bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Fused Optimization Algorithm of Genetic Algorithm and Ant Colony Optimization
Authors: Zhao FuTao , Yao Zhong , Luan Jing , Song Xin
Published: August 2016

A novel fused algorithm that delivers the benefits of both genetic algorithms (GAs) and ant colony optimization (ACO) is proposed to solve the supplier selection problem. The proposed method combines the evolutionary effect of GAs and the cooperative effect of ACO. A GA with a great global converging rate aims to produce an initial optimum for allocating initial pheromones of ACO. An ACO with great parallelism and effective feedback is then served to obtain the optimal solution. In this paper, the approach has been applied to the supplier selection problem. By conducting a numerical experiment, parameters of ACO are optimized using a traditional method and another hybrid algorithm of a GA and ACO, and the results of the supplier selection problem demonstrate the quality and efficiency improvement of the novel fused method with optimal parameters, verifying its feasibility and effectiveness. Adopting a fused algorithm of a GA and ACO to solve the supplier selection problem is an innovative solution that presents a clear methodological contribution to optimization algorithm research and can serve as a practical approach and management reference for various companies.
Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion
Authors: Chen Ting , Yuan Fahu , Wang Hualin , Tian Yu , He Lei , Shao Yang , Li Na , Liu Zhiguo
Published: August 2016

Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD). The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA) against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD) supplement with perilla oil (POH) for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.
Thin Film Nanofibrous Composite Membrane for Dead-End Seawater Desalination
Authors: Yalcinkaya Baturalp , Yalcinkaya Fatma , Chaloupek Jiri
Published: August 2016

The aim of the study was to prepare a thin film nanofibrous composite membrane utilized for nanofiltration technologies. The composite membrane consists of a three-layer system including a nonwoven part as the supporting material, a nanofibrous scaffold as the porous surface, and an active layer. The nonwoven part and the nanofibrous scaffold were laminated together to improve the mechanical properties of the complete membrane. Active layer formations were done successfully via interfacial polymerization. A filtration test was carried out using solutions of MgSO4, NaCl, Na2SO4, CaCl2, and real seawater using the dead-end filtration method. The results indicated that the piperazine-based membrane exhibited higher rejection of divalent salt ions (>98%) with high flux. In addition, them-phenylenediamine-based membrane exhibited higher rejection of divalent and monovalent salt ions (>98% divalent and >96% monovalent) with reasonable flux. The desalination of real seawater results showed that thin film nanofibrous composite membranes were able to retain 98% of salt ions from highly saline seawater without showing any fouling. The electrospun nanofibrous materials proved to be an alternative functional supporting material instead of the polymeric phase-inverted support layer in liquid filtration.
Lipid Regulation Effects of Raw and Processed Notoginseng Radix Et Rhizome on Steatotic Hepatocyte L02 Cell
Authors: Chen Zhu , Li Chunmei , Yang Caixia , Zhao Ronghua , Mao Xiaojian , Yu Jie
Published: August 2016

Introduction. Raw and processed Notoginseng Radix Et Rhizome (NRR) have been widely used in treatment of metabolic syndromes and related disease, including nonalcoholic fatty liver disease (NAFLD). This study was designed to investigate lipid regulation effects of raw and processed NRR in steatotic L02 cell.Materials and Methods. Steatotic L02 cells were obtained after being cultured with 5% fat emulsion-10% FBS-RPMI 1640 medium for 48 h. Contents of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in steatotic L02 cells were evaluated after treatment. Furthermore, the lipid metabolism regulation mechanism ofPanax notoginsengsaponins (PNS) and its monomers were evaluated by detecting the expressions of hydroxymethyl glutaric acyl coenzyme A reductase (HMG-CoAR), sterol regulating element binding protein-2 (SREBP-2), and cholesterol 7α-hydroxylase (CYP7α).Results. TG and TC contents were doubled in model group compared to those in normal L02 cells group. Raw NRR and NRR heated with sand (NRR-B) showed much remarkable lipid-lowering effects in steatotic L02 cells. PNS, notoginsenoside R1, ginsenoside Rg1, and ginsenoside Rb1displayed the best TG and TC regulation activity, which could significantly reduce contents of SREBP-2 and HMG-CoAR and increase the content of CYP7α.Conclusions. Our results may support the fact that both raw NRR and NRR-B might have more satisfactory effects in the treatment of NAFLD.
Insertion Success of the Laryngeal Tube in Emergency Airway Management
Authors: Bernhard Michael , Gries André , Ramshorn-Zimmer Alexandra , Wenzel Volker , Hossfeld Bjoern
Published: August 2016

Background. Emergency airway management (AM) is a priority when resuscitating critically ill or severely injured patients. The goal of this study was to determine the success rates of LT insertion during AM.Methods. Studies that included LT first-pass insertion (FPI) and overall-pass insertion (OPI) success by emergency medical services and in-hospital providers performing AM for emergency situations as well as for scheduled surgery published until July 2014 were searched systematically in Medline.Results. Data of 36 studies (n= 1,897) reported a LT FPI success by physicians of 82.5% with an OPI success of 93.6% (p<0.001). A cumulative analysis of all 53 studies (n= 3,600) led to FPI and OPI success of 80.1% and 92.6% (p<0.001), respectively. The results of 26 studies (n= 2,159) comparing the LT with the laryngeal mask airway (LMA) demonstrated a FPI success of 77.0 versus 78.7% (p=0.36) and an OPI success of 92.2 versus 97.7% (p<0.001).Conclusion. LT insertion failed in the first attempt in one out of five patients, with an overall failure rate in one out of 14 patients. When compared with the LT, the LMA had a cumulative 5.5% better OPI success rate.
Polymorphism of HDAC9 Gene Is Associated with Increased Risk of Acute Coronary Syndrome in Chinese Han Population
Authors: Han Zhenhua , Dong Xin , Zhang Chaoying , Wu Yue , Yuan Zuyi , Wang Xinhong
Published: August 2016

Recent genome-wide association studies (GWAS) have indicated an association of histone deacetylase 9 (HDAC9) genetic variant with large-vessel stroke and coronary artery disease, among the European population. However, whether HDAC9 gene is associated with an increased susceptibility to acute coronary syndrome (ACS) in Chinese Han population is not known. A total of 472 patients, including patients with ACS (N=309), and those with chest pain syndrome (controls,N=163) were enrolled. Genotyping for HDAC9 gene was performed using the ligation detection reaction assay. A series of statistical analyses were performed to investigate the correlation between HDAC9 gene SNPs and the susceptibility to ACS. The results revealed a significant association of rs2240419 with ACS risk in which the A allele (P= 0.047) and the A allele carriers (AA + AG) (P= 0.037) were more likely to be in ACS group as compared to those in the control group. None of two other SNPs, rs2389995 and rs2107595, were significantly associated with ACS risk (P> 0.05). Logistic regression analyses further revealed an increased risk for ACS in A allele carrier among rs2240419 genotypes, as compared to those with GG homozygotes (odds ratio: 1.869, 95% CI 1.143, 3.056,P= 0.013). A significant correlation between rs2240419 polymorphism of HDAC9 gene and the susceptibility to ACS in Chinese Han population was observed in this study.
Discrete Approaches to Continuous Boundary Value Problems: Existence and Convergence of Solutions
Authors: Anderson Douglas R. , Tisdell Christopher C.
Published: August 2016

We investigate two types of first-order, two-point boundary value problems (BVPs). Firstly, we study BVPs that involve nonlinear difference equations (the “discrete” BVP); and secondly, we study BVPs involving nonlinear ordinary differential equations (the “continuous” BVP). We formulate some sufficient conditions under which the discrete BVP will admit solutions. For this, our choice of methods involves a monotone iterative technique and the method of successive approximations (a.k.a. Picard iterations) in the absence of Lipschitz conditions. Our existence results for the discrete BVP are of a constructive nature and are of independent interest in their own right. We then turn our attention to applying our existence results for the discrete BVP to the continuous BVP. We form new existence results for solutions to the continuous BVP with our methods involving linear interpolation of the data from the discrete BVP, combined witha prioribounds and the convergence Arzela-Ascoli theorem. Thus, our use of discrete BVPs to yield results for the continuous BVP may be considered as a discrete approach to continuous BVPs.
Image Blocking Encryption Algorithm Based on Laser Chaos Synchronization
Authors: Wang Shu-Ying , Zhao Jian-Feng , Li Xian-Feng , Zhang Li-Tao
Published: August 2016

