bluuebunny/crossref_metadata_2025 huggingface dataset:
A multiproxy palaeoenvironmental reconstruction of Loch Sunart (NW Scotland) since the Last Glacial Maximum
Authors: Mokeddem Zohra , Baltzer Agnes , Goubert Evelyne , Clet-Pellerin Martine
Published: November 2010

Loch Sunart is located on the NW coast of Scotland and contains a sedimentary sequence that records Lateglacial to Holocene climatic variations. A 12 m core MD04-2833 was acquired in the main basin of the loch sampling this sequence. We present the palaeoenvironmental data and palaeoclimatical scenario based on a multiproxy approach using pollen concentrations, sortable silt variation, lithic fraction and marine benthic foraminifera assemblages. These analyses allow the identification of major climate fluctuations such as cooling events. Global temperature decreases are discriminated from local water temperature decreases due to ice-melting processes by the presence of
Elphidium subarcticum
and the assemblage of
Cassidulina obtusa
and
Haynesina germanica
. Two meltwater pulses (MWP) are distinguished, which correspond to the MWP-Ia (15.5–13 cal ka BP) and MWP-Ib (12.2–10.1 cal ka BP). After the maximum water stratification occurred at 7.5 cal ka BP, full marine conditions were established around 6 cal ka BP, which correspond to the highest relative sea-level reached in the loch.
The physics of mid-latitude fjords: a review
Authors: Inall M. E. , Gillibrand P. A.
Published: November 2010

A rich and wide variety of fluid dynamic processes occur in fjords. Although a fjord may at one level be simply defined a glacially formed coastal inlet, this simple definition belies a huge range of geomorphological manifestations and environmental forcing conditions. It is the interplay between geomorphology and environmental forcing which defines the relative importance of differing physical fluid processes within a given fjord. In this chapter we present a non-mathematical review of the dominant physical processes which are found to occur in fjordic systems, how their relative importance may depend on geomorphology and forcing, and how, in turn, the dominant physical processes effect circulation and sediment distribution. Our aim is to provide the non-physical oceanographer with an insight into the rich and varied fluid dynamical processes presented to us by the fascinating ‘mini-ocean’ geo-type generically referred to as a fjord.
A major change in the dinoflagellate cyst flora of Gullmar Fjord, Sweden, at around 1969/1970 and its possible explanation
Authors: Harland Rex , Nordberg Kjell , Filipsson Helena L.
Published: November 2010

An ultra high-resolution study of the latest Holocene dinoflagellate cysts from Gullmar Fjord, on the west coast of Sweden, provides evidence for the recognition of at least two major dinoflagellate communities within the fjord over the last 85 years. These communities may result from changes within the North Atlantic Oscillation (NAO) and hydrography of the fjord between the approximate years 1915 and 1999 and/or from the local pollution history. The dinoflagellate cyst populations were compared in detail with hydrographical parameters available from this fjord with its long historical instrumental records. The dinoflagellate cysts fail to demonstrate a convincing ongoing eutrophication for the fjord, although the reduction of
Lingulodinium polyedrum
partly coincides with the curtailment of activity at a sulphite pulp mill at Munkedal and canning activity at Lysekil, together with a cessation in the influx of untreated sewage from water closets. The significant change in the assemblage composition at about the late 1960s/early 1970s coincides with a change in the NAO from a negative phase to its present-day positive phase. The unravelling of local environmental effects from those associated with regional fluctuations is complex and needs to be approached with caution.
Dipeptidyl peptidase IV inhibitor sitagliptin reduces local inflammation in adipose tissue and in pancreatic islets of obese mice
Authors: Dobrian A. D. , Ma Q. , Lindsay J. W. , Leone K. A. , Ma K. , Coben J. , Galkina E. V. , Nadler J. L.
Published: November 2010

Adipose tissue inflammation and reduced pancreatic β-cell function are key issues in the development of cardiovascular disease and progressive metabolic dysfunction in type 2 diabetes mellitus. The aim of this study was to determine the effect of the DPP IV inhibitor sitagliptin on adipose tissue and pancreatic islet inflammation in a diet-induced obesity model. C57Bl/6J mice were placed on a high-fat (60% kcal fat) diet for 12 wk, with or without sitagliptin (4 g/kg) as a food admix. Sitagliptin significantly reduced fasting blood glucose by 21% as well as insulin by ∼25%. Sitagliptin treatment reduced body weight without changes in overall body mass index or in the epididymal and retroperitoneal fat mass. However, sitagliptin treatment led to triple the number of small adipocytes despite reducing the number of the very large adipocytes. Sitagliptin significantly reduced inflammation in the adipose tissue and pancreatic islet. Macrophage infiltration in adipose tissue evaluated by immunostaining for Mac2 was reduced by sitagliptin ( P < 0.01), as was the percentage of CD11b+/F4/80+ cells in the stromal vascular fraction ( P < 0.02). Sitagliptin also reduced adipocyte mRNA expression of inflammatory genes, including IL-6, TNFα, IL-12(p35), and IL-12(p40), 2.5- to fivefold as well as 12-lipoxygenase protein expression. Pancreatic islets were isolated from animals after treatments. Sitagliptin significantly reduced mRNA expression of the following inflammatory cytokines: MCP-1 (3.3-fold), IL-6 (2-fold), IL-12(p40) (2.2-fold), IL-12(p35) (5-fold, P < 0.01), and IP-10 (2-fold). Collectively, the results indicate that sitagliptin has anti-inflammatory effects in adipose tissue and in pancreatic islets that accompany the insulinotropic effect.
Location of Release Sites and Calcium-Activated Chloride Channels Relative to Calcium Channels at the Photoreceptor Ribbon Synapse
Authors: Mercer A. J. , Rabl K. , Riccardi G. E. , Brecha N. C. , Stella S. L. , Thoreson W. B.
Published: November 2010

