bluuebunny/crossref_metadata_2025 huggingface dataset:
Test–Retest Reliability of Two Patient-Report Measures for Use in Adults With ADHD
Authors: Matza Louis S. , Van Brunt David L. , Cates Charlotte , Murray Lindsey T.
Published: September 2010

Aims: Childhood attention-deficit/hyperactivity disorder (ADHD) frequently persists into adulthood and continues to impair health-related quality of life (HRQL). Thus, it is important to have validated symptom and HRQL measures for assessing treatment outcomes in this population. The purpose of the current analysis was to assess test-retest reliability of two measures designed specifically for adults with ADHD: the Adult ADHD Self-Report Screener (ASRS) and the Adult ADHD Quality of Life Measure (AAQoL). Methods: Data were collected at a US clinic specializing in the treatment of adult ADHD. Patients completed the ASRS (six-item ADHD symptom screening version) and the AAQoL (a 29-item condition-specific HRQL measure) at two visits, two weeks apart. At the second visit, patients also completed a measure of symptom stability so that test-retest reliability could be examined in the stable population. Test-retest reliability was examined through intraclass correlations (ICC) and t-tests comparing scores from the two visits. Results: A total of 74 participants were enrolled (62.2% male; mean age = 38.6 years), and 43 of these participants attended both visits and were stable between visits (65.1% male; mean age = 39.3 years). The ICC assessing the association between Visit 1 and Visit 2 ASRS scores was 0.86, and the ICCs for the AAQoL subscales were 0.88 (Life Productivity), 0.75 (Psychological Health), 0.74 (Life Outlook), 0.78 (Relationships), and 0.86 (total score). The t-tests found no statistically significant differences between Visit 1 and Visit 2 scores for the ASRS or AAQoL. Conclusions: The ASRS and AAQoL demonstrated good test-retest reliability. Findings add to previous results suggesting that these instruments are useful outcome measures for treatments of ADHD in adults. ( J. of Att. Dis. 2011; 15(7) 557-563)
Exploring Language Profiles for Children With ADHD and Children With Asperger Syndrome
Authors: Helland Wenche Andersen , Biringer Eva , Helland Turid , Heimann Mikael
Published: September 2010

Objective: The aims of the present study was to investigate communication impairments in a Norwegian sample of children with ADHD and children with Asperger syndrome (AS) and to explore whether children with ADHD can be differentiated from children with AS in terms of their language profiles on the Norwegian adaptation of the Children’s Communication Checklist Second Edition (CCC-2). Method: The CCC-2 was completed by the parents, and altogether, 77 children aged between 6 and 15 years participated in the study. Results: Communication impairments were as common in a group of children with ADHD as in a group of children with AS. Although a similar pattern appeared on most CCC-2 scales, children with ADHD and children with AS could be distinguished from each other in terms of their language profiles on the subscales assessing stereotyped language and nonverbal communication. Conclusion: Language abilities should be taken into account when standard assessments of ADHD and AS are performed and before therapies are initiated.
Teacher Management Practices for First Graders With Attention Problems
Authors: Murray Desiree W. , Rabiner David L. , Hardy Kristina K.
Published: September 2010

Objective: To examine whether teacher reports of accommodations and interventions for inattentive first graders are consistent with best practice guidelines. Method: A total of 36 teachers completed the Teacher Management Questionnaire (TMQ) for 92 students in five predominantly low-income, minority schools. The TMQ is a newly developed measure designed to assess the frequency with which teachers implement a variety of accommodations and interventions with individual students. Additional teacher and student background data were collected on the inattentive sample, including behavior ratings and academic testing. Results: Teachers reported variable implementation of different management strategies, with more frequent use of class-wide structure and organizational interventions, and less frequent assignment modifications and individual behavior plans. Greater use of some strategies was reported for inattentive students and those with additional risk characteristics such as oppositional behavior and school-based referrals. Conclusion: Teachers appear to differentiate some management strategies based on the presence of attention problems, although their self-reported implementation is not well aligned with best practice guidelines.
Self-Reported Inattention in Early Adolescence in a Community Sample
Authors: Connors Laura L. , Connolly Jennifer , Toplak Maggie E.
Published: September 2010

