bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Fetal Left Ventricular Volume Based on Two-Dimensional Echocardiography
Authors: Yu Li , Guo Yi , Wang Yuanyuan , Yu Jinhua , Chen Ping
Published: October 2017

Determination of fetal left ventricular (LV) volume in two-dimensional echocardiography (2DE) is significantly important for quantitative analysis of fetal cardiac function. A backpropagation (BP) neural network method is proposed to predict LV volume more accurately and effectively. The 2DE LV border and volume are considered as the input and output of BP neural network correspondingly. To unify and simplify the input of the BP neural network, 16 distances calculated from the border to its center with equal angle are used instead of the border. Fifty cases (forty frames for each) were used for this study. Half of them selected randomly are used for training, and the others are used for testing. To illustrate the performance of BP neural network, area-length method, Simpson’s method, and multivariate nonlinear regression equation method were compared by comparisons with the volume references in concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC), and Bland-Altman plots. The ICC and CCC for BP neural network with the volume references were the highest. For Bland-Altman plots, the BP neural network also shows the highest agreement and reliability with volume references. With the accurate LV volume, LV function parameters (stroke volume (SV) and ejection fraction (EF)) are calculated accurately.
Prevention of Memory Impairment and Neurotrophic Factors Increased by Lithium in Wistar Rats Submitted to Pneumococcal Meningitis Model
Authors: Simões Lutiana R. , Abreu Roberta R. E. S. , Generoso Jaqueline S. , Goularte Jéssica A. , Collodel Allan , Giridharan Vijayasree Vayalanellore , Arumanayagam Anitha Christy Sigamani , Valvassori Samira S. , Quevedo João , Barichello Tatiana
Published: October 2017

The aim of this study was to investigate the effects of lithium on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) expression in the hippocampus and on memory in experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a neuroprotective agent with many effects on the brain. In this study, animals received either artificial cerebrospinal fluid orStreptococcus pneumoniaesuspension at a concentration of 5 × 109CFU/mL. Eighteen hours after induction, all animals received ceftriaxone. The animals received saline or lithium (47.5 mg/kg) or tamoxifen (1 mg/kg) as adjuvant treatment, and they were separated into six groups: control/saline, control/lithium, control/tamoxifen, meningitis/saline, meningitis/lithium, and meningitis/tamoxifen. Ten days after meningitis induction, animals were subjected to open-field habituation and the step-down inhibitory avoidance tasks. Immediately after these tasks, the animals were killed and their hippocampus was removed to evaluate the expression of BDNF, NGF, and GDNF. In the meningitis group, treatment with lithium and tamoxifen resulted in improvement in memory. Meningitis group showed decreased expression of BDNF and GDNF in the hippocampus while lithium reestablished the neurotrophin expression. Lithium was able to prevent memory impairment and reestablishes hippocampal neurotrophin expression in experimental pneumococcal meningitis.
Study on the Instability of Two-Phase Flow in the Heat-Absorbing Tube of Trough Solar Collector
Authors: Zhang Ying , Liu Peiyao , Li Peisheng , Chen Yue , Pan Yanni
Published: October 2017

The Marangoni effect and Rayleigh-Benard effect in the two-phase region of solar trough heat-absorbing tube are simulated by FTM (front tracking method). Considering the Marangoni effect alone, although surface tension gradient and surface tension affect the interface wave, the two effects have different characteristics. The surface tension gradient caused by the temperature gradient is one of the factors that swing the interface. The amplitude attenuation of the interface wave decreases with the increase of the Marangoni number (Ma). In general, the surface tension gradient enhances the convection opposite to the temperature gradient. Under the gravity field, the Rayleigh-Benard effect influences the development of the vortex structure in the flow field, which in turn affects the velocity gradient near the interface to influence the evolution of the interface fluctuation. In a small Rayleigh number (Ra), the buoyancy convection reduces the velocity gradient, thus suppressing the evolution of the interfacial wave. In the range of Ra < 4.0E4, the larger the Ra, the stronger the inhibitory effect. However, when the Ra number is large (Ra > 4.0E4), the situation is just the opposite. The larger the Ra is, the stronger the promoting effect is.
Quantitative Serum Proteomic Analysis of Essential Hypertension Using iTRAQ Technique
Authors: Xu Jing-Wen , Li Yun-Lun , Zhang Shi-Jun , Yang Wen-Qing , Nie Wen-Ting , Jiang Hai-Qiang
Published: October 2017

