bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils
Authors: Alexander Shelia R , Kishimoto Takashi K , Walcheck Bruce 
Published: January 2018

Abstract
The signaling factors that direct the rapid shedding of L-selectin from neutrophils upon chemoattractant stimulation are poorly understood. Protein kinase C (PKC) has been implicated, yet previous studies have relied on the use of phorbol esters and nonselective kinase inhibitors. We treated neutrophils with various selective kinase inhibitors to evaluate their effects on N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced L-selectin shedding. We found that three selective inhibitors of PKC, structurally related to staurosporine, largely blocked both fMLP- and phorbol 12-myristate 13-acetate (PMA)-induced L-selectin shedding; however, these inhibitors did not affect fMLP-induced up-regulation of Mac-1 (CD11b/CD18) expression, which has been shown not to involve PKC. Other selective serine, threonine, and tyrosine kinase inhibitors were found not to block fMLP-induced L-selectin shedding. These findings provide more definitive evidence for the role of PKC in chemoattractant-induced L-selectin proteolysis. It is interesting that certain highly selective PKC inhibitors, not structurally related to staurosporine, were found to directly induce L-selectin shedding from neutrophils. J. Leukoc. Biol. 67: 415–422; 2000.
Regulation of adaptive immune responses by innate cells expressing NK markers and antigen-transporting macrophages
Authors: Stein-Streilein J , Sonoda K-H , Faunce D , Zhang-Hoover J 
Published: January 2018

Abstract
A continuing theme of work done in our laboratory involves regulation of adaptive immune response by innate cells, in general, and immune-regulation by natural killer (NK) and NKT cells, in particular. Studies include work with the lung and the eye. In addition to immune surveillance of tumor cells, the NK cell is often associated with secreting cytokines that contribute to the creation of microenvironments conducive to Th1 responses and with defense mechanisms that lessen the initial infecting viral load. Reported studies show that the NKT cells support both T helper cell responses (type 1 and 2), as well as their being absolutely central to the development of antigen-specific T-regulatory cells involved in peripheral tolerance. Because of the multifunctional capabilities of the NKT cell, we propose that yet another cell, such as the antigen-presenting cell (APC), may influence the effector pathway of the NKT cell. We postulate that the APC that transports the antigen from the entry environment provides both trafficking and activation signals for innate cells in the secondary lymphoid organs. Evidence is presented that macrophage-derived signals selectively recruit NKT cells and bias their cytokine synthesis. Data imply that, just as occurs in immune inflammation, a collection of innate and adaptive immune cells interact within the secondary lymphoid tissue to generate antigen-specific tolerance in the periphery. J. Leukoc. Biol. 67: 488–494; 2000.
NF-κB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1β, TNF-α, and LPS
Authors: Garcia Gabriela E , Xia Yiyang , Chen Shizhong , Wang Yibin , Ye Richard D , Harrison Jeffrey K , Bacon Kevin B , Zerwes Hans-Guenter , Feng Lili 
Published: January 2018

Abstract
Fractalkine is an endothelial cell-derived CX3C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleu-kin-1β (IL-1β), tumor necrosis factor α (TNF-α), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-κB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-κB subunits p50 and p65 were responsible for κB binding. Accordingly, we examined the role of NF-κB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IκB as a specific inhibitor. Delivery of a dominant-negative form of IκBα in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-κB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-κB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-κB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction. J. Leukoc. Biol. 67: 577–584; 2000.
Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function
Authors: Cosentino Marco , Marino Franca , Cattaneo Simona , Di Grazia Laura , Francioli Cristina , Fietta Anna Maria , Lecchini Sergio , Frigo Gianmario 
Published: January 2018

Abstract
We studied the effects of two diazepambinding inhibitor (DBI)-derived peptides, triakonta-tetraneuropeptide (DBI 17–50, TTN) and eiksoneuropeptide (DBI 51–70, ENP), on cytosolic free Ca2+ concentrations ([Ca2+]i), chemotaxis, superoxide anion (O) generation, and phagocytosis in human neutrophils. Both TTN and ENP induced a rapid and transient rise of [Ca2+]i. The effect of TTN depended on the presence of extracellular Ca2+, whereas the effect of ENP also persisted after extracellular Ca2+ chelation. TTN induced neutrophil chemotaxis, stimulated O generation, and enhanced phagocytosis. ENP did not affect cell migration and oxidative metabolism but enhanced phagocytosis. Both peptides modulated N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced O generation. Because neutrophils express benzodiazepine receptors of the peripheral type (pBRs) and DBI-derived peptides may interact with such receptors, we investigated the possible role of pBRs in TTN- or ENP-induced effects. The synthetic pBR ligand RO 5-4864 increased [Ca2+]i through extracellular Ca2+ influx and this effect was prevented by the pBR antagonist PK-11195. RO 5-4864, however, was ineffective on neutrophil migration and O generation and only slightly affected phagocytosis. Moreover, PK-11195 delayed the [Ca2+]i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca2+]i rise induced by ENP. We conclude that DBI-derived peptides induce [Ca2+]i changes and modulate neutrophil function mainly through pBR-independent pathways. In view of the wide cell and tissue distribution of DBI in the brain and in peripheral organs, modulation of neutrophil function by DBI-derived peptides may be relevant for both the neuroimmune network and the development and regulation of the inflammatory processes. J. Leukoc. Biol. 67:637–643; 2000.
Prognostic significance of nonsustained ventricular tachycardia in patients receiving cardiac resynchronization therapy for primary prevention: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Furushima Hiroshi , Sekiguchi Yukio , Manaka Tetsuyuki , Nishii Nobuhiro , Ueyama Takeshi , Morita Norishige , Okamura Hideo , Nitta Takashi , Hirao Kenzo , Okumura Ken ,   Members of the Implantable Cardioverter‐Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: January 2018

AbstractBackgroundWhether nonsustained ventricular tachycardia (NSVT) is a marker of increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be established in patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) for primary prevention.MethodsAmong the follow‐up data of the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2011 and August 2015, information regarding a history of NSVT before the CRT‐D implantation for primary prevention had been registered in 269 patients. Outcomes were compared between two groups with and without NSVT: NSVT group (n = 179) and No NSVT group (n = 90).ResultsThere was no significant difference with regard to age, gender, and NYHA class between the two groups. Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0% in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was 26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival free from heart failure death was reduced in the NSVT group, as compared with the No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A multivariate analysis identified a history of NSVT, anemia, and no use of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin‐receptor blocker (ARB) as predictors of heart failure death.ConclusionsNSVT appears to be a surrogate marker of severe heart failure rather than a substrate for subsequent sustained VTAs in patients with CRT‐D for primary prevention.
Validation of the Stanford Leisure‐Time Activity Categorical Item (L‐Cat) using armband activity monitor data
Authors: Ross K. M. , Leahey T. M. , Kiernan M. 
Published: January 2018