Objective : Inattention is typically associated with ADHD, but less research has been done to examine the correlates of self-reported inattention in youth in a community sample. Method: Associations among self-reported inattention, parent-reported inattention, and self-reported psychopathology in children aged 10 to 11 years are examined. Self-reported inattention is also examined as a predictor of outcomes in peer relationships and victimization at ages 10 and 11 and in peer relationships at ages 14 and 15. Results: Children’s self-reports of inattention correlate with parental reports and are associated with self-reports of hyperactivity-impulsivity, depression, anxiety, and conduct problems. Participants in the high-inattention group are at greater risk for victimization and poor peer relationships at ages 10 and 11 years after covarying for psychopathology ratings. Self-reported inattention uniquely predicts poor peer relationships longitudinally at age 14 and 15 years. Conclusion: This study highlights the importance of examining children’s self-report of inattention and identifies inattention as a risk factor for current and later outcomes.
Core ADHD Symptom Improvement With Atomoxetine Versus Methylphenidate
Authors: Hazell Philip L. , Kohn Michael R. , Dickson Ruth , Walton Richard J. , Granger Renee E. , van Wyk Gregory W.
Published: September 2010

Objective: Previous studies comparing atomoxetine and methylphenidate to treat ADHD symptoms have been equivocal. This noninferiority meta-analysis compared core ADHD symptom response between atomoxetine and methylphenidate in children and adolescents. Method: Selection criteria included randomized, controlled design; duration 6 weeks; and assessment of ADHD Rating Scale–IV–Parent Version: Investigator Administered and Scored (ADHDRS) scores. Six-week response rates, defined as ≥40% reduction in ADHDRS total score, were compared using a noninferiority margin of −15%. Results: Seven studies met inclusion criteria ( N = 1,368). After 6 weeks, 53.6% (95% confidence interval [CI] 48.6%-58.4%) of atomoxetine-treated patients ( n = 811) had responded compared with 54.4% (47.6%-61.1%) for methylphenidate ( n = 557), with atomoxetine demonstrating noninferiority to methylphenidate (absolute difference −0.9%, 95% CI −9.2%-7.5%). Conclusion: After 6 weeks of treatment atomoxetine and methylphenidate had comparable efficacy in reducing core ADHD symptoms in children and adolescents.
Guests and hosts — the global market in international higher education: Reflections on the Japan—UK axis in study abroad
Authors: Walker Patricia
Published: September 2010

Taking as a starting point the present ubiquity of international student mobility, contrasting paradigms of international study are offered through a critical examination of two nations. The UK is presented as a leading host nation and provider of international higher education, significant revenue from which is central to the prosperity of the country’s universities. Japan is viewed as historically a major consumer of international education abroad and importer of foreign educational goods and services. The article concludes with some thoughts on a re-positioning of Japan as provider of international education for South-East Asia.
The Irish press and the Iraq War: Real world cues, news values and the political calibration effect
Authors: O'Regan Mary
Published: September 2010

This article presents the findings of a descriptive content analysis of three Irish ‘quality’ newspapers’ coverage of issues relating to the Iraq War during the period from 1 September 2002 to 31 December 2007 — The Irish Times, the Irish Independent and the Sunday Independent. It addresses the shortcoming in existing research on the Irish media’s coverage of the Iraq War and also contributes to the body of research already undertaken on different international media’s coverage of this war. Its central focus explores the influences that different contextually specific political, cultural and news factors have on media reportage. It is broadly situated within the agenda-setting research paradigm, but advocates a number of theoretical extensions of this paradigm. In particular, it is argued that rather than viewing media foreign news agendas as simplistic byproducts of media—political relations, they can be more usefully conceptualized as the outcomes of different processes of interaction between ‘real world’ cues defining the wider political environment and media factors, such as news values and sourcing strategies.
Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques
Authors: Parker Raphaëlle , Dutrieux Jacques , Beq Stéphanie , Lemercier Brigitte , Rozlan Sandra , Fabre-Mersseman Véronique , Rancez Magali , Gommet Céline , Assouline Brigitte , Rancé Iann , Lim Annick , Morre Michel , Cheynier Rémi
Published: September 2010