Essential hypertension (EH) is a risk factor for some severe diseases. This study aimed to screen out serum special proteins and seek interaction between them, which would provide new therapeutic targets and elucidate the comprehensive pathophysiological mechanism for EH. Patients with EH (Group A, n=47) and healthy controls (HC) (Group B, n=47) were recruited in this study. Serums from the two groups were analyzed with isobaric tags for relative and absolute quantitation coupled two-dimensional liquid chromatography followed by electrospray ionization-tandem mass spectrometry technique, while the candidate special proteins were verified with ELISA and western blot. A total of 404 proteins were identified, of which 30 proteins were upregulated (>1.2-fold, p<0.05) and 81 proteins were downregulated (<0.833-fold, p<0.05) compared with HC group. With GO, KEGG analysis, and literature retrieval, 4 proteins, cathepsin G, transforming growth factor beta-1, hyaluronidase-1, and kininogen-1, were found jointly involved in the renin-angiotensin-aldosterone system and kallikrein-kinin system. The profiles of these 4 candidate proteins were confirmed with ELISA and western blot. The concentration variation of these 4 proteins could better predict the occurrence and illustrate the pathophysiological mechanism of EH. And their discovery may help pave the way for exploring new therapies of EH.
Design and Test Research on Cutting Blade of Corn Harvester Based on Bionic Principle
Authors: Tian Kunpeng , Li Xianwang , Zhang Bin , Chen Qiaomin , Shen Cheng , Huang Jicheng
Published: October 2017

Existing corn harvester cutting blades have problems associated with large cutting resistance, high energy consumption, and poor cut quality. Using bionics principles, a bionic blade was designed by extracting the cutting tooth profile curve of the B. horsfieldi palate. Using a double-blade cutting device testing system, a single stalk cutting performance contrast test for corn stalks obtained at harvest time was carried out. Results show that bionic blades have superior performance, demonstrated by strong cutting ability and good cut quality. Using statistical analysis of two groups of cutting test data, the average cutting force and cutting energy of bionic blades and ordinary blades were obtained as 480.24 N and 551.31 N and 3.91 J and 4.38 J, respectively. Average maximum cutting force and cutting energy consumption for the bionic blade were reduced by 12.89% and 10.73%, respectively. Variance analysis showed that both blade types had a significant effect on maximum cutting energy and cutting energy required to cut a corn stalk. This demonstrates that bionic blades have better cutting force and energy consumption reduction performance than ordinary blades.
Measuring Coupling of Rhythmical Time Series Using Cross Sample Entropy and Cross Recurrence Quantification Analysis
Authors: McCamley John , Denton William , Lyden Elizabeth , Yentes Jennifer M.
Published: October 2017

The aim of this investigation was to compare and contrast the use of cross sample entropy (xSE) and cross recurrence quantification analysis (cRQA) measures for the assessment of coupling of rhythmical patterns. Measures were assessed using simulated signals with regular, chaotic, and random fluctuations in frequency, amplitude, and a combination of both. Biological data were studied as models of normal and abnormal locomotor-respiratory coupling. Nine signal types were generated for seven frequency ratios. Fifteen patients with COPD (abnormal coupling) and twenty-one healthy controls (normal coupling) walked on a treadmill at three speeds while breathing and walking were recorded. xSE and the cRQA measures of percent determinism, maximum line, mean line, and entropy were quantified for both the simulated and experimental data. In the simulated data, xSE, percent determinism, and entropy were influenced by the frequency manipulation. The 1 : 1 frequency ratio was different than other frequency ratios for almost all measures and/or manipulations. The patients with COPD used a 2 : 3 ratio more often and xSE, percent determinism, maximum line, mean line, and cRQA entropy were able to discriminate between the groups. Analysis of the effects of walking speed indicated that all measures were able to discriminate between speeds.
Acoustic Sensor Self-Localization: Models and Recent Results
Authors: Haddad Diego B. , Lima Markus V. S. , Martins Wallace A. , Biscainho Luiz W. P. , Nunes Leonardo O. , Lee Bowon
Published: October 2017

