LA STIMOLAZIONE TRANSCRANICA A CORRENTI DIRETTE (TDCS) NEL TRATTAMENTO DELLA DEPRESSIONE: EFFETTI TERAPEUTICI E INTERAZIONE CON LA TERAPIA PSICOFARMACOLOGICA.

INTRODUZIONE La stimolazione transcranica con correnti dirette (transcranial Direct Current Stimulation, tDCS) \ue8 una metodica di stimolazione cerebrale non invasiva che consiste nell\u2019applicazione sullo scalpo di corrente continua di bassa intensit\ue0 non percepibile dal soggetto stimolato; la corrente \ue8 in grado di attraversare la teca cranica fino alla corteccia cerebrale. Negli ultimi anni tale metodica \ue8 stata utilizzata nello studio dei processi cognitivi, sia nei soggetti sani che nei pazienti affetti da disturbi neurologici e psichiatrici. Nessuno tra gli studi pubblicati ha sinora riportato gravi effetti collaterali o reazioni avverse. Nell\u2019ambito specifico delle patologie psichiatriche la tDCS ha trovato gi\ue0 dagli anni \u201860 numerose applicazioni evidenziando effetti benefici. Tali risultati sono ulteriormente consolidati in recenti studi in cui la tDCS sembra svolgere un ruolo importante nella modulazione di quelle aree che nella depressione risultano essere ipoattive e iperattive ed esercitare cos\uec un effetto antidepressivo. Gli studi sulla depressione lieve e moderata hanno dimostrato che la tDCS ha un\u2019efficacia terapeutica significativamente superiore al placebo e sovrapponibile a quella della Fluoxetina, ma con maggiore rapidit\ue0 di azione e minori effetti collaterali rispetto a quest\u2019ultima. In questo studio abbiamo esaminato le interazioni tra la tDCS e la terapia farmacologica in 82 pazienti depressi (unipolari e bipolari) che erano refrattari ad almeno un trattamento farmacologico. METODOLOGIA Il campione \ue8 composto da 82 pazienti affetti da depressione maggiore grave e farmaco resistente. Tutti i soggetti sono stati sottoposti ad un trattamento con tDCS (Corteccia Prefrontale Dorsolaterale), somministrato due volte al giorno a distanza di 4h, per 5 giorni consecutivi (intensit\ue0 di corrente: 2 mA per la durata di 20 minuti). Tutti i soggetti sono stati valutati in due tempi con la Beck depression Inventory (BDI), la Hamilton Depression Rating Scale: prima dell\u2019inizio del trattamento (T0), alla fine dei 5 giorni di trattamento (T1). RISULTATI Dopo cinque giorni di trattamento la metodica ha prodotto un miglioramento significativo in entrambe le scale (BDI 29% \ub1 36%, p<0.01; HDRS 18% \ub1 9%, p<0.01), I risultati hanno dimostrato che l\u2019uso delle benzodiazepine \ue8 associato ad un aumento dei punteggi alla scala BDI (+5.8 punti) (p<0.01) mentre gli altri antidepressivi hanno un effetto contrario (p<0.01). CONCLUSIONI In conclusione, la tDCS pu\uf2 essere una strategia terapeutica complementare ed adiuvante nella malattia depressiva. L'uso di benzodiazepine ostacola l'efficacia tDCS mentre l'uso degli antidepressivi sembra avere un effetto migliorativo, pertanto, il trattamento farmacologico deve essere sempre considerato nell'interpretazione dei dati.Background: Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression. Objective: To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment. Methods: This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20 minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome. Results: After 5 days of treatment BDI and HDRS scores decreased significantly (29% \ub1 36%, 18% \ub1 9%, respectively, p<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (\u3b2=4.92, p<0.01) and multivariate (\u3b2=5.8, p<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (\u3b2=-4.7, p=0.02). A similar trend was observed for tricyclics (\u3b2=-4, p=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs. Conclusion: Anodal tDCS over the left DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies

Marine magnetic investigation of the submarine base of Mt. Etna and Hyblean Plateau

Two marine magnetic surveys were carried out during 1997 and 1999 in the Ionian Sea off the eastern coast of Sicily to investigate the magnetic structures of the eastern base of Mt. Etna and the Hyblean Plateau. The investigated area is approximately 85 km long and 15 km wide, running from North to South, in the Western Ionian Sea. Models along two profiles parallel to the coast and over the entire area provide a possible distribution of volcanic bodies and volcaniclastic deposits off the eastern coast of Sicily and their relations with the sedimentary substratum. 3D modeling suggests the presence of magnetized bodies, inserted in the sedimentary substratum, plausibly related to Hyblean Plateau volcanism in the south sector and to Mt. Etna activity in the north. We speculate that the Malta Escarpment could have produced preferential ways for magma ascents off the Hyblean Plateau. The spatial continuity of the volcanism affecting the entire investigated area could testify spatial transition between Hyblean and Etnean volcanism supporting the hypothesis that the magma process migrated with time from south-east to north-west

Conceptual design of the enhanced coolant purification systems for the European HCLL and HCPB test blanket modules

The Coolant Purification Systems (CPSs) is one of the most relevant ancillary systems of European Helium Cooled Lead Lithium (HCLL) and Helium Cooled Pebble Bed (HCPB) Test Blanket Modules (TBMs) which are currently in the preliminary design phase in view of their installation and operation in ITER. The CPS implements mainly two functions: the extraction and concentration of the tritium permeated from the TBM modules into the primary cooling circuit and the chemistry control of helium primary coolant. During the HCLL and HCPB-TBSs (Test Blanket Systems) Conceptual Design Review (CDR) in 2015 it was recognized the need of reducing the tritium permeation into the Port Cell #16 of ITER. To achieve this and, then, to lower the tritium partial pressure in the Helium Cooling Systems in normal operation, the helium flow-rate treated by each CPS has been increased of almost one order of magnitude. In 2017, to satisfy the CDR outcomes and the new design requirements requested by Fusion for Energy (F4E, the European Domestic Agency for ITER), ENEA performed a preliminary design of the “enhanced” CPSs. This paper presents the current design of the “enhanced” CPSs, focusing on design requirements, assumptions, selection of technologies and preliminary components sizing

Molecular signals from primordial clouds at high redshift

The possibility to detect cosmological signals from the post-recombination Universe is one of the main aims of modern cosmology. In a previous paper we emphasized the role that elastic resonant scattering through LiH molecules can have in dumping primary CBR anisotropies and raising secondary signals. Here we extend our analysis to all the evolutionary stages of a primordial cloud, starting with the linear phase, through the turn-around and to the non linear collapse. We have done calculations for proto-clouds in a CDM scenario and, more generally, for a set of clouds with various masses and various turn-around redshifts, in this case without referring to any particular structure formation scenario. We found that the first phase of collapse, for $t/t_{free-fall}=0.05\div 0.2$ is the best one for simultaneous detection of the first two LiH rotational lines. The observational frequency falls between 30 and 250 GHz and the line width ${\Delta \nu\over \nu}$ is between $10^{-5}$ and $10^{-4}$. As far as we know this is the most favourable process to detect primordial clouds before they start star formation processes.Comment: 26 pages, uuencoded compressed postscript, 7 figures included. Accepted for publication in Ap.

A competitive cell-permeable peptide impairs Nme-1 (NDPK-A) and Prune-1 interaction: therapeutic applications in cancer.

The understanding of protein–protein interactions is crucial in order to generate a second level of functional genomic analysis in human disease. Within a cellular microenvironment, protein–protein interactions generate new functions that can be defined by single or multiple modes of protein interactions. We outline here the clinical importance of targeting of the Nme-1 (NDPK-A)–Prune-1 protein complex in cancer, where an imbalance in the formation of this protein–protein complex can result in inhibition of tumor progression. We discuss here recent functional data using a small synthetic competitive cell-permeable peptide (CPP) that has shown therapeutic efficacy for impairing formation of the Nme-1–Prune-1 protein complex in mouse preclinical xenograft tumor models (e.g., breast, prostate, colon, and neuroblastoma). We thus believe that further discoveries in the near future related to the identification of new protein–protein interactions will have great impact on the development of new therapeutic strategies against various cancers

Durability of Benefits From Supervised Treadmill Exercise in People With Peripheral Artery Disease.

Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6-minute walk distance and short physical performance battery at 6-month follow-up and have been reported previously. Secondary outcomes were change in 6-minute walk and short physical performance battery at 12-month follow-up and are reported here. A group of 134 participants (86%) completed the 12-month follow-up. At 6-month follow-up, compared with control, 6-minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI =13.9-58.3, P=0.001). Between 6- and 12-month follow-up, 6-minute walk distance significantly declined (-28.6 m, 95% CI=-52.6 to -4.5, P=0.020) and physical activity declined -272 activity units (95% CI =-546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12-month follow-up, 6 months after completing supervised treadmill exercise, change in 6-minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI =-17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6-month or 12-month follow-up. Conclusions A 6-month supervised treadmill exercise intervention that improved 6-minute walk distance at 6-month follow-up did not have persistent benefit at 12-month follow-up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Identifier: NCT 00106327

Transcranial cerebellar direct current stimulation (tcDCS): motor control, cognition, learning and emotions

The neurological manifestations of cerebellar diseases range from motor to cognitive or behavioral abnormalities. Experimental data in healthy subjects extend the cerebellar role to learning, emotional and mood control. The need for a non-invasive tool to influence cerebellar function in normal and pathological conditions led researchers to develop transcranial cerebellar direct current stimulation (tcDCS). tcDCS, like tDCS, depends on the principle that weak direct currents delivered at around 2. mA for minutes over the cerebellum through surface electrodes induce prolonged changes in cerebellar function. tcDCS modulates several cerebellar skills in humans including motor control, learning and emotional processing. tcDCS also influences the cerebello-brain interactions induced by transcranial magnetic stimulation (TMS), walking adaptation, working memory and emotional recognition. Hence tcDCS is a simple physiological tool that can improve our physiological understanding of the human cerebellum, and should prove useful also in patients with cerebellar dysfunction or psychiatric disorders and those undergoing neurorehabilitation to enhance neuroplasticity

Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index &lt;0.90 were identified from Chicago-area hospitals in 2002-2004. Weight and 6-minute walk distance were measured annually. Weight change categories were weight loss or gain (≥5 pounds/year at ≥1 visit) or stable (weight change &lt;5 pounds at each visit). Participants reported whether weight loss was "intentional" or "unintentional." Calf muscle area was measured with computed tomography every 2 years. Associations of weight change with changes in calf muscle area and 6-minute walk distance were analyzed using mixed-effects models and adjusted for age, body mass index, ankle-brachial index, physical activity, and other confounders. Among 389 participants, mean ankle-brachial index was 0.63±0.16, mean age was 74.5±7.8, and mean body mass index was 28.1±5.1 kg/m2. Over 3.23±1.37 years, muscle area declined more in adults with intentional weight loss versus stable or gain (pair-wise comparisons, P&lt;0.001). Intentional weight loss was associated with less annual decline in 6-minute walk distance than weight gain (intentional loss, 3.7 m; stable, -14.0 m; gain, -28.5 m; unintentional loss, -20.8 m; pair-wise comparison intentional loss versus gain, P=0.003). Conclusions Despite a greater loss of calf muscle area, adults with peripheral artery disease who intentionally lost ≥5 pounds experienced less functional decline than those who gained weight. A randomized trial is needed to establish whether benefits of weight loss in peripheral artery disease outweigh potential adverse effects

Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Background The effects of race on response to medical therapy in people with peripheral artery disease ( PAD ) are unknown. Methods and Results In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial, PAD participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte-macrophage colony-stimulating factor ( GM - CSF ) (Group 1), exercise+placebo (Group 2), attention control+ GM - CSF (Group 3), or attention control+placebo (Group 4). Change in 6-minute walk distance was measured at 12- and 26-week follow-up. In these exploratory analyses, groups receiving GM - CSF (Groups 1 and 3), placebo (Groups 2 and 4), exercise (Groups 1 and 2), and attention control (Groups 2 and 4) were combined, maximizing statistical power for studying the effects of race on response to interventions. Of 210 PAD participants, 141 (67%) were black and 64 (30%) were white. Among whites, GM - CSF improved 6-minute walk distance by +22.0 m (95% CI : -4.5, +48.5, P=0.103) at 12 weeks and +44.4 m (95% CI : +6.9, +82.0, P=0.020) at 26 weeks, compared with placebo. Among black participants, there was no effect of GM - CSF on 6-minute walk distance at 12-week ( P=0.26) or 26-week (-5.0 m [-27.5, +17.5, P=0.66]) follow-up, compared with placebo. There was an interaction of race on the effect of GM - CSF on 6-minute walk change at 26-week follow-up ( P=0.018). Exercise improved 6-minute walk distance in black ( P=0.006) and white ( P=0.034) participants without interaction. Conclusions GM - CSF improved 6-minute walk distance in whites with PAD but had no effect in black participants. Further study is needed to confirm racial differences in GM - CSF efficacy in PAD . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01408901