Interferon-α (IFN-α)–based therapy is presently the standard treatment for hepatitis C virus (HCV)–infected patients. Despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for HIV/HCV-coinfected patients. Interleukin-7 (IL-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate T-cell restoration in immunodeficient patients. The purpose of this study was to evaluate, in simian immunodeficiency virus-infected rhesus macaques, the relevance of IL-7 therapy as a means to overcoming IFN-α–induced lymphopenia. We showed that low-dose IFN-α treatment induced strong lymphopenia in chronically infected monkeys. In contrast, high-dose IFN-α treatment stimulated IL-7 production, leading to increased circulating T-cell counts. Moreover, IL-7 therapy more than abrogated the lymphopenic effect of low-dose IFN-α. Indeed, the association of both cytokines resulted in increased circulating T-cell counts, in particular in the naive compartments, as a consequence of central and peripheral homeostatic functions of the IL-7. Finally, reduced PD-1 expression by memory CD8+ T cells and transient T-cell repertoire diversification were observed under IL-7 therapy. Our data strongly suggest that IL-7 immunotherapy will be of substantial benefit in the treatment of HIV/HCV coinfection and should enhance the likelihood of HCV eradication in poorly responding patients.
B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy
Authors: Moir Susan , Buckner Clarisa M. , Ho Jason , Wang Wei , Chen Jenny , Waldner Amy J. , Posada Jacqueline G. , Kardava Lela , O'Shea Marie A. , Kottilil Shyam , Chun Tae-Wook , Proschan Michael A. , Fauci Anthony S.
Published: September 2010

Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4+ but not CD8+ T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early- compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage.
Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up
Authors: Burt Richard K. , Craig Robert M. , Milanetti Francesca , Quigley Kathleen , Gozdziak Paula , Bucha Jurate , Testori Alessandro , Halverson Amy , Verda Larissa , de Villiers Willem J. S. , Jovanovic Borko , Oyama Yu
Published: September 2010

We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti–tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34+ selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.
Multiple genetic switches spontaneously modulating bacterial mutability
Authors: Chen Fang , Liu Wei-Qiao , Eisenstark Abraham , Johnston Randal N , Liu Gui-Rong , Liu Shu-Lin
Published: September 2010

Background

All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. The DNA mismatch repair (MMR) system is essential for maintaining genetic stability and defects in MMR lead to high mutability. Evolution is driven by genetic novelty, such as point mutation and lateral gene transfer, both of which require genetic mutability. However, normally a functional MMR system would strongly inhibit such genomic changes. Our previous work indicated that MMR gene allele conversion between functional and non-functional states through copy number changes of small tandem repeats could occur spontaneously via slipped-strand mis-pairing during DNA replication and therefore may play a role of genetic switches to modulate the bacterial mutability at the population level. The open question was: when the conversion from functional to defective MMR is prohibited, will bacteria still be able to evolve by accepting laterally transferred DNA or accumulating mutations?

Results

To prohibit allele conversion, we "locked" the MMR genes through nucleotide replacements. We then scored changes in bacterial mutability and found that Salmonella strains with MMR locked at the functional state had significantly decreased mutability. To determine the generalizability of this kind of mutability 'switching' among a wider range of bacteria, we examined the distribution of tandem repeats within MMR genes in over 100 bacterial species and found that multiple genetic switches might exist in these bacteria and may spontaneously modulate bacterial mutability during evolution.

Conclusions

MMR allele conversion through repeats-mediated slipped-strand mis-pairing may function as a spontaneous mechanism to switch between high genetic stability and mutability during bacterial evolution.
Characterization of bacterial-type phosphoenolpyruvate carboxylase expressed in male gametophyte of higher plants
Authors: Igawa Tomoko , Fujiwara Masayuki , Tanaka Ichiro , Fukao Yoichiro , Yanagawa Yuki
Published: September 2010

Background

Phosphoenolpyruvate carboxylase (PEPC) is a critical enzyme catalyzing the β-carboxylation of phosphoenolpyruvate (PEP) to oxaloacetate, a tricarboxylic acid (TCA) cycle intermediate. PEPC typically exists as a Class-1 PEPC homotetramer composed of plant-type PEPC (PTPC) polypeptides, and two of the subunits were reported to be monoubiquitinated in germinating castor oil seeds. By the large-scale purification of ubiquitin (Ub)-related proteins from lily anther, two types of PEPCs, bacterial-type PEPC (BTPC) and plant-type PEPC (PTPC), were identified in our study as candidate Ub-related proteins. Until now, there has been no information about the properties of the PEPCs expressed in male reproductive tissues of higher plants.