In view of the digital image transmission security, based on laser chaos synchronization and Arnold cat map, a novel image encryption scheme is proposed. Based on pixel values of plain image a parameter is generated to influence the secret key. Sequences of the drive system and response system are pretreated by the same method and make image blocking encryption scheme for plain image. Finally, pixels position are scrambled by general Arnold transformation. In decryption process, the chaotic synchronization accuracy is fully considered and the relationship between the effect of synchronization and decryption is analyzed, which has characteristics of high precision, higher efficiency, simplicity, flexibility, and better controllability. The experimental results show that the encryption algorithm image has high security and good antijamming performance.
The Role of Fecal Calprotectin in Evaluating Intestinal Involvement of Behçet’s Disease
Authors: Özşeker Burak , Şahin Cem , Özşeker Havva Solak , Efe S. Cumali , Kav Taylan , Bayraktar Yusuf
Published: August 2016

One of the regions of involvement of Behçet’s disease (BD), a systematic inflammatory vasculitis with unknown etiology, is the gastrointestinal (GI) tract. Upper GI endoscopy, colonoscopy, and capsule endoscopy are frequently used methods to diagnose the intestinal involvement of BD. The aim of this study was to investigate the role of fecal calprotectin (FC) in the evaluation of intestinal involvement in BD.Material and Method. A total of 30 patients who were diagnosed with BD and had no GI symptoms and 25 individuals in the control group were included in this study.Results. Levels of FC were statistically significantly higher in patients with BD compared to the control group (p<0.001). The correlation analysis performed including FC and markers of disease activity revealed a positive and statistically significant correlation between FC level and CRP and erythrocyte sedimentation rate (r: 0.255,p<0.049, andr: 0.404,p<0.001, resp.). FC levels in patients who were detected to have ulcers in the terminal ileum and colon in the colonoscopic examination were statistically significantly higher compared to the patients with BD without intestinal involvement (p=0.01).Conclusion. The measurement of FC levels, in patients with BD who are asymptomatic for GI involvement, may be helpful to detect the possible underlying intestinal involvement.
Factors Associated with Hormonal and Intrauterine Contraceptive Use among HIV-Infected Men and Women in Lilongwe, Malawi: A Cross-Sectional Study
Authors: Tang Jennifer H. , Phiri Sam , Ng’ambi Wingston , Krashin Jamie W. , Mlundira Linly , Chaweza Thom , Samala Bernadette , Tweya Hannock , Hosseinipour Mina C. , Haddad Lisa B.
Published: August 2016

Background. Understanding the factors associated with the use of hormonal and intrauterine contraception among HIV-infected men and women may lead to interventions that can help reduce high unintended pregnancy rates.Materials and Methods. This study is a subanalysis of a cross-sectional survey of 289 women and 241 men who were sexually active and HIV-infected and were attending HIV care visits in Lilongwe, Malawi. We estimated adjusted prevalence ratios (PRs) to evaluate factors associated with hormonal and intrauterine contraceptive use for men and women in separate models.Results and Discussion. 39.8% of women and 33.2% of men (p=0.117) reported that they were using hormonal or intrauterine contraception at last intercourse. Having greater than 3 children was the only factor associated with hormonal and intrauterine contraceptive use among men. Among women, younger age, not wanting a pregnancy in 2 years, being with their partner for more than 4 years, and being able to make family planning decisions by themselves were associated with hormonal and intrauterine contraceptive use.Conclusions. The men and women in our study population differed in the factors associated with hormonal and intrauterine contraceptive use. Understanding these differences may help decrease unmet FP needs among HIV-infected men and women.
Effects of Irrigation and Nitrogen Fertilizer Input Levels on SoilNO3--N Content and Vertical Distribution in Greenhouse Tomato (Lycopersicum esculentumMill.)
Authors: Wang Xiukang , Xing Yingying
Published: August 2016

