bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Become One? Spouses and Agreement in Political Opinions
Authors: Osborn Tracy , Morehouse Mendez Jeanette
Published: April 2011

Spouses who talk about politics with each other have long been considered aberrant cases of political discussion because of the frequency of their interaction and the high levels of agreement between them. Using the 1996 Indianapolis-St. Louis Election Study, we challenge these assumptions. We find that compared with other types of discussion dyads, married dyads are no more likely to agree about a host of policy issues, even though they do talk about them more frequently. In addition, we find even when spouses do agree about their presidential vote choice more often, they do not perceive this agreement to exist. These findings indicate that within the microfoundations of married political behavior, spouses may experience less political variety because of the frequency of their interaction, but this does not necessarily mean they experience lower levels of disagreement.
How much for the Michelangelo? Valuation, Commoditization and Finitism in the Secondary Art Market
Authors: Pardo-Guerra Juan Pablo
Published: April 2011

This article is a sociological re-evaluation of the auction house, a central institution of the secondary art market. As an intermediary between buyers and sellers, the auction house is portrayed as an institution that straddles the poles of economic (calculative) and social (aesthetic) life. Relying on the work of Michel Callon and Barry Barnes, the process of the commoditization that takes place within auction houses is presented as a structuring mechanism through which symbolic, economic and cultural values are shaped and reinforced. In particular, the finitist calculative practices associated with commoditization (through the generation of estimated auction prices) are presented as responsible for reproducing the secondary art market and the aesthetic judgements on which it is based.
Systematic Review of the Balance Error Scoring System
Authors: Bell David R. , Guskiewicz Kevin M. , Clark Micheal A. , Padua Darin A.
Published: April 2011

Context: The Balance Error Scoring System (BESS) is commonly used by researchers and clinicians to evaluate balance.A growing number of studies are using the BESS as an outcome measure beyond the scope of its original purpose.

Objective: To provide an objective systematic review of the reliability and validity of the BESS.

Data Sources: PubMed and CINHAL were searched using Balance Error Scoring System from January 1999 through December 2010.

Study Selection: Selection was based on establishment of the reliability and validity of the BESS. Research articles were selected if they established reliability or validity (criterion related or construct) of the BESS, were written in English, and used the BESS as an outcome measure. Abstracts were not considered.

Results: Reliability of the total BESS score and individual stances ranged from poor to moderate to good, depending on the type of reliability assessed. The BESS has criterion-related validity with force plate measures; more difficult stances have higher agreement than do easier ones. The BESS is valid to detect balance deficits where large differences exist (concussion or fatigue). It may not be valid when differences are more subtle.

Conclusions: Overall, the BESS has moderate to good reliability to assess static balance. Low levels of reliability have been reported by some authors. The BESS correlates with other measures of balance using testing devices. The BESS can detect balance deficits in participants with concussion and fatigue. BESS scores increase with age and with ankle instability and external ankle bracing. BESS scores improve after training.
Smad4 binds Hoxa9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by Hoxa9 and leukemia transformation
Authors: Quéré Ronan , Karlsson Göran , Hertwig Falk , Rissler Marianne , Lindqvist Beata , Fioretos Thoas , Vandenberghe Peter , Slovak Marilyn L. , Cammenga Jörg , Karlsson Stefan
Published: April 2011

We studied leukemic stem cells (LSCs) in a Smad4−/− mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. Although Hoxa9-Smad4 complexes accumulate in the cytoplasm of normal hematopoietic stem cells and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic stabilization of HOXA9 in Smad4−/− HSPCs, and as a consequence increased levels of Hoxa9 is observed in the nucleus leading to increased immortalization in vitro. Loss of Smad4 accelerates the development of leukemia in vivo because of an increase in transformation of HSPCs. Therefore, the cytoplasmic binding of Hoxa9 by Smad4 is a mechanism to protect Hoxa9-induced transformation of normal HSPCs. Because Smad4 is a potent tumor suppressor involved in growth control, we developed a strategy to modify the subcellular distribution of Smad4. We successfully disrupted the interaction between Hoxa9 and Smad4 to activate the TGF-β pathway and apoptosis, leading to a loss of LSCs. Together, these findings reveal a major role for Smad4 in the negative regulation of leukemia initiation and maintenance induced by HOXA9/NUP98-HOXA9 and provide strong evidence that antagonizing Smad4 stabilization by these oncoproteins might be a promising novel therapeutic approach in leukemia.
Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML
Authors: Haefliger Simon , Klebig Christiane , Schaubitzer Kerstin , Schardt Julian , Timchenko Nikolai , Mueller Beatrice U. , Pabst Thomas
Published: April 2011

