Robot-assisted upper limb training for patients with multiple sclerosis: an evidence-based review of clinical applications and effectiveness

Upper extremities limitation is a common functional impairment in patients with Multiple Sclerosis (PwMS). Novel technological devices are increasingly used in neurorehabilitation to support motor function improvement and the quantitative assessment of motor performance during training in patients with neurological diseases. In this review, we systematically report the evidence on clinical applications and robotic-assisted arm training (RAT) in functional recovery in PwMS. PubMed/MEDLINE, the Cochrane Library, and the Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to March 2021. The 10-item PEDro scale assessed the study quality for the RCT, and the AMSTAR-2 was used to assess the quality of the systematic review. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 10 studies (161 subjects) were included. The selected studies included one systematic review, four RCTs, one randomized crossover, and four case series. The RCTs were scored as high-quality studies, while the systematic review was determined to be of low quality. Shoulder range of motion, handgrip strength, and proximal arm impairment improved after RAT. Manual dexterity, arm function, and use in daily life also ameliorated arm function. The high clinical heterogeneity of treatment programs and the variety of robot devices affects the generalizability of the study results; therefore, we emphasize the need to standardize the intervention type in future studies that evaluate the role of robotic-assisted training in PwMS. Robot-assisted treatment seems safe and useful to increase manual dexterity and the quality of movement execution in PwMS with moderate to severe disability. Additional studies with an adequate sample size and methodological rigour are warranted to drive definite conclusion

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

We report the detection of pulsed γ-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their γ-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the γ-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the γ-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the γ-ray light curves with high-energy beam models

Detection of High-Energy Gamma-Ray Emission from the Globular Cluster 47 Tucanae with Fermi

Gamma-Ray Pulsar Bonanza Most of the pulsars we know about were detected through their radio emission; a few are known to pulse gamma rays but were first detected at other wavelengths (see the Perspective by Halpern ). Using the Fermi Gamma-Ray Space Telescope, Abdo et al. (p. 840 , published online 2 July; see the cover) report the detection of 16 previously unknown pulsars based on their gamma-ray emission alone. Thirteen of these coincide with previously unidentified gamma-ray sources, solving the 30-year-old mystery of their identities. Pulsars are fast-rotating neutron stars. With time they slow down and cease to radiate; however, if they are in a binary system, they can have their spin rates increased by mass transfer from their companion stars, starting a new life as millisecond pulsars. In another study, Abdo et al. (p. 845 ) report the detection of gamma-ray emission from the globular cluster 47 Tucanae, which is coming from an ensemble of millisecond pulsars in the cluster's core. The data imply that there are up to 60 millisecond pulsars in 47 Tucanae, twice as many as predicted by radio observations. In a further companion study, Abdo et al. (p. 848 , published online 2 July) searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars outside of stellar clusters, finding gamma-ray pulsations for eight of them. Their properties resemble those of other gamma-ray pulsars, suggesting that they share the same basic emission mechanism. Indeed, both sets of pulsars favor emission models in which the gamma rays are produced in the outer magnetosphere of the neutron star

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

A Population of Gamma-Ray Millisecond Pulsars Seen with the Fermi Large Area Telescope

Gamma-Ray Pulsar Bonanza Most of the pulsars we know about were detected through their radio emission; a few are known to pulse gamma rays but were first detected at other wavelengths (see the Perspective by Halpern ). Using the Fermi Gamma-Ray Space Telescope, Abdo et al. (p. 840 , published online 2 July; see the cover) report the detection of 16 previously unknown pulsars based on their gamma-ray emission alone. Thirteen of these coincide with previously unidentified gamma-ray sources, solving the 30-year-old mystery of their identities. Pulsars are fast-rotating neutron stars. With time they slow down and cease to radiate; however, if they are in a binary system, they can have their spin rates increased by mass transfer from their companion stars, starting a new life as millisecond pulsars. In another study, Abdo et al. (p. 845 ) report the detection of gamma-ray emission from the globular cluster 47 Tucanae, which is coming from an ensemble of millisecond pulsars in the cluster's core. The data imply that there are up to 60 millisecond pulsars in 47 Tucanae, twice as many as predicted by radio observations. In a further companion study, Abdo et al. (p. 848 , published online 2 July) searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars outside of stellar clusters, finding gamma-ray pulsations for eight of them. Their properties resemble those of other gamma-ray pulsars, suggesting that they share the same basic emission mechanism. Indeed, both sets of pulsars favor emission models in which the gamma rays are produced in the outer magnetosphere of the neutron star

