bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of antinociceptive and antidiabetic effects of sertraline and amitriptyline on streptozotocin-induced diabetic rats
Authors: Mahmood Danish , Akhtar M. , Vohora Divya , Khanam Razia
Published: March 2010

Antidepressants (ADs) are frequently used for the treatment of persistent pain associated with diabetic neuropathy. The aim of this study is to investigate the antinociceptive effects of sertraline (Ser) and amitriptyline (Ami) in diabetic rats, and additionally monitoring their effects on grip strength, blood glucose and percentage glycosylated hemoglobin (GHb%) levels. Streptozotocin (STZ; 55 mg/kg, intraperitoneal [ip]) was injected in rats to induce diabetes. After 7 days, Ser (30 mg/kg) or Ami (15 mg/kg) was administered in diabetic rats orally. After 28 days drug treatment, the antinociceptive effects were evaluated using hot plate test both in diabetic and non-diabetic rats. The effects of these drugs on grip strength, blood glucose and GHb% were also measured. Ser and Ami showed antinociceptive effects in diabetic and non-diabetic rats. Both the drugs increased the grip strength reduction in STZ-induced diabetic rats. Ser reduces and Ami increases the serum glucose levels in diabetic and normal rats. Administration of Ami per se increased GHb% levels, while Ser per se has no effects. The effects of Ser (30 mg/kg, per os [po]) on glucose, GHb% and antinociceptive action on hot plate test showed an association between improved blood glucose levels and analgesia. However, the results of Ami treatment are controversial and needs further studies.
Cognitive and Linguistic Processing in the Bilingual Mind
Authors: Bialystok Ellen , Craik Fergus I. M.
Published: March 2010

The article reports research investigating the way bilingualism affects cognitive and linguistic performance across the life span. In general, bilingualism appears to have both benefits and costs. Regarding costs, bilinguals typically have lower formal language proficiency than monolinguals do; for example, they have smaller vocabularies and weaker access to lexical items. The benefits, however, are that bilinguals exhibit enhanced executive control in nonverbal tasks requiring conflict resolution, such as the Stroop and Simon tasks. These patterns and their consequences are illustrated and discussed. We also propose some suggestions regarding underlying mechanisms for these effects.
Goal-Driven Cognition and Functional Behavior
Authors: Kenrick Douglas T. , Neuberg Steven L. , Griskevicius Vladas , Becker D. Vaughn , Schaller Mark
Published: March 2010

Fundamental motives have direct implications for evolutionary fitness and orchestrate attention, memory, and social inference in functionally specific ways. Motivational states linked to self-protection and mating offer illustrative examples. When self-protective motives are aroused, people show enhanced attention to, and memory for, angry male strangers; they also perceive out-group members as especially dangerous. In contrast, when mating motives are aroused, men show enhanced attention to and memory for attractive members of the opposite sex; mating motives also lead men (but not women) to perceive sexual arousal in attractive members of the opposite sex. There are further functionally specific consequences for social behavior. For example, self-protective motives increase conformity among both men and women, whereas mating motives lead men (but not women) to engage in anticonformist behavior. Other motivational systems trigger different adaptive patterns of cognitive and behavioral responses. This body of research illustrates the highly specific consequences of fitness-relevant motivational states for cognition and behavior, and highlights the value of studying human motivation and cognition within an evolutionary framework.
Attention-Deficit/Hyperactivity Disorder
Authors: Nigg Joel T.
Published: March 2010

Several lines of research are revising our picture of attention-deficit/hyperactivity disorder (ADHD). I highlight four emerging themes. First, models from temperament and personality research have been fruitful in clarifying the basic pathways to ADHD and their relation to typical development. Second, many kinds of attention are normal in ADHD, but cognitive control and vigilance are not. These last two are among present candidates for clinical markers that may help identify causes of ADHD. Third, any one cognitive marker pertains to only a subset of the ADHD population; the syndrome’s heterogeneity increasingly is a focus of research. Fourth, along with energetic pursuit of genes related to ADHD, resurgent interest in environmental causes of ADHD is notable. New insights into environmental effects are illustrated by recent data concerning lead exposure and ADHD.
Stereotype Threat Deconstructed
Authors: Schmader Toni
Published: March 2010

