bluuebunny/crossref_metadata_2025 huggingface dataset:
Theta Burst Stimulation in the Rehabilitation of the Upper Limb
Authors: Talelli Penelope , Wallace Amanda , Dileone Michelle , Hoad Damon , Cheeran Binith , Oliver Rupert , VandenBos Mehdi , Hammerbeck Ulrike , Barratt Karen , Gillini Cecilia , Musumeci Gabriella , Boudrias Marie-Hélène , Cloud Geoffrey C. , Ball Joanna , Marsden Jonathan F. , Ward Nicholas S. , Di Lazzaro Vincenzo , Greenwood Richard G. , Rothwell John C.
Published: March 2012

Background. Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke. However, its clinical value, including anticipated size and duration of the treatment effects, remains largely unknown. Objective. The authors designed a small semi-randomized clinical trial to explore whether long-lasting clinically important gains can be achieved by adding theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), to a rehabilitation program for the hand. Methods. A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers; each active group was compared with a group receiving sham TBS. TBS was followed by physical therapy for 10 working days. Patients and therapists were blinded to the type of TBS. Primary outcome measures (9-hole Peg Test [9HPT], Jebsen Taylor Test [JTT], and grip and pinch-grip dynamometry) were assessed 4, 30, and 90 days post treatment. The clinically important difference was defined as 10% of the maximum score. Results. There were no differences between the active treatment and sham groups in any of the outcome measures. All patients achieved small sustainable improvements—9HPT, 5% of maximum (confidence interval [CI] = 3%-7%); JTT, 5.7% (CI = 3%-8%); and grip strength, 6% (CI = 2%-10%)—all below the defined clinically important level. Conclusions. Cortical stimulation did not augment the gains from a late rehabilitation program. The effect size anticipated by the authors was overestimated. These results can improve the design of future work on therapeutic uses of TMS.
Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 Months in a Goat Model
Authors: Chan Elaine F. , Liu I-Ling , Semler Eric J. , Aberman Harold M. , Simon Timothy M. , Chen Albert C. , Truncale Kate G. , Sah Robert L.
Published: March 2012

Objective:

The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-dimensional (3-D) geometrical match between grafted and contralateral joints at 6 and 12 months after surgery.

Design:

Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral nonoperated joints were harvested at 6 and 12 months and analyzed by indentation testing, micro–computed tomography, and histology to compare 1) histological indices of repair, 2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), 3) indentation stiffness, and 4) correlations between stiffness and 3-D structure.

Results:

Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of the operated MFC were lower than the nonoperated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to the nonoperated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness.

Conclusion:

The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure.
Pediatric Primary Care Physicians’ Practices Regarding Newborn Hearing Screening
Authors: Ross Danielle S. , Visser Susanna N.
Published: March 2012

Objective: Approximately 2 to 3 out of 1000 infants are born with hearing loss in the United States each year. Pediatric primary care physicians (PCPs) can play an important role in ensuring that infants with hearing loss are identified early and provided appropriate services. In this study, pediatric PCPs were surveyed about their practices regarding early hearing detection and intervention. Methods: Responses from the 2008 DocStyles survey were used to examine patient, physician, and practice variables associated with actions consistent with the 2007 Joint Committee on Infant Hearing position statement, which includes follow-up protocols for medical home providers. Results: Pediatricians working in a group setting were more likely to receive hearing screening results than were those in individual practices or hospitals and clinics. Family/general physicians with heavier caseloads were more likely to receive hearing screening results for their pediatric patients than were those with lighter caseloads. Few pediatric PCPs reported contacting their state’s early hearing detection and intervention program if they knew that an infant failed the newborn hearing screening. Although high proportions of pediatric PCPs reported referring an infant with hearing loss to an otolaryngologist, only about half reported referring a child with risk factors for hearing loss for audiological and speech-language assessment, even if the parents expressed concern or if the results of a developmental screening indicated a possible delay. Few respondents reported referring an infant with hearing loss under their care to an ophthalmologist. Conclusions: This study highlights the need to improve infrastructure for pediatric PCPs to receive and request infant hearing screening results to facilitate reporting and coordinate follow-up services for infants identified with hearing loss.
Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function
Authors: Westerberg Lisa S. , Dahlberg Carin , Baptista Marisa , Moran Christopher J. , Detre Cynthia , Keszei Marton , Eston Michelle A. , Alt Frederick W. , Terhorst Cox , Notarangelo Luigi D. , Snapper Scott B.
Published: March 2012

