bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenylethanolamine N-Methyltransferase Gene Polymorphisms and Adverse Outcomes in Acute Kidney Injury
Authors: Alam Ahsan , O’Connor Daniel T. , Perianayagam Mary C. , Kolyada Alexey Y. , Chen Yuqing , Rao Fangwen , Mahata Manjula , Mahata Sushil , Liangos Orfeas , Jaber Bertrand L.
Published: January 2010

Background/Aims: The catecholaminergic pathway is important in the physical stress response; however, its role is not well understood in acute kidney injury (AKI). We studied single nucleotide polymorphisms (SNPs) of phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholaminergic pathway, and their association with adverse outcomes in AKI. Methods: We performed a case-control study of 961 Caucasian subjects (194 with AKI and 767 controls). The PNMT promoter G–161A (rs876493) and coding A+1543G (rs5638) SNPs were genotyped and haplotypes generated. The outcomes of interest were the development of AKI, in-hospital mortality, dialysis requirement, oliguria, and hemodynamic shock. Urine catecholamines were measured in cases to explore genotype-phenotype correlations. Results: The PNMT +1543 G allele was associated with AKI [odds ratio (OR) 2.19, 95% confidence interval (CI): 1.04–4.60]. For AKI cases, each PNMT –161 A allele was associated with lower mortality (OR 0.58, 95% CI: 0.35–0.99) and hemodynamic shock (OR 0.63, 95% CI: 0.40–1.00). The PNMT +1543 G allele was associated with oliguria (OR 3.35, 95% CI: 1.13–9.95). Urine adrenaline was associated with increased hemodynamic shock and mortality, but was lowest in PNMT –161 A/A carriers. Conclusion: In Caucasians, PNMT SNPs are associated with the development of AKI, disease severity, and in-hospital mortality. The adrenergic pathway provides another area of focus in the study of AKI.
Low-Dose Alfacalcidol Controls Secondary Hyperparathyroidism in Predialysis Chronic Kidney Disease
Authors: Reichel Helmut
Published: January 2010

In the long term, secondary hyperparathyroidism (sHPT) causes severe osseous and non-osseous problems in patients with chronic kidney disease (CKD). Active vitamin D metabolites, i.e. calcitriol and alfacalcidol, have been utilized for sHPT treatment for more than 20 years. Yet, data on predialysis CKD patients are rather sparse. We monitored alfacalcidol therapy in 1,159 patients with CKD and sHPT in a 12-month multicenter observational study. Virtually all patients were in CKD stages 3–5 at study begin. The patients were recruited from 241 German nephrological centers. The mean alfacalcidol dose at study begin was 0.28 µg per day and 61.8% of patients received alfacalcidol daily (mean dose 0.34 µg); the remainder of the patients received intermittent therapy (mostly 3 times weekly, mean dose 0.19 µg/day). The initial alfacalcidol dose was maintained in 67.5% of patients; it was increased in 22% and decreased in 10.6%. At study end, the mean alfacalcidol dose was 0.32 µg/day. The mean calculated glomerular filtration rate decreased by 2.8 ml/min during the study (p < 0.001). The mean parathyroid hormone (PTH) concentration decreased from 27.5 to 23.1 pmol/l (p < 0.01) in the whole patient group. In the subgroup with intact PTH (iPTH) >20 pmol/l (48.3% of patients), the mean iPTH decreased from 41.3 to 30.9 pmol/l (p < 0.001). In the subgroups with iPTH <20 pmol/l at study begin, iPTH remained constant. The mean serum calcium increased from 2.23 to 2.31 mmol/l (p < 0.001) and 7.7% of patients had at least one serum calcium value above the normal range. Serum phosphate increased from 1.50 to 1.57 mmol/l (p < 0.001) and phosphate rose above 1.8 mmol/l in 21.5% of patients. Serum calcitriol increased significantly from 20.6 ng/l at baseline to 31.1 ng/l during the last quarter of the study (p < 0.001). iPTH was correlated negatively with kidney function, serum calcium and calcitriol and positively with serum phosphate. The frequency of side effects attributed to alfacalcidol was very low. Taken together, low-dose alfacalcidol prevented progression or caused regression of sHPT in a large cohort of CKD 3–5 patients. There were little effects on serum calcium and phosphate. Due to non-calciotropic activities of calcitriol, the alfacalcidol-induced rise in serum calcitriol could be clinically beneficial. The data support the concept that sHPT should be treated rather early in the course of CKD.
MicroRNA-1 and -499 Regulate Differentiation and Proliferation in Human-Derived Cardiomyocyte Progenitor Cells
Authors: Sluijter Joost P.G. , van Mil Alain , van Vliet Patrick , Metz Corina H.G. , Liu Jia , Doevendans Pieter A. , Goumans Marie-José
Published: January 2010

Objective—

To improve regeneration of the injured myocardium, it is necessary to enhance the intrinsic capacity of the heart to regenerate itself and/or replace the damaged tissue by cell transplantation. Cardiomyocyte progenitor cells (CMPCs) are a promising cell population, easily expanded and efficiently differentiated into beating cardiomyocytes. Recently, several studies have demonstrated that microRNAs (miRNAs) are important for stem cell maintenance and differentiation via translational repression. We hypothesize that miRNAs are also involved in proliferation/differentiation of the human CMPCs in vitro.