The purpose of this study is to investigate the interactions between irrigation and fertilizer treatments on soilNO3--N content and vertical distribution under drip fertigation in greenhouse tomatoes. Randomized block design with three replications and the treatments consisting of three levels of irrigation and three levels of N fertilizer were used. Three irrigation levels were W1 (100%  ET0), W2 (75%  ET0), and W3 (50%  ET0) and fertilizer levels were F1 (N240–P2O5120–K2O150 kg hm−2), F2 (N180–P2O590–K2O112.5 kg hm−2), and F3 (N120–P2O560–K2O75 kg hm−2). The result demonstrates that dynamics of soilNO3--N and its response to drip fertigation and levels of N moved toward the fore soil moist, and the average soilNO3--N content with W3 treatment was 1.23 times higher than that of the W1 treatment in 0–60 cm at 43 days after transplanting. The negative correlation between N use efficiency and levels of fertilizer N and the N recovery efficiency was increased with increases of N fertilizer application. The fertilizer nitrogen rate greatly significantly influenced soilNO3--N content. Avoiding N leaching through controlled matching N fertilizer application and controlled irrigation to tomato N demand is the key to maintain crop yield and improve N use efficiency.
The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models
Authors: Pomothy Judit , Szombath Gergely , Rokonál Patrik , Mátis Gábor , Neogrády Zsuzsanna , Steinmetzer Torsten , Pászti-Gere Erzsébet
Published: August 2016

Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models.Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2contents were analyzed by Amplex Red method.Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by62.21±26.8%in hepatocyte-Kupffer cell, 2 : 1, and by42.6±14.3%in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors.Conclusions. Based onin vitrofindings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.
Risk Factors for Six Types of Disability among the Older People in Thailand in 2002, 2007, and 2011
Authors: Khongboon Pattaraporn , Pongpanich Sathirakorn , Chapman Robert S.
Published: August 2016

Background. There is an important need to characterize risk factors for disability in Thailand, in order to inform effective prevention and control strategies. This study investigated factors associated with risk of 6 types of disability in Thailand’s ageing population in 2002, 2007, and 2011.Methods. Data came from the Cross-Sectional National Surveys of Older Persons in Thailand conducted by the National Statistical Office (NSO) in 2002, 2007, and 2011. Stratified two-stage sampling was employed. Interviews of 24,835, 30,427, and 34,173 elderly people aged 60 and above were conducted in the respective study years. Prevalence of disabilities was measured, and factors associated with disability risk were assessed with probability-weighted multiple logistic regression.Results. Disability prevalence decreased slightly over the study period. The characteristics with greatest positive impact on disability prevalence were not working over the past week (average impact: 61.2%), age (53.7% per decade), and suffering from one or more chronic illnesses (46.3%).Conclusions. The strong observed positive impact of not working on disability prevalence suggests that raising the mandatory retirement age might result in some reduction of disability risk. Also, the observed positive impact of living with others (versus alone) on disability risk was somewhat unexpected.
Effectiveness and Safety of Newer Antidiabetic Medications for Ramadan Fasting Diabetic Patients
Authors: Mudher Mikhael Ehab
Published: August 2016

Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan. This study reviews the safety and efficacy of newer glucose-lowering therapies during Ramadan. This study was accomplished through a careful literature search about studies that assess the benefit and side effects of these new glucose-lowering therapies during Ramadan during September 2015. Vildagliptin, sitagliptin, liraglutide, exenatide, and dapagliflozin were the only studied glucose-lowering therapies. All of the studied newer glucose-lowering therapies except dapagliflozin were associated with reduced risk to induce hypoglycemia. Gastrointestinal upset was common with the usage of liraglutide while increased thirst sensation was common with dapagliflozin. In conclusion DPP-4 inhibitors such as vildagliptin and sitagliptin may form a suitable glucose-lowering therapy option for Ramadan fasting patients.
Outcomes of Sutureless Iris-Claw Lens Implantation
Authors: Choragiewicz Tomasz , Rejdak Robert , Grzybowski Andrzej , Nowomiejska Katarzyna , Moneta-Wielgoś Joanna , Ozimek Małgorzata , Jünemann Anselm G. M.
Published: August 2016

Purpose. To evaluate the indications, refraction, and visual and safety outcomes of iris-claw intraocular lens implanted retropupillary with sutureless technique during primary or secondary operation.Methods. Retrospective study of case series. The Haigis formula was used to calculate intraocular lens power. In all cases the wound was closed without suturing.Results. The study comprised 47 eyes. The mean follow-up time was 15.9 months (SD 12.2). The mean preoperative CDVA was 0.25 (SD 0.21). The final mean CDVA was 0.46 (SD 0.27). No hypotony or need for wound suturing was observed postoperatively. Mean postoperative refractive error was −0.27 Dsph (−3.87 Dsph to +2.85 Dsph; median 0.0, SD 1.28). The mean postoperative astigmatism was −1.82 Dcyl (min −0.25, max −5.5; median −1.25, SD 1.07). Postoperative complications were observed in 10 eyes. The most common complication was ovalization of the iris, which was observed in 8 eyes. The mean operation time was 35.9 min (min 11 min, max 79 min; median 34, SD 15.4).Conclusion. Retropupilary iris-claw intraocular lens (IOL) implantation with sutureless wound closing is an easy and fast method, ensuring good refractive outcome and a low risk of complication. The Haigis formula proved to be predictable in postoperative refraction.
Thermal and Dielectric Behavior Studies of Poly(Arylene Ether Sulfone)s with Sulfonated and Phosphonated Pendants
Authors: Ganesh Shimoga D. , Pai Vasantakumar K. , Kariduraganavar Mahadevappa Y. , Jayanna Madhu B.
Published: August 2016

The present paper discusses the aspects of the synthesizing valeric acid based poly(ether sulfone)s with active carboxylic acid pendants (VALPSU) from solution polymerization technique via nucleophilic displacement polycondensation reaction among 4,4′-dichlorodiphenyl sulfone (DCDPS) and 4,4′-bis(4-hydroxyphenyl) valeric acid (BHPA). The conditions necessary to synthesize and purify the polymer were investigated in some detail. The synthesized poly(ether sulfone)s comprise sulfone and ether linkages in addition to reactive carboxylic acid functionality; these active carboxylic acid functional groups were exploited to hold the phenyl sulphonic acid and phenyl phosphonic acid pendants. The phenyl sulphonic acid pendants in VALPSU were easily constructed by altering active carboxylic acid moieties by sulfanilic acid using N,N′-dicyclohexylcarbodiimide (DCC) mediated mild synthetic route, whereas the latter one was built in two steps. Initially, polyphosphoric acid condensation with VALPSU by 4-bromoaniline and next straightforward palladium catalyzed synthetic route, in both of which acidic pendants are clenched by polymer backbone via amide linkage. Without impairing the primary polymeric backbone modified polymers were prepared by varying the stoichiometric ratios of respective combinations. All the polymers were physicochemically characterized and pressed into tablets; electrical contacts were established to study the dielectric properties. Finally, the influence of the acidic pendants on the dielectric properties was examined.
Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study
Authors: Siddiqui Ali Nasir , Khayyam Khalid Umer , Sharma Manju
Published: August 2016

Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539–2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310–4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114–11.494,p=0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence.
Role of Epidural Analgesia within an ERAS Program after Laparoscopic Colorectal Surgery: A Review and Meta-Analysis of Randomised Controlled Studies
Authors: Borzellino Giuseppe , Francis Nader Kamal , Chapuis Olivier , Krastinova Evguenia , Dyevre Valérie , Genna Michele
Published: August 2016

Introduction.Epidural analgesia has been a cornerstone of any ERAS program for open colorectal surgery. With the improvements in anesthetic and analgesic techniques as well as the introduction of the laparoscopy for colorectal resection, the role of epidural analgesia has been questioned. The aim of the review was to assess through a meta-analysis the impact of epidural analgesia compared to other analgesic techniques for colorectal laparoscopic surgery within an ERAS program.Methods.Literature research was performed on PubMed, Embase, and the Cochrane Library. All randomised clinical trials that reported data on hospital stay, postoperative complications, and readmissions rates within an ERAS program with and without an epidural analgesia after a colorectal laparoscopic resection were included.Results.Five randomised clinical trials were selected and a total of 168 patients submitted to epidural analgesia were compared to 163 patients treated by an alternative analgesic technique. Pooled data show a longer hospital stay in the epidural group with a mean difference of 1.07 (95% CI 0.06–2.08) without any significant differences in postoperative complications and readmissions rates.Conclusion.Epidural analgesia does not seem to offer any additional clinical benefits to patients undergoing laparoscopic colorectal surgery within an ERAS program.
Traditional Preparations and Methanol Extracts of Medicinal Plants from Papua New Guinea Exhibit Similar Cytochrome P450 Inhibition
Authors: Larson Erica C. , Pond Christopher D. , Rai Prem P. , Matainaho Teatulohi K. , Piskaut Pius , Franklin Michael R. , Barrows Louis R.
Published: August 2016

