bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial C5aR (CD88) expression correlates with amyloid‐β deposition in murine models of Alzheimer’s disease
Authors: Ager Rahasson R. , Fonseca Maria I. , Chu Shu‐Hui , Sanderson Sam D. , Taylor Stephen M. , Woodruff Trent M. , Tenner Andrea J. 
Published: February 2010

J. Neurochem. (2010) 113, 389–401.AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disease characterized by the accumulation of amyloid‐β protein and neuronal loss, is the leading cause of age‐related dementia in the world today. The disease is also associated with neuroinflammation, robust activation of astrocytes and microglia, and evidence of activation of the complement system, localized with both fibrillar amyloid‐β (fAβ) plaques and tangles. The observations are consistent with a complement‐dependent component of AD progression. We have previously shown that inhibition of the major complement receptor for C5a (CD88) with the antagonist PMX205 results in a significant reduction in pathology in two mouse models of AD. To further characterize the role of complement in AD‐related neuroinflammation, we examined the age‐ and disease‐associated expression of CD88 in brain of transgenic mouse models of AD and the influence of PMX205 on the presence of various complement activation products using flow cytometry, western blot, and immunohistochemistry. CD88 was found to be up‐regulated in microglia, in the immediate vicinity of amyloid plaques. While thioflavine plaque load and glial recruitment is significantly reduced after treatment with PMX205, C1q remains co‐localized with fAβ plaques and C3 is still expressed by the recruited astrocytes. Thus, with PMX205, potentially beneficial activities of these early complement components may remain intact, while detrimental activities resulting from C5a–CD88 interaction are inhibited. This further supports the targeted inhibition of specific complement mediated activities as an approach for AD therapy.
Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development
Authors: Kuo Emory , Park Daniel K. , Tzvetanova Iva D. , Leiton Cindy V. , Cho Brian S. , Colognato Holly 
Published: February 2010

J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06596.xAbstractOligodendrocyte progenitor cells first proliferate to generate sufficient cell numbers and then differentiate into myelin‐producing oligodendrocytes. The signal transduction mediators that underlie these events, however, remain poorly understood. The tyrosine phosphatase Shp1 has been linked to oligodendrocyte differentiation as Shp1‐deficient mice show hypomyelination. The Shp1 homolog, Shp2, has recently been shown to regulate astrogliogenesis, but its role in oligodendrocyte development remains unknown. Here, we report that Shp2 protein levels were developmentally regulated in oligodendrocytes, with Shp2 phosphorylation being promoted by oligodendroglial mitogens but suppressed by laminin, an extracellular matrix protein that promotes oligodendroglial differentiation. In contrast, oligodendrocyte progenitors were found to be unresponsive to mitogens following Shp2, but not Shp1, depletion. In agreement with previous studies, Shp1 depletion led to decreased levels of myelin basic protein in differentiating oligodendrocytes, as well as reduced outgrowth of myelin membrane sheets. Shp2 depletion in contrast did not prevent oligodendrocyte differentiation but promoted expanded myelin membrane outgrowth. Taken together these data suggest that Shp1 and Shp2 have distinct functions in oligodendrocyte development: Shp2 regulates oligodendrocyte progenitor proliferation and Shp1 regulates oligodendrocyte differentiation. Adhesion to laminin may additionally provide extrinsic regulation of Shp2 activity and thus promote the transition from progenitor to differentiating oligodendrocyte.
Principles of pharmacoeconomics and their impact on strategic imperatives of pharmaceutical research and development
Authors: Bodrogi József , Kaló Zoltán 
Published: February 2010

The importance of evidence‐based health policy is widely acknowledged among health care professionals, patients and politicians. Health care resources available for medical procedures, including pharmaceuticals, are limited all over the world. Economic evaluations help to alleviate the burden of scarce resources by improving the allocative efficiency of health care financing. Reimbursement of new medicines is subject to their cost‐effectiveness and affordability in more and more countries.There are three major approaches to calculate the cost‐effectiveness of new pharmaceuticals. Economic analyses alongside pivotal clinical trials are often inconclusive due to the suboptimal collection of economic data and protocol‐driven costs. The major limitation of observational naturalistic economic evaluations is the selection bias and that they can be conducted only after registration and reimbursement.Economic modelling is routinely used to predict the cost‐effectiveness of new pharmaceuticals for reimbursement purposes. Accuracy of cost‐effectiveness estimates depends on the quality of input variables; validity of surrogate end points; and appropriateness of modelling assumptions, including model structure, time horizon and sophistication of the model to differentiate clinically and economically meaningful outcomes. These economic evaluation methods are not mutually exclusive; in practice, economic analyses often combine data collection alongside clinical trials or observational studies with modelling.The need for pharmacoeconomic evidence has fundamentally changed the strategic imperatives of research and development (R&D). Therefore, professionals in pharmaceutical R&D have to be familiar with the principles of pharmacoeconomics, including the selection of health policy‐relevant comparators, analytical techniques, measurement of health gain by quality‐adjusted life‐years and strategic pricing of pharmaceuticals.
KMUP‐1 attenuates isoprenaline‐induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways
Authors: Yeh Jwu‐Lai , Hsu Jong‐Hau , Wu Ping‐Ju , Liou Shu‐Fen , Liu Chung‐Pin , Chen Ing‐Jun , Wu Bin‐Nan , Dai Zen‐Kong , Wu Jiunn‐Ren 
Published: February 2010

Background and purpose:  To determine whether KMUP‐1, a novel xanthine‐based derivative, attenuates isoprenaline (ISO)‐induced cardiac hypertrophy in rats, and if so, whether the anti‐hypertrophic effect is mediated by the nitric oxide (NO) pathway.Experimental approach:  In vivo, cardiac hypertrophy was induced by injection of ISO (5 mg·kg−1·day−1, s.c.) for 10 days in Wistar rats. In the treatment group, KMUP‐1 was administered 1 h before ISO. After 10 days, effects of KMUP‐1 on survival, cardiac hypertrophy and fibrosis, the NO/guanosine 3′5′‐cyclic monophosphate (cGMP)/protein kinase G (PKG) and hypertrophy signalling pathways [calcineurin A and extracellular signal‐regulated kinase (ERK)1/2] were examined. To investigate the role of nitric oxide synthase (NOS) in the effects of KMUP‐1, a NOS inhibitor, Nω‐nitro‐L‐arginine (L‐NNA) was co‐administered with KMUP‐1. In vitro, anti‐hypertrophic effects of KMUP‐1 were studied in ISO‐induced hypertrophic neonatal rat cardiomyocytes.Key results:  In vivo, KMUP‐1 pretreatment attenuated the cardiac hypertrophy and fibrosis and improved the survival of ISO‐treated rats. Plasma NOx (nitrite and nitrate) and cardiac endothelial NOS, cGMP and PKG were all increased by KMUP‐1. The activation of hypertrophic signalling by calcineurin A and ERK1/2 in ISO‐treated rats was also attenuated by KMUP‐1. All these effects of KMUP‐1 were inhibited by simultaneous administration of L‐NNA. Similarly, in vitro, KMUP‐1 attenuated hypertrophic responses and signalling induced by ISO in neonatal rat cardiomyocytes.Conclusions and implications:  KMUP‐1 attenuates the cardiac hypertrophy in rats induced by administration of ISO. These effects are mediated, at least in part, by NOS activation. This novel agent, which targets the NO/cGMP pathway, has a potential role in the prevention of cardiac hypertrophy.
Rapid Ventricular Pacing for Catheter Interventions in Congenital Aortic Stenosis and Coarctation: Effectiveness, Safety, and Rate Titration for Optimal Results
Authors: MEHTA CHETAN , DESAI TARAK , SHEBANI SUHAIR , STICKLEY JOHN , DE GIOVANNI JOSEPH 
Published: February 2010

