bluuebunny/crossref_metadata_2025 huggingface dataset:
Palatal Volume Following Rapid Maxillary Expansion in Mixed Dentition
Authors: Gracco Antonio , Malaguti Andrea , Lombardo Luca , Mazzoli Alida , Raffaeli Roberto
Published: October 2009

Objective: To evaluate volumetric variations in the palate following rapid expansion, both immediately after treatment and over time.

Materials and Methods: The sample was composed of 30 patients in early mixed dentition treated with a Haas-type device cemented onto the primary second molars. The mean age of the patients upon commencement of expansion was 7 years and 6 months (standard deviation [SD], 12 months). Measurement of palatal volume was conducted via 3D acquisition of plaster models using laser scanning before treatment (T1), upon device removal (T2), and 2.6 years afterward (T3).

Results: The volume of the palate increased in a statistically significant fashion from T1 to T2 and from T1 to T3, and it decreased in a nonsignificant fashion from T2 to T3.

Conclusions: Palatal volume significantly increases with rapid maxillary expansion (RME) treatment with insignificant relapse. The use of virtual 3D models with the aid of Apposite software permits evaluation of the morphologic and volumetric changes induced by orthodontic treatment.
Long-Term Effects of Rapid Maxillary Expansion Followed by Fixed Appliances
Authors: Gurel Hakan Gurcan , Memili Badel , Erkan Mustafa , Sukurica Yusuf
Published: October 2009

Objective: To evaluate the long-term changes in maxillary arch widths, overjet, and overbite in patients who were treated with rapid maxillary expansion (RME) followed by edgewise appliances.

Materials and Methods: The material for the study consisted of study casts taken from 41 patients (19 males, 22 females) on four different occasions (before treatment, T1; after RME, T2; after treatment, T3; and during follow-up period, T4). The upper intercanine, interpremolar, and intermolar widths and overjet and overbite were measured on each set of study casts. Mean age of the subjects was 13.2 ± 1.3 years (range, 11.2–16.9 years) at T1, 13.3 ± 1.3 years (range, 11.3–17 years) at T2, 15.5 ± 1.4 years (range, 13.1–18.8 years) at T3, and 20.4 ± 1.6 years (range, 17.9–24.8 years) at T4.

Results: The net increase in intercanine width, interpremolar width, intermolar width, overjet, and overbite was 1.4 ± 2.4 mm, 4.6 ± 2.6 mm, 4.3 ± 2.5 mm, 0.1 ± 0.6 mm, and 0.2 ± 0.6 mm, respectively, and the relapse rates were 37% for intercanine width, 19% for interpremolar width, and 17% for intermolar width at the end of the follow-up period.

Conclusions: A significant amount of relapse occurred in maxillary arch widths at the postretention assessment, the greatest being in intercanine width. RME significantly decreased overbite and increased overjet, and a statistically significant decrease was observed in both overbite and overjet at the postretention assessment.
Forces of Various Nickel Titanium Closed Coil Springs
Authors: Maganzini Anthony Louis , Wong Alan M. , Ahmed Mairaj K.
Published: October 2009

Objective: To compare the forces generated by 14 different 9 mm springs supplied by five different companies.

Materials and Methods: Five replicates of 14 different 9 mm springs were evaluated, resulting in 70 total specimens. Each was extended once from its resting length to 12 mm and then was deactivated. All tests were performed in a 37°C water bath. Forces were recorded at the 12 mm extension and deactivation distances of 9 mm, 6 mm, 3 mm, and 1 mm using an MTS force gauge. Data were collected with Testworks software, version 4.0, and were analyzed by analysis of variance (ANOVA) with one factor alternated.

Results: Mean peak load forces at 12 mm were significantly different between springs, and these forces varied from 147 to 474 grams. Mean unload forces measured at 9 mm, 6 mm, and 3 mm of deactivation values were highly variable, and only 6 of the 14 springs exhibited a “physiologic” mean unload force of 50 grams or less over the total deactivation range.

Conclusions: Few springs tested exhibited physiologic peak load forces and constant deactivation forces. This study suggests that labeling of nickel titanium closed coil springs is confusing and misleading.
A Photographic System for the Three-Dimensional Study of Facial Morphology
Authors: de Menezes Marcio , Rosati Riccardo , Allievi Cristina , Sforza Chiarella
Published: October 2009

Objectives: To test whether digital photographs supported by three-dimensional (3D) software are suitable for measuring the facial soft tissues of healthy subjects as compared with data obtained by a certified 3D computerized electromagnetic digitizer.

Materials and Methods: Three-dimensional soft tissue facial landmarks were obtained from the faces of 15 healthy young adults, using a 3D computerized electromagnetic digitizer and a new low-cost photogrammetry system. Twelve linear and 18 angular measurements were computed. Errors between methods and repeatability of the new method were calculated.

