Neurocognitive training for children with and without AD/HD

There is accumulating evidence that computerised cognitive training of inhibitory control and/or working memory can lead to behavioural improvement in children with AD/HD. Using a randomised waitlist control design, the present study examined the effects of combined working memory and inhibitory control training, with and without passive attention monitoring via EEG, for children with and without AD/HD. One hundred and twenty-eight children (60 children with AD/HD, 68 without AD/HD) were randomly allocated to one of three training conditions (waitlist; working memory and inhibitory control with attention monitoring; working memory and inhibitory control without attention monitoring) and completed with pre- and post-training assessments of overt behaviour (from 2 sources), trained and untrained cognitive task performance, and resting EEG activity. The two active training conditions completed 25 sessions of training at home over a 4- 5-week period. Results showed significant improvements in overt behaviour for children with AD/HD in both training conditions compared to the waitlist condition as rated by a parent and other adult. Post-training improvements in the areas of spatial working memory, ignoring distracting stimuli, and sustained attention were reported for children with AD/HD. Children without AD/HD showed behavioural improvements after training. The improvements for both groups were maintained over the 6-week period following training. The passive attention monitoring via EEG had a minor effect on training outcomes. Overall, the results suggest that combined WM/IC training can result in improved behavioural control for children with and without AD/HD.     

The Effectiveness of Neurofeedback and Stimulant Drugs in Treating AD/HD: Part II. Replication

This study replicated T. R. Rossiter and T. J. La Vaque (1995) with a larger sample, expanded age range, and improved statistical analysis. Thirty-one AD/HD patients who chose stimulant drug (MED) treatment were matched with 31 patients who chose a neurofeedback (EEG) treatment program. EEG patients received either office (n = 14) or home (n = 17) neurofeedback. Stimulants for MED patients were titrated using the Test of Variables of Attention (TOVA). EEG (effect size [ES] = 1.01–1.71) and MED (ES = 0.80–1.80) groups showed statistically and clinically significant improvement on TOVA measures of attention, impulse control, processing speed, and variability in attention. The EEG group demonstrated statistically and clinically significant improvement on behavioral measures (Behavior Assessment System for Children, ES = 1.16–1.78, and Brown Attention Deficit Disorder Scales, ES = 1.59). TOVA gain scores for the EEG and MED groups were not significantly different. More importantly, confidence interval and nonequivalence null hypothesis testing confirmed that the neurofeedback program produced patient outcomes equivalent to those obtained with stimulant drugs. An effectiveness research design places some limitations on the conclusions that can be drawn.     

营养性缺铁性贫血与注意缺陷多动障碍的临床关系研究——258例病例分析

目的:通过对营养性缺铁性贫血与注意缺陷多动障碍的病例研究,探讨两者之间的关系。方法:对258例NIDA的病因、临床表现和治疗进行临床分析,包括其中的31例中重度ADHD。结果:本组NIDA患儿病因主要为未及时添加富铁辅食、饮食结构不合理、消化道疾病、鼻衄等,临床主要表现为头晕、乏力、注意力不集中、记忆力减退等,对患者进行病因治疗以及服用生血宁片;ADHD的病因不明,临床表现为注意力不集中、活动过度、行为冲动等,通过综合治疗可以改善症状。NIDA的患儿ADHD的发病率较正常儿童为高。结论:NIDA与ADHD的关系密切。     

A pilot study of combined working memory and inhibition training for children with AD/HD

Building on recent favourable outcomes using working memory (WM) training, this study examined the behavioural and physiological effect of concurrent computer-based WM and inhibition training for children with attention-deficit hyperactivity disorder (AD/HD). Using a double-blind active-control design, 29 children with AD/HD completed a 5-week at-home training programme and pre- and post-training sessions which included the assessment of overt behaviour, resting EEG, as well as task performance, skin conductance level and event-related potentials (ERPs) during a Go/Nogo task. Results indicated that after training, children from the high-intensity training condition showed reduced frequency of inattention and hyperactivity symptoms. Although there were trends for improved Go/Nogo performance, increased arousal and specific training effects for the inhibition-related N2 ERP component, they failed to reach standard levels of statistical significance. Both the low- and high-intensity conditions showed resting EEG changes (increased delta, reduced alpha and theta activity) and improved early attention alerting to Go and Nogo stimuli, as indicated by the N1 ERP component, post-training. Despite limitations, this preliminary work indicates the potential for cognitive training that concurrently targets the interrelated processes of WM and inhibition to be used as a treatment for AD/HD.     