Results

Expression analyses showed that lily BTPC (LlBTPC) and Arabidopsis BTPC (AtBTPC) were significantly expressed in pollen. The fusion protein AtBTPC-Venus localized in the cytoplasm of the vegetative cell (VC). Both LlBTPC and AtBTPC expression initiated after the last mitosis before pollen germination. Lily PTPC (LlPTPC) and monoubiquitinated LlPTPC (Ub-LlPTPC) remained at constant levels during pollen development. In late bicellular pollen of lily, LlBTPC forms a hetero-octameric Class-2 PEPC complex with LlPTPC to express PEPC activity.

Conclusion

Our results suggest that an LlBTPC:Ub-LlPTPC:LlPTPC complex is formed in the VC cytoplasm during late pollen development. Both LlBTPC and AtBTPC expression patterns are similar to the patterns of the appearance of storage organelles during pollen development in lily and Arabidopsis, respectively. Therefore, BTPC is thought to accelerate the metabolic flow for the synthesis of storage substances during pollen maturation. Our study provides the first characterization of BTPC in pollen, the male gametophyte of higher plants.
Trends in HIV & syphilis prevalence and correlates of HIV infection: results from cross-sectional surveys among women attending ante-natal clinics in Northern Tanzania
Authors: Kumogola Yusufu , Slaymaker Emma , Zaba Basia , Mngara Julius , Isingo Raphael , Changalucha John , Mwidunda Patrick , Kimaro Daniel , Urassa Mark
Published: September 2010

Background

Sentinel surveillance for HIV in ante-natal clinics (ANC) remains the primary method for collecting timely trend data on HIV prevalence in most of sub-Saharan Africa. We describe prevalence of HIV and syphilis infection and trends over time in HIV prevalence among women attending ante-natal clinics (ANC) in Magu district and Mwanza city, part of Mwanza region in Northern Tanzania. HIV prevalence from ANC surveys in 2000 and 2002 was 10.5% and 10.8% respectively. In previous rounds urban residence, residential mobility, the length of time sexually active before marriage, time since marriage and age of the partner were associated with HIV infection.

Methods

A third round of HIV sentinel surveillance was conducted at ante-natal clinics in Mwanza region, Tanzania during 2006. We interviewed women attending 27 ante-natal clinics. In 15 clinics we also anonymously tested women for syphilis and HIV infection and linked these results to the questionnaire data.

Results

HIV prevalence was 7.6% overall in 2006 and 7.4% at the 11 clinics used in previous rounds. Geographical variations in HIV prevalence, apparent in previous rounds, have largely disappeared but syphilis prevalence is still higher in rural clinics. HIV prevalence has declined in urban clinics and is stable in rural clinics. The correlates of HIV infection have changed over time. In this round older age, lower gravidity, remarriage, duration of marriage, sexual activity before marriage, long interval between last birth and pregnancy and child death were all associated with infection.

Conclusions

HIV prevalence trends concur with results from a community-based cohort in the region. Correlates of HIV infection have also changed and more proximate, individual level factors are now more important, in line with the changing epidemiology of infection in this population.
Intraabdominal and retroperitoneal soft-tissue sarcomas - outcome of surgical treatment in primary and recurrent tumors
Authors: Sogaard Ane S , Laurberg Jacob M , Sorensen Mette , Sogaard Ole S , Wara Pal , Rasmussen Peter , Laurberg Soren
Published: September 2010

Background

Surgery is the only curative treatment for intraabdominal and retroperitoneal sarcoma (IaRS). Little is known about how to treat patients with recurrence. We here report the outcome in primary and recurrent sarcoma treated at the Sarcoma Center in Aarhus, Denmark.

Methods

All patients evaluated for IaRS from June 1998 to May 2008 were enrolled and data on symptoms, signs, means of diagnosis, extent of surgery, perioperative complications, mortality and long time survival were registered. Primary and first-recurrence sarcomas were analyzed separately.

Results

Sixty-five of 73 primary and 22 of 28 first-recurrence IaRS had surgery. Fifty-three (82%) and 11 (50%) patients achieved radical R0 resection. Age and radicality of surgery were independent predictors of death, while recurrence of sarcoma was not. Perioperative mortality was 2.3%. 5-year survival was 70.2% for primary and 51.8% for first-recurrent sarcomas. However, patients with radical surgery had 5-year survival of over 70% in both the primary and recurrent group.