The Wiskott-Aldrich syndrome protein (WASP) is a key cytoskeletal regulator of hematopoietic cells. Although WASP-knockout (WKO) mice have aberrant B-cell cytoskeletal responses, B-cell development is relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homolog of WASP, may serve some redundant functions with WASP in B cells. In the present study, we generated mice lacking WASP and N-WASP in B cells (conditional double knockout [cDKO] B cells) and show that cDKO mice had decreased numbers of follicular and marginal zone B cells in the spleen. Receptor-induced activation of cDKO B cells led to normal proliferation but a marked reduction of spreading compared with wild-type and WKO B cells. Whereas WKO B cells showed decreased migration in vitro and homing in vivo compared with wild-type cells, cDKO B cells showed an even more pronounced decrease in the migratory response in vivo. After injection of 2,4,6-trinitrophenol (TNP)–Ficoll, cDKO B cells had reduced antigen uptake in the splenic marginal zone. Despite high basal serum IgM, cDKO mice mounted a reduced immune response to the T cell–independent antigen TNP-Ficoll and to the T cell–dependent antigen TNP–keyhole limpet hemocyanin. Our results reveal that the combined activity of WASP and N-WASP is required for peripheral B-cell development and function.
Reordering based integrative expression profiling for microarray classification
Authors: Wu Xiaogang , Huang Hui , Sonachalam Madhankumar , Reinhard Sina , Shen Jeffrey , Pandey Ragini , Chen Jake Y
Published: March 2012

Background

Current network-based microarray analysis uses the information of interactions among concerned genes/gene products, but still considers each gene expression individually. We propose an organized knowledge-supervised approach - Integrative eXpression Profiling (IXP), to improve microarray classification accuracy, and help discover groups of genes that have been too weak to detect individually by traditional ways. To implement IXP, ant colony optimization reordering (ACOR) algorithm is used to group functionally related genes in an ordered way.

Results

Using Alzheimer's disease (AD) as an example, we demonstrate how to apply ACOR-based IXP approach into microarray classifications. Using a microarray dataset - GSE1297 with 31 samples as training set, the result for the blinded classification on another microarray dataset - GSE5281 with 151 samples, shows that our approach can improve accuracy from 74.83% to 82.78%. A recently-published 1372-probe signature for AD can only achieve 61.59% accuracy in the same condition. The ACOR-based IXP approach also has better performance than the IXP approach based on classic network ranking, graph clustering, and random-ordering methods in an overall classification performance comparison.

Conclusions

The ACOR-based IXP approach can serve as a knowledge-supervised feature transformation approach to increase classification accuracy dramatically, by transforming each gene expression profile to an integrated expression files as features inputting into standard classifiers. The IXP approach integrates both gene expression information and organized knowledge - disease gene/protein network topology information, which is represented as both network node weights (local topological properties) and network node orders (global topological characteristics).
Computational and experimental analyses of retrotransposon-associated minisatellite DNAs in the soybean genome
Authors: Mogil Lauren S , Slowikowski Kamil , Laten Howard M
Published: March 2012

Background

Retrotransposons are mobile DNA elements that spread through genomes via the action of element-encoded reverse transcriptases. They are ubiquitous constituents of most eukaryotic genomes, especially those of higher plants. The pericentromeric regions of soybean (Glycine max) chromosomes contain >3,200 intact copies of the Gmr9/GmOgre retrotransposon. Between the 3' end of the coding region and the long terminal repeat, this retrotransposon family contains a polymorphic minisatellite region composed of five distinct, interleaved minisatellite families. To better understand the possible role and origin of retrotransposon-associated minisatellites, a computational project to map and physically characterize all members of these families in the G. max genome, irrespective of their association with Gmr9, was undertaken.