Deregulation of the myeloid key transcription factor CEBPA is a common event in acute myeloid leukemia (AML). We previously reported that the chaperone calreticulin is activated in subgroups of AML patients and that calreticulin binds to the stem loop region of the CEBPA mRNA, thereby blocking CEBPA translation. In this study, we screened for additional CEBPA mRNA binding proteins and we identified protein disulfide isomerase (PDI), an endoplasmic reticulum (ER) resident protein, to bind to the CEBPA mRNA stem loop region. We found that forced PDI expression in myeloid leukemic cells in fact blocked CEBPA translation, but not transcription, whereas abolishing PDI function restored CEBPA protein. In addition, PDI protein displayed direct physical interaction with calreticulin. Induction of ER stress in leukemic HL60 and U937 cells activated PDI expression, thereby decreasing CEBPA protein levels. Finally, leukemic cells from 25.4% of all AML patients displayed activation of the unfolded protein response as a marker for ER stress, and these patients also expressed significantly higher PDI levels. Our results indicate a novel role of PDI as a member of the ER stress–associated complex mediating blocked CEBPA translation and thereby suppressing myeloid differentiation in AML patients with activated unfolded protein response (UPR).
The antifibrinolytic function of factor XIII is exclusively expressed through α2-antiplasmin cross-linking
Authors: Fraser Steven R. , Booth Nuala A. , Mutch Nicola J.
Published: April 2011

Factor XIII (FXIII) generates fibrin-fibrin and fibrin-inhibitor cross-links. Our flow model, which is sensitive to cross-linking, was used to assess the effects of FXIII and the fibrinolytic inhibitor, α2-antiplasmin (α2AP) on fibrinolysis. Plasma model thrombi formed from FXIII or α2AP depleted plasma lysed at strikingly similar rates, 9-fold faster than pooled normal plasma (PNP). In contrast, no change was observed on depletion of PAI-1 or thrombin activatable fibrinolysis inhibitor (TAFI). Inhibition of FXIII did not further enhance lysis of α2AP depleted thrombi. Addition of PNP to FXIII or α2AP depleted plasmas normalized lysis. Lysis rate was strongly inversely correlated with total cross-linked α2AP in plasma thrombi. Reconstitution of FXIII into depleted plasma stabilized plasma thrombi and normalized γ-dimers and α-polymers formation. However, the presence of a neutralizing antibody to α2AP abolished this stabilization. Our data show that the antifibrinolytic function of FXIII is independent of fibrin-fibrin cross-linking and is expressed exclusively through α2AP.
Microbial evaluation of proton-pump inhibitors and the risk of pneumonia
Authors: Meijvis S.C.A. , Cornips M.C.A. , Voorn G.P. , Souverein P.C. , Endeman H. , Biesma D.H. , Leufkens H.G.M. , van de Garde E.M.W.
Published: April 2011

Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment.

This was a population-based, case–control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed.

Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4–7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings.

This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.
Paediatrics in Barcelona: highlights from the 2010 ERS Annual Congress
Authors: Eber E. , Lødrup Carlsen K.C. , Ratjen F. , Turner S.W. , Dankert-Roelse J.E. , Ross-Russell R.I. , Midulla F. , Aurora P. , Hedlin G.
Published: April 2011

The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.
Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target
Authors: Rhodes C.J. , Wharton J. , Howard L. , Gibbs J.S.R. , Vonk-Noordegraaf A. , Wilkins M.R.
Published: April 2011

