total of 586 potentially eligible patients were retrospectively enrolled from four hospitals (primary cohort and external validation cohort 1–3). Quantitative imaging features were extracted from T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging before NAC for each patient. With features selected using a coarse to fine feature selection strategy, four radiomic signatures were constructed based on each of the three MRI sequences and their combination. RMM was developed based on the best radiomic signature incorporating with independent clinicopathologic risk factors. The performance of RMM was assessed with respect to its discrimination and clinical usefulness, and compared with that of clinical information–based prediction model.

Results:

Radiomic signature combining multiparametric MRI achieved an AUC of 0.79 (the highest among the four radiomic signatures). The signature further achieved good performances in hormone receptor–positive and HER2-negative group and triple-negative group. RMM yielded an AUC of 0.86, which was significantly higher than that of clinical model in two of the three external validation cohorts.

Conclusions:

The study suggested a possibility that RMM provided a potential tool to develop a model for predicting pCR to NAC in breast cancer.
Alcohol-metabolizing Enzymes' Gene Polymorphisms and Susceptibility to Multiple Head and Neck Cancers
Authors: Chien Huei-Tzu , Young Chi-Kuang , Chen Tzu-Ping , Liao Chun-Ta , Wang Hung-Ming , Cheng Sou-De , Huang Shiang-Fu
Published: March 2019

Multiple primary tumors (MPT), especially in the hypopharynx and esophagus, are challenging in patients with head and neck cancer (HNC). Alcohol and alcohol-metabolizing genes were reported to be related to upper digestive tract cancers. Here, we investigated whether the genotypes of alcohol-metabolizing enzymes (ADH1B, ADH1C, and ALDH2) affected patients' susceptibility to developing MPTs. We recruited 659 male patients with HNC between March 1996 and February 2017. Age- and gender-matched controls were also recruited. A total of 164 patients with HNC were identified to have second or third malignancies. The single-nucleotide polymorphisms in ADH1B (rs1229984), ADH1C (rs698), and ALDH2 (rs671) were analyzed by TaqMan assays. The prevalence of ALDH2 *2 allele carriers is significantly higher than that of *1*1 homozygotes for oral cavity (P = 0.013) and oropharyngeal cancers (P = 0.012). For ADH1B, the number of *1 allele carriers is significantly higher than that of *2*2 homozygotes for oropharyngeal (P = 0.017) and hypopharyngeal cancers (P < 0.001). ADH1C (rs698) SNPs are not significantly associated with tumor subsites (all P > 0.05). Polymorphisms in ALDH2 (*2 allele carriers) and ADH1B (*1 allele carriers) significantly increase the risk of developing MPTs in the upper digestive tract [P < 0.001, OR (95% confidence interval (CI): 5.186 (2.444–11.004) and P < 0.05, OR (95% CI): 2.093 (1.149–3.812), respectively]. ALDH2 (rs671) *2 and ADH1B (rs1229984) *1 allele carriers were shown to develop MPTs in the upper digestive tract. Genetic information may be used to identify high-risk patients for the development of MPTs.
Overexpression of TEL-MN1 Fusion Enhances Resistance of HL-60 Cells to Idarubicin
Authors: Gong Shenglan , Guo Mengqiao , Tang Gusheng , Yang Jianmin , Qiu Huiying
Published: March 2019