More than a decade of research has demonstrated that individuals underperform in situations that remind them that they are stereotyped to do poorly. This paper explores the psychological processes that underlie these stereotype threat effects. Specifically, reminders of negative stereotypes cue uncertainty and a search for evidence that one might be confirming the stereotype. This process of monitoring for failure and suppressing negative thoughts and feelings hijacks the very cognitive mechanism—working memory—that is necessary for success on complex cognitive tasks where group differences in performance are a concern. Fortunately evidence suggests that when stigmatized individuals reappraise their experience, group differences in performance can be reduced if not eliminated.
The Origin of Cultural Differences in Cognition
Authors: Varnum Michael E. W. , Grossmann Igor , Kitayama Shinobu , Nisbett Richard E.
Published: March 2010

A large body of research documents cognitive differences between Westerners and East Asians. Westerners tend to be more analytic and East Asians tend to be more holistic. These findings have often been explained as being due to corresponding differences in social orientation. Westerners are more independent and Easterners are more interdependent. However, comparisons of the cognitive tendencies of Westerners and East Asians do not allow us to rule out alternative explanations for the cognitive differences, such as linguistic and genetic differences, as well as cultural differences other than social orientation. In this review we summarize recent developments that provide stronger support for the social orientation hypothesis.
Social Cognition Unbound
Authors: Waytz Adam , Epley Nicholas , Cacioppo John T.
Published: March 2010

People conceive of wrathful gods, fickle computers, and selfish genes, attributing human characteristics to a variety of supernatural, technological, and biological agents. This tendency to anthropomorphize nonhuman agents figures prominently in domains ranging from religion to marketing to computer science. Perceiving an agent to be humanlike has important implications for whether the agent is capable of social influence, accountable for its actions, and worthy of moral care and consideration. Three primary factors—elicited agent knowledge, sociality motivation, and effectance motivation—appear to account for a significant amount of variability in anthropomorphism. Identifying these factors that lead people to see nonhuman agents as humanlike also sheds light on the inverse process of dehumanization, whereby people treat human agents as animals or objects. Understanding anthropomorphism can contribute to a more expansive view of social cognition that applies social psychological theory to a wide variety of both human and nonhuman agents.
Traditional Bullying, Cyber Bullying, and Deviance: A General Strain Theory Approach
Authors: Hay Carter , Meldrum Ryan , Mann Karen
Published: March 2010

Agnew’s general strain theory (GST) has received significant empirical attention, but important issues remain unresolved. This study addresses three such issues. First, the authors examine the effects of bullying—a source of strain that may be consequential, but that has been neglected in GST research to date. Second, drawing from recent research on deliberate self-harm among adolescents, the authors examine the effects of bullying not just on externalizing deviance (aggressive acts committed against others and their property) but also on internalizing deviance directed against the self. Third, the authors examine these relationships separately for males and females to assess sex differences in responses to strain. These three issues are examined with self-report data collected from a sample of middle and high school students in a Southeastern state. The analysis reveals that bullying is consequential for both externalizing and internalizing forms of deviance and that these relationships are in some instances moderated by sex.
Computer Controlled Rotational MR-brake for Wrist Rehabilitation Device
Authors: Avraam More , Horodinca Mihaita , Romanescu Iulian , Preumont André
Published: March 2010

This aricle presents a novel, computer controlled, magneto-rheological (MR) brake actuated, muscular rehabilitation, and evaluation device. The first part discusses various MR brake architectures and compares them. Simple analytical formulae are developed for a set of figures of merit, which point out the role played by the various parameters. Based on this analysis, a prototype with a T-shaped rotor has been designed, built and integrated into a portable rehabilitation device. In the second part of the article, the various exercise modes of the device and its control are described. Finally, results validating the performances of the device for the pronation/supination motion of the wrist are shown.
Comments on: ‘Curvature Mode Shape-based Damage Assessment of Carbon/Epoxy Composite Beams’
Authors: Dixit A. , Hanagud S.
Published: March 2010