SummaryObjectiveAccurate assessment of physical activity (PA) in public health and healthcare settings remains a challenge given limitations of existing brief assessment tools. The Stanford Leisure‐Time Activity Categorical Item (L‐Cat), a single item with six categories, has previously demonstrated excellent reliability and adequate validity relative to pedometer steps. However, pedometers cannot assess key dimensions of PA intensity or duration.MethodsWe evaluated the L‐Cat's criterion validity and sensitivity to change relative to objectively measured Sensewear armband activity monitors among 76 adults with overweight/obesity (mean age 50.8 ± 11.9 years, BMI = 33.1 ± 3.4 kg m−2) at baseline and end of a 6‐month behavioural weight management pilot trial.ResultsAt baseline, L‐Cat category was associated with armband‐measured daily steps (Spearman's ρ = 0.41, p < 0.001), total weekly minutes of moderate/vigorous‐intensity PA (MVPA) (ρ = 0.40, p < 0.001) and weekly minutes of MVPA accumulated in bouts ≥10 min (ρ = 0.47, p < 0.0001). Participants increasing ≥1 L‐Cat category from baseline to 6 months had greater increases in steps (1,110.1 ± 1,852.1 vs. −18.0 ± 2,005.6 steps/d, p = 0.032), total minutes of MVPA (145.7 ± 180.6 vs. −2.1 ± 215.8 min/week, p = 0.007) and greater weight losses (−7.4 ± 7.7% vs. −3.1 ± 4.8%, p = 0.013) than those who stayed the same/decreased L‐Cat categories.ConclusionThe L‐Cat demonstrated adequate criterion validity and excellent sensitivity to change relative to objectively measured PA among behavioural weight management pilot trial participants. The L‐Cat may be particularly useful for identifying individuals at lower activity levels and when using all six categories.
Protective effect of boiogito extract with glucosamine HCl against adjuvant‐induced arthritis in rats
Authors: Takenaga Mitsuko , Niimi Jun , Hamaguchi Akemi , Asano Teita , Tsuchiya Reiko , Ohta Yuki , Yudoh Kazuo , Inoue Hajime 
Published: January 2018

ABSTRACTAimThe effect of boiogito extract combined with glucosamine HCl was assessed in adjuvant‐induced arthritis (AIA) rats.MethodsRats received a daily oral mixture of boiogito extract (125 mg/kg) and glucosamine HCl (80 mg/kg) before and after once‐off adjuvant injection. Treatment was continued up to the day when blood and/or tissue were collected (day 12 or day 21). Paw swelling, arthritis score, and inflammatory mediators were assessed.ResultsCombined treatment was more effective for AIA than either agent alone. Both serum nitric oxide (NO) and tissue NO were significantly suppressed in the adjuvant‐uninjected hind paw on day 12. Boiogito extract significantly reduced the tissue level of matrix metalloproteinase (MMP)‐13. In addition, interleukin (IL)‐1β‐induced MMP‐13 by SW1353 chondrocytes was dose‐dependently suppressed by boiogito extract, while glucosamine HCl had little effect. IL‐1β‐induced phosphorylation of extracellular signal‐related kinase (ERK) was inhibited by the combination of boiogito extract and glucosamine HCl, but was most strongly suppressed by glucosamine HCl alone.ConclusionCombined treatment with boiogito extract and glucosamine HCl had a protective effect against AIA in rats. This effect was related to strong suppression of MMP‐13 production (mainly by boiogito extract) and inhibition of inflammatory mediator production via ERK signaling (mainly by glucosamine HCl).
Rethinking urban water management in Addis Ababa in the face of climate change: An urgent need to transform from traditional to sustainable system
Authors: Worku Hailu 
Published: January 2018

AbstractUrban water management in Addis Ababa, Ethiopia, is of significant concern to the city government owing to the growing demand for water, poor urban water management practices, insufficient and ineffective infrastructures, and climate change. The objective of this study is to review current water resources and management practices, consider the sustainability of the urban water cycle in relation to climate change, and devise a feasible strategy for a sustainable urban water management system. The results of this study show that the situation as it is now is not sustainable at current levels of demand and supply, either in terms of the systems’ management practices, or in terms of the challenges posed by climate change. An Integrated Urban Water Management strategy that covers the entire urban water cycle, including diversification of water sources, protection and conservation of water, sustainable exploitation, distribution, and consumption and wastewater management, water recycling, nutrient reuse, and safe wastewater disposal, should be implemented as soon as practicable.
Increased frequency of AMP‐activated protein kinase‐positive spinal motor neurons after sciatic nerve injury in a mouse model
Authors: Qi Bao , Cao Gui‐Jun , Li Qing‐Wei , Chen Guo‐Wu , Liang Xiao , Wang Yu‐Zhong , Meng Chun‐Yang 
Published: January 2018

