WordMelodies: supporting children with visual impairment in learning literacy

We present WordMelodies, an inclusive, cross platform, mobile app that supports children with visual impairments in the acquisition of basic literacy skills through 8 different exercises. WordMelodies has been designed and evaluated by three domain experts in assistive technologies and education for children with visual impairments. After three design and evaluation iterations the app is fully accessible, except for one limitation of the cross platform development toolkit used

A \u201cnoisy\u201d electrical stimulation protocol favors muscle regeneration in vitro through release of endogenous ATP

An in vitro system of electrical stimulation was used to explore whether an innovative \u201cnoisy\u201d stimulation protocol derived from human electromyographic recordings (EMGstim)could promote muscle regeneration. EMGstim was delivered to cultured mouse myofibers isolated from Flexor Digitorum Brevis, preserving their satellite cells. In response to EMGstim, immunostaining for the myogenic regulatory factor myogenin, revealed an increased percentage of elongated myogenin-positive cells surrounding the myofibers. Conditioned medium collected from EMGstim-treated cell cultures, promoted satellite cells differentiation in unstimulated myofiber cell cultures, suggesting that extracellular soluble factors could mediate the process. Interestingly, the myogenic effect of EMGstim was mimicked by exogenously applied ATP (0.1 \u3bcM), reduced by the ATP diphosphohydrolase apyrase and prevented by blocking endogenous ATP release with carbenoxolone. In conclusion, our results show that \u201cnoisy\u201d electrical stimulations favor muscle progenitor cell differentiation most likely via the release of endogenous ATP from contracting myofibres. Our data also suggest that \u201cnoisy\u201d stimulation protocols could be potentially more efficient than regular stimulations to promote in vivo muscle regeneration after traumatic injury or in neuropathological diseases

Asbestos Fibers Enhance the TMEM16A Channel Activity in Xenopus Oocytes

Background: The interaction of asbestos fibers with target cell membranes is still poorly investigated. Here, we detected and characterized an enhancement of chloride conductance in Xenopus oocyte cell membranes induced by exposure to crocidolite (Croc) asbestos fibers. Methods: A two-microelectrode voltage clamp technique was used to test the effect of Croc fiber suspensions on outward chloride currents evoked by step membrane depolarization. Calcium imaging experiments were also performed to investigate the variation of 'resting' oocyte [Ca2+]i following asbestos exposure. Results: The increase in chloride current after asbestos treatment, was sensitive to [Ca2+]e, and to specific blockers of TMEM16A Ca2+-activated chloride channels, MONNA and Ani9. Furthermore, asbestos treatment elevated the 'resting' [Ca2+]i likelihood by increasing the cell membrane permeability to Ca2 in favor of a tonic activation of TMEME16A channels. Western blot analysis confirmed that TMEME16A protein was endogenously present in the oocyte cell membrane and absorbed by Croc. Conclusion: the TMEM16A channels endogenously expressed by Xenopus oocytes are targets for asbestos fibers and represent a powerful tool for asbestos-membrane interaction studies. Interestingly, TMEM16A channels are highly expressed in many types of tumors, including some asbestos-related cancers, suggesting them, for the first time, as a possible early target of crocidolite-mediated tumorigenic effects on target cell membranes

Neuronal Agrin Promotes Proliferation of Primary Human Myoblasts in an Age-Dependent Manner

Neuronal agrin, a heparan sulphate proteoglycan secreted by the -motor neurons, promotes the formation and maintenance of the neuromuscular junction by binding to Lrp4 and activating muscle-specific kinase (MuSK). Neuronal agrin also promotes myogenesis by enhancing differentiation and maturation of myotubes, but its effect on proliferating human myoblasts, which are often considered to be unresponsive to agrin, remains unclear. Using primary human myoblasts, we determined that neuronal agrin induced transient dephosphorylation of ERK1/2, while c-Abl, STAT3, and focal adhesion kinase were unresponsive. Gene silencing of Lrp4 and MuSK markedly reduced the BrdU incorporation, suggesting the functional importance of the Lrp4/MuSK complex for myoblast proliferation. Acute and chronic treatments with neuronal agrin increased the proliferation of human myoblasts in old donors, but they did not affect the proliferation of myoblasts in young donors. The C-terminal fragment of agrin which lacks the Lrp4-binding site and cannot activate MuSK had a similar age-dependent effect, indicating that the age-dependent signalling pathways activated by neuronal agrin involve the Lrp4/MuSK receptor complex as well as an Lrp4/MuSK-independent pathway which remained unknown. Collectively, our results highlight an age-dependent role for neuronal agrin in promoting the proliferation of human myoblasts

