bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing
Authors: Sobrinho Cleyton R. , Gonçalves Christopher M. , Takakura Ana C. , Mulkey Daniel K. , Moreira Thiago S.
Published: July 2017

Evidence indicates that CO2/H+-evoked ATP released from retrotrapezoid nucleus (RTN) astrocytes modulates the activity of CO2-sensitive neurons. RTN astrocytes also sense H+by inhibition of Kir4.1 channels; however, the relevance of this pH-sensitive current remains unclear since ATP release appears to involve CO2-dependent gating of connexin 26 hemichannels. Considering that depolarization mediated by H+inhibition of Kir4.1 channels is expected to increase sodium bicarbonate cotransporter (NBC) conductance and favor Ca2+influx via the sodium calcium exchanger (NCX), we hypothesize that depolarization in the presence of CO2is sufficient to facilitate ATP release and enhance respiratory output. Here, we confirmed that acute exposure to fluorocitrate (FCt) reversibly depolarizes RTN astrocytes and increased activity of RTN neurons by a purinergic-dependent mechanism. We then made unilateral injections of FCt into the RTN or two other putative chemoreceptor regions (NTS and medullary raphe) to depolarize astrocytes under control conditions and during P2-recepetor blockade while measuring cardiorespiratory activities in urethane-anesthetized, vagotomized, artificially ventilated male Wistar rats. Unilateral injection of FCt into the RTN increased phrenic (PNA) amplitude and frequency without changes in arterial pressure. Unilateral injection of pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS, a P2-receptor antagonist) into the RTN dampened both PNA amplitude and frequency responses to FCt. Injection of MRS2179 (P2Y1-receptor antagonist) into the RTN did not affect the FCt-induced respiratory responses. Fluorocitrate had no effect on breathing when injected into the NTS or raphe. These results suggest that depolarization can facilitate purinergic enhancement of respiratory drive from the RTN.

NEW & NOTEWORTHY Astrocytes in the retrotrapezoid nucleus (RTN) are known to function as respiratory chemoreceptors; however, it is not clear whether changes in voltage contribute to astrocyte chemoreception. We showed that depolarization of RTN astrocytes at constant CO2levels is sufficient to modulate RTN chemoreception by a purinergic-dependent mechanism. These results support the possibility that astrocyte depolarization can facilitate purinergic enhancement of respiratory drive from the RTN.
The firing characteristics of foot sole cutaneous mechanoreceptor afferents in response to vibration stimuli
Authors: Strzalkowski Nicholas D. J. , Ali R. Ayesha , Bent Leah R.
Published: July 2017

Single unit microneurography was used to record the firing characteristics of the four classes of foot sole cutaneous afferents [fast and slowly adapting type I and II (FAI, FAII, SAI, and SAII)] in response to sinusoidal vibratory stimuli. Frequency (3–250 Hz) and amplitude (0.001–2 mm) combinations were applied to afferent receptive fields through a 6-mm diameter probe. The impulses per cycle, defined as the number of action potentials evoked per vibration sine wave, were measured over 1 s of vibration at each frequency-amplitude combination tested. Afferent entrainment threshold (lowest amplitude at which an afferent could entrain 1:1 to the vibration frequency) and afferent firing threshold (minimum amplitude for which impulses per cycle was greater than zero) were then obtained for each frequency. Increases in vibration frequency are generally associated with decreases in expected impulses per cycle ( P < 0.001), but each foot sole afferent class appears uniquely tuned to vibration stimuli. FAII afferents tended to have the lowest entrainment and firing thresholds ( P < 0.001 for both); however, these afferents seem to be sensitive across frequency. In contrast to FAII afferents, SAI and SAII afferents tended to demonstrate optimal entrainment to frequencies below 20 Hz and FAI afferents faithfully encoded frequencies between 8 and 60 Hz. Contrary to the selective activation of distinct afferent classes in the hand, application of class-specific frequencies in the foot sole is confounded due to the high sensitivity of FAII afferents. These findings may aid in the development of sensorimotor control models or the design of balance enhancement interventions.

NEW & NOTEWORTHY Our work provides a mechanistic look at the capacity of foot sole cutaneous afferents to respond to vibration of varying frequency and amplitude. We found that foot sole afferent classes are uniquely tuned to vibration stimuli; however, unlike in the hand, they cannot be independently activated by class-specific frequencies. Viewing the foot sole as a sensory structure, the present findings may aid in the refinement of sensorimotor control models and design of balance enhancement interventions.
Development and Validation of a HPLC‐UV Method for the Evaluation of Ellagic Acid in Liquid Extracts of Eugenia uniflora L. (Myrtaceae) Leaves and Its Ultrasound‐Assisted Extraction Optimization
Authors: Assunção Paulo Isaac Dias , Conceição Edemilson Cardoso da , Borges Leonardo Luiz , Paula Joelma Abadia Marciano de
Published: July 2017

