Immersive virtual reality and antigravity treadmill training for gait rehabilitation in Parkinson’s disease: A pilot and feasibility study

Introduction. Treadmill training is considered an effective intervention to improve gait ability in patients with Parkinson’s disease (PD). In parallel, virtual reality shows promising intervention with several applications in the inpatient medical setting. Aim. To evaluate the feasibility and preliminary efficacy of mechanical gait assistance combined with immersive virtual reality in patients with PD. Patients and methods. This pilot and feasibility study followed a pre-post study design. The intervention consisted of 12 sessions of 30 minutes, distributed regularly over four consecutive weeks. Participants walked on a treadmill with a body- weight support system set at approximately 20% of body weight and equipped with a virtual reality helmet controlled by a two-handed joystick. Feasibility and intervention outcomes were collected at baseline and after four weeks of intervention. Results. Twelve participants of 60 patients were finally enrolled. Nine of them (75%) completed the treatment intervention with an adherence rate of 97%. Two participants left the study, one of them due to sickness associated with virtual reality and another because of a lack of motivation. There were significant differences associated with small-medium effect sizes when comparing the pre and post values for walk distance, walk speed, balance, and quality of life. Conclusions. The present study provided preliminary evidence supporting the feasibility of the combination of antigravity treadmill and immersive virtual reality system for the rehabilitation of patients with PD

In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages

Plaque rupture and thromboembolism play a major role in atherosclerotic acute syndrome. Experimental studies have demonstrated the potential direct anti-atherosclerotic effects of calcium antagonists. We investigated the in vitro effect of lercanidipine (REC 15/2375), a third-generation, highly lipophilic calcium antagonist on cholesterol metabolism and matrix metalloproteinases secretion in macrophages, two functions that predispose plaques to rupture. Lercanidipine (10 126\u201310 125 M) inhibited cholesterol esterification in macrophagesand reduced cellular free and esterified cholesterol accumulation from acetylated LDL (63%, 62% of control P < 0.05, respectively). In addition, lercanidipine inhibited the release of metalloproteinases in the extracellular medium (50% and 95% inhibition at 10 125 M for MMP-9 and MMP-2, respectively). Experiments performed with lercanidipine enantiomers or other dihydropyridine derivatives, endowed with different lipophilicity and affinity for calcium channels, indicated that the above effects could be related to the lipophilic, but not to the calcium channel blocking properties of these molecules. When cells, after exposure to the drug, were allowed to equilibrate, lercanidipine inhibitory action could be observed at initial concentrations as low as 10 129 M, which is the actual concentration range observed in plasma in clinical settings. In conclusion, our data indicate that lercanidipine may exert potent anti-atherosclerotic effects by inhibiting macrophage functions involved in plaque stability

NaAlH4 production from waste aluminum by reactive ball milling

Due to its thermodynamic properties and high reversibility, Ti doped sodium alanateis considered as a prototype hydrogen storage material. In this work we show how sodium alanate can be synthesized by reactive ball milling using aluminum particles obtained from recycled waste incineration slag. The synthesis was monitoredwith an in situ milling vial and characterized stepwise by PXD and DTA analyses. The sorption properties of the material were investigated using in situ synchrotron radiation PXD and volumetric analyses. A complete conversion of the starting reactants was obtained

Development of the Prevent for Work questionnaire (P4Wq) for assessment of musculoskeletal risk in the workplace: part 1-literature review and domains selection

Objective This study aims to define appropriate domains and items for the development of a self-administered questionnaire to assess the risk of developing work-related musculoskeletal disorder (WMSD) and the risk of its progression to chronicity. Design Literature review and survey study. Setting and participants A literature review and a two-round interview with 15 experts in musculoskeletal pain were performed to identify the available domains for WMSD assessment. Interventions and outcome To ensure quality, only validated questionnaires were included for the Delphi process. A three-round Delphi method, with three round steps, was used to select the most pertinent and relevant domains and items. Results Nine questionnaires were identified through the expert discussion and literature review, comprising 38 candidate domains and 504 items. In the first round of the Delphi group, 17 domains reached more than 70% agreement and were selected. In the second round, 10 domains were rejected, while 11 were selected to complete the pool of domains. In the third and final round, 89 items belonging to 28 domains were defined as significant to develop a WMSDs risk assessment questionnaire. Conclusions No specific risk assessment questionnaires for WMSDs were identified from the literature. WMSD risk of presence and chronicity can be defined by an assessment tool based on the biopsychosocial model and the fear-avoidance components of chronic pain. The present study provides the formulation and operationalisation of the constructs in domains and items needed for developing and validating the questionnaire

