A recent systematic review and meta-analysis of randomised controlled trials of methylphenidate (MPH) in children and adolescents by a Cochrane group, led by Storebø, raised concern around the level ...of evidence supporting the use of this medication for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This led to several critical responses from a number of ADHD experts.
This paper reviews the conclusions reached from the Storebø meta-analysis by a critical analysis of methodologies used along with drawing on extant literature.
The controversy raised by the Cochrane meta-analysis should lead to a balanced reflection on the research priorities and needs for the field.
It is hoped the controversy will ultimately lead to improve the quality of the research on the efficacy, effectiveness and tolerability of MPH for ADHD.
Aim
Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children ...with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls.
Methods
We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers.
Results
Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001).
Conclusion
Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.
Until recently, no comprehensive guidance specifically on the conduction of systematic reviews and meta-analyses of pharmacoepidemiological studies of safety outcomes was available. In December 2015, ...the European Network of Centres for Pharmacoepidemiology and Pharamacovigilance (ENCePP), a network coordinated by the European Medicines Agency, published their ‘Guidance on conducting systematic reviews and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes’, filling an important gap in the field. This paper highlights the ENCePP recommendations in terms of study identification, data extraction, study quality appraisal and analytical plan. Although the ENCePP document should not be considered as definitive, since it will likely be refined following researchers’ feedback, it is expected that it will be highly influential and useful for the field, with the ultimate goal to improve and standardise the conduction and reporting of systematic reviews/meta-analyses of pharmacoepidemiological studies of safety outcomes.
The Database of Protein Disorder (DisProt) links structure and function information for intrinsically disordered proteins (IDPs). Intrinsically disordered proteins do not form a fixed ...three-dimensional structure under physiological conditions, either in their entireties or in segments or regions. We define IDP as a protein that contains at least one experimentally determined disordered region. Although lacking fixed structure, IDPs and regions carry out important biological functions, being typically involved in regulation, signaling and control. Such functions can involve high-specificity low-affinity interactions, the multiple binding of one protein to many partners and the multiple binding of many proteins to one partner. These three features are all enabled and enhanced by protein intrinsic disorder. One of the major hindrances in the study of IDPs has been the lack of organized information. DisProt was developed to enable IDP research by collecting and organizing knowledge regarding the experimental characterization and the functional associations of IDPs. In addition to being a unique source of biological information, DisProt opens doors for a plethora of bioinformatics studies. DisProt is openly available at http://www.disprot.org.
The aim of the study was to present nationally representative data on the lifetime independent association between attention deficit hyperactivity disorder (ADHD) and psychiatric co-morbidity, ...correlates, quality of life and treatment seeking in the USA.
Data were derived from a large national sample of the US population. Face-to-face surveys of more than 34 000 adults aged 18 years and older residing in households were conducted during the 2004-2005 period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version.
ADHD was associated independently of the effects of other psychiatric co-morbidity with increased risk of bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, specific phobia, and narcissistic, histrionic, borderline, antisocial and schizotypal personality disorders. A lifetime history of ADHD was also associated with increased risk of engaging in behaviors reflecting lack of planning and deficient inhibitory control, with high rates of adverse events, lower perceived health, social support and higher perceived stress. Fewer than half of individuals with ADHD had ever sought treatment, and about one-quarter had ever received medication. The average age of first treatment contact was 18.40 years.
ADHD is common and associated with a broad range of psychiatric disorders, impulsive behaviors, greater number of traumas, lower quality of life, perceived social support and social functioning, even after adjusting for additional co-morbidity. When treatment is sought, it is often in late adolescence or early adulthood, suggesting the need to improve diagnosis and treatment of ADHD.
Intrinsically disordered proteins and regions carry out varied and vital cellular functions. Proteins with disordered regions are especially common in eukaryotic cells, with a subset of these ...proteins being mostly disordered, e.g., with more disordered than ordered residues. Two distinct methods have been previously described for using amino acid sequences to predict which proteins are likely to be mostly disordered. These methods are based on the net charge−hydropathy distribution and disorder prediction score distribution. Each of these methods is reexamined, and the prediction results are compared herein. A new prediction method based on consensus is described. Application of the consensus method to whole genomes reveals that approximately 4.5% of Yersinia pestis, 5% of Escherichia coli K12, 6% of Archaeoglobus fulgidus, 8% of Methanobacterium thermoautotrophicum, 23% of Arabidopsis thaliana, and 28% of Mus musculus proteins are mostly disordered. The unexpectedly high frequency of mostly disordered proteins in eukaryotes has important implications both for large-scale, high-throughput projects and also for focused experiments aimed at determination of protein structure and function.
Alternative splicing of pre-mRNA generates two or more protein isoforms from a single gene, thereby contributing to protein diversity. Despite intensive efforts, an understanding of the protein ...structure-function implications of alternative splicing is still lacking. Intrinsic disorder, which is a lack of equilibrium 3D structure under physiological conditions, may provide this understanding. Intrinsic disorder is a common phenomenon, particularly in multicellular eukaryotes, and is responsible for important protein functions including regulation and signaling. We hypothesize that polypeptide segments affected by alternative splicing are most often intrinsically disordered such that alternative splicing enables functional and regulatory diversity while avoiding structural complications. We analyzed a set of 46 differentially spliced genes encoding experimentally characterized human proteins containing both structured and intrinsically disordered amino acid segments. We show that 81% of 75 alternatively spliced fragments in these proteins were associated with fully (57%) or partially (24%) disordered protein regions. Regions affected by alternative splicing were significantly biased toward encoding disordered residues, with a vanishingly small P value. A larger data set composed of 558 SwissProt proteins with known isoforms produced by 1,266 alternatively spliced fragments was characterized by applying the PONDR VSL1 disorder predictor. Results from prediction data are consistent with those obtained from experimental data, further supporting the proposed hypothesis. Associating alternative splicing with protein disorder enables the time-and tissue-specific modulation of protein function needed for cell differentiation and the evolution of multicellular organisms.
•Interoception is defined as the sense of the internal state of the body and dysfunctions in interoception are found in trauma-related conditions.•Mindfulness-Based Interventions (MBIs) have been ...shown to influence interoceptive processes.•We undertook a systematic review and meta-analysis to synthesize data from randomized controlled trials that have investigated whether MBIs impact symptoms and interoception in trauma-related disorders and exposure to traumatic events.
Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.
Hydrogen production by thermal decomposition of H2S in the presence of oxygen has been investigated at different operating conditions. It was studied the influence of the main operating parameters ...like temperature, O2/H2S ratio and residence time on H2S conversion, H2 yield and SO2 selectivity.
Experimental results allowed to identify the best values of operating parameters able to assure a high H2S conversion and a good hydrogen yield, minimizing the SO2 selectivity.
A kinetic model was developed through the identification of the main reactions that occur in the system. The accuracy of the model was tested under different experimental conditions to evidence the predictive capability of the model. A very good agreement between the mathematical model calculations and the experimental data by varying the feeding molar ratio (O2/H2S) was achieved.
•The thermal decomposition of H2S in presence of oxygen has been investigated.•The effect of the temperature, O2/H2S ratio and residence time was studied.•Highest hydrogen production at 1100 °C with O2/H2S ratio = 0.2.•Mathematical modelling through the identification of the main reactions.•A good agreement between the model and the experimental data was achieved.
Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein-protein interactions are organized ...into exquisitely complex networks. The architecture of protein-protein interaction networks was recently proposed to be scale-free, with most of the proteins having only one or two connections but with relatively fewer 'hubs' possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein-protein interaction in regulatory networks relies on intrinsic disorder.
PDF