A simple HPLC‐UV method has been developed and validated for the quantification of ellagic acid (EA) in ethanol extracts of Eugenia uniflora L. (Myrtaceae) leaves. The ultrasound‐assisted extraction (UAE) optimization was performed using a Box Behnken design (33) combined with response surface methodology to study the effects of the ethanol concentration (%, w/w), extraction time (minutes), and temperature (°C) on the EA concentration. The optimized results showed that the highest extraction yield of EA by UAE was 26.0 μg mL−1 when using 44% (w/w) ethanol as the solvent, 22 minutes as the extraction time, and 59°C as the extraction temperature. The concentration of EA in relation to the predicted value was 93.7%  ±  0.4. UAE showed a strong potential for EA extraction.
Application of Nanomaterials in Stem Cell Regenerative Medicine of Orthopedic Surgery
Authors: Pan Su , Yu Hongmei , Yang Xiaoyu , Yang Xiaohong , Wang Yan , Liu Qinyi , Jin Liliang , Yang Yudan
Published: July 2017

Regenerative medicine aims to achieve functional rehabilitation of tissue or cells injured through wound, disease, or aging. Recent findings suggest that nanotechnology provides advanced biomaterials with specified morphologies which can create a nanoscale extracellular environment capable of promoting the adhesion and proliferation of stem cells and accelerating stem cell differentiation in a controlled manner in tissue engineering. This review summarizes the biological effects of nanomaterials and their regenerative medicine applications in orthopedic surgery research, including bone, cartilage, tendons, and nerve tissue engineering.
Theoretical Study of High-Frequency Response of InGaAs/AlAs Double-Barrier Nanostructures
Authors: Grishakov Konstantin S. , Elesin Vladimir F. , Maslov Mikhail M. , Katin Konstantin P.
Published: July 2017

The presented article contains the numerical calculations of the InGaAs/AlAs resonant tunneling diode’s (RTD) response to the AC electric field of a wide range of amplitudes and frequencies. These calculations have been performed within the coherent quantum-mechanical model that is based on the solution of the time-dependent Schrödinger equation with exact open boundary conditions. It is shown that as the field amplitude increases, at high frequencies, where ħω>Γ (Γ is the width of the resonant energy level), the active current can reach high values comparable to the direct current value in resonance. This indicates the implementation of the quantum regime for RTD when radiative transitions are between quasi-energetic levels and the resonant energy level. Moreover, there is an excitement of higher quasi-energetic levels in AC electric fields, which in particular results in a slow droop of the active current as the field amplitude increases. It also results in potentially abrupt changes of the operating point position by the ħω value. This makes it possible to achieve relatively high output powers of InGaAs/AlAs RTD having an order of 105 W/cm2 at high frequencies.
A Review of Critical Conditions for the Onset of Nonlinear Fluid Flow in Rock Fractures
Authors: Yu Liyuan , Liu Richeng , Jiang Yujing
Published: July 2017

Selecting appropriate governing equations for fluid flow in fractured rock masses is of special importance for estimating the permeability of rock fracture networks. When the flow velocity is small, the flow is in the linear regime and obeys the cubic law, whereas when the flow velocity is large, the flow is in the nonlinear regime and should be simulated by solving the complex Navier-Stokes equations. The critical conditions such as critical Reynolds number and critical hydraulic gradient are commonly defined in the previous works to quantify the onset of nonlinear fluid flow. This study reviews the simplifications of governing equations from the Navier-Stokes equations, Stokes equation, and Reynold equation to the cubic law and reviews the evolutions of critical Reynolds number and critical hydraulic gradient for fluid flow in rock fractures and fracture networks, considering the influences of shear displacement, normal stress and/or confining pressure, fracture surface roughness, aperture, and number of intersections. This review provides a reference for the engineers and hydrogeologists especially the beginners to thoroughly understand the nonlinear flow regimes/mechanisms within complex fractured rock masses.
Synthesis of Spatially Correlated Earthquake Ground Motions Based on Hilbert Transform
Authors: Yao Erlei , Miao Yu , Wang Guobo
Published: July 2017

A simplified method for synthesizing spatially correlated earthquake ground motions is developed based on Hilbert transform and a reference earthquake record. In this method, one reference earthquake record is treated as the original ground motion, based on a series of generated ground motions. This procedure uses the instantaneous amplitude and the instantaneous phase of the record obtained using Hilbert transform to achieve the nonstationarity of ground motion. To establish the coherency between generated ground motions, an incoherence model is employed to describe the relation between the instantaneous phase at the present station and the instantaneous phases at previous stations. This type of phase is defined as the instantaneous coherence phase. In addition, time lag is included in the instantaneous coherence phase to prescribe the wave passage effect. The proposed Hilbert-transform-based method is efficient and avoids cumbersome parameter estimations as well as other drawbacks involved in some traditional synthesizing methods. Applications of this method demonstrate that the generated ground motions are statistically analogous with the reference record.
The Effect of Connected Vehicle Environment on Global Travel Efficiency and Its Optimal Penetration Rate
Authors: Dai Rongjian , Lu Yingrong , Ding Chuan , Lu Guangquan
Published: July 2017

