Robot training of upper limb in multiple sclerosis: comparing protocols with or without manipulative task components

In this pilot study, we compared two protocols for robot-based rehabilitation of upper limb in multiple sclerosis (MS): a protocol involving reaching tasks (RT) requiring arm transport only and a protocol requiring both objects' reaching and manipulation (RMT). Twenty-two MS subjects were assigned to RT or RMT group. Both protocols consisted of eight sessions. During RT training, subjects moved the handle of a planar robotic manipulandum toward circular targets displayed on a screen. RMT protocol required patients to reach and manipulate real objects, by moving the robotic arm equipped with a handle which left the hand free for distal tasks. In both trainings, the robot generated resistive and perturbing forces. Subjects were evaluated with clinical and instrumental tests. The results confirmed that MS patients maintained the ability to adapt to the robot-generated forces and that the rate of motor learning increased across sessions. Robot-therapy significantly reduced arm tremor and improved arm kinematics and functional ability. Compared to RT, RMT protocol induced a significantly larger improvement in movements involving grasp (improvement in Grasp ARAT sub-score: RMT 77.4%, RT 29.5%, p=0.035) but not precision grip. Future studies are needed to evaluate if longer trainings and the use of robotic handles would significantly improve also fine manipulation.     

Anti-listerial activity of a polymeric film coated with hybrid coatings doped with Enterocin 416K1 for use as bioactive food packaging

In this study, Enterocin 416K1, a bacteriocin produced by Enterococcus casseliflavus IM 416K1, was entrapped in an organic-inorganic hybrid coating applied to a LDPE (low-density polyethylene) film for its potential use in the active food packaging field. The antibacterial activity of the coated film was evaluated against Listeria monocytogenes NCTC 10888 by qualitative modified agar diffusion assay, quantitative determination in listeria saline solution suspension and direct contact with artificially contaminated food samples (frankfurters and fresh cheeses) stored at room and refrigeration temperatures. All investigations demonstrated that enterocin-activated coatings have a good anti-listeria activity. Qualitative tests showed a clear zone of inhibition in the indicator lawn in contact with and around the coated film. During the quantitative antibacterial evaluation the L. monocytogenes viable counts decreased to 1.5 log units compared to the control. The inhibitory capability was confirmed also in food-contact assays. In all food samples packed with coated films we observed a significant decrease in L. monocytogenes viable counts in the first 24 h compared to the control. This difference was generally maintained up to the seventh day and then decreased, with the exception of the cheese samples stored at refrigeration temperature.     

Yeast diversity in crop-growing environments in Cameroon

In the present study, we have investigated the occurrence of yeast flora on several agricultural products coming from crop-growing environments in Cameroon, to provide better knowledge of the biodiversity of yeast flora, and to thus define the impact of this biodiversity on food products. The yeast biodiversity was investigated using traditional culture-dependent methods, along with culture-independent methods. The culture-dependent approach was carried out using both direct and enrichment procedures, to detect the broadest possible presence of yeast species. A total of 151 strains belonging to 26 different yeast species were isolated and identified using restriction pattern analysis of the internal transcribed spacer region 5.8S-ITS and sequence analysis of D1/D2 domain of 26S rRNA gene. The enrichment isolation procedures carried out in high-sugar media allowed the recognition of fermentative species such as Saccharomyces cerevisiae and Torulaspora delbrueckii, which have previously not been detected using direct isolation methodology. The results of culture-independent method using DGGE patterns and sequencing of the DNA bands revealed a lower number of yeast species when compared with the culture-dependent methodology even if the identification of several yeast species not detected by traditional microbiological procedures such as Candida tropicalis and Hanseniaspora uvarum is allowed. Thus, these multiphasic approaches to study yeast biodiversity (culture-dependent and -independent methods) have allowed us to get a more complete picture of the microbial diversity in these natural environments.     

