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Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged.
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We study the deterministic dynamics of N point particles moving at a constant speed in a 2D table made of two polygonal urns connected by an active rectangular channel, which applies a feedback control on the particles, inverting the horizontal component of their velocities when their number in the channel exceeds a fixed threshold. Such a bounce-back mechanism is non-dissipative: it preserves volumes in phase space. An additional passive channel closes the billiard table forming a circuit in which a stationary current may flow. Under specific constraints on the geometry and on the initial conditions, the large N limit allows nonequilibrium phase transitions between homogeneous and inhomogeneous phases. The role of ergodicity in making a probabilistic theory applicable is discussed for both rational and irrational urns. The theoretical predictions are compared with the numerical simulation results. Connections with the dynamics of feedback-controlled biological systems are highlighted.
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Simulação por ComputadorRESUMO
Background: Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile. Methods: Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted. Results: Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence. Limitations: This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression. Conclusion: While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression. Systematic review registration: [https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).
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Background: Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning. Methods: After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up. Results: Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders' rates. Conclusion: Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables.