Modulation of functional network properties in major depressive disorder following electroconvulsive therapy (ECT): a resting-state EEG analysis

Electroconvulsive therapy (ECT) is a highly effective neuromodulatory intervention for treatment-resistant major depressive disorder (MDD). Presently, however, understanding of its neurophysiological effects remains incomplete. In the present study, we utilised resting-state electroencephalography (RS-EEG) to explore changes in functional connectivity, network topology, and spectral power elicited by an acute open-label course of ECT in a cohort of 23 patients with treatment-resistant MDD. RS-EEG was recorded prior to commencement of ECT and again within 48 h following each patient’s final treatment session. Our results show that ECT was able to enhance connectivity within lower (delta and theta) frequency bands across subnetworks largely confined to fronto-central channels, while, conversely, more widespread subnetworks of reduced connectivity emerged within faster (alpha and beta) bands following treatment. Graph-based topological analyses revealed changes in measures of functional segregation (clustering coefficient), integration (characteristic path length), and small-world architecture following ECT. Finally, post-treatment enhancement of delta and theta spectral power was observed, which showed a positive association with the number of ECT sessions received. Overall, our findings indicate that RS-EEG can provide a sensitive measure of dynamic neural activity following ECT and highlight network-based analyses as a promising avenue for furthering mechanistic understanding of the effects of convulsive therapies

Universality of Level Spacing Distributions in Classical Chaos

We suggest that random matrix theory applied to a classical action matrix can be used in classical physics to distinguish chaotic from non-chaotic behavior. We consider the 2-D stadium billiard system as well as the 2-D anharmonic and harmonic oscillator. By unfolding of the spectrum of such matrix we compute the level spacing distribution, the spectral auto-correlation and spectral rigidity. We observe Poissonian behavior in the integrable case and Wignerian behavior in the chaotic case. We present numerical evidence that the action matrix of the stadium billiard displays GOE behavior and give an explanation for it. The findings present evidence for universality of level fluctuations - known from quantum chaos - also to hold in classical physics

Delayed auditory feedback and transcranial direct current stimulation treatment for the enhancement of speech fluency in adults who stutter: Protocol for a randomized controlled trial

Background: Stuttering is a complex speech disorder that affects speech fluency. Recently, it has been shown that noninvasive brain stimulation may be useful to enhance the results of fluency interventions in adults who stutter. Delayed auditory feedback (DAF) is a method to enhance speech fluency in individuals who stutter. Adjunctive interventions are warranted to enhance the efficacy of this intervention. Objective: Individuals who stutter have pathological activation patterns in the primary and secondary auditory areas. Consequently, in this study, we hypothesize that stimulation of these areas might be promising as an adjunctive method to fluency training via DAF to enhance speech therapy success in individuals with a stutter. We will systematically test this hypothesis in this study. Methods: This study is designed as a randomized, double-blind, sham-controlled clinical trial. All participants will receive DAF. The intervention group will additionally receive real transcranial direct current stimulation, while the control group will be exposed to sham stimulation. The assignment of the participants to one of these groups will be randomized. Before starting the treatment program, 2 preintervention assessments will be conducted to determine the severity of stuttering. Once these assessments are completed, each subject will participate in 6 intervention sessions. Postintervention assessments will be carried out immediately and 1 week after the last intervention session. Subsequently, to explore the long-term stability of the treatment results, the outcome parameters will be obtained in follow-up assessments 6 weeks after the treatment. The primary outcome measurement�the percentage of stuttered syllables�will be calculated in pre-, post-, and follow-up assessments; the secondary outcomes will be the scores of the following questionnaires: the Stuttering Severity Instrument�Fourth Edition and the Overall Assessment of the Speaker�s Experience of Stuttering. Results: This protocol was funded in 2019 and approved by the Research Ethics Committee of the Iran University of Medical Sciences in June 2019. Data collection started in October 2019. As of February 2020, we have enrolled 30 participants. We expect data analysis to be completed in April 2020, and results will be published in summer 2020. Conclusions: We anticipate that this study will show an adjunctive effect of transcranial direct current stimulation, when combined with DAF, on stuttering. This should include not only a reduction in the percentage of stuttered syllables but also improved physical behavior and quality of life in adults who stutter. © 2020 Journal of Medical Internet Research. All rights reserved