Results: Systematic errors between methods were found for only two distances and three angles (paired t-test, P < .05). The mean absolute differences between methods were always lower than 3 mm and 3 degrees. Repeated digitization of photographs showed that the method was repeatable (no systematic differences; random errors lower than 1.6 mm and 3 degrees). Repeated sets of photographs showed random errors of up to 5.3 mm and 5.6 degrees, without systematic biases.

Conclusion: The 3D photogrammetry system can provide reliable facial measurements. The method is relatively fast and requires only inexpensive equipment. It is simple to use for private practice, research, or other practice.
Effects of Low-Level Laser Therapy and Orthodontic Tooth Movement on Dental Pulps in Rats
Authors: Abi-Ramia Luciana Baptista Pereira , Sasso Stuani Andrea , Sasso Stuani Adriana , Sasso Stuani Maria Bernadete , de Moraes Mendes Alvaro
Published: October 2009

Objectives: To describe the microscopic pulpal reactions resulting from orthodontically induced tooth movement associated with low-level laser therapy (LLLT) in rats.

Materials and Methods: Forty-five young male Wistar rats were randomly assigned to three groups. In group I (n = 20), the maxillary right first molars were submitted to orthodontic movement with placement of a coil spring. In group II (n = 20), the teeth were submitted to orthodontic movement plus LLLT at 4 seconds per point (buccal, palatal, and mesial) with a GaAlAs diode laser source (830 nm, 100 mW, 18 J/cm2). Group III (n = 5) served as a control (no orthodontic movement or LLLT). Groups I and II were divided into four subgroups according to the time elapsed between the start of tooth movement and sacrifice (12 hours, 24 hours, 3 days, and 7 days).

Results: Up until the 3-day period, the specimens in group I presented a thicker odontoblastic layer, no cell-free zone of Weil, pulp core with differentiated mesenchymal and defense cells, and a high concentration of blood vessels. In group II, at the 12- and 24-hour time points, the odontoblastic layer was disorganized and the cell-free zone of Weil was absent, presenting undifferentiated cells, intensive vascularization with congested capillaries, and scarce defense cells in the cell-rich zone. In groups I and II, pulpal responses to the stimuli were more intense in the area underneath the region of application of the force or force/laser.

Conclusions: The orthodontic-induced tooth movement and LLLT association showed reversible hyperemia as a tissue response to the stimulus. LLLT leads to a faster repair of the pulpal tissue due to orthodontic movement.
The Validity of In Vivo Tooth Volume Determinations From Cone-Beam Computed Tomography
Authors: Liu Yi , Olszewski Raphael , Alexandroni Emanuel Stefan , Enciso Reyes , Xu Tianmin , Mah James K.
Published: October 2009

Objective: To determine the accuracy of volumetric analysis of teeth in vivo using cone-beam computed tomography (CBCT).

Materials and Methods: The physical volume (Vw) of 24 bicuspids extracted for orthodontic purposes (16 were imaged with the I-CAT and 8 with the CB MercuRay) were determined using the water displacement technique. Corresponding pretreatment CBCT image data were uploaded into Amira 4.0 for segmentation and radiographic volume (Va). All measurements were performed twice by two observers. The statistical difference between Vw and Va was assessed using a paired t-test. The intraobserver and interobserver reliability were determined by calculating Pearson correlation coefficients and intraclass correlation coefficients.

Results: The overall mean Vw of teeth specimens was 0.553 ± 0.082 cm3, while the overall mean Va was 0.548 ± 0.079 cm3 (0.529 ± 0.078 cm3 for observer 1 and 0.567 ± 0.085 cm3 for observer 2). There were statistically significant differences between Va and Vw (P < .05). Between observer 1 and observer 2, Va measurements were statistically significantly different (P < .05). The interobserver and intraobserver correlation coefficient for Vw was high. Lastly, surface smoothing reduced the volume by 3% to 12%.

Conclusions: In vivo determination of tooth volumes from CBCT data is feasible. The measurements slightly deviate from the physical volumes within −4% to 7%. Smoothing operations reduce volume measurements. Currently, no requirements for accuracy of volumetric determinations of tooth volume have been established.
Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003–2008)
Authors: Marconato Laura , Romanelli Giorgio , Stefanello Damiano , Giacoboni Claudio , Bonfanti Ugo , Bettini Giuliano , Finotello Riccardo , Verganti Sara , Valenti Paola , Ciaramella Luigia , Zini Eric
Published: October 2009

Objective—To describe clinical characteristics, treatment, and outcome of dogs with inflammatory carcinoma (IC) and identify patient-, tumor-, and treatment-related factors associated with overall survival time.

Design—Retrospective case series.

Animals—43 client-owned dogs.

Procedures—Records of dogs with a clinical diagnosis of IC that had histologic evidence of dermal lymphatic invasion were reviewed. Data on clinical staging, treatment, toxicoses, response, and survival time were retrieved.

