bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey on Surgical Instrument Handle Design
Authors: Santos-Carreras Laura , Hagen Monika , Gassert Roger , Bleuler Hannes
Published: August 2011

Minimally invasive surgical approaches have revolutionized surgical care and considerably improved surgical outcomes. The instrumentation has changed significantly from open to laparoscopic and robotic surgery with various usability and ergonomics qualities. To establish guidelines for future designing of surgical instruments, this study assesses the effects of current surgical approaches and instruments on the surgeon. Furthermore, an analysis of surgeons’ preferences with respect to instrument handles was performed to identify the main acceptance criteria. In all, 49 surgeons (24 with robotic surgery experience, 25 without) completed the survey about physical discomfort and working conditions. The respondents evaluated comfort, intuitiveness, precision, and stability of 7 instrument handles. Robotic surgery procedures generally take a longer time than conventional procedures but result in less back, shoulder, and wrist pain; 28% of surgeons complained about finger and neck pain during robotic surgery. Three handles (conventional needle holder, da Vinci wrist, and joystick-like handle) received significantly higher scores for most of the proposed criteria. The handle preference is best explained by a regression model related only to comfort and precision ( R2 = 0.91) and is significantly affected by the surgeon’s background ( P < .001). Although robotic surgery seems to alleviate physical discomfort during and after surgery, the results of this study show that there is room for improvement in the sitting posture and in the ergonomics of the handles. Comfort and precision have been found to be the most important aspects for the surgeon’s choice of an instrument handle. Furthermore, surgeons’ professional background should be considered when designing novel surgical instruments.
Surgical Videos for Accident Analysis, Performance Improvement, and Complication Prevention
Authors: Gambadauro Pietro , Magos Adam
Published: August 2011

Conventional audit of surgical records through review of surgical results provides useful knowledge but hardly helps identify the technical reasons lying behind specific outcomes or complications. Surgical teams not only need to know that a complication might happen but also how and when it is most likely to happen. Functional awareness is therefore needed to prevent complications, know how to deal with them, and improve overall surgical performance. The authors wish to argue that the systematic recording and reviewing of surgical videos, a “surgical black box,” might improve surgical care, help prevent complications, and allow accident analysis. A possible strategy to test this hypothesis is presented and discussed. Recording and reviewing surgical interventions, apart from helping us achieve functional awareness and increasing the safety profile of our performance, allows us also to effectively share our experience with colleagues. The authors believe that those potential implications make this hypothesis worth testing.
Are Pedicled Flaps Feasible in Robotic Surgery? Report of an Anatomical Study of the Kite Flap in Conventional Surgery Versus Robotic Surgery
Authors: Huart Alexandra , Facca Sybille , Lebailly Frédéric , Garcia José Carlos , Liverneaux Philippe André
Published: August 2011

Reconstruction of cutaneous defects of the hand has dramatically progressed. It should also benefit from the development of robot-assisted surgery. The aim of the present study was to consider the feasibility of a kite flap in robotic surgery. Two cadaver hands were used in this study, one for a conventional procedure, and one for a robotic surgical procedure using a da Vinci Si robot. The operative duration was measured, and all difficulties encountered during the procedures were reported. The total duration of the intervention was 19 minutes with the conventional procedure and 30 minutes with the robotic technique. Some difficulties were encountered, related both to lack of specific instrumentation and haptic feedback. Robotic surgery presents interesting advantages such as the suppression of physiological tremor, increased degrees of freedom, and enhanced precision and accuracy of hand maneuvers. In this study, it allowed the realization of a pedicled flap without any external help.
Full-Thickness Laparoendoscopic Excision in the Stomach
Authors: Kennedy Robin H. , Cahill Ronan A. , Brigic Adela , Sibbons Paul , Fraser Chris
Published: August 2011