The effect of connected vehicle environment on the transportation systems and the relationship between the penetration rate of connected vehicle and its efficiency are investigated in this study. An example based on the classical two-route network is adopted in this study, in which the drivers consist of two types: informed and uninformed. The advantages and disadvantages of the connected vehicle environment are analyzed, and the concentration phenomenon is proposed and found to be mitigated when only a fraction of drivers are informed. The simulation tool embodying the characteristics of the connected vehicle environment is developed using the multiagent technology. Finally, different scenarios are simulated, such as the zero-information environment, the full-information environment, and the connected vehicle environment with various penetration rates. Moreover, simulation results of the global performance of the transportation system are compared. The results show that the connected vehicle environment can efficiently improve the performance of the transportation system, while the adverse effects due to concentration rise out from the excessive informed drivers. An optimal penetration rate of the connected vehicles is found to characterize the best performance of the system. These findings can aid in understanding the effect of the connected vehicle environment on the transportation system.
Antioxidant Properties of Crude Extract, Partition Extract, and Fermented Medium of Dendrobium sabin Flower
Authors: Abu Farahziela , Mat Taib Che Norma , Mohd Moklas Mohamad Aris , Mohd Akhir Sobri
Published: July 2017

Antioxidant properties of crude extract, partition extract, and fermented medium from Dendrobium sabin (DS) flower were investigated. The oven‐dried DS flower was extracted using 100% methanol (w/v), 100% ethanol (w/v), and 100% water (w/v). The 100% methanolic crude extract showed the highest total phenolic content (40.33 ± mg GAE/g extract) and the best antioxidant properties as shown by DPPH, ABTS, and FRAP assays. A correlation relationship between antioxidant activity and total phenolic content showed that phenolic compounds were the dominant antioxidant components in this flower extract. The microbial fermentation on DS flower medium showed a potential in increasing the phenolic content and DPPH scavenging activity. The TPC of final fermented medium showed approximately 18% increment, while the DPPH of fermented medium increased significantly to approximately 80% at the end of the fermentation. Dendrobium sabin (DS) flower showed very good potential properties of antioxidant in crude extract and partition extract as well as better antioxidant activity in the flower fermented medium.
Generalized Fractional-Order Discrete-Time Integrator
Authors: Mozyrska Dorota , Ostalczyk Piotr
Published: July 2017

We investigate a generalization of discrete-time integrator. Proposed linear discrete-time integrator is characterised by the variable, fractional order of integration/summation. Graphical illustrations of an analysis of particular vector matrices are presented. In numerical examples, we show relations between the order functions and element responses.
Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis
Authors: Sherigar Jagannath M. , Yavgeniy Arefiev , Guss Debra , Ngo Nhu , Mohanty Smruti
Published: July 2017

Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which results in immune-mediated liver injury with varied clinical presentations. Seronegative AIH follows a similar course to autoantibody-positive disease and diagnosis may be challenging. There are no single serologic tests of sufficient diagnostic specificity, and delay in appropriate treatment may lead to progression of the liver disease and liver failure. The revised conventional diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in the clinical practice. The more recent simplified diagnostic criteria (SDC) scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider application in routine practice facilitating the diagnosis of AIH with a specificity and sensitivity of ~90%. In this report, we describe a case of seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in our case was 4 and was not diagnostic for AIH. We subsequently used the complex revised diagnostic criteria for definitive diagnosis. Some of the patients previously diagnosed as cryptogenic active hepatitis of unknown etiology probably had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring may not be applicable in patients with seronegative autoimmune hepatitis. These patients should be reassessed by using RDC.
Dynamics Analysis for Hydroturbine Regulating System Based on Matrix Model
Authors: Wei Jiafu , Wang Hao , Cheng Yuanchu , Guo Xinran
Published: July 2017

The hydraulic turbine model is the key factor which affects the analysis precision of the hydraulic turbine governing system. This paper discusses the basic principle of the hydraulic turbine matrix model and gives two methods to realize. Using the characteristic matrix to describe unit flow and torque and their relationship with the opening and unit speed, it can accurately represent the nonlinear characteristics of the turbine, effectively improve the convergence of simulation process, and meet the needs of high precision real‐time simulation of power system. Through the simulation of a number of power stations, it indicates that, by analyzing the dynamic process of the hydraulic turbine regulating with 5‐order matrix model, the calculation results and field test data will have good consistency, and it can better meet the needs of power system dynamic simulation.
Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence
Authors: Garg Suneel Kumar , Singh Omender , Juneja Deven , Tyagi Niraj , Khurana Amandeep Singh , Qamra Amit , Motlekar Salman , Barkate Hanmant
Published: July 2017

Polymyxin B has resurged in recent years as a last resort therapy for Gram-negative multidrug-resistant (MDR) and extremely drug resistant (XDR) infections. Understanding newer evidence on polymyxin B is necessary to guide clinical decision making. Here, we present a literature review of polymyxin B in Gram-negative infections with update on its pharmacology.
The Effects of Aromatherapy Massage on Sleep Quality of Nurses on Monthly Rotating Night Shifts
Authors: Chang Ying-Ying , Lin Chao-Ling , Chang Li-Yin
Published: July 2017