The wide availability of mobile devices with embedded microphones opens up opportunities for new applications based on acoustic sensor localization (ASL). Among them, this paper highlights mobile device self-localization relying exclusively on acoustic signals, but with previous knowledge of reference signals and source positions. The problem of finding the sensor position is stated as a function of estimated times-of-flight (TOFs) or time-differences-of-flight (TDOFs) from the sound sources to the target microphone, and the main practical issues involved in TOF estimation are discussed. Least-squares ASL solutions are introduced, followed by other strategies inspired by sound source localization solutions: steered-response power, which improves localization accuracy, and a new region-based search, which alleviates complexity. A set of complementary techniques for further improvement of TOF/TDOF estimates are reviewed: sliding windows, matching pursuit, and TOF selection. The paper proceeds with proposing a novel ASL method that combines most of the previous material, whose performance is assessed in a real-world example: in a typical lecture room, the method achieves accuracy better than 20 cm.
Exploring the Concept of Degrees of Maternal Morbidity as a Tool for Surveillance of Maternal Health in Latin American and Caribbean Settings
Authors: Serruya Suzanne J. , de Mucio Bremen , Martinez Gerardo , Mainero Luis , de Francisco Andres , Say Lale , Sousa Maria H. , Souza Renato T. , Costa Maria L. , Mayrink Jussara , Cecatti Jose G.
Published: October 2017

Objectives. To assess a birth registry to explore maternal mortality and morbidity and their association with other factors. Study Design. Exploratory multicentre cross-sectional analysis with over 700 thousand childbirths from twelve Latin American and Caribbean countries between 2009 and 2012. The WHO criteria for maternal morbidity were employed to split women, following a gradient of severity of conditions, into (1) maternal death (MD); (2) maternal near miss (MNM); (3) potentially life-threatening conditions (PLTC); (4) less severe maternal morbidity (LSMM); (5) any maternal morbidity; and (6) women with no maternal morbidity. Their prevalence and estimated risks of adverse maternal outcomes were assessed. Results. 712,081 childbirths had a prevalence of MD and MNM of 0.14% and 3.1%, respectively, while 38% of women had experienced morbidity. Previous maternal morbidity was associated with higher risk of adverse maternal outcomes and also the extremes of reproductive ages, nonwhite ethnicity, no stable partner, no prenatal care, smoking, drug and alcohol use, elective C-section, or induction of labour. Poorer perinatal outcomes were proportional to the severity of maternal outcomes. Conclusions. The findings corroborate WHO concept regarding continuum of maternal morbidity, reinforcing its importance in preventing adverse maternal outcomes and improving maternal healthcare in different settings.
Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Keratoconus Eyes after Accelerated Corneal Collagen Crosslinking
Authors: Piñero David P. , Camps Vicente J. , Caravaca-Arens Esteban , de Fez Dolores , Blanes-Mompó Francisco J.
Published: October 2017

Purpose. To analyze the errors associated to corneal power calculation using the keratometric approach in keratoconus eyes after accelerated corneal collagen crosslinking (CXL) surgery and to obtain a model for the estimation of an adjusted corneal refractive index nkadj minimizing such errors. Methods. Potential differences (ΔPc) among keratometric (Pk) and Gaussian corneal power (PcGauss) were simulated. Three algorithms based on the use of nkadj for the estimation of an adjusted keratometric corneal power (Pkadj) were developed. The agreement between Pk1.3375 (keratometric power using the keratometric index of 1.3375), PcGauss, and Pkadj was evaluated. The validity of the algorithm developed was investigated in 21 keratoconus eyes undergoing accelerated CXL. Results. Pk1.3375 overestimated corneal power between 0.3 and 3.2 D in theoretical simulations and between 0.8 and 2.9 D in the clinical study (ΔPc). Three linear equations were defined for nkadj to be used for different ranges of r1c. In the clinical study, differences between Pkadj and PcGauss did not exceed ±0.8 D nk=1.3375. No statistically significant differences were found between Pkadj and PcGauss (p>0.05) and Pk1.3375 and Pkadj (p<0.001). Conclusions. The use of the keratometric approach in keratoconus eyes after accelerated CXL can lead to significant clinical errors. These errors can be minimized with an adjusted keratometric approach.
Adaptive Compressive Sensing of Images Using Spatial Entropy
Authors: Li Ran , Duan Xiaomeng , Guo Xiaoli , He Wei , Lv Yongfeng
Published: October 2017

