bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulant Medication and Prefrontal Functional Connectivity During Working Memory in ADHD
Authors: Sheridan Margaret A. , Hinshaw Stephen , D'Esposito Mark
Published: June 2010

Objective: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has been described elsewhere as inefficient. Method: Functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used during a working memory task for five female adolescents with ADHD, aged 11 to 17 years, both on and off their usual dose of stimulant medication. Results: On medication, adolescents with ADHD demonstrated less PFC activation and less functional connectivity between frontal and subcortical regions compared to off medication. Conclusions: Because of the small sample size, results are presented as preliminary findings which await replication in a larger sample. However, these findings lend support to the idea that remediation of inefficiencies in PFC function for individuals with ADHD by stimulant medication may be related, in part, to frontal-subcortical connectivity. ( J. of Att. Dis. 2010; 14(1) 69-78)
Influence of Anxiety on the Social Functioning of Children With and Without ADHD
Authors: Mikami Amori Yee , Ransone Megan L. , Calhoun Casey D.
Published: June 2010

Objective: This investigation examined the contribution of anxiety to the social functioning of children with and without ADHD. Method: Participants were 62 children with ADHD (ages 6-10 years and 68% boys) and 62 age- and sex-matched comparison children. Children’s social functioning was measured through parent and teacher reports, observations of social behaviors during a lab-based playgroup with previously unacquainted peers, and peer nominations during that lab-based playgroup. Results: Anxiety symptoms incrementally predicted adult-informant reports of poorer social functioning after controlling for demographic covariates, ADHD status, and oppositional-defiant disorder (ODD) status. However, anxiety was not associated with peer nominations received at the playgroup. There were some indications that anxiety may have greater influence on the functioning of comparison children relative to children with ADHD or ODD. Conclusion: Anxiety may contribute to the peer problems of children both with and without ADHD.
The Economic Effects of Bus Transit in Small Cities
Authors: Faulk Dagney , Hicks Michael
Published: June 2010

This analysis investigates the impact of public transit in counties with small to medium-sized cities. The objectives are to answer: Do counties with bus transit have lower growth in transfer payments such as food stamps, Temporary Aid to Needy Families (TANF), or higher income growth, employment growth, and population growth? Public transit is commonly viewed as a social service; this analysis explores the economic impact of this public investment. The authors find that relative to counties without bus transit, counties with bus systems have significantly lower unemployment rates, lower growth in family assistance, lower growth in food stamp payments, and higher population and employment growth. Yet, the positive impact on job access, which reduces payments for family assistance and food stamps is tempered by lack of discernable effects on income likely driven by supply-side effects in the labor market.
Cohort differences in personality in middle-aged women during a 36-year period. Results from the Population Study of Women in Gothenburg
Authors: André Malin , Lissner Lauren , Bengtsson Calle , Hällström Tore , Sundh Valter , Björkelund Cecilia
Published: June 2010

Aim: To investigate secular trends in personality traits in adult female populations. Methods: Two representative, population-based cohorts of women, 38 (n = 318) and 50 (n = 593) years of age participated in a health examination in 1968 and 2004 in Gothenburg, Sweden. The Eysenck Personality Inventory (EPI) and Cesarec-Marke Personality Schedule (CMPS) were used to measure personality traits. Socioeconomic and lifestyle variables (personal income, education, marital status, children at home, physical activity and smoking) were reported. Results: In both age groups, secular comparisons in psychological profile subscales showed an increase in dominance, exhibition, aggression and achievement. Only small divergences were seen concerning affiliation, guilt feelings, nurturance and succorance. EPI showed a corresponding rise in extroversion. Social data showed a statistically significant increase in percentage of unmarried women, personal income levels, and higher educational achievement. While around 70% of women in 1968—69 had elementary school education only, around 90% had high school or university education in 2004—05. Conclusions: The results indicate major transitions in the adult Swedish female population in the direction of a more stereotypically ‘‘male’’ personality profile, but not at the expense of traditionally socially important female traits, which remained constant. These results are consistent with the hypothesis that society and the environment influence personality.
Crush injuries and crush syndrome — a review. Part 1: the systemic injury
Authors: Jagodzinski Nikolas A , Weerasinghe Charitha , Porter Keith
Published: June 2010

Crush injuries can occur in large numbers following natural disasters or acts of war and terrorism. They can also occur sporadically after industrial accidents or following periods of unconsciousness from drug intoxication, anaesthesia, trauma or cerebral events. A common pathophysiological pathway has been elucidated over the last century describing traumatic rhabdomyolysis leading to myoglobinuric acute renal failure and a systemic ‘crush syndrome’ affecting many organ systems. If left unrecognised or untreated, then mortality rates are high. If treatment is commenced early and the systemic effects are minimised then patients are often faced with significant morbidity from the crushed limbs themselves. We have performed a thorough review of the English language literature from 1940 to 2009 investigating crush injuries and crush syndrome and present a comprehensive, two-part summary. Part 1: The systemic injury: In this part we concentrate on the systemic crush syndrome. We determine the pathophysiology, clinical and prognostic indicators and treatment options such as forced alkaline diuresis, mannitol therapy, dialysis and haemofiltration. We discuss more controversial treatment options such as allopurinol, potassium binders, calcium therapy and other diuretics. We also discuss the specific management issues of the secondary ‘renal disaster’ that can occur following earthquakes and other mass disasters. Part 2: The local injury: Here we look in more detail at the pathophysiology of skeletal muscle damage following crush injuries and discuss how to minimise morbidity by salvaging limb function. In particular we discuss the controversies surrounding fasciotomy of crushed limbs and compare surgical management with conservative techniques such as mannitol therapy, hyperbaric oxygen therapy, topical negative pressure therapy and a novel topical treatment called gastric pentadecapeptide BPC 157.
Producing intersubjectivity in silence: An ethnographic study of meditation practice
Authors: Pagis Michal
Published: June 2010

The ‘problem of other minds’ is central to sociological theory and of immediate importance to contemporary research on subjectivity and interiority. How do we cultivate and maintain an intersubjective space during silent, private, experiences? Drawing on Alfred Schutz’s phenomenology, this study challenges the common view which regards silence as an obstacle to social relations. The data consist of two years of participant observation of vipassana meditation practices in Israel and the United States. Vipassana meditation is conducted in complete silence, discouraging group sharing of meditation experiences, thus offering an extreme case of silence and privacy. The findings illustrate how, despite the absence of direct verbal communication, the practice of meditation still holds important intersubjective dimensions. I suggest that covert mechanisms of silent intersubjectivity play an important role in everyday social life and require further ethnographic attention.
Painting with permission: Legal graffiti in New York City
Authors: Kramer Ronald
Published: June 2010

Drawing extensively from interviews conducted with 20 New York City graffiti writers and from unobtrusive observations, this article seeks to further our understanding of graffiti writing culture in two important respects. On the one hand, previous scholars have tended to explore graffiti writing as an illegal and/or criminalized (sub)culture. On the other, they have found it to be a practice that embodies a ‘critical’ stance towards society. My findings indicate that since 1990 a subset of graffiti writers who paint with permission has emerged. Furthermore, I find that those who produce legal graffiti tend to lead lives and espouse values that most would not hesitate to recognize as ‘conventional’. I conclude by suggesting that graffiti writing needs to be acknowledged as a multifaceted and historically fluid culture, and by intimating some possible directions for further research.
In pursuit of experience: The postindustrial gentrification of the rural American West
Authors: Dwight Hines J.
Published: June 2010

Contemporary rural gentrification — the colonization of rural communities and small-towns by members of the ex-urban middle class — is a nationwide phenomenon that contradicts nearly two centuries of US urbanization. While previous research primarily describes such counter-urbanization as representing a profound divergence from previous patterns (i.e. urbanization, mass production/consumption, etc.), I contend that rural gentrification is best understood as the product of both continuity and change relative to the ideas/practices of Modernity and current postindustrialization. Based on ethnographic research conducted in a community in south-central Montana, I present evidence that the choice by middle-class newcomers to migrate to the rural US is simultaneously the product of: 1) the continued efficacy of the Modern ideals of authenticity and progress; and 2) their aspirations to distinguish themselves as members of an emerging class faction — the postindustrial middle class (PIMC) — through their emphasis upon the production and consumption of experiences.
Independent but coordinated trials: insights from the Practice-based Opportunities for Weight Reduction Trials Collaborative Research Group
Authors: Yeh Hsin-Chieh , Clark Jeanne M , Emmons Karen E , Moore Reneé H , Bennett Gary G , Warner Erica T , Sarwer David B , Jerome Gerald J , Miller Edgar R , Volger Sheri , Louis Thomas A , Wells Barbara , Wadden Thomas A , Colditz Graham A , Appel Lawrence J
Published: June 2010

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the ‘Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.’

Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach.

Methods The Collaborative Research Group consists of three individual studies: ‘Be Fit, Be Well’ (Washington University in St. Louis/Harvard University), ‘POWER Hopkins’ (Johns Hopkins), and ‘POWER-UP’ (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support.

Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial.

Limitations The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.
Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells
Authors: Hertlein Erin , Triantafillou Georgia , Sass Ellen J. , Hessler Joshua D. , Zhang Xiaoli , Jarjoura David , Lucas David M. , Muthusamy Natarajan , Goldenberg David M. , Lee Robert J. , Byrd John C.
Published: June 2010

Chronic lymphocytic leukemia (CLL) is an incurable progressive disease for which new therapies are required. Therapy with monoclonal antibodies (mAbs) has improved the outcome of patients with CLL, making further investigation of novel antibodies directed against alternative and specific targets on B cells an important area of translational research. We now describe functional properties of an antagonistic humanized mAb to CD74, milatuzumab, showing that milatuzumab combined with a crosslinking antibody induces cytotoxicity in vitro in CLL cells in a caspase- and stromal-independent manner associated with aggregation of CD74 on the cell surface. Furthermore, incorporation of milatuzumab into an immunoliposome induces even more of a cytotoxic response than in vitro crosslinking, representing a novel therapeutic formulation for this mAb. Based on these data, future development of the milatuzumab-immunoliposome formulation as a therapeutic agent for CLL is warranted.
Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein
Authors: Isakson Pauline , Bjørås Magnar , Bøe Stig Ove , Simonsen Anne
Published: June 2010

Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). The authors of previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy-induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease.
SOPRA: Scaffolding algorithm for paired reads via statistical optimization
Authors: Dayarian Adel , Michael Todd P , Sengupta Anirvan M
Published: June 2010

Background

High throughput sequencing (HTS) platforms produce gigabases of short read (<100 bp) data per run. While these short reads are adequate for resequencing applications,de novoassembly of moderate size genomes from such reads remains a significant challenge. These limitations could be partially overcome by utilizing mate pair technology, which provides pairs of short reads separated by a known distance along the genome.

Results

We have developed SOPRA, a tool designed to exploit the mate pair/paired-end information for assembly of short reads. The main focus of the algorithm is selecting a sufficiently large subset of simultaneously satisfiable mate pair constraints to achieve a balance between the size and the quality of the output scaffolds. Scaffold assembly is presented as an optimization problem for variables associated with vertices and with edges of the contig connectivity graph. Vertices of this graph are individual contigs with edges drawn between contigs connected by mate pairs. Similar graph problems have been invoked in the context of shotgun sequencing and scaffold building for previous generation of sequencing projects. However, given the error-prone nature of HTS data and the fundamental limitations from the shortness of the reads, the ad hoc greedy algorithms used in the earlier studies are likely to lead to poor quality results in the current context. SOPRA circumvents this problem by treating all the constraints on equal footing for solving the optimization problem, the solution itself indicating the problematic constraints (chimeric/repetitive contigs, etc.) to be removed. The process of solving and removing of constraints is iterated till one reaches a core set of consistent constraints. For SOLiD sequencer data, SOPRA uses a dynamic programming approach to robustly translate the color-space assembly to base-space. For assessing the quality of an assembly, we report the no-match/mismatch error rate as well as the rates of various rearrangement errors.

Conclusions

Applying SOPRA to real data from bacterial genomes, we were able to assemble contigs into scaffolds of significant length (N50 up to 200 Kb) with very few errors introduced in the process. In general, the methodology presented here will allow better scaffold assemblies of any type of mate pair sequencing data.
An integrated web medicinal materials DNA database: MMDBD (Medicinal Materials DNA Barcode Database)
Authors: Lou Shao-Ke , Wong Ka-Lok , Li Ming , But Paul Pui-Hay , Tsui Stephen Kwok-Wing , Shaw Pang-Chui
Published: June 2010

Background

Thousands of plants and animals possess pharmacological properties and there is an increased interest in using these materials for therapy and health maintenance. Efficacies of the application is critically dependent on the use of genuine materials. For time to time, life-threatening poisoning is found because toxic adulterant or substitute is administered. DNA barcoding provides a definitive means of authentication and for conducting molecular systematics studies. Owing to the reduced cost in DNA authentication, the volume of the DNA barcodes produced for medicinal materials is on the rise and necessitates the development of an integrated DNA database.

Description

We have developed an integrated DNA barcode multimedia information platform- Medicinal Materials DNA Barcode Database (MMDBD) for data retrieval and similarity search. MMDBD contains over 1000 species of medicinal materials listed in the Chinese Pharmacopoeia and American Herbal Pharmacopoeia. MMDBD also contains useful information of the medicinal material, including resources, adulterant information, medical parts, photographs, primers used for obtaining the barcodes and key references. MMDBD can be accessed athttp://www.cuhk.edu.hk/icm/mmdbd.htm.

Conclusions

This work provides a centralized medicinal materials DNA barcode database and bioinformatics tools for data storage, analysis and exchange for promoting the identification of medicinal materials. MMDBD has the largest collection of DNA barcodes of medicinal materials and is a useful resource for researchers in conservation, systematic study, forensic and herbal industry.
Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community
Authors: Moreno-Paz Mercedes , Gómez Manuel J , Arcas Aida , Parro Víctor
Published: June 2010

Background

Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Río Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community.

Results

Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions.

Conclusions

Our results indicate that the acidophilic filaments are dynamic structures in which different mechanisms for biofilm formation/dispersion are operating. Specific transcriptomic fingerprints can be inferred for both planktonic and sessile cells, having the former a more active TCA cycle, while the mixed acid fermentation process dominate in the latter. The excretion of acetate may play a relevant ecological role as a source of electron donor for heterotrophic Fe3+ reducers like some Alphaproteobacteria, Acidobacterium spp. and Sulfobacillus spp., also present in the biofilm. Additionally, acetate may have a negative effect on bioleaching by inhibiting the growth of chemolithotrophic bacteria.
Diverse set of microRNAs are responsive to powdery mildew infection and heat stress in wheat (Triticum aestivum L.)
Authors: Xin Mingming , Wang Yu , Yao Yingyin , Xie Chaojie , Peng Huiru , Ni Zhongfu , Sun Qixin
Published: June 2010

Background

MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. MiRNAs can have large-scale regulatory effects on development and stress response in plants.

Results

To test whether miRNAs play roles in regulating response to powdery mildew infection and heat stress in wheat, by using Solexa high-throughput sequencing we cloned the small RNA from wheat leaves infected by preponderant physiological strain Erysiphe graminis f. sp. tritici (Egt) or by heat stress treatment. A total of 153 miRNAs were identified, which belong to 51 known and 81 novel miRNA families. We found that 24 and 12 miRNAs were responsive to powdery mildew infection and heat stress, respectively. We further predicted that 149 target genes were potentially regulated by the novel wheat miRNA.

Conclusions

Our results indicated that diverse set of wheat miRNAs were responsive to powdery mildew infection and heat stress and could function in wheat responses to both biotic and abiotic stresses.
Application of a target array Comparative Genomic Hybridization to prenatal diagnosis
Authors: Park Ji Hyeon , Woo Jung Hoon , Shim Sung Han , Yang Song-Ju , Choi Young Min , Yang Kap-Seok , Cha Dong Hyun
Published: June 2010

Background

While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies.

Methods

We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray™ M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping.

Results

In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis.

Conclusions

We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically-uncertain genomic regions.
Attitudes of US medical trainees towards neurology education: "Neurophobia" - a global issue
Authors: Zinchuk Andrey V , Flanagan Eoin P , Tubridy Niall J , Miller Wendy A , McCullough Louise D
Published: June 2010

Background

Several studies in the United Kingdom and Asia have suggested that medical students and residents have particular difficulty in diagnosing and managing patients with neurological problems. Little recent information is available for US trainees. We examined whether students and residents at a US university have difficulty in dealing with patients with neurological problems, identified the perceived sources of these difficulties and provide suggestions for the development of an effective educational experience in neurology.

Methods

A questionnaire was administered to third and fourth year medical students at a US school of medicine and to residents of an internal medicine residency program affiliated with that school. Perceived difficulties with eight medical specialties, including neurology, were examined. Methods considered to be most useful for learning medicine were documented. Reasons why neurology is perceived as difficult and ways to improve neurological teaching were assessed.

Results

152 surveys were completed. Participation rates varied, with medical students having higher response rates (> 50%) than medical residents (27%-48%). Respondents felt that neurology was the medical specialty they had least knowledge in (p < 0.001) and was most difficult (p < 0.001). Trainees also felt they had the least confidence when dealing with patients with neurological complaints (p < 0.001). Residents felt more competent in neurology than students (p < 0.001). The paramount reasons for perceived difficulties with neurology were the complexity of neuroanatomy, limited patient exposure and insufficient teaching. Transition from pre-clinical to clinical medicine led to a doubling of "poor" ratings for neurological teaching. Over 80% of the respondents felt that neurology teaching could be improved through greater exposure to patients and more bedside tutorials.

Conclusions

Medical students and residents at this US medical university found neurology difficult. Although this is consistent with prior reports from Europe and Asia, studies in other universities are needed to confirm generalizability of these findings. The optimal opportunity for improvement is during the transition from preclinical to clinical years. Enhanced integration of basic neurosciences and clinical neurology with emphasis on increased bedside tutorials and patient exposure should improve teaching. Studies are needed to quantify the effect of these interventions on confidence of trainees when dealing with patients presenting with neurological complaints.
Medical student attitudes toward video games and related new media technologies in medical education
Authors: Kron Frederick W , Gjerde Craig L , Sen Ananda , Fetters Michael D
Published: June 2010

Background

Studies in K-12 and college students show that their learning preferences have been strongly shaped by new media technologies like video games, virtual reality environments, the Internet, and social networks. However, there is no known research on medical students' game experiences or attitudes towards new media technologies in medical education. This investigation seeks to elucidate medical student experiences and attitudes, to see whether they warrant the development of new media teaching methods in medicine.

Methods

Medical students from two American universities participated. An anonymous, 30-item, cross-sectional survey addressed demographics, game play experience and attitudes on using new media technologies in medical education. Statistical analysis identified: 1) demographic characteristics; 2) differences between the two universities; 3) how video game play differs across gender, age, degree program and familiarity with computers; and 4) characteristics of students who play most frequently.

Results

217 medical students participated. About half were female (53%). Respondents liked the idea of using technology to enhance healthcare education (98%), felt that education should make better use of new media technologies (96%), and believed that video games can have educational value (80%). A majority (77%) would use a multiplayer online healthcare simulation on their own time, provided that it helped them to accomplish an important goal. Men and women agreed that they were most inclined to use multiplayer simulations if they were fun (97%), and if they helped to develop skill in patient interactions (90%). However, there was significant gender dissonance over types of favorite games, the educational value of video games, and the desire to participate in games that realistically replicated the experience of clinical practice.

Conclusions

Overall, medical student respondents, including many who do not play video games, held highly favorable views about the use of video games and related new media technology in medical education. Significant gender differences in game play experience and attitudes may represent male video game design bias that stresses male cognitive aptitudes; medical educators hoping to create serious games that will appeal to both men and women must avoid this.
Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance
Authors: Almeda-Valdes Paloma , Cuevas-Ramos Daniel , Mehta Roopa , Gomez-Perez Francisco J , Cruz-Bautista Ivette , Arellano-Campos Olimpia , Navarrete-Lopez Mariana , Aguilar-Salinas Carlos A
Published: June 2010

Background

Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (SA index) for the identification of IR and related metabolic conditions.

Methods

A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the SA index were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated.

Results

The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 vs. 0.669, P = 0.74), obesity (0.592 vs. 0.610, P = 0.32), hypertriglyceridemia (0.661 vs. 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624 vs. 0.633, P = 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.

The area under the ROC curve of the SA index for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677].

Conclusions

Total adiponectin, HMWA and the SA index had similar utility for the identification of IR and metabolic disturbances.
Development of fluorescent Plasmodium falciparum for in vitro growth inhibition assays
Authors: Wilson Danny W , Crabb Brendan S , Beeson James G
Published: June 2010

Background

Plasmodium falciparum
in vitro growth inhibition assays are widely used to evaluate and quantify the functional activity of acquired and vaccine-induced antibodies and the anti-malarial activity of known drugs and novel compounds. However, several constraints have limited the use of these assays in large-scale population studies, vaccine trials and compound screening for drug discovery and development.

Methods

The D10 P. falciparum line was transfected to express green fluorescent protein (GFP). In vitro growth inhibition assays were performed over one or two cycles of P. falciparum asexual replication using inhibitory polyclonal antibodies raised in rabbits, an inhibitory monoclonal antibody, human serum samples, and anti-malarials. Parasitaemia was evaluated by microscopy and flow cytometry.

Results

Transfected parasites expressed GFP throughout all asexual stages and were clearly detectable by flow cytometry and fluorescence microscopy. Measurement of parasite growth inhibition was the same when determined by detection of GFP fluorescence or staining with ethidium bromide. There was no difference in the inhibitory activity of samples when tested against the transfected parasites compared to the parental line. The level of fluorescence of GFP-expressing parasites increased throughout the course of asexual development. Among ring-stages, GFP-fluorescent parasites were readily separated from uninfected erythrocytes by flow cytometry, whereas this was less clear using ethidium bromide staining. Inhibition by serum and antibody samples was consistently higher when tested over two cycles of growth compared to one, and when using a 1 in 10 sample dilution compared to 1 in 20, but there was no difference detected when using a different starting parasitaemia to set-up growth assays. Flow cytometry based measurements of parasitaemia proved more reproducible than microscopy counts.

Conclusions

Flow cytometry based assays using GFP-fluorescent parasites proved sensitive and highly reproducible for quantifying the growth-inhibitory activity of antibodies and anti-malarials, with superior reproducibility to light microscopy, and are suitable for high-throughput applications.
Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009
Authors: Thanh Ngo V , Toan Tran Q , Cowman Alan F , Casey Gerard J , Phuc Bui Q , Tien Nong T , Hung Nguyen M , Biggs Beverley-Ann
Published: June 2010

Background

Artemisinin derivatives have been used for malaria treatment in Vietnam since 1989. Reported malaria cases have decreased from 1,672,000 with 4,650 deaths in 1991, to 91,635 with 43 deaths in 2006. Current national guidelines recommend artemisinin-based combination therapy (ACT), although artesunate is still available as monotherapy through the private sector. Recent reports suggest that effectiveness of ACT and artesunate monotherapy has declined in western Cambodia. This study examinedPlasmodium falciparumresistance patterns over 10 years in southwest Vietnam in infected patients treated with artemisinin compounds.

Methods

The study was conducted in two communes in Phuoc Long district, Binh Phuoc province, 100 km west of the Cambodian border. This was chosen as a likely site for emerging artemisinin resistance because of the high prevalence ofP. falciparummalaria, and the length of time that artemisinin had been in use. Invivoandin vitromonitoring ofP. falciparumsusceptibility to anti-malarial drugs was conducted in 1998, 2001, 2004/5, and 2008/9. Patients with confirmedP. falciparummalaria received therapy with 5 or 7 days of artemisinin (1998 and 2001 respectively) or 7 days of artesunate

Results

In the four surveys, 270 patients were recruited and treated. The mean parasite clearance times differed between 1998, 2001 and 2004/5 (1.8, 2.3 and 2.1 days, P < 0.01) but not between 1998 and 2008/2009. The mean parasite clearance times were correlated with parasite density at day 0 (r = 0.4; P < 0.001). Treatment failure rates after PCR adjustment were 13.8%, 2.9%, 1.2%, and 0% respectively. Susceptibility ofP. falciparumto artemisinin inin vitrotests was stable during the period, except for a rise in EC90 and EC99 in 2001.

Conclusions

This study showed stable levels ofP. falciparumsensitivity to artemisinin compounds in the two sites over a ten-year period. The introduction of ACT in this area in 2003 may have protected against the development of artemisinin resistance. Adherence to the latest WHO and Vietnamese guidelines, which recommend ACT as first-line therapy in all malarious areas, and continued monitoring along the Vietnam-Cambodia border will be essential to prevent the spread of artemisinin resistance in Vietnam.
Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats
Authors: Honnma Hiroyuki , Endo Toshiaki , Kiya Tamotsu , Shimizu Ayumi , Nagasawa Kunihiko , Baba Tsuyoshi , Fujimoto Takashi , Henmi Hirofumi , Kitajima Yoshimitsu , Manase Kengo , Ishioka Shinichi , Ito Eiki , Saito Tsuyoshi
Published: June 2010

Background

Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.

Methods

In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).

Results

Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.

Conclusions

Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.
Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium
Authors: Zhang Lifang , Wang Dan , Jiang Wei , Edwards Dale , Qiu Weiliang , Barroilhet Lisa M , Rho Jung-hyun , Jin Lianjin , Seethappan Vanitha , Vitonis Allison , Wang Jianliu , Mok Samuel C , Crum Christopher , Cramer Daniel W , Ye Bin
Published: June 2010

Objectives

It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro-inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The major objective of this study was to explore and determine whether platelet activating factor (PAF) and receptor associated networking pathways might significantly induce malignant potential in BRCA1-mutant at-risk epithelial cells.

Methods

BRCA1-mutant ovarian epithelial cell lines including (HOSE-636, HOSE-642), BRCA1-mutant ovarian cancer cell (UWB1.289), wild type normal ovarian epithelial cell (HOSE-E6E7) and cancerous cell line (OVCA429), and the non-malignant BRCA1-mutant distal fallopian tube (fimbria) tissue specimens were used in this study. Mutation analysis, kinase microarray, western blot, immune staining, co-immune precipitation, cell cycle, apoptosis, proliferation and bioinformatic pathway analysis were applied.

Results

We found that PAF, as a potent pro-inflammatory mediator, induced significant anti-apoptotic effect in BRCA1- mutant ovarian surface epithelial cells, but not in wild type HOSE cells. With kinase microarray technology and the specific immune approaches, we found that phosphor-STAT1 was activated by 100 nM PAF treatment only in BRCA1-mutant associated at-risk ovarian epithelial cells and ovarian cancer cells, but not in BRCA1-wild type normal (HOSE-E6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that elevated PAFR expression is associated with protein-protein interactions of PAFR-FAK and FAK-STAT1 in BRCA1-mutant ovarian epithelial cells, but not in the wild-type control cells.

Conclusion

Previous studies showed that potent inflammatory lipid mediators such as PAF and its receptor (PAFR) significantly contribute to cancer progression and metastasis. Our findings suggest that these potent inflammatory lipids and receptor pathways are significantly involved in the early malignant transformation through PAFR-FAK-STAT1 networking and to block apoptosis pathway in BRCA1 dysfunctional at-risk ovarian epithelium.
A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia
Authors: Shiina Akihiro , Shirayama Yukihiko , Niitsu Tomihisa , Hashimoto Tasuku , Yoshida Taisuke , Hasegawa Tadashi , Haraguchi Tadashi , Kanahara Nobuhisa , Shiraishi Tetsuya , Fujisaki Mihisa , Fukami Goro , Nakazato Michiko , Iyo Masaomi , Hashimoto Kenji
Published: June 2010

Background

Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia.

Methods

A randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day) were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day) or placebo (n = 20) in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Positive and Negative Syndrome Scale (PANSS) scores were measured.

Results

In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention) task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial.

Conclusions

This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.
First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia
Authors: Zhou Li , Diefenbach Eve , Crossett Ben , Tran Sieu L , Ng Thomas , Rizos Helen , Rua Rejane , Wang Bin , Kapur Amit , Gandhi Kaushal , Brew Bruce J , Saksena Nitin K
Published: June 2010

Background

The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed.

Result

Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue proteome, 76 differentially expressed proteins (p < 0.05; fold change>1.25) were identified between HAD and HIV non-dementia patients, of which 36 protein spots (based on 3D appearance of spots on the images) were chosen for the mass spectrometry analysis. The large majority of identified proteins were represented in the energy metabolic (mitochondria) and signal transduction pathways. Furthermore, over 90% of the protein candidates are common to both HAD and other non-viral neurodegenerative disease, such as Alzheimer's disease. The data was further validated using specific antibodies to 4 proteins (CA2, GS, CKMT and CRMP2) by western blot (WB) in the same samples used for 2D-DIGE, with additional confirmation by immunohistochemitsry (IHC) using frontal lobe tissue from different HAD and HIV+ non-dementia patients. The validation for all 4 antibodies by WB and IHC was in concordance with the DIGE results, lending further credence to the current findings.

Conclusion

These results suggest not only convergent pathogenetic pathways for the two diseases but also the possibility of increased Alzheimer's disease (AD) susceptibility in HAD patients whose life expectancy has been significantly increased by highly active antiretroviral therapy.