bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Micronutrients on Behavior and Mood in Adults With ADHD: Evidence From an 8-Week Open Label Trial With Natural Extension
Authors: Rucklidge Julia , Taylor Mairin , Whitehead Kathryn
Published: January 2010

Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported transitory mild side effects. Significant improvements were noted across informants (self, observer, clinician) on measures of inattention and hyperactivity/impulsivity, mood, quality of life, anxiety, and stress all with medium to very large effect sizes (all ps < .01); however, the mean of inattention remained in a clinical range whereas the means on measures of mood and hyperactivity/impulsivity were normalized. Follow-up data showed maintenance of changes or further improvement for those who stayed on the micronutrients. Conclusions: Although this study, as an open trial, does not in itself prove efficacy, it provides preliminary evidence supporting the need for a randomized clinical trial of micronutrients as treatment for the more complex presentations of ADHD.
Characteristics of ADHD Among Omani Schoolchildren Using DSM-IV: Descriptive Study
Authors: Al-Sharbati Marwan M. , Zaidan Ziad A. J. , Dorvlo Atsu S. S. , Al-Adawi Samir
Published: January 2010

Background: There is a dearth of studies describing the characteristics of ADHD among schoolchildren attending child psychiatry clinics in the Arab world. Most of the previous quests have focused on community surveys or themes that hampered international comparison. Aim: This study screened for the presence of ADHD as well as investigates the psychosocial and educational history relevant for the diagnosis of ADHD among children. Method: Consecutive schoolchildren attending child psychiatric consultations were screened for the presence of ADHD according to the Diagnostic and Statistical Manual for Mental disorders ( DSM) criteria. Result: A total of 221 schoolchildren suffering from ADHD were identified according to the DSM. The year incidence was 0.16. Males constituted the majority presenting with ADHD. The contribution of consanguinity and a history of acquired brain injury were common features. The majority were attending mainstream education as pharmacotherapy is the only option available for managing ADHD. Conclusion: This study is one of the few from this part of the world using DSM criteria to diagnose ADHD. The implications of the present findings are discussed in the context of the available literature and the specific situation in Oman. ( J. of Att. Dis. 2011; 15(2) 139-146)
University-Based Evaluation Training Programs in the United States 1980—2008: An Empirical Examination
Authors: LaVelle John M. , Donaldson Stewart I.
Published: January 2010

Evaluation practice has grown in leaps and bounds in recent years. In contrast, the most recent survey data suggest that there has been a sharp decline in the number and strength of preservice evaluation training programs in the United States. In an effort to further understand this curious trend, an alternative methodology was used to examine the current state of university-based evaluation training programs in the United States. An online search and curricular document analysis suggest different trends, including a dramatic increase in the number of evaluation training programs in the United States, specifically within schools of education. The importance of using alternative methodologies for understanding the nature of evaluation training programs is discussed.
Comparing How to Compare: An Evaluation of Alternative Performance Measurement Systems in the Field of Social Care
Authors: Clarkson Paul , Challis David , Davies Sue , Donnelly Michael , Beech Roger , Hirano Takayuki
Published: January 2010

Comparative performance evaluation has taken different forms depending upon the purposes of performance monitoring and the types of measures available. This paper investigates the different performance measurement systems in place in the social care setting, in particular for older people receiving community care services. In England, earlier systems to assist performance management within organizations have been eclipsed by national systems of regulation with top— down implementation of standards and measures. In Northern Ireland, by contrast, organizations have been compared descriptively without the use of national targets. Internationally, in Japan, organizations arranging similar services have had more local information available collected in a bottom—up fashion with greater employment of service user-level data. These differences in performance evaluation are located within an analytical framework permitting comparisons of system design and the use of measures. Conclusions are drawn concerning the breadth of evidence available for successfully monitoring service provision in this setting.
Introduction
Authors: Verschik Anna
Published: January 2010

This special issue is partly based on the papers presented in the colloquium Language contacts in the post-Soviet space, organized by the guest-editor at the 6th International Symposium on Bilingualism in Hamburg in 2007. To the best of my knowledge, this is the first collection of articles dedicated to post-Soviet language contacts. In what follows I will try to situate the topic within the context of research in such established fields as contact linguistics, post-Soviet studies, and research on Russian in diaspora. These fields do have many aspects and viewpoints in common with the proposed topic of post-Soviet language contacts but, nonetheless, there are important theoretical and methodological differences as well.
A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression
Authors: Durkalski Valerie , Wenle Zhao  , Dillon Catherine , Kim Jaemyung
Published: January 2010

Background Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost.