Background: The translocation t(12; 22) (p13;q12) is a recurrent but infrequent chromosome abnormality in human myeloid malignancies. To date, the role of TEL-MN1 fusion in leukemogenic process and drug resistance is still largely unknown. Methods: In the present study, the TEL-MN1 fusion was transfected into HL-60 cells to upregulate TEL-MN1 expression via a retroviral vector. MTT assay was employed to examine cell viability and flow cytometry was performed to evaluate cell apoptosis. Idarubicin was used to treat HL-60 cells for estimating the effect of TEL-MN1 fusion on the chemotherapy resistance. Results: The results showed that overexpression of TEL-MN1 in HL-60 cells could promote cell proliferation, suggesting that TEL-MN1 may be involved in the leukemogenesis process. HL-60 cells treated with idarubicin showed a weakened cell viability, whereas TEL-MN1 overexpression attenuated the idarubicin-induced inhibition of cell viability and acceleration of cell apoptosis of HL-60 cells. Conclusion: Taken together, our results indicated that TEL-MN1 fusion is an oncogene involved in the leukemogenesis process and TEL-MN1 overexpression enhanced resistance of HL-60 cells to idarubicin, which may provide a useful tool for studying the mechanism of leukemogenesis and drug resistance.
1,000 Retroperitoneoscopic Procedures of the Upper Urinary Tract: Analysis of Complications
Authors: Klap Julia , Butow Zentia , Champy Cecile M. , Masson-Lecomte Alexandra , Defontaines Julien , De la Taille Alexandre , Salomon Laurent
Published: March 2019

Background and Objective: To evaluate risk factors and complications of retroperitoneoscopic procedures of upper urinary tract and adrenal gland. Methods: From 1994 to 2016, 1,000 retroperitoneal laparoscopies were performed – 476 nephrectomies, 201 adrenalectomies, 103 partial nephrectomies, 91 pyeloplasties, 70 nephro-ureterectomies, and 59 miscellaneous surgeries (diverticulectomy). Data collection was prospective. We analyzed age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, operative time, blood loss, hospitalization stay and complications. Risks factors were explored with univariate and multivariate analysis. Results: The mean BMI was 25 and median ASA 2. The mean operative time was 136 mn, mean blood loss 149 mL. There were 49 conversions. Of the patients, 41 required re-interventions, predominantly due to urinary fistula or post-operative bleeding. Post-operatively, 145 complications were recorded. In multivariate analysis, partial nephrectomies (OR 2.12, p = 0.031, 95% CI [1.07–4.22]) and pyeloplasties (OR 1.97, p = 0.02, 95% CI [1.11–3.48]) were significantly more at risk of complication than nephrectomies. An ASA score of 3 was also a significant risk factor of complications (OR 2.3, p = 0.014, 95% CI [1.17–4.47]) and an increased BMI carried a higher risk of conversion. There was no significant difference of conversion or complication rates between the first and last 500 patients. Conclusions: Upper urinary tract and adrenal surgeries can be performed by retroperitoneal laparoscopy. This surgical technic is safe and reproducible. The choice of the technic must be oriented by ASA, BMI and the type of surgery.
Myeloid Sarcoma
Authors: Magdy Mohamed , Abdel Karim Nagla , Eldessouki Ihab , Gaber Ola , Rahouma Mohamed , Ghareeb Mohamed
Published: March 2019

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences.
The Preoperative Prognostic Nutritional Index Predicts Short-Term and Long-Term Outcomes of Patients with Stage II/III Gastric Cancer: Analysis of a Multi-Institution Dataset
Authors: Sasahara Masahiro , Kanda Mitsuro , Ito Seiji , Mochizuki Yoshinari , Teramoto Hitoshi , Ishigure Kiyoshi , Murai Toshifumi , Asada Takahiro , Ishiyama Akiharu , Matsushita Hidenobu , Tanaka Chie , Kobayashi Daisuke , Fujiwara Michitaka , Murotani Kenta , Kodera Yasuhiro
Published: March 2019