Compressive Sensing (CS) realizes a low-complex image encoding architecture, which is suitable for resource-constrained wireless sensor networks. However, due to the nonstationary statistics of images, images reconstructed by the CS-based codec have many blocking artifacts and blurs. To overcome these negative effects, we propose an Adaptive Block Compressive Sensing (ABCS) system based on spatial entropy. Spatial entropy measures the amount of information, which is used to allocate measuring resources to various regions. The scheme takes spatial entropy into consideration because rich information means more edges and textures. To reduce the computational complexity of decoding, a linear mode is used to reconstruct each block by the matrix-vector product. Experimental results show that our ABCS coding system provides a better reconstruction quality from both subjective and objective points of view, and it also has a low decoding complexity.
Antihypertensive Effects of Roselle‐Olive Combination in L‐NAME‐Induced Hypertensive Rats
Authors: Abdel-Rahman Rehab F. , Hessin Alyaa F. , Abdelbaset Marwan , Ogaly Hanan A. , Abd-Elsalam Reham M. , Hassan Salah M.
Published: October 2017

This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle‐Olive), using N(G)‐nitro‐L‐arginine‐methyl ester‐ (L‐NAME‐) induced hypertensive model. Rats received L‐NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment with Roselle‐Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose‐dependent decrease in both systolic and diastolic blood pressure, reversed the L‐NAME‐induced suppression in serum nitric oxide (NO), and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle‐Olive significantly lowered the elevated angiotensin‐converting enzyme activity (ACE) and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle‐Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real‐time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS) gene and protein expression in both heart and kidney of Roselle‐Olive‐treated rats. To conclude, our data revealed that Roselle‐Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle‐Olive constituents. These findings provide evidences that Roselle‐Olive combination affords efficient antihypertensive effect with a broad end‐organ protective influence.
Experimental Study on the Influence of Sulfate Reducing Bacteria on the Metallic Corrosion Behavior under Disbonded Coating
Authors: Ding Qingmiao , Fang Liping , Cui Yanyu , Wang Yujun
Published: October 2017

A rectangle disbonded coating simulation device was used to research the effect of sulfate reducing bacteria (SRB) on the metallic corrosion behavior under disbonded coating by the electrochemical method. The results showed that the metal self-corrosion potential at the same test point had little change in the initial experiment stage, whether the solution was without or with SRB. The potential amplitude in the solution with SRB was larger than that without SRB in the later corrosion period. The corrosion current density of the metal at the same test point increased gradually over time in the solution with or without SRB, and SRB could accelerate the corrosion of the metal in the disbonded crevice. The metal self-corrosion potential in the crevice had little change in the SRB solution environment after adding the fungicide, but the corrosion current density decreased significantly. That meant the growth and reproduction of SRB were inhibited after adding the fungicide, so the metal corrosion rate slowed down. Among the three kinds of solution environment, increasing the coating disbonded thickness could accelerate the corrosion of the metal in the crevice, and it was the largest in the solution with SRB.
New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity
Authors: Wang Hangxiang , Lu Zhongjie , Wang Lijiang , Guo Tingting , Wu Jiaping , Wan Jianqin , Zhou Liqian , Li Hui , Li Zhen , Jiang Donghai , Song Penghong , Xie Haiyang , Zhou Lin , Xu Xiao , Zheng Shusen
Published: October 2017

The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these cabazitaxel derivatives, docosahexaenoic acid–derived compound 1 retained high antiproliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared with free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacologic efficacy while improving its safety profile. Cancer Res; 77(24); 6963–74. ©2017 AACR.
Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma
Authors: Wu Xin , Serna Vanida A. , Thomas Justin , Qiang Wenan , Blumenfeld Michael L. , Kurita Takeshi
Published: October 2017

Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12, suggesting an interaction between SMC and TAF to coordinate their growth. The higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due to the high concentration of collagen-producing TAF. SMC growth in a xenograft assay was driven by progesterone in both uterine leiomyoma subtypes. In contrast, TAF in MED12-LM proliferated in response to estradiol, whereas progesterone had no effect. The high concentration of estrogen-responsive TAF in MED12-LM explains the inconsistent discoveries between in vivo and in vitro studies on the mitogenic effect of estrogen and raises questions regarding the accuracy of previous studies utilizing MED12-LM cell culture. In addition, the differential effects of estradiol and progesterone on these uterine leiomyoma subtypes emphasize the importance of subtypes and genotypes in designing nonsurgical therapeutic strategies for uterine leiomyoma. Cancer Res; 77(24); 6891–901. ©2017 AACR.
Breast Cancer in Latinas: A Focus on Intrinsic Subtypes Distribution
Authors: Serrano-Gómez Silvia J. , Fejerman Laura , Zabaleta Jovanny
Published: October 2017