AbstractThe role of AMP‐activated protein kinase (AMPK) in the regulation of energy metabolism and the control of skeletal muscle regeneration post injury has been described previously. It remains unknown whether this metabolic sensor plays a role in the mechanism of axonal regeneration post injury. In this study, we used a sciatic nerve crushed mouse model to detect the expression of AMPK in sciatic nerve and spinal motor neurons at 1 week, 2 weeks and 3 weeks after injury by immunofluorescence staining. Electrophysiological and histopathological studies were used to confirm the nerve injury and regeneration. Our results showed that frequency of AMPK‐positive spinal motor neurons was significantly higher on day 7 after sciatic nerve crush (SNC) and peaked on day 14. No expression of AMPK was detected in axons of the sciatic nerve before and after the injury. Taken together, our study suggested a possible role of AMPK in the mechanism of motor nerve regeneration after injury.
Rethinking Institutions: Innovation and institutional change in India's informal economy
Authors: HARRISS-WHITE BARBARA 
Published: January 2018

AbstractIndia has the largest informal, unregistered economy in the world, infrastructurally backward, yet vital for both growth and livelihoods. In the first section of this article, five economic institutions that shape this economy are introduced: small firms, informality, non-metropolitan towns, innovation and innovation systems, and the state's regulative impact on the economy it does not directly regulate. In the second section, we trace the development of the commodity economy of a South Indian town taken for case study over 40 years, before exploring three kinds of innovation in the third section: invention, adaptive, and adoptive innovation. In the fourth section, the formal and informal institutions that nurture informal innovation are analysed: family business, business associations, banks and finance, informal insurance and gold, hybrid state–private institutions, and informal innovation inside the state. The conclusion confirms the innovative dynamism of the informal economy and the complex pathways of institutional change that both shape, and are shaped by, innovation.
OP01 Cross Border Cooperation On High-Cost-Capital Investments In Health
Authors: Rosian-Schikuta Ingrid , Bobek Julia , Laschkolnig Anja , Ostermann Herwig , Mildschuh Stephan , Pertl Daniela , Stürzlinger Heidi , Zsifkovits Johannes , Zuba Martin 
Published: January 2018

INTRODUCTION:The medical equipment sector is characterized by a large share of overall health budgets spent for the provision of capital investment goods such as medical scanners and radiotherapy units. A high variability in provision and utilization rates of medical equipment can be observed too. The objective for this study was to contribute to effective cross-border cooperation between European Union (EU)-Member States by pooling resources for high-cost medical equipment investments (1).METHODS:Potential cost-intensive and highly specialised medical equipment, where cross-border investment resource pooling may be recommended, were identified by a combined evidence search and expert consultation. An efficiency assessment of medical equipment potential savings for EU-countries was done by a benchmark-approach and a best-practice-approach. Furthermore six examples for cross-border cooperation were investigated and two surveys have been conducted.RESULTS:The following medical equipment can be considered as cost-intensive and highly specialized across EU-Member States: Magnetic Resonance Imaging (MRI) scanners, Computed Tomography (CT) scanners, Stereotactic systems and Surgical robots.The efficiency assessment using the benchmark approach was performed for MRI, CT scanners, Positron Emission Tomography (PET) scanners, Angiography units, Gamma cameras and Lithotriptors. The results of the best-practice approach showed potential cost savings due to under-or overutilization per device group and EU-Member State. However, as this analysis offers a view on health systems on a very macro level it was not possible to give detailed insights at the country-level.The six selected cross-border examples demonstrated a wide variety of options regarding the structure, extent and organization of cross-border cooperation: Five of six cross-border examples were cooperation close to the border, in four of six examples EU funds played an important role.CONCLUSIONS:The study highlighted that cross-border cooperation in the field of cost-intensive/highly specialized medical equipment could bring economic advantages for many EU-Member States. Despite this, still only little is done by EU-Member States in terms of cooperation. Reasons are diverse and can be ascribed to lacking information, differences of national health systems, organizational and administrative hurdles, and lacking political support.
OP75 Implementing Risk Stratification In Primary Care: A Qualitative Study
Authors: Porter Alison , Snooks Helen , Kingston Mark , Davies Jan , Hutchings Hayley , Whitman Shirley , Watkins Alan , Evans Bridie , Bailey-Jones Kerry , Burge-Jones Deborah , Dale Jeremy , Fitzsimmons Deborah , Harrison Jane , Howson Helen , Heaven Martin , John Gareth , Lewis Leo , Philips Ceri , Sewell Bernadette , Warm Daniel , Williams Victoria , Russell Ian 
Published: January 2018