Background/Aims: Identification of nutritional indicators to predict short-term and long-term outcomes is necessary to provide appropriate treatment to patients with gastric cancer. Methods: We designed an analysis of a multicenter dataset of patients with gastric cancer who underwent gastrectomy between 2010 and 2014. We enrolled 842 eligible patients who had stage II/III gastric cancer. The area under the curve (AUC) values were compared among prognostic nutritional index (PNI), calculated as 10 × albumin g/dL + 0.005 × total lymphocyte count/mm3, and its constituents, and the predictive value of preoperative PNI for postoperative short-term and long-term outcomes was evaluated. Results: Preoperative PNI exhibited higher AUC values (0.719) for 1-year survival than its constituents, and the optimal cutoff value was 47. The disease-free and overall survival of patients in the PNI-low group were significantly shorter compared with those in the PNI-high group. The prognostic difference between the PNI-high and PNI-low groups was significantly greater in the subgroup of patients who underwent total gastrectomy. Clinically relevant postoperative complications were more frequently observed in the PNI-low group. Conclusions: The preoperative PNI is a useful predictor reflecting the incidence of complications after gastrectomy and the prognosis of patients with stage II/III gastric cancer.
Salidroside Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis by Inhibiting the Hypoxia-Inducible Factor-1α Expression Through Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway
Authors: Liu Guoyong , He Liyu
Published: March 2019

Background: Focal segmental glomerulosclerosis (FSGS) is a common histologic pattern of kidney injury, which may eventually lead to end-stage renal disease. Objectives: Salidroside (SAL, p-hydroxyphenyl-β-D-glucoside) is an active component isolated from Rhodiolarosea, which has various pharmacological properties including anti-inflammation and antioxidation. SAL may attenuate FSGS, but the underlying mechanism is not clear. Thus, in this study, we focus on the renoprotective role of SAL in FSGS using Adriamycin nephropathy (AN) mouse models. Methods: In C57 BL/6 mice, AN was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then they were organized into 6 groups for the animal experiments: AN + saline group; AN + SAL group (40 mg/kg); AN + LY294002 (a selective phosphatidylinositol 3-kinase [PI3K] inhibitors, 50 mg/kg) group; AN + SAL + LY294002 group; AN + YC-1 (a selective hypoxia-inducible factor-1α [HIF-1α] inhibitors, 50 mg/kg) group; and AN + SAL + YC-1 group. All of the drugs were given on the day of Adriamycin injection and continued for 6 weeks, and the drugs were given by intraperitoneally. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: In FSGS mouse models, SAL treatment could ameliorate proteinuria, renal function, and markers of Nephrotic Syndrome inhibit alpha-smooth muscle actin and fibronectin expression and downregulates the expression of HIF-1α. Besides, the levels of PI3K and p-protein kinase B (Akt) in renal tissues were significantly decreased after SAL injection. Eventually, SAL treatment results reduced inflammatory cytokines and reactive oxygen species production. Conclusions: In summary, SAL ameliorates FSGS mainly by inhibiting the expression of HIF-1α through PI3K/Akt pathway, which might offer an array of hope for ameliorating FSGS.
Effectiveness of Multilevel Botulinum Toxin A Injection with Integrated Treatment Program on Spasticity Reduction in Non-Ambulatory Young Children with Cerebral Palsy
Authors: Aydil Sebahat , Akpinar Fatma Merih , Akpinar Evren , Beng Kubilay , Yagmurlu Mehmet Firat
Published: March 2019

Objective: The aim of the present study was to evaluate the effectiveness of multilevel Botulinum Toxin A (BTX-A) injection, as part of an integrated approach, for the treatment of spasticity in non-ambulatory young children with diplegic cerebral palsy (CP). Subjects and Methods: Seventeen non-ambulatory patients aged 4–8 years with diplegic CP (Gross Motor Function Classification System [GMFCS] level IV) were evaluated before and at 1st, 3rd, and 6th months after BTX-A injection. The effect of BTX-A on spasticity of gastrocnemius and hamstring muscles was assessed using the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). The velocity-dependent properties of spastic muscle as both slow (R2) and fast (R1) stretches were evaluated in MTS. Results: A statistically significant improvement was observed in R1 angles of gastrocnemius and hamstring muscles at 1st and 3rd months after BTX-A injection in non-ambulatory young children with CP. Statistically significant improvement was found in MAS of gastrocnemius and hamstring muscles and R2 angles of knee and ankle joint after 1st month of BTX-A injection. Conclusion: Multilevel BTX-A injection, as part of an integrated approach, can be used for focal treatment of spasticity, especially of hamstring and gastrocnemius muscles, in non-ambulatory young children with CP GMFCS level IV.
GENDER AND AGE ASPECTS OF BIOENERGETICS PROCESSES IN EXPERIMENTAL PASSIVE TOBACCO SMOKING AND MONOSODIUM GLUTAMATE ADMINISTRATION
Authors: Rutska A. V. , Krynytska I. Ya.
Published: March 2019