Background. The authors describe the initial validation of a novel full-thickness laparoendoscopic excision (FLEx) technique for the stomach. Methods. The technique was studied in seven 50-kg pigs. Secure full-thickness excision was ensured by inversion excision target with a 1-cm circumferential margin using laparoendoscopically placed brace bars passed intraluminally from the outside of the stomach, laparoscopic oversewing of the site of inversion, and endoscopic full-thickness excision using a dual scope approach. Pigs were sacrificed either immediately (n = 3) or between 7 and 10 days after surgery (n = 4). Results. The procedure achieved uncomplicated full-thickness excision in every case. Median procedure duration was 227 minutes (range = 210-245 minutes). Median specimen diameter was 5.5 cm (range = 2.5-8 cm). Investigative autopsy confirmed technical sufficiency in all animals. Median site bursting pressure was 130 mm Hg (range = 120-160 mm Hg). Conclusions. The FLEx technique proved useful for excision of small localized lesions of the stomach in this animal study.
Application of genetic algorithm for determination of water vapor diffusion parameters of building materials
Authors: Kočí Jan , Žumár Jaromír , Pavlík Zbyšek , Černý Robert
Published: August 2011

A combined experimental/computational technique for determination of water vapor transport properties of porous building materials based on the application of genetic algorithm is developed and tested on cellular concrete. The method allows obtaining water vapor transport properties in dependence on relative humidity which is a crucial factor for advanced computational modeling of hygrothermal performance of multi-layered systems of building materials. Moreover, in a comparison with the standard steady-state cup method, the presented technique requires less than half of the time necessary for measurement which, makes good prerequisites for its wider application in materials research.
A state-space approach for the control of multivariable dynamically substructured systems
Authors: Tu J Y , Stoten D P , Hyde R A , Li G
Published: August 2011

Dynamic substructuring is an experimental technique which decomposes a complete dynamical system into a number of sub-components. Critical components are physically tested at full-size and the remaining components are simultaneously simulated in real-time. High-quality control is required to synchronize the responses of the physical and numerical components and to compensate for additional dynamics introduced by actuator systems within the physical substructures. This paper presents a new state-space approach for the analysis and synthesis of dynamically substructured systems and the associated synchronizing controller design. A new state-space substructured framework is also developed to support the synthesis of state-space dynamic models, which then leads to design and analysis of state-feedback, H∞, and adaptive controllers. This framework is applied to an experimental single-mode, quasi-motorcycle substructuring problem, for illustration of the concepts and for the comparison of controller performance. Implementation results demonstrated the improved performance resulting from the new approach and also the effectiveness of adaptive control in coping with uncertain and changing parameters within the physical substructures.
Iodine
Authors: Meletis Chris D.
Published: August 2011

Iodine levels in the United States have dropped precipitously over the past few decades, whereas antagonists such as bromine, perchlorate, and fluoride have become more ubiquitous. These changes have placed a nutritional burden on the human body and increased the potential for pathophysiological change at the cellular level. This review examines the clinical and peer-reviewed literature and provides perspective related to health-compromising trends that warrant close scrutiny in clinical practice and future research mandates.
The Bill Henderson Protocol
Authors: Page Stacey , Mannion Cynthia , Bell Laurie Heilman , Verhoef Marja
Published: August 2011

This study sought to describe how consumers found the Bill Henderson protocol, a dietary intervention for cancer treatment, and to describe their perceptions and evaluation of its effects. In all, 630 surveys were completed online. Most respondents were ages 55 to 74 years old, well-educated, and had experience with a cancer diagnosis. Most respondents identified the Bill Henderson protocol through Internet searches. More than two thirds had used the protocol, although adherence to its components varied. A number of positive attributions were made to the protocol, including cancer cure (n = 73) and improvements in health status indicators (n = 170). Negative attributions included disease progression (n = 10) and death (n = 2). Consumers search for disease management options online. Attributions regarding this intervention’s success or failure are based on anecdotal experience. There has been no empirical investigation of the Bill Henderson protocol’s safety and efficacy to date, limiting the information on which choice can be made. This could place protocol adherents at risk.
p53 activation of mesenchymal stromal cells partially abrogates microenvironment-mediated resistance to FLT3 inhibition in AML through HIF-1α–mediated down-regulation of CXCL12
Authors: Kojima Kensuke , McQueen Teresa , Chen Ye , Jacamo Rodrigo , Konopleva Marina , Shinojima Naoki , Shpall Elizabeth , Huang Xuelin , Andreeff Michael
Published: August 2011