Methods

A computational pipeline was developed to map and analyze the organization and distribution of five Gmr9-associated minisatellites throughout the soybean genome. Polymerase chain reaction amplifications were used to experimentally assess the computational outputs.

Results

A total of 63,841 copies of Gmr9-associated minisatellites were recovered from the assembled G. max genome. Ninety percent were associated with Gmr9, an additional 9% with other annotated retrotransposons, and 1% with uncharacterized repetitive DNAs. Monomers were tandemly interleaved and repeated up to 149 times per locus.

Conclusions

The computational pipeline enabled a fast, accurate, and detailed characterization of known minisatellites in a large, downloaded DNA database, and PCR amplification supported the general organization of these arrays.
Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons
Authors: Lejeune François-Xavier , Mesrob Lilia , Parmentier Frédéric , Bicep Cedric , Vazquez-Manrique Rafael P , Parker J Alex , Vert Jean-Philippe , Tourette Cendrine , Neri Christian
Published: March 2012

Background

A central goal in Huntington's disease (HD) research is to identify and prioritize candidate targets for neuroprotective intervention, which requires genome-scale information on the modifiers of early-stage neuron injury in HD.

Results

Here, we performed a large-scale RNA interference screen in C. elegans strains that express N-terminal huntingtin (htt) in touch receptor neurons. These neurons control the response to light touch. Their function is strongly impaired by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch response in adult animals, providing an in vivo model in which to manipulate the early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined, revealing 662 gene inactivations that either reduce or aggravate defective touch response in 128Q animals. Several genes were previously implicated in HD or neurodegenerative disease, suggesting that this screen has effectively identified candidate targets for HD. Network-based analysis emphasized a subset of high-confidence modifier genes in pathways of interest in HD including metabolic, neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q-neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD mice, or both, were identified.

Conclusions

Collectively, these results highlight the relevance to HD pathogenesis, providing novel information on the potential therapeutic targets for neuroprotection in HD.
Ongoing monitoring of data clustering in multicenter studies
Authors: Guthrie Lauren B , Oken Emily , Sterne Jonathan AC , Gillman Matthew W , Patel Rita , Vilchuck Konstantin , Bogdanovich Natalia , Kramer Michael S , Martin Richard M
Published: March 2012

Background

Multicenter study designs have several advantages, but the possibility of non-random measurement error resulting from procedural differences between the centers is a special concern. While it is possible to address and correct for some measurement error through statistical analysis, proactive data monitoring is essential to ensure high-quality data collection.

Methods

In this article, we describe quality assurance efforts aimed at reducing the effect of measurement error in a recent follow-up of a large cluster-randomized controlled trial through periodic evaluation of intraclass correlation coefficients (ICCs) for continuous measurements. An ICC of 0 indicates the variance in the data is not due to variation between the centers, and thus the data are not clustered by center.

Results

Through our review of early data downloads, we identified several outcomes (including sitting height, waist circumference, and systolic blood pressure) with higher than expected ICC values. Further investigation revealed variations in the procedures used by pediatricians to measure these outcomes. We addressed these procedural inconsistencies through written clarification of the protocol and refresher training workshops with the pediatricians. Further data monitoring at subsequent downloads showed that these efforts had a beneficial effect on data quality (sitting height ICC decreased from 0.92 to 0.03, waist circumference from 0.10 to 0.07, and systolic blood pressure from 0.16 to 0.12).

Conclusions

We describe a simple but formal mechanism for identifying ongoing problems during data collection. The calculation of the ICC can easily be programmed and the mechanism has wide applicability, not just to cluster randomized controlled trials but to any study with multiple centers or with multiple observers.
HIV testing and willingness to get HIV testing at a peer-run drop-in centre for people who inject drugs in Bangkok, Thailand
Authors: Ti Lianping , Hayashi Kanna , Kaplan Karyn , Suwannawong Paisan , Fu Eric , Wood Evan , Kerr Thomas
Published: March 2012

Background

Regular HIV testing among people who inject drugs is an essential component of HIV prevention and treatment efforts. We explored HIV testing behaviour among a community-recruited sample of injection drug users (IDU) in Bangkok, Thailand.

Methods

Data collected through the Mitsampan Community Research Project were used to examine correlates of HIV testing behaviour among IDU and to explore reasons for not being tested. Multivariate logistic regression was used to examine factors associated with willingness to access HIV testing at the drug-user-run Mitsampan Harm Reduction Centre (MSHRC).

Results

Among the 244 IDU who participated in this study, 186 (76.2%) reported receiving HIV testing in the previous six months. Enrolment in voluntary drug treatment (odds ratio [OR] = 2.34; 95% confidence interval [CI]: 1.18 - 4.63) and the tenofovir trial (OR = 44.81; 95%CI: 13.44 - 149.45) were positively associated with having been tested, whereas MSHRC use (OR = 1.78; 95%CI: 0.96 - 3.29) was marginally associated with having been tested. 56.9% of those who had not been tested reported in engaging in HIV risk behaviour in the past six months. 181 (74.2%) participants were willing to be tested at the MSHRC if testing were offered there. In multivariate analyses, willingness to get HIV testing at the MSHRC was positively associated with ever having been to the MSHRC (adjusted odds ratio [AOR] = 2.42; 95%CI: 1.21 - 4.85) and, among females, being enrolled in voluntary drug treatment services (AOR = 9.38; 95%CI: 1.14 - 76.98).

Conclusions

More than three-quarters of IDU received HIV testing in the previous six months. However, HIV risk behaviour was common among those who had not been tested. Additionally, 74.2% of participants were willing to receive HIV testing at the MSHRC. These findings provide evidence for ongoing HIV prevention education, as well potential benefits of incorporating HIV testing for IDU within peer-led harm reduction programs.
Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients
Authors: Jung Chan-Hee , Kim Bo-Yeon , Kim Chul-Hee , Kang Sung-Koo , Jung Sang-Hee , Mok Ji-Oh
Published: March 2012

Background

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.

Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.

Methods

A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.

Results

Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022).

Conclusions

In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.
Anti-inflammatory effects of methoxyphenolic compounds on human airway cells
Authors: Houser Kenneth R , Johnson David K , Ishmael Faoud T
Published: March 2012

Background

The respiratory epithelium plays a central role in the inflammatory response in asthma and other diseases. Methoxyphenolic compounds are purported to be effective anti-inflammatory agents, but their effects on the airway epithelium have not been well characterized.

Methods

Human airway cells were stimulated with TNF-α in the presence or absence of 4-substituted methoxyphenols and resveratrol. The expression of various cytokines was measured by qPCR, ELISAs, and protein arrays. Reactive oxygen species (ROS) production was measured with a reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein). Activation of NF-κB was measured by nuclear translocation and phosphorylation. Ribonuclear protein association with mRNA was assessed with a biotin-RNA affinity isolation assay.

Results

Multiple inflammatory mediators were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF, CXCL1, CXCL10, and Serpin E1. IC50values were obtained for each compound that showed significant anti-inflammatory activity: diapocynin (20.3 μM), resveratrol (42.7 μM), 2-methoxyhydroquinone (64.3 μM), apocynin (146.6 μM), and 4-amino-2-methoxyphenol (410 μM). The anti-inflammatory activity did not correlate with inhibition of reactive oxygen species production or NF-κB activation. However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA, indicating that they may act post-transcriptionally.

Conclusions

Methoxyphenols demonstrate anti-inflammatory activity in human airway cells. More potent compounds that act via similar mechanisms may have therapeutic potential as novel anti-inflammatory agents.
Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor
Authors: Zhao Junfeng , Chen Congde , Zhang Haochuan , Shen Jinhui , Zhang Hua , Lin Xiaokun , Qin Le , Bao Xiaozhou , Lin Jie , Lu Wenqiang , Wang Xiangdong , Chen Xiaoming
Published: March 2012

The testicular yolk sac tumor (TYST) is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.
Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation
Authors: Soliman Mahmoud L , Smith Mark D , Houdek Heidi M , Rosenberger Thad A
Published: March 2012

Background

Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression.

Methods

In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively.

Results

We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9), histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein and mRNA levels were increased by 1.3- and 10-fold, respectively, and acetate supplementation reduced this expression to control levels.