Breast cancer is the most frequent cancer in women worldwide. It is classified into intrinsic subtypes characterized by different molecular profiles and prognosis. The prevalence of the different intrinsic subtypes varies between population groups. IHC surrogates based on the expression of the estrogen receptor, progesterone receptor, and HER2 have been widely used to study the distribution of intrinsic subtypes in non-Hispanic whites and African Americans, but data are limited for Hispanic/Latina women. Similarly, most studies analyzing gene expression profiles only include women of European descent. This review focuses on studies that describe the distribution of breast cancer subtypes in Hispanic/Latina women and highlights the need for more research in this population. Cancer Epidemiol Biomarkers Prev; 27(1); 3–10. ©2017 AACR.
Phase I Study of Enavatuzumab, a First-in-Class Humanized Monoclonal Antibody Targeting the TWEAK Receptor, in Patients with Advanced Solid Tumors
Authors: Lam Elaine T. , Eckhardt S. Gail , Messersmith Wells , Jimeno Antonio , O'Bryant Cindy L. , Ramanathan Ramesh K. , Weiss Glen J. , Chadha Manpreet , Oey Abbie , Ding Han Ting , Culp Patricia A. , Keller Stephan F. , Zhao Vivian Y. , Tsao L. Claire , Singhal Anil , Holen Kyle D. , Von Hoff Daniel
Published: October 2017

This phase I study evaluates the safety, MTD, pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment. Three patients were enrolled per dose level in a standard 3+3 design with response assessment by RECIST version 1.0, every 8 weeks. Thirty patients were enrolled at 6 dose levels ranging from 0.1 to 1.5 mg/kg. Dose-limiting toxicities included grade 4 (G4) lipase, G3 bilirubin, and G4 amylase elevations. There was no apparent correlation of liver or pancreatic enzyme elevation with drug exposure or the presence of liver metastases. Enavatuzumab exhibited a two-compartment linear PK model. Estimated systemic clearance was 23 to 33 mL/h with an elimination half-life of 7 to 18 days. The predicted target efficacious peak and trough concentrations occurred at 1.0 mg/kg following the second dose. There were no objective responses; 4 patients had stable disease. The MTD of enavatuzumab is 1.0 mg/kg i.v. every 2 weeks. Higher doses were not tolerated due to hepatopancreatic lab abnormalities. Further evaluation of the mechanisms of the liver and pancreatic enzyme toxicities is needed before embarking on further single-agent or combination strategies. Mol Cancer Ther; 17(1); 215–21. ©2017 AACR.
Growth Promotion Ethics and the Challenge to Resist Cosmetic Endocrinology
Authors: Allen David B.
Published: October 2017

The advancement of “human growth hormone (hGH)-for-height” – increasing height attainment in children short for reasons other than GH deficiency – arose from intuitive, deep-seated assumptions about the disability of short stature, its improvement with hGH-mediated height gain, and the safety of escalating dosages of hGH in healthy children. Evidence challenging these assumptions now strengthens criticism of hGH-for-height as cosmetic endocrinology. To counter this characterization, collective acceptance of guidelines is needed that advise nontreatment of the vast majority of short children, support strategies that minimize treatment duration and dosage, and restrain enhancement of normal adult stature. Through a clinical case analysis, ethical issues underlying these recommendations are explored. These include duties to provide informed assent and re-assent, protect children from unnecessary treatment, consider fairness to nontreated children, and allocate healthcare resources responsibly. Informed assent for hGH-for-height should ensure awareness of modest, variable height gain expectations, limited evidence for psychosocial benefit, ongoing studies for potential posttreatment adverse effects, and options for less expensive/invasive approaches, including nontreatment and counseling. Approaching growth pro­motion in this way fosters therapeutic restraint, resists the al lure of enhancement therapy, and minimizes contributions to society’s perception that to be taller is to be better.
Streptococcus mutans in Mother-Child Dyads and Early Childhood Caries: Examining Factors Underlying Bacterial Colonization
Authors: Costa Elizabeth L. , Costa José F. , Santos Matheus P. , Ladeira Lorena L.C. , Silva Rubenice A. , Ribeiro Cecília C.C.
Published: October 2017