Background. Active smoking and exposure to passive smoke are responsible for more than 5 million deaths each year. At the same time, a characteristic feature of present food technologies is the use of food additives that are not always safe for human health, such as monosodium glutamate (MSG).

Objective. The aim of the research was to determine the changes in mitochondrial enzymes activity in rats in case of passive tobacco smoke combined with prolonged administration of MSG in the sex and age aspects.

Methods. The evaluation of bioenergetics processes in the mitochondria of circulating neutrophils was carried out using succinate dehydrogenase (SDG) and cytochrome oxidase (CO) activity.

 Results. Passive tobacco smoke combined with the MSG administration in mature male-rats is accompanied by a significant inhibition of bioenergetics processes, as evidenced by a decrease in succinate dehydrogenase activity by 47.1% (p<0.001) compared to the intact animals, which is by 27.9% (p<0.001) below this index in case of the isolated effect of tobacco smoke and reduction of cytochrome oxidase activity by 27.5% (p<0.001) compared to the control group.

Conclusions. Thus, the findings suggest that low dose intake of monosodium glutamate enhances the ability of tobacco smoke to disrupt the cell's bioenergetics processes by affecting the respiratory chain function and generation of ATP. Therefore, it is advisable to investigate the established toxic doses of E621, as well as to study the molecular mechanisms of the ‘safe’ (allowed) doses of MSG effect on a living organism.
KIDNEY LESIONS IN HIV-INFECTED PATIENTS
Authors: Andrushchak М. О.
Published: March 2019

Introduction. HIV prevalence is one of the most important issues of contemporary medicine. Over a 30-year history of this disease more than 75 million people have been infected with HIV, nearly 30 million adults and children of died. In the future decades, its significance in world premature mortality rates continues to rise. The objective of the study was to establish clinical and laboratory features of kidney lesions in HIV infection.

Methods. The study involved 292 HIV-infected patients, who were managed outpatiently at the Chernivtsi Regional AIDS Center. Taking into account the main markers of kidney lesions: persistent proteinuria and glomerular filtration rate <60 mL/min/1.73 m2, 48 persons were diagnosed with chronic kidney disease (CKD), which was very frequently accompanied by dysfunction of these organs.

Results. Increasing proteinuria rate is accompanied by a significant renal dysfunction and more frequently is combined with arterial hypertension as well as hematuria without significant differences in the incidence of opportunistic diseases. The mean reciprocal correlation between the levels of proteinuria and glomerular filtration rate (r=-0.562, p<0.01), as well as between the levels of proteinuria and hemoglobin (r=-0.596, p<0.01) have been established as well.

Conclusions. Kidney lesions in HIV-infected are most often characterized by tubulointerstitial lesions. At the same time, glomerular kidney lesion, which is much less common, is accompanied by a significantly higher level of HIV RNA.
Procedimento de Manifestação de Interesse (PMI) Municipal
Authors: Gasiola Gustavo Gil
Published: March 2019

O PMI para estruturação integrada de empreendimento (PMI Integrado) é uma inovação legislativa trazida pelo Decreto nº 57.678/2017 do Município de São Paulo. O presente artigo discute os aspectos que o difere do PMI tradicional, abordando as características específicas da autorização, a neutralidade do autorizado e a abrangência da estruturação integrada.
Parceria público-privada como instrumento de concretização do direito à saúde
Authors: Silva Leire Taíze Ribeiro da , Silva Marcelo Alves da
Published: March 2019