Visita all'Osservatorio della Biodiversità marina e terrestre della Regione Sicilia - ORBS

Con il taglio inaugurale del nastro il 16 dicembre 2015, prende vita la struttura museale permanente dell'Osservatorio della Biodiversità marina e terrestre della Regione Sicilia che porta lo stesso nome del Progetto di Ricerca "ORBS – Sistema di comunicazione, informazione e diffusione dell'Osservatorio Regionale della Sicilia", intitolata il 21 dicembre 2018 al Dott. Sandro Fiorelli. Ad oggi, la struttura, è operativa presso la Sede Secondaria dell'Istituto per lo studio degli impatti Antropici e Sostenibilità in ambiente marino del Consiglio Nazionale delle Ricerche (IAS – CNR) di Capo Granitola. Il progetto ORBS, finanziato da Regione Siciliana - Assessorato alla Cooperazione, Commercio, Artigianato e Pesca - Dipartimento Pesca, con periodo di attività 2013 - 2015, si è concluso proprio con la realizzazione della struttura museale; l'Osservatorio è stato istituito dall'Assessorato del Territorio e dell'Ambiente della Regione Siciliana nell'ambito di un accordo quadro con ARPA, ISPRA e CNR. Grazie al progetto ORBS, docenti e allievi dell'Accademia di Belle Arti di Palermo e il personale CNR – IAS (ex IAMC) S. S. di Capo Granitola, hanno collaborato sinergicamente permettendo di realizzare delle azioni didattiche e creative di valore scientifico espresse con straordinaria forza e bellezza. Ricercatori e professori si sono confrontati al fine di combinare le proprie competenze riuscendo nel progetto ambizioso di coinvolgere e fondere i diversi ambiti scientifici sensibilizzando gli artisti ai temi della Biodiversità. Le opere prodotte, corredate da schede scientifiche, hanno oltre al valore artistico un aggiunto valore didattico. L'apertura della sezione espositiva dedicata alla diffusione e alla comunicazione della biodiversità rappresenta da un lato l'importante tappa conclusiva del progetto, dall'altro l'inizio di un percorso mirato alla diffusione della biodiversità verso il mondo giovanile, le scuole e per tutto il territorio. Questa strepitosa collaborazione "CNR – Accademia di Belle Arti di Palermo" conferma l'importanza e l'opportunità di unire arte e scienza per esaltare la percezione della ricerca scientifica da parte della comunità. La divulgazione della scienza è un'attività complessa e sicuramente necessita di competenze e attitudini multidisciplinari oltreché di motivazione ed entusiasmo. La comunicazione delle tematiche scientifiche, di per sé ardua nella traduzione al grande pubblico, grazie alla forza esplicativa dell'arte, diviene opportunità di riflessione, osservazione, confronto per le comunità di visitatori. Il coordinamento delle visite delle scuole di ogni ordine e grado, Enti Pubblici, Comunità Scientifica, Cariche Istituzionali, Delegazioni di Politici Italiani e Stranieri, Associazioni Culturali, Associazioni No-Profit di Volontariato, Associazioni di Promozione Sociale, Organizzazioni di Volontariato, Onlus, pubblico in generale, presso ORBS, è affidato al qualificato personale (tecnici, tecnologi e ricercatori) dell'IAS – CNR S. S. di Capo Granitola, che gestisce in prima persona i visitatori nel percorso didattico e promuove il valore della divulgazione scientifica perseguendo la terza missione degli Enti di Ricerca, attraverso l'applicazione diretta, la valorizzazione e l'impiego della conoscenza

ERRATUM: "FERMI DETECTION OF γ-RAY EMISSION FROM THE M2 SOFT X-RAY FLARE ON 2010 JUNE 12" (2012, ApJ, 745, 144)

Due to an error at the publisher, the times given for the major tick marks in the X-axis in Figure 1 of the published article are incorrect. The correctly labeled times should be "00:52:00," "00:54:00," ... , and "01:04:00." The correct version of Figure 1 and its caption is shown below. IOP Publishing sincerely regrets this error

Entwicklung von 17β-Hydroxysteroid Dehydrogenase Type 2 and Type 1 Inhibitoren für die Behandlung von Osteoporose und Östrogene bedingt Krankheiten

17β-HSD2 is a new promising target for the treatment of osteoporosis. In the first part of this thesis, a rational approach to overcome metabolic instability of the 2,5-thiophene amide class of 17β-HSD2 inhibitors is described, as well as a general overview of the occurring biotransformation in this series of molecules (Chapter 2.I). This information was then used to design and synthesize a new class of compounds, bearing a 1,4-phenyl amide core, which proved to be metabolically stable, potent inhibitors of both human and mouse 17β-HSD2 and selective over human and mouse 17β-HSD1 and ERs. The best compound in the series, II.17a is therefore a potential candidate for pre-clinical animal studies, prior to human studies (Chapter 2.II). Cell viability experiments, using an MTT assay, indicated that cell toxicity might constitute a drawback for II.17a. A preliminary study to address cell toxicity and maintain good inhibitory activity is also presented (Chapter 2.III). In the second part of this thesis (Chapter 2.IV) the theoretical basis for the treatment of NSCLC, through inhibition of 17β-HSD1, is given. The knowledge gained about metabolic stability of 2,5-thiophene amides is exploited to design and synthesize new potent, selective and metabolically stable 17β-HSD1 inhibitors. Compound IV.15 completely inhibits the growth of NSCLC Calu-1 cell at low nanomolar concentration, suggesting new treatment option for patients affected with NSCLC.17β-HSD2 ist ein neues vielversprechendes Target für die Behandlung von Osteoporose. Im ersten Teil dieser Arbeit wird ein rationaler Ansatz, die metabolische Instabilität der 2,5-Thiophenamid Klasse zu überwinden, beschrieben (Kapitel 2.I). Die erlangten Erkenntnisse wurden genutzt um eine neue Verbindungklasse mit 1,4-Phenylamid Core zu entwerfen und zu synthetisieren. Diese Verbindungen sind metabolisch stabile potente Hemmstoffe von humanem und murinem 17β-HSD2 und selektiv gegenüber den entsprechenden 17β-HSD1 Isoformen und ERs. Mit der besten Verbindung dieser Serie II.17a ist es gelungen einen potentiellen Kandidaten für präklinische Tierstudien zu synthetisieren (Kapitel 2.II).Toxizitätsstudien an menschlichen Zellen zeigten jedoch, dass diese Verbindung nicht frei von toxischen Effekten ist. Eine vorläufige Studie mit dem Ziel dieses Handikap zu überwinden und gleichzeitig die Hemmaktivität zu erhalten, wird in Kapitel 2.III vorgestellt.Im zweiten Teil dieser Arbeit (Kapitel 2.IV) wird die theoretische Basis für die Behandlungvon NSCLC durch Hemmung von 17β-HSD1 vorgestellt. Das in dieser Arbeit erlangte Wissen über die metabolische Stabilität der 2,5-Thiophenamide wurden beim Design und der Synthese neuer, potenter, selektiver und metabolisch stabiler 17β-HSD1 Hemmstoffe angewandt. Verbindung IV.15 hemmt bereits bei nanomolaren Konzentrationen vollständig das Wachstum von NSCLC Calu-1 Zellen. Diese Erkenntnisse eröffnen neue Behandlungswege für Patienten mit NSCLC