Methods and Results—

Human fetal CMPCs were isolated, cultured, and efficiently differentiated into beating cardiomyocytes. miRNA expression profiling demonstrated that muscle-specific miR-1 and miR-499 were highly upregulated in differentiated cells. Transient transfection of miR-1 and -499 in CMPC reduced proliferation rate by 25% and 15%, respectively, and enhanced differentiation into cardiomyocytes in human CMPCs and embryonic stem cells, likely via the repression of histone deacetylase 4 or Sox6. Histone deacetylase 4 and Sox6 protein levels were reduced, and small interference RNA (siRNA)-mediated knockdown of Sox6 strongly induced myogenic differentiation.

Conclusion—

miRNAs regulate the proliferation of human CMPC and their differentiation into cardiomyocytes. By modulating miR-1 and -499 expression levels, human CMPC function can be altered and differentiation directed, thereby enhancing cardiomyogenic differentiation.
Gap Junction Protein Cx37 Interacts With Endothelial Nitric Oxide Synthase in Endothelial Cells
Authors: Pfenniger Anna , Derouette Jean-Paul , Verma Vandana , Lin Xianming , Foglia Bernard , Coombs Wanda , Roth Isabelle , Satta Nathalie , Dunoyer-Geindre Sylvie , Sorgen Paul , Taffet Steven , Kwak Brenda R. , Delmar Mario
Published: January 2010

Objective—

The gap junction protein connexin37 (Cx37) plays an important role in cell-cell communication in the vasculature. A C1019T Cx37 gene polymorphism, encoding a P319S substitution in the regulatory C terminus of Cx37 (Cx37CT), correlates with arterial stenosis and myocardial infarction in humans. This study was designed to identify potential binding partners for Cx37CT and to determine whether the polymorphism modified this interaction.

Methods and Results—

Using a high-throughput phage display, we retrieved 2 binding motifs for Cx37CT: WHK … [K,R]XP … and FHK … [K,R]XXP … , the first being more common for Cx37CT-319P and the second more common for Cx37CT-319S. One of the peptides (WHRTPRLPPPVP) showed 77.7% homology with residues 843 to 854 of endothelial nitric oxide synthase (eNOS). In vitro binding of this peptide or of the homologous eNOS sequence to both Cx37CT isoforms was confirmed by cross-linking and surface plasmon resonance. Electrophysiological analysis of Cx37 single channel activity in transfected N2a cells showed that eNOS-like and eNOS(843–854) increased the frequency of events with conductances higher than 300 pS. We demonstrated that eNOS coimmunoprecipitated with Cx37 in a mouse endothelial cell (EC) line (bEnd.3), human primary ECs, and a human EC line transfected with Cx37-319P or Cx37-319S. Cx37 and eNOS colocalized at EC membranes. Moreover, a dose-dependent increase in nitric oxide production was observed in ECs treated with Cx37 antisense.

Conclusion—

Overall, our data show for the first time a functional and specific interaction between eNOS and Cx37. This interaction may be relevant for the control of vascular physiology both in health and in disease.
Cognitive and Psychosocial Characteristics of Gifted Students With Written Language Disability
Authors: Assouline Susan G. , Foley Nicpon Megan , Whiteman Claire
Published: January 2010

Gifted and talented students who also have a specific learning disability (SLD) are typically referred to as twice-exceptional and are among the most underserved students in our schools. Previous special education laws promoted a wait-to-fail approach; therefore, gifted students with SLD often were overlooked because their average academic performance was not “failure” enough. The flip side to this was the fact that students’ giftedness, as measured by general ability tests, often was masked by average, yet relatively weak, academic achievement. They were not only waiting to fail, they were failing to flourish. The authors present the data gathered from 14 gifted students with SLD, specifically a disorder of written expression. Students were determined to be gifted if they earned a score of 120 (Superior) on the Verbal Scale of a cognitive ability test. They were considered to have a written language disability through an evaluation of their written language skills. The average Verbal IQ for the group was close to a standard score of 130, whereas the average Written Language Score was close to a standard score of 99. In addition to the cognitive profile for these students, the authors obtained measures of their psychosocial functioning. On average, parents, teachers, and students reported typical adaptive behavior, yet group elevations also were present on several clinical scales. The authors’ main conclusion is that a comprehensive assessment plays a critical role in (a) determining whether a student is twice-exceptional, (b) identifying the possibility of psychosocial concerns, and (c) developing educational recommendations.

Putting the Research to Use

The results from our empirical study suggest that only through a comprehensive evaluation, which includes both individualized achievement and ability tests and allows for an analysis of the performance discrepancy between the two, is it possible to discover cognitively gifted students with a disorder of written expression. Diagnostic/identification procedures that do not include a comprehensive evaluation place gifted students at serious risk for “missed” diagnosis and ultimately, missed opportunity for intervention. The missed diagnosis arises from the observation that their written work is average relative to that of their peers. Equally important is the concern that some very capable students may be over-looked for screening for gifted programming because their achievement is average. Educators of students who appear to have high verbal ability while simultaneously demonstrating difficulty completing written assignments—and may even appear to be lazy or unmotivated—have a responsibility to further investigate the students’ difficulties and strengths.
Clinical Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Factor Xa Inhibitor Edoxaban in Healthy Volunteers
Authors: Ogata Koichiro , Mendell‐Harary Jeanne , Tachibana Masaya , Masumoto Hiroshi , Oguma Toshihiro , Kojima Masazumi , Kunitada Satoshi
Published: January 2010

This is a clinical safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) study of a single ascending dose (SAD) and a multiple ascending dose (MAD) of the oral direct factor Xa inhibitor edoxaban in healthy males. The placebo‐controlled, single‐blind, randomized, 2‐part study consists of a SAD arm with 85 subjects (10, 30, 60, 90, 120, 150 mg) and a MAD arm with 36 subjects (90 mg daily, 60 mg twice daily, 120 mg daily). Effects of food and formulation (tablet vs solution) are assessed in a crossover substudy. In the SAD, doses are well tolerated up to 150 mg. Exposure is proportional to dose. PK profiles are consistent across dose with rapid absorption, biphasic elimination, and terminal elimination half‐life of 5.8 to 10.7 hours. In the MAD, mean accumulation after daily dosing is 1.10 to 1.13 and consistent with elimination half‐life of 8.75 to 10.4 hours. Intrasubject variability ranges from 12% to 17% for area under the curve. In general, plasma edoxaban concentrations are linearly correlated with coagulation parameters. Edoxaban is safe and well tolerated with no dose‐dependent increases in adverse events. It is concluded that single and multiple doses of edoxaban are safe and well tolerated up to 150 mg with predictable PK and PD profiles.
Composite Functional Genetic and Comedication CYP2D6 Activity Score in Predicting Tamoxifen Drug Exposure Among Breast Cancer Patients
Authors: Borges Silvana , Desta Zeruesenay , Jin Yan , Faouzi Azzouz , Robarge Jason D. , Philip Santosh , Nguyen Anne , Stearns Vered , Hayes Daniel , Rae James M. , Skaar Todd C. , Flockhart David A. , Li Lang
Published: January 2010

Accurate assessment of CYP2D6 phenotypes from genotype is inadequate in patients taking CYP2D6 substrate together with CYP2D6 inhibitors. A novel CYP2D6 scoring system is proposed that incorporates the impact of concomitant medications with the genotype in calculating the CYP2D6 activity score. Training (n = 159) and validation (n = 81) data sets were obtained from a prospective cohort tamoxifen pharmacogenetics registry. Two inhibitor factors were defined: 1 genotype independent and 1 genotype based. Three CYP2D6 gene scoring systems, and their combination with the inhibitor factors, were compared. These 3 scores were based on Zineh, Zanger, and Gaedigk's approaches. Endoxifen/NDM‐Tam plasma ratio was used as the phenotype. The overall performance of the 3 gene scoring systems without consideration of CYP2D6‐inhibiting medications in predicting CYP2D6 phenotype was poor in both the training set (r2= 0.24, 0.22, and 0.18) and the validation set (r2= 0.30, 0.24, and 0.15). Once the CYP2D6 genotype‐independent inhibitor factor was integrated into the score calculation, the R2values in the training and validation data sets were nearly twice as high as the genotype‐only scoring model: (0.44, 0.43, 0.38) and (0.53, 0.50, 0.41), respectively. The integration of the inhibitory effect of concomitant medications with the CYP2D6 genotype into the composite CYP2D6 activity score doubled the ability to predict the CYP2D6 phenotype. However, endoxifen phenotypes still varied substantially, even with incorporation of CYD2D6 genotype and inhibiting factors, suggesting that other, as yet unidentified factors must be involved in tamoxifen activation.
A Medium-Term, Rapid Rat Bioassay Model for the Detection of Carcinogenic Potential of Chemicals
Authors: Tsuda Hiroyuki , Futakuchi Mitsuru , Fukamachi Katsumi , Shirai Tomoyuki , Imaida Katsumi , Fukushima Shoji , Tatematsu Masae , Furukawa Fumio , Tamano Seiko , Ito Nobuyuki
Published: January 2010

The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive. The false-positive detection of noncarcinogens was low; a single false-positive result was obtained from the 50 noncarcinogens tested. Since more than half of all known carcinogens are hepatocarcinogens in rodents, the initial 8-week bioassay is able to detect most carcinogens. The Ito Multi-organ Model is a 28-week bioassay system for the detection of carcinogens that were not identified by the Ito Liver Model. Results are evaluated by preneoplastic and neoplastic lesions in major organs. Forty-four compounds were tested using the Ito Multi-organ Model: 17 out of 17 liver carcinogens were positive, and 19 out of 22 (86%) nonliver carcinogens were positive. None of the five noncarcinogens tested positive.
Genomic Analyses as a Guide to Target Identification and Preclinical Testing of Mouse Models of Breast Cancer
Authors: Bennett Christina N. , Green Jeffrey E.
Published: January 2010

Cross-species genomic analyses have proven useful for identifying common genomic alterations that occur in human cancers and mouse models designed to recapitulate human tumor development. High-throughput molecular analyses provide a valuable tool for identifying particular animal models that may represent aspects of specific subtypes of human cancers. Corresponding alterations in gene copy number and expression in tumors from mouse and human suggest that these conserved changes may be mechanistically essential for cancer development and progression, and therefore, they may be critical targets for therapeutic intervention. Using a cross-species analysis approach, mouse models in which the functions of p53, Rb, and BRCA1 have been disrupted demonstrate molecular features of human, triple-negative (ER-, PR-, and ERBB2-), basal-type breast cancer. Using mouse tumor models based on the targeted abrogation of p53 and Rb function, we identified a large, integrated genetic network that correlates to poor outcome in several human epithelial cancers. This gene signature is highly enriched for genes involved in DNA replication and repair, chromosome maintenance, cell cycle regulation, and apoptosis. Current studies are determining whether inactivation of specific members within this signature, using drugs or siRNA, will identify potentially important new targets to inhibit triple-negative, basal-type breast cancer for which no targeted therapies currently exist.
Together we can: experiences from 7 years of cross-sectional studies in a Swedish palliative care clinical research network
Authors: Lundström Staffan , Gyllenhammar Eva , Martinsson Ulla , Strang Peter
Published: January 2010

During recent years, research networks and collaboratives focusing on palliative care research have been established both nationally and internationally resulting in several ongoing projects. In 2002, a clinician-based research network, the Palliative Care Research Network in Sweden (PANIS), was established to stimulate research and development of palliative care in Sweden. The growing network, which today includes 60 specialized palliative care units, has used a web-based survey generator to collect data on symptom prevalence, treatment traditions and important issues in palliative care. Eleven different studies involving almost 11,000 patients have been performed within the network including studies on prevalence of antitumoral treatment, the use of opioids, corticosteroids, blood transfusions, parenteral nutrition and prevalence of palliative sedation therapy in specialized palliative care. The working method of the research network is described, and demographic data from 9,298 patients in six cross-sectional studies are presented. Using a relatively simple research methodology, the network has succeeded in addressing key clinical questions and in this article we share experiences and challenges met during the journey.
Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study
Authors: Safarinejad Mohammad R
Published: January 2010

A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) report sexual dysfunction. SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens. This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction. Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index (primary efficacy outcome measure) and the Clinical Global Impression Scale adapted for sexual function (secondary efficacy outcome measure). End point treatment satisfaction was assessed using a Visual Analog Scale. A total of 218 women (25–45 years old) with SSRI-induced sexual dysfunction were randomized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d. ( n = 109) or placebo ( n = 109). The mean (SD) for Female Sexual Function Index total score was higher in the bupropion sustained release group (25.9 (5.12), 95% confidence interval (CI) 22.2–29.4) than in the placebo group (17.2 (4.9), 95% CI 15.8–20.1) ( p = 0.001). Mean (SD) Clinical Global Impression Scale score for the bupropion group (2.4 (0.6), 95% CI 2.0–3.6) was significantly lower than that for the placebo group (4.2 (0.8), 95% CI 3.4–5.4) ( p = 0.001). At the end of the trial the mean (SD) scores for desire (4.1 (0.7), 95% CI 3.5–4.8) ( p = 0.001), arousal (4.4 (0.6), 95% CI 3.7–4.8) ( p = 0.01), lubrication (4.4 (0.4), 95% CI 3.3–4.8) ( p = 0.001), orgasm (4.4 (0.5), 95% CI 3.7–4.7) ( p = 0.001), and satisfaction (4.2 (0.7), 95% CI 3.4–4.8) ( p = 0.001) were significantly higher in the bupropion group. The highest improvement was observed in sexual desire, followed by lubrication. Compared with baseline, desire and lubrication domains increased by 86.4% (95% CI 64.9–102.2%, p = 0.001) and 69.2% (95% CI 44.7–82.6%, p = 0.001) in the bupropion group. Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction.
Metformin for weight reduction in non-diabetic patients on antipsychotic drugs: a systematic review and meta-analysis
Authors: Björkhem-Bergman Linda , Asplund Annika B , Lindh Jonatan D
Published: January 2010

