bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the relative valuation of research impact: a best–worst scaling experiment of the general public and biomedical and health researchers
Authors: Pollitt Alexandra , Potoglou Dimitris , Patil Sunil , Burge Peter , Guthrie Susan , King Suzanne , Wooding Steven , Grant Jonathan
Published: August 2016

Objectives

(1) To test the use of best–worst scaling (BWS) experiments in valuing different types of biomedical and health research impact, and (2) to explore how different types of research impact are valued by different stakeholder groups.

Design

Survey-based BWS experiment and discrete choice modelling.

Setting

The UK.

Participants

Current and recent UK Medical Research Council grant holders and a representative sample of the general public recruited from an online panel.

Results

In relation to the study's 2 objectives: (1) we demonstrate the application of BWS methodology in the quantitative assessment and valuation of research impact. (2) The general public and researchers provided similar valuations for research impacts such as improved life expectancy, job creation and reduced health costs, but there was less agreement between the groups on other impacts, including commercial capacity development, training and dissemination.

Conclusions

This is the second time that a discrete choice experiment has been used to assess how the general public and researchers value different types of research impact, and the first time that BWS has been used to elicit these choices. While the 2 groups value different research impacts in different ways, we note that where they agree, this is generally about matters that are seemingly more important and associated with wider social benefit, rather than impacts occurring within the research system. These findings are a first step in exploring how the beneficiaries and producers of research value different kinds of impact, an important consideration given the growing emphasis on funding and assessing research on the basis of (potential) impact. Future research should refine and replicate both the current study and that of Milleret alin other countries and disciplines.
Non-accidental non-fatal poisonings attended by emergency ambulance crews: an observational study of data sources and epidemiology
Authors: John Ann , Okolie Chukwudi , Porter Alison , Moore Chris , Thomas Gareth , Whitfield Richard , Oretti Rossana , Snooks Helen
Published: August 2016

Background

Non-accidental non-fatal poisoning (NANFP) is associated with high risk of repeat episodes and fatality. This cross-sectional study aims to describe the data sources and epidemiology of non-fatal poisonings (NFPs) presenting to the emergency ambulance service.

Methods

We assessed incidents of NFP across Wales from electronic ambulance call centre records and paper records completed by attending ambulance crews, December 2007 to February 2008. We descriptively analysed data completed by attending crews.

Results

92 331 calls were made to the ambulance call centre, of which 3923 (4.2%) were coded as ‘overdose’ or ‘poisoning’. During the same period, ambulance crews recorded 1827 attended NANFP incidents in those categories, of which 1287 (70.4%) had been identified in the call centre. 76.1% (1356/1782) were aged 15–44 years and 54.2% (991/1827) were female. 75.0% (1302/1753) of incidents occurred in areas from the lower 2 quintiles of deprivation in Wales. Substance taken was reported in 90% of cases (n=1639). Multiple ingestion was common (n=886, 54.1%). Psychotropic was the most frequently taken group of substances (n=585, 32.0%) and paracetamol (n=484, 26.5%) was the most frequently taken substance prehospital. Almost half of patients had taken alcohol alongside other substances (n=844, 46.2%). Naloxone was the most frequently administered treatment (n=137, 7.5%). Only 142/1827 (7.8%) patients were not transported to hospital, of whom 4 were recorded to have been given naloxone.

Conclusions

We report new data on the epidemiology of NFP across substance types at national level, highlighting deficiencies in information systems and high levels of multiple ingestion. In order to develop policy and practice for this patient group prehospital and further along the care pathway, information systems need to be developed to allow accurate routine monitoring of volume, presentation and outcomes.
A UK survey of driving behaviour, fatigue, risk taking and road traffic accidents
Authors: Smith Andrew P
Published: August 2016

Objective

The aim of the present research was to examine associations between poor driving behaviour (DB), driving when fatigued (DF), risk taking (RT) and road traffic accidents (RTAs).

Design

The study involved a cross-sectional online survey of clients of an insurance company. The survey measured DB (speeding, distraction, lapses of attention and aggression), RT and frequency of driving when fatigued (DF, driving late at night, prolonged driving, driving after a demanding working day and driving with a cold). Demographic, lifestyle, job characteristics and psychosocial factors were also measured and used as covariates.

Setting

Cardiff, UK.

Sample

3000 clients of an insurance company agreed to participate in the study, and 2856 completed the survey (68% woman, 32% man; mean age: 34 years, range 18–74 years).

Main outcome measures

The outcomes were RTAs (requiring medical attention; not requiring medical attention), where the person was the driver.