Introduction: Infants and children with congenital aortic stenosis and coarctation of the aorta can be treated by catheter intervention. There are several pharmacological and mechanical techniques described to overcome the balloon movement; none, however, have proved entirely satisfactory. An alternative method to achieve balloon stability is the use of rapid ventricular pacing. We describe our experience with titrating the pacing rate and the use of this technique.
Methods: A retrospective review of database was performed, to identify patients who underwent transcatheter intervention with rapid ventricular pacing. Invasive systemic pressures were documented with a catheter in the aorta. Rapid ventricular pacing was initiated at the rate of 180 per minute and increased by increments of 20 per minute to a rate required to achieve a drop in systemic pressure by 50% and a drop in pulse pressure by 25%. The balloon was inflated only after the desired pacing rate was reached. Pacing was continued until the balloon was completely deflated.
Results: Thirty patients were identified, 29 of whom had interventions with rapid ventricular pacing. Balloon valvuloplasty of aortic valve was performed on 25 patients while 4 patients had stenting for coarctation by this technique. The rate of ventricular pacing required ranged from 200 to 260 per minute with a median rate of 240. Balloon stability at the time of intervention was achieved in 27 patients.
Conclusion: Rapid ventricular pacing is a safe and effective method to provide transient decrease in cardiac output at the time of transcatheter interventions to achieve balloon stability. (J Interven Cardiol 2010;23:7–13)
Sirolimus‐Eluting Stents versus Paclitaxel‐Eluting Stents in Patients with Chronic Renal Insufficiency
Authors: SYED ASMIR I. , BEN‐DOR ITSIK , COLLINS SARA D. , GONZALEZ MANUEL A. , GAGLIA, Jr. MICHAEL A. , TORGUSON REBECCA , SATLER LOWELL F. , SUDDATH WILLIAM O. , PICHARD AUGUSTO D. , LINDSAY JOSEPH , WAKSMAN RON 
Published: February 2010

Background: Chronic renal insufficiency (CRI) is associated with an increased incidence of restenosis and stent thrombosis. Drug‐eluting stents (DES), when compared to bare metal stents (BMS), reduce the incidence of restenosis in these patients. This study aimed to examine whether there are differences in clinical outcome after implantation of sirolimus‐eluting stents (SES) versus paclitaxel‐eluting stents (PES) in patients with CRI who are subjected to coronary intervention.
Methods: A cohort of 570 patients with CRI who underwent intervention with DES (346 with SES and 224 with PES) were followed clinically up to 1 year and the clinical events were recorded and compared between groups.
Results: Baseline and procedural characteristics were similar, with a slightly higher number of diseased vessels in the SES group as compared to the PES group (2.3 ± 0.9 vs 2.1 ± 0.9, P = 0.06). The overall rates of major adverse cardiac events (MACE) and stent thrombosis were similar. The PES group had lower revascularization rates when compared to the SES group. After covariate adjustment, however, there was no difference seen in target vessel revascularization between stent types (hazard ratio [HR]: 2.3 [0.8–6.2], P = 0.110). The strongest predictor of death and MACE at 1 year was the number of diseased vessels.
Conclusions: Patients with CRI who undergo PCI with either SES or PES have similar repeat revascularization rates and acceptable stent thrombosis rates, although they continue to have high MACE and death rates. (J Interven Cardiol 2010;23:33–39)
A comparison of two implant techniques on patient‐based outcome measures: a report of flapless vs. conventional flapped implant placement
Authors: Lindeboom Jerome A. , Van Wijk Arjen J. 
Published: February 2010

AbstractBackground: Flapless implant surgery is considered to offer advantages over the traditional flap access approach. There may be minimized bleeding, decreased surgical times and minimal patient discomfort. Controlled studies comparing patient outcome variables to support these assumptions, however, are lacking.Aim: The objective of this clinical study was to compare patient outcome variables using flapless and flapped implant surgical techniques.Patients and methods: From January 2008 to October 2008, 16 consecutive patients with edentulous maxillas were included in the study. Patients were randomly allocated to either implant placement with a flapless procedure (eight patients, mean age 54.6±2.9 years) or surgery with a conventional flap procedure (eight patients, mean age 58.7±7.2 years). All implants were placed using a Nobel guide® CT‐guided surgical template. Outcome measures were the Dutch version of the Impact of Event Scale‐Revised (IES‐R), dental anxiety using the s‐DAI and oral health‐related quality of life (OHIP‐14).Results: Ninety‐six implants were successfully placed. All implants were placed as two‐phase implants and the after‐implant placement dentures were adapted. No differences could be shown between conditions on dental anxiety (s‐DAI), emotional impact (IES‐R), anxiety, procedure duration or technical difficulty, although the flapless group did score consistently higher. The flap procedure group reported less impact on quality of life and included more patients who reported feeling no pain at all during placement.Conclusions: Differences found in the patient outcome variables do suggest that patients in the flapless implant group had to endure more than patients in the flap group. To cite this article:
Lindeboom JA, van Wijk AJ. A comparison of two implant techniques on patient‐based outcome measures: a report of flapless vs. conventional flapped implant placement. Clin. Oral Impl. Res. 21, 2010; 366–370. doi: 10.1111/j.1600‐0501.2009.01866.x
Alterations in the salivary proteome associated with periodontitis
Authors: Haigh Brendan J. , Stewart Kevin W. , Whelan John R. K. , Barnett Matthew P.G. , Smolenski Grant A. , Wheeler Thomas T. 
Published: February 2010