The hypothesis underlying this current work is that fresh juice expressed from Papua New Guinea (PNG) medicinal plants (succus) will inhibit human Cytochrome P450s (CYPs). The CYP inhibitory activity identified in fresh material was compared with inhibition in methanol extracts of dried material. Succus is the most common method of traditional medicine (TM) preparation for consumption in PNG. There is increasing concern that TMs might antagonize or complicate drug therapy. We have previously shown that methanol extracts of commonly consumed PNG medicinal plants are able to induce and/or inhibit human CYPs in vitro. In this current work plant succus was prepared from fresh plant leaves. Inhibition of three major CYPs was determined using human liver microsomes and enzyme‐selective model substrates. Of 15 species tested, succus from 6/15 was found to inhibit CYP1A2, 7/15 inhibited CYP3A4, and 4/15 inhibited CYP2D6. Chi‐squared tests determined differences in inhibitory activity between succus and methanol preparations. Over 80% agreement was found. Thus, fresh juice from PNG medicinal plants does exhibit the potential to complicate drug therapy in at risk populations. Further, the general reproducibility of these findings suggests that methanol extraction of dried material is a reasonable surrogate preparation method for fresh plant samples.
Preventive Effect of Dihydromyricetin against Cisplatin‐Induced Nephrotoxicity In Vitro and In Vivo
Authors: Wu Fei , Li Yi , Song Haibo , Zhang Yuan , Zhang Yuzhu , Jiang Miao , Wang Fang , Mu Qian , Zhang Wen , Li Liang , Tang Dongqi
Published: August 2016

Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves of Ampelopsis grossedentata. Previous studies have demonstrated the anti‐inflammatory and antioxidative effects of Dihydromyricetin both in vitro and in vivo, but little is known about the effects of Dihydromyricetin on cisplatin‐induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin‐induced oxidative stress, as well as protecting against cisplatin‐induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin.
Toward an Agile Approach to Managing the Effect of Requirements on Software Architecture during Global Software Development
Authors: Alsahli Abdulaziz , Khan Hameed , Alyahya Sultan
Published: August 2016

Requirement change management (RCM) is a critical activity during software development because poor RCM results in occurrence of defects, thereby resulting in software failure. To achieve RCM, efficient impact analysis is mandatory. A common repository is a good approach to maintain changed requirements, reusing and reducing effort. Thus, a better approach is needed to tailor knowledge for better change management of requirements and architecture during global software development (GSD).The objective of this research is to introduce an innovative approach for handling requirements and architecture changes simultaneously during global software development. The approach makes use of Case-Based Reasoning (CBR) and agile practices. Agile practices make our approach iterative, whereas CBR stores requirements and makes them reusable. Twin Peaks is our base model, meaning that requirements and architecture are handled simultaneously. For this research, grounded theory has been applied; similarly, interviews from domain experts were conducted. Interview and literature transcripts formed the basis of data collection in grounded theory. Physical saturation of theory has been achieved through a published case study and developed tool. Expert reviews and statistical analysis have been used for evaluation. The proposed approach resulted in effective change management of requirements and architecture simultaneously during global software development.
Mirror Visual Feedback Training Improves Intermanual Transfer in a Sport-Specific Task: A Comparison between Different Skill Levels
Authors: Steinberg Fabian , Pixa Nils Henrik , Doppelmayr Michael
Published: August 2016

Mirror training therapy is a promising tool to initiate neural plasticity and facilitate the recovery process of motor skills after diseases such as stroke or hemiparesis by improving the intermanual transfer of fine motor skills in healthy people as well as in patients. This study evaluated whether these augmented performance improvements by mirror visual feedback (MVF) could be used for learning a sport-specific skill and if the effects are modulated by skill level. A sample of 39 young, healthy, and experienced basketball and handball players and 41 novices performed a stationary basketball dribble task at a mirror box in a standing position and received either MVF or direct feedback. After four training days using only the right hand, performance of both hands improved from pre- to posttest measurements. Only the left hand (untrained) performance of the experienced participants receiving MVF was more pronounced than for the control group. This indicates that intermanual motor transfer can be improved by MVF in a sport-specific task. However, this effect cannot be generalized to motor learning per se since it is modulated by individuals’ skill level, a factor that might be considered in mirror therapy research.
CEACAM1: Expression and Role in Melanocyte Transformation
Authors: Turcu Gabriela , Nedelcu Roxana Ioana , Ion Daniela Adriana , Brînzea Alice , Cioplea Mirela Daniela , Jilaveanu Lucia Beatrice , Zurac Sabina Andrada
Published: August 2016

Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.
HHLA2, a New Immune Checkpoint Member of the B7 Family, Is Widely Expressed in Human Lung Cancer and Associated with EGFR Mutational Status
Authors: Cheng Haiying , Janakiram Murali , Borczuk Alain , Lin Juan , Qiu Wanglong , Liu Huijie , Chinai Jordan M. , Halmos Balazs , Perez-Soler Roman , Zang Xingxing
Published: August 2016

Purpose: Immunotherapy with antibodies against B7/CD28 family members, including PD-1, PD-L1, and CTLA-4 has shifted the treatment paradigm for non–small cell lung carcinoma (NSCLC) with improved clinical outcome. HHLA2 is a newly discovered member of the family. By regulating T-cell function, HHLA2 could contribute to tumor immune suppression and thus be a novel target for cancer immunotherapy. There is limited information and critical need to characterize its expression profile and clinical significance in NSCLC.

Experimental Design: We performed IHC with an HHLA2-specific antibody (clone 566.1) using tissue microarrays constructed from 679 NSCLC tumor tissues, including 392 cases in the discovery set and 287 cases in the validation cohort. We also studied clinicopathologic characteristics of these patients.

Results: Overall, HHLA2 was not detected in most of normal lung tissue but expressed in 66% of NSCLC across different subtypes. In particular, EGFR-mutated NSCLC was significantly associated with higher tumor HHLA2 expression in both discovery (EGFR vs. WT: 76% vs. 53%, P = 0.01) and validation cohorts (89% vs. 69%, P = 0.01). In one of the two cohorts, HHLA2 expression was higher in lung adenocarcinoma as compared with squamous and large cell histology, non-Hispanic White versus Hispanics, and tumors with high tumor-infiltrating lymphocyte (TIL) density. In the multivariate analysis, EGFR mutation status and high TIL intensity were independently associated with HHLA2 expression in lung adenocarcinoma.

Conclusions: HHLA2 is widely expressed in NSCLC and is associated with EGFR mutation and high TILs in lung adenocarcinoma. It is potentially a novel target for lung cancer immunotherapy. Clin Cancer Res; 23(3); 825–32. ©2016 AACR.
PI3K–mTOR Pathway Inhibition Exhibits Efficacy Against High-grade Glioma in Clinically Relevant Mouse Models
Authors: Lin Fan , de Gooijer Mark C. , Hanekamp Diana , Chandrasekaran Gayathri , Buil Levi C.M. , Thota Nishita , Sparidans Rolf W. , Beijnen Jos H. , Würdinger Tom , van Tellingen Olaf
Published: August 2016

Purpose: The PI3K–AKT–mTOR signaling pathway is frequently activated in glioblastoma and offers several druggable targets. However, clinical efficacy of PI3K/mTOR inhibitors in glioblastoma has not yet been demonstrated. Insufficient drug delivery may limit the efficacy of PI3K/mTOR inhibitors against glioblastoma. The presence of the efflux transporters ABCB1/Abcb1 (P-glycoprotein, MDR1) and ABCG2/Abcg2 (BCRP) at the blood–brain barrier (BBB) restricts the brain penetration of many drugs.

Experimental Design: We used in vitro drug transport assays and performed pharmacokinetic/pharmacodynamic studies in wild-type and ABC-transporter knockout mice. The efficacy of PI3K-mTOR inhibition was established using orthotopic allograft and genetically engineered spontaneous glioblastoma mouse models.

Results: The mTOR inhibitors rapamycin and AZD8055 are substrates of ABCB1, whereas the dual PI3K/mTOR inhibitor NVP-BEZ235 and the PI3K inhibitor ZSTK474 are not. Moreover, ABCG2 transports NVP-BEZ235 and AZD8055, but not ZSTK474 or rapamycin. Concordantly, Abcb1a/b−/−;Abcg2−/− mice revealed increased brain penetration of rapamycin (13-fold), AZD8055 (7.7-fold), and NVP-BEZ235 (4.5-fold), but not ZSTK474 relative to WT mice. Importantly, ABC transporters limited rapamycin brain penetration to subtherapeutic levels, while the reduction in NVP-BEZ235 brain penetration did not prevent target inhibition. NVP-BEZ235 and ZSTK474 demonstrated antitumor efficacy with improved survival against U87 orthotopic gliomas, although the effect of ZSTK474 was more pronounced. Finally, ZSTK474 prolonged overall survival in Cre-LoxP conditional transgenic Pten;p16Ink4a/p19Arf;K-Rasv12;LucR mice, mainly by delaying tumor onset.