Results

Factor analyses showed that DB, RT and fatigue loaded on independent factors. Logistic regressions showed that poor DB, frequently DF and taking risks predicted medical and non-medical RTAs. These effects were additive and those who reported poor DB, driving when fatigue and taking risks were twice as likely to have an RTA. These effects remained significant when demographic, lifestyle, medical, driving, work and psychosocial factors were covaried.

Conclusions

Poor DB, DF and RT predict RTAs. There are now short measuring instruments that can assess these, and driver education programmes must increase awareness of these risk factors.
Inherent variability in airway characteristics of simulation manikins: is it time we standardised assessments of crisis management skills?
Authors: Ashokka Balakrishnan , Narendiran Krishnasamy , Bhattacharya Abhijit , Pai Dinker , Liang Shen , Subramanian Shoba , Larmie Ernest T , Chen Fun Gee
Published: August 2016

Introduction

Learning of simulation-based crisis management skills involves technologically advanced manikins and use of automated scenarios. Progressions in preprogrammed scenarios require finite task completion such as successful airway intubations for achieving optimal learning outcomes aligned to curricular goals. The study was set to explore the existing variability among various simulation manikins in use at our institute for undergraduate medical education.

Methods

56 final-year undergraduate students, who had received prior training in airway management skills, performed intubations on each of the 5 different manikins (56×5=280 intubations). The manikins used were the Human Patient Simulator (HPS), iStan & Emergency Care Simulator (ECS) from CAE Healthcare and Mega Code Kelly (MCK) and Airway Trainer (AWTR) from Laerdal. The students’ performances were compared for success rates, ease of intubation, grade of laryngeal visualisation and presence of tooth injury on the manikins, Data from the intubations were cross-tabulated and evaluated by general estimating equation analysis using the Poisson model.

Results

iStan had the higher rates of failure to intubate (64.3%). iStan (62.5%) and HPS (57.1%) had statistically significant teeth injury (p<0.0001) compared to other manikins. HPS and AWTR had the least difficult grades of laryngeal visualisation (Cormack Lehane grades 1 and 2), while the most difficult grade of visualisation (Cormack Lehane grades 3 and 4) was reported in ECS (44.6%).

Conclusions

Each of the high-technology manikins used in automated scenarios for crisis management teaching and learning has heterogeneity in airway features. Since frequent airway management is a critical component of simulation scenarios, this can affect student performance when these manikins are used for formative and summative high-stakes assessments.
Do not throw the baby out with the bath water: a guide for using non-significant results in practice
Authors: Tello Mouaffaa , Zaiem Feras , Tolcher Mary Catherine , Murad Mohammad Hassan
Published: August 2016

Acting on results that are not statistically significant is challenging for clinicians. Such results are often interpreted as evidence of lack of association or as useless evidence. We provide a framework for interpreting and applying non-significant results at the point of care using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Republished: Solitaire stentectomy: ‘deploy and engage’ and ‘loop and snare’ techniques
Authors: Parthasarathy Rajsrinivas , Gupta Vipul , Goel Gaurav , Mahajan Anshu
Published: August 2016

Solitaire FR stent-based mechanical thrombectomy provides clinical benefit in selected patients with acute ischaemic stroke due to large vessel occlusion. A dreaded device complication that is associated with poor technical and clinical outcome is stent detachment. Retrieval of the detached stent can be technically challenging and has been attempted with variable success. The key benefit of this strategy is the lack of need to administer fibrinolytic/antiplatelet agents that can potentially be catastrophic in the setting of acute stroke. Therefore, retrieval may be preferred to other strategies (balloon angioplasty, lytic/glycoprotein 2b/3a inhibitors administration) to address detached stent. We report two patients in whom the detached stent was retrieved using alternative techniques—‘deploy and engage’ and ‘loop and snare’—as snare retrieval failed.
Genetic population structure in Greenland halibut (Reinhardtius hippoglossoides) and its relevance to fishery management
Authors: Westgaard Jon-Ivar , Saha Atal , Kent Matthew , Hansen Hanne Hellerud , Knutsen Halvor , Hauser Lorenz , Cadrin Steven X. , Albert Ole Thomas , Johansen Torild
Published: August 2016

