bluuebunny/crossref_metadata_2025 huggingface dataset:
pH buffering of single rat skeletal muscle fibers in the in vivo environment
Authors: Tanaka Yoshinori , Inagaki Tadakatsu , Poole David C. , Kano Yutaka
Published: March 2016

Homeostasis of intracellular pH (pHi) has a crucial role for the maintenance of cellular function. Several membrane transporters such as lactate/H+cotransporter (MCT), Na+/H+exchange transporter (NHE), and Na+/HCO3−cotransporter (NBC) are thought to contribute to pHiregulation. However, the relative importance of each of these membrane transporters to the in vivo recovery from the low pHicondition is unknown. Using an in vivo bioimaging model, we pharmacologically inhibited each transporter separately and all transporters together and then evaluated the pHirecovery profiles following imposition of a discrete H+challenge loaded into single muscle fibers by microinjection. The intact spinotrapezius muscle of adult male Wistar rats ( n = 72) was exteriorized and loaded with the fluorescent probe 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethyl ester (10 μM). A single muscle fiber was then loaded with low-pH solution [piperazine- N, N′-bis(2-ethanesulfonic acid) buffer, pH 6.5, ∼2.33 × 10−3μl] by microinjection over 3 s. The rats were divided into groups for the following treatments: 1) no inhibitor (CONT), 2) MCT inhibition (by α-Cyano-4-hydroxyciannamic acid; 4 mM), 3) NHE inhibition (by ethylisopropyl amiloride; 0.5 mM), 4) NBC inhibition (by DIDS; 1 mM), and 5) MCT, NHE, and NBC inhibition (All blockade). The fluorescence ratio (F500 nm/F445 nm) was determined from images captured during 1 min (60 images/min) and at 5, 10, 15, and 20 min after injection. The pHiat 1–2 s after injection significantly decreased from resting pHi(ΔpHi= −0.73 ± 0.03) in CONT. The recovery response profile was biphasic, with an initial rapid and close-to-exponential pHiincrease (time constant, τ: 60.0 ± 7.9 s). This initial rapid profile was not affected by any pharmacological blockade but was significantly delayed by carbonic anhydrase inhibition. In contrast, the secondary, more gradual, return toward baseline that restored CONT pHito 84.2% of baseline was unimpeded by MCT, NHE, and NBC blockade separately but abolished by All blockade (ΔpHi= −0.60 ± 0.07, 72.8% initial pHi, P < 0.05 vs. CONT). After injection of H+into, or superfusion onto, an adjacent fiber pHiof the surrounding fibers decreased progressively for the 20-min observation period (∼7.0, P < 0.05 vs. preinjection/superfusion). In conclusion, these results support that, after an imposed H+load, the MCT, NHE, and NBC transporters are not involved in the initial rapid phase of pHirecovery. In contrast, the gradual recovery phase was abolished by inhibiting all three membrane transporter systems simultaneously. The alteration of pHiin surrounding fibers suggest that H+uptake by neighboring fibers can help alleviate the pH consequences of myocyte H+exudation.
Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin
Authors: O'Flynn Joseph , van der Pol Pieter , Dixon Karen O. , Prohászka Zoltán , Daha Mohamed R. , van Kooten Cees
Published: March 2016

Previous studies have shown that complement activation on renal tubular cells is involved in the induction of interstitial fibrosis and cellular injury. Evidence suggests that the tubular cell damage is initiated by the alternative pathway (AP) of complement with properdin having an instrumental role. Properdin is a positive regulator of the AP, which can bind necrotic cells as well as viable proximal tubular epithelial cells (PTECs), inducing complement activation. Various studies have indicated that in the circulation there is an unidentified inhibitor of properdin. We investigated the ability of C-reactive protein (CRP), both in its monomeric (mCRP) and pentameric (pCRP) form, to inhibit AP activation and injury in vitro on renal tubular cells by fluorescent microscopy, ELISA, and flow cytometry. We demonstrated that preincubation of properdin with normal human serum inhibits properdin binding to viable PTECs. We identified mCRP as a factor able to bind to properdin in solution, thereby inhibiting its binding to PTECs. In contrast, pCRP exhibited no such binding and inhibitory effect. Furthermore, mCRP was able to inhibit properdin-directed C3 and C5b-9 deposition on viable PTECs. The inhibitory ability of mCRP was not unique for viable cells but also demonstrated for binding to necrotic Jurkat cells, a target for properdin binding and complement activation. In summary, mCRP is an inhibitor of properdin in both binding to necrotic cells and viable renal cells, regulating complement activation on the cell surface. We propose that mCRP limits amplification of tissue injury by controlling properdin-directed complement activation by damaged tissue and cells.
Nitric oxide/cGMP/PKG signaling pathway activated by M1-type muscarinic acetylcholine receptor cascade inhibits Na+-activated K+currents in Kenyon cells
Authors: Hasebe Masaharu , Yoshino Masami
Published: March 2016

The interneurons of the mushroom body, known as Kenyon cells, are essential for the long-term memory of olfactory associative learning in some insects. Some studies have reported that nitric oxide (NO) is strongly related to this long-term memory in Kenyon cells. However, the target molecules and upstream and downstream NO signaling cascades are not completely understood. Here we analyzed the effect of the NO signaling cascade on Na+-activated K+(KNa) channel activity in Kenyon cells of crickets ( Gryllus bimaculatus). We found that two different NO donors, S-nitrosoglutathione (GSNO) and S-nitroso- N-acetyl-dl-penicillamine (SNAP), strongly suppressed KNachannel currents. Additionally, this inhibitory effect of GSNO on KNachannel activity was diminished by 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), and KT5823, an inhibitor of protein kinase G (PKG). Next, we analyzed the role of ACh in the NO signaling cascade. ACh strongly suppressed KNachannel currents, similar to NO donors. Furthermore, this inhibitory effect of ACh was blocked by pirenzepine, an M1muscarinic ACh receptor antagonist, but not by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) and mecamylamine, an M3muscarinic ACh receptor antagonist and a nicotinic ACh receptor antagonist, respectively. The ACh-induced inhibition of KNachannel currents was also diminished by the PLC inhibitor U73122 and the calmodulin antagonist W-7. Finally, we found that ACh inhibition was blocked by the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME). These results suggested that the ACh signaling cascade promotes NO production by activating NOS and NO inhibits KNachannel currents via the sGC/cGMP/PKG signaling cascade in Kenyon cells.
Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents
Authors: Suresh Jyothsna , Radojicic Mihailo , Pesce Lorenzo L. , Bhansali Anita , Wang Janice , Tryba Andrew K. , Marks Jeremy D. , van Drongelen Wim
Published: March 2016

The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while short-timescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Nap) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABAA, AMPA, and NMDA receptors and riluzole to selectively block Napchannels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABAA+ NMDA + AMPA, NMDA + AMPA, GABAA+ AMPA, GABAA+ NMDA, AMPA, NMDA, GABAA, and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Napcurrents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties.
Achievement of Vancomycin Therapeutic Goals in Critically Ill Patients: Early Individualization May Be Beneficial
Authors: Shahrami Bita , Najmeddin Farhad , Mousavi Sarah , Ahmadi Arezoo , Rouini Mohammad Reza , Sadeghi Kourosh , Mojtahedzadeh Mojtaba
Published: March 2016

Objective.The aim of our study was to assess and validate the effectiveness of early dose adjustment of vancomycin based on first dose monitoring in achieving target recommended goal in critically ill patients.Methods.Twenty critically ill patients with sepsis received loading dose of 25 mg/kg of vancomycin and then were randomly assigned to 2 groups. Group 1 received maximum empirical doses of vancomycin of 15 mg/kg every 8 hrs. In group 2, the doses were individualized based on serum concentrations of vancomycin. First dose nonsteady state sampling was used to calculate pharmacokinetic parameters of the patients within 24 hours.Results.Steady state trough serum concentrations were significantly higher in group 2 in comparison with group 1 (19.4 ± 4.4 mg/L versus 14.4 ± 4.3 mg/L) (P=0.03). Steady state AUCs were significantly higher in group 2 compared with group 1 (665.9 ± 136.5 mg·hr/L versus 490.7 ± 101.1 mg·hr/L) (P=0.008).Conclusions.With early individualized dosing regimen, significantly more patients achieved peak and trough steady state concentrations. In the context of pharmacokinetic/pharmacodynamic goal of area under the time concentration curve to minimum inhibitory concentration (AUC/MIC) ≥400 and also to obtain trough serum concentration of vancomycin of ≥15 mg/L, it is necessary to individualize doses of vancomycin in critically ill patients.
Electroacupuncture Reduces Postoperative Pain and Analgesic Consumption in Patients Undergoing Thoracic Surgery: A Randomized Study
Authors: Chen Tongyu , Wang Ke , Xu Jianjun , Ma Wen , Zhou Jia
Published: March 2016

The aim of this study was to evaluate the effect of electroacupuncture (EA) on postoperative pain management in patients undergoing thoracic surgery. A randomized study was conducted. Ninety‐two thoracic surgical patients were randomly divided into an EA group and a sham group. Postoperative intravenous analgesia was applied with a half dose of the conventional drug concentration in both groups. In the EA group, EA treatment was administered for three consecutive days after the surgery with 6 sessions of 30 min each. Compared with the sham group, patients in the EA group had a lower visual analogue scale (VAS) score at 2, 24, 48, and 72 hours and consumed less analgesic after surgery. The incidence of opioid‐related adverse effects of nausea was lower in the EA group. The time to first flatus and defecation was also shorter in the EA group. Furthermore, the plasma β‐endorphin (β‐EP) level was higher by radioimmunoassay and the plasma 5‐hydroxytryptamine (5‐HT) level was lower in the EA group by enzyme‐linked immunosorbent assay during the first 72 hr after thoracic surgery. Therefore, EA is suitable as an adjunct treatment for postoperative pain management after thoracic surgery.
Burden of Suicidal Ideation and Attempt among Persons Living with HIV and AIDS in Semiurban Uganda
Authors: Rukundo Godfrey Zari , Mishara Brian Leslie , Kinyanda Eugene
Published: March 2016

Although the impact of HIV/AIDS has changed globally, it still causes considerable morbidity and mortality, including suicidality, in countries like Uganda. This paper describes the burden and risk factors for suicidal ideation and attempt among 543 HIV-positive attending two HIV specialized clinics in Mbarara municipality, Uganda. The rate of suicidal ideation was 8.8% (n=48; 95% CI: 6.70–11.50) and suicidal attempt was 3.1% (17, 95% CI 2.00–5.00). The factors associated with increased risk for suicidal ideation and attempts were state anger (OR = 1.06, 95% CI: 1.03–1.09;p=0.001); trait anger (OR 1.10, 95% CI 1.04–1.16,p=0.002); depression (OR 1.13, 95% CI 1.07–1.20,p=0.001); hopelessness (OR 1.12, 95% CI 1.02–1.23,p=0.024); anxiety (OR 1.06, 95% CI 1.03–1.09); low social support (OR 0.19, 95% CI 0.07–0.47,p=0.001); inability to provide for others (OR 0.19, 95% CI 0.07–0.47,p=0.001); and stigma (OR 2.48, 95% CI 1.11–5.54,p=0.027). At multivariate analysis, only state anger remained statistically significant. HIV/AIDS is associated with several clinical, psychological, and social factors which increase vulnerability to suicidal ideation and attempts. Making suicide risk assessment and management an integral part of HIV care is warranted.
Cooperative Downloading in Mobile Ad Hoc Networks: A Cost-Energy Perspective
Authors: Li He , Yang Yang , Qiu Xuesong , Gao Zhipeng , Ma Guizhen
Published: March 2016

Cooperative downloading in mobile ad hoc networks is an effective way to improve the efficiency of downloading files. This work addresses the problem while distributing content to a group of mobile terminals (MTs) that cooperate during the download process by forming mobile ad hoc networks. However, the efficiency, cost, and energy consumption of cooperative downloading are sensitive by content distribution, which is a challenge to get the optimal in mobile ad hoc networks. This paper proposes a cost distribution (OCD) algorithm and a content distribution algorithm based on auction (OCDA) for mobile ad hoc networks based on relative location of nodes and local optimization theory. In order to make cooperative users take part when the downloading is beginning, several rounds of content distribution approach are designed based on users' relative location in the cooperative ad hoc network. To satisfy users' personal demands, the paper also designs a local optimization mechanism based on cost and energy. The simulation results show that the cost and content distribution method can achieve better performance, higher downloading efficiency, and lower energy consumption than the self-organized market algorithm (SOMA) and the average distribution algorithm (ADA).
Research on Mathematical Model of Composite Micromachining of Laser and Electrolysis Based on the Electrolyte Fluid
Authors: Sun Aixi , Hao Bo , Hu Yulan , Yang Dewei
Published: March 2016

