Metabolic profile and root development of Hypericum perforatum L. in vitro roots under stress conditions due to chitosan treatment and culture time

The responses of Hypericum perforatum root cultures to chitosan elicitation had been investigated through 1H-NMR-based metabolomics associated with morpho-anatomical analyses. The root metabolome was influenced by two factors, i.e., time of culture (associated with biomass growth and related “overcrowding stress”) and chitosan elicitation. ANOVA simultaneous component analysis (ASCA) modeling showed that these factors act independently. In response to the increase of biomass density over time, a decrease in the synthesis of isoleucine, valine, pyruvate, methylamine, etanolamine, trigonelline, glutamine and fatty acids, and an increase in the synthesis of phenolic compounds, such as xanthones, epicatechin, gallic, and shikimic acid were observed. Among the xanthones, brasilixanthone B has been identified for the first time in chitosan-elicited root cultures of H. perforatum. Chitosan treatment associated to a slowdown of root biomass growth caused an increase in DMAPP and a decrease in stigmasterol, shikimic acid, and tryptophan levels. The histological analysis of chitosan-treated roots revealed a marked swelling of the root apex, mainly due to the hypertrophy of the first two sub-epidermal cell layers. In addition, periclinal divisions in hypertrophic cortical cells, resulting in an increase of cortical layers, were frequently observed. Most of the metabolic variations as well as the morpho-anatomical alterations occurred within 72 h from the elicitation, suggesting an early response of H. perforatum roots to chitosan elicitation. The obtained results improve the knowledge of the root responses to biotic stress and provide useful information to optimize the biotechnological production of plant compounds of industrial interest

Near-field propagation of tsunamis from megathrust earthquakes

We investigate controls on tsunami generation and propagation in the near-field of great megathrust earthquakes using a series of numerical simulations of subduction and tsunamigenesis on the Sumatran forearc. The Sunda megathrust here is advanced in its seismic cycle and may be ready for another great earthquake. We calculate the seafloor displacements and tsunami wave heights for about 100 complex earthquake ruptures whose synthesis was informed by reference to geodetic and stress accumulation studies. Remarkably, results show that, for any near-field location: (1) the timing of tsunami inundation is independent of slip-distribution on the earthquake or even of its magnitude, and (2) the maximum wave height is directly proportional to the vertical coseismic displacement experienced at that location. Both observations are explained by the dominance of long wavelength crustal flexure in near-field tsunamigenesis. The results show, for the first time, that a single estimate of vertical coseismic displacement might provide a reliable short-term forecast of the maximum height of tsunami waves

Durability of repair mortars used in restoration of a Sardinian coastal tower: assessment after ten years

[EN] This study reports the results of investigations on conservation conditions of an ancient tower, called Torre del Pozzo, located in the S-W coast of Sardinia, restored about ten years ago. The tower suffers from serious problems related to vulnerability of building materials, particularly limestone and sandstones and aerial lime mortar with poor physical-mechanical properties. Over the centuries the materials were subjected to aggressive actions (wind corrasion and salt crystallization) causing an intense erosion of the walls with consequent partial collapse of the structure. About ten years ago a restoration involved the mortars and only the replacement and integration of ashlars deteriorated. After about 10 years from this intervention, some inspections have been carried out in order to assess the effectiveness of the intervention and the state of preservation of the tower. This paper focuses on analyses and tests carried out to assess condition and durability of the repair mortars.Meloni, P.; Carcangiu, G.; Palomba, M.; Enzo, S.; Carboni, M.; Cocco, O.; Casti, M.... (2015). Durability of repair mortars used in restoration of a Sardinian coastal tower: assessment after ten years. En Defensive architecture of the mediterranean: XV to XVIII centuries. Vol. II. Editorial Universitat Politècnica de València. 397-44. https://doi.org/10.4995/FORTMED2015.2015.1761OCS3974

Overcoming treatment-resistant depression with machine-learning based tools: a study protocol combining EEG and clinical data to personalize glutamatergic and brain stimulation interventions (SelecTool Project)

© 2024 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD’s clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool’s recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.Peer reviewe

TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study

Background: Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. Objectives: The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Methods: Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Results: Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. Conclusions: We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

The Effects of \u201cVelaMente?!\u201d Project on Social Functioning of People With Severe Psychosocial Disabilities

Abstract: Introduction: Physical activity helps to improve several clinical outcomes of people with severe psychosocial disabilities. The aims of this study were; 1) to assess the efficacy of a psychosocial rehabilitative intervention focused on sailing in a crew on: a) social functioning; b) severity of the psychosocial disability; c) general functioning; d) dysregulation of biorhythms of people with severe psychosocial disabilities, and 2) to evaluate the attenders\u2019 satisfaction about the project. Methods: A randomized waitlist controlled trial with parallel groups was carried out involving 51 people with severe psychosocial disabilities. The intervention was a 3 months-lasting course to learn sailing in a crew. Just after the randomization, a group began the sailing course and the other group (wait list) attended the sailing course after 3 months of treatments as usual. Before and after the sailing course, as well as the waiting list period, all attenders were assessed by HoNOS, GAF, CGI-S and BRIAN. At the end of the sailing course, they completed also a self-report satisfaction questionnaire. Results: Social functioning significantly improved after the sailing course (HoNOS total score \u201ctime X group\u201d: p=0.011), mainly because of the improvement of psychopathological symptoms (HoNOS symptoms score \u201ctime X group\u201d: p=0.003). Furthermore, participants greatly appreciated the rehabilitative program based on sailing in a crew. Conclusions: When compared to more traditional rehabilitative activities that are usually carried out in mental health services, a psychosocial rehabilitative intervention based on sailing in a crew significantly improve the social functioning of people with severe psychosocial disabilities

Therapeutic choices and disease activity after 2 years of treatment with cladribine: An Italian multicenter study (CladStop)

background and purpose: cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited. methods: this retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2-year course of cladribine treatment. the primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2-year treatment course. results: a total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. the study found a significant reduction in annualized relapse rate at the 12-month follow-up after cladribine completion compared to the year prior to starting therapy (0.07 +/- 0.25 vs. 0.82 +/- 0.80, p < 0.001). furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. the safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event. conclusions: this study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. real-world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. however, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long-term impact are necessary

NEDA-3 achievement in early highly active relapsing remitting multiple sclerosis patients treated with Ocrelizumab or Natalizumab

background: in the early stages of multiple sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. this study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years. methods: we retrospectively enrolled treatment-naïve HAMS patients undergoing NAT or OCR, collecting demographic, clinical, and instrumental data before and after treatment initiation to compare with propensity score analysis disease activity, time to disability worsening, and NEDA-3 achievement. results: we recruited 281 HAMS patients with a mean age of 32.7 years (SD 10.33), treated with NAT (157) or OCR (124). after three years, the kaplan-meier probability of achieving NEDA-3 was 66.0 % (95 % CI: 57.3 % - 76.0 %) with OCR and 68.2 % (95 % CI: 59.9 % - 77.7 %) with NAT without significant differences between the two groups (p = 0.27) DISCUSSION AND CONCLUSION: starting HE DMT with monoclonal antibodies for HAMS could achieve NEDA-3 in a high percentage of patients without differences between NAT or OCR

TGF DETECTION BY AGILE

We report the detection by the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite of terrestrial gamma ray flashes (TGFs) obtained with the minicalorimeter (MCAL) detector operating in the ..