Vesicle release from photoreceptor ribbon synapses is regulated by L-type Ca2+ channels, which are in turn regulated by Cl− moving through calcium-activated chloride [Cl(Ca)] channels. We assessed the proximity of Ca2+ channels to release sites and Cl(Ca) channels in synaptic terminals of salamander photoreceptors by comparing fast (BAPTA) and slow (EGTA) intracellular Ca2+ buffers. BAPTA did not fully block synaptic release, indicating some release sites are <100 nm from Ca2+ channels. Comparing Cl(Ca) currents with predicted Ca2+ diffusion profiles suggested that Cl(Ca) and Ca2+ channels average a few hundred nanometers apart, but the inability of BAPTA to block Cl(Ca) currents completely suggested some channels are much closer together. Diffuse immunolabeling of terminals with an antibody to the putative Cl(Ca) channel TMEM16A supports the idea that Cl(Ca) channels are dispersed throughout the presynaptic terminal, in contrast with clustering of Ca2+ channels near ribbons. Cl(Ca) currents evoked by intracellular calcium ion concentration ([Ca2+]i) elevation through flash photolysis of DM-nitrophen exhibited EC50 values of 556 and 377 nM with Hill slopes of 1.8 and 2.4 in rods and cones, respectively. These relationships were used to estimate average submembrane [Ca2+]i in photoreceptor terminals. Consistent with control of exocytosis by [Ca2+] nanodomains near Ca2+ channels, average submembrane [Ca2+]i remained below the vesicle release threshold (∼400 nM) over much of the physiological voltage range for cones. Positioning Ca2+ channels near release sites may improve fidelity in converting voltage changes to synaptic release. A diffuse distribution of Cl(Ca) channels may allow Ca2+ influx at one site to influence relatively distant Ca2+ channels.
A gene expression signature for insulin resistance
Authors: Konstantopoulos Nicky , Foletta Victoria C. , Segal David H. , Shields Katherine A. , Sanigorski Andrew , Windmill Kelly , Swinton Courtney , Connor Tim , Wanyonyi Stephen , Dyer Thomas D. , Fahey Richard P. , Watt Rose A. , Curran Joanne E. , Molero Juan-Carlos , Krippner Guy , Collier Greg R. , James David E. , Blangero John , Jowett Jeremy B. , Walder Ken R.
Published: November 2010

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made “insulin resistant” by treatment with tumor necrosis factor-α (TNF-α) and then reversed with aspirin and troglitazone (“resensitized”). The GES consisted of five genes whose expression levels best discriminated between the insulin-resistant and insulin-resensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed with aspirin and troglitazone. This screen identified both known and new insulin-sensitizing compounds including nonsteroidal anti-inflammatory agents, β-adrenergic antagonists, β-lactams, and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study ( n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that GES technology can be used for both the discovery of insulin-sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.
A Pharmacodynamic Study of Docetaxel in Combination with the P-glycoprotein Antagonist Tariquidar (XR9576) in Patients with Lung, Ovarian, and Cervical Cancer
Authors: Kelly Ronan J. , Draper Deborah , Chen Clara C. , Robey Robert W. , Figg William D. , Piekarz Richard L. , Chen Xiaohong , Gardner Erin R. , Balis Frank M. , Venkatesan Aradhana M. , Steinberg Seth M. , Fojo Tito , Bates Susan E.
Published: November 2010

Purpose: P-glycoprotein (Pgp) antagonists have been difficult to develop because of complex pharmacokinetic interactions and a failure to show meaningful results. Here we report the results of a pharmacokinetic and pharmacodynamic trial using a third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576), in combination with docetaxel.

Experimental Design: In the first treatment cycle, the pharmacokinetics of docetaxel (40 mg/m2) were evaluated after day 1 and day 8 doses, which were administered with or without tariquidar (150 mg). 99mTc-sestamibi scanning and CD56+ mononuclear cell rhodamine efflux assays were conducted to assess Pgp inhibition. In subsequent cycles, 75 mg/m2 docetaxel was administered with 150 mg tariquidar every 3 weeks.

Results: Forty-eight patients were enrolled onto the trial. Nonhematologic grade 3/4 toxicities in 235 cycles were minimal. Tariquidar inhibited Pgp-mediated rhodamine efflux from CD56+ cells and reduced 99mTc-sestamibi clearance from the liver. There was striking variability in basal sestamibi uptake; a 12% to 24% increase in visible lesions was noted in 8 of 10 patients with lung cancer. No significant difference in docetaxel disposition was observed in pairwise comparison with and without tariquidar. Four partial responses (PR) were seen (4/48); 3 in the non–small cell lung cancer (NSCLC) cohort, measuring 40%, 57%, and 67% by RECIST, and 1 PR in a patient with ovarian cancer.

Conclusions: Tariquidar is well tolerated, with less observed systemic pharmacokinetic interaction than previous Pgp antagonists. Variable effects of tariquidar on retention of sestamibi in imageable lung cancers suggest that follow-up studies assessing tumor drug uptake in this patient population would be worthwhile. Clin Cancer Res; 17(3); 569–80. ©2010 AACR.
Virtual Reality in Pediatric Neurorehabilitation: Attention Deficit Hyperactivity Disorder, Autism and Cerebral Palsy
Authors: Wang Michelle , Reid Denise
Published: November 2010

This paper presents the current status and use of virtual reality (VR) for children with attention deficit hyperactivity disorder (ADHD), autism and cerebral palsy. This literature review explores how VR systems have been used as treatment tools to address the primary impairments of these disorders. Three major classes of VR display systems are identified that can be characterized by the type of human-computer interaction provided: (1) feedback-focused interaction, (2) gesture-based interaction, and (3) haptic-based interaction. The demonstrated effectiveness and potential effectiveness of each class are discussed in the context of remediating the primary impairments of children with ADHD, autism and cerebral palsy. Three major themes for future research are discussed to support continued research interest in using VR in pediatric neurorehabilitation.
Acute Spiral Ganglion Cell Degeneration following Acoustic Overstimulation: An Experimental Study
Authors: Eskiizmir Görkem , Yücetürk Ali Vefa , İnan Sevinç , Gürgen Seren Gülşen
Published: November 2010

Background: To evaluate acoustic overstimulation-induced spiral ganglion cell (SGC) degeneration, and determine the relationship between the duration of acoustic overstimulation and rate of SGC degeneration. Methods: Fifteen guinea pigs were randomized equally to 4 experimental groups, which were exposed to different durations (7.5, 15, 30 and 60 min) of acoustic overstimulation (120 dB at 4 kHz), and a control group. Every bulla was examined histopathologically and immunohistochemically. A quantitative and statistical analysis of acidophilic and TUNEL-positive SGCs was performed. Results: In the control group, 2.1% of SGCs were acidophilic and no TUNEL-positive SGC was detected. In contrast, a statistically significant number of acidophilic (p = 0.000) and TUNEL-positive SGCs (p = 0.002) was determined in the experimental groups. Moreover, a positive correlation between the duration of acoustic overstimulation and acidophilic SGCs (p = 0.000), and a statistically significant relationship between the duration of acoustic overstimulation and TUNEL-positive SGCs (p = 0.000) were demonstrated. Conclusion: Acoustic overstimulation may induce acute SGC degeneration. A positive correlation was determined between the duration of acoustic overstimulation and rate of degenerated SGCs.
Risk of Recurrent Cerebrovascular Events in Patients with Cryptogenic Stroke or Transient Ischemic Attack and Patent Foramen Ovale: The FORI (Foramen Ovale Registro Italiano) Study
Authors: Paciaroni Maurizio , Agnelli Giancarlo , Bertolini Andrea , Pezzini Alessandro , Padovani Alessandro , Caso Valeria , Venti Michele , Alberti Andrea , Palmiero Rosa Antonietta , Cerrato Paolo , Silvestrelli Giorgio , Lanari Alessia , Previdi Paolo , Corea Francesco , Balducci Alessandro , Ferri Roberto , Falcinelli Francesca , Filippucci Esmeralda , Chiocchi Paolo , Grandi Fabio Chiodo , Ferigo Laura , Musolino Rosa , Bersano Anna , Ghione Isabella , Sacco Simona , Carolei Antonio , Baldi Antonio , Ageno Walter ,   for the FORI (Foramen Ovale Registro Italiano) Investigators
Published: November 2010

Background: The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale (PFO) at diagnostic workup remains unclear. The aims of this observational multicenter study were to evaluate: (1) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack (TIA) and PFO who either underwent percutaneous PFO closure or received only medical treatment, and (2) the risk factors associated with recurrent events. Methods: Consecutive patients (aged 55 years or less) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years. Results: 238 patients were included in the study (mean age 42.2 ± 10.0 years; 118 males); 117 patients (49.2%) received only antithrombotic therapy while 121 patients underwent percutaneous PFO closure (50.8%). Stroke as the qualifying event was more common in the medical treatment group (p = 0.01). The presence of atrial septal aneurysm and evidence of 20 bubbles or more on transcranial Doppler were more common in the PFO closure group (p = 0.002 and 0.02). Eight patients (6.6%) experienced a nonfatal complication during PFO closure. At the 2-year follow-up, 17 recurrent events (TIA or stroke; 3.6% per year) were observed; 7 of these events (2.9% per year) occurred in the percutaneous PFO closure group and 10 events (4.2% per year) in the medical treatment group. The rate of recurrent stroke was 0.4% per year in patients who underwent percutaneous closure (1 event) and 3.4% per year in patients who received medical treatment (8 events). On multivariate analysis, percutaneous closure was not protective in preventing recurrent TIA or stroke (OR = 0.1, 95% CI = 0.02–1.5, p = 0.1), while it was barely protective in preventing recurrent stroke (OR = 0.1, 95% CI = 0.0–1.0, p = 0.053). Conclusions: The results of this observational, nonrandomized study suggest that PFO closure might be superior to medical therapy for the prevention of recurrent stroke. Periprocedural complications were the trade-off for this clinical benefit. Controlled randomized clinical trials comparing percutaneous closure with medical management are required.
Low Lymphocyte Ratio as a Novel Prognostic Factor in Acute Heart Failure: Results from the Pre-RELAX-AHF Study
Authors: Milo-Cotter Olga , Teerlink John R. , Metra Marco , Felker G. Michael , Ponikowski Piotr , Voors Adriaan A. , Edwards Christopher , Weatherley Beth Davison , Greenberg Barry , Filippatos Gerassimos , Unemori Elaine , Teichman Sam L. , Cotter Gad
Published: November 2010

Background: Previous studies have suggested that a lower lymphocyte ratio (Ly%) in the white blood cell (WBC) differential count is related to worse outcomes in patients with acute heart failure (AHF) and other cardiovascular disorders. Methods: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood pressure >125 mm Hg and brain natriuretic peptide ≧350 pg/ml or equivalent were randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for 6 months following randomization. Complete blood count and differential were performed by a central laboratory at baseline and then daily to day 5 and on day 14. Results: The WBC count by itself was not associated with measures of disease severity or outcome, and patients with Ly% <13% had similar baseline characteristics to patients with Ly% >13%, except for a higher baseline WBC count, elevated baseline glucose, older age and higher rates of peripheral vascular disease. However, patients with Ly% <13% had less improvement of dyspnea, greater worsening of heart failure, longer length of initial hospital stay and fewer days alive and out of hospital. Statistical significance was reached for all-cause death by days 60 and 180 (hazard ratio = 1.11 per percent decrease, 95% confidence interval 1.03–1.19; p = 0.0048). Conclusions: Despite no association with any baseline characteristic known to strongly predict outcome in AHF, low Ly% is associated with less symptom relief and worse in-hospital and postdischarge clinical outcomes.
Violence, Anti-Convention and Desires for Transformation amongst Pakistan’s Mohajirs in Karachi
Authors: Khan Nichola
Published: November 2010

This article investigates practices of militancy amongst young men who became political mercenaries during the (1984—2002) Karachi conflict involving Pakistan’s ethno-nationalist Mohajir party, the MQM. It explores the affective domain which emerges out of ethnicized positions on identity, and its role in structuring political subjectivity and violent action. Political killings were not solely driven through class, deprivation or ethnic politics, but also by idealized images of manhood and desires for creating and restoring selfhood in meaningful ties with other militants. While the violence led MQM into government, for militants it produced an incommensurable relationship between generativeness and violence in which deep disappointments and fractured masculinities were powerfully inscribed.
Paullinia cupana Mart. var. Sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity
Authors: de Oliveira Diêgo Madureira , Barreto George , Galeano Pablo , Romero Juan Ignacio , Holubiec Mariana Inés , Badorrey Maria Sol , Capani Francisco , Giraldez Alvarez Lisandro Diego
Published: November 2010

Paullinia cupana Mart. var. Sorbilis, commonly known as Guaraná, is a Brazilian plant frequently cited for its antioxidant properties and different pharmacological activities on the central nervous system. The potential beneficial uses of Guaraná in neurodegenerative disorders, such as in Parkinson's disease (PD), the pathogenesis of which is associated with mitochondrial dysfunction and oxidative stress, has not yet been assessed. Therefore, the main aim of the present study was to evaluate if an extract of commercial powdered seeds of Guaraná could protect human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Two concentration of Guaraná dimethylsulfoxide extract (0.312 and 0.625 mg/mL) were added to SH-SY5Y cells treated with 300 nM rotenone for 48 h, and the cytoprotective effects were assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, measuring lactate dehydrogenase (LDH) levels, and analyzing nuclear integrity with Hoechst33258 stain. Results showed that the addition of Guaraná extract significantly increased the cell viability of SH-SY5Y cells treated with rotenone, in a dose-dependent manner. On the other hand, LDH levels were significantly reduced by addition of 0.312 mg/mL of Guaraná, but unexpectedly, no changes were observed with the higher concentration. Moreover, chromatin condensation and nuclear fragmentation were significantly reduced by addition of any of both concentrations of the extract. The results obtained in this work could provide relevant information about the mechanisms underlying the degeneration of dopaminergic neurons in PD and precede in vivo experiments. Further studies are needed to investigate which active constituent is responsible for the cytoprotective effect produced by Paullinia cupana.
Joking Aside, Insights to Employee Dignity in “Dilbert” Cartoons: The Value of Comic Art in Understanding the Employer—Employee Relationship
Authors: Doherty Elizabeth M.
Published: November 2010

Catholic social teaching makes the moral argument for the importance of dignity at work, and organization studies scholars have documented workers’ plight. Yet, neither perspective sufficiently provides a sense of the feelings that managers and employees have toward one another. Adopting an aesthetics approach, and drawing from comic art and the cartoon strip Dilbert, this research provides an alternative view to understand challenges to employee dignity. Like aesthetics and art, comic art reflects feelings and attitudes and aims to provide insight into contemporary life. The results from surveying Dilbert found that managers often viewed their subordinates as exploitable commodities and threatened them with abuse. They point to a possible structural explanation for why employers view their workers so disparagingly and why employees feel their dignity challenged. This research makes evident the potential value of an aesthetics/comic arts perspective to understand and address issues concerning human behavior in the workplace.
Problematizing Actors and Institutions in Institutional Work
Authors: Hwang Hokyu , Colyvas Jeannette A.
Published: November 2010

The growing popularity of institutional work suggests a broad agentic turn in institutional approaches to organizational studies. We briefly describe the contribution of the evolving institutional-work research agenda. Then, we identify two problematic areas in this line of research: the privileged causal status of “actors” and the under-theorized nature of institutions. We suggest that re-engagement with insights of the earlier, foundational work in neo-institutional theory would benefit this emerging research agenda.
Pulmonary rehabilitation reduces depression and enhances health-related quality of life in COPD patients - especially in patients with mild or moderate disease
Authors: Bratås O. , Espnes GA , Rannestad T. , Walstad R.
Published: November 2010

The first objective of the study was to evaluate a 4-week inpatient pulmonary rehabilitation program on exercise capacity, health-related quality of life (HRQL) and psychological distress in patients with COPD. The second objective was to investigate the influence of gender, age, disease severity, co-morbidity, anxiety and depression on improved HRQL after rehabilitation. The study comprised 136 consecutive patients from baseline to follow-up with mild-to-severe COPD. Exercise capacity was measured by the 6-min walking distance test, disease severity by spirometric tests, HRQL by The St. George’s Respiratory Questionnaire and psychological distress by the The Hospital Anxiety and Depression Scale. Variables on socio-demography and co-morbidity were self-reported. Exercise capacity was improved from baseline to follow-up with a score difference of +44 metres (p = 000). Except for the activity score, HRQL was significantly improved: a change of -3.5 for the symptom score (p = 014), —3.1 for the total score (p = 003) and a clinical significant change of — 4.0 for the impact score (p = 002). The anxiety score did not change significantly after rehabilitation (—0.1, p = 545), though there was a significant reduction of the depression score (—0.8, p = 002) and a 10.4% reduction in the prevalence of possible depression cases (p = 017). Patients with forced expiratory volume in 1 second ≥50% predicted were 4.2 times more likely to achieve a clinical significant improved HRQL after rehabilitation than patients with forced expiratory volume in 1 second <50% predicted (95% confidence interval [CI] 1.7—10.3, p = 002). A 4-week inpatient rehabilitation program improves HRQL and exercise capacity and reduces depression in COPD patients. Patients with mild or moderate disease are more likely to achieve an improved HRQL after rehabilitation than patients with severe or very severe disease.
Strategies to engage clinical staff in subject recruitment
Authors: Serge Lisa S. , Buckwalter Kathleen C. , Friedemann Marie-Luise
Published: November 2010

Purpose. In many countries, meeting subject recruitment goals is challenging for researchers relying on clinical staff members (CSMs) to identify or recruit subjects. This paper describes research strategies that improved staff engagement in three different studies conducted in US clinical settings.

Method. The recruitment strategies described in this paper were identified during the process of consultation among three US researchers recruiting via CSMs. Strategies which successfully engaged CSMs are described.

Results. Our approach improved engagement with CSMs in three different US studies. Early engagement strategies included establishing trust, gathering input from CSMs, and using succinct training procedures as well as a study logo. Middle phase strategies included assigning recruitment, publishing a study newsletter, giving the CSMs compensation and appreciation for their participation, and expanding the subject pool. Completion strategies included closing with an appreciation meeting and adding merit letters to personnel files.

