bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in co‐prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland
Authors: Wan Md Adnan Wan A. H. , Zaharan Nur L. , Bennett Kathleen , Wall Catherine A. 
Published: October 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Renin‐angiotensin‐aldosterone system inhibition confers cardio‐renal protection and may be achieved by monotherapy with an angiotensin enzyme converting inhibitor (ACEI) or an angiotensin‐II receptor blocker (ARB).• Dual ACEI and ARB therapy has been examined in major clinical trials with conflicting results.• The prescribing pattern of dual therapy in general primary care population is not known. WHAT THIS STUDY ADDS • An increase in the co‐prescribing of ACEIs and ARBs was observed in the Irish primary care population.• Co‐prescribing of ACEIs and ARBs in the primary care population did not appear to be influenced by results from major clinical trials.• ACEIs and ARBs were more likely to be co‐prescribed in special cohorts of the population with diabetes, hypertension and heart failure.AIMS(i) To examine the trends in co‐prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin‐II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co‐prescribing.METHODSThe Irish HSE‐Primary Care Reimbursement Services database was used to identify patients ≥16 years old co‐prescribed ACEIs and ARBs between January 2000 and April 2009 (n= 266 554 prescriptions). The rate of prescribing per 1000 general medical services (GMS) scheme population was calculated for each month. Patients with diabetes, hypertension, heart failure and ischaemic heart disease were also identified by prescribing of certain medications. A linear trend test was used to examine prescribing trends. Logistic regression was used to examine prescribing according to patient characteristics. The effects of the major trials on prescribing were examined using segmented regression analysis for 12 months pre‐ and post‐trials.RESULTSThere was a significant linear trend in overall ACEI and ARB co‐prescribing over the study period (P < 0.001). Rate of co‐prescribing in January 2000 and April 2009 was 0.16 and 5.72, per 1000 eligible population, respectively. Those 45–64 years old (OR = 2.88, 95% confidence interval (CI) 2.71, 3.06) and ≥65 years (OR = 2.52, 95% CI 2.36, 2.68) were more likely to receive dual therapy compared with those <45 years old. Those with hypertension (OR = 8.85, 95% CI 8.45, 9.27), diabetes (OR = 4.10, 95% CI 3.97, 4.23) and heart failure (OR = 1.78, 95% CI 1.72, 1.84) were more likely to receive dual therapy compared with the general population. Significant increases in prescribing were observed only after the CALM (P= 0.03) and VALIANT (P= 0.007) trials.CONCLUSIONIncreased co‐prescribing of ACEIs and ARBs was observed in Ireland during 2000–09. Prescribing patterns did not appear to be affected by results from major trials.
Improving the quality of drug research or simply increasing its cost? An evidence‐based study of the cost for data monitoring in clinical trials
Authors: Pronker Esther , Geerts Bart F. , Cohen Adam , Pieterse Herman 
Published: October 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Current knowledge is based on practical experience. This paper presents the first novel, quantitative and qualitative view on the efficacy of the sponsor query system widely applied in the pharmaceutical industry, used for quality control purposes by data management for clinical data. WHAT THIS STUDY ADDS • This study presents a structured view on the process of clinical data management and sponsor queries, the efficacy and cost effectiveness of sponsor queries and dual data entry and the conclusion to advocate a more evidence‐based approach to clinical data validation.AIMProcedures for verification of data from clinical studies are intended to maintain reliability for clinical trial results. Guidelines or legislations relating to clinical data management are of limited value and no study has yet demonstrated its effectiveness.METHODSponsor queries and dual entry procedures from one CRO on three different phase I trials are analysed on content, impact and cost.RESULTIn this study, sponsor queries and dual entry procedures proved time and cost inefficient in detecting data discrepancies.CONCLUSIONWe advocate a more evidence‐based approach for enhancing data integrity throughout the process of clinical data management.
A point prevalence survey of antibiotic prescriptions: benchmarking and patterns of use
Authors: Aldeyab Mamoon A. , Kearney Mary P. , McElnay James C. , Magee Fidelma A. , Conlon Geraldine , Gill Dianne , Davey Peter , Muller Arno , Goossens Herman , Scott Michael G. ,   on behalf of the ESAC Hospital Care Subproject Group
Published: October 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Inappropriate antimicrobial use has been associated with increased morbidity and hospital costs.• Antibiotic policies aim to improve patient outcomes whilst reducing adverse effects associated with antimicrobial use.• More insight into the actual implementation of antibiotic policies is needed in order to explore patterns of antibiotic prescribing. WHAT THIS STUDY ADDS • This study assessed the current patterns of antibiotic prescribing and the impact of a hospital antibiotic policy on these practices.• It demonstrated the value of point prevalence surveys in informing antibiotic stewardship and identifying targets for quality improvements.• The study emphasized the importance of participating in international networks, such as the European Surveillance of Antimicrobial Consumption (ESAC), in supporting optimal antibiotic use.AIM The aim of the study was to assess current patterns of antibiotic prescribing and the impact of a hospital antibiotic policy on these practices.METHODS The study involved collecting information regarding hospitalized patients utilizing the ESAC audit tool.RESULTS In the study site hospital, the use of the restricted agents was low whilst the use of the non‐restricted agents was high. Compliance with the hospital antibiotic guidelines was 70%.DISCUSSION The findings identified monitoring non‐restricted antibiotics and compliance with guidelines as targets for quality improvements in our hospital. Point prevalence surveys may offer a simple method of monitoring antibiotic policies, thus, informing antibiotic stewardship.
Ion channels in volume regulation of clonal kidney cells
Authors: Da Silva M. B. , Costa V. M. A. , Pereira V. R. A. , De Albertim G. J. B. , De Melo E. B. B. , Bezerra D. P. , Da Silva R. P. , Rodrigues C. G. , Carneiro C. M. M. , Yuldasheva L. N. , Krasilnikov O. V. 
Published: October 2010

AbstractObjectives:  Clonal kidney cells (Vero cells) are extensively utilized in the manufacture of biological preparations for disease diagnostics and therapeutics and also in preparation of vaccines. In all cells, regulation of volume is an essential function coupled to a variety of physiological processes and is a topic of interest. The objective here was to investigate involvement of ion channels in the process of volume regulation of Vero cells.Methods:  Involvement of ion channels in cell volume regulation was studied using video‐microscopy and flow cytometry. Pharmacologically unaltered cells of different sizes, which are presumably at different phases of the cell cycle, were used.Results:  Ion transport inhibitors altered all phases of regulatory volume decrease (RVD) of Vero cells, rate of initial cell swelling, Vmax and volume recovery. Effects were dependent on type of inhibitor and on cell size (cell cycle phase). Participation of aquaporins in RVD was suggested. Inhibitors decelerated growth, arresting Vero cells at the G0/G1 phase boundary. Electrophysiological study confirmed presence of volume‐activated Cl− channels and K+ channels in plasmatic membranes of the cells.Conclusion:  Vero cells of all sizes maintained the ability to recover from osmotic swelling. Activity of ion channels was one of the key factors that controlled volume regulation and proliferation of the cells.
Coupled mathematical model of tumorigenesis and angiogenesis in vascular tumours
Authors: Cooper M. D. , Tanaka M. L. , Puri I. K. 
Published: October 2010