Iron deficiency is known to be common and detrimental in chronic left heart failure, where parenteral iron treatment has been shown to improve exercise capacity, New York Heart Association functional class and patient wellbeing. There is now increasing interest in the role of iron in the natural history of pulmonary arterial hypertension (PAH). Iron availability influences the pulmonary vasoconstrictor response to hypoxia and accumulating evidence indicates that iron deficiency is prevalent in idiopathic and heritable forms of PAH, iron status being related to exercise capacity, symptoms and poorer survival in patients with idiopathic PAH (IPAH). Potential mechanisms behind iron deficiency in IPAH include inhibition of dietary iron uptake by the master iron regulator hepcidin. High hepcidin levels underlie the anaemia of chronic disease. Possible stimuli of the observed high levels of hepcidin in IPAH include dysfunctional bone morphogenetic protein receptor type II signalling and inflammation. Iron status may influence outcomes through modulation of the pulmonary circulation as well as myocardial and skeletal muscle function. Two parallel studies, from our centre (Hammersmith Hospital, London, UK) and others in the UK and Amsterdam (the Netherlands), investigating the safety and potential benefit of iron supplementation in patients with PAH are currently under way.
Computed tomography score and pulmonary function in infants with chronic lung disease of infancy
Authors: Sarria E.E. , Mattiello R. , Rao L. , Wanner M.R. , Raske M.E. , Tiller C. , Kimmel R. , Tepper R.S.
Published: April 2011

Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed.

We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group.

CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4–33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function.

CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.
Occurrence of multipolar mitoses and association with Aurora-A/-B kinases and p53 mutations in aneuploid esophageal carcinoma cells
Authors: Fichter Christiane D , Herz Corinna , Münch Claudia , Opitz Oliver G , Werner Martin , Lassmann Silke
Published: April 2011

Background

Aurora kinases and loss of p53 function are implicated in the carcinogenesis of aneuploid esophageal cancers. Their association with occurrence of multipolar mitoses in the two main histotypes of aneuploid esophageal squamous cell carcinoma (ESCC) and Barrett's adenocarcinoma (BAC) remains unclear. Here, we investigated the occurrence of multipolar mitoses, Aurora-A/-B gene copy numbers and expression/activation as well as p53 alterations in aneuploid ESCC and BAC cancer cell lines.

Results

A control esophageal epithelial cell line (EPC-hTERT) had normal Aurora-A and -B gene copy numbers and expression, was p53 wild type and displayed bipolar mitoses. In contrast, both ESCC (OE21, Kyse-410) and BAC (OE33, OE19) cell lines were aneuploid and displayed elevated gene copy numbers of Aurora-A (chromosome 20 polysomy: OE21, OE33, OE19; gene amplification: Kyse-410) and Aurora-B (chromosome 17 polysomy: OE21, Kyse-410). Aurora-B gene copy numbers were not elevated in OE19 and OE33 cells despite chromosome 17 polysomy. Aurora-A expression and activity (Aurora-A/phosphoT288) was not directly linked to gene copy numbers and was highest in Kyse-410 and OE33 cells. Aurora-B expression and activity (Aurora-B/phosphoT232) was higher in OE21 and Kyse-410 than in OE33 and OE19 cells. The mitotic index was highest in OE21, followed by OE33 > OE19 > Kyse-410 and EPC-hTERT cells. Multipolar mitoses occurred with high frequency in OE33 (13.8 ± 4.2%), followed by OE21 (7.7 ± 5.0%) and Kyse-410 (6.3 ± 2.0%) cells. Single multipolar mitoses occurred in OE19 (1.0 ± 1.0%) cells. Distinct p53 mutations and p53 protein expression patterns were found in all esophageal cancer cell lines, but complete functional p53 inactivation occurred in OE21 and OE33 only.

Conclusions

High Aurora-A expression alone is not associated with overt multipolar mitoses in aneuploid ESCC and BAC cancer cells, as specifically shown here for OE21 and OE33 cells, respectively. Additional p53 loss of function mutations are necessary for this to occur, at least for invasive esophageal cancer cells. Further assessment of Aurora kinases and p53 interactions in cells or tissue specimens derived from non-invasive dysplasia (ESCC) or intestinal metaplasia (BAC) are necessary to disclose a potential causative role of Aurora kinases and p53 for development of aneuploid, invasive esophageal cancers.
The comprehensive cohort model in a pilot trial in orthopaedic trauma
Authors: Kearney Rebecca S , Achten Juul , Parsons Nick R , Costa Matthew L
Published: April 2011

Background

The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting.

Methods

Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury.

Results

At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management.

Conclusions

Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions.

Trial registration

ISRCTN: ISRCTN29053307
Perforated acute appendicitis resulting from appendiceal villous adenoma presenting with small bowel obstruction: a case report
Authors: Chen Yu-Guang , Chang Hao-Ming , Chen Yen-Lin , Cheng Yi-Chiao , Hsu Chin-Hui
Published: April 2011

Background

A villous adenoma is an extremely rare benign tumour in the appendix, in contrast to other benign appendiceal lesions. The clinical features are usually asymptomatic. Acute appendicitis is the most common complication with the lesion obstructing the orifice of the appendiceal lumen. Thus, a villous adenoma is usually found during surgical intervention for acute appendicitis. Mechanical obstruction induced by acute perforated appendicitis has been previously reported. Acute appendicitis caused by a villous adenoma presenting with acute intestinal obstruction has not been previously reported.

Case presentation

A 78-year-old woman presented to our Emergency Department with diffuse abdominal pain and tenderness. The abdominal plain film and computed tomography revealed an intestinal obstruction. After surgical intervention, the ruptured appendix was shown to be associated with intestinal obstruction. The post-operative pathologic diagnosis was an appendiceal villous adenoma.

Conclusions

This is the first report describing an appendiceal villous adenoma, which is an occasional cause of perforated acute appendicitis, presenting as a complete intestinal obstruction. We emphasize that in elderly patients without a surgical history, the occult cause of complete intestinal obstruction must be determined. If an appendiceal tumour is diagnosed, an intra-operative frozen section is suggested prior to selecting a suitable method of surgical intervention.
Did the pandemic have an impact on influenza vaccination attitude? a survey among health care workers
Authors: Arda Bilgin , Durusoy Raika , Yamazhan Tansu , Sipahi Oğuz Reşat , Taşbakan Meltem , Pullukçu Hüsnü , Erdem Esra , Ulusoy Sercan
Published: April 2011

Background

Health care workers' (HCWs) influenza vaccination attitude is known to be negative. The H1N1 epidemic had started in mid 2009 and made a peak in October-November in Turkey. A national vaccination campaign began on November 2nd, 2009. Despite the diligent efforts of the Ministry of Health and NGOs, the attitudes of the media and politicians were mostly negative. The aim of this study was to evaluate whether HCWs' vaccination attitudes improved during the pandemic and to assess the related factors.

Methods

This cross-sectional survey was carried out at the largest university hospital of the Aegean Region-Turkey. A self-administered questionnaire with 12 structured questions was applied to 807 HCWs (sample coverage 91.3%) before the onset of the vaccination programme. Their final vaccination status was tracked one week afterwards, using immunization records. Factors influencing vaccination rates were analyzed using ANOVA, t-test, chi-square test and logistic regression.

Results

Among 807 participants, 363 (45.3%) were doctors and 293 (36.6%) nurses. A total of 153 (19.0%) had been vaccinated against seasonal influenza in the 2008-2009 season. Regarding H1N1 vaccination, 143 (17.7%) were willing to be vaccinated vs. 357 (44.2%) unwilling. The number of indecisive HCWs was 307 (38.0%) one week prior to vaccination. Only 53 (11.1%) stated that they would vaccinate their children. Possible side effects (78%, n = 519) and lack of comprehensive field evaluation before marketing (77%, n = 508) were the most common reasons underlying unwillingness or hesitation.

Among the 749 staff whose vaccination status could be tracked, 228 (30.4%) actually received the H1N1 vaccine. Some of the 'decided' staff members had changed their mind one week later. Only 82 (60%) of those willing, 108 (37%) of those indecisive and 38 (12%) of those unwilling were vaccinated.

Indecisive HCWs were significantly younger (p = 0.017). Females, nurses, and HCWs working in surgical departments were more likely to reject vaccination (p < 0.05). Doctors, HCWs working in medical departments, and HCWs previously vaccinated against seasonal influenza were more likely to accept vaccination (p < 0.05). Being younger than 50 and having been vaccinated in the previous season were important predictors of attitude towards pandemic influenza vaccination.

Conclusions

Vaccination rates increased substantially in comparison to the previous influenza season. However, vaccination rates could have been even higher since hesitation to be vaccinated increased dramatically within one week (only 60% of those willing and the minority of those indecisive were finally vaccinated). We speculate that this may be connected with negative media at the time.
Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis
Authors: Gao Xiaofei , Cui Qian , Shi Xiang , Su Jing , Peng Zhihang , Chen Xin , Lei Na , Ding Keqin , Wang Lu , Yu Rongbin , Wang Ning
Published: April 2011

Background

Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.

Methods

A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.

Results

Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% vs 7.9%).

Conclusions

The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.
A transferable heterogeneous two-hybrid system in Escherichia coli based on polyhydroxyalkanoates synthesis regulatory protein PhaR
Authors: Wang Zhi-Hui , Ma Ping , Chen Jiong , Zhang Jing , Chen Chong-Bo , Chen Guo-Qiang
Published: April 2011

Background

Polyhydroxyalkanoate (PHA) synthesis regulatory protein PhaR contains a DNA binding domain (DBD) and a PHA granule binding domain (GBD), it anchors to the promoter region of PHA granule-associated protein (PhaP) to repress phaP expression. However, PhaR will bind to PHB granules and be released from phaP promoter region when PHA granules are formed in vivo, initiating expression of phaP gene. Based on this regulatory mechanism, a bacterial two-hybrid system was developed: PhaR was separated into two parts: DBD was used to fuse with the bait, GBD with the prey, and phaP was replaced by a reporter gene lacZ. However, GBD protein expressed in vivo formed inclusion bodies. Thus, PhaP with strong binding ability to PHB granules was employed to replace GBD.

Results

Three model interaction partners bFos, bJun and bATF2 were used to study the feasibility of this bacterial two-hybrid system compared with the controls lacking one or more essential elements of this system. Results showed that bFos, bJun and bATF2 bound tightly in pairs to allow strong expression of β-galactosidase in different expression levels. In contrast, very weak β-galactosidase activity was detected in all control groups.

Conclusion

β-Galactosidase activity level precisely correlated with the interaction force of tested protein pairs, and very weak β-galactosidase expression was detected throughout the control groups, which demonstrated the feasibility of this system for studying protein interactions.
Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin
Authors: Kelly Ronan J , Lopez-Chavez Ariel , Citrin Deborah , Janik John E , Morris John C
Published: April 2011

Survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) family that inhibits caspases and blocks cell death is highly expressed in cancer and is associated with a poorer clinical outcome. Functioning simultaneously during cell division and apoptosis inhibition, survivin plays a pivotal role in determining cell survival. Survivin has consistently been identified by molecular profiling analysis to be associated with higher tumor grade, more advanced disease, abbreviated survival, accelerated rates of recurrence, and chemotherapy and radiation resistance. Survivin's differential expression in cancer compared to normal tissue and its role as a nodal protein in a number of cellular pathways make it a highly flexible therapeutic target, suitable for small-molecule inhibitiors, molecular antagonists, and vaccination-based therapies. By targeting survivin it is hoped that multiple tumor signaling circuitries may be simultaneously disabled. This effect may be applicable to many tumor histologies irrespective of specific genetic makeup. To date, survivin inhibitors have shown modest activity as single agents, but it is anticipated that when given in combination with cytotoxic chemotherapy or monoclonal antibodies they may exhibit enhanced efficacy. This review discusses the complex circuitry of survivin in human cancers and highlights clinical trials involving novel agents that target this important protein.
Boundary layer flow past a stretching/shrinking surface beneath an external uniform shear flow with a convective surface boundary condition in a nanofluid
Authors: Yacob Nor Azizah , Ishak Anuar , Pop Ioan , Vajravelu Kuppalapalle
Published: April 2011

The problem of a steady boundary layer shear flow over a stretching/shrinking sheet in a nanofluid is studied numerically. The governing partial differential equations are transformed into ordinary differential equations using a similarity transformation, before being solved numerically by a Runge-Kutta-Fehlberg method with shooting technique. Two types of nanofluids, namely, Cu-water and Ag-water are used. The effects of nanoparticle volume fraction, the type of nanoparticles, the convective parameter, and the thermal conductivity on the heat transfer characteristics are discussed. It is found that the heat transfer rate at the surface increases with increasing nanoparticle volume fraction while it decreases with the convective parameter. Moreover, the heat transfer rate at the surface of Cu-water nanofluid is higher than that at the surface of Ag-water nanofluid even though the thermal conductivity of Ag is higher than that of Cu.
Expression of tumor necrosis factor-α and interleukin-1β genes in the cochlea and inferior colliculus in salicylate-induced tinnitus
Authors: Hwang Juen-Haur , Chen Jin-Cherng , Yang Shan-Ying , Wang Ming-Fu , Chan Yin-Ching
Published: April 2011

Background

Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate.