Haigh BJ, Stewart KW, Whelan JRK, Barnett MPG, Smolenski GA, Wheeler TT. Alterations in the salivary proteome associated with periodontitis. J Clin Periodontol 2010. 37: 241–247. doi: 10.1111/j.1600‐051X.2009.01525.xAbstractAim: To identify changes in the salivary proteome associated with active periodontitis.Materials and Methods: Quantitative proteomics (two‐dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis) was used to investigate whole saliva from individuals with severe periodontitis and their proteomic profiles before and after periodontal treatment were compared.Results: A comparison of 128 proteins across all saliva samples identified 15 protein spots with altered abundance. The predominant alteration observed was an increase in the abundance of the S100 proteins S100A8/A9/A6. Of the remaining proteins with altered abundance, haptoglobin, prolactin inducible protein and parotid secretory protein have previously been associated with host defence.Conclusion: These results highlight the predominant involvement of S100 proteins in the host response during periodontitis, identify host defence components that have not been linked previously to this disease and suggest new potential biomarkers for monitoring disease activity in periodontitis.
Fcγ receptor polymorphisms and their association with periodontal disease: a meta‐analysis
Authors: Dimou Niki L. , Nikolopoulos Georgios K. , Hamodrakas Stavros J. , Bagos Pantelis G. 
Published: February 2010

Dimou NL, Nikolopoulos GK, Hamodrakas SJ, Bagos PG. Fcγ receptor polymorphisms and their association with periodontal disease: a meta‐analysis. J Clin Periodontol 2010. 37: 255–265 doi: 10.1111/j.1600‐051X.2009.01530.x.AbstractAim: A systematic review and a meta‐analysis were conducted in order to investigate the potential association of Fcγ receptor (FcγR) polymorphisms with susceptibility to aggressive and chronic periodontal disease.Materials and Methods: A database search yielded a total of 17 studies involving 1685 cases and 1570 controls. Three polymorphisms were included in the meta‐analysis: FcγRIIA H131R (rs1801274), FcγRIIIA F158V (rs396991) and FcγRIIIB NA1/NA2. Random‐effect models were used in the analysis. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls.Results and Conclusions: The FcγRIIIB NA1/NA2 polymorphism was associated with both aggressive (per‐allele OR 2.005, 95% CI: 1.044, 3.851) and chronic periodontitis (recessive contrast NA2NA2 versus NA1NA1+NA1NA2 OR 1.397, 95% CI: 1.039, 1.878). The analysis showed weak evidence for association between the FcγRIIA H131R polymorphism and aggressive periodontitis in Asians (R versus H allele OR 1.579, 95% CI: 1.025, 2.432). On the contrary, no relationship was identified between FcγRIIIA F158V and periodontal disease. Accumulating evidence from basic research makes the suggested association between FcγRIIIB NA1/NA2 polymorphism and periodontitis biologically plausible. Further research, however, is needed in order to assess possible gene–gene or gene–environment interactions (i.e. with smoking).
The essential role of toll like receptor‐4 in the control of Aggregatibacter actinomycetemcomitans infection in mice
Authors: Lima Hayana Ramos , Gelani Valéria , Fernandes Ana Paula , Gasparoto Thaís Helena , Torres Sérgio Aparecido , Santos Carlos Ferreira , Garlet Gustavo Pompermaier , Da Silva João Santana , Campanelli Ana Paula 
Published: February 2010