The goal of this study is to examine the effects of aromatherapy massage on sleep quality of nurses with monthly rotating night shifts. Subjects were enrolled at a medical center in central Taiwan with overall score ≥ 5 of Pittsburgh Sleep Quality Index (PSQI) and randomly assigned to the treatment or control groups. They were validated by pretests during their first graveyard shift in the trial period and the sleep quality information was collected by using the PSQI and sleep detectors. During the second graveyard shift, the treatment group received aromatherapy massage and the control group rested in the same aromatherapy room after work. All subjects filled out the PSQI surveys and the sleep quality information was collected during massage or resting and the following night. We found that the total PSQI was significantly decreased in the treatment group following the aromatherapy massage. Specifically, the components such as subjective sleep quality, sleep disturbance, and daytime dysfunction were significantly decreased. However, there were no significant changes of average PSQI scores between the two groups before and after intervention. Taken together, our study suggested that aromatherapy massage could improve sleep quality of nurses with monthly rotating night shift.
Properties and Biodegradability of Thermoplastic Starch Obtained from Granular Starches Grafted with Polycaprolactone
Authors: Cuevas-Carballo Z. B. , Duarte-Aranda S. , Canché-Escamilla G.
Published: July 2017

Granular starches grafted with polycaprolactone (St-g-PCL) were obtained using N-methylimidazole (NMI) as a catalyst. The effect of the starch/monomer ratio and catalyst content was studied to obtain different levels of grafted PCL. The highest grafting percentage (76%) and addition (43%) were achieved for reactions with a starch/monomer ratio of 50/50 and 25% catalyst. The grafting of PCL on the starch granule was verified by the emergence of the carbonyl group in the FTIR spectra and the increased diameter of the grafted starch granule. Thermoplastic starch from ungrafted starch (TPS) and grafted starch (TPGS) was obtained by mixing ungrafted or grafted starch granules with water, glycerol, or sorbitol in a mixer. TPS and TPGS behave as plastic materials, and their mechanical properties depend on the type of plasticizer used. Materials with glycerol as the plasticizer exhibited less rigidity. The presence of starch-g-PCL results in a dramatic increase in the elongation of the thermoplastic material. The starch present in the TPS or TPGS was completely biodegraded while the grafted PCL was partially biodegraded after the enzymatic degradation of the materials.
High Precision Laser Scanning of Metallic Surfaces
Authors: Amir Yousaf Muhamad , Thörnberg Benny
Published: July 2017

Speckle noise, dynamic range of light intensity, and spurious reflections are major challenges when laser scanners are used for 3D surface acquisition. In this work, a series of image processing operations, that is, Spatial Compound Imaging, High Dynamic Range Extension, Gray Level Transformation, and Most Similar Nearest Neighbor are proposed to overcome the challenges coming from the target surface. A prototype scanner for metallic surfaces is designed to explore combinations of these image processing operations. The main goal is to find the combination of operations that will lead to the highest possible robustness and measurement precision at the lowest possible computational load. Inspection of metallic tools where the surface of its edge must be measured at micrometer precision is our test case. Precision of heights measured without using the proposed image processing is firstly analyzed to be ±7.6 μm at 68% confidence level. The best achieved height precision was ±4.2 μm. This improvement comes at 24 times longer processing time and five times longer scanning time. Dynamic range extension of the image capture improves robustness since the numbers of saturated or underexposed pixels are substantially reduced. Using a high dynamic range (HDR) camera offers a compromise between processing time, robustness, and precision.
Technical Details of Laparoscopic Sleeve Gastrectomy Leading to Lowered Leak Rate: Discussion of 1070 Consecutive Cases
Authors: Warner David L. , Sasse Kent C.
Published: July 2017

Introduction. Laparoscopic sleeve gastrectomy is a widely utilized and effective surgical procedure for dramatic weight loss in obese patients. Leak at the sleeve staple line is the most serious complication of this procedure, occurring in 1–3% of cases. Techniques to minimize the risk of sleeve gastrectomy leaks have been published although no universally agreed upon set of techniques exists. This report describes a single-surgeon experience with an approach to sleeve leak prevention resulting in a progressive decrease in leak rate over 5 years. Methods. 1070 consecutive sleeve gastrectomy cases between 2012 and 2016 were reviewed retrospectively. Patient characteristics, sleeve leaks, and percent body weight loss at 6 months were reported for each year. Conceptual and technical changes aimed towards leak reduction are presented. Results. With the implementation of the described techniques of the sleeve gastrectomy, the rate of sleeve leaks fell from 4% in 2012 to 0% in 2015 and 2016 without a significant change in weight loss, as depicted by 6-month change in body weight and percent excess BMI lost. Conclusion. In this single-surgeon experience, sleeve gastrectomy leak rate has fallen to 0% since the implementation of specific technical modifications in the procedure.
Incidental Discovery of Multiorgan Extramedullary Plasmacytomas in the Setting of Newly Diagnosed Multiple Myeloma and Delayed Hemolytic Transfusion Reaction
Authors: Cook Joselle , Song Steven , Ventimiglia Anthony , Luhrs Carol
Published: July 2017