Weight gain is a clinically important side effect of antipsychotic drug therapy. The aim of this study was to determine the effect of the antidiabetic drug metformin on antipsychotic-induced weight gain in non-diabetic patients. In a systematic literature review we identified 195 citations from which seven randomized, placebo-controlled studies (398 patients) were included in the final analysis. Studies in adults ( n = 5) and in children ( n = 2) were analysed separately. Compared with placebo, metformin treatment caused a significant body weight reduction in adult non-diabetic patients treated with atypical antipsychotics (4.8%, 95% CI 1.6 to 8.0) and in children (4.1%, 95% CI 2.2 to 6.0). There was evidence of substantial heterogeneity among studies, and when the analysis was restricted to patients with a manifest (>10%) body weight increase prior to randomisation metformin reduced weight by 7.5% (95% CI 2.9 to 12.0). The effect was larger in Asians (7.8%, 95% CI 4.4 to 11.2) than in Hispanics (2.0%, 95% CI 0.7 to 3.3). In conclusion, metformin has a pronounced weight-reducing effect in antipsychotic-treated patients, especially in those with a manifest weight gain. Although direct comparisons are lacking, the observed effect on body weight compares favourably with the effect of sibutramine and orlistat, approved for weight reduction. However, metformin is not approved for use in non-diabetic patients and it is still not generally advisable to recommend metformin to counteract antipsychotic-induced weight gain.
Perturbed reward processing in pediatric bipolar disorder: an antisaccade study
Authors: Mueller Sven C , Ng Pamela , Temple Veronica , Hardin Michael G , Pine Daniel S , Leibenluft Ellen , Ernst Monique
Published: January 2010

Pediatric bipolar disorder is a severe and impairing illness. Characterizing the impact of pediatric bipolar disorder on cognitive function might aid in understanding the phenomenology of the disorder. While previous studies of pediatric bipolar disorder have reported deficits in cognitive control and reward behavior, little is understood about how affective processes influence behavioral control. Relative to prior studies using manual-response paradigms, eye movement tasks provide a more precise assessment of reward sensitivity and cognitive and motor control. The current study compares 20 youths with bipolar disorder (mean age = 13.9 years ± 2.22) and 23 healthy subjects (mean age = 13.8 years ± 2.49) on a mixed pro—antisaccade task with monetary incentives. On both types of saccades, participants were presented with three types of incentives: those where subjects can win money, lose money, or neither win nor lose money. Impaired reward processing was found in youths with bipolar disorder relative to controls, particularly on antisaccades. This difference was reflected in lower error rates during incentive trials in the control but not in the bipolar disorder group. By comparison, no group differences were found on prosaccade trials. The results provide further evidence for deficits in cognitive and reward processing in bipolar disorder.
Induction of c-Fos in ‘panic/defence’-related brain circuits following brief hypercarbic gas exposure
Authors: Johnson Philip L , Fitz Stephanie D , Hollis Jacob H , Moratalla Rosario , Lightman Stafford L , Shekhar Anantha , Lowry Christopher A
Published: January 2010

Inspiration of air containing high concentrations of carbon dioxide (CO2; hypercarbic gas exposure) mobilizes respiratory, sympathetic and hypothalamic–pituitary–adrenal axis responses and increases anxiety-like behaviour in rats and humans. Meanwhile the same stimulus induces panic attacks in the majority of panic disorder patients. However, little is known about the neural circuits that regulate these acute effects. In order to determine the effects of acute hypercarbic gas exposure on forebrain and brainstem circuits, conscious adult male rats were placed in flow cages and exposed to either atmospheric air or increasing environmental CO2 concentrations (from baseline concentrations up to 20% CO2) during a 5 min period. The presence of immunoreactivity for the protein product of the immediate-early gene c-fos was used as a measure of functional cellular responses. Exposing rats to hypercarbic gas increased anxiety-related behaviour and increased numbers of c-Fos-immunoreactive cells in subcortical regions of the brain involved in: (1) the initiation of fear- or anxiety-associated behavioural responses (i.e. the dorsomedial hypothalamus, perifornical nucleus and dorsolateral and ventrolateral periaqueductal gray); (2) mobilization of the hypothalamic-pituitary-adrenal axis (i.e. the dorsomedial hypothalamus, perifornical nucleus and paraventricular hypothalamic nucleus); and (3) initiation of stress-related sympathetic responses (i.e. the dorsomedial hypothalamus, dorsolateral periaqueductal grey and rostroventrolateral medulla). These findings have implications for understanding how the brain senses changes in environmental CO2 concentrations and the neural mechanisms underlying the subsequent adaptive changes in stress-related physiology and behaviour.
The influence of 5-HTT and COMT genotypes on verbal fluency in ecstasy users
Authors: Fagundo Ana B , Cuyàs Elisabet , Verdejo-Garcia Antonio , Khymenets Olha , Langohr Klaus , Martín-Santos Rocio , Farré Magí , de la Torre Rafael
Published: January 2010

Deficits in verbal fluency associated with ecstasy use have been well established; however, the mechanisms underlying this impairment have yet to be elucidated. In this study we investigated for the first time whether there was a disproportionate impairment in two cognitive subcomponents of verbal fluency: clustering (ability to generate words within the same subcategory) and switching (ability to change the subcategory). We also investigated a possible association between ecstasy use and verbal fluency in subjects genotyped for 5-HTT (5-HTTLPR and 5-HTTVNTR) and COMT (val108/158met, rs165599 and rs2097603) polymorphisms, in order to find a potential implication of genetic factors. Ecstasy polydrug users (n = 30) and non-ecstasy users (n = 41) were evaluated in both semantic and phonemic fluency. Results showed that ecstasy users had poorer semantic (but not phonemic) fluency performance than controls. Detailed analysis of clustering and switching performance revealed that this impairment was associated with poorer clustering mechanisms. Clustering was also modulated by the COMT rs165599 polymorphism independently of the group. A specific effect of the 5-HTTLPR polymorphism on switching performance was also found, with ss carriers performing significantly worse than ls and ll carriers, suggesting a serotonin modulation of frontal-executive flexibility. Based on the impaired clustering and switching strategies observed in ecstasy users, it might be proposed that both semantic knowledge and retrieval are impaired in this population. The verbal fluency deficit in ecstasy users may be attributable to a disruption of frontal-striatal circuits directly related with the serotonin function as well as a depletion of lexical-semantic stores mediated by temporal structures.
Effectiveness of a Sex Offender Treatment Programme: A Risk Band Analysis
Authors: Woodrow Anna C. , Bright David A.
Published: January 2010

This article reports an evaluation of a New South Wales Department of Corrective Services custody-based treatment programme for adult male sexual offenders. A risk band analysis was used to compare observed and predicted sexual and violent recidivism rates in a sample of 117 treated and released offenders. Risk bands and predicted recidivism were determined using the Static-99 risk assessment measure. Results demonstrated that during an average follow-up period of 3.75 years, observed sexual recidivism rates were lower than Static-99 predictions for the overall sample (8.5% vs. 26%). The same pattern was observed for violent recidivism (12.8% vs. 36%). At each Static-99 level of risk (low, low—moderate, moderate—high, and high), observed sexual and violent recidivism rates were lower than predicted rates. These findings were consistent with the general consensus that well-implemented cognitive—behavioural treatment can have a positive effect on offending behaviour.
Compassion Fatigue: What Is It? Why Does It Matter? Recognizing the Symptoms, Acknowledging the Impact, Developing the Tools to Prevent Compassion Fatigue, and Strengthen the Professional Already Suffering From the Effects
Authors: Showalter Sherry E.
Published: January 2010

Compassion fatigue (CF) is recognizable. It erodes the professional’s ability to function at an optimum level. Depression, caregiver stress, secondary trauma, and post traumatic stress syndrome (PTSD) are very much a part of the daily landscape for today’s professional. The costs are many: staff turnover, loss of self-worth, diminished productivity, poor morale, and more. We in the helping professions must acknowledge the syndrome and validate its impact on professional staff. Giving lip service to ‘‘staff support’’ is not enough. We must fully understand how CF comes about and how we can effectively support those suffering its debilitating consequences.
Impact of Group Size on Classroom On-Task Behavior and Work Productivity in Children With ADHD
Authors: Hart Katie C. , Massetti Greta M. , Fabiano Gregory A. , Pariseau Meaghan E. , Pelham William E.
Published: January 2010

This study sought to systematically examine the academic behavior of children with ADHD in different instructional contexts in an analogue classroom setting. A total of 33 children with ADHD participated in a reading comprehension activity followed by a testing period and were randomly assigned within days to either small-group instruction, whole-group instruction, or independent seatwork. The effects of instructional contexts on on-task behavior during instruction and on-task behavior and work productivity during testing were examined. Children with ADHD were found to be more on task during small-group instruction than both whole-group and independent seatwork instructional conditions. In the testing context, children with ADHD were found to be less productive in small-group than in the whole-group and independent seatwork conditions. The findings of this study have implications for future research evaluating the standard educational practices and accommodations made for children with ADHD in the classroom setting.
Automated Link-16 Testing Using the Discrete Event System Specification and Extensible Markup Language
Authors: Mak Eddie , Mittal Saurabh , Hwang Moon-Ho , Nutaro James J.
Published: January 2010

With the modernization of Department of Defense (DoD) systems and the growing complexity of communication equipment, traditional test methods and processes have to evolve in order to maintain their effectiveness. DoD acquisition policy requires the use of modeling and simulation (M&S) in all phases of system development life-cycles in order to ensure technical certification and mission effectiveness. The complexity of these systems poses significant challenges over traditional interoperability test methodologies. The Automated Test Case Generator (ATC-Gen), funded by the Joint Interoperability Test Command (JITC), captures a Military Standard (MIL-STD) 6016C document and translates it into rules. These are in turn formalized into test cases using the Discrete Event System Specification (DEVS). In this paper, we present a new methodology to generate the test models and perform conformance testing using system theory, the DEVS M&S framework, the System Entity Structure (SES), and Extensible Markup Language (XML). This new methodology promotes the separation of the models, the simulator, and the distributed simulation. These separations distinguish and promote reusability by developing models, the simulator, and distributed simulation independently. The DEVS test models are generated from the test cases by the Test Model Generator using the system specifications. These models are written in an XML-SES format; the resulting C++ DEVS source code is generated based on the test model XML file. The Test Driver (TD) was designed based on the Model/Simulator/View/Control (MSVC) design pattern and developed to execute the DEVS test models. MSVC supports model and simulator separation design. It was also designed to support multiple network simulation protocols and rapid software modifications in order to incorporate new network protocols into the simulation software. This methodology was used to verify the conformance of the Integrated Architecture Behavior Model (IABM) to the MIL-STD 6016C, and the results of the test scenarios were validated using the JITC’s Simple J network packet-monitoring tool. The network packet monitor captured the transmissions and the receipt of the tactical data messages from the TD. The system analyst interpreted and verified the messages, and determined whether these messages were the intended behavior of the TD.
Preliminary Report on Dietitians’ Views and Confidence Related to Nutrition Care for Eating Disorders
Authors: Ozier Amy D. , Henry Beverly W.
Published: January 2010

Evidence suggests that nutrition professionals have gaps in knowledge and skills related to prevention and treatment of eating disorders and disordered eating, thus inhibiting effective interventions. The purpose of this study was to explore registered dietitians’ (RDs’) views and confidence levels regarding nutrition care across the spectrum of eating disorders. An online survey management tool was used to collect data from a convenience sample of RDs (N = 291) participating in Pedi-RD list servs and dietetic practice groups including the Pediatric Nutrition Practice Group. Participants answered closed- and open-ended questions about their knowledge, beliefs, and practices related to eating disorders and disordered eating. On average, participants responded that genetics was least important in the development of eating disorders and that psychological issues and obsession with food were most important. Participants indicated that working with a multidisciplinary team was most important to improve the RDs’ knowledge and skills about eating disorders. Analysis of variance results revealed that RDs who worked with individuals with eating disorders had significantly higher ratings of comfort level and self-efficacy counseling for eating disorders than those RDs who did not work with eating disorders (P < .05), although these ratings were still low overall. RDs’ job emphasis also appeared to be an influence, with differences between groups on a variety of questions. This study highlights the need for educational opportunities for RDs to expand their knowledge, skills, and self-efficacy base related to eating disorders and disordered eating.
Changes in Proton Dynamics in Articular Cartilage Caused by Phosphate Salts and Fixation Solutions
Authors: Zheng ShaoKuan , Xia Yang
Published: January 2010

The objective was to study the effect of phosphate salts and fixation solutions on the proton dynamics in articular cartilage in vitro. Microscopic magnetic resonance imaging (µMRI) T2 anisotropy and nuclear magnetic resonance (NMR) double quantum–filtered (DQF) spectroscopy were used to study the full-thickness articular cartilage from several canine humeral heads. The in-plane pixel size across the depth of the cartilage tissue was 13 µm. The acid phosphate salt was an effective exchange catalyst for proton exchange in the cartilage with an organized structure of collagen fibrils, while the alkaline phosphate salt was not. For cartilage tissue containing less organized collagen fibrils, both acid and alkaline phosphate salts have no significant effect on the T2 value at low concentration but decrease the T2 value at high concentration. The solutions of NaCl, KCl, CaCl2, and D-PBS were found to have no significant effect on T2 and DQF in cartilage. This study demonstrates the ability to modify the proton exchange in articular cartilage using the solutions of phosphate salts. The ability to modify the proton exchange in articular cartilage can be used to modulate the laminar appearance of articular cartilage in MRI.
Proinflammatory state, hepcidin, and anemia in older persons
Authors: Ferrucci Luigi , Semba Richard D. , Guralnik Jack M. , Ershler William B. , Bandinelli Stefania , Patel Kushang V. , Sun Kai , Woodman Richard C. , Andrews Nancy C. , Cotter Robert J. , Ganz Tomas , Nemeth Elizabeta , Longo Dan L.
Published: January 2010

In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, “Aging in the Chianti Area”) study, a population-based study of aging in Tuscany, Italy. Compared with nonanemic persons, urinary hepcidin (nanograms/milligram of urinary creatinine) was significantly lower in iron deficiency and inflammation anemia compared with no anemia or other anemia types. Urinary hepcidin was positively correlated with log(ferritin) and negatively correlated with the soluble transferrin receptor/log(ferritin) ratio but not correlated with markers of inflammation: interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α, and C-reactive protein (CRP). Lower iron was significantly correlated with higher IL-6 and CRP. Adjusting for confounders, IL-6 and CRP remained significantly associated with serum iron, with no evidence that such a relationship was accounted for by variability in urinary hepcidin. In conclusion, elevated proinflammatory markers were associated with anemia and low iron status, but not with higher urinary hepcidin. Future studies should test whether hepcidin production becomes up-regulated only in situations of overt inflammation.
An automatic method for identifying surface proteins in bacteria: SLEP
Authors: Giombini Emanuela , Orsini Massimiliano , Carrabino Danilo , Tramontano Anna
Published: January 2010

