Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?:

Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames ("exergames"). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy

Assessing Perfusion in Steno-Occlusive Cerebrovascular Disease Using Transient Hypoxia-Induced Deoxyhemoglobin as a Dynamic Susceptibility Contrast Agent

BACKGROUND AND PURPOSE Resting brain tissue perfusion in cerebral steno-occlusive vascular disease can be assessed by MR imaging using gadolinium-based susceptibility contrast agents. Recently, transient hypoxia-induced deoxyhemoglobin has been investigated as a noninvasive MR imaging contrast agent. Here we present a comparison of resting perfusion metrics using transient hypoxia-induced deoxyhemoglobin and gadolinium-based contrast agents in patients with known cerebrovascular steno-occlusive disease. MATERIALS AND METHODS Twelve patients with steno-occlusive disease underwent DSC MR imaging using a standard bolus of gadolinium-based contrast agent compared with transient hypoxia-induced deoxyhemoglobin generated in the lungs using an automated gas blender. A conventional multi-slice 2D gradient echo sequence was used to acquire the perfusion data and analyzed using a standard tracer kinetic model. MTT, relative CBF, and relative CBV maps were generated and compared between contrast agents. RESULTS The spatial distributions of the perfusion metrics generated with both contrast agents were consistent. Perfusion metrics in GM and WM were not statistically different except for WM MTT. CONCLUSIONS Cerebral perfusion metrics generated with noninvasive transient hypoxia-induced changes in deoxyhemoglobin are very similar to those generated using a gadolinium-based contrast agent in patients with cerebrovascular steno-occlusive disease

Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study

Background: Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors. Methods: A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI. Results: Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps. Conclusion: Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion

Cosmology with the Laser Interferometer Space Antenna

254 pags:, 44 figs.The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational-wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational-wave observations by LISA to probe the universe.This work is partly supported by: A.G. Leventis Foundation; Academy of Finland Grants 328958 and 345070; Alexander S. Onassis Foundation, Scholarship ID: FZO 059-1/2018-2019; Amaldi Research Center funded by the MIUR program “Dipartimento di Eccellenza” (CUP: B81I18001170001); ASI Grants No. 2016-24-H.0 and No. 2016-24-H.1-2018; Atracción de Talento Grant 2019-T1/TIC-15784; Atracción de Talento contract no. 2019-T1/TIC-13177 granted by the Comunidad de Madrid; Ayuda ‘Beatriz Galindo Senior’ by the Spanish ‘Ministerio de Universidades’, Grant BG20/00228; Basque Government Grant (IT-979-16); Belgian Francqui Foundation; Centre national d’Etudes spatiales; Ben Gurion University Kreitman Fellowship, and the Israel Academy of Sciences and Humanities (IASH) & Council for Higher Education (CHE) Excellence Fellowship Program for International Postdoctoral Researchers; Centro de Excelencia Severo Ochoa Program SEV-2016-0597; CERCA program of the Generalitat de Catalunya; Cluster of Excellence “Precision Physics, Fundamental Interactions, and Structure of Matter” (PRISMA? EXC 2118/1); Comunidad de Madrid, Contrato de Atracción de Talento 2017-T1/TIC-5520; Czech Science Foundation GAČR, Grant No. 21-16583M; Delta ITP consortium; Department of Energy under Grant No. DE-SC0008541, DE-SC0009919 and DESC0019195; Deutsche Forschungsgemeinschaft (DFG), Project ID 438947057; Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy - EXC 2121 Quantum Universe - 390833306; European Structural and Investment Funds and the Czech Ministry of Education, Youth and Sports (Project CoGraDS - CZ.02.1.01/0.0/0.0/15 003/0000437); European Union’s H2020 ERC Consolidator Grant “GRavity from Astrophysical to Microscopic Scales” (Grant No. GRAMS-815673); European Union’s H2020 ERC, Starting Grant Agreement No. DarkGRA-757480; European Union’s Horizon 2020 programme under the Marie Sklodowska-Curie Grant Agreement 860881 (ITN HIDDeN); European Union’s Horizon 2020 Research and Innovation Programme Grant No. 796961, “AxiBAU” (K.S.); European Union’s Horizon 2020 Research Council grant 724659 MassiveCosmo ERC-2016-COG; FCT through national funds (PTDC/FIS-PAR/31938/2017) and through project “BEYLA – BEYond LAmbda” with Ref. Number PTDC/FIS-AST/0054/2021; FEDER-Fundo Europeu de Desenvolvimento Regional through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI-01-0145- FEDER-031938) and research Grants UIDB/04434/2020 and UIDP/04434/2020; Fondation CFM pour la Recherche in France; Foundation for Education and European Culture in Greece; French ANR project MMUniverse (ANR-19-CE31-0020); FRIA Grant No.1.E.070.19F of the Belgian Fund for Research, F.R. S.-FNRS Fundação para a Ciência e a Tecnologia (FCT) through Contract No. DL 57/2016/CP1364/ CT0001; Fundação para a Ciência e a Tecnologia (FCT) through Grants UIDB/04434/2020, UIDP/04434/ 2020, PTDC/FIS-OUT/29048/2017, CERN/FIS-PAR/0037/2019 and “CosmoTests – Cosmological tests of gravity theories beyond General Relativity” CEECIND/00017/2018; Generalitat Valenciana Grant PROMETEO/2021/083; Grant No. 758792, project GEODESI; Government of Canada through the Department of Innovation, Science and Economic Development and Province of Ontario through the Ministry of Colleges and Universities; Grants-in-Aid for JSPS Overseas Research Fellow (No. 201960698); I?D Grant PID2020-118159GB-C41 of the Spanish Ministry of Science and Innovation; INFN iniziativa specifica TEONGRAV; Israel Science Foundation (Grant No. 2562/20); Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Nos. 20H01899 and 20H05853; IFT Centro de Excelencia Severo Ochoa Grant SEV-2; Kavli Foundation and its founder Fred Kavli; Minerva Foundation; Ministerio de Ciencia e Innovacion Grant PID2020-113644GB-I00; NASA Grant 80NSSC19K0318; NASA Hubble Fellowship grants No. HST-HF2-51452.001-A awarded by the Space Telescope Science Institute with NASA contract NAS5-26555; Netherlands Organisation for Science and Research (NWO) Grant Number 680-91-119; new faculty seed start-up grant of the Indian Institute of Science, Bangalore, the Core Research Grant CRG/2018/002200 of the Science and Engineering; NSF Grants PHY-1820675, PHY-2006645 and PHY-2011997; Polish National Science Center Grant 2018/31/D/ ST2/02048; Polish National Agency for Academic Exchange within the Polish Returns Programme under Agreement PPN/PPO/2020/1/00013/U/00001; Pró-Reitoria de Pesquisa of Universidade Federal de Minas Gerais (UFMG) under Grant No. 28359; Ramón y Cajal Fellowship contract RYC-2017-23493; Research Project PGC2018-094773-B-C32 [MINECO-FEDER]; Research Project PGC2018-094773-B-C32 [MINECO-FEDER]; ROMFORSK Grant Project. No. 302640; Royal Society Grant URF/R1/180009 and ERC StG 949572: SHADE; Shota Rustaveli National Science Foundation (SRNSF) of Georgia (Grant FR/18-1462); Simons Foundation/SFARI 560536; SNSF Ambizione grant; SNSF professorship Grant (No. 170547); Spanish MINECO’s “Centro de Excelencia Severo Ochoa” Programme Grants SEV-2016- 0597 and PID2019-110058GB-C22; Spanish Ministry MCIU/AEI/FEDER Grant (PGC2018-094626-BC21); Spanish Ministry of Science and Innovation (PID2020-115845GB-I00/AEI/10.13039/ 501100011033); Spanish Proyectos de I?D via Grant PGC2018-096646-A-I00; STFC Consolidated Grant ST/T000732/1; STFC Consolidated Grants ST/P000762/1 and ST/T000791/1; STFC Grant ST/ S000550/1; STFC Grant ST/T000813/1; STFC Grants ST/P000762/1 and ST/T000791/1; STFC under the research Grant ST/P000258/1; Swiss National Science Foundation (SNSF), project The Non-Gaussian Universe and Cosmological Symmetries, Project Number: 200020-178787; Swiss National Science Foundation Professorship Grants No. 170547 and No. 191957; SwissMap National Center for Competence in Research; “The Dark Universe: A Synergic Multi-messenger Approach” Number 2017X7X85K under the MIUR program PRIN 2017; UK Space Agency; UKSA Flagship Project, Euclid.Peer reviewe

Cerebral hemodynamic in patients with acute symptomatic internal carotid artery occlusion: correlation and agreement analysis between transcranial Doppler (TCD) and quantitative magnetic resonance angiography (q-MRA) with non-invasive optimal vascular analysis (NOVA)

The management of patients with symptomatic carotid artery occlusion after the acute phase is based on the extensive assessment of hemodynamic parameters with particular focus on activated collateral pathways and cerebral blood flow (CBF). Transcranial Doppler (TCD) represents the standard in the assessment of blood flow velocity and direction in the main cerebral vessels. Quantitative magnetic resonance angiography (q-MRA) with non-invasive optimal vessel analysis (NOVA) is a unique MRI technique that enables precise non-invasive quantitative measurements (in mL/min) of the flow in cerebral vessels. The purpose of this work was to test correlation and agreement between these two examinations for the flow and velocities measurements in cerebral arteries of a specific patient population with acute symptomatic, persisting unilateral occlusion of the internal carotid artery (ICA)

Human muscle aging: ROS-mediated alterations in rectus abdominis and vastus lateralis muscles

: Aging is related to the accumulation of reactive oxygen species (ROS)-mediated oxidative damage. Considering the heterogeneity of age-related changes and the involvement of muscles in different functions, we compared the aging process in different functional muscles. We studied age-related changes in rectus abdominis (RA) and vastus lateralis (VL) in subjects of different age (18-48- and 66-90-year-old). We analysed fiber distribution, antioxidant enzymatic systems: Mn and CuZn superoxide dismutase (MnSOD, CuZnSOD), glutathione peroxidase (GSHPx), catalase (CAT), as well as oxidative damage markers: lipoperoxide levels (LPO), carbonylated proteins (CP), reduced and oxidized glutathione (GSH, GSSG) content and the GSH/GSSG ratio. In the muscles analysed, type I fiber increases during aging with a consequent decrease in type II distribution. In the elderly group RA MnSOD showed higher activity than VL. Furthermore, in RA MnSOD was higher in the elder group than in the younger group. CuZnSOD, as well as GSHPx and CAT activities remained unchanged. LPO levels in VL increase with age; moreover, in the elderly group VL showed higher value than RA. CP, GSH and GSSG remained unchanged, while GSH/GSSG decreases in RA during aging. In conclusion, a relationship between aging and ROS seems to exist, but oxidative processes could evolve in different ways in muscles with different functions

Human muscle aging: ROS-mediated alterations in rectus abdominis and vastus lateralis muscles

Aging is related to the accumulation of reactive oxygen species (ROS)-mediated oxidative damage. Considering the heterogeneity of age-related changes and the involvement of muscles in different functions, we compared the aging process in different functional muscle

Otto studi sul sonetto. Dai Siciliani al Manierismo

Questo libro affida a otto giovani studiosi altrettanti capitoli sulla storia del sonetto, il genere metrico pi\uf9 diffuso nella tradizione lirica italiana ed europea. Ciascuno degli autori si occupa di un poeta o di una stagione di quella vicenda, dai Siciliani al Manierismo di secondo Cinquecento, e mette a fuoco la fisionomia della forma sulla base di parametri coerenti e omogenei. In tal modo la \u201cgrammatica\u201d del sonetto individuata in un canzoniere, o in un gruppo di canzonieri, finisce per diventare un fatto storicamente rilevante, un singolo punto che prende senso perch\ue9 parte di un sistema in divenire, che lo ingloba ma anche lo trascende, e che coincide in ultima analisi con la tradizione, appunto, storica di questo metro. Tanto che il disegnare quel sistema per intero, nello spazio e nel tempo, potrebbe essere indicato come l\u2019orizzonte ideale che orienta questo tipo di ricerche

Otto studi sul sonetto

Questo libro affida a otto giovani studiosi altrettanti capitoli sulla storia del sonetto, il genere metrico pi\uf9 diffuso nella tradizione lirica italiana ed europea. Ciascuno degli autori si occupa di un poeta o di una stagione di quella vicenda, dai Siciliani al Manierismo, e mette a fuoco la fisionomia della forma sulla base di parametri coerenti e omogenei. In tal modo la \u201cgrammatica\u201d del sonetto individuata in un canzoniere, o in un gruppo di canzonieri, finisce per diventare un fatto storicamente rilevante, un singolo punto che prende senso perch\ue9 parte di un sistema in divenire, che lo ingloba e insieme lo trascende, e che coincide, appunto, con la tradizione storica di questo metro. Tanto che il disegnare quel sistema per intero, nello spazio e nel tempo, potrebbe essere indicato come l\u2019orizzonte ideale cui questo tipo di ricerche tende