Extramedullary plasmacytomas (EMPs) are defined by the presence of clonal plasma cell proliferation outside of the bone marrow, portending an overall poor prognosis. This case highlights extramedullary plasmacytomas as an unusual presenting manifestation of multiple myeloma. Through incidental discovery during a delayed hemolytic transfusion reaction workup, EMPs were found in the liver, spleen, and possibly the lung. Though rare at presentation, this case emphasizes that the presence of EMPs should be considered at the outset as it not only impacts the treatment regimen for such patients but also considerably affects prognosis.
A Mesoscopic Simulation Model for Airport Curbside Management
Authors: Harris Tyler M. , Nourinejad Mehdi , Roorda Matthew J.
Published: July 2017

Airport curbside congestion is a growing problem as airport passenger traffic continues to increase. Many airports accommodate the increase in passenger traffic by relying on policy and design measures to alleviate congestion and optimize operations. This paper presents a mesoscopic simulation model to assess the effectiveness of such policies. The mesoscopic simulation model combines elements of both microscopic simulation which provides a high level of detail but requires large amounts of data and macroscopic simulation which requires very little data but provides few performance measures. The model is used to simulate scenarios such as double parking, alternative parking space allocation, increased passenger demand, and enforced dwell times at Pearson International Airport in Toronto, Canada. Scenario analysis shows that adjusting model inputs provides reasonable results, demonstrating the value in using this approach to evaluate curbside management policies. The results show that double parking reduces the utilization ratio and the level of service of the outer curbside but cuts down the passenger and vehicle waiting time. Inclement weather conditions reduce the utilization ratio of the inner curbside and the supply of commercial vehicles since it takes them longer to return to the airport. Finally, reducing the allowable parking time at the curbside decreases the average dwell time of private vehicles from 89 seconds to 75 seconds but increases the number of circulating vehicles by 30%.
Study on Triopoly Dynamic Game Model Based on Different Demand Forecast Methods in the Market
Authors: Ma Junhai , Sun Lijian , Zhan Xueli
Published: July 2017

The impact of inaccurate demand beliefs on dynamics of a Triopoly game is studied. We suppose that all the players make their own estimations on possible demand with errors. A dynamic Triopoly game with such demand belief is set up. Based on this model, existence and local stable region of the equilibriums are investigated by 3D stable regions of Nash equilibrium point. The complex dynamics, such as bifurcation scenarios and route to chaos, are displayed in 2D bifurcation diagrams, in which e1 and α are negatively related to each other. Basins of attraction are investigated and we found that the attraction domain becomes smaller with the increase in price modification speed, which indicates that all the players’ output must be kept within a certain range so as to keep the system stable. Feedback control method is used to keep the system at an equilibrium state.
Effects of Exercise Training on Fat Loss and Lean Mass Gain in Mexican-American and Korean Premenopausal Women
Authors: Wu Shenghui , Park Kyung-Shin , McCormick Joseph B.
Published: July 2017

We investigated the effect of exercise training on body composition change in women. Nineteen Mexican-American and 18 Korean premenopausal overweight/obese women were randomized into one of the following groups: control, low-intensity training group (LI), and high-intensity training group (HI). Subjects completed 12 weeks of training at 50–56% maximal oxygen consumption (LI) or 65–70% maximal oxygen consumption (HI). Body composition components were measured at baseline and after training using dual-energy X-ray absorptiometry for Mexican-Americans, while whole-body composition was measured by the direct segmental multifrequency bioelectrical impedance analysis and abdominal fat was measured by single-slice computed tomography for Koreans. Data were analyzed using mixed-model repeated measures independent of age, ethnicity, and body mass index (BMI). Exercise training showed a significant effect on BMI, fat percentage, fat mass, lean mass, and visceral adipose tissue area. HI significantly decreased fat mass and fat percentage but increased lean mass (all P<0.05). LI significantly reduced BMI, fat mass, fat percentage, and visceral adipose tissue area but increased lean mass (all P<0.05). Exercise training had a beneficial effect on reducing BMI, fat percentage, fat mass, and visceral adipose tissue area but had no effect on increasing lean mass for Mexican-American and Korean premenopausal overweight/obese women.
Relying on Visiting Foreign Doctors for Fistula Repair: The Profile of Women Attending Fistula Repair Surgery in Somalia
Authors: Gele Abdi A. , Salad Abdulwahab M. , Jimale Liban H. , Kour Prabhjot , Austveg Berit , Kumar Bernadette
Published: July 2017

Obstetric fistula is treatable by surgery, although access is usually limited, particularly in the context of conflict. This study examines the profile of women attending fistula repair surgery in three hospitals in Somalia. A cross-sectional study was conducted in Somalia from August to September 2016. Structured questionnaires were administered to 81 women who registered for fistula repair surgery in the Garowe, Daynile, and Kismayo General Hospitals in Somalia. Findings revealed that 70.4% of the study participants reported obstetric labor as the cause of their fistula, and 29.6% reported iatrogenic causes. Regarding the waiting time for the repair surgery, 45% waited for the surgery for over one year, while the rest received the surgery within a year. The study suggests that training for fistula surgery has to be provided for healthcare professionals in Somalia, fistula centers should be established, and access to these facilities has to be guaranteed for all patients who need these services.
Investigation of the Influence of Ni Doping on the Structure and Hardness of Ti-Ni-C Coatings
Authors: Daniel J. , Souček P. , Bernátová K. , Zábranský L. , Stupavská M. , Buršíková V. , Vašina P.
Published: July 2017

Nanocomposite nc-TiC/a-C:H thin films exhibit unique combination of mechanical properties, high hardness, low friction, and wear. Selective doping by weak-carbide forming element can be used in order to specifically design the physical and chemical properties of nc-TiC/a-C:H coatings. In this paper we report on an effect of nickel addition on structure and hardness of the nc-TiC/a-C:H coatings. The effect of Ni alloying on the coating structure under conditions of DCMS and HiPIMS depositions was studied. The coating structure was correlated with the coating hardness. The grain size, the grain carbon vacancy concentration, and the mean grain separation were found to be the key parameters determining the coating hardness. Ni doping proved to have a significant effect on the coating microstructure which resulted in changes of the hardness of the deposited coatings.
Mitochondria‐Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice
Authors: Demyanenko Ilya A. , Zakharova Vlada V. , Ilyinskaya Olga P. , Vasilieva Tamara V. , Fedorov Artem V. , Manskikh Vasily N. , Zinovkin Roman A. , Pletjushkina Olga Yu , Chernyak Boris V. , Skulachev Vladimir P. , Popova Ekaterina N.
Published: July 2017

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound‐healing processes in both diabetic humans and animals. We have applied the mitochondria‐targeted antioxidant 10‐(6′‐plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full‐thickness excisional dermal wounds in diabetic C57BL/KsJ‐db−/db− mice was significantly enhanced after long‐term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α‐smooth muscle actin‐positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL‐6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch‐wound assay in vitro under hyperglycemic condition. Thus, a mitochondria‐targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.
Association between HLA-DQ Gene Polymorphisms and HBV-Related Hepatocellular Carcinoma
Authors: Lv Jingzhu , Xu Tao , Qian Zhongqing , Wang Hongtao
Published: July 2017

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Host gene variants may influence hepatitis B virus- (HBV-) related HCC. Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Previous studies have investigated the HLA-DQ (rs2856718 and rs9275572) polymorphisms that may be associated with the development of HBV-related HCC. However, the results are controversial or inconclusive. Hence, we conducted a meta-analysis to derive a more precise estimation of the associations. A total of 6 articles were used to evaluate the effect of the two polymorphisms on the risk of HBV-related HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We found that rs2856718 and rs9275572 in HLA-DQ significantly decreased HBV-related HCC in total population, especially in Chinese, but not in Saudi Arabian. Further validation of our results in larger populations and different ethnicities are required.
Design of an Edge Slotted Waveguide Antenna Array Based on T-Shaped Cross-Section Waveguide
Authors: Li Teng , Dou Wenbin
Published: July 2017

An edge slotted waveguide antenna array based on T-shaped cross-section radiating waveguide is proposed. The T-shaped waveguide is analyzed and designed to operate in dominant mode around the center frequency, which has a lower profile compared with the rectangular one. The radiating slots are etched and rotated alternatively on the broadened top plate without cutting into the adjacent walls. The metal fences are inserted between slots to reduce the mutual coupling and surface wave. Therefore, the sidelobe level in E-plane is well suppressed. A 2 × 8 antenna array working at Ka-band is designed and fabricated. The measured results agree well with simulations which demonstrate this novel waveguide structure.
Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression
Authors: Guimarães Deborah de Almeida Bauer , De Castro Danielle dos Santos Bonfim , Oliveira Felipe Leite de , Nogueira Eduardo Matos , Silva Marco Antônio Mota da , Teodoro Anderson Junger
Published: July 2017

Breast cancer is one of the most prevalent cancers in the world and is also the leading cause of cancer death in women. The use of bioactive compounds of functional foods contributes to reduce the risk of chronic diseases, such as cancer and vascular disorders. In this study, we evaluated the antioxidant potential and the influence of pitaya extract (PE) on cell viability, colony formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and Erα in breast cancer cell lines (MCF‐7 and MDA‐MB‐435). PE showed high antioxidant activity and high values of anthocyanins (74.65 ± 2.18). We observed a selective decrease in cell proliferation caused by PE in MCF‐7 (ER+) cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1 phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF‐7 (ER+) cell line and suppressed BRCA1, BRCA2, PRAB, and Erα gene expression. Finally, we also demonstrate that no effect was observed with MDA‐MB‐435 cells (ER−) after PE treatment. Taken together, the present study suggests that pitaya may have a protective effect against breast cancer.
Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model
Authors: Park Jae Gwang , Son Young-Jin , Lee Tae Ho , Baek Nam Joon , Yoon Deok Hyo , Kim Tae Woong , Aravinthan Adithan , Hong Sungyoul , Kim Jong-Hoon , Sung Gi-Ho , Cho Jae Youl
Published: July 2017