Conclusions

The radicality of surgery is the most important prognostic factor. Patients with recurrence have an equally good prognosis as those with primary sarcoma if radicality is achieved and such surgery should not be considered only as a palliative effort.
Dual targeting of CCR2 and CX3CR1 in an arterial injury model of vascular inflammation
Authors: Jerath Maya R , Liu Peng , Struthers Mary , DeMartino Julie A , Peng Roche , Peterson Laurence B , Cumiskey Anne-Marie , Yang Lihu , Rojas Mauricio , Patel Dhavalkumar D , Fong Alan M
Published: September 2010

Objectives

The chemokine receptors CCR2 and CX3CR1 are important in the development of coronary artery disease. The purpose of this study is to analyze the effect of a novel CCR2 inhibitor in conjunction with CX3CR1 deletion on vascular inflammation.

Methods

The novel CCR2 antagonist MRL-677 was characterized using an in vivo model of monocyte migration. To determine the relative roles of CCR2 and CX3CR1 in vascular remodeling, normal or CX3CR1 deficient mice were treated with MRL-677. After 14 days, the level of intimal hyperplasia in the artery was visualized by paraffin sectioning and histology of the hind limbs.

Results

MRL-677 is a CCR2 antagonist that is effective in blocking macrophage trafficking in a peritoneal thioglycollate model. Intimal hyperplasia resulting from vascular injury was also assessed in mice. Based on the whole-blood potency of MRL-677, sufficient drug levels were maintained for the entire 14 day experimental period to afford good coverage of mCCR2 with MRL-677. Blocking CCR2 with MRL-677 resulted in a 56% decrease in the vascular injury response (n = 9, p < 0.05) in normal animals. Mice in which both CCR2 and CX3CR1 pathways were targeted (CX3CR1 KO mice given MRL-677) had an 88% decrease in the injury response (n = 6, p = 0.009).

Conclusion

In this study we have shown that blocking CCR2 with a low molecular weight antagonist ameliorates the inflammatory response to vascular injury. The protective effect of CCR2 blockade is increased in the presence of CX3CR1 deficiency suggesting that CX3CR1 and CCR2 have non-redundant functions in the progression of vascular inflammation.
Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion
Authors: Jiang Wanglin , Zhang Shuping , Fu Fenghua , Zhu Haibo , Hou Jian
Published: September 2010

Background

Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of Lamiophlomis rotata (Benth.) Kudo. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo.

Methods

For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h.

Results

ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation.

Conclusion

These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway.
Isolation and characterization of a virus (CvV-BW1) that infects symbiotic algae of Paramecium bursaria in Lake Biwa, Japan
Authors: Hoshina Ryo , Shimizu Mayumi , Makino Yoichi , Haruyama Yoshihiro , Ueda Shin-ichiro , Kato Yutaka , Kasahara Masahiro , Ono Bun-ichiro , Imamura Nobutaka
Published: September 2010

Background

We performed an environmental study of viruses infecting the symbiotic single-celled algae of Paramecium bursaria (Paramecium bursaria Chlorella virus, PBCV) in Lake Biwa, the largest lake in Japan. The viruses detected were all Chlorella variabilis virus (CvV = NC64A virus). One of them, designated CvV-BW1, was subjected to further characterization.

Results

CvV-BW1 formed small plaques and had a linear DNA genome of 370 kb, as judged by pulsed-field gel electrophoresis. Restriction analysis indicated that CvV-BW1 DNA belongs to group H, one of the most resistant groups among CvV DNAs. Based on a phylogenetic tree constructed using the dnapol gene, CvV was classified into two clades, A and B. CvV-BW1 belonged to clade B, in contrast to all previously identified virus strains of group H that belonged to clade A.

Conclusions

We conclude that CvV-BW1 composes a distinct species within C. variabilis virus.
Facilitation of the Inhibitory Transmission by Gastrin-Releasing Peptide in the Anterior Cingulate Cortex
Authors: Cao XiaoYan , Mercaldo Valentina , Li Pingyang , Wu Long-Jun , Zhuo Min
Published: September 2010