The primary motivation for the article sprouts from the article by Lestari et al. [Lestari, W., Qiao, P. and Hanagud, S, 2007. ‘‘Curvature Mode Shape-based Damage Assesment of Carbon/Epoxy Composite Beams,’’ Journal of Intelligent Material System and Structures, 18:189—208], published in a previous issue of this journal. The article although very useful and informative, as it conducts a wide array of experiments on different types of damages for a beam, has some discrepancies in the solution to the perturbed ordinary differential equation. The inconsistency manifests itself as a higher order effect. A possible solution to the equations is presented. Also, in this article the process is extended and the change in mass is taken into account along with change of stiffness. Only stiffness change is modeled in the original article.
3D Finite Element Analyses of Multilayer Dielectric Elastomer Actuators with Metallic Compliant Electrodes for Space Applications
Authors: Lampani Luca , Gaudenzi Paolo
Published: March 2010

A special actuator device with passive sensing capability based on dielectric elastomer was studied and specialized to be used in space applications. The work illustrates the research project modeling procedure adopted to simulate the mechanical behavior of this material based on a finite-element theory approach. The Mooney-Rivlin’s hyperelastic and Maxwell’s electrostatic models provide the theoretical basis to describe its electromechanic behavior. The validation of the procedure is performed through a numerical—experimental correlation between the response of a prototype of actuator developed by the Risø Danish research center and the 3D finite-element model simulations. An investigation concerning a possible application in the space environment of dielectric elastomer actuators is also presented.
Beam Shape Optimization for Power Harvesting
Authors: Dietl John M. , Garcia Ephrahim
Published: March 2010

A problem in piezoelectric bimorph energy harvesting is to generate the most power with limits in system mass. The authors propose a new approach: to change the shape of the beam to concentrate the strain in sections of the beam where it can contribute the most to transduction. A vibration model of beams with non-uniform width is developed and validated with shaker table tests. Three beams with different shapes are tested over a wide band, encompassing the lowest two modes of vibration. An optimal beam shape is calculated using a heuristic optimization code and the attributes of this optimal beam are discussed. Then, beam shapes are optimized to allow for increased base excitation and constrained by maximum root strain. Finally, the tip mass-to-beam mass ratio is studied parametrically, correlating increased transduction with increased beam mass.
Contesting the European Union? Why the Dutch and the French Rejected the European Constitution
Authors: Binzer Hobolt Sara , Brouard Sylvain
Published: March 2010

The process of establishing a constitution for Europe came to an end when voters in France and the Netherlands rejected the proposal. Analyzing both media coverage and survey data, this article seeks to disentangle the reasons why a majority of voters rejected the European Constitution. The authors’ findings suggest that the campaign played an important role in priming certain attitudes and that vote choices, in turn, were driven by specific issue concerns rather than general dissatisfaction with the European Union or national governments. These findings have implications not only for our understanding of direct democracy in Europe but also for the study of campaign effects.
Legal Archaeology
Authors: Novkov Julie
Published: March 2010

This article proposes a mode of analysis drawing from historical institutionalism and American political development but that is generated more organically from within the study of law. This approach, legal archaeology, focuses on the production of legal discourse while attending to the institutional boundaries and conditions around this production. Legal archaeology is particularly useful for understanding the role of law in constructing subordinated identities. Illuminating legal struggles over the boundaries of subordinated identities facilitates consideration of how subordination is institutionalized, though archaeology maintains legal institutions at the center of the analysis. The article concludes with examples of the analysis.
Bringing back the subject into management education
Authors: Vidaillet Bénédicte , Vignon Christophe
Published: March 2010

Among the critical approaches to management and organizations, one has been little explored: it is the Lacanian approach. Furthermore, this perspective has not yet been used to help develop new pedagogical approaches in the field of management education.This is what, for the last 10 years, we have undertaken to do. In this article, we first show that Lacan’s work is particularly relevant in addressing the question of subjectivity and of the construction of one’s identity in the context of work. We then present the management education programme we have implemented in order to enable the participants to question their imaginary beliefs at work and to modify their place in the organizational narratives so as to recover new scope for action. A case study helps us illustrate the processes and the effects of the method we have used. Finally, we discuss the limitations and benefits of this approach, and the precautions that should be taken by those who might wish to use it in one way or another.
Fatigue, mood and quality of life improve in MS patients after progressive resistance training
Authors: Dalgas U. , Stenager E. , Jakobsen J. , Petersen T. , Hansen HJ , Knudsen C. , Overgaard K. , Ingemann-Hansen T.
Published: March 2010