The production of hydrogen peroxide is not a common mechanism by which olive oil phenols induce apoptosis on HL60 cells

We have recently demonstrated that hydroxytyrosol (3,4-DHPEA), the most representative olive oil phenol, induces apoptosis on HL60 cells through the production of considerable amount of extracellular hydrogen peroxide (H₂O₂). The aims of the present investigation were first to assess the ability of different phenolic compounds to both produce extracellular H₂O₂ and induce apoptosis on HL60 cells, and second to elucidate whether the pro-apoptotic activity was mediated by the production of H₂O₂ in the cell culture medium. Based on the results phenols can be classified as follows: (1) those which were not able to induce both apoptosis and H₂O₂ accumulation (tyrosol, homovanillic alcohol and protocatechuic, o-coumaric, vanillic, homovanillic, ferulic and syringic acids); (2) those which showed a pro-apoptotic activity mediated, at least in part, by the production of H₂O₂, as evidenced by the ability of catalase to inhibit apoptosis (3,4-DHPEA, dopamine, 3,4-dihydroxyphenylacetic, 3,4-dihydroxy-hydrocinnamic, caffeic and gallic acids); and (3) those which induced apoptosis without the involvement of H₂O₂ (the secoiridoid derivatives of both hydroxytyrosol and tyrosol). Oleuropein showed a peculiar behaviour since, and although it caused an abundant production of H₂O₂ in the cell culture medium, it exerted a weak pro-apoptotic effect. From these results we may conclude that the cathecol moiety of the phenol molecule is necessary for the H₂O₂ producing activity, and that the 3,4-DHPEA metabolism to homovanillic alcohol and homovanillic acid may significantly reduce its pro-apoptotic potential. The real in vivo meaning of the phenol-induced H₂O₂ production remains to be investigated.     

A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.     

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC₅₀ values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.     

Performance of geosynthetic-reinforced flexible pavements in full-scale field trials

The paper presents the results of a series of full-scale trials carried out in Thailand examining the performance of geosynthetics as reinforcement for flexible pavements. The geosynthetics were embedded at different pavement depths and the structural response was monitored across four test sections by means of strain gauges, pressure sensors, deflection points and deflection plates. The results show that all reinforcement configurations helped reduce the vertical static stresses developed at the base of the pavement by up to 66% and by up to 72% for dynamic stresses. The performance enhancement expected to prolong the lifespan of the base layers. The reinforcement layers closer to the base experienced the highest lateral strains of up to 0.13%, providing evidence that geosynthetics can also effectively reduce lateral spreading. All reinforcement configurations helped enhance rut resistance with maximum traffic benefit ratio (TBR) of 13.70, effectiveness ratio (EF) of 12.70 and minimum rutting reduction ratio (RRR) of 0.74. The best configuration included a geotextile within the asphalt concrete layer and a geogrid under the base layer. Non-linear finite element analyses of the test sections predicted very well the strains and stresses in the pavement. The study provides a benchmark for future studies in this field and concludes that geosynthetics can help increase maintenance periods and extend the lifetime of flexible pavements.     

Evaluation of the occurrence of mechanical constriction of the Arc in A-TIG welding of austenitic stainless steels

This paper evaluates indications of arc constriction by the thermal and electrical insulation caused by oxides of a single component in A-TIG welding of austenitic stainless steels. Changes in arc dimensions, in its electric voltage and in weld bead morphology caused by three oxide fluxes (SiO₂, Cr₂O₃ e Al₂O₃) applied with two surface densities (30 e 60 g/m2), and with and without a flux-free central strip (of 1, 2 and 4 mm) were studied. Results showed no significant change in the width of the electric arc for the experimental conditions used, therefore not supporting a possible mechanical constriction in the electric arc by oxide electrical and thermal insulation. Lateral filming indicated that the arc is delayed by the fluxes with silica causing the strongest effect. The presence of a clean central strip in the flux layer decreased weld penetration and weld bead cross section, besides the reduction of the width of the bead. Therefore, the results of the present work seem to support Marangoni convection as the main mechanism responsible for increasing penetration in A-TIG welding of stainless austenitic steels.