Purpose To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression.

Methods The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems.

Results The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports.

Limitations Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is increased and the value of using this system for other trials is reduced.

Conclusion Web-based central computerized systems offer time-saving, secure options for managing clinical trial data. The choice of a commercially available system or an internally developed system is determined by the requirements of the study and users. Pros and cons to both approaches were discussed. If the intention is to use the system for various trials (single and multi-center, phases I—III) across various therapeutic areas, then the overall design should be a generic structure that simplifies the general application with minimal loss of functionality.
Current evidence for osteoarthritis treatments
Authors: Anandacoomarasamy Ananthila , March Lyn
Published: January 2010

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disability among older people. The burden of the disease is expected to rise with an aging population and the increasing prevalence of obesity. Despite this, there is as yet no cure for OA. However, in recent years, a number of potential therapeutic advances have been made, in part due to improved understanding of the underlying pathophysiology. This review provides the current evidence for symptomatic management of OA including nonpharmacological, pharmacological and surgical approaches. The current state of evidence for disease-modifying therapy in OA is also reviewed.
Histidine-rich glycoprotein is a novel plasma pattern recognition molecule that recruits IgG to facilitate necrotic cell clearance via FcγRI on phagocytes
Authors: Poon Ivan K. H. , Hulett Mark D. , Parish Christopher R.
Published: January 2010

Under normal physiologic conditions, necrotic cells resulting from tissue injury are rapidly removed from the circulation and tissues by phagocytes, thus preventing the exposure of intracellular antigenic and immunostimulatory molecules that can aid the development of autoimmune disease. Histidine-rich glycoprotein (HRG), a relatively abundant plasma glycoprotein, has a multidomain structure that can interact with many ligands including components of the fibrinolytic and immune systems. Recently, it has been reported that HRG can bind strongly to cytoplasmic ligand(s) exposed in necrotic cells to enhance clearance by phagocytes. Here we describe the molecular mechanisms underpinning this process. A complex consisting of both HRG and immunoglobulin G (IgG) was found as necessary to aid necrotic cell uptake by monocytes, predominantly via an FcγRI-dependent mechanism. The findings in this study also show that HRG can potentially interact with anionic phospholipids exposed in necrotic cells. Furthermore, the enhanced phagocytosis of necrotic cells induced by HRG-IgG complexes triggers phagocytes to release proinflammatory cytokines such as interleukin-8 and tumor necrosis factor. Thus, HRG has the unique property of complexing with IgG and facilitating a proinflammatory innate immune response to promote the clearance of necrotic cells.
Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors
Authors: Ostrovsky Olga , Shimoni Avichai , Rand Avital , Vlodavsky Israel , Nagler Arnon
Published: January 2010

Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase compared with their human leukocyte antigen (HLA)–matched donors. In addition, HPSE gene SNPs disclosed a correlation with extensive chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates involvement of heparanase in the development of acute and extensive chronic GVHD. Moreover, it suggests a possible mechanism for the aggressive behavior of T lymphocytes leading to GVHD when the recipients possess genotype combinations that dictate high levels of heparanase mRNA compared with their HLA-matched donors expressing low levels of heparanase.
13q14 deletions in CLL involve cooperating tumor suppressors
Authors: Palamarchuk Alexey , Efanov Alexey , Nazaryan Natalya , Santanam Urmila , Alder Hansjuerg , Rassenti Laura , Kipps Thomas , Croce Carlo M. , Pekarsky Yuri
Published: January 2010

B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. 13q14 deletions are most common chromosomal alterations in CLL. We previously reported that miR-15/16 is a target of 13q14 deletions and plays a tumor suppressor role by targeting BCL2. Because DLEU7 is located near miR-15/16 and is also positioned within a minimal deleted region, we investigated whether DLEU7 could also play a tumor suppressor role. Recent studies of transgenic mouse models demonstrated the importance of the nuclear factor-κB (NF-κB) pathway in CLL. To examine the possible role of DLEU7 in CLL, we investigated the effect of DLEU7 expression on NF-κB and nuclear factor of activated T cells (NFAT) activity. We found that DLEU7 functions as a potent NF-κB and NFAT inhibitor by physically interacting and inhibiting TACI and BCMA, members of the tumor necrosis factor (TNF) receptor family involved in B-CLL. In addition, DLEU7 expression in A549 lung cancer cells resulted in a decrease in S phase and increased apoptosis. The results suggest that loss of DLEU7 may cooperate with the loss of miR-15/16 in the pathogenesis of CLL.
Active learning for human protein-protein interaction prediction
Authors: Mohamed Thahir P , Carbonell Jaime G , Ganapathiraju Madhavi K
Published: January 2010

