Association between chronic irritability and depressive symptoms in children and adolescents.

Association between chronic irritability and depressive symptoms in children and adolescents. Busto-Garrido, M.; Gutierrez-Castillo, D; Navas- Gonzalez, JR; Gutierrez-Bedmar, M; Gutierrez-Casares, JR; Martin-Lunar, MT; Rodríguez-Rosado, A; Pena-Andreu, JM. European Psychiatry 415(2017) 5221.Chronic irritability is the most frequently reported symptom in child and adolescent depression. The association of both has been linked with high rates of chronicity, comorbility and impairment. Objectives To study the association between chronic irritability and depressive symptoms in children and adolescents. Methods We have studied 857 participants recruited from the only Child and Adolescent Mental Health Clinic in a catchment area of 122968 people under 18 (2004-2010). A sample of 677 participants (57 controls and 620 patients) was included to carry out a cross-sectional study. Chronic irritability was measured by a Visual Analog Scale (VAS irritability) -scored from 0 to 10-, and depressive symptoms by the Children's Depression Inventory (CDI). The participants were categorized into controls and patients, and according to their chronic irritability (≤4 [I],5 [II] and ≥6 [III]). The mean of CDI score was calculated for each of the groups, adjusted by sex and age, and analyzed by ANCOVA. Results The following means were obtained from the controls: 13,71 (group I), 9,82 (group II) and 17,45 (group III). Regarding to the patients: 13,92 (group I), 11,54 (group II) and 15,64 (group III). A quadratic association (p <0,0015) was found between VAS irritability score and CDI score. Conclussions There is not a lineal association between chronic irritability and depressive symptoms in children and adolescent. High rates of depressive symptoms were associated both with high and low rates of irritability. Several questions remain unexplained about the status of irritability in psychiatry as Stringaris group has been pointed out. Disclosure statement I have no potential conflict of interest to discloseUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Structural Variations Induced by Temperature Changes in Rotavirus VP6 Protein Immersed in an Electric Field and Their Effects on Epitopes of The Region 300-396

Rotavirus diarrhea is an infectious intestinal disease that causes about 215 thousand deaths annually in infants under five years old. This virus is formed by three layers of concentric proteins that envelop its genome, from which VP6 structural protein is the most conserved among rotavirus serotypes and an excellent vaccine candidate. Recent studies have shown that structural proteins are susceptible to losing their biological function when their conformation is modified by moderate temperature increments, and in the case of VP6, its antigen efficiency decreases. We performed an in silicoanalysis to identify the structural variations in the epitopes 301-315, 357-366, and 376-384 of the rotavirus VP6 protein -in a hydrated medium- when the temperature is increased from 310 K to 322 K. In the latter state, we applied an electric field equivalent to a low energy laser pulse and calculated the fluctuations per amino acid residue. We identified that the region 301-315 has greater flexibility and density of negative electrical charge; nevertheless, at 322 K it experiences a sudden change of secondary structure that could decrease its efficiency as an antigenic determinant. The applied electric field induces electrical neutrality in the region 357-366, whereas in 376-384 inverts the charge, implying that temperature changes in the range 310 K-322 K are a factor that promotes thermoelectric effects in the VP6 protein epitopes in the region 300-396

Dna methylation changes in fibromyalgia suggest the role of the immune‐inflammatory response and central sensitization

Fibromyalgia (FM) has been explained as a result of gene‐environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain

Status of global fits to neutrino oscillations

We review the present status of global analyses of neutrino oscillations, taking into account the most recent neutrino data including the latest KamLAND and K2K updates presented at Neutrino2004, as well as state-of-the-art solar and atmospheric neutrino flux calculations. We give the two-neutrino solar + KamLAND results, as well as two-neutrino atmospheric + K2K oscillation regions, discussing in each case the robustness of the oscillation interpretation against departures from the Standard Solar Model and the possible existence of non-standard neutrino physics. Furthermore, we give the best fit values and allowed ranges of the three-flavour oscillation parameters from the current worlds' global neutrino data sample and discuss in detail the status of the small parameters \alpha \equiv \Dms/\Dma as well as $\sin^2\theta_{13}$, which characterize the strength of CP violating effects in neutrino oscillations. We also update the degree of rejection of four-neutrino interpretations of the LSND anomaly in view of the most recent developments.Comment: v6: In the last Appendix we provide updated neutrino oscillation results which take into account the relevant oscillation data released by the MINOS and KamLAND collaboration

Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis

Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD(+)) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD(+). Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD(+). EPC quantification in peripheral blood from 80 individuals (20 RA-ILD(+) patients, 25 RA-ILD(-) patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34(+), CD45(low), CD309(+) and CD133(+). A significant increase in EPC frequency in RA-ILD(+) patients, as well as in RA-ILD(-) and IPF patients, was found when compared with controls (p < 0.001, p = 0.02 and p < 0.001, respectively). RA-ILD(+) patients exhibited a higher EPC frequency than the RA-ILD(-) ones (p = 0.003), but lower than IPF patients (p < 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD(+). The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD(+) from IPF

Models of Neutrino Masses and Mixings

We review theoretical ideas, problems and implications of neutrino masses and mixing angles. We give a general discussion of schemes with three light neutrinos. Several specific examples are analyzed in some detail, particularly those that can be embedded into grand unified theories.Comment: 44 pages, 2 figures, version accepted for publication on the Focus Issue on 'Neutrino Physics' edited by F.Halzen, M.Lindner and A. Suzuki, to be published in New Journal of Physics

Damping of supernova neutrino transitions in stochastic shock-wave density profiles

Supernova neutrino flavor transitions during the shock wave propagation are known to encode relevant information not only about the matter density profile but also about unknown neutrino properties, such as the mass hierarchy (normal or inverted) and the mixing angle theta_13. While previous studies have focussed on "deterministic" density profiles, we investigate the effect of possible stochastic matter density fluctuations in the wake of supernova shock waves. In particular, we study the impact of small-scale fluctuations on the electron (anti)neutrino survival probability, and on the observable spectra of inverse-beta-decay events in future water-Cherenkov detectors. We find that such fluctuations, even with relatively small amplitudes, can have significant damping effects on the flavor transition pattern, and can partly erase the shock-wave imprint on the observable time spectra, especially for sin^2(theta_13) > O(10^-3).Comment: v2 (23 pages, including 6 eps figures). Typos removed, references updated, matches the published versio

Relationship Between Quorum Sensing and Secretion Systems

Quorum sensing (QS) is a communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation, virulence factor expression, production of secondary metabolites and stress adaptation mechanisms such as bacterial competition systems including secretion systems (SS). These SS have an important role in bacterial communication. SS are ubiquitous; they are present in both Gram-negative and Gram-positive bacteria and in Mycobacterium sp. To date, 8 types of SS have been described (T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, T7SS, and T9SS). They have global functions such as the transport of proteases, lipases, adhesins, heme-binding proteins, and amidases, and specific functions such as the synthesis of proteins in host cells, adaptation to the environment, the secretion of effectors to establish an infectious niche, transfer, absorption and release of DNA, translocation of effector proteins or DNA and autotransporter secretion. All of these functions can contribute to virulence and pathogenesis. In this review, we describe the known types of SS and discuss the ones that have been shown to be regulated by QS. Due to the large amount of information about this topic in some pathogens, we focus mainly on Pseudomonas aeruginosa and Vibrio spp

Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway

During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog

Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm

Over the past five decades, k-means has become the clustering algorithm of choice in many application domains primarily due to its simplicity, time/space efficiency, and invariance to the ordering of the data points. Unfortunately, the algorithm's sensitivity to the initial selection of the cluster centers remains to be its most serious drawback. Numerous initialization methods have been proposed to address this drawback. Many of these methods, however, have time complexity superlinear in the number of data points, which makes them impractical for large data sets. On the other hand, linear methods are often random and/or sensitive to the ordering of the data points. These methods are generally unreliable in that the quality of their results is unpredictable. Therefore, it is common practice to perform multiple runs of such methods and take the output of the run that produces the best results. Such a practice, however, greatly increases the computational requirements of the otherwise highly efficient k-means algorithm. In this chapter, we investigate the empirical performance of six linear, deterministic (non-random), and order-invariant k-means initialization methods on a large and diverse collection of data sets from the UCI Machine Learning Repository. The results demonstrate that two relatively unknown hierarchical initialization methods due to Su and Dy outperform the remaining four methods with respect to two objective effectiveness criteria. In addition, a recent method due to Erisoglu et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms (Springer, 2014). arXiv admin note: substantial text overlap with arXiv:1304.7465, arXiv:1209.196