Exploited marine resources can be managed more effectively when accurate information on geographic population structure is available. Genetic markers offer a powerful tool for fisheries management, because they reveal biologically sound management units. Single nucleotide polymorphisms (SNPs) markers derived from restriction-site associated DNA sequencing (RAD-seq) were developed and used to investigate the stock structure of Greenland halibut (Reinhardtius hippoglossoides). A total of 96 SNPs were analyzed from 384 individuals and eight locations across the Atlantic. Our results suggest a subdivision of Greenland halibut into two populations, an eastern Atlantic population and a western Atlantic population, with a proposed border across the Denmark Strait. In general, Greenland halibut display weak but significant population structure (overall FST= 0.003; p < 0.001), which can be explained by connectivity among populations owing to the migratory behavior or egg and larval drift.
Harmonic analysis tools for stochastic magnetohydrodynamics equations in Besov spaces
Authors: Sango Mamadou , Tegegn Tesfalem Abate
Published: August 2016

We establish a regularity result for stochastic heat equations in probabilistic evolution spaces of Besov type and we use it to prove a global in time existence and uniqueness of solution to a stochastic magnetohydrodynamics equation. The existence result holds with a positive probability which can be made arbitrarily close to one. The work is carried out by blending harmonic analysis tools such as Littlewood–Paley decomposition, Jean–Micheal Bony paradifferential calculus and stochastic calculus. The law of large numbers is a key tool in our investigation. Our global existence result is new in three-dimensional spaces.
First-principle study on electronic structure and optical properties of GaN nanowires with different cross-sections
Authors: Kong Yike , Liu Lei , Xia Sihao , Wang Honggang , Wang Meishan
Published: August 2016

This paper explores the properties of intrinsic gallium nitride (GaN) nanowires (NWs) in terms of formation energy, band structure, density of state (DOS) and optical properties with plane-wave ultrasoft pseudopotential method based on first-principles. Results show that after relaxation, N atoms of the outer layers move outwards, while Ga atoms move inwards, and the relaxation of surface atomic structure appears less obvious with the increasing cross-sectional area. Comparing different cross-sections of GaN NWs, it is found that the formation energy decreases and the stability goes stronger with the increasing size. With the increasing cross-section, the bandgap is decreased. Moreover, through comparative investigation in optical properties between GaN NWs and bulk GaN, a valuable phenomenom is found that the static dielectric constants of GaN NWs are notably lower, which contributes remarkably to the excellent absorbing performance of GaN NWs.
COMPUTATIONAL EVIDENCE FROM TWO CORRELATED DATA SOURCES AT DIFFERENT MOLECULAR LEVELS FOR AF-VHD-SPECIFIC MICRORNA SIGNATURE
Authors: FENG WEI , RAO NINI , WAN YONGLI , LI SAN , ZHENG JI , ZENG WEI , WANG GUANGBIN , CHEN XU
Published: August 2016

The important roles of microRNAs (miRNAs) in the pathological process of the cardiovascular system have been recognized. However, identification of miRNAs related to valvular heart disease with atrial fibrillation (AF-VHD) has been difficult and very slow because of complex pathological mechanism of AF-VHD. Analysis of microarray expression profiles provides the possibility to rapid prediction of disease-regulating miRNAs and can lay a theoretical foundation for further experimental studies. A computational method is proposed to predict AF-VHD-specific miRNAs by combining miRNA and gene expression data, which are strongly correlated. Using the proposed method, a 45-miRNA AF-VHD-specific signature is predicted. Compared with other related results, 15 of 45 miRNAs are the same and the rest 30 miRNAs are different. Our analysis shows that 11 of 30 new miRNAs are associated with the diseases inducing AF-VHD and the remaining 19 miRNAs have good combinational discrimination power. Therefore, the AF-VHD signature we have predicted is confirmed to be reliable and specific. In a word, this study proposes an effective computational strategy in prediction of disease-regulating miRNAs and finds some AF-VHD-specific miRNAs, which provides new insight into the further experimental study and molecular mechanism leading to the development of AF-VHD.
IDENTIFICATION OF A HIGHLY TRANSFECTABLE CELL LINE PERMISSIVE TO PORCINE EPIDEMIC DIARRHEA VIRUS INFECTION AND REPLICATION
Authors: Yang Ching , Chang Yen-Chen , Chang Chia-Yu , Tsai Pei-Shiue , Jeng Chian-Ren , Pang Victor Fei , Cheng Ivan-Chen , Chang Hui-Wen
Published: August 2016