Background

Biological processes in cells are carried out by means of protein-protein interactions. Determining whether a pair of proteins interacts by wet-lab experiments is resource-intensive; only about 38,000 interactions, out of a few hundred thousand expected interactions, are known today. Active machine learning can guide the selection of pairs of proteins for future experimental characterization in order to accelerate accurate prediction of the human protein interactome.

Results

Random forest (RF) has previously been shown to be effective for predicting protein-protein interactions. Here, four different active learning algorithms have been devised for selection of protein pairs to be used to train the RF. With labels of as few as 500 protein-pairs selected using any of the four active learning methods described here, the classifier achieved a higher F-score (harmonic mean of Precision and Recall) than with 3000 randomly chosen protein-pairs. F-score of predicted interactions is shown to increase by about 15% with active learning in comparison to that with random selection of data.

Conclusion

Active learning algorithms enable learning more accurate classifiers with much lesser labelled data and prove to be useful in applications where manual annotation of data is formidable. Active learning techniques demonstrated here can also be applied to other proteomics applications such as protein structure prediction and classification.
Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
Authors: Manthey Carolin , Mern Demissew S , Gutmann Anja , Zielinski Anne J , Herz Corinna , Lassmann Silke , Hasskarl Jens
Published: January 2010

Background

ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.

Results

Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

Conclusions

This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant
Authors: Nagabhushana Ananthamurthy , Chalasani Madhavi L , Jain Nishant , Radha Vegesna , Rangaraj Nandini , Balasubramanian Dorairajan , Swarup Ghanshyam
Published: January 2010

Background

Optineurin is a multifunctional protein involved in several functions such as vesicular trafficking from the Golgi to the plasma membrane, NF-κB regulation, signal transduction and gene expression. Mutations in optineurin are associated with glaucoma, a neurodegenerative eye disease that causes blindness. Genetic evidence suggests that the E50K (Glu50Lys) is a dominant disease-causing mutation of optineurin. However, functional alterations caused by mutations in optineurin are not known. Here, we have analyzed the role of optineurin in endocytic recycling and the effect of E50K mutant on this process.

Results

We show that the knockdown of optineurin impairs trafficking of transferrin receptor to the juxtanuclear region. A point mutation (D474N) in the ubiquitin-binding domain abrogates localization of optineurin to the recycling endosomes and interaction with transferrin receptor. The function of ubiquitin-binding domain of optineurin is also needed for trafficking of transferrin to the juxtanuclear region. A disease causing mutation, E50K, impairs endocytic recycling of transferrin receptor as shown by enlarged recycling endosomes, slower dynamics of E50K vesicles and decreased transferrin uptake by the E50K-expressing cells. This impaired trafficking by the E50K mutant requires the function of its ubiquitin-binding domain. Compared to wild type optineurin, the E50K optineurin shows enhanced interaction and colocalization with transferrin receptor and Rab8. The velocity of Rab8 vesicles is reduced by co-expression of the E50K mutant. These results suggest that the E50K mutant affects Rab8-mediated transferrin receptor trafficking.

Conclusions

Our results suggest that optineurin regulates endocytic trafficking of transferrin receptor to the juxtanuclear region. The E50K mutant impairs trafficking at the recycling endosomes due to altered interactions with Rab8 and transferrin receptor. These results also have implications for the pathogenesis of glaucoma caused by the E50K mutation because endocytic recycling is vital for maintaining homeostasis.
Non-consensus GLI binding sites in Hedgehog target gene regulation
Authors: Winklmayr Martina , Schmid Carmen , Laner-Plamberger Sandra , Kaser Alexandra , Aberger Fritz , Eichberger Thomas , Frischauf Anna-Maria
Published: January 2010

Background

The GLI transcription factors, mediators of the hedgehog signal bind with high affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions in GLI binding sites has been measured systematically, but the affinities of the variant binding sites appears low compared to the frequency of occurrence of variant sites in known GLI target gene promoters.