Fatigue occurs in the majority of multiple sclerosis patients and therapeutic possibilities are few. Fatigue, mood and quality of life were studied in patients with multiple sclerosis following progressive resistance training leading to improvement of muscular strength and functional capacity. Fatigue (Fatigue Severity Scale, FSS), mood (Major Depression Inventory, MDI) and quality of life (physical and mental component scores, PCS and MCS, of SF36) were scored at start, end and follow-up of a randomized controlled clinical trial of 12 weeks of progressive resistance training in moderately disabled (Expanded Disability Status Scale, EDSS: 3—5.5) multiple sclerosis patients including a Control group ( n = 15) and an Exercise group ( n = 16). Fatigue (FSS > 4) was present in all patients. Scores of FSS, MDI, PCS—SF36 and MCS—SF36 were comparable at start of study in the two groups. Fatigue improved during exercise by —0.6 (95% confidence interval (CI) —1.4 to 0.4) a.u. vs. 0.1 (95% CI —0.4 to 0.6) a.u. in controls ( p = 0.04), mood improved by —2.4 (95% CI —4.1 to 0.7) a.u. vs. 1.1 (—1.2 to 3.4) a.u. in controls ( p = 0.01) and quality of life (PCS—SF36) improved by 3.5 (95% CI 1.4—5.7) a.u. vs. —1.0 (95% CI —3.4—1.4) a.u. in controls ( p = 0.01). The beneficial effect of progressive resistance training on all scores was maintained at follow-up after further 12 weeks. Fatigue, mood and quality of life all improved following progressive resistance training, the beneficial effect being maintained for at least 12 weeks after end of intervention.
The McDonald Criteria for Multiple Sclerosis: time for clarification
Authors: Hawkes Christopher H , Giovannoni Gavin
Published: March 2010

The McDonald Criteria for Multiple Sclerosis in general have replaced the Poser criteria. Despite this, many consider that there are still areas of ambiguity. In this study, neurologists completed a questionnaire about familiarity with, usefulness and applicability of the McDonald Criteria for Multiple Sclerosis. Understanding of ‘attack’; objective clinical evidence; ‘two or more lesions’ and their ability to interpret case scenarios was evaluated. Responses were analysed overall and by skill group. Ninety-seven consultants and 30 trainees responded, of whom 37 operated a multiple sclerosis clinic (‘experts’). Some (62%) thought the McDonald Criteria for Multiple Sclerosis were useful, and 31% found them confusing or difficult to apply; 38% thought the criteria should be applied universally, others (14—28%) favoured their use for drug trials/research, and 17% rarely used them. Thirty-six (29.1%) thought the McDonald Criteria for Multiple Sclerosis specified two categories: ‘MS and not MS’, but others considered ‘possible’ or ‘probable’ multiple sclerosis were permitted. Experts understood better ‘an attack’ and ‘objective clinical evidence’. All skill groups comprehended poorly what constituted an episode of demyelination, and whether Lhermitte’s phenomenon was acceptable as evidence for cervical cord demyelination. A consistent response was given by 44—50% to ‘two or more lesions’, although this is not well defined. Criteria for primary progressive multiple sclerosis were understood well. We conclude that the McDonald Criteria for Multiple Sclerosis have improved diagnosis but areas of misinterpretation remain, particularly the definition of ‘an attack’, ‘objective clinical evidence’ and ‘two or more lesions’. There was uncertainty about how many multiple sclerosis categories were permitted and whether the terms ‘possible’ and ‘probable’ were allowable. Further clarification might allow the criteria to be applied more consistently.
Cerebrospinal fluid ATP metabolites in multiple sclerosis
Authors: Lazzarino G. , Amorini AM , Eikelenboom MJ , Killestein J. , Belli A. , Di Pietro V. , Tavazzi B. , Barkhof F. , Polman CH , Uitdehaag BMJ , Petzold A.
Published: March 2010

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis.

Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis.

The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up.

Central ATP depletion (sum of ATP metabolites >19.7 µmol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p< 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort ( r= 0.66, p= 0.001) and subgroups (relapsing—remitting patients: r= 0.79, p< 0.05 and secondary progressive/primary progressive patients: r= 0.69, p< 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration.