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm‐EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell‐derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm‐EE. Interestingly, cancer sizes and mass were reduced in a C. militaris‐administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm‐EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p‐GSK3β) and cleaved caspase‐3 were increased with orally administered Cm‐EE. In addition, Cm‐EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm‐EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT‐dependent or GSK3β‐related caspase‐3‐dependent apoptosis.
Panretinal Photocoagulation Using Short-Pulse Laser Induces Less Inflammation and Macular Thickening in Patients with Diabetic Retinopathy
Authors: Takamura Yoshihiro , Arimura Shogo , Miyake Seiji , Matsumura Takehiro , Gozawa Makoto , Iwasaki Kentaro , Inatani Masaru
Published: July 2017

We compared the effect of panretinal photocoagulation (PRP) using short-pulse laser (SPL) and conventional laser, regardless of the number of spots, in terms of their effect on the progression of diabetic macular edema (DME) and anterior flare intensity (AFI) in patients with high-risk nonproliferative diabetic retinopathy (non-PDR). Forty-two eyes of 42 patients were subjected to PRP using the conventional argon laser (Conv group) or SPL (SPL group). CRT and AFI levels in the SPL group were significantly lower than those in the Conv group (CRT at 4, 6, and 10 weeks; AFI at 6, 10, and 18 weeks). Eyes of rabbits were photocoagulated using conventional laser with 500 spots (Conv 500s), SPL with 500 spots (SPL 500s), or 1000 spots (SPL 1000s). Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) levels in vitreous humor were measured using an immunoassay. Compared to conventional laser, VEGF, IL-6, and MCP-1 levels were significantly lower in the SPL 1000s and SPL 500s groups. In patients with high-risk non-PDR, SPL has a greater preventive effect on the progression of DME and AFI and produces less inflammatory cytokines than conventional lasers.
Mission Overview and Initial Observation Results of the X-Ray Pulsar Navigation-I Satellite
Authors: Zhang Xinyuan , Shuai Ping , Huang Liangwei , Chen Shaolong , Xu Lihong
Published: July 2017

The newly launched X-ray pulsar navigation-I (XPNAV-1) is an experimental satellite of China that is designed for X-ray pulsar observation. This paper presents the initial observation results and aims to recover the Crab pulsar’s pulse profile to verify the X-ray instrument’s capability of observing pulsars in space. With the grazing-incidence focusing type instrument working at the soft X-ray band (0.5–10 keV), up to 162 segments of observations of the Crab pulsar are fulfilled, and more than 5 million X-ray events are recorded. Arrival times of photons are corrected to the solar system barycentre, and the 33 ms pulse period is sought out for Crab. Epoch folding of all the corrected photon times generates the refined pulse profile of Crab. The characteristic two-peak profile proves that the Crab pulsar has been clearly seen, so that the conclusion is made that XPNAV-1’s goal of being capable of observing pulsars is achieved.
Extended Peritoneal Dialysis and Renal Recovery in HIV-Infected Patients with Prolonged AKI: A Report of 2 Cases
Authors: Saengpanit Donlawat , Puapatanakul Pongpratch , Towannang Piyaporn , Kanjanabuch Talerngsak
Published: July 2017

Peritoneal dialysis (PD) has recently been established as a treatment option for renal replacement therapy (RRT) in patients with acute kidney injury (AKI). Its efficacy in providing fluid and small solute removal has also been demonstrated in clinical trials and is equivalent to hemodialysis (HD). However, effect of RRT modality on renal recovery after AKI remains a controversy. Moreover, the setting of human immunodeficiency virus- (HIV-) infected patients with AKI requiring RRT makes the decision on RRT initiation and modality selection more complicated. The authors report here 2 cases of HIV-infected patients presenting with severe AKI requiring protracted course of acute RRT. PD had been performed uneventfully in both cases for 4–9 months before partial renal recovery occurred. Both patients eventually became dialysis independent but were left in chronic kidney disease (CKD) stage 4. These cases highlight the example of renal recovery even after a prolonged course of dialysis dependence. Thus, PD might be a suitable option for HIV patients with protracted AKI.
Inkjet Printing as High-Throughput Technique for the Fabrication of NiCo2O4 Films
Authors: Bacelis-Martínez Reyna Dianela , Oskam Gerko , Rodriguez Gattorno Geonel , Ruiz-Gómez Miguel Angel
Published: July 2017