AbstractObjectives: Mathematical models are useful for studying vascular and avascular tumours, because these allow for more logical experimental design and provide valuable insights into the underlying mechanisms of their growth and development. The processes of avascular tumour growth and the development of capillary networks through tumour‐induced angiogenesis have already been extensively investigated, albeit separately. Despite the clinical significance of vascular tumours, few studies have combined these approaches to develop a single comprehensive growth and development model.Materials and methods: We develop a continuum‐based mathematical model of vascular tumour growth. In the model, angiogenesis is initiated through the release of angiogenic growth factors (AGFs) by cells in the hypoxic regions of the tumour. The nutrient concentration within the tumour reflects the influence of capillary growth and invasion induced by AGF.Results and conclusions: Parametric and sensitivity studies were performed to evaluate the influence of different model parameters on tumour growth and to identify the parameters with the most influence, which include the rates of proliferation, apoptosis and necrosis, as well as the diffusion of sprout tips and the size of the region affected by angiogenesis. An optimization was performed for values of the model parameters that resulted in the best agreement with published experimental data. The resulting model solution matched the experimental data with a high degree of correlation (r = 0.85).
Improved procedure for the measurement of telomere length in whole cells by PNA probe and flow cytometry
Authors: Carbonari M. , Mancaniello D. , Cibati M. , Catizone A. , Fiorilli M. 
Published: October 2010

AbstractObjectives:  Peptide nucleic acid (PNA) probes hybridize to denatured telomeric sequences in cells permeabilized in hot formamide. In reported protocols, the hybridization was conducted in solutions with high formamide concentrations to avoid the DNA renaturation that can hamper binding of the oligo‐PNA probe to specific sequences. We postulated that telomeric DNA, confined in the nuclear microvolume, is not able to properly renature after hot formamide denaturation. Therefore, to improve hybridization conditions between the probe and the target sequences, it might be possible to add probe to sample after the complete removal of formamide.Materials and methods:  After telomeric DNA denaturation in hot formamide solution and several washes to remove the ionic solvent, cells were hybridized overnight at room temperature with human telomere‐specific PNA probe conjugated with Cy5 fluorochrome, Cy5‐OO‐(CCCTAA)3. After stringency washes and staining with ethidium bromide, the cells were analysed by flow cytometry and by using a confocal microscope.Results:  Using three continuous cell lines, different in DNA content and telomere length, and resting human peripheral blood T and B lymphocytes, we demonstrated that the oligo‐PNA probe hybridized to telomeric sequences after complete removal of formamide and that in the preserved nucleus, telomeric sequence denaturation is irreversible.Conclusion:  According to our experience, oligo‐PNA binding results is efficient, specific and proportional to telomere length. These, our original findings, can form the technological basis of actual in situ hybridization on preserved whole cells.
Assessment of cell proliferation and muscular structure following surgical tongue volume reduction in pigs
Authors: Ye W. , Abu A. F. , Liu Z. J. 
Published: October 2010

AbstractObjectives:  Tongue volume reduction is an adjunct treatment in several orofacial orthopaedic procedures for various craniofacial deformities; it may affect structural reconstitution and functional recovery as a result of the repair process. The aim of this study was to investigate myogenic regeneration and structural alteration of the tongue following surgical tongue volume reduction.Materials and methods:  Five 12‐week‐old sibling pairs of Yucatan minipigs (three males and two females) were used. Midline uniform glossectomy was performed on one of each pair (reduction); siblings had identical incisions without tissue removal (sham). All pigs were raised for a further 4 weeks and received 5‐bromo‐2‐deoxyuridine (BrdU) injection intravenously 1 day before killing. Tissue sections of tongues were stained with anti‐BrdU antibody to evaluate numbers of replicating cells. Haematoxylin and eosin plus trichrome staining were performed to assess muscular structure.Results:  Reduction tongues contained significantly more BrdU+ cells compared to sham tongues (P < 0.01). However, these BrdU+ cells were mostly identified in reparative connective tissues (fibroblasts) rather than in regenerating muscle tissue (myoblasts). Trichrome‐stained sections showed disorganized collagen fibres linked to few intermittent muscle fibres in the reduction tongues. These myofibres presented signs of atrophy with reduced perimysium and endomysium. Matrix between reduced perimysium and endomysium was filled with fibrous tissue.Conclusions:  Fibrosis without predominant myogenic regeneration was the major histological consequence of surgical tongue volume reduction.
Identification of tyrosine‐nitrated proteins in HT22 hippocampal cells during glutamate‐induced oxidative stress
Authors: Yoon S.‐W. , Kang S. , Ryu S.‐E. , Poo H. 
Published: October 2010