Gastrin-releasing peptide (GRP) has been proposed as a peptidergic molecule for behavioral fear and itching. Immunohistochemistry and in situ hybridization studies have shown that GRP and GRP receptor are widely distributed in forebrain areas. Less information is available for the functional action for GRP in the prefrontal cortex including the anterior cingulate cortex (ACC). Here we used whole-cell patch-clamp recording technique to study the modulation of synaptic transmission by GRP in the ACC. We found that GRP increased the frequency of sIPSCs recorded while had no significant effect on sEPSCs in ACC pyramidal neurons. The facilitatory effect of GRP on sIPSCs was blocked by the GRP receptor antagonist, RC3095. In the presence of TTX, however, GRP had no effect on the mIPSCs. Therefore, activation of GRP receptor may facilitate the excitation of the interneurons and enhanced spontaneous GABAergic, but not glutamatergic neurotransmission. Similar results on GRP modulation of GABAergic transmission were observed in the insular cortex and amygdala, suggesting a general possible effect of GRP on cortical inhibitory transmission. Our results suggest that GRP receptor is an important regulator of inhibitory circuits in forebrain areas.
Differential Expression of ATP7A, ATP7B and CTR1 in Adult Rat Dorsal Root Ganglion Tissue
Authors: Ip Virginia , Liu Johnson J , Mercer Julian FB , McKeage Mark J
Published: September 2010

Background:

ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg) or drug vehicle twice weekly for 8 weeks.

Results:

In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H). High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals.

Conclusions:

In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of distinct subsets of sensory neurons, and could influence the transport and neurotoxicity of oxaliplatin.
Injury Induced Activation of Extracellular Signal-Regulated Kinase (ERK) in the Rat Rostral Ventromedial Medulla (RVM) is Age Dependant and Requires the Lamina I Projection Pathway
Authors: Géranton Sandrine M , Tochiki Keri K , Chiu Winnie WY , Stuart Sarah A , Hunt Stephen P
Published: September 2010

Descending controls originating in part from the rostral ventromedial medulla (RVM) regulate the excitability of dorsal horn neurons and maintain peripheral pain states. Activation of extracellular signal regulated kinase (ERK) in RVM neurons has been shown following peripheral inflammation and is involved in generating the accompanying inflammatory hyperalgesia. Here, we show that spared nerve injury (SNI), a model of neuropathic pain, results in an increase in ERK activity in RVM neurons of adult rats 3 and 8 days following surgery. We carried out two experimental procedures to demonstrate that this increase in ERK activation was related to the increased mechanical sensitivity associated with SNI. First, we showed that lesions of the lamina I/III ascending pathway from the dorsal horn attenuated both mechanical hyperalgesia and ERK activation in the RVM. Second, we performed SNI in P10 rats. At this age, SNI did not result in mechanical hypersensitivity, as previously shown, and did not activate ERK in the RVM. Finally, the percentage of pERK expressing neurones that were also serotonergic was always around 60%, independent of pain state and age, indicating an important role for serotonin in descending controls of pain states.
Meis1 specifies positional information in the retina and tectum to organize the zebrafish visual system
Authors: Erickson Timothy , French Curtis R , Waskiewicz Andrew J
Published: September 2010

Background

During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.

Results

meis1 is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1 expression and an upregulation in follistatin expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates ephrin gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.

Conclusions

In this work we describe a novel role for Meis1 in regulating Bmp signalling and in specifying temporal identity in the retina. By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system.
Intronic motif pairs cooperate across exons to promote pre-mRNA splicing
Authors: Ke Shengdong , Chasin Lawrence A
Published: September 2010

Background

A very early step in splice site recognition is exon definition, a process that is as yet poorly understood. Communication between the two ends of an exon is thought to be required for this step. We report genome-wide evidence for exons being defined through the combinatorial activity of motifs located in flanking intronic regions.

Results

Strongly co-occurring motifs were found to specifically reside in four intronic regions surrounding a large number of human exons. These paired motifs occur around constitutive and alternative exons but not pseudo exons. Most co-occurring motifs are limited to intronic regions within 100 nucleotides of the exon. They are preferentially associated with weaker exons. Their pairing is conserved in evolution and they exhibit a lower frequency of single nucleotide polymorphism when paired. Paired motifs display specificity with respect to distance from the exon borders and in constitutive versus alternative splicing. Many resemble binding sites for heterogeneous nuclear ribonucleoproteins. Specific pairs are associated with tissue-specific genes, the higher expression of which coincides with that of the pertinent RNA binding proteins. Tested pairs acted synergistically to enhance exon inclusion, and this enhancement was found to be exon-specific.

Conclusions

The exon-flanking sequence pairs identified here by genomic analysis promote exon inclusion and may play a role in the exon definition step in pre-mRNA splicing. We propose a model in which multiple concerted interactions are required between exonic sequences and flanking intronic sequences to effect exon definition.
A novel MEK2/PI3Kδ pathway controls the expression of IL-1 receptor antagonist in IFN-β-activated human monocytes
Authors: Brandt Karim J , Carpintero Rakel , Gruaz Lyssia , Molnarfi Nicolas , Burger Danielle
Published: September 2010

sIL-1Ra production induced by IFN-β in human monocytes requires the activation of MEK2 upstream of PI3Kδ, MEK1, and ERK1/2 activation being dispensable.

