GABAergic neuroactive steroids: A new frontier in bipolar disorders?

Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane neurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in the investigation of the etiology and treatment of mood disorders, particularly bipolar disorders

Non-perturbative renormalisation and running of BSM four-quark operators in Nf=2 QCD

We perform a non-perturbative study of the scale-dependent renormalisation factors of a complete set of dimension-six four-fermion operators without power subtractions. The renormalisation-group (RG) running is determined in the continuum limit for a specific Schrödinger Functional (SF) renormalisation scheme in the framework of lattice QCD with two dynamical flavours (Nf= 2). The theory is regularised on a lattice with a plaquette Wilson action and O(a)-improved Wilson fermions. For one of these operators, the computation had been performed in Dimopoulos et al. (JHEP 0805, 065 (2008). arXiv:0712.2429); the present work completes the study for the rest of the operator basis, on the same simulations (configuration ensembles). The related weak matrix elements arise in several operator product expansions; in Δ F= 2 transitions they contain the QCD long-distance effects, including contributions from beyond-Standard Model (BSM) processes. Some of these operators mix under renormalisation and their RG-running is governed by anomalous dimension matrices. In Papinutto et al. (Eur Phys J C 77(6), 376 (2017). arXiv:1612.06461) the RG formalism for the operator basis has been worked out in full generality and the anomalous dimension matrix has been calculated in NLO perturbation theory. Here the discussion is extended to the matrix step-scaling functions, which are used in finite-size recursive techniques. We rely on these matrix-SSFs to obtain non-perturbative estimates of the operator anomalous dimensions for scales ranging from O(Λ QCD) to O(MW)

PRIMI RISULTATI DI UN INDAGINE SULLO STATO DELLE SISTEMAZIONI IDRAULICO-FORESTALI NEL BACINO DELL’ARNO

Il presente lavoro è relativo ai risultati ottenuti con il primo stato d’avanzamento di una ricerca sullo stato delle Sistemazioni Idraulico-Forestali per assegnate aree di indagine comprese nel bacino del fiume Arno affidata dall’ Autorità di Bacino del Fiume Arno al Dipartimento di Ingegneria Agraria e Forestale dell’Università degli Studi di Firenze. Innanzi tutto, è stata condotta un’analisi preventiva, mediante un database, di documentazione relativa alle opere idrauliche già censite in precedenti lavori (prof. Grazi) con identificazione della posizione geografica delle opere stesse con l’ausilio di software GIS. A questa prima fase sono seguiti la predisposizione di una opportuna scheda di rilievo (sia cartacea sia elettronica) e quindi sopralluoghi in campo condotti mediante l’ausilio di un GPS collegato a computer palmare per il supporto cartografico di base. Rilievi di dettaglio sono stati condotti nei torrenti dell’area del Mugello, già oggetto di studi risalenti a una trentina di anni fa per la valutazione delle pendenze di compensazione (Falciai et al.) che sono stati utilizzati spesso in letteratura (Ferro et al., Pica et al., etc.). Con riferimento ad altre zone campione del bacino (es. Casentino e Area Fiorentina), la documentazione storica ed il sopralluogo in campo (su base statistica) ha avuto lo scopo di rintracciare le opere esistenti e verificare l’attendibilità e la confrontabilità dei vari censimenti eseguiti anche da altri Enti preposti. In particolare si è analizzato il dimensionamento delle opere ed il loro stato attuale di conservazione ed efficienza, confrontandolo con quanto riportato in eventuali elaborati progettuali e nei censimenti precedenti. Eventuali danneggiamenti dei manufatti possono essere derivati dalle valutazioni in sede progettuale, da scarsa o inesistente manutenzione o da mutate caratteristiche in alveo e nel bacino. Per avere qualche indicazione in proposito si è valutata la portata di progetto a partire dalle dimensioni delle gavete considerate come stramazzi in parete grossa e se ne è stimato il tempo di ritorno, mediante i modelli AlTo (Regione Toscana) e Idrarno (Autorità di Bacino). Questa fase ha richiesto un lavoro preventivo di queries spaziali che hanno lo scopo di attribuire il codice dell’asta a cui appartengono le opere idrauliche in esame (all’interno del reticolo idrografico del modello AlTo e all’interno del reticolo “Sistema Acque” dell’Autorità di Bacino dell’Arno). Questa operazione consente, inoltre, il collegamento tra il contenuto informativo del geodatabase dell’Autorità di Bacino con il sistema di regionalizzazione delle portate di piena della Regione Toscana. Mediante la misura delle caratteristiche dimensionali dell’opera si sono cercate di ricavare anche indicazioni statistiche riguardo alla pendenza di compensazione dei corsi d’acqua in esame. Le verifiche in campo ha permesso anche una descrizione delle condizioni generali dell’alveo in cui sono situate le opere e dei versanti siti in prossimità delle opere stesse. I dati raccolti sono stati immessi in un geodatabase opportunamente costruito secondo lo standard di quello esistente presso l’Autorità di Bacino del Fiume Arno e quindi elaborati per la ricerca delle relazioni tra le caratteristiche delle opere e la pendenza attuale dell’alveo nonché la stima della necessità, per i corsi d’acqua esaminati, di opere atte a garantire la continuità fluviale per la ittiofauna (Pini Prato e Barneschi)

Insight into susceptibility genes associated with bipolar disorder: A systematic review

Objective: Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by suicide. All these characteristics suggest that the disorders within the bipolar spectrum are a crucial public health problem. With the development of molecular genetics in recent decades, it was possible to more easily detect risk genes associated with this disorder. This study aimed at summarizing the findings of systematic reviews and meta-analyses on the topic and assessing the quality of the available evidence. Materials and Methods: PubMed/Medline and Web of Science were searched to identify systematic reviews and meta-analyses published during 2013-2019. Standard methodology was applied to synthesize and assess the retrieved literature. Results: This systematic review identifies a number of potential risk genes associated with bipolar disorder whose mechanism of action has yet to be confirmed. They are divided into several groups: 1) a list of the most significant susceptibility genetic factors associated with BD; 2) the implication of the ZNF804A gene in BD; 3) the role of genes involved in calcium signaling in BD; 4) DNA methylation in BD; 5) BD and risk suicide genes; 6) susceptibility genes for early-onset BD; 7) candidate genes common to both BD and schizophrenia; 8) genes involved in cognitive status in BD cases; 9) genes involved in structural alteration in BD brain tissue; 10) genes involved in lithium response in BD. Conclusions: Future research should concentrate on molecular mechanisms by which genetic variants play a major role in BD. Supplemental research is needed to replicate the applicable results

The Current Quality of Web-Based Information on the Treatment of Bipolar Disorder: A Systematic Search

Background: An important aspect of managing chronic disorders like bipolar disorder is to have access to relevant health information. This study investigates and compares the quality of information on the treatments of bipolar disorder that is available on English websites, as an international language, and on Italian websites, as a popular local language. Methods: A systematic review search was obtained from four search engines. We excluded unrelated materials, scientific papers, and duplicates. We analyzed popularity with PageRank; technological quality with Nibbler; readability with the Flesh Reading Ease test and Gulpease index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and on the extent of adherence to the HONCode. Results: 35 English and 31 Italian websites were included. The English websites were found to have a higher level of quality information and technological quality than the Italian ones. Overall, the websites were found to be difficult to read, requiring a high level of education. Conclusions: These results can be important to inform guidelines for the improvement of health information and help users to reach a higher level of evidence on the websites. Users should find the benefits of treatment, support for shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing treatment

Quality of information of websites dedicated to obesity: a systematic search to promote high level of information for Internet users and professionals

Background: The Internet is increasingly used as a source of information. This study investigates with a multidimensional methodology the quality of information of websites dedicated to obesity treatment and weight-loss interventions. We compared websites in English, a language that it is used for the international scientific divulgation, and in Italian, a popular local language. Methods: Level of Evidence: Level I, systematic review search on four largely used search engines. Duplicated and unrelated websites were excluded. We checked: popularity with PageRank; technological quality with Nibbler; readability with the Flesch Reading Ease test or the Gulpease readability index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and the adherence to the Health on the Net Code. Results: 63 Italian websites and 41 English websites were evaluated. English websites invested more in the technological quality especially for the marketing, experience of the user, and mobile accessibility. Both the Italian and English websites were of poor quality and readability. Conclusions: These results can inform guidelines for the improvement of health information and help Internet users to achieve a higher level of information. Users must find benefits of treatment, support to the shared decision-making, the sources used, the medical editor's supervision, and the risk of postponing the treatment