Results

We quantified transcriptional activation by GLI using PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI consensus binding site. As expected variants with very low affinity did not activate the reporter. Many lower affinity binding sequences are, however, functional in the presence of moderate GLI concentration. Using two natural non-consensus GLI site promoters we showed that substitution of the variant sequences by consensus leads to comparable activity.

Conclusions

Variant GLI binding sites with relatively low affinity can within natural promoters lead to strong transcriptional activation. This may facilitate the identification of additional direct GLI target genes.
Differential requirement of the epidermal growth factor receptor for G protein-mediated activation of transcription factors by lysophosphatidic acid
Authors: Oyesanya Regina A , Greenbaum Susie , Dang David , Lee Zendra , Mukherjee Abir , Wu Jinhua , Dent Paul , Fang Xianjun
Published: January 2010

Background

The role of the epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTKs) in provoking biological actions of G protein-coupled receptors (GPCRs) has been one of the most disputed subjects in the field of GPCR signal transduction. The purpose of the current study is to identify EGFR-mediated mechanisms involved in activation of G protein cascades and the downstream transcription factors by lysophosphatidic acid (LPA).

Results

In ovarian cancer cells highly responsive to LPA, activation of AP-1 by LPA was suppressed by inhibition of EGFR, an effect that could be reversed by co-stimulation of another receptor tyrosine kinase c-Met with hepatocyte growth factor, indicating that LPA-mediated activation of AP-1 requires activity of a RTK, not necessarily EGFR. Induction of AP-1 components by LPA lied downstream of Gi, G12/13, and Gq. Activation of the effectors of Gi, but not Gq or G12/13 was sensitive to inhibition of EGFR. In contrast, LPA stimulated another prominent transcription factor NF-κB via the Gq-PKC pathway in an EGFR-independent manner. Consistent with the importance of Gi-elicited signals in a plethora of biological processes, LPA-induced cytokine production, cell proliferation, migration and invasion require intact EGFR.

Conclusions

An RTK activity is required for activation of the AP-1 transcription factor and other Gi-dependent cellular responses to LPA. In contrast, activation of G12/13, Gq and Gq-elicited NF-κB by LPA is independent of such an input. These results provide a novel insight into the role of RTK in GPCR signal transduction and biological functions.
Physical activity correlates in young women with depressive symptoms: a qualitative study
Authors: Azar Denise , Ball Kylie , Salmon Jo , Cleland Verity J
Published: January 2010

Background

Young women are at high risk for developing depression and participation in physical activity may prevent or treat the disorder. However, the influences on physical activity behaviors of young women with depression are not well understood. The aim of this study was to gather in-depth information about the correlates of physical activity among young women with and without depressive symptoms.

Methods

A sample of 40 young women (aged 18-30 years), 20 with depressive symptoms (assessed using the CES-D 10) and 20 without depressive symptoms participated in one-on-one semi-structured interviews. A social-ecological framework was used, focusing on the individual, social and physical environmental influences on physical activity. Thematic analyses were performed on transcribed interview data.

Results

The results indicated several key themes that were unique to women with depressive symptoms. These women more often described negative physical activity experiences during their youth, more barriers to physical activity, participating in more spontaneous than planned activity, lower self-efficacy for physical activity and being influenced by their friends' and family's inactivity.

Conclusions

Interventions designed to promote physical activity in this important target group should consider strategies to reduce/overcome early life negative experiences, engage support from family and friends and plan for activity in advance.
Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report
Authors: Mejia-Gaviria Natalia , Gil-Peña Helena , Coto Eliecer , Pérez-Menéndez Teresa M , Santos Fernando
Published: January 2010

Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.
Hemangiopericytoma in the sacrococcygeal space: a case report
Authors: Kitahata Yuji , Yokoyama Shozo , Takifuji Katsunari , Hotta Tsukasa , Matsuda Kenji , Tominaga Toshiji , Oku Yoshimasa , Watanabe Takashi , Ieda Junji , Yamaue Hiroki
Published: January 2010

Introduction

A hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.

Case presentation

We describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.

