bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study of primary care clinicians' views of treating childhood obesity
Authors: Walker Olivia , Strong Mark , Atchinson Rebecca , Saunders Joanna , Abbott Jo 
Published: September 2007

AbstractBackgroundThe prevalence of childhood obesity is rising and the UK Government have stated a commitment to addressing obesity in general. One method has been to include indicators relating to obesity within the GP pay-for-performance Quality and Outcomes Framework (QOF) contract. This study aimed to explore general practitioners' and practice nurses' views in relation to their role in treating childhood obesity.MethodsWe interviewed eighteen practitioners (twelve GPs and six nurses) who worked in general practices contracting with Rotherham Primary Care Trust. Interviews were face to face and semi structured. The transcribed data were analysed using framework analysis.ResultsGPs and practice nurses felt that their role was to raise the issue of a child's weight, but that ultimately obesity was a social and family problem. Time constraint, lack of training and lack of resources were identified as important barriers to addressing childhood obesity. There was concern that the clinician-patient relationship could be adversely affected by discussing what was often seen as a sensitive topic. GPs and practice nurses felt ill-equipped to tackle childhood obesity given the lack of evidence for effective interventions, and were sceptical that providing diet and exercise advice would have any impact upon a child's weight.ConclusionGPs and practice nurses felt that their role in obesity management was centred upon raising the issue of a child's weight, and providing basic diet and exercise advice. Clinicians may find it difficult to make a significant impact on childhood obesity while the evidence base for effective management remains poor. Until the lack of effective interventions is addressed, implementing additional targets (for example through the QOF) may not be effective.
Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms
Authors: Vlaar Annemarie MM , Bouwmans Angela EP , van Kroonenburgh Marinus JPG , Mess Werner H , Tromp Selma C , Wuisman Piet GWM , Kessels Alfons GH , Winogrodzka Ania , Weber Wim EJ 
Published: September 2007

Abstract

Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.
We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin.

Methods/Design
We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain.

Discussion
As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.

Trial registration

(ITRSCC) NCT00368199
Over-expression of 14-3-3zeta is an early event in oral cancer
Authors: Matta Ajay , Bahadur Sudhir , Duggal Ritu , Gupta Siddhartha D , Ralhan Ranju 
Published: September 2007

Abstract

Background
The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display.

Methods
The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2.

Results
Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (ptrend < 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells.

Conclusion
Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer.
Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma
Authors: Lei Ke-Feng , Wang Yan-Fang , Zhu Xiao-Qun , Lu Peng-Cheng , Sun Bing-Sheng , Jia Hu-Liang , Ren Ning , Ye Qing-Hai , Sun Hui-Chuan , Wang Lu , Tang Zhao-You , Qin Lun-Xiu 
Published: September 2007

Abstract

Background
The prognosis of patients with hepatocellular carcinoma (HCC) still remains very dismal, which is mainly due to metastasis. In our previous studies, we found that chromosome 8p deletions might contribute to metastasis of HCC. In this study, we aimed to identify the candidate metastatic suppressor gene on chromosome 8p.

Methods
Oligo-nucleotide microarrays which included 322 genes on human chromosome 8p were constructed to analyze the difference in gene expression profiles between HCC tissues with and without metastasis. The leading differentially expressed genes were identified and selected for further analysis by real-time PCR and Western blotting. Recombinant expression plasmid vectors for each target gene were constructed and transfected into HCC cells and its in vitro effects on proliferation and invasion of HCC cells were also investigated.

Results
Sixteen leading differentially expressed genes were identified from the HCC tissues with metastasis compared with those without metastasis (p < 0.01, q < 16 %). Among of the 10 significantly down-regulated genes in HCC with metastasis, methionine sulfoxide reductase A (MSRA) had the lowest p value and false discovery rate (FDR), and was considered as a potential candidate for metastasis suppressor gene. Real-time PCR and Western blotting confirmed that the mRNA and protein expression levels of MSRA were significantly decreased in HCC with metastasis compared with those without metastasis (p < 0.001), and MSRA mRNA level in HCCLM6 cells (with high metastatic potential) was also much lower than that of other HCC cell lines. Transfection of a recombinant expression plasmid vector and overexpression of MSRA gene could obviously inhibit cell colony formation (4.33 ± 2.92 vs. 9.17 ± 3.38, p = 0.008) and invasion (7.40 ± 1.67 vs. 17.20 ± 2.59, p= 0.0001) of HCCLM6 cell line.