Conclusion. Recruitment of an adequate number of subjects is often challenging, even within clinical settings where subject populations are abundant. CSMs have rightly prioritised clinical care over directing subjects to research studies. It is therefore critical that researchers recruiting in such clinical settings anticipate recruitment challenges and plan to implement appropriate engagement strategies in all phases of research.
Validation of a new concept: aptitudes of psychiatric nurses caring for depressed patients
Authors: Haspeslagh Marc , Eeckloo Kristof , Delesie Lucas B.
Published: November 2010

Validation is vital for operationalising a new concept into a measurement instrument. The measurement of human attributes is usually done with questionnaire items in ordered categories. Our objective was to validate a questionnaire capable of measuring, at the ordinal level, the aptitude of psychiatric nurses caring for depressed patients. We used expert panels, experimentation, categorical principal component analysis, and parametric and non-parametric item response theory to develop such a questionnaire and assess its validity. Expert panels delineated five aspects and 29 components of aptitude and formulated 32 items. Four consecutive exploratory experiments were performed to gauge and calibrate the items and their response categories into a semantic frame of reference and a socio-cultural and job context of nurses. This resulted in a questionnaire comprising three aspects of aptitude. Fourteen questionnaire items with a different number of response categories assessed aptitude. Appropriate techniques shed light onto how nurses understand and respond to items in the questionnaire. Before it can be reliably used in a different context, the questionnaire needs to be re-evaluated for validity. Moreover, validity needs to be re-established for translated versions. In conclusion, validation is a process. Understanding that the scope and limitations of a questionnaire develop as it is being used requires validity to be re-established at each step of development.
Allogeneic transplant for chronic myeloid leukemia in 2010
Authors: Radich Jerald P.
Published: November 2010

Tyrosine kinase inhibitor (TKI) therapy has revolutionized the therapy of chronic myeloid leukemia (CML). Thus, while in the near past allogeneic transplantation was the curative option for CML, imatinib, nilotinib, and dasatinib have pushed transplantation to the role of salvage therapy in CML. Still, TKI therapy still fails some patients, and so the clinical challenge is to integrate transplantation in a safe and sane manner. This manuscript reviews the data on the variables that have an influence on outcome following transplantation, and discusses the variables to consider in determining who and when patients should receive transplantation.
Postnatal development of depth-dependent collagen density in ovine articular cartilage
Authors: van Turnhout Mark C , Schipper Henk , van Lagen Barend , Zuilhof Han , Kranenbarg Sander , van Leeuwen Johan L
Published: November 2010

Background

Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for the functions of adult AC. Collagen is the most abundant solid component and it affects the mechanical behaviour of AC. The current objective is to quantify the postnatal development of depth-dependent collagen density in sheep (Ovis aries) AC between birth and maturity. We use Fourier transform infra-red micro-spectroscopy to investigate collagen density in 48 sheep divided over ten sample points between birth (stillborn) and maturity (72 weeks). In each animal, we investigate six anatomical sites (caudal, distal and rostral locations at the medial and lateral side of the joint) in the distal metacarpus of a fore leg and a hind leg.

Results

Collagen density increases from birth to maturity up to our last sample point (72 weeks). Collagen density increases at the articular surface from 0.23 g/ml ± 0.06 g/ml (mean ± s.d.,n= 48) at 0 weeks to 0.51 g/ml ± 0.10 g/ml (n= 46) at 72 weeks. Maximum collagen density in the deeper cartilage increases from 0.39 g/ml ± 0.08 g/ml (n= 48) at 0 weeks to 0.91 g/ml ± 0.13 g/ml (n= 46) at 72 weeks. Most collagen density profiles at 0 weeks (85%) show a valley, indicating a minimum, in collagen density near the articular surface. At 72 weeks, only 17% of the collagen density profiles show a valley in collagen density near the articular surface. The fraction of profiles with this valley stabilises at 36 weeks.

Conclusions

Collagen density in articular cartilage increases in postnatal life with depth-dependent variation, and does not stabilize up to 72 weeks, the last sample point in our study. We find strong evidence for a valley in collagen densities near the articular surface that is present in the youngest animals, but that has disappeared in the oldest animals. We discuss that the retardance valley (as seen with polarised light microscopy) in perinatal animals reflects a decrease in collagen density, as well as a decrease in collagen fibril anisotropy.
Analyses of genome architecture and gene expression reveal novel candidate virulence factors in the secretome of Phytophthora infestans
Authors: Raffaele Sylvain , Win Joe , Cano Liliana M , Kamoun Sophien
Published: November 2010

Background

Phytophthora infestans is the most devastating pathogen of potato and a model organism for the oomycetes. It exhibits high evolutionary potential and rapidly adapts to host plants. The P. infestans genome experienced a repeat-driven expansion relative to the genomes of Phytophthora sojae and Phytophthora ramorum and shows a discontinuous distribution of gene density. Effector genes, such as members of the RXLR and Crinkler (CRN) families, localize to expanded, repeat-rich and gene-sparse regions of the genome. This distinct genomic environment is thought to contribute to genome plasticity and host adaptation.