Conclusion

A complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.
Transcription-dependent silencing of inducible convergent transgenes in transgenic mice
Authors: Calero-Nieto Fernando J , Bert Andrew G , Cockerill Peter N
Published: January 2010

Background

Silencing of transgenes in mice is a common phenomenon typically associated with short multi-copy transgenes. We have investigated the regulation of the highly inducible human granulocyte-macrophage colony-stimulating-factor gene (Csf2) in transgenic mice.

Results

In the absence of any previous history of transcriptional activation, this transgene was expressed in T lineage cells at the correct inducible level in all lines of mice tested. In contrast, the transgene was silenced in a specific subset of lines in T cells that had encountered a previous episode of activation. Transgene silencing appeared to be both transcription-dependent and mediated by epigenetic mechanisms. Silencing was accompanied by loss of DNase I hypersensitive sites and inability to recruit RNA polymerase II upon stimulation. This pattern of silencing was reflected by increased methylation and decreased acetylation of histone H3 K9 in the transgene. We found that silenced lines were specifically associated with a single pair of tail-to-tail inverted repeated copies of the transgene embedded within a multi-copy array.

Conclusions

Our study suggests that epigenetic transgene silencing can result from convergent transcription of inverted repeats which can lead to silencing of an entire multi-copy transgene array. This mechanism may account for a significant proportion of the reported cases of transgene inactivation in mice.
Evaluation of myosin VI, E-cadherin and beta-catenin immunostaining in renal cell carcinoma
Authors: Ronkainen Hanna , Kauppila Saila , Hirvikoski Pasi , Vaarala Markku H
Published: January 2010

Background

Renal cell carcinoma (RCC) is a cancer of increasing incidence and mortality. Currently, there are no immunohistochemical prognostic markers for RCCs in routine use. The aim of this study was to examine for the first time the immunostaining of myosin VI in RCCs as well as its association with E-cadherin and beta-catenin immunostaining and the prognostic significance of these markers in RCCs.

Methods

Our study population consisted of 152 patients who underwent surgery for RCCs between 1990 and 1999. The tumours were examined with three immunohistochemical markers: myosin VI, E-cadherin and beta-catenin.

Results

The immunostaining for cytoplasmic myosin VI was common (72%). One-third of the tumours were immunopositive for nuclear myosin VI. Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades (p = 0.04 and p = 0.005, respectively), but not stages. There was no significant association between myosin VI immunostaining and the histological subtype of RCC. Nuclear myosin VI was associated with the nuclear expression of beta-catenin. A direct association could also be proven between membranous E-cadherin and cytoplasmic beta-catenin. Cytoplasmic myosin VI immunostaining was a marker of poorer prognosis in multivariate Cox regression model adjusted with stage and Fuhrman grade with hazard ratio 2.4 (95% confidence interval 1.1 to 5.0 with p = 0.024).

Conclusions

Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades, and there was a strong positive relationship between E-cadherin immunostaining and beta-catenin immunostaining in RCCs. Cytoplasmic myosin VI immunostaining was associated with poorer prognosis in RCCs.
Adenovirus-mediated delivery of bFGF small interfering RNA increases levels of connexin 43 in the glioma cell line, U251
Authors: Zhang Biao , Feng Xuequan , Wang Jinhuan , Xu Xinnu , Liu Hongsheng , Lin Na
Published: January 2010

Background

bFGF is an important growth factor for glioma cell proliferation and invasion, while connexin 43 is implicated in the suppression of glioma growth. Correspondingly, gliomas have been shown to have reduced, or compromised, connexin 43 expression.

Methods

In this study, a bFGF-targeted siRNA was delivered to the glioma cell line, U251, using adenovirus (Ad-bFGF-siRNA) and the expression of connexin 43 and its phosphorylation state were evaluated. U251 cells were infected with Ad-bFGF-siRNA (100, 50, or 25 MOI), and infection with adenovirus expressing green fluorescent protein (Ad-GFP) at 100 MOI served as a control. Western blotting and immunofluorescence were used to detect the expression levels, phosphorylation, and localization of connexin 43 in U251 cells infected, and not infected, with Ad-bFGF-siRNA.

Results

Significantly higher levels of connexin 43 were detected in U251 cells infected with Ad-bFGF-siRNA at 100 and 50 MOI than in cells infected with Ad-GFP, and the same amount of connexin 43 was detected in Ad-GFP-infected and uninfected U251 cells. Connexin 43 phosphorylation did not differ between Ad-bFGF-siRNA-infected and uninfected U251 cells. However, the ratio of phosphorylated to unphosphorylated connexin 43 in Ad-bFGF-siRNA cells was lower, and connexin 43 was predominantly localized to the cytoplasm. Using a scrape loading dye transfer assay, more Lucifer Yellow was transferred to neighboring cells in the Ad-bFGF-siRNA treated group than in the control group.