AbstractObjectives:  Nitration of tyrosine residues in protein is a post‐translational modification, which occurs under oxidative stress, and is associated with several neurodegenerative diseases. To understand the role of nitrated proteins in oxidative stress‐induced cell death, we identified nitrated proteins and checked correlation of their nitration in glutamate‐induced HT22 cell death.Materials and methods:  Nitrated proteins were detected by western blotting using an anti‐nitrotyrosine antibody, extracted from matching reference 2‐dimensional electrophoresis gels, and identified with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry.Results:  Glutamate treatment induced apoptosis in HT22 cells, while reactive oxygen species (ROS) inhibitor or neuronal nitric oxide synthase (nNOS) inhibitor blocked glutamate‐induced HT22 cell death. Nitration levels of 13 proteins were increased after glutamate stimulation; six of them were involved in regulation of energy production and two were related to apoptosis. The other nitrated proteins were associated with calcium signal modulation, ER dysfunction, or were of unknown function.Conclusions:  The 13 tyrosine‐nitrated proteins were detected in these glutamate‐treated HT22 cells. Results demonstrated that cell death, ROS accumulation and nNOS expression were related to nitration of protein tyrosine in the glutamate‐stimulated cells.
Genistein and daidzein repress adipogenic differentiation of human adipose tissue‐derived mesenchymal stem cells via Wnt/β‐catenin signalling or lipolysis
Authors: Kim M.‐H. , Park J.‐S. , Seo M.‐S. , Jung J.‐W. , Lee Y.‐S. , Kang K.‐S. 
Published: October 2010

AbstractObjectives:  One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/β‐catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti‐adipogenic Wnt/β‐catenin signalling.Materials and methods:  Adipose tissue‐derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01–100 μm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs).Results:  Genistein and daidzein suppressed adipogenic differentiation of AD‐MSCs in a dose‐dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP‐1c and Glut 4, from mid‐phase differentiation. Microarrays showed that anti‐adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs‐dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co‐activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA‐mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD‐MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.
Schwann‐like cell differentiation of rat adipose‐derived stem cells by indirect co‐culture with Schwann cells in vitro
Authors: Wei Y. , Gong K. , Zheng Z. , Liu L. , Wang A. , Zhang L. , Ao Q. , Gong Y. , Zhang X. 
Published: October 2010

AbstractObjectives:  Schwann cell (SC) transplantation is a promising therapy for peripheral nerve transaction, however, clinical use of SCs is limited due to their very limited availability. Adipose‐derived stem cells (ADSCs) have been identified as an alternative source of adult stem cells in recent years. The aim of this study was to evaluate the feasibility of using ADSCs as a source of stem cells for differentiation into Schwann‐like cells by an indirect co‐culture approach, in vitro.Materials and methods:  Multilineage differentiation potential of the obtained ADSCs was assayed by testing their ability to differentiate into osteoblasts and adipocytes. The ADSCs were co‐cultured with SCs to be induced into Schwann‐like cells through proximity, using a Millicell system. Expression of typical SC markers S‐100, GFAP and P75NTR of the treated ADSCs was determined by immunocytochemical staining, western blotting and RT‐PCR. Myelination capacity of the differentiated ADSCs (dADSCs) was evaluated in dADSC/dorsal root ganglia neuron (DRGN) co‐cultures.Results:  The treated ADSCs adopted a spindle shaped‐like morphology after co‐cultured with SCs for 6 days. All results of immunocytochemical staining, western blotting and RT‐PCR showed that the treated cells expressed S‐100, GFAP and P75NTR, indications of differentiation. dADSCs could form Schwann‐like cell myelin in co‐culture with DRGNs. Undifferentiated ADSCs (uADSCs) did not form myelin compared to DRGNs cultured alone, but could produce neurite extension.Conclusions:  These results demonstrate that this indirect co‐culture microenvironment could induce ADSCs to differentiate into Schwann‐like cells in vitro, which may be beneficial for treatment of peripheral nerve injuries in the near future.
Chronic colitis induces expression of β-defensins in murine intestinal epithelial cells
Authors: Rahman A , Fahlgren A , Sundstedt C , Hammarström S , Danielsson Å , Hammarström M-L 
Published: October 2010