Owing to its distinctive physicochemical properties, nickel-cobalt mixed oxide (NiCo2O4) has become a promising and innovative material for applications in many technological fields. The design of fast and reliable techniques for the deposition of this material is essential in the development of applications. In this work, NiCo2O4 films were successfully prepared by an inkjet printing technique using a suitable ink obtained from metal nitrates in a glycerol-water mixture. In order to deposit well-defined and uniform film patterns, the instrumental parameters such as drop spacing and inkjet voltage have been explored. The pure crystalline bimetallic nickel cobaltite oxide is obtained at 500°C with a homogeneous compositional distribution along the film. The average thickness observed by scanning electron microscopy is around 490 nm, whereas X-ray photoelectron spectroscopy analysis revealed that the film surface presents mixed oxidation states for both metals: Co2+, Co3+, Ni2+, and Ni3+. The electrocatalytic performance of inkjet-printed NiCo2O4 films for the water oxidation reaction is comparable with earlier reports.
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Authors: Menderes Gulden , Bonazzoli Elena , Bellone Stefania , Black Jonathan , Predolini Federica , Pettinella Francesca , Masserdotti Alice , Zammataro Luca , Altwerger Gary , Buza Natalia , Hui Pei , Wong Serena , Litkouhi Babak , Ratner Elena , Silasi Dan-Arin , Azodi Masoud , Schwartz Peter E. , Santin Alessandro D.
Published: July 2017

Purpose: Carcinosarcomas (CS) are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements with heterogeneous HER2/neu expression. We compared the efficacy of SYD985 (Synthon Biopharmaceuticals BV), a novel HER2-targeting antibody–drug conjugate (ADC), to trastuzumab emtansine (T-DM1, Genentech-Roche) against primary uterine and ovarian CS.

Experimental Design: Eight primary CS cell lines were evaluated for HER2/neu surface expression by IHC and gene amplification by FISH assays. The in vitro experiments included cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing. In vivo activity was studied in mouse xenograft and patient-derived xenograft (PDX) models.

Results: SYD985 and T-DM1 induced similar levels of ADCC against CS cell lines with low and high HER2/neu expression when challanged in the presence of effector cells. In contrast, SYD985 was 7- to 54-fold more potent than T-DM1 in the absence of effector cells. SYD985, unlike T-DM1, was active against CS demonstrating low or heterogeneous HER2/neu expression. Specifically, the mean IC50 values were 0.060 μg/mL and 3.221 μg/mL (P < 0.0001) against HER2/neu 0/1+ cell lines and 0.013 μg/mL and 0.096 μg/mL (P < 0.0001) against HER2/neu 3+ cell lines for SYD985 versus T-DM1, respectively. Importantly, unlike T-DM1, SYD985 induced efficient bystander killing of HER2/neu 0/1+ tumor cells admixed with HER2/neu 3+ cells. In vivo studies confirmed that SYD985 is more active than T-DM1 in CS and highly effective against HER2/neu expressing xenografts and PDX.

Conclusions: SYD985 may represent a novel and highly effective ADC against HER2-expressing CS. Clinical studies with SYD985 in patients harboring chemotherapy-resistant CS with low/moderate and high HER2 expression are warranted. Clin Cancer Res; 23(19); 5836–45. ©2017 AACR.
Sym015: A Highly Efficacious Antibody Mixture against MET-Amplified Tumors
Authors: Poulsen Thomas Tuxen , Grandal Michael Monrad , Skartved Niels Jørgen Østergaard , Hald Rikke , Alifrangis Lene , Koefoed Klaus , Lindsted Trine , Fröhlich Camilla , Pollmann Sofie Ellebæk , Eriksen Karsten Wessel , Dahlman Anna , Jacobsen Helle Jane , Bouquin Thomas , Pedersen Mikkel Wandahl , Horak Ivan David , Lantto Johan , Kragh Michael
Published: July 2017

Purpose: Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target MET more effectively, we developed an antagonistic antibody mixture, Sym015, consisting of two humanized mAbs directed against nonoverlapping epitopes of MET.

Experimental Design/Results: We screened a large panel of well-annotated human cancer cell lines and identified a subset with highly elevated MET expression. In particular, cell lines of lung cancer and gastric cancer origin demonstrated high MET expression and activation, and Sym015 triggered degradation of MET and significantly inhibited growth of these cell lines. Next, we tested Sym015 in patient- and cell line–derived xenograft models with high MET expression and/or MET exon 14 skipping alterations, and in models harboring MET amplification as a mechanism of resistance to EGFR-targeting agents. Sym015 effectively inhibited tumor growth in all these models and was superior to an analogue of emibetuzumab, a monoclonal IgG4 antibody against MET currently in clinical development. Sym015 also induced antibody-dependent cellular cytotoxicity (ADCC) in vitro, suggesting that secondary effector functions contribute to the efficacy of Sym015.

Retrospectively, all responsive, high MET-expressing models were scored as highly MET-amplified by in situ hybridization, pointing to MET amplification as a predictive biomarker for efficacy. Preclinical toxicology studies in monkeys showed that Sym015 was well tolerated, with a pharmacokinetic profile supporting administration of Sym015 every second or third week in humans.

Conclusions: The preclinical efficacy and safety data provide a clear rationale for the ongoing clinical studies of Sym015 in patients with MET-amplified tumors. Clin Cancer Res; 23(19); 5923–35. ©2017 AACR.