The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.
Playing with Gladys: A case study integrating drama therapy with behavioural interventions for the treatment of selective mutism
Authors: Phei Phei Oon
Published: March 2010

This case study examines an integrative approach combining drama therapy and the behavioural skill “shaping”, as offered to Gladys, a 5-year-old girl diagnosed with selective mutism. This study found that shaping, when implemented in the context of play, with play as the primary reinforcer, elicited from Gladys vocalization and eventually speech within a very short time. Her vocalizations allowed her to enter dramatic play, which in turn propelled spontaneous speech. This article looks at how the three elements of dramatherapy — the playspace, role-playing and dramatic projection — brought about therapeutic changes for Gladys. Aside from spontaneous speech, Gladys also developed positive self-esteem and a heightened sense of spontaneity. Subsequently, these two qualities helped her generalize her speech to new settings on her own. Gladys’s newly harnessed spontaneity further helped her become more sociable and resilient.This study advances the possibility of integrating a behavioural skill with drama therapy for the therapeutic benefits of a child with an anxiety-related condition like selective mutism.
Self-protective strategies are adaptive and increasingly complex: A beginner’s look at the DMM and ABCD models of attachment
Authors: Stacks Ann M.
Published: March 2010

Clinicians understand the importance of their clients’ past relationships on current functioning. The notion of attachment disorganization is especially salient to many clinicians because based on the traditional model of attachment it is the category in which clients with a history of relational trauma are most likely to fall. Unfortunately, lumping together what so many clinicians feel is clinically important may not inform clinical practice and the process by which attachment is assessed is beyond the reach of many clinicians. A different model of attachment, the Dynamic Maturational Model of Attachment and Adaptation offers a new lens through which to view relational trauma and to understand the ways in which danger is processed. This article describes the similarities and differences in the two models of attachment.
Benefiting from deep-level diversity: How congruence between knowledge and decision rules improves team decision making and team perceptions
Authors: Rink Floor , Ellemers Naomi
Published: March 2010

In two experiments we show how teams can benefit from the presence of multiple sources of deep-level task-related diversity. We manipulated differences (vs. similarities) in task information and personal decision rules in dyads (Study 1) and three-person teams (Study 2). The results indicate that when both sources of diversity are present, partners and team members integrate their unique knowledge and decision rules into the collaboration and report perceptions of common interests, commitment and outcome satisfaction afterwards. This is not the case when there is just one source of diversity, causing the partners and team members to possess different information, but endorse similar decision rules or vice versa. The results are discussed in light of research on congruency and identity processes.
Concerns about appearing prejudiced: Implications for anxiety during daily interracial interactions
Authors: Shelton J. Nicole , West Tessa V. , Trail Thomas E.
Published: March 2010

We investigated the relationship between Whites’ and ethnic minorities’ concerns about appearing prejudiced and anxiety during daily interracial interactions. College roommate pairs completed an individual difference measure of concerns about appearing prejudiced at the beginning of the semester. Then they completed measures of anxiety and perceptions of their roommates’ anxiety-related behaviors for 15 days. Results indicated that among interracial roommate pairs, Whites’ and ethnic minorities’ concerns about appearing prejudiced were related to their self-reported anxiety on a daily basis; but this was not the case among same-race roommate pairs. In addition, among interracial roommate pairs, roommates who were concerned about appearing prejudiced began to “leak” their anxiety towards the end of the diary period, as indicated by their out-group roommate who perceived their anxious behaviors as increasing across time, and who consequently liked them less. The implications of these findings for intergroup relations are discussed in this article.
Social exclusion of Gypsies and Travellers: health impact
Authors: Van Cleemput P.
Published: March 2010

There are striking inequalities in the health of Gypsies and Travellers, even when compared with people from other ethnic minorities or from socio-economically deprived White UK groups. In this paper we explore the long-term health impact associated with a history of persecution, social pathologisation and social exclusion of Gypsies and Travellers. A society that has demonstrated entrenched and widespread hostility towards Gypsies and Travellers has contributed to wariness about trust in outsiders and contributes to the communication barriers with health staff that are implicated in their poor access to healthcare. Many of the problems identified by health staff mirrored those identified by Gypsies and Travellers, particularly with regards to mismatched expectations and resulting conflicts. Whilst the Department of Health has recognised the extreme health inequalities experienced by Gypsies and Travellers and the need for specific action to reduce them and improve access to health care, this paper emphasises the need for an associated improved effort at all levels to seriously tackle the wider determinants of health, including societal attitudes towards Gypsies and Travellers, as well as focusing on delivery of health services. Nurses are identified as needing to play a key part as role models in challenging prejudice and discrimination.
The Effect of Teaching Experience and Specialty (Vocal or Instrumental) on Vocal Health Ratings of Music Teachers
Authors: Hackworth Rhonda S.
Published: March 2010

The current study sought to determine the relationship among music teachers’ length of teaching experience, specialty (vocal or instrumental), and ratings of behaviors and teaching activities related to vocal health. Participants ( N = 379) were experienced ( n = 208) and preservice ( n = 171) music teachers, further categorized by specialty, either vocalists ( n = 198) or instrumentalists ( n = 181). Teachers provided demographic information, vocal health ratings for selected behaviors, and ratings of perceived vocal stress in selected teaching activities. Years of teaching experience had a significant effect for four behaviors and one teaching activity. Specialty had a significant effect for two behaviors and three teaching activities. The interaction of years of teaching experience and specialty was significant for the following behaviors: clearing the throat, getting adequate sleep, and breathing secondhand smoke. The interaction of years of teaching experience and specialty was significant for the following teaching activities: verbal instruction while students play instruments, speaking over noisy classroom conditions, hall duty, and lunch duty. Overall, ratings provided by preservice teachers tend to reflect healthier practices. Suggestions for further research include instrumentalists’ perceived vocal stress, how perceptions can be shaped to aid prevention of vocal disorders in teachers, and vocal health opinions where diverse experience levels are explored more deeply.
Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation
Authors: Sieniawski Michal , Angamuthu Nithia , Boyd Kathryn , Chasty Richard , Davies John , Forsyth Peter , Jack Fergus , Lyons Simon , Mounter Philip , Revell Paul , Proctor Stephen J. , Lennard Anne L.
Published: March 2010

Enteropathy associated T-cell lymphoma (EATL) is a rare type of peripheral T-cell lymphoma. At present, there are no standardized diagnostic or treatment protocols for EATL. We describe EATL in a population-based setting and evaluate a new treatment with aggressive chemotherapy and autologous stem cell transplantation (ASCT). From 1979 onward the Scotland and Newcastle Lymphoma Group prospectively collected data on all patients newly diagnosed with lymphoma in the Northern Region of England and Scotland. Between 1994 and 1998, records of all patients diagnosed with EATL were reviewed, and 54 patients had features of EATL. Overall incidence was 0.14/100 000 per year. Treatment was systemic chemotherapy (mostly anthracycline-based chemotherapy) with or without surgery in 35 patients and surgery alone in 19 patients. Median progression-free survival (PFS) was 3.4 months and overall survival (OS) was 7.1 months. The novel regimen IVE/MTX (ifosfamide, vincristine, etoposide/methotrexate)–ASCT was piloted from 1998 for patients eligible for intensive treatment, and 26 patients were included. Five-years PFS and OS were 52% and 60%, respectively, and were significantly improved compared with the historical group treated with anthracycline-based chemotherapy (P = .01 and P = .003, respectively). EATL is a rare lymphoma with an unfavorable prognosis when treated with conventional therapies. The IVE/MTX-ASCT regimen is feasible with acceptable toxicity and significantly improved outcome.
Improved survival of children and adolescents with sickle cell disease
Authors: Quinn Charles T. , Rogers Zora R. , McCavit Timothy L. , Buchanan George R.
Published: March 2010

The survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.
Promoter choice and translational repression determine cell type–specific cell surface density of the inhibitory receptor CD85j expressed on different hematopoietic lineages
Authors: Lamar David L. , Weyand Cornelia M. , Goronzy Jörg J.
Published: March 2010

CD85j (ILT2/LILRB1/LIR-1) is an inhibitory receptor that recognizes major histocompatibility complex (MHC) class Ia and Ib alleles that are widely expressed on all cell types. On ligand recognition, CD85j diminishes kinase activity by recruiting phosphatases to motifs within its cytoplasmic domain. Within the hematopoietic system, CD85j is expressed with cell-specific patterns and cell surface densities that reflect the different roles of cell contact-mediated inhibition in these lineages. While monocytes ubiquitously have high cell surface expression, B lymphocytes start to express CD85j at intermediate levels during early B-cell maturation and natural killer (NK) cells and T cells exhibit a low level of expression on only a subset of cells. The cell-specific expression pattern is accomplished by 2 complementing but not independent mechanisms. Lymphocytes and monocytes use distinct promoters to drive CD85j expression. The lymphocyte promoter maps 13 kilobases (kb) upstream of the monocyte promoter; its use results in the inclusion of a distant exon into the 5′-untranslated region. A short sequence stretch within this exon has the unique function of repressing CD85j protein translation and is responsible for the subdued expression in lymphocytes. These cell-specific mechanisms allow tailoring of CD85j levels to the distinct roles it plays in different hematopoietic lineages.
The Apcmin mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS
Authors: Lane Steven W. , Sykes Stephen M. , Al-Shahrour Fatima , Shterental Sebastian , Paktinat Mahnaz , Lo Celso Cristina , Jesneck Jonathan L. , Ebert Benjamin L. , Williams David A. , Gilliland D. Gary
Published: March 2010

Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apcmin allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apcmin mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apcmin bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apcmin mice developed a MDS/myeloproliferative phenotype. Our data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies. These data provide a cautionary note for HSC-expansion strategies through Wnt pathway activation, provide evidence that cell extrinsic factors can contribute to the development of myeloid disease, and indicate that loss of function of APC may contribute to the phenotype observed in patients with MDS and del(5q).
Automated design of genomic Southern blot probes
Authors: Croning Mike DR , Fricker David G , Komiyama Noboru H , Grant Seth GN
Published: March 2010

Background

Sothern blotting is a DNA analysis technique that has found widespread application in molecular biology. It has been used for gene discovery and mapping and has diagnostic and forensic applications, including mutation detection in patient samples and DNA fingerprinting in criminal investigations. Southern blotting has been employed as the definitive method for detecting transgene integration, and successful homologous recombination in gene targeting experiments.

The technique employs a labeled DNA probe to detect a specific DNA sequence in a complex DNA sample that has been separated by restriction-digest and gel electrophoresis. Critically for the technique to succeed the probe must be unique to the target locus so as not to cross-hybridize to other endogenous DNA within the sample.

Investigators routinely employ a manual approach to probe design. A genome browser is used to extract DNA sequence from the locus of interest, which is searched against the target genome using a BLAST-like tool. Ideally a single perfect match is obtained to the target, with little cross-reactivity caused by homologous DNA sequence present in the genome and/or repetitive and low-complexity elements in the candidate probe. This is a labor intensive process often requiring several attempts to find a suitable probe for laboratory testing.

Results

We have written an informatic pipeline to automatically design genomic Sothern blot probes that specifically attempts to optimize the resultant probe, employing a brute-force strategy of generating many candidate probes of acceptable length in the user-specified design window, searching all against the target genome, then scoring and ranking the candidates by uniqueness and repetitive DNA element content. Using these in silico measures we can automatically design probes that we predict to perform as well, or better, than our previous manual designs, while considerably reducing design time.

We went on to experimentally validate a number of these automated designs by Southern blotting. The majority of probes we tested performed well confirming our in silico prediction methodology and the general usefulness of the software for automated genomic Southern probe design.

Conclusions

Software and supplementary information are freely available at: http://www.genes2cognition.org/software/southern_blot
Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public
Authors: Balkhy Hanan H , Abolfotouh Mostafa A , Al-Hathlool Rawabi H , Al-Jumah Mohammad A
Published: March 2010

Background

During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1) among the Saudi public.

Methods

A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic.

Results

More than half (54.3%, 840/1548) of the participants showed high concern, 43.7%(677/1548) showed a low level of knowledge, and 60.8%(941/1548) had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p < 0.001), while greater precautionary measures were taken by participants who were male (p < 0.001), older (p = 0.047), better educated (p = 0.04), and more knowledgeable (p < 0.001). More than one-third (38.3%) of participants were not convinced that the MOH reports about the disease were true, and only 16.1% of the participants reported receiving information from health providers.

Conclusions

High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.
Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: A molecular epidemiological study
Authors: Hu Yi , Hoffner Sven , Jiang Weili , Wang Weibing , Xu Biao
Published: March 2010

Background

The aim of this study was to investigate the molecular characteristics of isoniazid resistant Mycobacterium tuberculosis (MTB), as well as its contribution to the dissemination of multi-drug resistant TB (MDR-TB) in rural areas of eastern China.

Methods

A population-based epidemiological study was conducted in two rural counties of eastern China from 2004 to 2005. In total, 131 isoniazid resistant MTB isolates were molecularly characterized by DNA sequencing and genotyped by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping.

Results

The katG315Thr mutation was observed in 74 of 131 isoniazid resistant isolates and more likely to be MDR-TB (48.6%) and have mutations in rpoB gene (47.3%). Spoligotyping identified 80.2% of isoniazid resistant MTB isolates as belonging to the Beijing family. Cluster analysis by genotyping based on IS6110 RFLP, showed that 48.1% isoniazid resistant isolates were grouped into 26 clusters and katG315Thr mutants had a significantly higher clustering proportion compared to those with katG wild type (73%.vs.18%; OR, 12.70; 95%CI, 6.357-14.80). Thirty-one of the 53 MDR-TB isolates were observed in 19 clusters. Of these clusters, isoniazid resistance in MDR-TB isolates was all due to the katG315Thr mutation; 18 clusters also contained mono-isoniazid resistant and other isoniazid resistant isolates.

Conclusions

These results highlighted that isoniazid resistant MTB especially with katG315Thr is likely to be clustered in a community, develop extra resistance to rifampicin and become MDR-TB in Chinese rural settings.
HAX-1 overexpression, splicing and cellular localization in tumors
Authors: Trebinska Alicja , Rembiszewska Alina , Ciosek Karolina , Ptaszynski Konrad , Rowinski Sebastian , Kupryjanczyk Jolanta , Siedlecki Janusz A , Grzybowska Ewa A
Published: March 2010

Background

HAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis. Its involvement in regulation of apoptosis and cell migration along with some data indicating its overexpression in cancer cell lines and tumors suggests that HAX-1 may play a role in neoplastic transformation. Here we present the first systematic analysis of HAX-1 expression in several solid tumors.

Methods

Using quantitative RT-PCR, we have determined the mRNA levels ofHAX1splice variant I in several solid tumors. We have also analyzed by semiquantitative and quantitative RT-PCR the expression of fiveHAX-1splice variants in breast cancer samples and in normal tissue from the same individuals. Quantitative PCR was also employed to analyze the effect of estrogen onHAX1expression in breast cancer cell line. Immunohistochemical analysis of HAX-1 was performed on normal and breast cancer samples.

Results

The results reveal statistically importantHAX1up-regulation in breast cancer, lung cancer and melanoma, along with some minor variations in the splicing pattern. HAX-1 up-regulation in breast cancer samples was confirmed by immunohistochemical analysis, which also revealed an intriguing HAX-1 localization in the nuclei of the tumor cells, associated with strong ER status.

Conclusion

HAX-1 elevated levels in cancer tissues point to its involvement in neoplastic transformation, especially in breast cancer. The connection between HAX-1 nuclear location and ER status in breast cancer samples remains to be clarified.
Pregnane × Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation
Authors: Raynal Caroline , Pascussi Jean-Marc , Leguelinel Géraldine , Breuker Cyril , Kantar Jovana , Lallemant Benjamin , Poujol Sylvain , Bonnans Caroline , Joubert Dominique , Hollande Frédéric , Lumbroso Serge , Brouillet Jean-Paul , Evrard Alexandre
Published: March 2010

Background

Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11) is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR), we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan.

Results

PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies.

Conclusion

Our results demonstrate that tumoral metabolism of SN38 is affected by PXR and point to potential therapeutic significance of PXR quantification in the prediction of irinotecan response. Furthermore, our observations are pharmacologically relevant since many patients suffering from cancer diseases are often exposed to co-medications, food additives or herbal supplements able to activate PXR. A substantial part of the variability observed among patients might be caused by such interactions
Nitric Oxide Synthase Modulates CFA-Induced Thermal Hyperalgesia through Cytokine Regulation in Mice
Authors: Chen Yong , Boettger Michael K , Reif Andreas , Schmitt Angelika , Üçeyler Nurcan , Sommer Claudia
Published: March 2010

Background:

Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process.

Results:

Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-10), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-10, and IL-10 following CFA, overall corroborating the inhibitor data.

Conclusion:

These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.