Conclusion

MSRA gene on chromosome 8p might possess metastasis suppressor activity in HCC.
The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers
Authors: Delage Barbara , Rullier Anne , Capdepont Maylis , Rullier Eric , Cassand Pierrette 
Published: September 2007

Abstract

Background
Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoid-activated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC.

Method
The mRNA expression of the different nuclear receptor subtypes and of COX-2 was measured in 20 resected samples of CRC and paired non-tumor tissues. The association between expression patterns and weight status defined as a body mass index (BMI) was statistically analyzed.

Results
No changes were observed in PPARγ mRNA expression while the expression of PPARδ, retinoid-activated receptors and COX-2 were significantly increased in cancer tissues compared to normal colon mucosa (P ≤ 0.001). The weight status appeared to be an independent factor, although we detected an increased level of COX-2 expression in the normal mucosa from overweight patients (BMI ≥ 25) compared to subjects with healthy BMI (P = 0.002).

Conclusion
Our findings show that alterations in the pattern of nuclear receptor expression observed in CRC do not appear to be correlated with patient weight status. However, the analysis of COX-2 expression in normal colon mucosa from subjects with a high BMI suggests that COX-2 deregulation might be driven by excess weight during the colon carcinogenesis process.
A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model
Authors: Munoz Lenka , Ranaivo Hantamalala Ralay , Roy Saktimayee M , Hu Wenhui , Craft Jeffrey M , McNamara Laurie K , Chico Laura Wing , Van Eldik Linda J , Watterson D Martin 
Published: September 2007

Abstract

Background
An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD). This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ) and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes.

Methods
A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model.

Results
A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM) was developed. Oral administration of the compound at a low dose (2.5 mg/kg) resulted in attenuation of excessive proinflammatory cytokine production in the hippocampus back towards normal in the animal model. Animals with attenuated cytokine production had reductions in synaptic dysfunction and hippocampus-dependent behavioral deficits.

Conclusion
The p38α MAPK pathway is quantitatively important in the Aβ-induced production of proinflammatory cytokines in hippocampus, and brain p38α MAPK is a viable molecular target for future development of potential disease-modifying therapeutics in AD and related neurodegenerative disorders.
The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists
Authors: Huang Da Wei , Sherman Brad T , Tan Qina , Collins Jack R , Alvord W Gregory , Roayaei Jean , Stephens Robert , Baseler Michael W , Lane H Clifford , Lempicki Richard A 
Published: September 2007

AbstractThe DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.
Sex hormones and mental health
Authors: Golightly Louise , Young Allan 
Published: September 2007

Hormones are widely considered to cause powerful psychological effects and because of this psychiatrists may be asked to advise general practitioners, consultants in other specialities or patients about the relationship between hormones (including sex hormones) and psychiatric disorder. Sex hormones may be relevant to psychiatry in three ways:(a) Sex hormones may play a role in the pathophysiology of psychiatric disorders.(b) These agents may be utilised for treatment of psychiatric disorder.(c) Administration of sex hormones may cause psychiatric side-effects.
Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs
Authors: Munirah S. , Samsudin O. C. , Chen H. C. , Salmah S. H. Sharifah , Aminuddin B. S. , Ruszymah B. H. I. 
Published: September 2007

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.
Delayed recovery and late development of complex regional pain syndrome in patients with an isolated fracture of the distal radius
Authors: Goris R. J. A. , Leixnering M. , Huber W. , Figl M. , Jaindl M. , Redl H. 
Published: September 2007

We studied prospectively the regional inflammatory response to a unilateral distal radial fracture in 114 patients at eight to nine weeks after injury and again at one year. Our aim was to identify patients at risk for a delayed recovery and particularly those likely to develop complex regional pain syndrome. In order to quantify clinically the inflammatory response, a regional inflammatory score was developed. In addition, blood samples were collected from the antecubital veins of both arms for comparative biochemical and blood-gas analysis. The severity of the inflammatory response was related to the type of treatment (Kruskal-Wallis test, p = 0.002). A highly significantly-positive correlation was found between the regional inflammatory score and the length of time to full recovery (r2 = 0.92, p = 0.01, linear regession). A regional inflammatory score of 5 points with a sensitivity of 100% but a specificity of only 16% also identified patients at risk of complex regional pain syndrome. None of the biochemical parameters studied correlated with regional inflammatory score or predicted the development of complex regional pain syndrome. Our study suggests that patients with a distal radial fracture and a regional inflammatory score of 5 points or more at eight to nine weeks after injury should be considered for specific anti-inflammatory treatment.
Narrowing of the neck in resurfacing arthroplasty of the hip
Authors: Hing C. B. , Young D. A. , Dalziel R. E. , Bailey M. , Back D. L. , Shimmin A. J. 
Published: September 2007