Fms-like tyrosine kinase-3 (FLT3) inhibitors have been used to overcome the dismal prognosis of acute myeloid leukemia (AML) with FLT3 mutations. Clinical results with FLT3 inhibitor monotherapy have shown that bone marrow responses are commonly less pronounced than peripheral blood responses. We investigated the role of p53 in bone marrow stromal cells in stromal cell-mediated resistance to FLT3 inhibition in FLT3 mutant AML. While the FLT3 inhibitor FI-700 induced apoptosis in FLT3 mutant AML cells, apoptosis induction was diminished under stromal coculture conditions. Protection appeared to be mediated, in part, by CXCL12 (SDF-1)/CXCR4 signaling. The protective effect of stromal cells was significantly reduced by pre-exposure to the HDM2 inhibitor Nutlin-3a. p53 activation by Nutlin-3a was not cytotoxic to stromal cells, but reduced CXCL12 mRNA levels and secretion of CXCL12 partially through p53-mediated HIF-1α down-regulation. Results show that p53 activation in stroma cells blunts stroma cell-mediated resistance to FLT3 inhibition, in part through down-regulation of CXCL12. This is the first report of Nutlin effect on the bone marrow environment. We suggest that combinations of HDM2 antagonists and FLT3 inhibitors may be effective in clinical trials targeting mutant FLT3 leukemias.
Implications of discrepancy in morphologic diagnosis of myelodysplastic syndrome between referral and tertiary care centers
Authors: Naqvi Kiran , Jabbour Elias , Bueso-Ramos Carlos , Pierce Sherry , Borthakur Gautam , Estrov Zeev , Ravandi Farhad , Faderl Stefan , Kantarjian Hagop , Garcia-Manero Guillermo
Published: August 2011

Patients referred to tertiary care centers occasionally may have their diagnostic procedures repeated and have a final diagnosis that differs from that of the referring center. The aim of this study was to evaluate discordance rates and their clinical implications in the diagnosis of patients with myelodysplastic syndrome (MDS) referred to a tertiary center. We analyzed 915 patients with MDS who were referred to M. D. Anderson Cancer Center between September 2005 and December 2009. Discordance in the diagnosis was documented in 109 (12%) patients, with a majority reclassified as having higher-risk disease by French-American-British (67%) or by International Prognostic Scoring System (77%) with implications for therapy selection and prognosis calculation. These results demonstrate the complexity of the diagnosis of MDS and highlight the need for confirmation of diagnosis when in doubt.
A novel inhibitor of focal adhesion signaling induces caspase-independent cell death in diffuse large B-cell lymphoma
Authors: Bosch Rosa , Dieguez-Gonzalez Rebeca , Céspedes Maria Virtudes , Parreño Matilde , Pavón Miguel Ángel , Grañena Albert , Sierra Jorge , Mangues Ramon , Casanova Isolda
Published: August 2011

Focal adhesion (FA) proteins have been associated with transformation, migration, metastasis, and poor outcome in many neoplasias. We previously showed that these proteins were inhibited by E7123, a new celecoxib derivative with antitumor activity, in acute myeloid leukemia. However, little is known about FAs in diffuse large B cell lymphoma (DLBCL). This paper aimed to determine whether E7123 was effective against DLBCL and whether FAs were involved in its action. We evaluated the cytotoxicity and mechanism of action of E7123 and celecoxib in DLBCL cell lines. We also assessed the E7123 in vivo activity in a DLBCL xenograft model and studied FA signaling in primary DLBCL patient samples. We found that E7123 showed higher antitumor effect than celecoxib against DLBCL cells. Its mechanism of action involved deregulation of FA, AKT, and Mcl-1 proteins, a pathway that is activated in some patient samples, apoptosis-inducing factor release and induction of caspase-independent cell death. Moreover, E7123 showed suppression of in vivo tumor growth. These findings indicate that E7123 is effective against DLBCL in vitro and in vivo, with a mechanism of action that differs from that of most current therapies for this malignancy. Our results support further preclinical evaluation of E7123.
Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation
Authors: Kohrt Holbrook E. , Müller Antonia , Baker Jeanette , Goldstein Matthew J. , Newell Evan , Dutt Suparna , Czerwinski Debra , Lowsky Robert , Strober Samuel
Published: August 2011