Lima HR, Gelani V, Fernandes AP, Gasparoto TH, Torres SA, Santos CF, Garlet GP, da Silva JS, Campanelli AP. The essential role of toll like receptor‐4 in the control of Aggregatibacter actinomycetemcomitans infection in mice. J Clin Periodontol 2010; 37: 248–254. doi: 10.1111/j.1600‐051X.2009.01531.x.AbstractObjective: Aggregatibacter actinomycetemcomitans is an oral Gram‐negative bacterium that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll‐like receptors (TLRs). In this study, we evaluated the role of TLR4 in the control of A. actinomycetemcomitans infection.Material and Methods: We examined the mechanisms that modulate the outcome of A. actinomycetemcomitans‐induced periodontal disease in TLR4−/− mice. The production of cytokines was evaluated by ELISA. The bacterial load was determined by counting the number of colony‐forming units per gram of tissue.Results: The results showed that TLR4‐deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. However, the absence of TLR4 facilitated the A. actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in the periodontal tissue of TLR4−/− mice. We observed a significant reduction in the production of tumour necrosis factor‐alpha (TNF‐α) and interleukin (IL)‐1β in the periodontal tissue of TLR4−/− mice.Conclusion: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.
Sexual Function and Quality of Life in Women with Urinary Incontinence Treated by a Complete Pelvic Floor Rehabilitation Program (Biofeedback, Functional Electrical Stimulation, Pelvic Floor Muscles Exercises, and Vaginal Cones)
Authors: Rivalta Massimo , Sighinolfi Maria Chiara , Micali Salvatore , De Stefani Stefano , Bianchi Giampaolo 
Published: February 2010

ABSTRACT

Introduction
Urinary incontinence (UI) is a debilitating condition that can cause discomfort, embarrassment, loss of confidence; it can lead to withdrawal from social life, and adversely affects physical and mental health, sexual function and quality of life (QoL) in women.

Aim
The aim is to determine the impact of combined pelvic floor rehabilitation (PFR) on UI, female sexual dysfunction, and QoL.

Main Outcome Measures
Female Sexual Function Index questionnaire (FSFI) and King’s Health Questionnaire (KHQ).

Methods
Sixteen patients with UI were selected and underwent a complete PFR program (biofeedback, functional electrical stimulation, pelvic floor muscles exercises, and vaginal cones). Patient filled out the FSFI questionnaire and the KHQ at the baseline and at follow-up.

Results
After PFR none of the patients reported urine leakage during sexual activity. Resolution of incontinence was achieved in 13 (81.25%) women. Only three (18.75%) patients had positive 1-hour pad test after the treatment. There was significant difference between pad test leakage before and after the PFR (P &lt;0.001).
The mean Stamey incontinence score was 1.37 ± 0.5 at the baseline vs. 0.25 ± 0.57 at the follow up (P &lt;0.001). Before PFR, FSFI total score ranged from 25.8 to 2 (mean 14.65 ± 6.88), after treatment the FSFI total score ranged from 36 to 2 (mean 22.65 ± 9.5) (P &lt;0.001). The improvement of the scores in the six FSFI domains, 5 months after the conclusion of PFR, was statistically significant (desire, arousal, lubrication, orgasm, satisfaction, and pain). All the nine domains in the KHQ presented a low average score after treatment and the improvements were statistically significant.

Conclusions
PFR led to a significant difference in the daily use of pads, 1-hour pad test, and Stamey incontinence scores. The treatment caused an improvement in patient’s QoL index and sexual function.
The Anti‐Immigrant Fervor in Georgia: Return of the Nativist or Just Politics as Usual?
Authors: SABIA DEBRA 
Published: February 2010

This paper provides a review of various literatures on immigration, immigration policy formation, and immigrant reception with a particular focus on the state of Georgia. Existing scholarship has largely failed to explain why immigration policy outcomes have varied from state to state or how underlying factors might influence immigrant assimilation or exclusion. In the case of Georgia, the legislative response to newcomers has become increasingly inhospitable. What factors may account for this culture of exclusion? What variables have influenced Georgia officials to take up the anti‐immigrant cause? What has been the impact on the Hispanic community, and, finally, how may policy consequences influence future immigrant legislation in Georgia?Este artículo provee una revisión de varias fuentes sobre inmigración, formación de políticas de inmigración, y la recepción de inmigrantes con un enfoque particular en el estado de Georgia. Las investigaciones académicas existentes en gran parte han omitido explicar por qué los resultados de las políticas de inmigración han variado de estado a estado o cómo los factores subyacentes podrían influir la asimilación o exclusión del inmigrante. En el caso de Georgia, la respuesta legislativa a los recién llegados ha sido cada vez menos hospitalaria. ¿Qué factores pueden considerarse para esta cultura de exclusión? ¿Qué variables han influido en los oficiales de Georgia para hacer suya la causa anti‐inmigrante? ¿Qué variables han impactado a la comunidad Hispana? y finalmente ¿cómo pueden influir las consecuencias de las políticas en la futura legislación sobre inmigrantes en Georgia?