Conclusions: PI3K/mTOR inhibitors with weak affinities for ABC transporters can achieve target inhibition in brain (tumors), but have modest single-agent efficacy and combinations with (BBB penetrable) inhibitors of other activated pathways may be required. Clin Cancer Res; 23(5); 1286–98. ©2016 AACR.
Rnd3 in Cancer: A Review of the Evidence for Tumor Promoter or Suppressor
Authors: Paysan Lisa , Piquet Léo , Saltel Frédéric , Moreau Violaine
Published: August 2016

Rho-GTPases are members of the Ras superfamily of small GTPases and are general modulators of important cellular processes in tumor biology such as migration and proliferation. Among these proteins, Rnd3/RhoE, an atypical Rho-GTPase devoid of GTP hydrolytic activity, has recently been studied for its putative role in tumorigenesis. Indeed, Rnd3 is implicated in processes, such as proliferation and migration, whose deregulation is linked to cancer development and metastasis. The aim of this review is to provide an overview of the data surrounding Rnd3 deregulation in cancers, its origin, and consequences. Presented here is a comprehensive account of the expression status and biological output obtained in prostate, liver, stomach, colon, lung, and brain cancers as well as in melanoma and squamous cell carcinoma. Although there appears to be no general consensus about Rnd3 expression in cancers as this protein is differently altered according to the tumor context, these alterations overwhelmingly favor a protumorigenic role. Thus, depending on the tumor type, it may behave either as a tumor suppressor or as a tumor promoter. Importantly, the deregulation of Rnd3, in most cases, is linked to patient poor outcome.

Implications: Rnd3 has prognostic marker potential as exemplified in lung cancers and Rnd3 or Rnd3-associated signaling pathways may represent a new putative therapeutic target. Mol Cancer Res; 14(11); 1033–44. ©2016 AACR.
Factors That Modulate Neurogenesis: A Top-Down Approach
Authors: LaDage Lara D.
Published: August 2016

Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This ‘top-down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis.
Plasticity and Adult Neurogenesis in Amphibians and Reptiles: More Questions than Answers
Authors: Powers Alice Schade
Published: August 2016

Studies of the relationship between behavioral plasticity and new cells in the adult brain in amphibians and reptiles are sparse but demonstrate that environmental and hormonal variables do have an effect on the amount of cell proliferation and/or migration. The variables that are reviewed here are: enriched environment, social stimulation, spatial area use, season, photoperiod and temperature, and testosterone. Fewer data are available for amphibians than for reptiles, but for both groups many issues are still to be resolved. It is to be hoped that the questions raised here will generate more answers in future studies.
Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room
Authors: Beltz Barbara S. , Brenneis Georg , Benton Jeanne L.
Published: August 2016

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.
Assessing the Impact of Atopic Dermatitis on the Patients' Parents with the Visual Instrument ‘Caregiver-PRISM'
Authors: Marinello Elena , Linder Dennis , Spoto Andrea , Palmer Katie , Rohrer Peter Michael , Büchi Stefan , Trapp Michael , Trapp Eva-Maria , Hoerlesberger Nina , Piaserico Stefano , Peserico Andrea , Gatta Michela , Belloni Fortina Anna
Published: August 2016

Background: There is a need to improve the quality of communication between clinicians and parents of young patients with atopic eczema (AE). Objective: To create a tool to measure the suffering that caregivers experience in association with their child's AE (Caregiver Pictorial Representation of Illness and Self-Measure, Caregiver-PRISM), assess the validity and reliability, and identify factors associated with caregiver suffering. Methods: Caregiver-PRISM was administered to 45 parents of patients from an AE outpatient service (Padua, Italy). Results: Caregiver-PRISM had a good test-retest reliability (r = 0.85; t7 = 4.13; p < 0.05), content validity and construct validity when used in parents of AE children. Parents with a less positive family affective climate, higher education, or with children following a diet experienced higher suffering associated with their child's AE, demonstrated by lower Caregiver-PRISM scores (p < 0.05). Conclusion: Our results support the use of Caregiver-PRISM in parents of AE patients to assess suffering associated with patients' illness.