Methods

Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10.

Results

Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea.

Conclusion

We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.
Effects of an omega-3 fatty acid-enriched lipid emulsion on eicosanoid synthesis in acute respiratory distress syndrome (ARDS): A prospective, randomized, double-blind, parallel group study
Authors: Sabater Joan , Masclans Joan Ramon , Sacanell Judit , Chacon Pilar , Sabin Pilar , Planas Mercè
Published: April 2011

Background

The use of lipid emulsions has been associated with changes in lung function and gas exchange which may be mediated by biologically active metabolites derived from arachidonic acid. The type and quantity of the lipid emulsions used could modulate this response, which is mediated by the eicosanoids. This study investigates the use of omega-3 fatty acid-enriched lipid emulsions in ARDS patients and their effects on eicosanoid values.

Methods

Prospective, randomized, double-blind, parallel group study carried out at the Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men; age: 58 ± 13 years; APACHE II score 17.8 ± 2.3; Lung Injury Score: 3.1 ± 0.5; baseline PaO2/FiO2 ratio: 149 ± 40). Patients were randomized into two groups: Group A (n = 8) received the study emulsion Lipoplus® 20%, B. Braun Medical (50% MCT, 40% LCT, 10% fish oil (FO)); Group B (n = 8) received the control emulsion Intralipid® Fresenius Kabi (100% LCT). Lipid emulsions were administered for 12 h at a dose of 0.12 g/kg/h. We measured LTB4, TXB2, and 6-keto prostaglandin F1α values at baseline [immediately before the administration of the lipid emulsions (T-0)], at the end of the administration (T-12) and 24 hours after the beginning of the infusion (T 24) in arterial and mixed venous blood samples.

Results

In group A (FO) LTB4, TXB2, 6-keto prostaglandin F1α levels fell during omega-3 administration (T12). After discontinuation (T24), levels of inflammatory markers (both systemic and pulmonary) behaved erratically. In group B (LCT) all systemic and pulmonary mediators increased during lipid administration and returned to baseline levels after discontinuation, but the differences did not reach statistical significance. There was a clear interaction between the treatment in group A (fish oil) and changes in LTB4 over time.

Conclusions

Infusion of lipids enriched with omega-3 fatty acids produces significant short- term changes in eicosanoid values, which may be accompanied by an immunomodulatory effect.

Trial registration

ISRCTN63673813.
Cholestasis in patients with Cockayne syndrome and suggested modified criteria for clinical diagnosis
Authors: Abdel Ghaffar Tawhida Y , Elsobky Ezzat S , Elsayed Solaf M
Published: April 2011

Background

Cockayne syndrome is a rare autosomal recessive neurodegenerative disease characterized by low-to-normal birth weight; growth failure; brain dysmyelination with calcium deposits, cutaneous photosensitivity; pigmentary retinopathy, cataract, and sensorineural hearing loss. To the best of our knowledge, cholestatic liver disease was not previously reported in these patients.

Aim

To highlight the presence of cholestasis and liver dysfunction in this group of patients and to suggest modified criteria for clinical diagnosis.

Methods

The study included nine patients with Cockayne from four different families (five males and four females) in which Cockayne was suspected clinically. In all patients chromosomal breakage studies revealed mild (45%) to moderate (60%) increase in frequency of chromatid and chromosome gaps and breaks versus 25% in normal controls. Diagnosis was confirmed by DNA repair assay.

Results

During routine follow up of these patients, seven of them had evident liver affection ranging from mild elevation in liver enzymes to cholestatic liver disease and liver cell failure. The attacks were recurrent in two patients and were sometimes preceded by infection. The attack may lead to deterioration of neurological and/or liver condition. It may end in liver cell failure that either recovers completely or may lead to death.

Conclusions

liver disease could be considered common in Egyptian patients with Cockayne with the cholestatic form being the most evident. The syndrome should be included in the list of causes of cholestatic liver disease. Chromosomal breakage study and positive family history should be included as major criteria for clinical diagnosis of Cockayne especially in a population like ours where consanguineous marriage is very high and molecular testing and UV sensitivity tests are considered unaffordable.
The rapid growth of a pleomorphic adenoma of the parotid gland in the third trimester of pregnancy
Authors: Palluch Frederike , Lehmann Martin , Volz Joachim , Upile Tahwinder , Sudhoff Holger
Published: April 2011

Introduction

We report a case highlighting the multidisciplinary management of a giant pleomorphic adenoma of the parotid gland that showed rapid growth in the third trimester of pregnancy.