IFN-β and sIL-1Ra play crucial roles in the regulation of innate immunity and inflammation. IFN-β, which is widely used to improve the course of relapsing, remitting multiple sclerosis, induces the production of sIL-1Ra in human monocytes through mechanisms that remain largely unknown. In this study, we identified PI3Kδ and MEK2 as key elements that control sIL-1Ra production in isolated human monocytes activated by IFN-β. Blockade of MEK2, but not of MEK1, by inhibitors and siRNA prevented IFN-β-induced PI3Kδ recruitment to the membrane, Akt phosphorylation, and sIL-1Ra production, suggesting that MEK2 acted upstream of PI3Kδ. Furthermore, ERK1/2, the only identified substrates of MEK1/2 to date, are dispensable for sIL-1Ra production in response to IFN-β stimulation. Upon IFN-β activation, MEK2 and PI3Kδ are translocated to monocyte membranes. These data suggest that MEK1 and MEK2 display different, nonredundant functions in IFN-β signaling. That neither MEK1 nor ERK1/2 play a part in this mechanism is also an unexpected finding that gives rise to a better understanding of the MAPK signaling network. Together, these findings demonstrate that IFN-β triggers an atypical MEK2/PI3Kδ signaling cascade to regulate sIL-1Ra expression in monocytes. The premise that MEK1 and MEK2 play a part in the induction of the proinflammatory cytokine, IL-1β in human monocytes provides a rationale for an alternative, IFN-β-mediated pathway to induce/enhance sIL-1Ra production and thus, to dampen inflammation.
Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium
Authors: Smith Sonali M. , van Besien Koen , Karrison Theodore , Dancey Janet , McLaughlin Peter , Younes Anas , Smith Scott , Stiff Patrick , Lester Eric , Modi Sanjiv , Doyle L. Austin , Vokes Everett E. , Pro Barbara
Published: September 2010

Purpose

Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.

Patients and Methods

We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas).

Results

Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis.

Conclusions

Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.
Administrative Challenges Facing Nonprofit Worksites Providing Work or Work-like Experiences for Welfare Recipients
Authors: Kissane Rebecca Joyce
Published: September 2010

Over the last decade, neoliberal welfare policies expanded nonprofit organizations' role in the welfare state. This change resulted in the organizational emergence of numerous “welfare internships” (i.e., situations where welfare recipients engage in work experiences to fulfill work requirements for little or no pay), whose existence and impacts have been understudied. Using qualitative interviews with nonprofit directors, this article explores the bureaucratic face of neoliberal welfare policies through detailing how two types of welfare internships (“intermediary internships” and “client internships”) develop, the motivations behind them, and the problems they present. This article examines the relevance of these impacts for the welfare-to-work and nonstandard employment literatures and describes potential implications for policymakers.
Fatal Hydrocodone Overdose in a Child: Pharmacogenetics and Drug Interactions
Authors: Madadi Parvaz , Hildebrandt Doris , Gong Inna Y. , Schwarz Ute I. , Ciszkowski Catherine , Ross Colin J. D. , Sistonen Johanna , Carleton Bruce C. , Hayden Michael R. , Lauwers Albert E. , Koren Gideon
Published: September 2010

Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.
Changes in Children's Physical Activity Over 12 Months: Longitudinal Results From the SPEEDY Study
Authors: Corder Kirsten , van Sluijs Esther M. F. , Ekelund Ulf , Jones Andrew P. , Griffin Simon J.
Published: September 2010

OBJECTIVE:

We measured physical activity changes among 10-year-old British children over 12 months and assessed biological and demographic determinants.

METHODS:

Physical activity was measured with accelerometers (counts per minute) over ≥3 days at baseline and 1 year later in a prospective study of 844 children (41.6% male; mean ± SD baseline age: 10.2 ± 0.3 years) from 92 schools. Meeting physical activity recommendations was defined as ≥60 minutes/day at ≥2000 counts per minute. Biological (height, weight, and fat percentage) and demographic factors (gender, rural/urban home location, and socioeconomic status) were assessed at baseline. Associations between physical activity changes and multiple factors were studied.