Este estudo objetiva analisar a possibilidade da participação da iniciativa privada, por meio das Parcerias Público-Privadas, como forma de garantir o acesso digno e eficiente ao serviço público de saúde no Brasil, considerando os problemas enfrentados por aqueles que recorrem ao Sistema Único de Saúde. Para tanto, buscou-se sistematizar as informações relacionadas ao tema, explanando acerca de sua importância e a possibilidade do seu emprego dentro do atual quadro de saúde pública existente. Pontua-se, neste sentido, que as PPP’s serão apresentadas como alternativa executável para a prestação do serviço público essencial, em observância aos princípios da universalidade, equidade e integralidade, previstos na Lei nº 8.080/1900, que regulamenta o SUS. Além do estudo acerca do conceito, objeto suscetível de concessão e, ainda, das modalidades previstas na Lei 11.079/2004, que trata das Parcerias Público-Privadas, também será feita uma breve análise a respeito do panorama do Sistema Único de Saúde, apresentando os seus antecedentes, os principais problemas e a possibilidade de que os serviços de saúde sejam prestados de forma complementar pela iniciativa privada, em conformidade com a Constituição Federal.
Inconstitucionalidade da subcontratação na prestação de serviços públicos por particulares sem prévia licitação
Authors: Valente Larissa Peixoto , Souza Clara Santos
Published: March 2019

O objetivo deste trabalho é analisar as razões que justificam a inconstitucionalidade da subcontratação na prestação de serviços públicos por particulares sem prévia licitação na ordem econômica brasileira. Para tanto, a metodologia utilizada no presente artigo foi o método hipotético dedutivo. Razões serão listadas para demonstrar a inconstitucionalidade da subcontratação sem prévia licitação, sob a luz dos aspectos dos princípios Direito Administrativo, da Constituição Federal de 1988 e dos princípios constitucionais.
Experiências municipais de regulação do transporte por aplicativo
Authors: Morais Cesar André Machado de
Published: March 2019

Nos últimos anos, foram amplamente introduzidos em vários municípios brasileiros os serviços de transporte por aplicativo, os quais pertencem a um modelo econômico cuja natureza disruptiva levou à necessidade de se revisar a regulação dos transportes em todo o mundo. A partir desse panorama, o presente trabalho tem como objetivo analisar os modelos de regulação municipais, examinando suas prováveis eficácias, bem como suas respectivas compatibilidades à Lei Federal 12.587/12. Para tanto, foi necessária a adoção de uma metodologia comparativa e dedutiva, para ao final concluir-se que as normativas municipais vêm adotando medidas ambíguas em relação à natureza dos serviços da economia do compartilhamento. E ainda, conclui-se que as normativas em questão atuam de modo a forçar a adequação dos serviços de transporte por aplicativo aos princípios estabelecidos pela Lei 12.587/12.
Os limites do teto remuneratório na acumulação lícita de cargos e funções públicas e as transformações do Direito Administrativo
Authors: Moron Eduardo Daniel Lazarte
Published: March 2019

A função pública submetida ao regime estatutário não foi preservada das recentes transformações do Direito Administrativo. Não somente o modelo jurídico constitucional em matéria de servidor público estatutário passou em período recente por alterações no texto constitucional, como também a interpretação dos dispositivos constitucionais, conferida pelo Supremo Tribunal Federal tem evoluído, coincidindo com o novo paradigma pós-positivista do Direito Administrativo. O presente artigo analisa o recente julgado do STF em sede de repercussão geral que afastou a observância do teto remuneratório quanto à soma das remunerações do agente público nos casos constitucionalmente autorizados de acumulação de cargos e funções para fins de incidência do artigo 37, inciso XI da Constituição federal. Analisando os votos proferidos, verifica-se que aspectos importantes foram debatidos a respeito das transformações do Direito Administrativo, com destaque para o novo paradigma pós-positivista que consiste na concretização dos direitos fundamentais. Por fim, no que diz respeito à metodologia utilizada, recorre-se ao modelo analítico-dedutivo, tendo como parâmetro o Direito Constitucional aplicado.