A new technology of composite micromachining of laser and electrolysis is presented through a combination of technological advantages of laser processing and electrolytic machining. The implication of its method is that laser processing efficiently removes metallic materials and that pulse electrolytic machining removes recast layer and controls shape precisely. Machining accuracy and efficiency can be improved. The impacts that electrolyte fluid effectively cools the microstructure edge in the laser machining process and that gas-liquid two-phase flow makes the electrolyte conductivity produce uneven distribution in the electrolytic processing are considered. Some approximate assumptions are proposed on the actual conditions of machining process. The mathematical model of composite micromachining of laser and electrolysis based on the electrolyte fluid is built. The validity of the model can be verified by experimentation. The experimental results show that processing accuracy meets accuracy requirements which are ±0.05 mm. Machining efficiency increases more than 20 percent compared to electrolytic processing.
A Joint Scheduling Optimization Model for Wind Power and Energy Storage Systems considering Carbon Emissions Trading and Demand Response
Authors: Aiwei Yin , Congwei Xu , Liwei Ju
Published: March 2016

To reduce the influence of wind power random on system operation, energy storage systems (ESSs) and demand response (DR) are introduced to the traditional scheduling model of wind power and thermal power with carbon emission trading (CET). Firstly, a joint optimization scheduling model for wind power, thermal power, and ESSs is constructed. Secondly, DR and CET are integrated into the joint scheduling model. Finally, 10 thermal power units, a wind farm with 2800 MW of installed capacity, and3×80 MW ESSs are taken as the simulation system for verifying the proposed models. The results show backup service for integrating wind power into the grid is provided by ESSs based on their charge-discharge characteristics. However, system profit reduces due to ESSs’ high cost. Demand responses smooth the load curve, increase profit from power generation, and expand the wind power integration space. After introducing CET, the generation cost of thermal power units and the generation of wind power are both increased; however, the positive effect of DR on the system profit is also weakened. The simulation results reach the optimum when both DR and CET are introduced.
Contractile Force of Human Extraocular Muscle: A Theoretical Analysis
Authors: Guo Hongmei , Gao Zhipeng , Chen Weiyi
Published: March 2016

Aim. The length-contractile force relationships of six human extraocular muscles (EOMs) in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships.Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained.Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results.Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely.
Data Gathering Techniques for Wireless Sensor Networks: A Comparison
Authors: Campobello Giuseppe , Segreto Antonino , Serrano Salvatore
Published: March 2016

We study the problem of data gathering in wireless sensor networks and compare several approaches belonging to different research fields; in particular, signal processing, compressive sensing, information theory, and networking related data gathering techniques are investigated. Specifically, we derived a simple analytical model able to predict the energy efficiency and reliability of different data gathering techniques. Moreover, we carry out simulations to validate our model and to compare the effectiveness of the above schemes by systematically sampling the parameter space (i.e., number of nodes, transmission range, and sparsity). Our simulation and analytical results show that there is no best data gathering technique for all possible applications and that the trade-off between energy consumptions and reliability could drive the choice of the data gathering technique to be used. In this context, our model could be a useful tool.
Numerical Study of Pollutant Emissions in a Jet Stirred Reactor under Elevated Pressure Lean Premixed Conditions
Authors: Mazaheri Karim , Shakeri Alireza
Published: March 2016

Numerical study of pollutant emissions (NO and CO) in a Jet Stirred Reactor (JSR) combustor for methane oxidation under Elevated Pressure Lean Premixed (EPLP) conditions is presented. A Detailed Flow-field Simplified Chemistry (DFSC) method, a low computational cost method, is employed for predicting NO and CO concentrations. Reynolds Averaged Navier Stokes (RANS) equations with species transport equations are solved. Improved-coefficient five-step global mechanisms derived from a new evolutionary-based approach were taken as combustion kinetics. For modeling turbulent flow field, Reynolds Stress Model (RSM), and for turbulence chemistry interactions, finite rate-Eddy dissipation model are employed. Effects of pressure (3, 6.5 bars) and inlet temperature (408–573 K) over a range of residence time (1.49–3.97 ms) are numerically examined. A good agreement between the numerical and experimental distribution of NO and CO was found. The effect of decreasing the operating pressure on NO generation is much more than the effect of increase in the inlet temperature.
Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD
Authors: Tsilimbaris Miltiadis K. , López-Gálvez Maria I. , Gallego-Pinazo Roberto , Margaron Philippe , Lambrou George N.
Published: March 2016

Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response.Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology.Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review.Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.
Protective Effects of Sheng‐Mai‐San on Right Ventricular Dysfunction during Chronic Intermittent Hypoxia in Mice
Authors: Chai Cheng-Zhi , Mo Wei-Lan , Zhuang Xian-Fei , Kou Jun-Ping , Yan Yong-Qing , Yu Bo-Yang
Published: March 2016

Right ventricular (RV) dysfunction and failure contribute to the increasing morbidity and mortality of cardiovascular diseases; however, current treatment strategies are grossly inadequate. Sheng‐Mai‐San (SMS) has been used to treat heart diseases for hundreds of years in China, and its protective effects on RV have not been observed. The present study was to investigate the protective effects of SMS aqueous extract on RV dysfunction in chronic intermittent hypoxia (CIH) mice model. The results showed that CIH mice model presented RV dysfunction and maladaptive compensation after 28‐day‐CIH and SMS treatment significantly reversed these changes. Diastolic function of RV was restored and systolic dysfunction was attenuated, including elevation of RV stroke volume and fractional shortening, as well as pulmonary circulation. Structurally, SMS treatment inhibited RV dilation, cardiomyocytes vacuolization, ultrastructure abnormalities, and the expression of cleaved caspase‐3. Of importance, SMS showed remarkable antioxidant activity by decreasing the levels of malondialdehyde (MDA) and 4‐hydroxynonenal (4‐HNE), increasing the levels of superoxide dismutase (SOD) and heme oxygenase‐1 (HO‐1), as well as inhibiting the overexpression of 3‐NT in RV. Our results indicate that SMS preserve RV structure and function in CIH‐exposed mice by involving regulation in both ROS and Reactive Nitrogen Species (RNS) production.
Morphine Suppository versus Indomethacin Suppository in the Management of Renal Colic: Randomized Clinical Trial
Authors: Zamanian Forough , Jalili Mohammad , Moradi-Lakeh Maziar , Kia Maryam , Aghili Rokhsareh , Aghili Seyed Mojtaba
Published: March 2016

Background. Renal colic is a medical emergency due to the rapid onset and devastating nature of its pain. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are both used as first-line choices in its management. Aim. This study aimed to compare the efficacy and safety of opioids and NSAIDs in the management of acute renal colic. Methods. One hundred and fifty-eight patients were divided into two groups (n=79) and received either 10 mg morphine or 100 mg indomethacin suppositories. The severity of pain was measured using verbal numeric rating scale at baseline and 20, 40, 60, and 90 minutes after the administration of analgesics. Drug side effects as well as patients’ vital signs were also recorded. Results. The mean decrease in the pain score during the first 20 minutes was significantly higher among those who received morphine suppository. However, no significant difference was observed between the two groups regarding the mean decrease in pain score during the first 40, 60, and 90 minutes after the admission. Prevalence of drug side effects or changes in the vital signs was not significantly different between the two groups. Conclusions. Morphine suppositories seem to be more efficient in achieving rapid pain relief comparing to indomethacin.
Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders
Authors: Lee Hyeong-Min , Kim Yuna
Published: March 2016

Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.
Renal Blood Flow Response to Angiotensin 1-7 versus Hypertonic Sodium Chloride 7.5% Administration after Acute Hemorrhagic Shock in Rats
Authors: Maleki Maryam , Nematbakhsh Mehdi
Published: March 2016

Background.Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS.Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg−1 min−1), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4).Results. MAP was increased in a time-related fashion (Ptime<0.0001) in all groups; however, there was a tendency for the increase in MAP in response to hypertonic solution (P=0.09). Ang1-7, hypertonic solution, or combination of both increased RBF in groups 2-4, and these were significantly different from saline group (P=0.05); that is, Ang1-7 leads to a significant increase in RBF to 1.35 ± 0.25 mL/min compared with 0.55 ± 0.12 mL/min in saline group (P<0.05).Conclusion. Although Ang1-7 administration unlike hypertonic solution could not elevate MAP after HS, it potentially could increase RBF similar to hypertonic solution. This suggested that Ang1-7 recovers RBF after HS when therapeutic opportunities of hypertonic solution are limited.
The Effectiveness of Cupping Therapy on Relieving Chronic Neck and Shoulder Pain: A Randomized Controlled Trial
Authors: Chi Lee-Mei , Lin Li-Mei , Chen Chien-Lin , Wang Shu-Fang , Lai Hui-Ling , Peng Tai-Chu
Published: March 2016

The research aimed to investigate the effectiveness of cupping therapy (CT) in changes on skin surface temperature (SST) for relieving chronic neck and shoulder pain (NSP) among community residents. A single‐blind experimental design constituted of sixty subjects with self‐perceived NSP. The subjects were randomly allocated to two groups. The cupping group received CT at SI 15, GB 21, and LI 15 acupuncture points, and the control group received no intervention. Pain was assessed using the SST, visual analog scale (VAS), and blood pressure (BP). The main results were SST of GB 21 acupuncture point raised from 30.6°C to 32.7°C and from 30.7°C to 30.6°C in the control group. Neck pain intensity (NPI) severity scores were reduced from 9.7 to 3.6 in the cupping group and from 9.7 to 9.5 in the control group. The SST and NPI differences between the groups were statistically significant (P  <  0.001). One treatment of CT is shown to increase SST. In conjunction with the physiological effect the subjective experience of NSP is reduced in intensity. Further studies are required to improve the understanding and potential long‐term effects of CT.
Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats
Authors: Ragy Merhan , Ali Fatma , Ramzy Maggie M.
Published: March 2016

In the brain, the heme oxygenase (HO) system has been reported to be very active and its modulation seems to play a crucial role in the pathophysiology of neurodegenerative disorders. Hemin as HO-1 inducer has been shown to attenuate neuronal injury so the goal of this study was to assess the effect of hemin therapy on the acute stress and how it would modulate neurological outcome. Thirty male albino rats were divided into three groups: control group and stressed group with six-hour water immersion restraint stress (WIRS) and stressed group, treated with hemin, in which each rat received a single intraperitoneal injection of hemin at a dose level of 50 mg/kg body weight at 12 hours before exposure to WIRS. Stress hormones, oxidative stress markers, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured and expressions of neuroglobin and S100B mRNA in brain tissue were assayed. Our results revealed that hemin significantly affects brain alterations induced by acute stress and this may be through increased expression of neuroglobin and through antioxidant effect. Hemin decreased blood-brain barrier damage as it significantly decreased the expression of S100B. These results suggest that hemin may be an effective therapy for being neuroprotective against acute stress.
Recent Development of Catalysts for Removal of Volatile Organic Compounds in Flue Gas by Combustion: A Review
Authors: Tomatis Marco , Xu Hong-Hui , He Jun , Zhang Xiao-Dong
Published: March 2016

Volatile organic compounds (VOCs) emitted from anthropogenic sources pose direct and indirect hazards to both atmospheric environment and human health due to their contribution to the formation of photochemical smog and potential toxicity including carcinogenicity. Therefore, to abate VOCs emission, the catalytic oxidation process has been extensively studied in laboratories and widely applied in various industries. This report is mainly focused on the benzene, toluene, ethylbenzene, and xylene (BTEX) with additional discussion about chlorinated VOCs. This review covers the recent developments in catalytic combustion of VOCs over noble metal catalysts, nonnoble metal catalysts, perovskite catalysts, spinel catalysts, and dual functional adsorbent-catalysts. In addition, the effects of supports, coke formation, and water effects have also been discussed. To develop efficient and cost-effective catalysts for VOCs removal, further research in catalytic oxidation might need to be carried out to strengthen the understanding of catalytic mechanisms involved.
Growth Rate Analysis of an Untreated Glomus Vagale on MRI
Authors: Wang Jeffrey Tzu-Yu , Wang Allen Yu-Yu , Cheng Sheila , Gomes Lavier , Da Cruz Melville
Published: March 2016

Paragangliomas are slow growing, hypervascular neuroendocrine tumors that develop in the extra-adrenal paraganglion tissues. Paraganglioma involving the vagus nerve ganglia is termed glomus vagale. The slow growth of head and neck paragangliomas especially in the absence of symptom may obviate the necessity for any active intervention, in which case, a “wait and scan” policy is implemented involving long-term clinical and radiologic follow-ups. We present a case of a 71-year-old female with an untreated left glomus vagale who underwent a conservative “wait and rescan” plan of management and the tumor was observed with 8 serial MRI scans over a period of 7.4 years. A growth rate analysis was conducted which demonstrated a slow growth. A literature review of radiologic studies examining the natural history of head and neck paragangliomas was also performed.
Causality in Statistical Power: Isomorphic Properties of Measurement, Research Design, Effect Size, and Sample Size
Authors: Heidel R. Eric
Published: March 2016

Statistical power is the ability to detect a significant effect, given that the effect actually exists in a population. Like most statistical concepts, statistical power tends to induce cognitive dissonance in hepatology researchers. However, planning for statistical power by ana priorisample size calculation is of paramount importance when designing a research study. There are five specific empirical components that make up ana priorisample size calculation: the scale of measurement of the outcome, the research design, the magnitude of the effect size, the variance of the effect size, and the sample size. A framework grounded in the phenomenon of isomorphism, or interdependencies amongst different constructs with similar forms, will be presented to understand the isomorphic effects of decisions made on each of the five aforementioned components of statistical power.
Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment
Authors: Günter Julia , Wolint Petra , Bopp Annina , Steiger Julia , Cambria Elena , Hoerstrup Simon P. , Emmert Maximilian Y.
Published: March 2016

More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell‐based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single‐cell suspensions have failed to demonstrate long‐lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo‐like microenvironment. Of great interest is the use of so‐called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next‐generation therapeutic approach.
Delayed Presentation of Gluteal Compartment Syndrome: The Argument for Fasciotomy
Authors: Lawrence John E. , Cundall-Curry Duncan J. , Stohr Kuldeep K.
Published: March 2016

A male patient in his fifties presented to his local hospital with numbness and weakness of the right leg which left him unable to mobilise. He reported injecting heroin the previous morning. Following an initial diagnosis of acute limb ischaemia the patient was transferred to a tertiary centre where Computed Tomography Angiography was reported as normal. Detailed neurological examination revealed weakness in hip flexion and extension (1/5 on the Medical Research Council scale) with complete paralysis of muscle groups distal to this. Sensation to pinprick and light touch was globally reduced. Blood tests revealed acute kidney injury with raised creatinine kinase and the patient was treated for rhabdomyolysis. Orthopaedic referral was made the following day and a diagnosis of gluteal compartment syndrome (GCS) was made. Emergency fasciotomy was performed 56 hours after the onset of symptoms. There was immediate neurological improvement following decompression and the patient was rehabilitated with complete nerve recovery and function at eight-week follow-up. This is the first documented case of full functional recovery following a delayed presentation of GCS with sciatic nerve palsy. We discuss the arguments for and against fasciotomy in cases of compartment syndrome with significant delay in presentation or diagnosis.
Hydrogen Peroxide and Sodium Transport in the Lung and Kidney
Authors: Shlyonsky V. , Boom A. , Mies F.
Published: March 2016

Renal and lung epithelial cells are exposed to some significant concentrations of H2O2. In urine it may reach 100 μM, while in the epithelial lining fluid in the lung it is estimated to be in micromolar to tens-micromolar range. Hydrogen peroxide has a stimulatory action on the epithelial sodium channel (ENaC) single-channel activity. It also increases stability of the channel at the membrane and slows down the transcription of the ENaC subunits. The expression and the activity of the channel may be inhibited in some other, likely higher, oxidative states of the cell. This review discusses the role and the origin of H2O2in the lung and kidney. Concentration-dependent effects of hydrogen peroxide on ENaC and the mechanisms of its action have been summarized. This review also describes outlooks for future investigations linking oxidative stress, epithelial sodium transport, and lung and kidney function.
Adaptive Corrosion Protection System Using Continuous Corrosion Measurement, Parameter Extraction, and Corrective Loop
Authors: Patel Jasbir N. , Chang Andre , Shahbazbegian Haleh , Kaminska Bozena
Published: March 2016

A simple current-sourced adaptive corrosion protection system (ACPS) along with a technology to extract the protection current from the Tafel plot is presented. For reliable protection of the target metal, first, the Tafel plot of the target metal is obtained. Subsequently, a novel technique proposed in this paper is used to extract the protection current from the Tafel plot. This extracted protection current is fed to the target metal to protect the metal in the existing corrosive environment. This three-part system is adaptively used to update the required protection current to effectively protect the target metal continuously. All these functionalities are integrated in a stand-alone ACPS that effectively diagnoses the corrosion status and updates the protection parameters without any manual interaction or physical modification of the set-up to offer modularity, reliability, and cost saving. To validate the technique, a laboratory scale system is realized and tested using various metal samples and various corrosive mediums. Using the experimental system, A36 metal coupons are effectively protected with protection (inhibition) efficiency of 40–100%in different corrosive mediums that can extend the life expectancy of the target metal from ~2 times to more than 100 times for the tested corrosive mediums.
Energy-Efficient Reliability-Aware Scheduling Algorithm on Heterogeneous Systems
Authors: Tang Xiaoyong , Tan Weizhen
Published: March 2016

The amount of energy needed to operate high-performance computing systems increases regularly since some years at a high pace, and the energy consumption has attracted a great deal of attention. Moreover, high energy consumption inevitably contains failures and reduces system reliability. However, there has been considerably less work of simultaneous management of system performance, reliability, and energy consumption on heterogeneous systems. In this paper, we first build the precedence-constrained parallel applications and energy consumption model. Then, we deduce the relation between reliability and processor frequencies and get their parameters approximation value by least squares curve fitting method. Thirdly, we establish a task execution reliability model and formulate this reliability and energy aware scheduling problem as a linear programming. Lastly, we propose a heuristic Reliability-Energy Aware Scheduling (REAS) algorithm to solve this problem, which can get good tradeoff among system performance, reliability, and energy consumption with lower complexity. Our extensive simulation performance evaluation study clearly demonstrates the tradeoff performance of our proposed heuristic algorithm.
Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry
Authors: Lai Yongquan , Yu Rui , Hartwell Hadley J. , Moeller Benjamin C. , Bodnar Wanda M. , Swenberg James A.
Published: March 2016

DNA–protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally specific manner. We exposed experimental animals to stable isotope–labeled formaldehyde ([13CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous (13CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues but were absent in tissues distant to the site of contact. This observation, together with the finding that endogenous formaldehyde–induced DPCs were present in all tissues examined, suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for the persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde and may inform improved disease prevention and treatment strategies. Cancer Res; 76(9); 2652–61. ©2016 AACR.
Dual Targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells
Authors: Tögel Lars , Nightingale Rebecca , Chueh Anderly C. , Jayachandran Aparna , Tran Hoanh , Phesse Toby , Wu Rui , Sieber Oliver M. , Arango Diego , Dhillon Amardeep S. , Dawson Mark A. , Diez-Dacal Beatriz , Gahman Timothy C. , Filippakopoulos Panagis , Shiau Andrew K. , Mariadason John M.
Published: March 2016

Inhibitors of the bromodomain and extraterminal domain (BET) protein family attenuate the proliferation of several tumor cell lines. These effects are mediated, at least in part, through repression of c-MYC. In colorectal cancer, overexpression of c-MYC due to hyperactive WNT/β-catenin/TCF signaling is a key driver of tumor progression; however, effective strategies to target this oncogene remain elusive. Here, we investigated the effect of BET inhibitors (BETi) on colorectal cancer cell proliferation and c-MYC expression. Treatment of 20 colorectal cancer cell lines with the BETi JQ1 identified a subset of highly sensitive lines. JQ1 sensitivity was higher in cell lines with microsatellite instability but was not associated with the CpG island methylator phenotype, c-MYC expression or amplification status, BET protein expression, or mutation status of TP53, KRAS/BRAF, or PIK3CA/PTEN. Conversely, JQ1 sensitivity correlated significantly with the magnitude of c-MYC mRNA and protein repression. JQ1-mediated c-MYC repression was not due to generalized attenuation of β-catenin/TCF-mediated transcription, as JQ1 had minimal effects on other β-catenin/TCF target genes or β-catenin/TCF reporter activity. BETi preferentially target super-enhancer–regulated genes, and a super-enhancer in c-MYC was recently identified in HCT116 cells to which BRD4 and effector transcription factors of the WNT/β−catenin/TCF and MEK/ERK pathways are recruited. Combined targeting of c-MYC with JQ1 and inhibitors of these pathways additively repressed c-MYC and proliferation of HCT116 cells. These findings demonstrate that BETi downregulate c-MYC expression and inhibit colorectal cancer cell proliferation and identify strategies for enhancing the effects of BETi on c-MYC repression by combinatorial targeting the c-MYC super-enhancer. Mol Cancer Ther; 15(6); 1217–26. ©2016 AACR.