Genome-scale gene/reaction essentiality and synthetic lethality analysis

Synthetic lethals are to pairs of non-essential genes whose simultaneous deletion prohibits growth. One can extend the concept of synthetic lethality by considering gene groups of increasing size where only the simultaneous elimination of all genes is lethal, whereas individual gene deletions are not. We developed optimization-based procedures for the exhaustive and targeted enumeration of multi-gene (and by extension multi-reaction) lethals for genome-scale metabolic models. Specifically, these approaches are applied to iAF1260, the latest model of Escherichia coli, leading to the complete identification of all double and triple gene and reaction synthetic lethals as well as the targeted identification of quadruples and some higher-order ones. Graph representations of these synthetic lethals reveal a variety of motifs ranging from hub-like to highly connected subgraphs providing a birds-eye view of the avenues available for redirecting metabolism and uncovering complex patterns of gene utilization and interdependence. The procedure also enables the use of falsely predicted synthetic lethals for metabolic model curation. By analyzing the functional classifications of the genes involved in synthetic lethals, we reveal surprising connections within and across clusters of orthologous group functional classifications

Recipients' experiences after organ transplantation

Background: After organ transplantation, many patients have diverse experiences; they face many changes in the physical and emotional aspects of their life. Patients' understandings of the post-transplantation period influence their adaptation to the changes. There is a need to improving the knowledge of patients' unique experiences of post-transplantation period and the changes occur in their life. Objective: To explore the experiences of organ recipients in the post-transplantation period. Methods: In a qualitative research using a hermeneutical phenomenological approach, data were collected from April 2015 to June 2016. Participants were consisted of 15 patients who received organ chosen using a purposive sampling method. In-depth semi-structured interviews were held with them. The collected data were analyzed using Diekelmann's hermeneutical analysis approach. Results: The data analyses led to the development of 3 main themes and 17 subthemes as "back from the grave" with the subthemes of "organ as the God's deposit," "God as the source of life," and "new life" "chapter of prosperity" with the subthemes of "the spring of the body," "recovery," "peace and joy," "benevolent and good behavior," "renewal," "opportunity of being together again," "golden age," "positive perspective," "the sense of normality," "the return of health," and "spiritual evolution" and "the fall" with the subthemes of "a lack of energy," "the mirage of transplantation," and "hell on the earth." Conclusion: The patients had diverse experiences of the post-transplantation period, which varied from the feeling of exhilaration and youth to losing energy and the wish for not undertaking organ transplantation. © 2018, Iranian Society for Organ Transplantation

Recipients' experiences after organ transplantation

Background: After organ transplantation, many patients have diverse experiences; they face many changes in the physical and emotional aspects of their life. Patients' understandings of the post-transplantation period influence their adaptation to the changes. There is a need to improving the knowledge of patients' unique experiences of post-transplantation period and the changes occur in their life. Objective: To explore the experiences of organ recipients in the post-transplantation period. Methods: In a qualitative research using a hermeneutical phenomenological approach, data were collected from April 2015 to June 2016. Participants were consisted of 15 patients who received organ chosen using a purposive sampling method. In-depth semi-structured interviews were held with them. The collected data were analyzed using Diekelmann's hermeneutical analysis approach. Results: The data analyses led to the development of 3 main themes and 17 subthemes as "back from the grave" with the subthemes of "organ as the God's deposit," "God as the source of life," and "new life" "chapter of prosperity" with the subthemes of "the spring of the body," "recovery," "peace and joy," "benevolent and good behavior," "renewal," "opportunity of being together again," "golden age," "positive perspective," "the sense of normality," "the return of health," and "spiritual evolution" and "the fall" with the subthemes of "a lack of energy," "the mirage of transplantation," and "hell on the earth." Conclusion: The patients had diverse experiences of the post-transplantation period, which varied from the feeling of exhilaration and youth to losing energy and the wish for not undertaking organ transplantation. © 2018, Iranian Society for Organ Transplantation

Impact of stoichiometry representation on simulation of genotype-phenotype relationships in metabolic networks.

<div><p>Genome-scale metabolic networks provide a comprehensive structural framework for modeling genotype-phenotype relationships through flux simulations. The solution space for the metabolic flux state of the cell is typically very large and optimization-based approaches are often necessary for predicting the active metabolic state under specific environmental conditions. The objective function to be used in such optimization algorithms is directly linked with the biological hypothesis underlying the model and therefore it is one of the most relevant parameters for successful modeling. Although linear combination of selected fluxes is widely used for formulating metabolic objective functions, we show that the resulting optimization problem is sensitive towards stoichiometry representation of the metabolic network. This undesirable sensitivity leads to different simulation results when using numerically different but biochemically equivalent stoichiometry representations and thereby makes biological interpretation intrinsically subjective and ambiguous. We hereby propose a new method, Minimization of Metabolites Balance (MiMBl), which decouples the artifacts of stoichiometry representation from the formulation of the desired objective functions, by casting objective functions using metabolite turnovers rather than fluxes. By simulating perturbed metabolic networks, we demonstrate that the use of stoichiometry representation independent algorithms is fundamental for unambiguously linking modeling results with biological interpretation. For example, MiMBl allowed us to expand the scope of metabolic modeling in elucidating the mechanistic basis of several genetic interactions in <em>Saccharomyces cerevisiae</em>.</p> </div