Background

Bacterial infections represent a global health challenge. The identification of novel antibacterial targets for both therapy and vaccination is needed on a constant basis because resistance continues to spread worldwide at an alarming rate. Even infections that were once easy to treat are becoming difficult or, in some cases, impossible to cure. Ideal targets for both therapy and vaccination are bacterial proteins exposed on the surface of the organism, which are often involved in host-pathogen interaction. Their identification can greatly benefit from technologies such as bioinformatics, proteomics and DNA microarrays.

Results

Here we describe a pipeline named SLEP (Surface Localization Extracellular Proteins), based on an automated optimal combination and sequence of usage of reliable available tools for the computational identification of the surfome, i.e. of the subset of proteins exposed on the surface of a bacterial cell.

Conclusions

The tool not only simplifies the usage of these methods, but it also improves the results by selecting the specifying order and combination of the instruments. The tool is freely available at http://www.caspur.it/slep.
An insight into the sialotranscriptome of the West Nile mosquito vector, Culex tarsalis
Authors: Calvo Eric , Sanchez-Vargas Irma , Favreau Amanda J , Barbian Kent D , Pham Van M , Olson Kenneth E , Ribeiro José MC
Published: January 2010

Background

Saliva of adult female mosquitoes help sugar and blood feeding by providing enzymes and polypeptides that help sugar digestion, control microbial growth and counteract their vertebrate host hemostasis and inflammation. Mosquito saliva also potentiates the transmission of vector borne pathogens, including arboviruses. Culex tarsalis is a bird feeding mosquito vector of West Nile Virus closely related to C. quinquefasciatus, a mosquito relatively recently adapted to feed on humans, and the only mosquito of the genus Culex to have its sialotranscriptome so far described.

Results

A total of 1,753 clones randomly selected from an adult female C. tarsalis salivary glands (SG) cDNA library were sequenced and used to assemble a database that yielded 809 clusters of related sequences, 675 of which were singletons. Primer extension experiments were performed in selected clones to further extend sequence coverage, allowing for the identification of 283 protein sequences, 80 of which code for putative secreted proteins.

Conclusion

Comparison of the C. tarsalis sialotranscriptome with that of C. quinquefasciatus reveals accelerated evolution of salivary proteins as compared to housekeeping proteins. The average amino acid identity among salivary proteins is 70.1%, while that for housekeeping proteins is 91.2% (P < 0.05), and the codon volatility of secreted proteins is significantly higher than those of housekeeping proteins. Several protein families previously found exclusive of mosquitoes, including only in the Aedes genus have been identified in C. tarsalis. Interestingly, a protein family so far unique to C. quinquefasciatus, with 30 genes, is also found in C. tarsalis, indicating it was not a specific C. quinquefasciatus acquisition in its evolution to optimize mammal blood feeding.
Detection of HPV DNA in esophageal cancer specimens from different regions and ethnic groups: a descriptive study
Authors: Wang Xueqian , Tian Xiuyun , Liu Fangfang , Zhao Yiqiang , Sun Min , Chen Dafang , Lu Changdong , Wang Zhong , Shi Xiaotian , Zhang Qingying , Zhang Donghong , Shen Zhongying , Li Feng , Harris Curtis C , Cai Hong , Ke Yang
Published: January 2010

Background

HPV has been found repeatedly in esophageal carcinoma tissues. However, reported detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types, and geographic regions of sample origin have been suggested as potential causes of this discrepancy.

Methods

HPV L1 DNA and HPV genotypes were evaluated in 435 esophageal carcinoma specimens collected from four geographic regions with different ethnicities including Anyang in north China, Shantou in south China, Xinjiang in west China, and the United States. The HPV L1 fragment was detected using SPF1/GP6+ primers. HPV genotyping was performed using genotype specific PCR.

Results

Two hundred and forty four of 435 samples (56.1%) tested positive for HPV L1. Significant differences in detection rate were observed neither among the three areas of China nor between China and the US. HPV6, 16, 18, 26, 45, 56, 57, and 58 were identified in L1 positive samples. HPV16 and 57 were the most common types in all regions, followed by HPV26 and HPV18.

Conclusions

HPV infection is common in esophageal carcinoma independent of region and ethnic group of origin. Findings in this study raise the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size over broader geographic areas may be warranted.
Ryanodine Receptors Contribute to the Induction of Nociceptive Input-Evoked Long-Term Potentiation in the Rat Spinal Cord Slice
Authors: Cheng Long-Zhen , Lü Ning , Zhang Yu-Qiu , Zhao Zhi-Qi
Published: January 2010

Background:

Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.

Results:

By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP3R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]i in small DRG neurons.

Conclusions:

These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.