The curative potential of MHC-matched allogeneic bone marrow transplantation (BMT) is in part because of immunologic graft-versus-tumor (GvT) reactions mediated by donor T cells that recognize host minor histocompatibility antigens. Immunization with leukemia-associated antigens, such as Wilms Tumor 1 (WT1) peptides, induces a T-cell population that is tumor antigen specific. We determined whether allogeneic BMT combined with immunotherapy using WT1 peptide vaccination of donors induced more potent antitumor activity than either therapy alone. WT1 peptide vaccinations of healthy donor mice induced CD8+ T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells. We found that peptide immunization was effective as a prophylactic vaccination before tumor challenge, yet was ineffective as a therapeutic vaccination in tumor-bearing mice. BMT from vaccinated healthy MHC-matched donors, but not syngeneic donors, into recipient tumor-bearing mice was effective as a therapeutic maneuver and resulted in eradication of FBL3 leukemia. The transfer of total CD8+ T cells from immunized donors was more effective than the transfer of WT1-tetramer+CD8+ T cells and both required CD4+ T-cell help for maximal antitumor activity. These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
Analysis of high-identity segmental duplications in the grapevine genome
Authors: Giannuzzi Giuliana , D'Addabbo Pietro , Gasparro Marica , Martinelli Maurizio , Carelli Francesco N , Antonacci Donato , Ventura Mario
Published: August 2011

Background

Segmental duplications (SDs) are blocks of genomic sequence of 1-200 kb that map to different loci in a genome and share a sequence identity > 90%. SDs show at the sequence level the same characteristics as other regions of the human genome: they contain both high-copy repeats and gene sequences. SDs play an important role in genome plasticity by creating new genes and modeling genome structure. Although data is plentiful for mammals, not much was known about the representation of SDs in plant genomes. In this regard, we performed a genome-wide analysis of high-identity SDs on the sequenced grapevine (Vitis vinifera) genome (PN40024).

Results

We demonstrate that recent SDs (> 94% identity and >= 10 kb in size) are a relevant component of the grapevine genome (85 Mb, 17% of the genome sequence). We detected mitochondrial and plastid DNA and genes (10% of gene annotation) in segmentally duplicated regions of the nuclear genome. In particular, the nine highest copy number genes have a copy in either or both organelle genomes. Further we showed that several duplicated genes take part in the biosynthesis of compounds involved in plant response to environmental stress.

Conclusions

These data show the great influence of SDs and organelle DNA transfers in modeling the Vitis vinifera nuclear DNA structure as well as the impact of SDs in contributing to the adaptive capacity of grapevine and the nutritional content of grape products through genome variation. This study represents a step forward in the full characterization of duplicated genes important for grapevine cultural needs and human health.
Ontology-based Brucella vaccine literature indexing and systematic analysis of gene-vaccine association network
Authors: Hur Junguk , Xiang Zuoshuang , Feldman Eva L , He Yongqun
Published: August 2011

Background

Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines forBrucella, the causative agent of brucellosis in humans and animals.

Results

The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67Brucellavaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related toBrucellavaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrievingBrucellavaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuatedBrucellavaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947Brucella-related papers, VO-SciMiner identified 140Brucellagenes associated withBrucellavaccines. These genes included known protective antigens, virulence factors, and genes closely related toBrucellavaccines. These VO-interactingBrucellagenes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network ofBrucellavaccines and genes were identified. The asserted and inferred VO hierarchies provide semantic support for inferring novel knowledge of association of vaccines and genes from the retrieved data. New hypotheses were generated based on this analysis approach.

Conclusion

VO-SciMiner can be used to improve the efficiency for PubMed searching in the vaccine domain.
Psychopathological features of irritable bowel syndrome patients with and without functional dyspepsia: a cross sectional study
Authors: Piacentino Daria , Cantarini Rosanna , Alfonsi Marianna , Badiali Danilo , Pallotta Nadia , Biondi Massimo , Corazziari Enrico S
Published: August 2011

Background

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) show considerable overlap and are both associated with psychiatric comorbidity. The present study aimed to investigate whether IBS patients with FD show higher levels of psychopathology than those without FD. As a preliminary analysis, it also evaluated the psychopathological differences, if any, between IBS patients featuring the two Rome III-defined FD subtypes, i.e. postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).

Methods

Consecutive outpatients (n = 82, F = 67, mean age 41.6 ± 12.7 years) referred to our third level gastroenterological centre, matching the Rome III criteria for IBS and, if present, for concurrent FD, were recruited. They were asked to complete a 90-item self-rating questionnaire, the Symptom Checklist 90 Revised (SCL-90-R), in order to assess the psychological status. Comparisons between groups were carried out using the non-parametric Mann-Whitney U test.

Results

Patients with IBS only were 56 (68.3%, F = 43, mean age 41.6 ± 13.3 years) and patients with both IBS and FD were 26 (31.7%, F = 24, mean age 41.8 ± 11.5 years), 17 of whom had PDS and 9 EPS. Patients with both IBS and FD scored significantly higher on the SCL-90-R GSI and on eight out of the nine subscales than patients with IBS only (P ranging from 0.000 to 0.03). No difference was found between IBS patients with PDS and IBS patients with EPS (P ranging from 0.07 to 0.97), but this result has to be considered provisional, given the small sample size of the two subgroups.

Conclusions

IBS-FD overlap is associated with an increased severity of psychopathological features. This finding suggests that a substantial subset of patients of a third level gastroenterological centre with both IBS and FD may benefit from psychological assessment and treatment.
An increased risk of urinary tract infection precedes development of primary biliary cirrhosis
Authors: Varyani Fumi K , West Joe , Card Timothy R
Published: August 2011

Background

Primary Biliary Cirrhosis is known to be associated with Urinary Tract Infections (UTIs), but whether these precede or follow the liver disease is unclear. We have therefore attempted to determine whether UTIs are more common in people with Primary Biliary Cirrhosis (PBC) prior to their diagnosis.

Methods

We conducted a case control study in the General Practice Research Database. All cases of PBC first recorded at least one year after entry to the dataset were selected along with up to 10 controls matched for age, sex. A second unmatched control group who had Chronic Liver Diseases but not PBC were chosen. The main exposures studied were the occurrence of Urinary tract infections and pyelonephritis at least one or at least five years before diagnosis. We also performed an analysis restricted to those younger than 55 at diagnosis, as we hypothesized the relationship to be stronger in the younger age group.

Results

PBC is associated with UTI prior to diagnosis, OR 1.50 (CI 1.26-1.78), which was similar 5 years prior to diagnosis and after adjusting for smoking. The strongest relationships were observed in pyelonephritis exposures five years before diagnosis in cases under 55 years: adjusted odds ratios were 2.60 (1.02-6.63) in comparison with matched general population controls and adjusted odds ratios were OR 2.45 (1.02-5.59) in the comparison with chronic liver disease controls.

Conclusions

We found that the association between urosepsis and PBC is specific to this disease and precedes the diagnosis of PBC in a manner not previously observed in human data. This is consistent with a causal relationship.
Predictors of adherence to a multifaceted podiatry intervention for the prevention of falls in older people
Authors: Spink Martin J , Fotoohabadi Mohammad R , Wee Elin , Landorf Karl B , Hill Keith D , Lord Stephen R , Menz Hylton B
Published: August 2011

Background

Despite emerging evidence that foot problems and inappropriate footwear increase the risk of falls, there is little evidence as to whether foot-related intervention strategies can be successfully implemented. The aim of this study was to evaluate adherence rates, barriers to adherence, and the predictors of adherence to a multifaceted podiatry intervention for the prevention of falls in older people.

Methods

The intervention group (n = 153, mean age 74.2 years) of a randomised trial that investigated the effectiveness of a multifaceted podiatry intervention to prevent falls was assessed for adherence to the three components of the intervention: (i) foot orthoses, (ii) footwear advice and footwear cost subsidy, and (iii) a home-based foot and ankle exercise program. Adherence to each component and the barriers to adherence were documented, and separate discriminant function analyses were undertaken to identify factors that were significantly and independently associated with adherence to the three intervention components.

Results

Adherence to the three components of the intervention was as follows: foot orthoses (69%), footwear (54%) and home-based exercise (72%). Discriminant function analyses identified that being younger was the best predictor of orthoses use, higher physical health status and lower fear of falling were independent predictors of footwear adherence, and higher physical health status was the best predictor of exercise adherence. The predictive accuracy of these models was only modest, with 62 to 71% of participants correctly classified.

Conclusions

Adherence to a multifaceted podiatry intervention in this trial ranged from 54 to 72%. People with better physical health, less fear of falling and a younger age exhibited greater adherence, suggesting that strategies need to be developed to enhance adherence in frailer older people who are most at risk of falling.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12608000065392.
Clusters of spatial, temporal, and space-time distribution of hemorrhagic fever with renal syndrome in Liaoning Province, Northeastern China
Authors: Wu Wei , Guo Junqiao , Guan Peng , Sun Yingwei , Zhou Baosen
Published: August 2011

Background

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney damage, and hypotension. HFRS is recognized as a notifiable public health problem in China, and Liaoning Province is one of the most seriously affected areas with the most cases in China. It is necessary to investigate the spatial, temporal, and space-time distribution of confirmed cases of HFRS in Liaoning Province, China for future research into risk factors.

Methods

A cartogram map was constructed; spatial autocorrelation analysis and spatial, temporal, and space-time cluster analysis were conducted in Liaoning Province, China over the period 1988-2001.

Results

When the number of permutation test was set to 999, Moran's I was 0.3854, and was significant at significance level of 0.001. Spatial cluster analysis identified one most likely cluster and four secondary likely clusters. Temporal cluster analysis identified 1998-2001 as the most likely cluster. Space-time cluster analysis identified one most likely cluster and two secondary likely clusters.

Conclusions

Spatial, temporal, and space-time scan statistics may be useful in supervising the occurrence of HFRS in Liaoning Province, China. The result of this study can not only assist health departments to develop a better prevention strategy but also potentially increase the public health intervention's effectiveness.
Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
Authors: Opstal-van Winden Annemieke WJ , Krop Esmeralda JM , Kåredal Monica H , Gast Marie-Christine W , Lindh Christian H , Jeppsson Marina C , Jönsson Bo AG , Grobbee Diederick E , Peeters Petra HM , Beijnen Jos H , van Gils Carla H , Vermeulen Roel CH
Published: August 2011

Background

Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.

Methods

In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).

Results

Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3adesArg and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.

Conclusions

We show that serum protein profiles are already altered up to three years before breast cancer detection.
Massively multiplayer online role-playing games: comparing characteristics of addict vsnon-addict online recruited gamers in a French adult population
Authors: Achab Sophia , Nicolier Magali , Mauny Frédéric , Monnin Julie , Trojak Benoit , Vandel Pierre , Sechter Daniel , Gorwood Philip , Haffen Emmanuel
Published: August 2011

Background

Massively Multiplayer Online Role-Playing Games (MMORPGs) are a very popular and enjoyable leisure activity, and there is a lack of international validated instruments to assess excessive gaming. With the growing number of gamers worldwide, adverse effects (isolation, hospitalizations, excessive use, etc.) are observed in a minority of gamers, which is a concern for society and for the scientific community. In the present study, we focused on screening gamers at potential risk of MMORPG addiction.

Methods

In this exploratory study, we focused on characteristics, online habits and problematic overuse in adult MMORPG gamers. In addition to socio-demographical data and gamer behavioral patterns, 3 different instruments for screening addiction were used in French MMORPG gamers recruited online over 10 consecutive months: the substance dependence criteria for the Diagnostic and Statistical Manual of Mental Disorder, fourth revised edition (DSM-IV-TR) that has been adapted for MMORPG (DAS), the qualitative Goldberg Internet Addiction Disorder scale (GIAD) and the quantitative Orman Internet Stress Scale (ISS). For all scales, a score above a specific threshold defined positivity.

Results

The 448 participating adult gamers were mainly young adult university graduates living alone in urban areas. Participants showed high rates of both Internet addiction (44.2% for GIAD, 32.6% for ISS) and DAS positivity (27.5%). Compared to the DAS negative group, DAS positive gamers reported significantly higher rates of tolerance phenomenon (increased amount of time in online gaming to obtain the desired effect) and declared significantly more social, financial (OR: 4.85), marital (OR: 4.61), family (OR: 4.69) and/or professional difficulties (OR: 4.42) since they started online gaming. Furthermore, these gamers self-reported significantly higher rates (3 times more) of irritability, daytime sleepiness, sleep deprivation due to play, low mood and emotional changes since online gaming onset.

Conclusions

The DAS appeared to be a good first-line instrument to screen MMORPG addiction in online gamers. This study found high MMORPG addiction rates, and self-reported adverse symptoms in important aspects of life, including mood and sleep. This confirms the need to set up relevant prevention programs against online game overuse.
Calcium sparks in the intact gerbil spiral modiolar artery
Authors: Krishnamoorthy Gayathri , Regehr Keil , Berge Samantha , Scherer Elias Q , Wangemann Philine
Published: August 2011

Background

Calcium sparks are ryanodine receptor mediated transient calcium signals that have been shown to hyperpolarize the membrane potential by activating large conductance calcium activated potassium (BK) channels in vascular smooth muscle cells. Along with voltage-dependent calcium channels, they form a signaling unit that has a vasodilatory influence on vascular diameter and regulation of myogenic tone. The existence and role of calcium sparks has hitherto been unexplored in the spiral modiolar artery, the end artery that controls blood flow to the cochlea. The goal of the present study was to determine the presence and properties of calcium sparks in the intact gerbil spiral modiolar artery.

Results

Calcium sparks were recorded from smooth muscle cells of intact arteries loaded with fluo-4 AM. Calcium sparks occurred with a frequency of 2.6 Hz, a rise time of 17 ms and a time to half-decay of 20 ms. Ryanodine reduced spark frequency within 3 min from 2.6 to 0.6 Hz. Caffeine (1 mM) increased spark frequency from 2.3 to 3.3 Hz and prolonged rise and half-decay times from 17 to 19 ms and from 20 to 23 ms, respectively. Elevation of potassium (3.6 to 37.5 mM), presumably via depolarization, increased spark frequency from 2.4 to 3.2 Hz. Neither ryanodine nor depolarization changed rise or decay times.

Conclusions

This is the first characterization of calcium sparks in smooth muscle cells of the spiral modiolar artery. The results suggest that calcium sparks may regulate the diameter of the spiral modiolar artery and cochlear blood flow.
Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma
Authors: Obchoei Sumalee , Weakley Sarah M , Wongkham Sopit , Wongkham Chaisiri , Sawanyawisuth Kanlayanee , Yao Qizhi , Chen Changyi
Published: August 2011

Background

Cyclophilin A (CypA) expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA) are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines.

Methods

CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot.

Results

CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase) activity using cyclosporin A (CsA) decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation.

Conclusions

CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of CypA activity also reduces CCA cell proliferation. The ERK1/2 pathway may be involved in the CypA-mediated CCA cell proliferation. Thus, CypA may represent an important new therapeutic target for liver fluke-associated CCA.
Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro
Authors: Takata Fuyuko , Dohgu Shinya , Matsumoto Junichi , Takahashi Hiroyuki , Machida Takashi , Wakigawa Tomoya , Harada Eriko , Miyaji Haruki , Koga Mitsuhisa , Nishioku Tsuyoshi , Yamauchi Atsushi , Kataoka Yasufumi
Published: August 2011

Background

Increased matrix metalloproteinase (MMP)-9 in the plasma and brain is associated with blood-brain barrier (BBB) disruption through proteolytic activity in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and its vicinity, where brain microvascular endothelial cells (BMECs), pericytes and astrocytes constitute the BBB. Little is known about the cellular source and role of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9 and migrate in response to inflammatory mediators in comparison with BMECs and astrocytes, using primary cultures isolated from rat brains.

Methods

The culture supernatants were collected from primary cultures of rat brain endothelial cells, pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were measured by gelatin zymography and western blot, respectively. The involvement of signaling molecules including mitogen-activated protein kinases (MAPKs) and phosphoinositide-3-kinase (PI3K)/Akt in the mediation of tumor necrosis factor (TNF)-α-induced MMP-9 release was examined using specific inhibitors. The functional activity of MMP-9 was evaluated by a cell migration assay.

Results

Zymographic and western blot analyses demonstrated that TNF-α stimulated pericytes to release MMP-9, and this release was much higher than from BMECs or astrocytes. Other inflammatory mediators [interleukin (IL)-1β, interferon-γ, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from pericytes. TNF-α-induced MMP-9 release from pericytes was found to be mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast to BMECs and astrocytes the extent of pericyte migration was significantly increased by TNF-α. This pericyte migration was inhibited by anti-MMP-9 antibody.