Flame-Made Cu/TiO2 and Cu-Pt/TiO2 Photocatalysts for Hydrogen Production

The effect of Cu or Cu-Pt nanoparticles in TiO2 photocatalysts prepared by flame spray pyrolysis in one step was investigated in hydrogen production from methanol photo-steam reforming. Two series of titanium dioxide photocatalysts were prepared, containing either (i) Cu nanoparticles (0.05\u20130.5 wt%) or (ii) both Cu (0 to 0.5 wt%) and Pt (0.5 wt%) nanoparticles. In addition, three photocatalysts obtained either by grafting copper and/or by depositing platinum by wet methods on flame-made TiO2 were also investigated. High hydrogen production rates were attained with copper-containing photocatalysts, though their photoactivity decreased with increasing Cu loading, whereas the photocatalysts containing both Cu and Pt nanoparticles exhibit a bell-shaped photoactivity trend with increasing copper content, the highest hydrogen production rate being attained with the photocatalyst containing 0.05 wt% Cu

Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex

Objectives To define the maximum tolerated dose (MTD), the toxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods Fourteen patients with advanced solid tumors not responsive to previous antitumor treatments received BBR 3464 on a daily × 5 schedule every twenty-eighth day. The drug was given as a one-hour infusion with pre-and post-treatment hydration (500 ml in one hour) and no antiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. A modified accelerated titration escalation design was used. Total and free platinum (Pt) concentrations in plasma and urine were assessed by ICP-MS on days 1 and 5 of the first cycle. Results Dose was escalated four times up to 0.17 mg/m2/ day. Short-lasting neutropenia and diarrhea of late onset were dose-limiting and defined the MTD at 0.12 mg/m2 Nausea and vomiting were rare, neither neuro- nor renal toxic effects were observed. BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-life of several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 were higher than on day 1, indicating drug accumulation. Approximately 10% of the equivalent dose of BBR3464 (2.2%-13.4%) was recovered in a 24-hour urine collection. Conclusions The higher than expected incidence of neutropenia and GI toxicity might be related to the prolonged half-life and accumulation of total and free Pt after daily administrations. Lack of nephrotoxicity and the low urinary excretion support the use of the drug without hydration. The single intermittent schedule has been selected for clinical developmen

Cu and Pt clusters deposition on TiO2 powders by DC magnetron sputtering for photocatalytic hydrogen production

Titanium dioxide-based photocatalyst powders were obtained by deposition of copper and/or platinum clusters by means of pulsed direct current magnetron sputtering with different deposition times and plasma composition during Cu/Pt sputtering. A top-down configuration was employed with the sputtering source facing the powder holder mounted on a shaker mechanism, which continuously mixed the powder during the sputtering process. HRTEM analyses revealed the presence of well dispersed, subnanometric sized metal clusters, even for long deposition times, while XRPD analysis showed no modification of the TiO2crystal structure upon metal deposition. The so obtained powders were tested as photocatalysts in methanol photo-steam reforming for hydrogen production. The presence of Pt clusters increased the photoactivity with respect to that of bare TiO2. The plasma composition during Cu sputtering was found to strongly affect the photoactivity of the obtained materials, Cu alone deposited as co-catalyst in an Ar-only atmosphere imparting better photoactivity than Cu sputtered in Ar/O2. When the deposition of Cu clusters was coupled with the deposition of Pt clusters, an additive effect of the two metals in increasing TiO2photoactivity was observed if Cu clusters were sputtered in the absence of oxygen

Air pollution and lung function among susceptible adult subjects: a panel study

BACKGROUND: Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. METHODS: Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM(10–2.5)) and fine (PM(2.5)) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO(2)), carbon monoxide (CO), ozone (O(3)), and sulphur dioxide (SO(2)) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. RESULTS: Decrements in lung function indices (FVC and/or FEV(1)) associated with increasing concentrations of PM(2.5), NO(2 )and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO(2 )was associated with a decrease in FEV(1). No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. CONCLUSION: This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function of the relatively young and mild asthmatics included in this study seems to worsen when ambient levels of NO(2 )increase