Investigating Thought Disorder in Schizophrenia: Evidence for Pathological Activation

Background

Previous research has yielded evidence for enhanced semantic priming in formal thought-disordered schizophrenia patients, a result that fits well with the hypothesis of disinhibited processes of spreading activation in this population.

Objective

The current study examined whether hyper priming among schizophrenia patients is an outcome of further spreading of activation of a node or a result of farther activation of nodes in the semantic network. We also try to shed light on the fate of this activation.

Methods

The present study tested this hypothesis by using semantic and identical priming in two different experiments. SOA (stimulus onset asynchrony) was manipulated (240 ms vs. 740 ms) within block. It is assumed that among healthy individuals, performance relies on a balance between activation and inhibition processes, contrary to in schizophrenic individuals. In order to examine this hypothesis, we compared formal thought-disordered schizophrenia patients, non thought-disordered schizophrenia patients, and healthy controls.

Results

For thought-disordered schizophrenia patients, we found a large positive semantic effect and identical priming effect (129 ms and 154 ms, respectively) only with short SOA. SOA and type of priming did not modulate priming effects in the control groups.

Conclusions

This result supports the claim that there is a lack of inhibitory processes among thought-disordered patients. Hyper priming in the thought-disorder group may be an outcome of hyper activation followed by rapid decay below baseline threshold.     

Evidence for a Distinct Light-Induced Calcium-Dependent Potassium Current in Hermissenda Crassicornis

A model of phototransduction is developed as a first step toward a model for investigating the critical interaction of light and turbulence stimuli within the type B photoreceptor of Hermissenda crassicronis. The model includes equations describing phototransduction, release of calcium from intracellular stores, and other calcium regulatory mechanisms, as well as equations describing ligand-gating of a rhabdomeric sodium current. The model is used to determine the sources of calcium in the soma, whether calcium or IP₃ is a plausible ligand of the light-induced sodium current, and whether the light-induced potassium current is equivalent to the calcium-dependent potassium current activated by light-induced calcium release. Simulations show that the early light-induced calcium elevation is due to influx through voltage-dependent channels, whereas the later calcium elevation is due to release from intracellular stores. Simulations suggest that the ligand of the fast, light-induced sodium current is IP₃ but that there is a smaller, prolonged component of the light-induced sodium current that is activated by calcium. In the model, the calcium-dependent potassium current, located in the soma, is activated only slightly by light-induced calcium elevation, leading to the prediction that a calcium-dependent potassium current, active at resting potential, is located in the rhabdomere and is responsible for the light-induced potassium current.     

Clinical Evidence for Three Distinct Gastric Cancer Subtypes: Time for a New Approach

Background

Recently, a new classification for gastric cancer (GC) has been proposed, based on Lauren''s histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome according to different GC subtypes (1,2,3) in metastatic GC patients receiving first-line chemotherapy.

Patients and Methods

Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3) as previously defined.

Results

A total of 248 advanced GC pts were included: 45.2% belonged to type 2, 43.6% to type 3 and 11.2% to type 1. Patients received a fluoropyrimidine-based chemotherapy doublet or three drugs regimens including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. RR was higher in type 1 pts (RR = 46.1%) and type 3 (34,3%) compared to type 2 (20,4%), (p = 0.015). Type 2 presented a shorter PFS, median PFS = 4.2 months, compared to type 1, mPFS = 7.2 months, and type 3, mPFS = 5.9 months (p = 0.011) and also a shorter OS (p = 0.022).

Conclusions

Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients.     

The Effectiveness of Neurofeedback and Stimulant Drugs in Treating AD/HD: Part I. Review of Methodological Issues

The paper examines major criticisms of AD/HD (Attention Deficit/Hyperactivity Disorder) neurofeedback research using T. R. Rossiter and T. J. La Vaque (1995) as an exemplar and discusses relevant aspects of research methodology. J. Lohr, S. Meunier, L. Parker, and J. P. Kline (2001), D. A. Waschbusch and G. P. Hill (2001), and J. P. Kline, C. N. Brann, and B. R. Loney (2002) criticized Rossiter and La Vaque for (1) using an active treatment control; (2) nonrandom assignment of patients; (3) provision of collateral treatments; (4) using nonstandardized and invalid assessment instruments; (5) providing artifact contaminated EEG feedback; and (6) conducting multiple non-alpha protected t tests. The criticisms, except those related to statistical analysis, are invalid or are not supported as presented by the authors. They are based on the critics' unsubstantiated opinions; require redefining Rossiter and La Vaque as an efficacy rather than an effectiveness study; or reflect a lack of familiarity with the research literature. However, there are broader issues to be considered. Specifically, what research methodology is appropriate for studies evaluating the effectiveness of neurofeedback and who should make that determination? The uncritical acceptance and implementation of models developed for psychotherapy, pharmacology, or medical research is premature and ill-advised. Neurofeedback researchers should develop models that are appropriate to the technology, treatment paradigms, and goals of neurofeedback outcome studies. They need to explain the rationale for their research methodology and defend their choices.     

Evidence for Distinct Aggregation Factors and Receptors in Cells

SINCE the original observations by Wilson¹ that dissociated sponge cells could reassociate in vitro, cell aggregation (or reaggregation) has been widely used as an operational criterion for the study of intercellular adhesion². The introduction of rotation-mediated methods to promote cell aggregation^3,4 led to the possibility of obtaining reproducible quantitative data. In these methods, suspensions of dissociated single cells are shaken under defined conditions of speed and temperature and cell aggregation is measured by either the size of aggregates or the number of single cells. The aggregation of dissociated cells from sponges⁵, chick and mouse embryos⁴ and tissue culture cells⁶ has been investigated with this method. Cells maintained in vitro seemed particularly suitable for studying mechanisms of cell aggregation as they represent a histotypically homogeneous population.     

Molecular Evidence for Gender Differences in the Migratory Behaviour of a Small Seabird

Molecular sexing revealed an unexpectedly strong female bias in the sex ratio of pre-breeding European Storm Petrels (Hydrobates pelagicus), attracted to playback of conspecific calls during their northwards migration past SW Europe. This bias was consistent across seven years, ranging from 80.8% to 89.7% female (mean annual sex ratio ± SD = 85.5% female ±4.1%). The sex ratio did not differ significantly from unity (i.e., 50% female) among (i) Storm Petrel chicks at a breeding colony in NW France, (ii) adults found dead on beaches in Southern Portugal, (iii) breeding birds attending nest burrows in the UK, captured by hand, and (iv) adults captured near a breeding colony in the UK using copies of the same sound recordings as used in Southern Europe, indicating that females are not inherently more strongly attracted to playback calls than males. A morphological discriminant function analysis failed to provide a good separation of the sexes, showing the importance of molecular sexing for this species. We found no sex difference in the seasonal or nocturnal timing of migration past Southern Europe, but there was a significant tendency for birds to be caught in sex-specific aggregations. The preponderance of females captured in Southern Europe suggests that the sexes may differ in migration route or in their colony-prospecting behaviour during migration, at sites far away from their natal colonies. Such differences in migration behaviour between males and females are poorly understood but have implications for the vulnerability of seabirds to pollution and environmental change at sea during the non-breeding season.     

Presenilin-2 polymorphisms and risk of sporadic AD: Evidence from a meta-analysis

Association studies of presenilin-2 (PSEN2) polymorphisms and sporadic Alzheimer's disease (AD) have yielded inconsistent results, possibly because single studies often lack sufficient statistical power. In this study, we performed a meta-analysis to evaluate the association of the two most extensively studied PSEN2 polymorphisms, rs8383 and 5′indel, with the risk of sporadic AD. We systematically reviewed relevant studies retrieved by Medline, Pubmed, Embase, AlzGene, and CNKI. Data were analyzed using the Stata (v11.0) software package. The fixed effects model or random-effects model were applied depending on between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's funnel plots. Overall, the meta-analysis included 6 case–control studies for each polymorphism with 2186 confirmed AD cases and 2507 healthy controls in total. Analysis suggested a significant association between SNP rs8383 polymorphism and AD risk with no evidence of between-study heterogeneity or publication bias. In contrast, we found no evidence for an association between the 5′indel polymorphism and AD risk. Further stratified analyses by apolipoprotein ε4 status or ethnicity also failed to reveal a statistically significant association between the 5′indel polymorphism of PSEN2 and AD risk. Our analysis supports the hypothesis that the PSEN2 rs8383 polymorphism is associated with an enlarged risk of sporadic AD. However, larger scale association studies are necessary to further validate the association of PSEN2 polymorphisms with sporadic AD risk and to define potential gene–gene interactions.     

Evidence for a Distinct D1Like Dopamine Receptor that Couples to Activation of Phosphoinositide Metabolism in Brain

Abstract: Dopamine and the D₁, receptor agonist SKF 38393 activate the phospholipase C-rnediated hydrolysis of phosphoinositides in brain slices. This action is selectively inhibited by SCH-23390, thus suggesting its mediation through the dopamine D₁ receptor. To determine if the dopamine receptor that mediates Phosphoinositide hydrolysis is the adenylyl, cyclase-linked D₁ receptor or a different subtype of the dopamine D₁ receptor, 20 benzazepine compounds that were previously characterized as selective dopamine D₁ receptor agonists were tested for stimulation of Phosphoinositide hydrolysis in rat striatal slices and for activation of adenylyl cyclase in rat striatal membranes. The compounds displayed a range of potencies and efficacies in stimulating adenylyl cyclase or Phosphoinositide hydrolysis. Compounds such as SKF 81427 and SKF 38393 were as efficacious as dopamine in stimulating Phosphoinositide hydrolysis, whereas other compounds, including SKF 85174 and SKF 86284, although showing high efficacy in stimulating cyclic AMP, failed to stimulate inositol phosphate formation. There was no correlation between the potencies (r= 0.016; p < 0.95) or efficacies (r=?0.294; p < 0.24) of the tested compounds in stimulating cyclic AMP formation and phosphoinositide hydrolysis. These observations indicate that the D₁-like dopamine receptor that mediates phosphoinositide hydrolysis is pharmacologically distinct from the classic D₁ receptor that is coupled to stimulation of cyclic AMP formation.     

Evidence for Distinct Functions of MRE11 in Arabidopsis Meiosis

The evolutionary conserved Mre11/Rad50/Nbs1 complex functions as one of the guardians of genome integrity in eukaryotes; it is required for the double-strand break repair, meiosis, DNA checkpoint, and telomere maintenance. To better understand the role of the MRE11 gene in Arabidopsis, we performed comparative analysis of several mre11 alleles with respect to genome stability and meiosis. The mre11-4 and mre11-2 alleles presumably produce truncated MRE11 proteins composed of the first 499 and 529 amino acids, respectively. Although the putative MRE11 truncated proteins differ only by 30 amino acids, the mutants exhibited strikingly different phenotypes in regards to growth morphology, genome stability and meiosis. While the mre11-2 mutants are fully fertile and undergo normal meiosis, the mre11-4 plants are sterile due to aberrant repair of meiotic DNA breaks. Structural homology analysis suggests that the T-DNA insertion in the mre11-4 allele probably disrupted the putative RAD50 interaction and/or homodimerization domain, which is assumed to be preserved in mre11-2 allele. Intriguingly, introgression of the atm-2 mutant plant into the mre11-2 background renders the double mutant infertile, a phenotype not observed in either parent line. This data indicate that MRE11 partially compensates for ATM deficiency in meiosis of Arabidopsis.     

Evidence for Distinct 5-Hydroxytryptamine2 Binding Site Subtypes in Cortical Membrane Preparations

5-Hydroxytryptamine (5-HT) displays a sixfold higher affinity for 5-HT2 binding sites labeled by [3H]ketanserin in rat (IC50 = 200 +/- 40 nM) and human (IC50 = 190 +/- 50 nM) cortex than for 5-HT2 sites in bovine cortex (IC50 = 1,200 +/- 130 nM). The Hill slopes of the 5-HT competition curves are 0.67 +/- 0.04 in rat, 0.69 +/- 0.08 in human, and 0.96 +/- 0.02 in bovine cortex. Scatchard analysis of (+/-)-[3H]4-bromo-2,5-dimethoxyamphetamine ([3H]DOB) binding in the rat indicates a population of binding sites with a KD of 0.38 +/- 0.04 nM and a Bmax of 1.5 +/- 0.05 pmol/g tissue. In contrast, specific [3H]DOB binding cannot be detected in bovine cortical membranes. These data indicate that species variations exist in 5-HT2 binding site subtypes and that [3H]ketanserin appears to label a homogeneous population of 5-HT2 binding site subtypes in bovine cortex.     

Distinct Behaviour of Sorafenib in Experimental Cachexia-Inducing Tumours: The Role of STAT3

The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways.     

Variation in Vocal Performance in the Songs of a Wood-Warbler: Evidence for the Function of Distinct Singing Modes

Male North American wood‐warblers (family Parulidae) subdivide their song repertoires into two different categories, or modes, of singing (first and second category songs). These two modes are thought to be specialized for interacting with females and males, although the data are inconclusive. I conducted an acoustic analysis of the song types used by yellow warblers (Dendroica petechia) for type I (first category) and type II (second category) singing to ask whether there are consistent structural differences between them which could provide insight into how they might function as separate signals. I found that type I songs are performed closer to the upper boundary of a song performance limit, measured in terms of the difficulty of production, compared with type II songs. By contrast, the performance of specific song types did not depend on whether they were used for type I singing vs. type II singing by different males. In addition, type I songs had a greater amplitude increase across the first two syllables compared with type II songs. There was no relationship between the performance of type I or type II songs and male condition. These results suggest that wood‐warblers might subdivide their song repertoire into distinct categories to highlight the relative vocal performance of their songs.     

Evidence for Two Distinct Forms of Fatty Acid Cyclooxygenase in Brain

Abstract: The enzymatic metabolism of [¹⁴C]arachidonic acid (AA) was studied with microsomes prepared from rabbit medulla. Prostaglandin E₂ (PGE₂) levels, measured either by radiochemistry or radioimmunoassay, rose rapidly and abruptly plateaued within 5 min, while prostaglandin F_2a (PGF_2a) levels continued to rise for 30 min. The rapid termination of PGE2 biosynthesis was not the result of limited cofactor, substrate, or product feedback inhibition, nor was it due to PGE₂-9-ketoreductase activity. Inhibition of the PGH₂→ PGE₂ isomerase by arachidonic acid or its metabolites could not explain the abrupt halt in PGE₂ biosynthesis. Proof for two separate cyclooxygenases comes from our observation that a preincubation of the brain microsomes with unlabeled AA eliminated PGE₂ biosynthesis while PGF2o production continued. Further evidence to suggest two cyclooxygenases in brain is derived from the observation that indomethacin inhibited PGE₂ production at concentrations that did not affect PGF_2a biosynthesis. These results suggest that one fatty acid cyclooxygenase is closely associated with PGH₂→ PGE₂ isomerase and readily undergoes autodestruction and the second cyclooxygenase is associated with a PGH₂→ PGF_2a reductase and is somewhat resistant to arachidonate-induced destruction and to nonsteroidal antiinflammatory agents.     

Polarized Sphingolipid Transport from the Subapical Compartment: Evidence for Distinct Sphingolipid Domains

In polarized HepG2 cells, the sphingolipids glucosylceramide and sphingomyelin (SM), transported along the reverse transcytotic pathway, are sorted in subapical compartments (SACs), and subsequently targeted to either apical or basolateral plasma membrane domains, respectively. In the present study, evidence is provided that demonstrates that these sphingolipids constitute separate membrane domains at the luminal side of the SAC membrane. Furthermore, as revealed by the use of various modulators of membrane trafficking, such as calmodulin antagonists and dibutyryl-cAMP, it is shown that the fate of these separate sphingolipid domains is regulated by different signals, including those that govern cell polarity development. Thus under conditions that stimulate apical plasma membrane biogenesis, SM is rerouted from a SAC-to-basolateral to a SAC-to-apical pathway. The latter pathway represents the final leg in the transcytotic pathway, followed by the transcytotic pIgR-dIgA protein complex. Interestingly, this pathway is clearly different from the apical recycling pathway followed by glucosylceramide, further indicating that randomization of these pathways, which are both bound for the apical membrane, does not occur. The consequence of the potential coexistence of separate sphingolipid domains within the same compartment in terms of "raft" formation and apical targeting is discussed.