Case presentation

A 43-year-old Caucasian woman presented in her 32nd week of gestation with a tumor of the parotid gland. Ultrasonography of her neck showed a parotid lesion of 40 × 30 × 27.5 mm. A follow-up magnetic resonance imaging scan of the neck four weeks later revealed that the tumor had grown to 70 × 60 × 60 mm, reaching the parapharyngeal space with marked obstruction of the oropharynx of about 50%. After discussing the case with our multidisciplinary tumor board and the gynecologists it was decided to deliver the baby by caesarean section in the 38th week of gestation, and then to perform a surgical resection of the tumor.

Conclusion

Indications for early surgical intervention of similar cases should be discussed on an individual patient basis in a multidisciplinary setting.
Anterior cruciate ligament reconstruction using quadriceps tendon autograft for adolescents with open physes- a technical note
Authors: Mauch Christian , Arnold Markus P , Wirries André , Mayer Ralph R , Friederich Niklaus F , Hirschmann Michael T
Published: April 2011

Background

One major concern in the treatment of ACL lesions in children and adolescents with open physes is the risk of iatrogenic damage to the physes and a possibly resulting growth disturbance.

Purpose

The primary purpose of this article is to describe our technique of a transphyseal ACL reconstruction using quadriceps tendon-bone autograft in children and adolescents with open growth plates. The secondary aim is to report our early results in terms of postoperative growth disturbances which are considered to be a major concern in this challenging group of patients. It was our hypothesis that with our proposed technique no significant growth disturbances would occur.

Methods

From January 1997 to December 2007 49 consecutive children and adolescents with open growth plates were treated for a torn ACL using the aforementioned surgical technique. The patients (28 males and 21 females) with a median age at surgery of 13 (range 8-15) years were retrospectively evaluated. Outcome measures were follow-up radiographs (weight-bearing long leg radiographs of the injured and uninjured knee, anteroposterior and lateral views, a tangential view of the patella and a tunnel view of the injured knee) and follow-up notes (6 weeks, 3, 6, 12 months and until closing of physes) for occurrence of any tibial and/or femoral growth changes.

Results: All of the 49 patients had a sufficient clinical and radiological follow-up (minimum 5 years, rate 100%). 48 cases did not show any clinical and radiological growth disturbance. One case of growth disturbance in a 10.5 years old girl was observed. She developed a progressive valgus-flexion deformity which was attributed to a malplacement of the autograft bone block within the femoral posterolateral epiphyseal plate leading to an early localized growth stop. None of the patients were reoperated due to ACL graft failure. Five of the patients underwent revision ACL surgery due to another adequate sports trauma after the growth-stop. The tibial fixation screw had to be removed under local anaesthesia in 10 patients.

Conclusions

The described ACL reconstruction technique represents a promising alternative to previously described procedures in the treatment of children and adolescents with open growth plates. Using quadriceps tendon future graft availability is not compromised, as the most frequently used autograft-source, ipsilateral hamstring tendons, remains untouched.
Caspase-3, myogenic transcription factors and cell cycle inhibitors are regulated by leukemia inhibitory factor to mediate inhibition of myogenic differentiation
Authors: Hunt Liam C , Upadhyay Aradhana , Jazayeri Jalal A , Tudor Elizabeth M , White Jason D
Published: April 2011

Background

Leukemia inhibitory factor (LIF) is known to inhibit myogenic differentiation as well as to inhibit apoptosis and caspase-3 activation in non-differentiating myoblasts. In addition caspase-3 activity is required for myogenic differentiation. Therefore the aim of this study was to further investigate mechanisms of the differentiation suppressing effect of LIF in particular the possibility of a caspase-3 mediated inhibition of differentiation.

Results

LIF dependent inhibition of differentiation appeared to involve several mechanisms. Differentiating myoblasts that were exposed to LIF displayed increased transcripts for c-fos. Transcripts for the cell cycle inhibitor p21 as well as muscle regulatory factors myoD and myogenin were decreased with LIF exposure. However, LIF did not directly induce a proliferative effect under differentiation conditions, but did prevent the proportion of myoblasts that were proliferating from decreasing as differentiation proceeded. LIF stimulation decreased the percentage of cells positive for active caspase-3 occurring during differentiation. Both the effect of LIF inhibiting caspase-3 activation and differentiation appeared dependent on mitogen activated protein kinase and extracellular signal regulated kinase kinase (MEK) signalling. The role of LIF in myogenic differentiation was further refined to demonstrate that myoblasts are unlikely to secrete LIF endogenously.

Conclusions

Altogether this study provides a more comprehensive view of the role of LIF in myogenic differentiation including LIF and receptor regulation in myoblasts and myotubes, mechanisms of inhibition of differentiation and the link between caspase-3 activation, apoptosis and myogenic differentiation.
Prevalence of pathogens causing subclinical mastitis in 15 dairy herds in the Republic of Ireland
Authors: Barrett Damien J. , Healy Anne M. , Leonard Finola C. , Doherty Michael L.
Published: April 2011

Milk samples from 285 cows in 15 dairy herds were collected for bacteriological analysis. Cows were selected on the basis of a somatic cell count (SCC) exceeding 200,000 cells per ml at the three most recent milk recordings prior to sampling.Staphylococcus aureusandStreptococcus uberiswere the predominant isolates accounting for 21% (n = 61) and 19% (n = 53) of isolates, respectively.Streptococcus uberiswas more frequently isolated from split-calving herds than from spring-calving herds and this difference was statistically significant (P < 0.005). Herds with suboptimal housing had a significantly greater prevalence ofS. uberisthan did herds where housing was adequate (P < 0.005). The isolation rates forS. aureuswas significantly greater in herds where parlour hygiene was suboptimal (P < 0.05).
A case of hypospadias in a dog
Authors: Ndikuwera Jason
Published: April 2011

This clinical case report described a three-month-old mongrel dog that had the urethral orifice opening 3 cm from the tip of the penis and lacked a completely formed preputial sheath. It was presented to the clinic with an exposed penile shaft that was dry. The dog had urinary incontinence that was not of neurological origin. It also had unilateral agenesis of the right testicle. The preputial sheath was successfully reconstructed. Urinary incontinence stopped soon after surgery, suggesting that it had been probably due to an ascending urethritis. A large preputial opening was left because of the location of the urethral opening.
A group IIA-secreted phospholipase A2 from snake venom induces lipid body formation in macrophages: the roles of intracellular phospholipases A2 and distinct signaling pathways
Authors: Leiguez Elbio , Zuliani Juliana Pavan , Cianciarullo Aurora Marques , Fernandes Cristina Maria , Gutiérrez José Maria , Teixeira Catarina
Published: April 2011

We investigated the ability of the sPLA2, known as MT-III, isolated from the viperid snake Bothrops asper, to induce LB formation in macrophages and the major cellular signaling pathways involved in this process. The effects of MT-III on ADRP localization and expression and macrophage ultrastructure were assessed. Our results showed that this sPLA2 induced a marked increase in LB numbers in macrophages, induced the recruitment of ADRP in macrophages, and up-regulated ADRP expression. Ultrastructural analysis showed the presence of weakly and strongly osmiophilic LBs in sPLA2-stimulated cells. Enlargement of the ER and Golgi cisterns was also observed. Pretreatment of cells with H7 or staurosporine (PKC inhibitors), LY294002 or wortmannin (PI3K inhibitors), SB202190 or PD98059 (p38MAPK and ERK1/2 inhibitors, respectively), or Pyr-2 or Bel (cPLA2 and iPLA2 inhibitors, respectively) significantly reduced sPLA2-induced LB formation. Herbimycin (a PTK inhibitor) and indomethacin or etoricoxib (COX inhibitors) failed to alter sPLA2-induced effects. In conclusion, our results show for the first time the ability of a venom sPLA2 to induce the formation of LBs and the expression of ADRP in macrophages. Venom PLA2-induced LB formation is dependent on PKC, PI3K, p38MAPK, ERK1/2, cPLA2, and iPLA2 signaling pathways but not on PTK, COX-1, or COX-2 pathways. Activation of the ER and Golgi complex may play an important role in the formation of LBs induced by this sPLA2 in macrophages.