Conclusion

Based on these results, we conclude that dietary acetate supplementation attenuates neuroglial activation by effectively reducing pro-inflammatory cytokine expression by a mechanism that may involve a distinct site-specific pattern of histone acetylation and histone deacetylase expression in the brain.
Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level
Authors: Nogueira Juan-Patricio , Maraninchi Marie , Béliard Sophie , Lorec Anne Marie , Berthet Bruno , Bégu-Le Corroller Audrey , Dubois Noémie , Grangeot Rachel , Mattei Catherine , Gaudart Jean , Nicolay Alain , Portugal Henri , Vialettes Bernard , Valéro René
Published: March 2012

Background

Low plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients.

Methods

Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects.

Results

Insulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients (p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group (p = 0.032).

Conclusions

These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.
Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis or rheumatoid arthritis
Authors: Krüger Jan Philipp , Endres Michaela , Neumann Katja , Stuhlmüller Bruno , Morawietz Lars , Häupl Thomas , Kaps Christian
Published: March 2012

Background

Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP.

Methods

CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3.

Results

CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA.

Conclusion

These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.
Ectopic pancreas tissue appearing in a mediastinal cyst
Authors: Szabados Sandor , Lénárd László , Tornóczky Tamás , Várady Edit , Verzár Zsófia
Published: March 2012

Heterotopia of pancreatic tissue is a common developmental anomaly. Although ectopic pancreatic tissue is mostly found in the gastrointestinal tract, localization in the mediastinum is extremely rare. We report a 32-year-old male patient who had an urgent thoracotomy two years ago due to a thoracic surgery. During the thoracotomy fragments of a partly necrotic cystic mass in the right thorax were removed and decortication was performed. Two years later the patient was hospitalized again because of haemoptoe and atypical chest pain. A residual cystic mass was detected between the right hilum and the ascending aorta connecting to the pericardium, the superior vena cava and the aorta on the chest CT. After the operation a mediastinal cyst was diagnosed, with a pancreatic tissue by histology.
The song remains the same although the instruments are changing: complications following selective non-operative management of blunt spleen trauma: a retrospective review of patients at a level I trauma centre from 1996 to 2007
Authors: Clancy Aisling A , Tiruta Corina , Ashman Dianne , Ball Chad G , Kirkpatrick Andrew W
Published: March 2012

Background

Despite a widespread shift to selective non-operative management (SNOM) for blunt splenic trauma, there remains uncertainty regarding the role of adjuncts such as interventional radiological techniques, the need for follow-up imaging, and the incidence of long-term complications. We evaluated the success of SNOM (including splenic artery embolization, SAE) for the management of blunt splenic injuries in severely injured patients.

Methods

Retrospective review (1996-2007) of the Alberta Trauma Registry and health records for blunt splenic trauma patients, aged 18 and older, with injury severity scores of 12 or greater, admitted to the Foothills Medical Centre.

Results

Among 538 eligible patients, 150 (26%) underwent early operative intervention. The proportion of patients managed by SNOM rose from 50 to 78% over the study period, with an overall success rate of SNOM of 87%, while injury acuity remained unchanged over time. Among SNOM failures, 65% underwent surgery within 24 hours of admission. Splenic arterial embolization (SAE) was used in only 7% of patients managed non-operatively, although at least 21% of failed SNOM had contrast extravasation potentially amenable to SAE. Among Calgary residents undergoing SNOM, hospital readmission within six months was required in three (2%), all of whom who required emergent intervention (splenectomy 2, SAE 1) and in whom none had post-discharge follow-up imaging. Overall, the use of post-discharge follow-up CT imaging was low following SNOM (10%), and thus no CT images identified occult hemorrhage or pseudoaneurysm. We observed seven cases of delayed splenic rupture in our population which occurred from five days to two months following initial injury. Three of these occurred in the post-discharge period requiring readmission and intervention.