C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation

Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of repeat-containing C9orf72 RNA results in the production of neurotoxic dipeptide-repeat proteins (DPRs). Here, we developed a high-throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP-elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA-catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient-derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD

Application of hydrides in hydrogen storage and compression: Achievements, outlook and perspectives

Metal hydrides are known as a potential efficient, low-risk option for high-density hydrogen storage since the late 1970s. In this paper, the present status and the future perspectives of the use of metal hydrides for hydrogen storage are discussed. Since the early 1990s, interstitial metal hydrides are known as base materials for Ni – metal hydride rechargeable batteries. For hydrogen storage, metal hydride systems have been developed in the 2010s [1] for use in emergency or backup power units, i. e. for stationary applications. With the development and completion of the first submarines of the U212 A series by HDW (now Thyssen Krupp Marine Systems) in 2003 and its export class U214 in 2004, the use of metal hydrides for hydrogen storage in mobile applications has been established, with new application fields coming into focus. In the last decades, a huge number of new intermetallic and partially covalent hydrogen absorbing compounds has been identified and partly more, partly less extensively characterized. In addition, based on the thermodynamic properties of metal hydrides, this class of materials gives the opportunity to develop a new hydrogen compression technology. They allow the direct conversion from thermal energy into the compression of hydrogen gas without the need of any moving parts. Such compressors have been developed and are nowadays commercially available for pressures up to 200 bar. Metal hydride based compressors for higher pressures are under development. Moreover, storage systems consisting of the combination of metal hydrides and high-pressure vessels have been proposed as a realistic solution for on-board hydrogen storage on fuel cell vehicles. In the frame of the “Hydrogen Storage Systems for Mobile and Stationary Applications” Group in the International Energy Agency (IEA) Hydrogen Task 32 “Hydrogen-based energy storage”, different compounds have been and will be scaled-up in the near future and tested in the range of 500 g to several hundred kg for use in hydrogen storage applications.Fil: Bellosta von Colbe, Jose. Helmholtz-Zentrum Geesthacht; AlemaniaFil: Ares Fernández, José Ramón. Universidad Autónoma de Madrid; EspañaFil: Jussara, Barale. Università di Torino; ItaliaFil: Baricco, Marcello. Università di Torino; ItaliaFil: Buckley, Craig E.. Curtin University; AustraliaFil: Capurso, Giovanni. Helmholtz Zentrum Geesthacht; AlemaniaFil: Gallandat, Noris. GRZ Technologies Ltd; SuizaFil: Grant, David M.. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino Unido. University of Nottingham; Estados UnidosFil: Guzik, Matylda N.. University of Oslo; NoruegaFil: Jacob, Isaac. Ben Gurion University of the Negev; IsraelFil: Jensen, Emil H.. University of Oslo; NoruegaFil: Jensen, Torben. University Aarhus; DinamarcaFil: Jepsen, Julian. Helmholtz Zentrum Geesthacht; AlemaniaFil: Klassen, Thomas. Helmholtz Zentrum Geesthacht; AlemaniaFil: Lototskyy, Mykhaylol V.. University of Cape Town; SudáfricaFil: Manickam, Kandavel. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Montone, Amelia. Casaccia Research Centre; ItaliaFil: Puszkiel, Julián Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Helmholtz Zentrum Geesthacht; AlemaniaFil: Sartori, Sabrina. University of Oslo; NoruegaFil: Sheppard, Drew A.. Curtin University; AustraliaFil: Stuart, Alastair. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Walker, Gavin. University of Nottingham; Estados Unidos. Science and Technology Facilities Council of Nottingham. Rutherford Appleton Laboratory; Reino UnidoFil: Webb, Colin J.. Griffith University; AustraliaFil: Yang, Heena. Empa Materials Science & Technology; Suiza. École Polytechnique Fédérale de Lausanne; SuizaFil: Yartys, Volodymyr. Institute for Energy Technology; NoruegaFil: Züttel, Andreas. Empa Materials Science & Technology; Suiza. École Polytechnique Fédérale de Lausanne; SuizaFil: Dornheim, Martin. Helmholtz Zentrum Geesthacht; Alemani

Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria

<p>Abstract</p> <p>Background</p> <p>The sun-dried rind of the immature fruit of pomegranate (<it>Punica granatum</it>) is presently used as a herbal formulation (OMARIA, Orissa Malaria Research Indigenous Attempt) in Orissa, India, for the therapy and prophylaxis of malaria. The pathogenesis of cerebral malaria, a complication of the infection by <it>Plasmodium falciparum</it>, is an inflammatory cytokine-driven disease associated to an up-regulation and activity of metalloproteinase-9 and to the increase of TNF production. The <it>in vitro </it>anti-plasmodial activity of <it>Punica granatum (Pg) </it>was recently described. The aim of the present study was to explore whether the anti-malarial effect of OMARIA could also be sustained via other mechanisms among those associated to the host immune response.</p> <p>Methods</p> <p>From the methanolic extract of the fruit rind, a fraction enriched in tannins (<it>Pg</it>-FET) was prepared. MMP-9 secretion and expression were evaluated in THP-1 cells stimulated with haemozoin or TNF. The assays were conducted in the presence of the <it>Pg</it>-FET and its chemical constituents ellagic acid and punicalagin. The effect of urolithins, the ellagitannin metabolites formed by human intestinal microflora, was also investigated.</p> <p>Results</p> <p><it>Pg</it>-FET and its constituents inhibited the secretion of MMP-9 induced by haemozoin or TNF. The effect occurred at transcriptional level since MMP-9 mRNA levels were lower in the presence of the tested compounds. Urolithins as well inhibited MMP-9 secretion and expression. <it>Pg</it>-FET and pure compounds also inhibited MMP-9 promoter activity and NF-kB-driven transcription.</p> <p>Conclusions</p> <p>The beneficial effect of the fruit rind of <it>Punica granatum </it>for the treatment of malarial disease may be attributed to the anti-parasitic activity and the inhibition of the pro-inflammatory mechanisms involved in the onset of cerebral malaria.</p

ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age

BACKGROUND: The ɛ2, ɛ3, and ɛ4 alleles of the apolipoprotein E gene (APOE) encode three isoforms, apoE2, E3, and E4, respectively. The apoE isoforms circulate in different plasma concentrations, but plasma concentrations of the same isoform also differ between individuals. Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown. METHODS AND FINDINGS: We assessed APOE genotypes, plasma levels of apoE, cardiovascular risk factors, and mortality in a population-based sample of 546 individuals aged 85 y who participated in the Leiden 85-plus Study and were prospectively followed for specific causes of death for 5 y. Participants in the highest tertile of apoE levels suffered a twofold-increased risk of cardiovascular mortality (hazard ratio compared to lowest tertile, 2.08; 95% confidence interval [CI], 1.30 to 3.33). Among the 324 participants with the ɛ3ɛ3 genotype, the hazard from cardiovascular disease was threefold increased (highest versus lowest tertile 3.01; 95% CI 1.60 to 5.66), with similar estimates for men and women. Other causes of death were not increased significantly. Plasma levels of apoE in ɛ3ɛ3 participants were positively correlated with total cholesterol ( p < 0.001), low-density lipoprotein cholesterol ( p < 0.001) and triglycerides ( p < 0.001) and negatively with high-density lipoprotein cholesterol levels ( p = 0.010). Adjustment for plasma lipids did not change the hazard ratios, whereas interaction was absent. The risk associated with high levels of apoE, however, was strongest in participants from the lowest tertile of C-reactive protein (CRP) levels and absent in those from the highest tertile ( p (interaction) < 0.001). Among participants from the lowest tertile of CRP levels, those with a high apoE levels had a significantly steeper increase in CRP than those with low apoE levels ( p = 0.020). Similar cardiovascular mortality risks as in ɛ3ɛ3 participants were found in ɛ2 and ɛ4 carriers. CONCLUSIONS: In old age, high plasma apoE levels precede an increase of circulating CRP and strongly associates with cardiovascular mortality, independent of APOE genotype and plasma lipids

Magnesium based materials for hydrogen based energy storage: Past, present and future

Magnesium hydride owns the largest share of publications on solid materials for hydrogen storage. The “Magnesium group” of international experts contributing to IEA Task 32 “Hydrogen Based Energy Storage” recently published two review papers presenting the activities of the group focused on magnesium hydride based materials and on Mg based compounds for hydrogen and energy storage. This review article not only overviews the latest activities on both fundamental aspects of Mg-based hydrides and their applications, but also presents a historic overview on the topic and outlines projected future developments. Particular attention is paid to the theoretical and experimental studies of Mg-H system at extreme pressures, kinetics and thermodynamics of the systems based on MgH2, nanostructuring, new Mg-based compounds and novel composites, and catalysis in the Mg based H storage systems. Finally, thermal energy storage and upscaled H storage systems accommodating MgH2 are presented