Vero cell line has been routinely used for isolation and propagation of porcine epidemic diarrhea virus (PEDV), but isolation rate of PEDV in Vero cells has been demonstrated low, and the virus may gradually lose host infectivity upon in vitro passages. Besides, the entry mechanism of PEDV into Vero cells is also known to be cellular receptor (porcine aminopeptidase N; pAPN; CD13)-independent, which suggests that Vero cells might not be a suitable cell line for studying the interaction of PEDV with its receptor. To explore alternatives, a HEK 293 cell line stably expressing pAPN (HEK 293-pAPN) was established, and its susceptibility to PEDV infection was compared with Vero, HEK 293, and PK-15 cells. Interestingly, cytopathic effects characterized by cell fusion and multinuclear syncytial cells were observed in HEK 293, HEK 293-pAPN, and Vero cells after 48 h of inoculation, but not in PK-15 cells. Moreover, evidence of PEDV replication in these cell lines was also confirmed by immunocytochemistry staining and real-time quantitative PCR analysis. In conclusion, we demonstrated that HEK 293 cells, regardless of overexpression of pAPN molecules, are permissive to PEDV. HEK 293 cell line with its highly transfectable characteristic might not only serve as an alternative tool for studying the entry mechanisms of PEDV, but also a replication permissive cell line for virus rescue such as from the infectious clone of PEDV. Furthermore, the identification of a cell line of human origin, HEK 293, permissive to PEDV raises the concern of possible interspecies transmission.
An Improved Fault-to-Site Analysis Tool Towards Fully HPC-Enhanced Physics-Based Urban Area Response Estimation
Authors: Quinay Pher Errol B. , Ichimura Tsuyoshi
Published: August 2016

This paper describes the improvement to a fault-to-site analysis tool for use in a fully HPC-enhanced physics-based urban earthquake response analysis. We developed a three-step procedure, involving coarse and refined partitioning for the preprocessing stage, that achieves good balance in computational load and FE nodes used in communications. An end-to-end approach to computing in K computer was also implemented. The results of strong- and weak-scaling tests validate the capability of the tool for application to dynamic analysis involving billions of unknowns. In application to reproduction of observed ground motions, improvements in solution in comparison with previously conducted validations were obtained. The tool was also used to generate synthetic ground motions for analyzing the response of thousands of buildings in an urban area due to a scenario earthquake.
Climate Econometrics
Authors: Hsiang Solomon
Published: August 2016

Identifying the effect of climate on societies is central to understanding historical economic development, designing modern policies that react to climatic events, and managing future global climate change. Here, I review, synthesize, and interpret recent advances in methods used to measure effects of climate on social and economic outcomes. Because weather variation plays a large role in recent progress, I formalize the relationship between climate and weather from an econometric perspective and discuss the use of these two factors as identifying variation, highlighting trade-offs between key assumptions in different research designs and deriving conditions when weather variation exactly identifies the effects of climate. I then describe recent advances, such as the parameterization of climate variables from a social perspective, use of nonlinear models with spatial and temporal displacement, characterization of uncertainty, measurement of adaptation, cross-study comparison, and use of empirical estimates to project the impact of future climate change. I conclude by discussing remaining methodological challenges.
Tombusvirus-Host Interactions: Co-Opted Evolutionarily Conserved Host Factors Take Center Court
Authors: Nagy Peter D.
Published: August 2016

Plant positive-strand (+)RNA viruses are intracellular infectious agents that reorganize subcellular membranes and rewire the cellular metabolism of host cells to achieve viral replication in elaborate replication compartments. This review describes the viral replication process based on tombusviruses, highlighting common strategies with other plant and animal viruses. Overall, the works on Tomato bushy stunt virus (TBSV) have revealed intriguing and complex functions of co-opted cellular translation factors, heat shock proteins, DEAD-box helicases, lipid transfer proteins, and membrane-deforming proteins in virus replication. The emerging picture is that many of the co-opted host factors are from highly expressed and conserved protein families. By hijacking host proteins, phospholipids, sterols, and the actin network, TBSV exerts supremacy over the host cell to support viral replication in large replication compartments. Altogether, these advances in our understanding of tombusvirus-host interactions are broadly applicable to many other viruses, which also usurp conserved host factors for various viral processes.
Epstein-Barr Virus: The Path from Latent to Productive Infection
Authors: Chiu Ya-Fang , Sugden Bill
Published: August 2016

The intrinsic properties of different viruses have driven their study. For example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. Epstein-Barr virus, another herpesvirus, has two properties that have driven its study: It causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. Here, we review our understanding of the path Epstein-Barr virus follows to move from a latent infection to and through its productive cycle. We use information from human infections to provide a framework for describing studies in cell culture and, where possible, the molecular resolutions from these studies. We also pose questions whose answers we think are pivotal to understanding this path, and we provide answers where we can.
Tetrahydrobiopterin oral therapy recouples eNOS and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs
Authors: Dikalova Anna , Aschner Judy L. , Kaplowitz Mark R. , Summar Marshall , Fike Candice D.
Published: August 2016