RESULTS:

Physical activity decreased over 1 year (baseline: 665.7 ± 209.8 counts per minute; follow-up: 623.2 ± 179.2 counts per minute; P < .001), with 70.4% of children meeting physical activity recommendations at the baseline evaluation and 65.8% at the follow-up evaluation (P < .001). The decrease occurred mainly on weekends (−47.2 ± 395.8 counts per minute; P = .002), with no significant change on weekdays (8.0 ± 201.6 counts per minute; P = .20). Girls (P < .001), participants with greater body fat percentage (P = .001), and participants of higher socioeconomic status (P = .008) were more likely to exhibit physical activity decreases.

CONCLUSIONS:

Physical activity decreased over 1 year among children in primary school, predominantly during the weekend. Because these children were relatively active at baseline, prevention of physical activity decreases in childhood, particularly among girls and on weekends, may be a suitable health promotion target.
Heritability of Apnea of Prematurity: A Retrospective Twin Study
Authors: Bloch-Salisbury Elisabeth , Hall Mei Hua , Sharma Priya , Boyd Theonia , Bednarek Francis , Paydarfar David
Published: September 2010

BACKGROUND:

Apnea of prematurity (AOP) is a disturbance in respiratory rhythm defined by idiopathic pauses in breathing that reduce blood oxygen levels and/or heart rate. It is a major clinical problem among preterm infants.

OBJECTIVES:

The primary goal of this study was to estimate the genetic susceptibility to AOP in a cohort of preterm twins. A secondary aim was to identify risk factors associated with AOP in this cohort.

METHODS:

A single-center, retrospective study (2000–2008) was performed by using data from 317 premature twin pairs (<36 weeks' gestational age). Heritability estimates were determined by comparing intrapair AOP concordance between 56 monozygotic and 161 dizygotic twin pairs by using structural equation modeling. Risk factors of AOP among a cohort of 543 premature twins were assessed by using mixed-effects logistic regression.

RESULTS:

The heritability of AOP was 87% (95% confidence interval [CI]: 0.64–0.97) among same-gender twins. A gender-dependent model revealed that genetic factors accounted for 99% of the variance in male twins (95% CI: 0.89–1.00) and 78% of the variance in female twins (95% CI: 0.49–0.94). Significant risk factors for AOP were low gestational age (P < .001), cesarean delivery (P = .017), and conception through assisted reproductive technologies (P = .008).

CONCLUSIONS:

These findings suggest that AOP has an important genetic basis underlying this developmental-related disorder of respiratory control. Future genomic studies may provide information on pathophysiological mechanisms that underlie AOP.
Retinol Status of Newborn Infants Is Associated With Congenital Diaphragmatic Hernia
Authors: Beurskens Leonardus W. J. E. , Tibboel Dick , Lindemans Jan , Duvekot Johannes J. , Cohen-Overbeek Titia E. , Veenma Danielle C. M. , de Klein Annelies , Greer John J. , Steegers-Theunissen Régine P. M.
Published: September 2010

OBJECTIVE:

Genetic analyses in humans suggest a role for retinoid-related genes in the pathogenesis of congenital diaphragmatic hernia (CDH). The goal of this study was to investigate the vitamin A status of mothers and their newborns in association with CDH.

METHODS:

We conducted a hospital-based, case-control study with 22 case and 34 control mothers and their newborns. In maternal and cord blood samples, retinol and retinol-binding protein (RBP) levels were measured with high-performance liquid chromatography and an enzyme-linked immunosorbent assay, respectively. Univariate and multivariate logistic regression analyses were performed to determine crude and adjusted risk estimates.

RESULTS:

Case newborns had significantly lower levels of retinol (0.60 vs 0.76 μmol/L; P = .003) and RBP (5.42 vs 7.11 mg/L; P = .02) than did control newborns. The multivariate logistic regression analysis showed lower levels of retinol and RBP in association with CDH risk; the odds ratio for retinol levels of <15th percentile (<0.61 μmol/L) was 11.11 (95% confidence interval: 2.54–48.66; P = .001), and that for RBP levels of <15th percentile (<4.54 mg/L) was 4.00 (95% confidence interval: 1.00–15.99; P = .05). Retinol and RBP levels were not different between case and control mothers.

CONCLUSIONS:

CDH is strongly associated with low retinol and RBP levels in newborns, independent of maternal retinol status. This is an important finding supporting the idea that human CDH is linked with abnormal retinoid homeostasis.