Results—26 (60%) dogs had primary IC and 17 (40%) had secondary IC. Thirty-five (81%) dogs had distant metastases and 2 (5%) had local metastases at the time of initial examination. Six of 29 (21%) dogs had a coagulopathy. Sixteen (37%) dogs did not receive specific treatment for IC, 24 (56%) received medical treatment only, 2 (5%) underwent surgical excision and received medical treatment, and 1 (2%) underwent surgical excision only. Forty-one (95%) dogs had progressive disease, and 2 (5%) had stable disease. Mean survival time for all dogs was 60 days (range, 1 to 300 days). Dogs with a coagulopathy survived a significantly shorter time than did dogs without a coagulopathy (odds ratio, 0.28), and dogs that received medical treatment survived significantly longer than dogs that did not (odds ratio, 2.54).

Conclusions and Clinical Relevance—Results suggested that mammary IC is a biologically aggressive condition in dogs associated with a guarded prognosis. In addition, results suggested that medical treatment may improve outcome, thereby supporting its use in dogs with IC.
Serum antibody titers following routine rabies vaccination in African elephants
Authors: Miller Michele A. , Olea-Popelka Francisco
Published: October 2009

Objective—To evaluate serum antibody titers in captive African elephants (Loxodonta africana) following routine vaccination with a commercially available, inactivated rabies vaccine.

Design—Seroepidemiologic study.

Animals—14 captive African elephants from a single herd.

Procedures—Elephants were vaccinated as part of a routine preventive health program. Initially, elephants were vaccinated annually (2 mL, IM), and blood was collected every 4 or 6 months for measurement of rabies virus–neutralizing antibody titer by means of the rapid fluorescent focus inhibition test. Individual elephants were later switched to an intermittent vaccination schedule to allow duration of the antibody response to be determined.

Results—All elephants had detectable antibody responses following rabies vaccination, although there was great variability among individual animals in regard to antibody titers, and antibody titers could be detected as long as 24 months after vaccine administration. Young animals were found to develop an antibody titer following administration of a single dose of the rabies vaccine. Age and time since vaccination had significant effects on measured antibody titers.

Conclusions and Clinical Relevance—Results indicated that African elephants developed detectable antibody titers in response to inoculation with a standard large animal dose of a commercially available, inactivated rabies vaccine. The persistence of detectable antibody titers in some animals suggested that vaccination could be performed less frequently than once a year if antibody titers were routinely monitored.
Development and physicochemical evaluation of pharmacosomes of diclofenac
Authors: Semalty Ajay , Semalty Mona , Singh Devendra , Rawat M.
Published: October 2009

Development and physicochemical evaluation of pharmacosomes of diclofenac

Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80%) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) andin vitrodissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 ± 1.1%. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 μg mL-1as compared to 10.5 μg mL-1of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8% while the free diclofenac acid showed a total of only 60.4% drug release at the end of 10 h of dissolution study.
Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations
Authors: Chakraborty Santanu , Khandai Madhusmruti , Sharma Anuradha , Patra Ch. , Patro V. , Sen Kalyan
Published: October 2009

Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations

The purpose of the present research work was to observe the effects of drug solubility on their release kinetics of water soluble verpamil hydrochloride and insoluble aceclofenac from hydrophilic polymer based matrix formulations. Matrix formulations were prepared by the direct compression method. The formulations were evaluated for various physical parameters. Along with the dynamics of water uptake and erosion, SEM and in vitro drug release of the tablets were studied. Applying an exponential equation, it was found that the kinetics of soluble drug release followed anomalous non-Fickian diffusion transport whereas insoluble drug showed zero-order release. SEM study showed pore formation on the tablet surface that differed depending on drug solubility. t-Test pointed to a significant difference in amount of both drugs released due to the difference in solubility. Solubility of the drug effects kinetics and the mechanism of drug release.
Butyl acrylate/4-acryloyloxy benzophenone copolymers as photoreactive UV-crosslinkable pressure-sensitive adhesives
Authors: Czech Zbigniew , Butwin Agnieszka
Published: October 2009

Butyl acrylate/4-acryloyloxy benzophenone copolymers as photoreactive UV-crosslinkable pressure-sensitive adhesives

It has previously been shown that copolymers of butyl acrylate with 4-acryloyloxy benzophenone can be used as pressure-sensitive adhesives (PSAs). This paper presents the synthesis and application of a solvent-borne polymer system for the preparation of photoreactive UV-crosslinkable acrylic pressure-sensitive adhesives. Butyl acrylate/benzophenone copolymers with molecular mass in the range 180 000 to 480 000 Dalton were prepared by carrying out free-radical solution polymerization. These copolymers were found to be tacky but in some cases to possess insufficient cohesive strength after UV-crosslinking to be useful as PSAs. The other copolymers resulted in materials with the balance of cohesive and adhesive characteristics required of good PSAs. Some of the parameters affecting the pressure-sensitive adhesive properties of the copolymers are the concentration of 4-acryloyloxy benzophenone, the molecular mass of the polymeric components, the UV-reactivity, and properties such as tack, peel adhesion, and cohesion.
The Offending Trajectories of Youthful Aboriginal Offenders
Authors: Yessine Annie K. , Bonta James
Published: October 2009