Conclusion

To our knowledge, this is the first description of a role for connexin 43 in the inhibition of U251 growth using Ad-bFGF-siRNA.
Synchronous testicular liposarcoma and prostate adenocarcinoma: a case report
Authors: Demirci Umut , Buyukberber Suleyman , Cakir Asli , Ozturk Banu , Akyurek Nalan , Unver Basak , Baykara Meltem , Benekli Mustafa , Coskun Ugur
Published: January 2010

Prostate adenocarcinoma is the most common malignancy and the second leading cause of cancer related deaths in men. Testicular liposarcomas are uncommon soft tissue neoplasms. We report coexistence of prostate cancer and testicular liposarcoma in a 69 year-old-man because while orchiectomy endications are decreasing day by day, these second malignancies should not be missed.
Development of bone marrow lesions is associated with adverse effects on knee cartilage while resolution is associated with improvement - a potential target for prevention of knee osteoarthritis: a longitudinal study
Authors: Davies-Tuck Miranda L , Wluka Anita E , Forbes Andrew , Wang Yuanyuan , English Dallas R , Giles Graham G , O'Sullivan Richard , Cicuttini Flavia M
Published: January 2010

Introduction

To examine the relationship between development or resolution of bone marrow lesions (BMLs) and knee cartilage properties in a 2 year prospective study of asymptomatic middle-aged adults.

Methods

271 adults recruited from the Melbourne Collaborative Cohort Study, underwent a magnetic resonance imaging scan (MRI) of their dominant knee at baseline and again approximately 2 years later. Cartilage volume, cartilage defects and BMLs were determined at both time points.

Results

Among 234 subjects free of BMLs at baseline, 33 developed BMLs over 2 years. The incidence of BMLs was associated with progression of tibiofemoral cartilage defects (OR 2.63 (95% CI 0.93, 7.44), P = 0.07 for medial compartment; OR 3.13 (95% CI 1.01, 9.68), P = 0.048 for lateral compartment). Among 37 subjects with BMLs at baseline, 17 resolved. Resolution of BMLs was associated with reduced annual loss of medial tibial cartilage volume (regression coefficient -35.9 (95%CI -65, -6.82), P = 0.02) and a trend for reduced progression of medial tibiofemoral cartilage defects (OR 0.2 (95% CI 0.04, 1.09), P = 0.06).

Conclusions

In this cohort study of asymptomatic middle-aged adults the development of new BMLs was associated with progressive knee cartilage pathology while resolution of BMLs prevalent at baseline was associated with reduced progression of cartilage pathology. Further work examining the relationship between changes and BML and cartilage may provide another important target for the prevention of knee osteoarthritis.
Who Is Responsible? The Role of Family Physicians in the Provision of Supportive Cancer Care
Authors: Brazil Kevin , Sussman Jonathan , Bainbridge Daryl , Whelan Tim
Published: January 2010

Many family physicians do not view coordinating patients' supportive cancer care as a primary responsibility and do not wish to assume this role. Models involving them as team members in care coordination are more feasible for reducing patient need.
Physician Assistant Perspective on the ASCO Workforce Study Regarding the Use of Physician Assistants and Nurse Practitioners
Authors: Polansky Maura , Ross Alicia C. , Coniglio David
Published: January 2010

A shortage of 2,350 to 3,800 oncologists by 2020 has been predicted, and increased use of physician assistants and nurse practitioners is one proposed solution. This report examines their role in oncology.
American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer
Authors: Azzoli Christopher G. , Giaccone Giuseppe , Temin Sarah
Published: January 2010

ASCO published a guideline on use of chemotherapy in advanced stage non–small-cell lung cancer in 1997. The latest update covers treatment with chemotherapy and biologic agents and reviews literature from 2002 to 2009.
Ensuring Quality Cancer Care Through the Oncology Workforce
Authors: Levit Laura , Smith Alison P. , Benz Edward J. , Ferrell Betty
Published: January 2010

A summary of the discussion at the Institute of Medicine National Cancer Policy Forum Workshop to examine oncology workforce shortages and describe current and potential solutions.
Role of Advanced Nurse Practitioners and Physician Assistants in Washington State
Authors: Britell Jonathan C.
Published: January 2010