Summary
Anti-microbial peptides are important effectors in innate immunity. In the gut they defend against pathogens, shape the commensal microbiota and probably control intestinal homeostasis. Ulcerative colitis (UC), but not Crohn's disease, shows increased expression of inducible β-defensins (hBD-2, hBD-3 and hBD-4) in colonic epithelial cells. Does inducible defensin production precede the chronic intestinal inflammation characteristic of UC, or is it a consequence of the T cell-driven chronic inflammation? The aim was to analyse defensin mRNA and protein expression in colonic epithelial cells in two colitis mouse models resembling UC, the interleukin (IL)-2−/− mouse and the dextran sulphate sodium (DSS)-induced colitis mouse. Defensin mRNA was assayed by in situ hybridization and quantitative real-time reverse transcription–polymerase chain reaction (RT–PCR). Defensin peptide was assayed by immunohistochemistry. Mouse β-defensin 3 (mBD-3, orthologue to hBD-2) was up-regulated strongly in colonic epithelium of 15-week-old IL-2−/− mice and DSS-induced colitis mice with chronic bowel inflammation, but not in apparently healthy IL-2−/− 5-week-old mice, IL-2+/− 15-week-old mice or in acute stage DSS mice. Up-regulation was seen both at the mRNA- and at the protein level (only mBD-3 investigated). IL-17, but not several other cytokines, including interferon (IFN)-γ, induced mBD-3 mRNA expression in mouse colon carcinoma cells. The mRNA expression level of the constitutively expressed α-defensin, cryptdin-4, was up-regulated marginally in acute stage DSS-colitis mice and in IL-2−/− mice before signs of colitis. Inducible β-defensin expression in colonic epithelium is the consequence of the chronic bowel inflammation caused by activated T cells releasing cytokines including IL-17.
Genetic variation and community change – selection, evolution, and feedbacks
Authors: Genung Mark A. , Schweitzer Jennifer A. , Úbeda Francisco , Fitzpatrick Benjamin M. , Pregitzer Clara C. , Felker‐Quinn Emmi , Bailey Joseph K. 
Published: October 2010

Summary 1. There is relatively little information on how evolutionary processes that alter genetic variation in a focal species may affect interactions with other species, impact the structure or function of the community and ecosystem, and affect evolutionary feedbacks among interacting species through time. 2. Because evolution can occur at ecological time‐scales, it is important to understand how major selective events, such as climatic changes, can impact the community of interacting species and ecosystem processes by changing intraspecific genetic variation. 3. The evidence linking genetic variation and evolution to community change and feedbacks has arisen from several different approaches whose results have not been synthesized into one conceptual framework, and whose commonalities may not be fully understood. 4. This review synthesizes several different experimental approaches on how evolution may impact communities and ecosystems and focuses on five main issues: (i) the genetic basis to communities and ecosystems; (ii) the community and ecosystem consequences of among‐population genetic differentiation; (iii) the role of local adaptation and co‐evolution; (iv) the effects of trans‐generational feedbacks and the eco‐evo dynamic and; (v) the integration of community and ecosystem genetics and multi‐level selection. 5. Evolution can alter intraspecific genetic variation to affect indirect genetic effects and feedbacks. Future studies should investigate how communities and ecosystems are affected when evolution causes the strength of feedbacks to change.
Diversity in immunological synapse structure
Authors: Thauland Timothy J. , Parker David C. 
Published: October 2010

SummaryImmunological synapses (ISs) are formed at the T cell–antigen‐presenting cell (APC) interface during antigen recognition, and play a central role in T‐cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T‐cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non‐classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non‐classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T‐cell function.