Conclusions

SNOM was the initial treatment strategy for most patients with blunt splenic trauma with 13% requiring subsequent operative intervention intended for the spleen. Cases of delayed splenic rupture occurred up to two months following initial injury. The low use of both follow-up imaging and SAE make assessment of the utility of these adjuncts difficult and adherence to formalized protocols will be required to fully assess the benefit of multi-modality management strategies.
Expression and localization of claudins-3 and -12 in transformed human brain endothelium
Authors: Schrade Anja , Sade Hadassah , Couraud Pierre-Olivier , Romero Ignacio A , Weksler Babette B , Niewoehner Jens
Published: March 2012

Background

The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model of the human Blood Brain Barrier (BBB) for the expression of brain endothelial specific claudins-3 and -12.

Findings

hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture.

Conclusions

These results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell line and make claudin-3 a potential marker for BBB characteristics in vitro.
Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?
Authors: Paquet Joseph , Goebel Jean-Christophe , Delaunay Camille , Pinzano Astrid , Grossin Laurent , Cournil-Henrionnet Christel , Gillet Pierre , Netter Patrick , Jouzeau Jean-Yves , Moulin David
Published: March 2012

Introduction

We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis.

Methods

We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease.

Results

The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed.

Conclusions

Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.
Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II
Authors: Rice Megan S , Tamimi Rulla M , Connolly James L , Collins Laura C , Shen Dejun , Pollak Michael N , Rosner Bernard , Hankinson Susan E , Tworoger Shelley S
Published: March 2012

Introduction

Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans.

Methods

We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to exposure status, classified lobule type in normal adjacent tissue on available biopsy slides according to the number of acini per lobule. For each participant, the pathologist determined the predominant lobule type (that is, type 1, type 2, or type 3) and whether any type 1 or any type 3 lobules were present. Lobule type was then classified as: predominant type 1/no type 3 lobules, which is suggestive of complete involution; or other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and the ratio of IGF-1:IGFBP-3 levels with lobule type.

Results

In univariate analyses, greater age, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type 1/no type 3 lobules (P < 0.05). In multivariate models adjusting for age and assay batch, higher IGF-1 levels were associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.37, 95% confidence interval = 0.15 to 0.89). Greater ratios of IGF-1:IGFBP-3 levels were also associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.26, 95% confidence interval = 0.11 to 0.64). These results were slightly attenuated after adjustment for other potential predictors of lobule type.

Conclusions

Higher IGF-1 levels and a greater IGF-1:IGFBP-3 ratio were associated with decreased odds of having predominant type 1 lobules/no type 3 lobules among women with proliferative BBD in the NHSII. This study provides further evidence for the role of insulin-like growth factors in the structure of breast lobules and lobular involution.
Fatigue, Inflammation, and ω-3 and ω-6 Fatty Acid Intake Among Breast Cancer Survivors
Authors: Alfano Catherine M. , Imayama Ikuyo , Neuhouser Marian L. , Kiecolt-Glaser Janice K. , Smith Ashley Wilder , Meeske Kathleen , McTiernan Anne , Bernstein Leslie , Baumgartner Kathy B. , Ulrich Cornelia M. , Ballard-Barbash Rachel
Published: March 2012

Purpose

Evidence suggests that inflammation may drive fatigue in cancer survivors. Research in healthy populations has shown reduced inflammation with higher dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), which could potentially reduce fatigue. This study investigated fatigue, inflammation, and intake of ω-3 and ω-6 PUFAs among breast cancer survivors.

Methods

Six hundred thirty-three survivors (mean age, 56 years; stage I to IIIA) participating in the Health, Eating, Activity, and Lifestyle Study completed a food frequency/dietary supplement questionnaire and provided a blood sample assayed for C-reactive protein (CRP) and serum amyloid A (30 months after diagnosis) and completed the Piper Fatigue Scale and Short Form-36 (SF-36) vitality scale (39 months after diagnosis). Analysis of covariance and logistic regression models tested relationships between inflammation and fatigue, inflammation and ω-3 and ω-6 PUFA intake, and PUFA intake and fatigue, controlling for three incremental levels of confounders. Fatigue was analyzed continuously (Piper scales) and dichotomously (SF-36 vitality ≤ 50).

Results

Behavioral (P = .003) and sensory (P = .001) fatigue scale scores were higher by increasing CRP tertile; relationships were attenuated after adjustment for medication use and comorbidity. Survivors with high CRP had 1.8 times greater odds of fatigue after full adjustment (P < .05). Higher intake of ω-6 relative to ω-3 PUFAs was associated with greater CRP (P = .01 after full adjustment) and greater odds of fatigue (odds ratio, 2.6 for the highest v lowest intake; P < .05).

Conclusion

Results link higher intake of ω-3 PUFAs, decreased inflammation, and decreased physical aspects of fatigue. Future studies should test whether ω-3 supplementation may reduce fatigue among significantly fatigued breast cancer survivors.
Population-Based 20-Year Survival Among People Diagnosed With Thin Melanomas in Queensland, Australia
Authors: Green Adèle C. , Baade Peter , Coory Michael , Aitken Joanne F. , Smithers Mark
Published: March 2012

Purpose

The 20-year survival rates are unknown for the majority of melanoma patients—those with thin melanomas. We determined 20-year survival rates of patients diagnosed with thin melanomas (≤ 1.00 mm) in the general population and also determined the main prognostic factors.

Patients and Methods

Available clinical and histologic data from the Queensland Cancer Registry were obtained for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006 and matched against national death registration data. Melanoma-specific survival estimates to December 31, 2007, were assessed, and subgroup differences in prognosis were determined by fitting multivariate Cox proportional hazard models.

Results

Among 26,736 people in the state of Queensland diagnosed with thin melanomas, the 20-year survival was 96%. The most influential determinants of prognosis were tumor thickness ≥ 0.75 mm (adjusted hazard ratio [HR], 4.33; 95% CI, 2.8 to 6.8 compared with tumors < 0.25 mm) and patient age at diagnosis older than 65 years (HR, 2.8; 95% CI, 1.8 to 4.5) compared with age younger than 25 years. Acral lentiginous and nodular tumors, male sex, tumor site on the scalp or neck, or tumor invasion of the entire papillary dermis each independently increased the risk of dying from thin invasive melanoma.

Conclusion

The outlook for patients with thin invasive melanoma is positive, although continued clinical vigilance is warranted for patients with nodular melanoma and those with the thickest tumors.
Salvage Chemotherapy for Pretreated Gastric Cancer: A Randomized Phase III Trial Comparing Chemotherapy Plus Best Supportive Care With Best Supportive Care Alone
Authors: Kang Jung Hun , Lee Soon Il , Lim Do Hyoung , Park Keon-Woo , Oh Sung Yong , Kwon Hyuk-Chan , Hwang In Gyu , Lee Sang-Cheol , Nam Eunmi , Shin Dong Bok , Lee Jeeyun , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Park Se Hoon
Published: March 2012

Purpose

When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons.

Patients and Methods

Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC—either docetaxel 60 mg/m2 every 3 weeks or irinotecan 150 mg/m2 every 2 weeks—was left to the discretion of investigators. Primary end point was overall survival (OS).

Results

Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116).

Conclusion

To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.
A New Quality Standard: The Integration of Psychosocial Care Into Routine Cancer Care
Authors: Jacobsen Paul B. , Wagner Lynne I.
Published: March 2012

There is a growing consensus that psychosocial care should be integrated into the routine care of patients with cancer. This consensus is consistent with the considerable body of evidence about the deleterious effects of allowing psychosocial needs to remain unmet and the growing body of evidence about the beneficial effects of providing psychosocial services to address unmet needs. Despite this evidence, available data suggest that a considerable portion of the population of patients with cancer does not receive needed psychosocial care. Three lines of professional activity initiated in recent years have the potential to address this issue in fundamental ways: the formulation of standards of cancer care that address the psychosocial component of care, the issuance of clinical practice guidelines for psychosocial care of patients with cancer, and the development and implementation of measurable indicators of the quality of psychosocial care in oncology settings. This article provides an overview of accomplishments in each of these areas; it is designed to ensure that oncologists and other cancer treatment providers are knowledgeable about current standards for psychosocial care, existing consensus- and evidenced-based recommendations for clinical practice in this area, and resources and tools for evaluating and, if indicated, improving the quality of the psychosocial care their patients are receiving. The article concludes with a critical appraisal of these activities and a consideration of how current efforts might be enhanced.