The current study examine the offending trajectories of Aboriginal youths under a probation sentence in Manitoba, Canada, and compared them to those of non-Aboriginal juvenile probationers. The results from growth-mixture analyses indicated that, for both sub-samples, a two-group latent trajectory model best represented the shape of the developmental progression in criminal behaviour from early adolescence to middle adulthood. While a small proportion of the offenders showed serious and persistent offending behaviour over their life-course, the majority of the juvenile probationers engaged in relatively less frequent and/or serious criminal activity over time. The size of the chronic high-offending trajectory group was slightly larger among the Aboriginal offenders (18.7%) than among the non-Aboriginal offenders (12.3%). Additional analyses revealed that the Aboriginal offenders were more likely to come from an impoverished background, characterized by an unstable familial environment, substance use, and negative peer associations. These criminogenic risk/needs contributed to their serious and persistent pattern of criminality. In contrast, accommodation problems predicted increased odds of membership in the chronic high group of the non-Aboriginal offenders. The article concludes with a discussion of potential implications and suggestions for future research.
Emotions and the Campaign for Victims’ Rights in Canada
Authors: Stanbridge Karen , Kenney J. Scott
Published: October 2009

Prevailing explanations of the increase in collective action surrounding victims’ rights in early 1980s Canada generally follow the precepts of political process, resource mobilization, and framing approaches in social-movements research by depicting the movement as a corollary of contemporary organizational, political, and cultural conditions. We find that the increase in activism, while certainly influenced by such factors, also required that victim-advocate groups properly manage, display, and frame the strong emotions associated with the victim experience – grief, fear, injustice, and anger – to maintain the internal integrity of the group as well as its external or public legitimacy. Our analysis contributes to social-movements analyses of how understandings of movement dynamics can be deepened by paying attention to how emotions play out in the process of collective action.
The location of the grounding zone of Evans Ice Stream, Antarctica, investigated using SAR interferometry and modelling
Authors: Sykes Helena J. , Murray Tavi , Luckman Adrian
Published: October 2009

Evans Ice Stream, West Antarctica, has five tributaries and a complex grounding zone. The grounding zone of Evans Ice Stream, between the landward and seaward limits of tidal flexing, was mapped using SAR interferometry. The width of the mapped grounding zone was compared with that derived from an elastic beam model, and the tidal height changes derived from interferometry were compared with the results of a tidal model. Results show that in 1994 and 1996 the Evans grounding zone was located up to 100 km upstream of its location in the BEDMAP dataset. The grounding line of Evans Ice Stream is subjected to 5 m vertical tidal forcing, which would clearly affect ice-stream flow.
Characterization of Primary Standards for Use in the HPLC Analysis of the Procyanidin Content of Cocoa and Chocolate Containing Products
Authors: Hurst William  J. , Stanley Bruce , Glinski Jan  A. , Davey Matthew , Payne Mark  J. , Stuart David  A.
Published: October 2009

This report describes the characterization of a series of commercially available procyanidin standards ranging from dimers DP = 2 to decamers DP = 10 for the determination of procyanidins from cocoa and chocolate. Using a combination of HPLC with fluorescence detection and MALDI-TOF mass spectrometry, the purity of each standard was determined and these data were used to determine relative response factors. These response factors were compared with other response factors obtained from published methods. Data comparing the procyanidin analysis of a commercially available US dark chocolate calculated using each of the calibration methods indicates divergent results and demonstrate that previous methods may significantly underreport the procyanidins in cocoa-containing products. These results have far reaching implications because the previous calibration methods have been used to develop data for a variety of scientific reports, including food databases and clinical studies.
Neural Network Emulation of the Integral Equation Model with Multiple Scattering
Authors: Pulvirenti Luca , Ticconi Francesca , Pierdicca Nazzareno
Published: October 2009

The Integral Equation Model with multiple scattering (IEMM) represents a well-established method that provides a theoretical framework for the scattering of electromagnetic waves from rough surfaces. A critical aspect is the long computational time required to run such a complex model. To deal with this problem, a neural network technique is proposed in this work. In particular, we have adopted neural networks to reproduce the backscattering coefficients predicted by IEMM at L- and C-bands, thus making reference to presently operative satellite radar sensors, i.e., that aboard ERS-2, ASAR on board ENVISAT (C-band), and PALSAR aboard ALOS (L-band). The neural network-based model has been designed for radar observations of both flat and tilted surfaces, in order to make it applicable for hilly terrains too. The assessment of the proposed approach has been carried out by comparing neural network-derived backscattering coefficients with IEMM-derived ones. Different databases with respect to those employed to train the networks have been used for this purpose. The outcomes seem to prove the feasibility of relying on a neural network approach to efficiently and reliably approximate an electromagnetic model of surface scattering.
Anti-hepatitis C Virus Activity of Novel β-D-2′-C-methyl-4′-azido Pyrimidine Nucleoside Phosphoramidate Prodrugs
Authors: Rondla Ramu , Coats Steven J , McBrayer Tamara R , Grier Jason , Johns Melissa , Tharnish Phillip M , Whitaker Tony , Zhou Longhu , Schinazi Raymond F
Published: October 2009

Background:

2′- C-methyl and 4′-azido nucleosides have previously demonstrated inhibition of hepatitis C virus (HCV) replication by targeting the RNA-dependent RNA polymerase NS5B. In an effort to discover new and more potent anti-HCV agents, we envisioned synthesizing nucleoside analogues by combining the 2′- C-methylmoiety with the 4′-azido-moiety into one molecule.