Results

We used in silico approaches to predict and describe the repertoire of P. infestans secreted proteins (the secretome). We defined the "plastic secretome" as a subset of the genome that (i) encodes predicted secreted proteins, (ii) is excluded from genome segments orthologous to the P. sojae and P. ramorum genomes and (iii) is encoded by genes residing in gene sparse regions of P. infestans genome. Although including only ~3% of P. infestans genes, the plastic secretome contains ~62% of known effector genes and shows >2 fold enrichment in genes induced in planta. We highlight 19 plastic secretome genes induced in planta but distinct from previously described effectors. This list includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine-rich proteins and repeat containing proteins that we propose to be novel candidate virulence factors.

Conclusions

This work revealed a remarkably diverse plastic secretome. It illustrates the value of combining genome architecture with comparative genomics to identify novel candidate virulence factors from pathogen genomes.
Functionally relevant microsatellites in sugarcane unigenes
Authors: Parida Swarup K , Pandit Awadhesh , Gaikwad Kishor , Sharma Tilak R , Srivastava Prem Shankar , Singh Nagendra K , Mohapatra Trilochan
Published: November 2010

Background

Unigene sequences constitute a rich source of functionally relevant microsatellites. The present study was undertaken to mine the microsatellites in the available unigene sequences of sugarcane for understanding their constitution in the expressed genic component of its complex polyploid/aneuploid genome, assessing their functional significance in silico, determining the extent of allelic diversity at the microsatellite loci and for evaluating their utility in large-scale genotyping applications in sugarcane.

Results

The average frequency of perfect microsatellite was 1/10.9 kb, while it was 1/44.3 kb for the long and hypervariable class I repeats. GC-rich trinucleotides coding for alanine and the GA-rich dinucleotides were the most abundant microsatellite classes. Out of 15,594 unigenes mined in the study, 767 contained microsatellite repeats and for 672 of these putative functions were determined in silico. The microsatellite repeats were found in the functional domains of proteins encoded by 364 unigenes. Its significance was assessed by establishing the structure-function relationship for the beta-amylase and protein kinase encoding unigenes having repeats in the catalytic domains. A total of 726 allelic variants (7.42 alleles per locus) with different repeat lengths were captured precisely for a set of 47 fluorescent dye labeled primers in 36 sugarcane genotypes and five cereal species using the automated fragment analysis system, which suggested the utility of designed primers for rapid, large-scale and high-throughput genotyping applications in sugarcane. Pair-wise similarity ranging from 0.33 to 0.84 with an average of 0.40 revealed a broad genetic base of the Indian varieties in respect of functionally relevant regions of the large and complex sugarcane genome.

Conclusion

Microsatellite repeats were present in 4.92% of sugarcane unigenes, for most (87.6%) of which functions were determined in silico. High level of allelic diversity in repeats including those present in the functional domains of proteins encoded by the unigenes demonstrated their use in assay of useful variation in the genic component of complex polyploid sugarcane genome.
Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells
Authors: Yang Ke , Wang Xiao Qun , He Yu Song , Lu Lin , Chen Qiu Jing , Liu Jing , Shen Wei Feng
Published: November 2010

Background

Advanced glycation products (AGEs), as endogenous inflammatory mediator, compromise the physiological function of mesenchymal stem cells (MSCs). MSCs have a potential role in cell replacement therapy in acute myocardial infarction and ischemic cardiomyopathy. However, mechanisms of AGEs on MSCs are still not unveiled.

Methods

Reactive oxygen species (ROS), genes regulation, cell proliferation and migration have been detected by AGE-BSA stimulated MSCs.

Results

We found that in vitro stimulation with AGE-BSA induced generation of reactive oxygen species (ROS), and inhibited dose-dependently proliferation and migration of MSCs. Microarray and molecular biological assessment displayed an increased expression and secretion of Ccl2, Ccl3, Ccl4 and Il1b in a dose- and time-dependent manner. These chemokines/cytokines of equivalent concentration to those in conditioned medium exerted an inhibitory effect on MSC proliferation and migration after stimulation for 24 h. Transient elevation of phospho-p38 in MSCs upon AGE-BSA stimulation was blocked with p38 inhibitor.

Conclusions

The study indicates that AGE-BSA induces production of chemokines/cytokines in a dose- and time-dependent manner via activation of ROS-p38 mediated pathway. These chemokines/cytokines exert an inhibitory effect on MSC growth and migration, suggesting an amplified dysfunction of MSCs by AGEs.
Metabolic abnormalities in adolescents with polycystic ovary syndrome in south china
Authors: Huang Jia , Ni Renmin , Chen Xiaoli , Huang Lili , Mo Yaqin , Yang Dongzi
Published: November 2010

Background

Adults with polycystic ovary syndrome (PCOS) can have multiple metabolic abnormalities. However, studies in the adolescent population are still limited and these results seem to vary widely. This study was to investigate the metabolic abnormalities in adolescents with PCOS in South China and the potential risk factors contributed to these health risks.

Methods

Anthropometric measurements and biochemical parameters were evaluated in 128 adolescents with PCOS and their age- and BMI-matched controls.

Results

The prevalence of pre-diabetes, insulin resistance, hyperinsulinemia, dyslipidemia and metabolic syndrome in adolescents with PCOS was 11.7%, 46.9%, 29.7%, 22.7% and 4.7%, respectively. 16.3%, 74.4%, 67.4%, 39.5% and 14% of the PCOS subjects with BMI > 85th had pre-diabetes, insulin resistance, hyperinsulinemia, dyslipidemia and metabolic syndrome, whereas 9.4%, 32.9%, 10.6%, 14.1% and 0% of the PCOS subjects with BMI < 85th had such disturbances.

Conclusions

Adolescents with PCOS in South China had more metabolic abnormalities than their age- and BMI-matched non-PCOS counterparts. Obesity could worsen insulin resistance, hyperinsulinemia and metabolic syndrome in PCOS adolescents.
Lifetime health effects and medical costs of integrated stroke services - a non-randomized controlled cluster-trial based life table approach
Authors: Baeten Stefan A , van Exel N Job A , Dirks Maaike , Koopmanschap Marc A , Dippel Diederik WJ , Niessen Louis W
Published: November 2010

Background

Economic evaluation of stroke services indicates that such services may lead to improved quality of life at affordable cost. The present study assesses lifetime health impact and cost consequences of stroke in an integrated service setting.

Methods

The EDISSE study is a prospective non-randomized controlled cluster trial that compared stroke services (n = 151 patients) to usual care (n = 187 patients). Health status and cost trial-data were entered in multi-dimensional stroke life-tables. The tables distinguish four levels of disability which are defined by the modified Rankin scale. Quality-of-life scores (EuroQoL-5D), transition and survival probabilities are based on concurrent Dutch follow-up studies. Outcomes are quality-adjusted life years lived and lifetime medical cost by disability category. An economic analysis compares outcomes from a successful stroke service to usual care, by bootstrapping individual costs and effects data from patients in each arm.

Results

Lifetime costs and QALYs after stroke depend on age-of-onset of first-ever stroke. Lifetime QALYs after stroke are 2.42 (90% CI - 0.49 - 2.75) for male patients in usual care and 2.75 (-0.61; 6.26) for females. Lifetime costs for men in the usual care setting are €39,335 (15,951; 79,837) and €42,944 (14,081; 95,944) for women. A comparison with the stroke service results in an ICER of €11,685 saved per QALY gained (€14,211 and €7,745 for men and women respectively). This stroke service is with 90% certainty cost-effective.

Conclusions

Our analysis shows the potential of large health benefits and cost savings of stroke services, taking a lifetime perspective, also in other European settings.
Co-receptor usage and prediction of v3 genotyping algorithms in hiv-1 subtype b' from paid blood donors experienced anti-retroviral therapy in chinese central province
Authors: Qu Shuiling , Ma Liying , Yuan Lin , Xu Wesi , Hong Kunxue , Xing Hui , Huang Yang , Yu Xiaoling , Shao Yiming
Published: November 2010

Background

This study explored co-receptor usage and prediction of V3 genotyping algorithms in HIV-1 subtype B' from paid blood donors experienced anti-retroviral therapy in Chinese central province in order to design effectively therapeutic regimen.

Methods

HIV-1 strains were isolated in treatment HIV-1 infections and treatment-naïve HIV-1 infections, then co-receptor usage of HIV-1 strains was identified based on Ghost cell lines using flow cytometry. HIV-1 V3 region was amplified and submitted into web-server (WebPSSM and geno2pheno) to predict HIV-1 co-receptor usage. The feasibility of prediction HIV-1 usage with Web-server assay was analyzed by comparing prediction of V3 genotyping algorithms with HIV phenotype assay based on Ghost cell line.

Results

45 HIV-1 strains and 114 HIV-1 strains were isolated from HIV-1 infections exposed anti-retroviral therapy and treatment-naïve, respectively. 41% clinical viruses from ART patients and 18% from treatment-naïve patients used CXCR4 as co-receptor. The net charge in the V3 loop was significantly difference in both groups. The sensitivity and specificity for predicting co-receptor capacity is 54.6% and 90.0% on 11/25 rule, 50.0% and 90% on Web-PSSMx4r5, 68.2% and 40.0% on Geno2pheno[co-receptor].

Conclusion

Dual/mixed/X4 co-receptor utilization was higher in ART patients than treatment-naïve patients. It is should paid attention to predicting HIV-1 co-receptor usage based on V3 genotyping algorithms in HIV-1 subtype B' from paid blood donors experienced anti-retroviral therapy in Chinese central province.
Imaging the Functional Connectivity of the Periaqueductal Gray during Genuine and Sham Electroacupuncture Treatment
Authors: Zyloney Carolyn E , Jensen Karin , Polich Ginger , Loiotile Rita E , Cheetham Alexandra , LaViolette Peter S , Tu Peichi , Kaptchuk Ted J , Gollub Randy L , Kong Jian
Published: November 2010

Background:

Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA.

Results:

Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels.

Conclusions:

Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.