We previously showed that newborn piglets who develop pulmonary hypertension during exposure to chronic hypoxia have diminished pulmonary vascular nitric oxide (NO) production and evidence of endothelial NO synthase (eNOS) uncoupling (Fike CD, Dikalova A, Kaplowitz MR, Cunningham G, Summar M, Aschner JL. Am J Respir Cell Mol Biol 53: 255–264, 2015). Tetrahydrobiopterin (BH4) is a cofactor that promotes eNOS coupling. Current clinical strategies typically invoke initiating treatment after the diagnosis of pulmonary hypertension, rather than prophylactically. The major purpose of this study was to determine whether starting treatment with an oral BH4 compound, sapropterin dihydrochloride (sapropterin), after the onset of pulmonary hypertension would recouple eNOS in the pulmonary vasculature and ameliorate disease progression in chronically hypoxic piglets. Normoxic (control) and hypoxic piglets were studied. Some hypoxic piglets received oral sapropterin starting on day 3 of hypoxia and continued throughout an additional 7 days of hypoxic exposure. Catheters were placed for hemodynamic measurements, and pulmonary arteries were dissected to assess eNOS dimer-to-monomer ratios (a measure of eNOS coupling), NO production, and superoxide (O2·−) generation. Although higher than in normoxic controls, pulmonary vascular resistance was lower in sapropterin-treated hypoxic piglets than in untreated hypoxic piglets. Consistent with eNOS recoupling, eNOS dimer-to-monomer ratios and NO production were greater and O2·− generation was less in pulmonary arteries from sapropterin-treated than untreated hypoxic animals. When started after disease onset, oral sapropterin treatment inhibits chronic hypoxia-induced pulmonary hypertension at least in part by recoupling eNOS in the pulmonary vasculature of newborn piglets. Rescue treatment with sapropterin may be an effective strategy to inhibit further development of pulmonary hypertension in newborn infants suffering from chronic cardiopulmonary conditions associated with episodes of prolonged hypoxia.
Pathophysiologic evaluation of the transgenic CFTR “gut-corrected” porcine model of cystic fibrosis
Authors: Ballard Stephen T. , Evans Jessica W. , Drag Holly S. , Schuler Michele
Published: August 2016

This study evaluated the pulmonary pathophysiology of pigs with transgenic CFTR “gut-corrected” cystic fibrosis (CF). Four sows produced 18 piglets of which 11 were stillborn, with only 2 animals surviving beyond 2 wk. Failure to survive beyond the neonatal period by five piglets was judged to result from metabolic dysfunction related to genetic manipulation for CFTR gut expression or due to cloning artifact. Plasma analysis showed very low plasma proteins, highly elevated liver enzymes, and severe acidosis. All surviving offspring received furosemide for systemic edema. Physiologic evaluation was performed with lung tissues from the two surviving pigs. Both acetylcholine and forskolin induced mucous liquid secretion that was significantly lower in bronchi of pigs with CF than those without CF. The percent of nonvolatile solids in mucus secreted from CF bronchi was elevated following acetylcholine or forskolin treatment. Mucociliary transport in excised tracheas was reduced in the CF tracheas relative to non-CF tracheas. The diameter of tracheas in pigs with CF was less than that of pigs without CF despite their greater body weight. Despite exhibiting severe metabolic dysfunction during the neonatal period, this CF animal model appears to express important characteristics of human CF pulmonary disease.
Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat
Authors: Matsukawa Kanji , Ishii Kei , Asahara Ryota , Idesako Mitsuhiro
Published: August 2016

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade.
Attenuation of exercise effect on inflammatory responses via novel role of TLR4/PI3K/Akt signaling in rat splenocytes
Authors: Chen Chien-Wei , Chen Chih-Chieh , Jian Cai-Yun , Lin Po-Han , Chou Jou-Chun , Teng Hsueh-Su , Hu Sindy , Lieu Fu-Kong , Wang Paulus S. , Wang Shyi-Wu
Published: August 2016

Moderate exercise diminishes proinflammation cytokine production in various types of immune cells, but the intracellular signaling pathways involved are not completely understood. Phosphoinositide 3-kinase (PI3K)/Akt, a crucial downstream protein of toll-like receptor 4 (TLR4), may modulate inflammation. The present study aimed to investigate the effects of exercises on lipopolysaccharide (LPS)-stimulated inflammatory response in splenocytes and to explore potential mechanisms of the PI3K/Akt pathway. Male rats were divided into sedentary and exercise groups. Animals in the exercise group underwent endurance training 30 min/day, 7 days/wk, at the speed of 20 m/min on a treadmill for 1 wk. Here, we showed that exercise 1) attenuated TLR4, 2) increased PI3K/phospho-Akt (p-Akt), and 3) diminished phospho-nuclear factor-κB (p-NF-κB) expression. In addition, administration of splenocytes isolated from trained rats with LPS in vitro showed 1) reduced tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and nitric oxide secretion and 2) decreased splenocyte proliferation. The plasma corticosterone (CCS) level in the exercise group was higher than that in the sedentary group. We confirmed that CCS down-regulated TNF-α and IL-6 secretion in response to LPS in rat splenocytes. Dexamethasone also significantly attenuated LPS-evoked release of TNF-α and IL-6 in a dose-dependent manner. These findings suggested that exercise dampened the secretion of inflammation mediators probably through partial inhibition of TLR4 and p-NF-κB and activation of PI3K/p-Akt expression in the spleen.
In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use
Authors: Kent Jane A. , Fitzgerald Liam F.
Published: August 2016

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo. These changes include both the maximal capacity for oxidative production of energy (ATP), as well as the relative use of mitochondrial ATP production for powering muscular activity. It has been known for nearly 50 yr that muscle mitochondrial content is highly plastic; exercise training can induce an ∼2-fold increase in mitochondrial content, while disuse has the opposite effect. Here, we suggest that a portion of the age-related changes in mitochondrial function that have been reported are likely the result of behavioral effects, as physical activity influences have not always been accounted for. Further, there is emerging evidence that various muscles may be affected differently by age-related changes in physical activity and movement patterns. In this review, we will focus on age-related changes in oxidative capacity and flux measured in vivo in human skeletal muscle.
Influence of exercise and aging on extracellular matrix composition in the skeletal muscle stem cell niche
Authors: Garg Koyal , Boppart Marni D.
Published: August 2016

Skeletal muscle is endowed with a remarkable capacity for regeneration, primarily due to the reserve pool of muscle resident satellite cells. The satellite cell is the physiologically quiescent muscle stem cell that resides beneath the basal lamina and adjacent to the sarcolemma. The anatomic location of satellite cells is in close proximity to vasculature where they interact with other muscle resident stem/stromal cells (e.g., mesenchymal stem cells and pericytes) through paracrine mechanisms. This mini-review describes the components of the muscle stem cell niche, as well as the influence of exercise and aging on the muscle stem cell niche. Although exercise promotes ECM reorganization and stem cell accumulation, aging is associated with dense ECM deposition and loss of stem cell function resulting in reduced regenerative capacity and strength. An improved understanding of the niche elements will be valuable to inform the development of therapeutic interventions aimed at improving skeletal muscle regeneration and adaptation over the life span.
Sister Mary Joseph Nodule as a First Manifestation of a Metastatic Ovarian Cancer
Authors: Calongos Giannina , Ogino Mai , Kinuta Takatoshi , Hori Masateru , Mori Tatsuo
Published: August 2016

A 76-year-old female presented to our hospital with a 2 cm firm, nontender, protuberant umbilical nodule. She received treatment with antibiotics for suspected granuloma, with no improvement after two months. High levels of CA125 as well as an ovarian cyst and intrathoracic and intra-abdominal lesions on imaging studies made us suspect an ovarian cancer with a Sister Mary Joseph nodule (SMJN) and other metastases. A bilateral salpingo-oophorectomy and umbilical and omentum tumor resections were performed and a metastatic ovarian serous adenocarcinoma was diagnosed by histopathology. After surgery, the patient received chemotherapy with paclitaxel, carboplatin, and bevacizumab; however paclitaxel allergy was observed. As a result, chemotherapy continued with carboplatin and bevacizumab every three weeks for a total of 6 courses. Currently, she is still undergoing treatment with bevacizumab and CA125 levels have been progressively decreasing. SMJN is a rare umbilical metastasis which needs to be considered as a differential diagnosis in the presence of an umbilical tumor for prompt treatment initiation.
S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure
Authors: Koo Sue-jie , Spratt Heidi M. , Soman Kizhake V. , Stafford Susan , Gupta Shivali , Petersen John R. , Zago Maria P. , Kuyumcu-Martinez Muge N. , Brasier Allan R. , Wiktorowicz John E. , Garg Nisha Jain
Published: August 2016

Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can affect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL-maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls,n=30/group). We identified 93 differentially abundant (59-increased/34-decreased) and 111 S-NO-modified (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change| ≥1.5|,p≤0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes’ migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identified a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profiling identified ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top differentially abundant and S-NO-modified proteins, and these proteins were verified by Western blotting and ELISA in different set of HF subjects. We conclude that differential abundance and S-NO modification of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure.
Selection of an Interval for Variable Shape Parameter in Approximation by Radial Basis Functions
Authors: Biazar Jafar , Hosami Mohammad
Published: August 2016

In radial basis function approximation, the shape parameter can be variable. The values of the variable shape parameter strategies are selected from an interval which is usually determined by trial and error. As yet there is not any algorithm for determining an appropriate interval, although there are some recipes for optimal values. In this paper, a novel algorithm for determining an interval is proposed. Different variable shape parameter strategies are examined. The results show that the determined interval significantly improved the accuracy and is suitable enough to count on in variable shape parameter strategies.
Oral Chinese Herbal Medicine for Treatment of Dilated Cardiomyopathy: A Systematic Review and Meta‐Analysis
Authors: Zhu Yu-Shuo , Li Yun-Lun , Ju Jian-Qing , Du Feng , Zang Yan-Ping , Wang Xiao-Bing , Sheng Jie
Published: August 2016

Dilated cardiomyopathy (DCM) is one of the main causes of heart failure and could increase death, hospitalization, and rehospitalization rate. The effect of conventional medicine treatment (CMT) is limited; meanwhile, the combination of CMT and Oral Chinese Herbal Medicine (OCHM) represents exciting adjunctive therapies. In this study, we ascertained the therapeutic effect of OCHM in combination with CMT for dilated cardiomyopathy by using meta‐analysis methods for controlled clinical trials. We searched studies from five databases and extracted data from these studies. We also assessed the methodological quality of the included studies. We evaluated the following outcome measures to estimate the prognosis in patients with DCM: left ventricular ejection fraction (LVEF), left ventricular end‐diastolic dimension (LVEDD), stroke volume (SV), brain natriuretic peptide (BNP), 6‐minute walk test (6MWT), and overall efficacy. The result showed that OCHM combined with CMT for the improvement of therapeutic effect in DCM patients. However, the evidence remains weak due to the small sample size, high clinical heterogeneity, and poor methodological quality of the included trials. Further, large sample size and well‐designed trials are needed.
Applications of Chondrocyte-Based Cartilage Engineering: An Overview
Authors: Phull Abdul-Rehman , Eo Seong-Hui , Abbas Qamar , Ahmed Madiha , Kim Song Ja
Published: August 2016

Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes.
Modulatory Effect of Eui‐E‐In‐Tang on Serum Leptin Concentration in Obese Korean Female Adults: A Randomized Controlled Trial
Authors: Song Yun-Kyung , Lee Ji-Young , Park Wansu
Published: August 2016

Background. Obesity is associated with chronic inflammation and cytokines. However, to date, the relationship between the serum levels of cytokines in obese individuals and taking herbal drugs remains largely unexplored. Methods. Serum cytokines were assessed by multiplex cytokine profiling assay. Serum samples of obese female Korean adults (obese group; n = 20) as well as normal female Korean adults (normal group; n = 21) were collected at the start and end of study period. Twenty obese female Korean adults were randomized to receive Eui‐E‐In‐Tang (Eui‐E‐In‐Tang group; n = 9) at a daily dose of 9 g or a matched placebo (placebo group; n = 11) for 12 weeks. Results. According to investigating serum cytokine levels at the start point of this study, the serum C‐peptide, insulin, leptin, lipocalin‐2, and adipsin levels in the obese group were found to be significantly higher than in the normal group. And the investigation of serum cytokine levels at the end point of this study demonstrated that mean serum leptin of Eui‐E‐In‐Tang group was found to be significantly reduced (P = 0.037). Conclusions. This study provides preliminary evidence that Eui‐E‐In‐Tang may exert immunomodulatory effect via altering the circulating concentration of leptin in Korean female adults.
Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications
Authors: Tarnowski Maciej , Czerewaty Michał , Deskur Anna , Safranow Krzysztof , Marlicz Wojciech , Urasińska Elżbieta , Ratajczak Mariusz Z. , Starzyńska Teresa
Published: August 2016

Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined.Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status.Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine.Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p<0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients.Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells.
Presynaptic Proteins as Markers of the Neurotoxic Activity of BmjeTX-I and BmjeTX-II Toxins fromBothrops marajoensis(Marajó Lancehead) Snake Venom
Authors: Lisboa Antonio , Melaré Rodolfo , Franco Junia R. B. , Bis Carolina V. , Gracia Marta , Ponce-Soto Luis A. , Marangoni Sérgio , Rodrigues-Simioni Léa , da Cruz-Höfling Maria Alice , Rocha Thalita
Published: August 2016

Neuromuscular preparations exposed toB. marajoensisvenom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposedin vitroto BmjeTX-I and BmjeTX-II toxins fromB. marajoensisvenom. CBC incubated with toxins showed irreversible twitch tension blockade and unaffected KCl- and ACh-evoked contractures, and the positive colabelling of acetylcholine receptors confirmed that their action was primarily at the motor nerve terminal. Hypercontraction and loose myofilaments and synaptic vesicle depletion and motor nerve damage indicated that the toxins displayed both myotoxic and neurotoxic effect. The blockade resulted from interference on synaptophysin, synaptobrevin, and SNAP25 proteins leading to the conclusion that BmjeTX-I and BmjeTX-II affected neurotransmitter release machinery by preventing the docking of synaptic vesicles to the axolemma of the nerve terminal.
In VitroandIn VivoAnti-HelicobacterActivities ofEryngium foetidum(Apiaceae),Bidens pilosa(Asteraceae), andGalinsoga ciliata(Asteraceae) againstHelicobacter pylori
Authors: Kouitcheu Mabeku Laure brigitte , Eyoum Bille Bertrand , Nguepi Eveline
Published: August 2016

This study was performed to evaluate the antimicrobial activities of extracts ofBidens pilosa, Galinsoga ciliata,andEryngium foetidumagainst 6 clinical strains ofHelicobacter pylori in vitroandin vivo. Broth microdilution method was usedin vitro.In vivo, Swiss mice were inoculated withH.pyloriand divided into 5 groups; the control group received the vehicle and the four others received 125, 250, and 500 mg/kg of methanol extract ofEryngium foetidumand ciprofloxacin (500 mg/kg) for 7 days, respectively.Helicobacter pyloricolonization and number of colonies in gastric biopsies culture were assessed on days 1 and 7 after treatment. The lowest MIC value (64 μg/mL) and the best spectrum of bactericidal effect (MBC/MIC = 1) were obtained with the methanol extract ofEryngium foetidum. The number ofH.pyloriinfected animals was 17% (plant-extract) and 0% (ciprofloxacin) compared to 100% for the infected untreated group. Plant-extract (381.9±239.5 CFU) and ciprofloxacin (248±153.2 CFU) significantly reduced bacterial load in gastric mucosa compared to untreated, inoculated mice (14350±690 CFU).Conclusion. The present data provided evidence that methanol extract ofEryngium foetidumcould be a rich source of metabolites with antimicrobial activity to fightHelicobacter pyloriinfections.
Longitudinal/Lateral Stability Analysis of Vehicle Motion in the Nonlinear Region
Authors: Chen Keji , Pei Xiaofei , Ma Guocheng , Guo Xuexun
Published: August 2016

We focus on the study of motion stability of vehicle nonlinear dynamics. The dynamic model combining with Burckhardt tire model is firstly derived. By phase portrait method, the vehicle stability differences of three cases, front wheels steering/four-wheel steering case, front/rear/four-wheel braking case, and high/low road friction case, are characterized. With the Jacobian matrix, the stable equilibrium point is found and stable areas are calculated out. Similarly, the stability boundaries corresponding to different working conditions are also captured. With vehicle braking or accelerating in the steering process, the relationship between front/rear wheel slippage and the stable area is examined. Comparing with current literatures, the research method and its results present the novelty and provide a guideline for new vehicle controller design.
Estimation of the Relative Contribution of Postprandial Glucose Exposure to Average Total Glucose Exposure in Subjects with Type 2 Diabetes
Authors: Ahrén Bo , Foley James E.
Published: August 2016

We hypothesized that the relative contribution of fasting plasma glucose (FPG) versus postprandial plasma glucose (PPG) to glycated haemoglobin (HbA1c) could be calculated using an algorithm developed by the A1c-Derived Average Glucose (ADAG) study group to make HbA1c values more clinically relevant to patients. The algorithm estimates average glucose (eAG) exposure, which can be used to calculate apparent PPG (aPPG) by subtracting FPG. The hypothesis was tested in a large dataset (comprising 17 studies) from the vildagliptin clinical trial programme. We found that 24 weeks of treatment with vildagliptin monotherapy (n=2523) reduced the relative contribution of aPPG to eAG from 8.12% to 2.95% (by 64%,p<0.001). In contrast, when vildagliptin was added to metformin (n=2752), the relative contribution of aPPG to eAG insignificantly increased from 1.59% to 2.56%. In conclusion, glucose peaks, which are often prominent in patients with type 2 diabetes, provide a small contribution to the total glucose exposure assessed by HbA1c, and the ADAG algorithm is not robust enough to assess this small relative contribution in patients receiving combination therapy.