Methods:

2′- C-methyl-4′-azido pyrimidine nucleosides were synthesized by first converting 2′- C-methyl ribonucleosides to the corresponding 4′-exocyclic methylene nucleosides. Treatment with iodine azide, benzoylation of the 2′- and 3′-hydroxy groups, oxidative displacement of the 5′-iodo group with meta-chloroperoxybenzoic acid, and debenzoylation gave the desired 2′- C-methyl-4′-azido uridine and thymidine analogues in good yield. Standard conversion of uridine to cytidine via the 4-triazole yielded 2′- C-methyl-4′-azido cytidine. In addition, 5′-phosphoramidate derivatives of 2′-C-methyl-4′-azido uridine and cytidine were synthesized to bypass the initial phosphorylation step.

Results:

The prepared nucleosides and their 5′-monophosphate prodrugs were evaluated for their ability to inhibit replication of the hepatitis C virus in a subgenomic replicon cell based assay. Cytotoxicity in Huh7 cells was determined simultaneously with anti-HCV activity by extraction and amplification of both HCV RNA and ribosomal RNA. Among the newly synthesized compounds, only the 5′-monophosphate nucleoside prodrugs had modest and selective anti-HCV activity. All prepared pyrimidine nucleosides and 5′-monophosphate nucleoside prodrugs displayed no evidence of cytotoxicity at high concentrations.

Conclusions:

This work is the first example of both inactive uridine and cytidine analogues of a nucleoside being converted to active anti-HCV nucleosides via 5′-monophosphate prodrugs.
Ethnic Differences in Pediatric Systemic Lupus Erythematosus
Authors: HIRAKI LINDA T. , BENSELER SUSANNE M. , TYRRELL PASCAL N. , HARVEY ELIZABETH , HEBERT DIANE , SILVERMAN EARL D.
Published: October 2009

Objective.

Prevalence and severity of systemic lupus erythematosus (SLE) in adults is suggested to be distinctly different between ethnic groups. The impact of ethnicity is not as well delineated in pediatric SLE (pSLE). We compared prevalence and extent of major organ involvement, disease activity, and damage in pSLE between different ethnic groups.

Methods.

Ethnic demographic profiles of an inception cohort of 265 patients with pSLE followed at Sick Kids Hospital in Toronto were determined and compared to the Metropolitan Toronto at-risk population. Patients were categorized into ethnic subsets based on self-designated ethnic origins. Disease characteristics including major organ involvement, disease activity, and damage measures were longitudinally determined and compared among ethnic groups.

Results.

Ethnicity data were available on 259/265 pSLE patients (99.6%); the majority were non-Caucasian (60%) compared to the Metropolitan Toronto at-risk population (40%) (p < 0.0001). Non-Caucasian patients were younger at diagnosis than Caucasian patients, Black patients being the youngest at diagnosis (12.6 vs 14.6 yrs; p = 0.007). Renal disease was significantly more common in non-Caucasian than in Caucasian pSLE patients (62% vs 45%; p = 0.01). There was a trend toward increased prevalence of central nervous system disease in Black patients compared to Asian patients (p = 0.108). There was no difference in gender ratio, SLE Disease Activity Index, or damage scores between ethnic groups.

Conclusion.

Non-Caucasian ethnicity is associated with increased pSLE disease prevalence. Non-Caucasian pSLE patients were significantly younger and more likely to have nephritis. However, disease activity and damage were strongly associated with major organ disease independent of the patient’s ethnicity.
What Makes Patients with Fibromyalgia Feel Better? Correlations Between Patient Global Impression of Improvement and Changes in Clinical Symptoms and Function: A Pooled Analysis of 4 Randomized Placebo-controlled Trials of Duloxetine
Authors: HUDSON JAMES I. , ARNOLD LESLEY M. , BRADLEY LAURENCE A. , CHOY ERNEST H. S. , MEASE PHILIP J. , WANG FUJUN , AHL JONNA , WOHLREICH MADELAINE M.
Published: October 2009

Objective.

To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I).

Methods.

Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings.

Results.

Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r ≥ 0.5 or r ≤ −0.5) with endpoint PGI-I. Moderate correlation with endpoint PGI-I (0.30 ≤ r < 0.5 or −0.5 < r ≤ −0.30) included changes in variables that assessed physical functioning, depression, anxiety, fatigue, and several variables related to impact on daily living. Independent predictor variables of endpoint PGI-I identified by stepwise linear regression included assessments for pain, physical function, vitality, anxiety, social function, and tender point thresholds.

Conclusion.

In addition to pain reduction, what makes patients with FM feel better may include improvement in fatigue, physical functioning, mood, and impact on daily living. An assessment of these domains may be important in clinical trials of FM and in the management of patients with FM.
Research Education for Clinical Nurses: A Pilot Study to Determine Research Self-Efficacy in Critical Care Nurses
Authors: Swenson-Britt Evelyn , Reineck Carol
Published: October 2009

Background:

Translating research into practice is essential to providing care that promotes both cost-efficient and effective health care delivery. Nurses practicing in the intensive care unit are in need of education that can build research self-efficacy and promote understanding and the ability to apply research findings.

Methods:

This pilot study evaluated the Critical Reading of Research Publications Plus course with intensive care unit nurses to determine whether this experience would affect their research self-efficacy. The Nursing Research Self-Efficacy Scale was administered before and after the course.

Results:

Paired
t
tests showed a significant increase on three of the four subscales in research self-efficacy.

Conclusion:

This study shows that using a course along with mentors may increase the research self-efficacy of practicing nurses.

J Contin Educ Nurs
2009;40(10):454–461.
What About Social Networking?
Authors: McKenzie Ann Barrow
Published: October 2009

This column offers a general overview of social networking.

J Contin Educ Nurs
2009;40(10):436–437.
Providing Holistic Care to Bariatric Patients
Authors: Lansing Ramona , McGuire Jennifer , Palmersheim Patty , Baird Gayle
Published: October 2009

Bariatric patients often encounter challenging physical environments and sometimes encounter negative attitudes from health professionals when seeking care. Most facilities have the basic equipment needed to care for these patients. Using ceiling lifts or limb slings to facilitate repositioning or transfer has benefits for patients and staff. Environment, equipment, education, and resources are important to providing sensitive, respectful, safe, and high-quality patient care. This column describes strategies to promote holistic care for the bariatric population.

J Contin Educ Nurs
2009;40(10):438–439.
From the Outside In: A Unique Model for Stimulating Curricula Reform in Nursing Education
Authors: Simmonds Katherine , Foster Angel M. , Zurek Melanie
Published: October 2009

Given the current demands on nursing education, the introduction of new content into curricula can present significant challenges for nursing faculty. This is particularly true when the content being introduced is the subject of deep ethical, religious, or political controversy. This article offers a unique model for approaching curricula reform that draws on a decade-long effort to increase abortion-related content in nursing programs in New England and other regions of the United States mounted by a nonprofit organization. Strategies used and successes of the project are discussed. Faculty interested in introducing controversial topics into curricula, as well as advocacy groups that seek to stimulate curricula reform, may find this discussion to be particularly relevant and instructive to their efforts.
Amino Acid Deprivation Links BLIMP-1 to the Immunomodulatory Enzyme Indoleamine 2,3-Dioxygenase
Authors: Barnes Nicholas A. , Stephenson Sophie J. , Tooze Reuben M. , Doody Gina M.
Published: October 2009

Catabolism of tryptophan by IDO1 plays an important role in the control of immune responses. Activation of the eukaryotic initiation factor 2α (eIF2α) kinase general control nonderepressible-2 (GCN2) following tryptophan depletion is a major pathway mediating this effect. However, immunomodulatory target genes of GCN2 activation are poorly defined. The transcriptional repressor B lymphocyte-induced maturation protein-1 (BLIMP-1) is a target of the eIF2α kinase1, protein kinase-like ER kinase (PERK) during the unfolded protein response of the endoplasmic reticulum. Thus, BLIMP-1 might also be a mediator of the GCN2 stress response pathway activated by IDO1 and tryptophan depletion. Indeed, in human monocytes BLIMP-1 mRNA and protein are up-regulated in response to both a pharmacological activator of GCN2 and tryptophan-depletion generated by IDO1-transfected cells. This suggests a functional role for BLIMP-1 in the immunomodulatory effects of the IDO1-GCN2 axis. BLIMP-1 has been shown to repress IFN-γ-regulated promoters. As IDO1 is itself highly responsive to IFN-γ, we hypothesized that BLIMP-1 functions in a feedback loop to regulate IDO1 expression. We found that BLIMP-1 binds to IFN-responsive sites in the IDO1 promoter and represses IFN-dependent IDO1 activation. We propose that BLIMP-1 acts in a negative feedback loop to successfully balance the outcome of tolerance vs inflammation.
The Lupus Susceptibility Locus Sle1 Breaches Peripheral B Cell Tolerance at the Antibody-Forming Cell and Germinal Center Checkpoints
Authors: Vuyyuru Raja , Mohan Chandra , Manser Tim , Rahman Ziaur S. M.
Published: October 2009