A survey in response to Washington oncology practices' workforce shortage on employment patterns for advanced nurse practitioners and physician assistants found that practices have embraced these roles.
Filling the Gap: Development of the Oncology Nurse Practitioner Workforce
Authors: Nevidjon Brenda , Rieger Paula , Miller Murphy Cynthia , Rosenzweig Margaret Quinn , McCorkle Michele R. , Baileys Kristen
Published: January 2010

A new strategy for oncology care delivery that includes increasing the numbers and expanding the roles of nonphysician practitioners is critically important to meet the current and potential cancer care needs of the US population.
Conversion of metaplastic Barrett’s epithelium into post-mitotic goblet cells by γ-secretase inhibition
Authors: Menke Vivianda , van Es Johan H. , de Lau Wim , van den Born Maaike , Kuipers Ernst J. , Siersema Peter D. , de Bruin Ron W. F. , Kusters Johannes G. , Clevers Hans
Published: January 2010

Barrett’s esophagus (BE) affects approximately 2% of the Western population and progresses to esophageal adenocarcinoma (EAC) in 0.5% of these patients each year. In BE, the stratified epithelium is replaced by an intestinal-type epithelium owing to chronic gastroduodenal reflux. Since self-renewal of intestinal crypts is driven by Notch signaling, we investigated whether this pathway was active in the proliferative crypts of BE. Immunohistochemistry confirmed the presence of an intact and activated Notch signaling pathway in metaplastic BE epithelium, but not in the normal human esophagus. Similar observations were made in two well-known human Barrett’s-derived EAC cell lines, OE33 and SKGT-5. We then sought to investigate the effects of Notch inhibition by systemic treatment with a γ-secretase inhibitor in a well-validated rodent model for BE. As we have shown previously in normal intestinal epithelium, Notch inhibition converted the proliferative Barrett’s epithelial cells into terminally differentiated goblet cells, whereas the squamous epithelium remained intact. These data imply that local application of γ-secretase inhibitors may present a simple therapeutic strategy for this increasingly common pre-malignant condition.
Development of animal models for schizophrenia
Authors: Arguello P. Alexander , Markx Sander , Gogos Joseph A. , Karayiorgou Maria
Published: January 2010

Schizophrenia is a devastating psychiatric disorder that affects around 1% of the population worldwide. The disease is characterized by ‘positive symptoms’, ‘negative symptoms’ and cognitive deficits. Over the last 60 years, a large number of family, twin and adoption studies have clearly demonstrated a strong genetic component for schizophrenia, but the mode of inheritance of the disease is complex and, in all likelihood, involves contribution from multiple genes in conjunction with environmental and stochastic factors. Recently, several genome-wide scans have demonstrated that rare alleles contribute significantly to schizophrenia risk. Assessments of rare variants have identified specific and probably causative, disease-associated structural mutations or copy number variants (CNVs, which result from genomic gains or losses). The fact that the effects of such lesions are transparent allows the generation of etiologically valid animal models and the opportunity to explore the molecular, cellular and circuit-level abnormalities underlying the expression of psychopathology. To date, the most common genomic structural rearrangements that are unequivocally associated with the development of schizophrenia, are de novo microdeletions of the 22q11.2 locus. Fortunately, the human 22q11.2 locus is conserved within the syntenic region of mouse chromosome 16, which harbors nearly all orthologues of the human genes. This has made it possible to engineer genetically faithful, and thus etiologically valid, animal models of this schizophrenia susceptibility locus.
Leading the way: canine models of genomics and disease
Authors: Shearin Abigail L. , Ostrander Elaine A.
Published: January 2010

In recent years Canis familiaris, the domestic dog, has drawn considerable attention as a system in which to investigate the genetics of disease susceptibility, morphology and behavior. Because dogs show remarkable intrabreed homogeneity, coupled with striking interbreed heterogeneity, the dog offers unique opportunities to understand the genetic underpinnings of natural variation in mammals, a portion of which is disease susceptibility. In this review, we highlight the unique features of the dog, such as population diversity and breed structure, that make it particularly amenable to genetic studies. We highlight recent advances in understanding the architecture of the dog genome, which propel the system to the forefront of consideration when selecting a system for disease gene studies. The most notable benefit of using the dog for genetic studies is that dogs get many of the same diseases as humans, with a similar frequency, and the same genetic factors are often involved. We discuss two approaches for localizing disease genes in the dog and provide examples of ongoing studies.
Primates as a model for research
Authors: Garbarini Nicole
Published: January 2010

Despite the political, ethical and financial complexities, there are some human diseases that researchers feel can only be understood by working with non-human primates. Nicole Garbarini investigates.
The accidental biologist: an interview with Jim Smith
Authors: Weston Kathy
Published: January 2010

Jim Smith has made fundamental contributions to our understanding of early embryonic development. Here, in conversation with DMM Consulting Editor Kathy Weston, he discusses his stutter, how he became interested in developmental biology, and his role in helping establish what will be the UK’s biggest multidisciplinary research laboratory, the UK Centre for Medical Research and Innovation (UKCMRI).
Narrative Review of the Uk Patient Safety Research Portfolio
Authors: Waring Justin , Rowley Emma , Dingwall Robert , Palmer Cecily , Murcott Toby
Published: January 2010

Objectives

The UK Patient Safety Research Portfolio (PSRP) commissioned 38 studies investigating the threats to patient safety in various clinical settings and evaluating safety-related service interventions. This paper reviews 27 of these studies, drawing out emergent and cross-cutting themes in terms of theory, research methods and thematic findings.

Methods

Given the diversity of PSRP studies, the paper takes a narrative approach that allows for qualitative description, interpretation and synthesis of the studies and their findings.

Results

The theoretical review shows the majority of PSRP studies draw upon a patient safety ‘orthodoxy’, developed from the concepts and models associated with the human factors approach. The methodological review shows that a diverse range of research designs and techniques have been utilized. Although many follow in the ‘scientific’ tradition, interpretative, mixed and innovative methods have been integral to research. The thematic review of findings highlights significant contributions to knowledge in the areas of ‘people’, ‘organizations’, and ‘technology’. As well as identifying the various sources of risk in the organization and delivery of patient care, the studies also evaluate and make recommendations about service change and improvement.

Conclusions

The PSRP has provided the foundations for significant theoretical, methodological and empirical advances in the area of patient safety. The findings and recommendations make important contributions to policy formulation and implementation as well as professional and managerial practice. Through this body of research the PSRP has supported the formation and growth of a thriving research community across academic, policy and professional communities.
Errors in the Operating Theatre - How to Spot and Stop Them
Authors: Catchpole Ken
Published: January 2010

The study, first published in 2005, looks at errors made in the operating theatre by observing operations at first hand, recording them for closer scrutiny and evaluation of non-technical skills such as human error, system problems and teamwork, questioning health professionals to assess safety culture, and using computer simulations to study how hospital systems might increase the chances of surgical error.
Failures in Childbirth Care
Authors: Ashcroft Brenda
Published: January 2010

The study, first published in 2003, looks at the root causes of adverse events and near misses in obstetrics at seven hospital maternity units by interviewing 93 members of staff, identifying the areas of mismanagement in each case and thematically analysing them.
Communication with Patients after Errors
Authors: Fallowfield Lesley
Published: January 2010

The study, published in 2003, looks at more than 120 sources of existing research, studies, and policies to consider errors and adverse incidents, particularly involving doctors, and the quality of communication with patients after an incident has happened. The researchers, however, said the research evidence was inadequate and nothing was clear cut.
Feedback from Reporting Patient Safety Incidents - Are Nhs Trusts Learning Lessons?
Authors: Wallace Louise
Published: January 2010

For the study, first published in 2006, the researchers examined how well NHS organisations had attempted to use the information they gathered from adverse clinical incidents and whether they were learning from it. By looking at existing relevant research worldwide, interviewing experts, surveying NHS organizations (acute, community and ambulance), consulting health care and other high-risk industry safety experts and NHS risk managers, and investigating case studies of good practice, they developed a model to assess how ready NHS systems were to learn from incidents. This is known as Safety Action and Information Feedback from Incident Reporting (SAIFIR).
How Well Do Nhs Trusts React to Patient Safety Alerts?
Authors: Lowson Karin
Published: January 2010

The study, first published in 2007, used several methods to study the nature of patient safety alerts, find out how trusts received and implemented them, assessed their impact and recommended improvements. Methods included surveys and interviews of staff at different levels from 41 NHS organizations and an in-depth study of 11 alerts.