Conclusion

These findings suggest that pericytes are most sensitive to TNF-α in terms of MMP-9 release, and are the major source of MMP-9 at the BBB. This pericyte-derived MMP-9 initiated cellular migration of pericytes, which might be involved in pericyte loss in the damaged BBB.
Is ultra-violet radiation the main force shaping molecular evolution of varicella-zoster virus?
Authors: Vaughan Gilberto , Rodríguez-Castillo Araceli , Cruz-Rivera Mayra Y , Ruiz-Tovar Karina , Ramírez-González José E , Rivera-Osorio Pilar , Fonseca-Coronado Salvador , Carpio-Pedroza Juan C , Cazares Fernando , Vazquez-Pichardo Mauricio , Anaya Luis , Escobar-Gutiérrez Alejandro
Published: August 2011

Background

Varicella (chickenpox) exhibits a characteristic epidemiological pattern which is associated with climate. In general, primary infections in tropical regions are comparatively less frequent among children than in temperate regions. This peculiarity regarding varicella-zoster virus (VZV) infection among certain age groups in tropical regions results in increased susceptibility during adulthood in these regions. Moreover, this disease shows a cyclic behavior in which the number of cases increases significantly during winter and spring. This observation further supports the participation of environmental factors in global epidemiology of chickenpox. However, the underlying mechanisms responsible for this distinctive disease behavior are not understood completely. In a recent publication, Philip S. Rice has put forward an interesting hypothesis suggesting that ultra-violet (UV) radiation is the major environmental factor driving the molecular evolution of VZV.

Discussion

While we welcomed the attempt to explain the mechanisms controlling VZV transmission and distribution, we argue that Rice's hypothesis takes lightly the circulation of the so called "temperate VZV genotypes" in tropical regions and, to certain degree, overlooks the predominance of such lineages in certain non-temperate areas. Here, we further discuss and present new information about the overwhelming dominance of temperate VZV genotypes in Mexico regardless of geographical location and climate.

UV radiation does not satisfactorily explain the distribution of VZV genotypes in different tropical and temperate regions of Mexico. Additionally, the cyclic behavior of varicella does not shown significant differences between regions with different climates in the country. More studies should be conducted to identify the factors directly involved in viral spreading. A better understanding of the modes of transmissions exploited by VZV and their effect on viral fitness is likely to facilitate the implementation of preventive measures for disease control.
Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010
Authors: de Felipe Beatriz , Pérez-Romero Pilar , Abad-Fernández María , Fernandez-Cuenca Felipe , Martinez-Fernandez Francisco J , Trastoy Mónica , Mata Rosario del Carmen , López-Cortés Luis F , Leal Manuel , Viciana Pompeyo , Vallejo Alejandro
Published: August 2011

Background

Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations.

Methods

Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA.

Results

From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I.

Conclusions

The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.
DNA Methylation of SPARC and Chronic Low Back Pain
Authors: Tajerian Maral , Alvarado Sebastian , Millecamps Magali , Dashwood Thomas , Anderson Kathleen M , Haglund Lisbet , Ouellet Jean , Szyf Moshe , Stone Laura S
Published: August 2011

Background:

The extracellular matrix protein SPARC (Secreted Protein, Acidic, Rich in Cysteine) has been linked to degeneration of the intervertebral discs and chronic low back pain (LBP). In humans, SPARC protein expression is decreased as a function of age and disc degeneration. In mice, inactivation of the SPARC gene results in the development of accelerated age-dependent disc degeneration concurrent with age-dependent behavioral signs of chronic LBP. DNA methylation is the covalent modification of DNA by addition of methyl moieties to cytosines in DNA. DNA methylation plays an important role in programming of gene expression, including in the dynamic regulation of changes in gene expression in response to aging and environmental signals. We tested the hypothesis that DNA methylation down-regulates SPARC expression in chronic LBP in pre-clinical models and in patients with chronic LBP.

Results:

Our data shows that aging mice develop anatomical and behavioral signs of disc degeneration and back pain, decreased SPARC expression and increased methylation of the SPARC promoter. In parallel, we show that human subjects with back pain exhibit signs of disc degeneration and increased methylation of the SPARC promoter. Methylation of either the human or mouse SPARC promoter silences its activity in transient transfection assays.

Conclusions:

This study provides the first evidence that DNA methylation of a single gene plays a role in chronic pain in humans and animal models. This has important implications for understanding the mechanisms involved in chronic pain and for pain therapy.