We have described a line of VH knock-in mice termed HKIR in which the transgenic Igh locus partially encodes “dual-reactive” antichromatin and anti-p-azophenylarsonate (Ars) BCRs. HKIR B cells termed canonical, expressing a particular Vκ L chain, evade central tolerance by down-regulating BCR levels. Canonical HKIR B cells can be recruited into the primary germinal center (GC) and Ab-forming cell (AFC) compartments via Ars immunization. However, their participation in the GC response rapidly wanes and they do not efficiently contribute to the memory compartment, indicating that they are regulated by a GC tolerance checkpoint. We analyzed the influence of the Sle1 genetic interval, shown to break tolerance of chromatin-reactive B cells, on the behavior of HKIR B cells during the anti-Ars response. Canonical B cells from congenic HKIR.Sle1 mice gave rise to elevated short and long-lived AFC responses, and the attenuated GC and memory responses characteristic of these B cells were relieved in adoptive, wild-type recipients. HKIR GC B cells containing Sle1 expressed increased levels of Bcl-2 and c-FLIP and decreased levels of Fas RNA compared with HKIR controls, suggesting direct alteration of the regulation of the GC response by Sle1. High titers of canonical and anti-dsDNA Abs spontaneously developed in many aged HKIR.Sle1 mice. Together, these data indicate that Sle1 perturbs the action of peripheral tolerance checkpoints operative on antinuclear Ag B cells in both the AFC and GC pathways in a cell autonomous fashion.
The α-Isoform of p38 MAPK Specifically Regulates Arthritic Bone Loss
Authors: Böhm Christina , Hayer Silvia , Kilian Anita , Zaiss Mario M. , Finger Susann , Hess Andreas , Engelke Klaus , Kollias George , Krönke Gerhard , Zwerina Jochen , Schett Georg , David Jean-Pierre
Published: October 2009

Pharmacological inhibitors have provided evidence for the key role of p38 MAPK in osteoclast differentiation and in inflammation-induced bone loss. However, these inhibitors block more than one of the four p38 isoforms, usually p38α and p38β, and sometimes also other kinases such as JNK3. We show in this study that p38α is the main p38 isoenzyme expressed in the osteoclast precursors and in the mature osteoclasts. p38α as well as its downstream substrates were phosphorylated in osteoclast progenitors stimulated by TNF-α. Using Mx-cre-mediated conditional gene inactivation we demonstrated that mice lacking p38α were protected against TNF-α-induced bone destruction at the site of inflammation as well as against TNF-α-mediated systemic bone loss. The bone protection was associated to decreased osteoclast numbers in vivo as well as a decreased IL-1β expression in the inflamed tissue and in the isolated monocytes. The phenotype was cell autonomous because, similarly to p38α-deficient cells, knockdown of p38α in monocytes resulted in a decreased osteoclast differentiation in vitro. It was not caused by major changes in RANKL-mediated ERK or JNK activation but rather associated to an increased NF-κB activation caused by a decrease in IκBα recovery. Thus, our data show that developing specific inhibitors of the α-isoenzyme of p38 would be beneficial for the treatment of inflammation-induced bone destruction as observed in rheumatoid arthritis.
RANKL Is Necessary and Sufficient to Initiate Development of Antigen-Sampling M Cells in the Intestinal Epithelium
Authors: Knoop Kathryn A. , Kumar Nachiket , Butler Betsy R. , Sakthivel Senthilkumar K. , Taylor Rebekah T. , Nochi Tomonori , Akiba Hisaya , Yagita Hideo , Kiyono Hiroshi , Williams Ifor R.
Published: October 2009

Microfold cells (M cells) are specialized epithelial cells situated over Peyer’s patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-κB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have <2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-mediated neutralization of RANKL in adult wild-type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.
Ethanol Augments RANTES/CCL5 Expression in Rat Liver Sinusoidal Endothelial Cells and Human Endothelial Cells via Activation of NF-κB, HIF-1α, and AP-1
Authors: Yeligar Samantha M. , Machida Keigo , Tsukamoto Hidekazu , Kalra Vijay K.
Published: October 2009

Chronic alcohol consumption leads to liver inflammation and cirrhosis. Alcoholic liver disease patients have increased levels of hepatic RANTES/CCL5. However, less is known about the molecular mechanisms for ethanol-induced RANTES up-regulation. In this study, we observed that liver sinusoidal endothelial cells derived from ethanol-fed rats (E-rLSECs) showed severalfold increases in RANTES and hypoxia-inducible factor 1α (HIF-1α) mRNAs compared with control rLSECs (C-rLSECs). Similar effects were seen in acute ethanol treatment of isolated rLSECs and human dermal microvascular endothelial cells. Ethanol-induced RANTES mRNA expression required ethanol metabolism, p38 MAPK, HIF-1α, and JNK-2, but not JNK-1. EMSA experiments showed increased HIF-1α binding to wild-type hypoxia response elements (HREs; −31 to −9 bp) within the RANTES promoter in response to ethanol. RANTES promoter analysis showed that cis elements proximal to the transcription start site, HRE-1 (nt −22 to −19), HRE-2 (nt −32 to −29), and AP-1 (nt −250 to −244) were required for ethanol-mediated RANTES expression. These results were corroborated by chromatin immunoprecipitation assays showing augmented HIF-1α binding to HRE-1. Additionally, promoter analysis revealed c-Jun, c-Jun/c-Fos, and JunD, but not JunB, bound to the AP-1 site of the RANTES promoter. Ethanol-mediated activation of NF-κB led to HIF-1α activation and concomitant RANTES expression. Plasma of ethanol-fed c-Junflox/flox-Mx-1-Cre mice showed attenuated levels of RANTES compared with ethanol-fed control mice, supporting the role of c-Jun in ethanol-induced RANTES expression. Our studies showed that ethanol-mediated RANTES/CCL5 expression occurs via HIF-1α activation independently of hypoxia. The identification of HIF-1α and AP-1 in ethanol-induced RANTES expression provides new strategies to ameliorate ethanol-induced inflammatory responses.
Pulmonary IL-17E (IL-25) Production and IL-17RB+ Myeloid Cell-Derived Th2 Cytokine Production Are Dependent upon Stem Cell Factor-Induced Responses during Chronic Allergic Pulmonary Disease
Authors: Dolgachev Vladislav , Petersen Bryan C. , Budelsky Alison L. , Berlin Aaron A. , Lukacs Nicholas W.
Published: October 2009

In the present studies local neutralization of allergen-induced stem cell factor (SCF) leads to decreased production of Th2 cytokines, a reduction in inflammation, allergen-specific serum IgE/IgG1, and attenuation of severe asthma-like responses. The local blockade of pulmonary SCF also resulted in a significant reduction of IL-17E (IL-25). Sorted cell populations from the lung indicated that IL-25 was produced from c-kit+ cells, whereas Th2 cytokine production was primarily from c-kit− cell populations. SCF stimulated c-kit+ eosinophils produced IL-25, whereas bone marrow-derived mast cells did not. Using 4get mice that contain a IL-4-IRES-eGFP that when transcribed coexpress GFP and IL-4, our studies identified cells that comprised a CD11b+, GR1+, Ly6C+/−, c-kit−, CD4−, CD11c−, MHC class IIlow cell population as a source of IL-4 in the lung after chronic allergen challenge. In the bone marrow a similar cell was identified with approximately a third of the IL-4+ cells also expressing c-kit+. The pulmonary and bone marrow IL-4+ cell populations were significantly reduced upon local pulmonary anti-SCF treatment. Subsequently, when IL-25R was examined during the chronic allergen responses the expression was found on the IL-4+ myeloid cell population that expressed CD11b+GR1+. Interestingly, the IL-25R+ cells in the bone marrow were also all CD11b+GR1+, similar to the lung cells, but they were also all c-kit+, potentially suggesting a maturation of the bone marrow cell once it enters the lung and/or is stimulated by SCF. Overall, these studies suggest a complex relationship between SCF, bone marrow-derived IL-25-responsive myeloid cells, Th2 cytokines, and chronic allergic disease.
Targeted Inhibition of the Complement Alternative Pathway with Complement Receptor 2 and Factor H Attenuates Collagen Antibody-Induced Arthritis in Mice
Authors: Banda Nirmal K. , Levitt Brandt , Glogowska Magdalena J. , Thurman Joshua M. , Takahashi Kazue , Stahl Gregory L. , Tomlinson Stephen , Arend William P. , Holers V. Michael
Published: October 2009

The alternative pathway (AP) of complement is required for the induction of collagen Ab-induced arthritis (CAIA) in mice. The objective of this study was to examine the effect of a recombinant AP inhibitor containing complement receptor 2 and factor H (CR2-fH) on CAIA in mice. CR2 binds to tissue-fixed activation fragments of C3, and the linked fH is a potent local inhibitor of the AP. CAIA was induced in C57BL/6 mice by i.p. injections of 4 mAb to type II collagen (CII) on day 0 and LPS on day 3. PBS or CR2-fH (250 or 500 μg) were injected i.p. 15 min after the mAb to CII on day 0 and 15 min after LPS on day 3; the mice were sacrificed on day 10. The disease activity score (DAS) was decreased significantly (p < 0.001) in both groups receiving CR2-fH compared with the PBS. Histology scores for inflammation, pannus, bone damage, and cartilage damage decreased in parallel with the DAS. C3 deposition in the synovium and cartilage was significantly reduced (p < 0.0001) in the mice treated with CR2-fH. In vitro studies with immune complexes containing type II collagen and mAb to CII showed that CR2-fH specifically inhibited the AP with minimal effect on the classical pathway (CP) and no effect on the lectin pathway (LP). The relative potency of CR2-fH in vitro was superior to mAbs to factor B and C5. Thus, CR2-fH specifically targets and inhibits the AP of complement in vitro and is effective in CAIA in vivo.
Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits
Authors: Boullier Séverine , Tanguy Myriam , Kadaoui Khalil A. , Caubet Cécile , Sansonetti Philippe , Corthésy Blaise , Phalipon Armelle
Published: October 2009

Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer’s patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer’s patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer’s patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-α, IL-6, Cox-2, and IFN-γ, was observed, consistent with preserved morphology. In contrast, in Peyer’s patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA.