bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats
Authors: Gui Le , LaGrange Lila P. , Larson Robert A. , Gu Mingjun , Zhu Jianhua , Chen Qing-Hui
Published: May 2012

Small conductance Ca2+-activated K+(SK) channels regulate membrane properties of rostral ventrolateral medulla (RVLM) projecting hypothalamic paraventricular nucleus (PVN) neurons and inhibition of SK channels increases in vitro excitability. Here, we determined in vivo the role of PVN SK channels in regulating sympathetic nerve activity (SNA) and mean arterial pressure (MAP). In anesthetized rats, bilateral PVN microinjection of SK channel blocker with peptide apamin (0, 0.125, 1.25, 3.75, 12.5, and 25 pmol) increased splanchnic SNA (SSNA), renal SNA (RSNA), MAP, and heart rate (HR) in a dose-dependent manner. Maximum increases in SSNA, RSNA, MAP, and HR elicited by apamin (12.5 pmol, n = 7) were 330 ± 40% ( P < 0.01), 271 ± 40% ( P < 0.01), 29 ± 4 mmHg ( P < 0.01), and 34 ± 9 beats/min ( P < 0.01), respectively. PVN injection of the nonpeptide SK channel blocker UCL1684 (250 pmol, n = 7) significantly increased SSNA ( P < 0.05), RSNA ( P < 0.05), MAP ( P < 0.05), and HR ( P < 0.05). Neither apamin injected outside the PVN (12.5 pmol, n = 6) nor peripheral administration of the same dose of apamin (12.5 pmol, n = 5) evoked any significant changes in the recorded variables. PVN-injected SK channel enhancer 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO, 5 nmol, n = 4) or N-cyclohexyl- N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidin]amine (CyPPA, 5 nmol, n = 6) did not significantly alter the SSNA, RSNA, MAP, and HR. Western blot and RT-PCR analysis of punched PVN tissue showed abundant expression of SK1-3 channels. We conclude that SK channels expressed in the PVN play an important role in the regulation of sympathetic outflow and cardiovascular function.
Possible role of brain salt-inducible kinase 1 in responses to central sodium in Dahl rats
Authors: Huang Bing S. , White Roselyn A. , Leenen Frans H. H.
Published: May 2012

In Dahl salt-sensitive (S) rats, Na+ entry into the cerebrospinal fluid (CSF) and sympathoexcitatory and pressor responses to CSF Na+ are enhanced. Salt-inducible kinase 1 (SIK1) increases Na+/K+-ATPase activity in kidney cells. We tested the possible role of SIK1 in regulation of CSF [Na+] and responses to Na+ in the brain. SIK1 protein and activity were lower in hypothalamic tissue of Dahl S (SS/Mcw) compared with salt-resistant SS.BN13 rats. Intracerebroventricular infusion of the protein kinase inhibitor staurosporine at 25 ng/day, to inhibit SIK1 further increased mean arterial pressure (MAP) and HR but did not affect the increase in CSF [Na+] or hypothalamic aldosterone in Dahl S on a high-salt diet. Intracerebroventricular infusion of Na+-rich artificial CSF caused significantly larger increases in renal sympathetic nerve activity, MAP, and HR in Dahl S vs. SS.BN13 or Wistar rats on a normal-salt diet. Intracerebroventricular injection of 5 ng staurosporine enhanced these responses, but the enhancement in Dahl S rats was only one-third that in SS.BN13 and Wistar rats. Staurosporine had no effect on MAP and HR responses to intracerebroventricular ANG II or carbachol, whereas the specific protein kinase C inhibitor GF109203X inhibited pressor responses to intracerebroventricular Na+-rich artificial CSF or ANG II. These results suggest that the SIK1-Na+/K+-ATPase network in neurons acts to attenuate sympathoexcitatory and pressor responses to increases in brain [Na+]. The lower hypothalamic SIK1 activity and smaller effect of staurosporine in Dahl S rats suggest that impaired activation of neuronal SIK1 by Na+ may contribute to their enhanced central responses to sodium.
Ca2+/calmodulin-dependent protein kinase II is associated with pelvic pain of neurogenic cystitis
Authors: Yang Wenbin , Rudick Charles N. , Hoxha Eneda , Allsop Stephen A. , Dimitrakoff Jordan D. , Klumpp David J.
Published: May 2012

Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. Interstitial cystitis is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area. In this study, we used a murine neurogenic cystitis model to identify genes participating in the development of pelvic pain. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic pain. The sacral spinal cord was harvested on postinfection days (PID) 2 and 4, and gene expression was analyzed by microarrays and confirmed by quantitative RT-PCR. On PID 2, the overall expression profile was similar to that of uninfected sacral spinal cord; by PID 4, there were substantial differences in expression of multiple functional classes of genes, especially inflammation. Analysis of pain-signaling pathways at the dorsal horn suggested that Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain. Consistent with this, CaMKIIδ expression exhibited a mast cell-dependent increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII immunoreactivity in the dorsal horn was increased on postinfection day (PID) 4 during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN-93 attenuated the PRV pain response. These data suggest that CaMKII plays a functional role in pelvic pain due to neurogenic cystitis.
Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses
Authors: Witkowska Kate , Smith Kyla M. , Yao Sylvia Y. M. , Ng Amy M. L. , O'Neill Debbie , Karpinski Edward , Young James D. , Cheeseman Christopher I.
Published: May 2012

Human SLC2A9 (GLUT9) is a novel high-capacity urate transporter belonging to the facilitated glucose transporter family. In the present study, heterologous expression in Xenopus oocytes has allowed us to undertake an in-depth radiotracer flux and electrophysiological study of urate transport mediated by both isoforms of SLC2A9 (a and b). Addition of urate to SLC2A9-producing oocytes generated outward currents, indicating electrogenic transport. Urate transport by SLC2A9 was voltage dependent and independent of the Na+ transmembrane gradient. Urate-induced outward currents were affected by the extracellular concentration of Cl−, but there was no evidence for exchange of the two anions. [14C]urate flux studies under non-voltage-clamped conditions demonstrated symmetry of influx and efflux, suggesting that SLC2A9 functions in urate efflux driven primarily by the electrochemical gradient of the cell. Urate uptake in the presence of intracellular hexoses showed marked differences between the two isoforms, suggesting functional differences between the two splice variants. Finally, the permeant selectivity of SLC2A9 was examined by testing the ability to transport a panel of radiolabeled purine and pyrimidine nucleobases. SLC2A9 mediated the uptake of adenine in addition to urate, but did not function as a generalized nucleobase transporter. The differential expression pattern of the two isoforms of SLC2A9 in the human kidney's proximal convoluted tubule and its electrogenic transport of urate suggest that these transporters play key roles in the regulation of plasma urate levels and are therefore potentially important participants in hyperuricemia and hypouricemia.
HIV-induced kidney cell injury: role of ROS-induced downregulated vitamin D receptor
Authors: Salhan Divya , Husain Mohammad , Subrati Ashaan , Goyal Rohan , Singh Tejinder , Rai Partab , Malhotra Ashwani , Singhal Pravin C.
Published: May 2012

Reactive oxygen species (ROS) have been demonstrated to contribute to HIV-induced tubular cell injury. We hypothesized that HIV-induced ROS generation may be causing tubular cell injury through downregulation of vitamin D receptor (VDR) and associated downstream effects. In the present study, HIV not only downregulated tubular cell VDR expression but also inflicted DNA injury. On the other hand, EB-1089, a VDR agonist (VD), inhibited both downregulation of VDR and tubular cell DNA injury in the HIV milieu. H2O2(an O−donor) directly downregulated tubular cell VDR, whereas catalase, a free radical scavenger, inhibited HIV-induced downregulation of tubular cell VDR expression. HIV also stimulated the tubular cell renin-angiotensin system (RAS) through downregulation of VDR. Because losartan (an ANG II blolcker) partially inhibited HIV-induced tubular cell ROS generation while ANG II directly stimulated tubular cell ROS generation, it appears that HIV-induced ROS production was partly contributed by the RAS activation. VD not only inhibited HIV-induced RAS activation but also attenuated tubular cell ROS generation. Tubular cells displayed double jeopardy in the HIV milieu induction of double-strand breaks and attenuated DNA repair; additionally, in the HIV milieu, tubular cells exhibited enhanced expression of phospho-p53 and associated downstream signaling. A VDR agonist and an ANG II blocker not only preserved expression of tubular cell DNA repair proteins but also inhibited induction of double-strand breaks. In in vivo studies, renal cortical sections of Tg26 mice displayed attenuated expression of VDR both in podocytes and tubular cells. In addition, renal cortical sections of Tg26 mice displayed enhanced oxidative stress-induced kidney cell DNA damage. These findings indicated that HIV-induced tubular cell downregulation of VDR contributed to the RAS activation and associated tubular cell DNA damage. However, both VD and RAS blockade provided protection against these effects of HIV.
Acute Exercise Increases Adiponectin Levels in Abdominally Obese Men
Authors: Saunders Travis J. , Palombella Andrew , McGuire K. Ashlee , Janiszewski Peter M. , Després Jean-Pierre , Ross Robert
Published: May 2012

Objective. To examine the effect of acute and short-term (~1 week) aerobic exercise training on plasma adiponectin levels in inactive, abdominally obese men.Materials and Methods. Inactive and abdominally obese men (n=38, waist circumference ≥102 cm) recruited from Kingston, Canada were randomly allocated to perform three bouts of aerobic treadmill exercise at either low (50% VO2peak) or high (75% VO2peak) intensity during a 1-week period. Blood samples were taken before and after the first exercise session and 24–72 hours following the completion of the final exercise session.Results. Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities (High:5.79±0.42versus5.05±0.41 ug/mL; Low:5.24±0.44versus4.37±0.44 ug/mL,P<0.05) and remained elevated following 30 minutes of rest. In comparison to baseline, adiponectin levels were also elevated 24–72 hours following the final exercise session (High:5.47±0.48versus4.88±0.48 ug/mL; Low:5.18±0.49versus4.47±0.49 ug/mL,P<0.05).Conclusion. Both acute and short-term aerobic exercise result in a significant increase in plasma adiponectin levels in inactive, abdominally obese men independent of intensity.
Stabilization of Bilateral Progressive Rheumatoid Corneal Melt with Infliximab
Authors: Antao Sheelah F. , Ayoub Tariq , Tahir Hasan , Parmar Dipak N.
Published: May 2012

Purpose. To report the use of infliximab in the rapid stabilization of a case of progressive, bilateral rheumatoid peripheral ulcerative keratitis (PUK) that failed to respond to conventional immunosuppressive therapy.Methods. A single interventional case report.Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN) and methotrexate (MTX) were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT), and penetrating keratoplasty (PKP). Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation.Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment.
Treadmill Training in Multiple Sclerosis: Can Body Weight Support or Robot Assistance Provide Added Value? A Systematic Review
Authors: Swinnen Eva , Beckwée David , Pinte Droesja , Meeusen Romain , Baeyens Jean-Pierre , Kerckhofs Eric
Published: May 2012

Purpose. This systematic review critically analyzes the literature on the effectiveness of treadmill training (TT), body-weight-supported TT (BWSTT), and robot-assisted TT (RATT) in persons with multiple sclerosis (MS), with focus on gait-related outcome measurements.Method. Electronic databases (Pubmed, Pedro, Web of Science, and Cochrane Library) and reference lists of articles and narrative reviews were searched. Pre-, quasi- and true-experimental studies were included if adult persons with MS were involved in TT, BWSTT, or RATT intervention studies published before 2012. Descriptive analysis was performed and two researchers scored the methodological quality of the studies.Results. 5 true- and 3 preexperimental studies (mean quality score: 66%) have been included. In total 161 persons with MS were involved (TT, BWSTT, or RATT, 6–42 sessions; 2–5x/week; 3–21 weeks). Significant improvements in walking speed and endurance were reported. Furthermore, improvements of step length, double-support time, and Expanded Disability Status Scale were found.Conclusions. There is a limited number of published papers related to TT in persons with MS, concluding that TT, BWSTT, and RATT improve the walking speed and endurance. However, it is not clear what type of TT is most effective. RCTs with larger but more homogeneous populations are needed.
Antimicrobial Constituents ofArtemisia afraJacq. ex Willd. against Periodontal Pathogens
Authors: More Garland , Lall Namrita , Hussein Ahmed , Tshikalange Thilivhali Emmanuel
Published: May 2012

The phytochemical investigation of an ethanol extract ofArtemisia afraled to the isolation of six known compounds, acacetin(1), 12α,4α-dihydroxybishopsolicepolide(2), scopoletin(3),α-amyrin(4), phytol(5), and a pentacyclic triterpenoid betulinic acid(6). The compounds were evaluated for antimicrobial activity against Gram positive (Actinomyces naeslundii, Actinomyces israelii,andStreptococcus mutans), Gram negative bacteria (Prevotella intermedia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitanspreviously known asActinobacillus actinomycetemcomitans), andCandida albicans. The crude extract ofA. afrainhibited the growth of all tested microbial species at concentration range of 1.6 mg/mL to 25 mg/mL. The compounds 1–6 also showed activity range at 1.0 mg/mL to 0.25 mg/mL. Three best compounds (scopoletin, betulinic acid, and acacetin) which showed good antimicrobial activity were selected for further studies. Cytotoxicity of extract and compounds was determined using the XTT cell proliferation kit. The antioxidant activity of the extract and compounds was done using the DPPH scavenging method. The extract showed good antioxidant activity with an IC50value of 22.2 μg/mL. Scopoletin had a strong transformation of the DPPH radical into its reduced form, with an IC50value of 1.24 μg/mL which was significant to that of vitamin C (1.22 μg/mL). Acacetin and betulinic acid exhibited a decreased scavenging activity with the IC50of 2.39 and 2.42 μg/mL, respectively. The extract and compounds showed moderate toxicity on McCoy fibroblast cell line and scopoletin was relatively nontoxic with an IC50value of 132.5 μg/mL. Acacetin and betulinic acid also showed a smooth trend of non-toxic effects with IC50values of 35.44 and 30.96 μg/mL. The obtained results in this study confirm the use ofA. afrain the treatment of microbial infections.
Yang-Dan-Tang, Identified from 15 Chinese Herbal Formulae, Inhibits Human Lung Cancer Cell Proliferation via Cell Cycle Arrest
Authors: Wang Tien-Chun , Fang Chih-Nan , Shen Chih-Chien , Wei Hui-Yu , Weng Yui-Ping , Lin Jung-Yaw , Hsieh-Li Hsiu Mei , Lee Chen-Yu
Published: May 2012

Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients.
Negative Pressure Wound Therapy Literature Review of Efficacy, Cost Effectiveness, and Impact on Patients' Quality of Life in Chronic Wound Management and Its Implementation in the United Kingdom
Authors: Othman Diaa
Published: May 2012

This is a paper reviewing the National Health Service (NHS) agenda in relation to the use of Negative Pressure Wound Therapy (NPWT) in chronic wound management and assesses the evidence behind it, its cost effectiveness and the outcome it has on patients’ satisfaction and life style. Multiple studies over the last 10 years looking at clinical efficacy of NPWT with its cost effectiveness and the implementation of this service in the UK were reviewed. NPWT has showed a reasonable body of evidence to support its usage in chronic wounds with potential positive outcomes on finance and patients’ satisfaction. However, the NHS system shows significant variations in the availability and implementation of this useful tool, depending on care providers and resources availabilities. The paper concluded that the NPWT can be a useful source of cutting down costs of chronic wound managements and saving money by its effect on expediting wound healing, which can address a part of the financial crises facing the NHS, however, has to be considered according to specific case needs. There should also be a national standard for the availability and indication of this tool to assure equal opportunities for different patients in different areas in the country.
Biocompatible Single‐Crystal Selenium Nanobelt Based Nanodevice as a Temperature‐Tunable Photosensor
Authors: Niu Yongshan , Qin Aimiao , Song Wei , Wang Menghang , Gu Xuenan , Zhang Yangfei , Yu Min , Zhao Xiaoguang , Dai Ming , Yan Ling , Li Zhou , Fan Yubo
Published: May 2012

Selenium materials are widely used in photoelectrical devices, owing to their unique semiconductive properties. Single‐crystal selenium nanobelts with large specific surface area, fine photoconductivity, and biocompatibility provide potential applications in biomedical nanodevices, such as implantable artificial retina and rapid photon detector/stimulator for optogenetics. Here, we present a selenium nanobelt based nanodevice, which is fabricated with single Se nanobelt. This device shows a rapid photo response, different sensitivities to visible light of variable wave length, and temperature‐tunable property. The biocompatibility of the Se nanobelts was proved by MTT test using two cell lines. Our investigation introduced a photosensor that will be important for multiple potential applications in human visual system, photocells in energy or MEMS, and temperature‐tunable photoelectrical device for optogenetics research.
Reactive Oxygen Species-Mediated Control of Mitochondrial Biogenesis
Authors: Yoboue Edgar D. , Devin Anne
Published: May 2012

Mitochondrial biogenesis is a complex process. It necessitates the contribution of both the nuclear and the mitochondrial genomes and therefore crosstalk between the nucleus and mitochondria. It is now well established that cellular mitochondrial content can vary according to a number of stimuli and physiological states in eukaryotes. The knowledge of the actors and signals regulating the mitochondrial biogenesis is thus of high importance. The cellular redox state has been considered for a long time as a key element in the regulation of various processes. In this paper, we report the involvement of the oxidative stress in the regulation of some actors of mitochondrial biogenesis.
Energy and Redox Homeostasis in Tumor Cells
Authors: de Oliveira Marcus Fernandes , Amoêdo Nívea Dias , Rumjanek Franklin David
Published: May 2012

Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1). The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.
Endocarditis-Induced Mycotic Brain Aneurysm following Right MCA Stroke
Authors: Allen Brandon , Desai Bobby , Falgiani Michael
Published: May 2012

The diagnosis of cerebrovascular accident is extremely common in emergency medicine; however, CVA resulting from hemorrhage following mycotic brain aneurysm following embolic stroke is extremely uncommon. This case reports such an event.
Magnetic Plasmon Sensing in Twisted Split-Ring Resonators
Authors: Cao J. X. , Liu H. , Wang S. M. , Zheng Y. J. , Zhu C. , Wang Y. , Zhu S. N.
Published: May 2012

We studied the sensing properties of stereo-SRRs metamaterials composed from two twisted split-ring resonators (SRRs). Due to the strong hybridization effect in the system, the polarization state of the transmitted wave is greatly changed at resonances. Since the stereo-SRRs structure is strongly coupled to the surrounding medium, the polarization change of the transmitted waves is quite sensitive to the refractive index change of the environment medium. The polarization ratio PRtran = Ty/Tx is used as sensing parameter and its figure of merit can reach 22.3 at the hybridized magnetic plasmon resonance. The results showed that the stereo-SRRs metamaterial can be applied to optical sensors an or other related field.
Sex Differences Associated with Primary Biliary Cirrhosis
Authors: Smyk Daniel S. , Rigopoulou Eirini I. , Pares Albert , Billinis Charalambos , Burroughs Andrew K. , Muratori Luigi , Invernizzi Pietro , Bogdanos Dimitrios P.
Published: May 2012

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of autoimmune origin, characterised by the destruction of small intrahepatic bile ducts. The disease has an unpredictable clinical course but may progress to fibrosis and cirrhosis. The diagnostic hallmark of PBC is the presence of disease-specific antimitochondrial antibodies (AMA), which are pathognomonic for the development of PBC. The disease overwhelmingly affects females, with some cases of male PBC being reported. The reasons underlying the low incidence of males with PBC are largely unknown. Epidemiological studies estimate that approximately 7–11% of PBC patients are males. There does not appear to be any histological, serological, or biochemical differences between male and female PBC, although the symptomatology may differ, with males being at higher risk of life-threatening complications such as gastrointestinal bleeding and hepatoma. Studies on X chromosome and sex hormones are of interest when studying the low preponderance of PBC in males; however, these studies are far from conclusive. This paper will critically analyze the literature surrounding PBC in males.
Mesenchymal Stromal Cells Do Not Increase the Risk of Viral Reactivation Nor the Severity of Viral Events in Recipients of Allogeneic Stem Cell Transplantation
Authors: Lucchini Giovanna , Dander Erica , Pavan Fabio , Di Ceglie Irene , Balduzzi Adriana , Perseghin Paolo , Gaipa Giuseppe , Algarotti Alessandra , Introna Martino , Rambaldi Alessandro , Rovelli Attilio , Biondi Andrea , Biagi Ettore , D'Amico Giovanna
Published: May 2012

Mesenchymal stromal cells (MSC) are tested in clinical trials to treat graft versus host disease (GvHD) after stem cell transplantation (SCT).In vitrostudies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts) receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.
Video Classification and Adaptive QoP/QoS Control for Multiresolution Video Applications on IPTV
Authors: Shyh-Fang Huang
Published: May 2012

With the development of heterogeneous networks and video coding standards, multiresolution video applications over networks become important. It is critical to ensure the service quality of the network for time-sensitive video services. Worldwide Interoperability for Microwave Access (WIMAX) is a good candidate for delivering video signals because through WIMAX the delivery quality based on the quality-of-service (QoS) setting can be guaranteed. The selection of suitable QoS parameters is, however, not trivial for service users. Instead, what a video service user really concerns with is the video quality of presentation (QoP) which includes the video resolution, the fidelity, and the frame rate. In this paper, we present a quality control mechanism in multiresolution video coding structures over WIMAX networks and also investigate the relationship between QoP and QoS in end-to-end connections. Consequently, the video presentation quality can be simply mapped to the network requirements by a mapping table, and then the end-to-end QoS is achieved. We performed experiments with multiresolution MPEG coding over WIMAX networks. In addition to the QoP parameters, the video characteristics, such as, the picture activity and the video mobility, also affect the QoS significantly.
Biomass, Carbon and Nitrogen Distribution in Living Woody Plant Parts ofRobinia pseudoacaciaL. Growing on Reclamation Sites in the Mining Region of Lower Lusatia (Northeast Germany)
Authors: Quinkenstein Ansgar , Pape Dirk , Freese Dirk , Schneider Bernd Uwe , Hüttl Reinhard F.
Published: May 2012

In the lignite mining region of Lower Lusatia (NE-Germany),Robinia pseudoacaciaL. is an increasingly popular tree for the biomass production with short rotation coppices (SRCs) on reclamation sites. In order to evaluate biomass production, C and N allocation patterns inR. pseudoacaciastands between shoot, stump, coarse, and fine roots samples were collected from seedlings and three adjacent plantations and plants that were one, two and twelve years old. Results indicated that the summarized average dry matter production (DM) of the woody plant parts increased with plant age up to 7.45 t DM ha−1yr−1with a corresponding shoot increment of up to 4.77 t DM ha−1 yr−1in the twelve-year-old stands. The shoot to root ratio changed from 0.2 for the one-year-old trees to 2.0 in the twelve-year-old plantation, whereby an average amount of 3.4 t C ha−1 yr−1and 0.1 t N ha−1 yr−1was annually bound in the living woody plant parts over the period of twelve years. Summing up, the results suggest a high potential for C and N storage ofR. pseudoacaciawhat is also beneficial for land reclamation due to positive implications on soil humus and general site fertility.
Laser-Based Propagation of Human iPS and ES Cells Generates Reproducible Cultures with Enhanced Differentiation Potential
Authors: Hohenstein Elliott Kristi A. , Peterson Cory , Soundararajan Anuradha , Kan Natalia , Nelson Brandon , Spiering Sean , Mercola Mark , Bright Gary R.
Published: May 2012

Proper maintenance of stem cells is essential for successful utilization of ESCs/iPSCs as tools in developmental and drug discovery studies and in regenerative medicine. Standardization is critical for all future applications of stem cells and necessary to fully understand their potential. This study reports a novel approach for the efficient, consistent expansion of human ESCs and iPSCs using laser sectioning, instead of mechanical devices or enzymes, to divide cultures into defined size clumps for propagation. Laser-mediated propagation maintained the pluripotency, quality, and genetic stability of ESCs/iPSCs and led to enhanced differentiation potential. This approach removes the variability associated with ESC/iPSC propagation, significantly reduces the expertise, labor, and time associated with manual passaging techniques and provides the basis for scalable delivery of standardized ESC/iPSC lines. Adoption of standardized protocols would allow researchers to understand the role of genetics, environment, and/or procedural effects on stem cells and would ensure reproducible production of stem cell cultures for use in clinical/therapeutic applications.
Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response
Authors: Wong Harvey , Choo Edna F. , Alicke Bruno , Ding Xiao , La Hank , McNamara Erin , Theil Frank-Peter , Tibbitts Jay , Friedman Lori S. , Hop Cornelis E.C.A. , Gould Stephen E.
Published: May 2012

Purpose: Immunodeficient mice transplanted with subcutaneous tumors (xenograft or allograft) are widely used as a model of preclinical activity for the discovery and development of anticancer drug candidates. Despite their widespread use, there is a widely held view that these models provide minimal predictive value for discerning clinically active versus inactive agents. To improve the predictive nature of these models, we have carried out a retrospective population pharmacokinetic–pharmacodynamic (PK–PD) analysis of relevant xenograft/allograft efficacy data for eight agents (molecularly targeted and cytotoxic) with known clinical outcome.

Experimental Design: PK–PD modeling was carried out to first characterize the relationship between drug concentration and antitumor activity for each agent in dose-ranging xenograft or allograft experiments. Next, simulations of tumor growth inhibition (TGI) in xenografts/allografts at clinically relevant doses and schedules were carried out by replacing the murine pharmacokinetics, which were used to build the PK–PD model with human pharmacokinetics obtained from literature to account for species differences in pharmacokinetics.

Results: A significant correlation (r = 0.91, P = 0.0008) was observed between simulated xenograft/allograft TGI driven by human pharmacokinetics and clinical response but not when TGI observed at maximum tolerated doses in mice was correlated with clinical response (r = 0.36, P = 0.34).

Conclusions: On the basis of these analyses, agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, are more likely to lead to responses in the clinic. A proposed strategy for the use of murine subcutaneous models for compound selection in anticancer drug discovery is discussed. Clin Cancer Res; 18(14); 3846–55. ©2012 AACR.
Effect of Genetic Polymorphism of ALOX15 on Aspirin-Exacerbated Respiratory Disease
Authors: Song Young-Sin , Yang Eun-Mi , Kim Seung-Hyun , Jin Hyun Jung , Park Hae-Sim
Published: May 2012

Background: Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma. Eosinophils are the key inflammatory cells in the development of AERD. AERD has been attributed to abnormalities of the arachidonic acid metabolism, but the pathogenesis of AERD is not fully understood. Our aim was to investigate the genetic contribution of the arachidonate 15-lipoxygenase gene (ALOX15) to the development of AERD. Methods: We enrolled 171 patients with AERD, 229 patients with aspirin-tolerant asthma, and 195 normal healthy controls in a Korean population. Three polymorphisms (–427G/A, –272C/A, –217G/C) in the promoter region of ALOX15 were genotyped. The functional variability of the promoter polymorphisms were analyzed by luciferase reporter activity assay. Result: No significant difference in the genotype frequency of the ALOX15 genetic polymorphism was found. Peripheral total eosinophil count was significantly higher in the patients carrying the GG genotype of the –427G/A polymorphism (p = 0.016). Similarly, the patients carrying haplotype 1 (ht1) (GCG) of –427G/A, –272C/A and –217G/C showed a significantly higher total eosinophil count compared to the other haplotypes (p = 0.008) in the AERD group. The promoter activity of the ht1 (GCG) construct was significantly higher compared to that of the ht3 (AGG) construct in A549 and U937 cells (both p < 0.001). Conclusion: These results suggest that the promoter polymorphisms of the ALOX15 gene affect ALOX15 activity leading to increased eosinophil infiltration in AERD patients.
Hemodialysis with a Dialyzer Loaded with Argatroban May Be Performed in vivo without a Systemic Anticoagulant
Authors: Zhang Yixiong , Ning Jianping , Veeraragoo Pouranan , Li Yanchao , Dai Siyuan
Published: May 2012

Background/Aims: Anticoagulation in hemodialysis (HD) patients at high risk of bleeding remains an intractable problem. Simulating endothelial cells by releasing anticoagulant on the membrane may be a promising alternative. Methods: We modified a polyacrylonitrile (PAN) dialyzer by loading argatroban into its membrane and verified its anticoagulation efficiency and its influence on coagulation markers such as activated partial thromboplastin time (aPTT), D-dimer and thrombin-antithrombin complex (TAT) in an animal HD model. Results: All HD sessions with the argatroban dialyzer were completed successfully with either no or minimal fiber clotting. D-dimer was lower in the argatroban group than in the PAN group; TAT and aPTT values were similar in the two groups, which suggests better anticoagulation and a similar influence on the coagulation system. Conclusion: HD with the argatroban dialyzer is feasible, safe and simple, and could be used in patients at high risk of bleeding.
Impact of Maternal Allergy and Use of Probiotics during Pregnancy on Breast Milk Cytokines and Food Antibodies and Development of Allergy in Children until 5 Years
Authors: Kuitunen Mikael , Kukkonen Anna Kaarina , Savilahti Erkki
Published: May 2012

Background: Whether breast milk (BM) can protect against allergy has been studied extensively, with conflicting results. Variations in mothers’ BM composition may explain some of the conflicting results. Our aim was to assess the impact of maternal allergy and probiotic intervention on BM food antibodies, transforming growth factor (TGF)-β2 and interleukin (IL)-10 and their impact on allergy development in children until the ages of 2 and 5. Methods: We measured total IgA, IgA antibodies to cow’s milk (CM), casein, β-lactoglobulin and ovalbumin (OVA), TGF-β2 and IL-10 in 364 colostrum samples and 321 BM samples taken at 3 months from mothers participating in a prospective study evaluating the allergy-preventive effect of probiotics in a cohort with an increased risk for allergy. Results: CM, casein and OVA antibodies, TGF-β2 and IL-10 were detectable in most samples. Maternal allergy was associated with raised levels of IgA to casein (p = 0.04) and lower levels of TGF-β2 (p = 0.006) in mature BM. Probiotic supplementation was associated with increased IL-10 (p = 0.046) and decreased casein IgA antibodies (p = 0.027) in mature BM. High OVA IgA antibodies in colostrum were associated with the development of atopy by the age of 2, while low levels in mature BM were a significant risk factor for the development of eczema by the age of 2. TGF-β2 levels in BM constituted a risk for development of allergy by the age of 2. Conclusions: The immunologic composition of BM was only slightly affected by maternal atopy and could be altered by probiotic supplementation. Small effects of BM components on allergy development in children were evident.
Long-Term Efficacy of Pulmonary Rehabilitation in Patients with Occupational Respiratory Diseases
Authors: Ochmann Uta , Kotschy-Lang Nicola , Raab Wolfgang , Kellberger Jessica , Nowak Dennis , Jörres Rudolf A.
Published: May 2012

Background: Pulmonary rehabilitation is a well-recognized treatment option in chronic obstructive lung disease improving exercise performance, respiratory symptoms and quality of life. In occupational respiratory diseases, which can be rather cost-intensive due to the compensation needs, very little information is available. Objectives: This study aims at the evaluation of the usefulness of pulmonary rehabilitation in patients with occupational respiratory diseases, partly involving complex alterations of lung function and of the sustainability of effects. Methods: We studied 263 patients with occupational respiratory diseases (asthma, silicosis, asbestosis, chronic obstructive pulmonary disease) using a 4-week inpatient rehabilitation program and follow-up examinations 3 and 12 months later. The outcomes evaluated were lung function, 6-min walking distance (6MWD), maximum exercise capacity (Wmax), skeletal muscle strength, respiratory symptoms, exacerbations and associated medical consultations, quality of life (SF-36, SGRQ), anxiety/depression (HADS) and Medical Research Council and Baseline and Transition Dyspnea Index scores. Results: Compared to baseline, there were significant (p < 0.05) improvements in 6MWD, Wmax and muscle strength immediately after rehabilitation, and these were maintained over 12 months (p < 0.05). Effects were less pronounced in asbestosis. Overall, a significant reduction in the rate of exacerbations by 35%, antibiotic therapy by 27% and use of health care services by 17% occurred within 12 months after rehabilitation. No changes were seen in the questionnaire outcomes. Conclusions: Pulmonary rehabilitation is effective even in the complex settings of occupational respiratory diseases, providing sustained improvement of functional capacity and reducing health care utilization.
Factors Associated with Sustained Attention during an Activity Intervention in Persons with Dementia
Authors: Kolanowski Ann , Bossen Ann , Hill Nikki , Guzman-Velez Edmarie , Litaker Mark
Published: May 2012

Background/Aims: Are the noncognitive factors of self-reported mood and personality related to sustained attention in nursing home residents with dementia during an activity intervention? Methods: Intervention data from a randomized clinical trial were used to address the aim of this project. Subjects were 128 nursing home residents who were assessed for mood, personality, behavioral indicators of attention, time on task and number of disengagements during an activity intervention. Results: More positive self-reported mood was associated with greater behavioral displays of attention during activities, greater time spent engaged in the activities and less disengagement. Conclusion: To our knowledge, this is the first study to report on the association of mood, personality and sustained attention in nursing home residents with dementia. While the findings are preliminary, they can be used to inform the design of future research.
Ability of Emergency Physicians to Detect Early Ischemic Changes of Acute Ischemic Stroke on Cranial Computed Tomography
Authors: Ünlüer Erden Erol , Yaka Erdem , Akhan Galip , Limon Önder , Kara Pinar Hanife , Yavaşi Özcan , Vandenberk Nergiz , Nazli Yasemin Ece , Kutluk Kürşad
Published: May 2012

Objective: The objective of this study was to evaluate the ability of emergency physicians (EPs) to diagnose early ischemic changes due acute ischemic stroke on cranial computed tomography (CT). Subjects and Methods: Three EPs interpreted CT scans obtained within 3 h of symptom onset in 50 patients with acute stroke. The CT scans were interpreted by the EPs and compared to official neuroradiologist reports as a gold standard. ĸ statistics were calculated to determine agreement among the three readers. Sensitivities and specificities were analyzed for each reader. Results: The EPs’ sensitivities were 50, 45.5, and 45.5%, and specificities were 64.3, 82.1, and 64.3%, respectively. Focal parenchymal hypodensity was the criterion for which the EPs were the most sensitive (77.3%). The ability of EPs to recognize early ischemic changes on CT scans in acute ischemic stroke was moderate based on sensitivities. Conclusion: Based on this study, EPs must be trained especially for recognizing early ischemic changes in acute ischemic stroke to improve their accuracy of interpretation.
A Case Study of Processes Impacting Precipitation Phase and Intensity during the Vancouver 2010 Winter Olympics
Authors: Thériault Julie M. , Rasmussen Roy , Smith Trevor , Mo Ruping , Milbrandt Jason A. , Brugman Melinda M. , Joe Paul , Isaac George A. , Mailhot Jocelyn , Denis Bertrand
Published: May 2012

Accurate forecasting of precipitation phase and intensity was critical information for many of the Olympic venue managers during the Vancouver 2010 Olympic and Paralympic Winter Games. Precipitation forecasting was complicated because of the complex terrain and warm coastal weather conditions in the Whistler area of British Columbia, Canada. The goal of this study is to analyze the processes impacting precipitation phase and intensity during a winter weather storm associated with rain and snow over complex terrain. The storm occurred during the second day of the Olympics when the downhill ski event was scheduled. At 0000 UTC 14 February, 2 h after the onset of precipitation, a rapid cooling was observed at the surface instrumentation sites. Precipitation was reported for 8 h, which coincided with the creation of a nearly 0°C isothermal layer, as well as a shift of the valley flow from up valley to down valley. Widespread snow was reported on Whistler Mountain with periods of rain at the mountain base despite the expectation derived from synoptic-scale models (15-km grid spacing) that the strong warm advection would maintain temperatures above freezing. Various model predictions are compared with observations, and the processes influencing the temperature, wind, and precipitation types are discussed. Overall, this case study provided a well-observed scenario of winter storms associated with rain and snow over complex terrain.
To Resist or Not to Resist?
Authors: Balemba Samantha , Beauregard Eric , Mieczkowski Tom
Published: May 2012

Circumstances under which a sexual assault takes place and how these circumstances affect offenders’ reactions to victim resistance are not well understood. Previous studies have not thoroughly examined the interactions that take place between situational factors and resistance. Using a combination of logistic regression and Chi-square Automatic Interaction Detection (CHAID) analyses, we examine victim, situational, and crime characteristics of 426 sexual assaults involving victim resistance to determine which of these factors increase the likelihood of offender violence. Findings suggest that violence is affected by both the attack strategy employed by the offender and the type of resistance by the victim, along with several other qualifying factors.
Commentary
Authors: Keyton Joann
Published: May 2012

In this commentary, the author reflects on the articles chosen for the special section on communications analysis. These articles problematize communication and raise an interesting set of questions for both human factors and communication scholars to ponder. In the end, both sets of scholars seek the same goal: How do we better examine communication to improve it? Problematizing communication requires scholars to challenge their fundamental assumptions about the phenomenon as well as to tease out the distinctions of methodological approaches typically used by both human factors and communication scholars. Human factors scholars tend to favor forms of communication in which technology or task roles control who can communicate and how. Communication scholars tend to favor contexts in which information flows more freely with fewer explicit restrictions. Creating opportunities to collaborate in research on the communication process may create the best understanding of technology that can better serve our understanding of communication.
Work engagement and work-family facilitation: Making homes happier through positive affective spillover
Authors: Culbertson Satoris S , Mills Maura J , Fullagar Clive J
Published: May 2012

Although work engagement has been shown to be associated with positive job attitudes and behaviors, no research has investigated its relationship with work-family issues. To address this, the current longitudinal, experience-sampling study aimed to determine the relationship between daily work engagement and work-to-family facilitation. A total of 52 extension agents responded to two daily surveys for two weeks. Results indicate that both work engagement and work-to-family facilitation vary considerably from day to day. Daily work engagement had a positive effect on family life. The effect of daily engagement in facilitating work-family relations was partially mediated by positive mood, and the relationship between work engagement and facilitation of work-family relations was moderated by work-family capitalization, or the sharing of positive work experiences at home. Implications and future research directions are discussed.