Narrowing of the femoral neck after resurfacing arthroplasty of the hip has been described previously in both cemented and uncemented hip resurfacing. The natural history of narrowing of the femoral neck is unknown. We retrospectively measured the diameter of the femoral neck in a series of 163 Birmingham hip resurfacings in 163 patients up to a maximum of six years after operation to determine the extent and progression of narrowing. There were 105 men and 58 women with a mean age of 52 years (18 to 82). At a mean follow-up of five years, the mean Harris hip score was 94.8 (47 to 100) and the mean flexion of the hip 112.5° (80° to 160°). There was some narrowing of the femoral neck in 77% (125) of the patients reviewed, and in 27.6% (45) the narrowing exceeded 10% of the diameter of the neck. A multiple logistic regression analysis showed a significant association (chi-squared test (derived from logistic regression) p = 0.01) of narrowing with female gender and a valgus femoral neck/shaft angle. There was no significant association between the range of movement, position or size of the component or radiological lucent lines and narrowing of the neck (chi-squared test; p = 0.10 (flexion), p = 0.08 (size of femoral component), p = 0.09 (size of acetabular component), p = 0.71 (femoral component angulation), p = 0.99 (lucent lines)). There was no significant difference between the diameter of the neck at a mean of three years (2.5 to 3.5) and that at five years (4.5 to 5.5), indicating that any change in the diameter of the neck had stabilised by three years (sign rank test, p = 0.60). We conclude that narrowing of the femoral neck which is found with the Birmingham hip resurfacing arthroplasty is in most cases associated with no adverse clinical or radiological outcome up to a maximum of six years after the initial operation.
Stem cells and debrided waste
Authors: Biant L. C. , Bentley G. 
Published: September 2007

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells. Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.
Bone transport using hydroxyapatite loaded with bone morphogenetic protein in rabbits
Authors: Watanabe K. , Tsuchiya H. , Sakurakichi K. , Tomita K. 
Published: September 2007

The feasibility of bone transport with bone substitute and the factors which are essential for a successful bone transport are unknown. We studied six groups of 12 Japanese white rabbits. Groups A to D received cylindrical autologous bone segments and groups E and F hydroxyapatite prostheses. The periosteum was preserved in group A so that its segments had a blood supply, cells, proteins and scaffold. Group B had no blood supply. Group C had proteins and scaffold and group D had only scaffold. Group E received hydroxyapatite loaded with recombinant human bone morphogenetic protein-2 and group F had hydroxyapatite alone. Distraction osteogenesis occurred in groups A to C and E which had osteo-conductive transport segments loaded with osteo-inductive proteins. We conclude that scaffold and proteins are essential for successful bone transport, and that bone substitute can be used to regenerate bone.
The open modified Bankart procedure
Authors: Berendes T. D. , Wolterbeek R. , Pilot P. , Verburg H. , te Slaa R. L. 
Published: September 2007

We report the outcome of a modified Bankart procedure using suture anchors in 31 patients (31 shoulders) with a mean follow-up of 11 years (10 to 15). The mean age of the patients was 28 years (16 to 39). At follow-up, the mean Rowe score was 90 points (66 to 98) and the Constant score was 96 points (85 to 100). A total of 26 shoulders (84%) had a good or excellent result. The rate of recurrence varied between 6.7% and 9.7% and depended on how recurrence was defined. Two patients had a significant new injury at one and nine years, respectively after operation. The overall rate of instability (including subluxations) varied between 12.9% and 22.6%. All patients returned to work, with 29 (94%) resuming their pre-operative occupation and level of activity. Mild radiological osteoarthritis was seen in nine shoulders (29%) and severe osteoarthritis in one. We conclude that the open modified Bankart procedure is a reliable surgical technique with good long-term results.