INTRODUCTION:A predictive risk stratification tool (PRISM) to estimate a patient's risk of an emergency hospital admission in the following year was trialled in general practice in an area of the United Kingdom. PRISM's introduction coincided with a new incentive payment (‘QOF’) in the regional contract for family doctors to identify and manage the care of people at high risk of emergency hospital admission.METHODS:Alongside the trial, we carried out a complementary qualitative study of processes of change associated with PRISM's implementation. We aimed to describe how PRISM was understood, communicated, adopted, and used by practitioners, managers, local commissioners and policy makers. We gathered data through focus groups, interviews and questionnaires at three time points (baseline, mid-trial and end-trial). We analyzed data thematically, informed by Normalisation Process Theory (1).RESULTS:All groups showed high awareness of PRISM, but raised concerns about whether it could identify patients not yet known, and about whether there were sufficient community-based services to respond to care needs identified. All practices reported using PRISM to fulfil their QOF targets, but after the QOF reporting period ended, only two practices continued to use it. Family doctors said PRISM changed their awareness of patients and focused them on targeting the highest-risk patients, though they were uncertain about the potential for positive impact on this group.CONCLUSIONS:Though external factors supported its uptake in the short term, with a focus on the highest risk patients, PRISM did not become a sustained part of normal practice for primary care practitioners.
OP78 Patient Involvement In European Health Technology Assessment Focus Group With Cardiac Patients
Authors: Ettinger Sabine , Mayer Julia , Stanak Michal , Wild Claudia 
Published: January 2018

INTRODUCTION:Involving patients in defining the scope of health technology assessments is recognized as a valuable strategy that ensures that patient-relevant outcomes are considered.The aim of this project was to pilot the focus group approach with cardiac patients in a European rapid assessment on the wearable cardioverter defibrillator, to improve involvement processes, to identify neglected outcomes, and to explore the potential of this methodology for eliciting the patients views on their disease and the wearable cardioverter defibrillator therapy.METHODS:An e-mail was sent to members of the nine regional associations of the Austrian Organization for Heart and Lung Transplant Patients to identify eligible participants. Guiding questions for the discussion were developed based upon a hand search of patient involvement initiatives and a review of appropriate literature. The 4-hour meeting was moderated by a patient support expert and recorded upon approval of participants. The anonymized transcript was analyzed using framework analysis.RESULTS:Ten eligible patients responded, of which five men, aged between 55 and 73 years (mean 65 years) from Austria and Germany, were able to participate. All respondents experienced heart transplantation, and four had received an implantable cardioverter defibrillator before.Participants reported that experiencing a sense of security was crucial to them and that they expected to do sports and live a life with few limitations, despite receiving a therapy. A wearable cardioverter defibrillator was hence not considered a long-term solution due to expected restrictions in living a ‘normal’ life.Challenges included the identification of participants representative of this patient group and the complexity of patient histories.CONCLUSIONS:The focus group approach proved useful in the wearable cardioverter defibrillator assessment. Gathered results informed the inclusion of outcomes relevant to the target group and revealed patients views on health-related quality of life. Lessons learned guide us in further improving patient involvement processes within the European Network for HTA (EUnetHTA) project.