This study investigated the association between colonization of mother-child dyads with Streptococcus mutans (SM) and early childhood caries (ECC), with consideration of the mediator and confounders, using a theoretical model. Four hundred mothers and their children from São Luís, Brazil, were included in the study. A diagram based on directed acyclic graphs was elaborated to analyze the association between SM colonization of the mother, mediated by child SM, and ECC. Other maternal (socioeconomic, waist circumference, sugar consumption, DMFT index, and visible plaque) and child factors (sugar consumption, visible plaque, and child age) composed the theoretical model. A total effect model (maternal SM on ECC) and a direct effect model, adjusted by the mediation effect of child SM (maternal SM via child SM) on ECC, were analyzed. The outcome of interest in this study was ECC (number of teeth with caries experience, dmft), which was analyzed as a discrete variable by Poisson regression. The Paramed test was used to analyze mediation. The following variables were associated with ECC in the total effect model: maternal SM, maternal waist circumference ≥80 cm, DMFT, maternal visible plaque, child age ≥4 years, and increased sugar consumption of the child (>3 times/day). In the direct effect model, high maternal SM levels remained associated with ECC, while moderate and high colonization of the child with SM was also associated with ECC. Child SM colonization just partially mediated the effect of maternal SM on ECC (33%). Thus, factors other than the mechanism of bacterial colonization should be considered in mother-child dyads, including eating habits, oral hygiene practices, and a family history of caries.
Clinical investigation of the Nucleus Slim Modiolar Electrode
Authors: Aschendorff Antje , Briggs Robert , Brademann Goetz , Helbig Silke , Hornung Joachim , Lenarz Thomas , Marx Mathieu , Ramos Angel , Stöver Timo , Escudé Bernard , James Chris J.
Published: October 2017

Aims: The Nucleus CI532 cochlear implant incorporates a new precurved electrode array, i.e., the Slim Modiolar electrode (SME), which is designed to bring electrode contacts close to the medial wall of the cochlea while avoiding trauma due to scalar dislocation or contact with the lateral wall during insertion. The primary aim of this prospective study was to determine the final position of the electrode array in clinical cases as evaluated using flat-panel volume computed tomography. Methods: Forty-five adult candidates for unilateral cochlear implantation were recruited from 8 centers. Eleven surgeons attended a temporal bone workshop and received further training with a transparent plastic cochlear model just prior to the first surgery. Feedback on the surgical approach and use of the SME was collected via a questionnaire for each case. Computed tomography of the temporal bone was performed postoperatively using flat-panel digital volume tomography or cone beam systems. The primary measure was the final scalar position of the SME (completely in scala tympani or not). Secondly, medial-lateral position and insertion depth were evaluated. Results: Forty-four subjects received a CI532. The SME was located completely in scala tympani for all subjects. Pure round window (44% of the cases), extended round window (22%), and inferior and/or anterior cochleostomy (34%) approaches were successful across surgeons and cases. The SME was generally positioned close to the modiolus. Overinsertion of the array past the first marker tended to push the basal contacts towards the lateral wall and served only to increase the insertion depth of the first electrode contact without increasing the insertion depth of the most apical electrode. Complications were limited to tip fold-overs encountered in 2 subjects; both were attributed to surgical error, with both reimplanted successfully. Conclusions: The new Nucleus CI532 cochlear implant with SME achieved the design goal of producing little or no trauma as indicated by consistent scala tympani placement. Surgeons should be carefully trained to use the new deployment method such that tip fold-overs and over insertion may be avoided.
Nasonia Parasitic Wasps Escape from Haller's Rule by Diphasic, Partially Isometric Brain-Body Size Scaling and Selective Neuropil Adaptations
Authors: Groothuis Jitte , Smid Hans M.
Published: October 2017

Haller's rule states that brains scale allometrically with body size in all animals, meaning that relative brain size increases with decreasing body size. This rule applies both on inter- and intraspecific comparisons. Only 1 species, the extremely small parasitic wasp Trichogramma evanescens, is known as an exception and shows an isometric brain-body size relation in an intraspecific comparison between differently sized individuals. Here, we investigated if such an isometric brain-body size relationship also occurs in an intraspecific comparison with a slightly larger parasitic wasp, Nasonia vitripennis, a species that may vary 10-fold in body weight upon differences in levels of scramble competition during larval development. We show that Nasonia exhibits diphasic brain-body size scaling: larger wasps scale allometrically, following Haller's rule, whereas the smallest wasps show isometric scaling. Brains of smaller wasps are, therefore, smaller than expected and we hypothesized that this may lead to adaptations in brain architecture. Volumetric analysis of neuropil composition revealed that wasps of different sizes differed in relative volume of multiple neuropils. The optic lobes and mushroom bodies in particular were smaller in the smallest wasps. Furthermore, smaller brains had a relatively smaller total neuropil volume and larger cellular rind than large brains. These changes in relative brain size and brain architecture suggest that the energetic constraints on brain tissue outweigh specific cognitive requirements in small Nasonia wasps.
Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial
Authors: Malizia Velia , Fasola Salvatore , Ferrante Giuliana , Cilluffo Giovanna , Montalbano Laura , Landi Massimo , Marchese Donatella , Passalacqua Giovanni , La Grutta Stefania
Published: October 2017

Background: Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. Methods: In this 21-day, open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS delivered through a nasal douche. Efficacy measures were least square mean changes (LSmc) in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. Results: BHS improved the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p < 0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not. Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc -0.57, p = 0.009), whereas the improvement in PSQI score was comparable between the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall, BHS was well tolerated. Conclusions: In children with SAR, BHS is effective in improving nasal symptoms and NCC, with an associated beneficial effect on quality of life.
Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient Hereditary Angioedema
Authors: Demirturk Mustafa , Akpinar Timur Selcuk , Kose Murat , Gelincik Aslı , Colakoğlu Bahattin , Buyukozturk Suna
Published: October 2017

Background: Hereditary angioedema (HAE) related to C1-inhibitor deficiency is a rare autosomal dominant disorder. Vascular cell adhesion molecules (VCAM) are known as endothelial activation markers. Endocan (also called ESM-1) is proposed as an endothelial dysfunction indicator. We aimed to investigate endothelial activation in attack-free periods in HAE patients by measuring their levels of endocan and VCAM-1. Methods: Twenty-six HAE patients (22 female, mean age 40 ± 13 years) and 38 healthy control patients (13 female, mean age 36.9 ± 12 years) were included in the study. Peripheral blood samples were collected from HAE patients during symptom-free periods and control subjects. Endocan and VCAM-1 levels were measured using the enzyme-linked immunosorbent assay method. Results: The median serum levels of endocan (647 ± 101 ng/mL) and VCAM-1 (500 ± 79 ng/mL) in the HAE patients were significantly higher than in the control patients (391 ± 41 and 325 ± 4; p < 0.001 for both). Conclusion: The increased endocan and VCAM-1 levels may reflect an endothelial activation even in attack-free periods in HAE patients.
Chromosome Banding in Amphibia. XXXV. Highly Mobile Nucleolus Organizing Regions in Craugastor fitzingeri (Anura, Craugastoridae)
Authors: Schmid Michael , Steinlein Claus , Feichtinger Wolfgang , Nanda Indrajit
Published: October 2017

A 7-year cytogenetic study on the leaf litter frog Craugastor fitzingeri from Costa Rica and Panama revealed the existence of highly mobile nucleolus organizing regions (NORs) in their genomes. Silver (Ag)-staining of the active NORs demonstrated an exceptional interindividual pattern of NOR distribution at the telomeres of the chromosomes. All individuals examined showed a different and specific NOR location in their karyotypes. Furthermore, intraindividual variation in the NOR sites was found. This observation suggested the existence of mobile NORs in C. fitzingeri. Confirmation of this phenomenon was possible by systematic FISH analysis using an 18S + 28S rDNA probe. The extremely variable number and position of the NORs in C. fitzingeri is best explained by highly mobile NORs that move freely between the telomeres of the chromosomes. These transpositions must occur preferentially in premeiotic, meiotic, or postmeiotic stages, but also at a lower incidence in the somatic tissues of the animals. It is hypothesized that transposable (mobile) elements are closely linked to the NORs or are inserted into the major 18S + 28S rDNA spacers of C. fitzingeri. When such transposable elements spread by transpositions, they can carry with them complete or partial NORs. The present study provides detailed information on various differential chromosome banding techniques, in situ hybridization experiments, chromosomal hypermethylation patterns, determination of the genome size, and analyses of restriction fragment length polymorphisms of the DNA.
Socioeconomic Inequalities in Frailty among Older Adults: Results from a 10-Year Longitudinal Study in the Netherlands
Authors: Hoogendijk Emiel O. , Heymans Martijn W. , Deeg Dorly J.H. , Huisman Martijn
Published: October 2017

Background: Frailty is an important risk factor for adverse outcomes in older people. Substantial variation in frailty prevalence between socioeconomic groups exists, but longitudinal evidence for the association between socioeconomic position (SEP) and frailty is scarce. Objective: To investigate the course of socioeconomic inequalities in frailty among older adults during 10 years of follow-up. Methods: Data were used from the Longitudinal Aging Study Amsterdam (n = 1,509). Frailty was measured with the functional domains approach, based on deficiencies in four domains: physical, nutritive, cognitive, and sensory. Mixed-model analyses were performed to estimate the course of frailty and its association with SEP during a 10-year follow-up. We investigated whether similar patterns of associations held in different scenarios, comparing results of survivor analyses with those based on two imputation methods accounting for dropout due to death (substitution of first missing value and missing values imputed with a prediction model). Results: All scenarios showed a linear increase in frailty with aging (survivor analyses OR = 1.87, 95% CI = 1.66-2.11) and associations of low education and low income with frailty (adjusted OR for low education = 1.76, 95% CI = 1.05-2.97; adjusted OR for low income = 1.90, 95% CI = 1.20-3.01; both for survivor analyses). Sex-stratified analyses indicated that socioeconomic inequalities were mainly present in men, not in women. Similar patterns of associations of SEP with frailty were observed in all scenarios, but the increase in frailty prevalence over time differed substantially between the scenarios. There were no statistically significant interactions between time and SEP on frailty (all scenarios), suggesting that inequalities in frailty did not increase or decrease during follow-up. Conclusion: SEP inequalities in frailty among older adults were observed, mainly among men, and persisted during 10 years of follow-up.
Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to Low Plasma Nitric Oxide in Polycystic Ovary Syndrome
Authors: Krishna Meera B. , Joseph Annu , Thomas Philip Litto , Dsilva Belinda , Pillai Sathy M. , Laloraya Malini
Published: October 2017

Background: Though oxidative stress is associated with Polycystic Ovary Syndrome (PCOS), the status of nitric oxide is still unclear. Nitric Oxide (NO) plays pivotal roles in many physiological functions which are compromised in PCOS. Our recent study reveals lowered T-regulatory cells (Tregs) in PCOS, and Treg generation is known to be regulated by NO levels. However concrete evidences are lacking on mechanisms modulating NO levels under PCOS. Methods: This is a retrospective case-control cohort study, comprised of PCOS women (N=29) and normal menstruating women as controls (N=20). We analysed NOx (nitrite+nitrate) and hydrogen peroxide (H2O2) concentrations, transcript levels of endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and arginine modulators, hydrogen peroxide regulators in the cohort. Results: PCOS women showed reduced plasma NOx(nitrate+nitrite) and H2O2 compared to controls. We report reduction in transcript levels of iNOS/NOS2 and eNOS/NOS3 in PCOS peripheral blood. The transcripts involved in arginine bioavailability: Argininosuccinate lyase (ASL), Solute Carrier Family1, member 7 (SLC7A1) and Arginase 1 (ARG1) and Asymmetric Dimethyl Arginine (ADMA) metabolism: Protein arginine methyltransferase 1 (PRMT1) and Dimethylarginine dimethylaminohydrolase 2 (DDAH2) also showed differential expression. H2O2 concentration in PCOS women was also found to be reduced. The reduction can be attributed to increase in catalase levels as a consequence of the body’s effort to alleviate the oxidative burden in the system. Conclusion: Our study advocates that PCOS women have lowered NO due to reduced iNOS/eNOS expression, low H2O2, high ADMA synthesis and reduced arginine bioavailability. An in-depth analysis of redox biology of PCOS to open up potential therapeutic strategies is highly recommended.
Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells
Authors: Qu Qiu-Xia , Xie Fang , Huang Qin , Zhang Xue-Guang
Published: October 2017

Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1+CD8+T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.
Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma
Authors: Tang Lingling , Chen Qingge , Meng Ziyu , Sun Li , Zhu Linyun , Liu Jinjin , Hu Junsheng , Ni Zhenhua , Wang Xiongbiao
Published: October 2017

Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.
Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats
Authors: Bai Yan , Su Zhenli , Sun Hanqi , Zhao Wei , Chen Xue , Hang Pengzhou , Zhu Wenliang , Du Zhimin
Published: October 2017

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.