Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.     

Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA

Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity. Its deficiency in man results in the neurodegenerative lysosomal storage disorder galactosialidosis (GS). The mouse model of this disease resembles the human early onset phenotype and results in severe nephropathy and ataxia. To understand better the pathophysiology of the disease, we compared the occurrence of lysosomal PPCA mRNA and protein in normal adult mouse tissues with the incidence of lysosomal storage in PPCA(-/-) mice. PPCA expression was markedly variable among different tissues. Most sites that produced both mRNA and protein at high levels in normal mice showed extensive and overt storage in the knockout mice. However, this correlation was not consistent as some cells that normally expressed high levels of PPCA were unaffected in their storage capability in the PPCA(-/-) mice. In addition, some normally low expressing cells accumulated large amounts of undegraded products in the GS mouse. This apparent discrepancy may reflect a requirement for the catalytic rather than the protective function of PPCA and/or the presence of cell-specific substrates in certain cell types. A detailed map showing the cellular distribution of PPCA in nomal mouse tissues as well as the sites of lysosomal storage in deficient mice is critical for accurate assessment of the effects of therapeutic interventions.     

Effects of intrathecal administration of adrenergic agonists on the frequency of copulatory pelvic thrusting of the male rat

The effects of the intrathecal perispinal administration of adrenergic agonists on the characteristics of frequency, duration, and vigor of pelvic thrusting displayed by male rats during copulation was assessed by an accelerometric technique. A different dose of one drug (noradrenaline, clonidine or isoproterenol) and saline as control was administered at the lumbosacral level of the spinal cord to sexually active male rats in tests of sexual behavior performed at weekly intervals. The intrathecal administration of noradrenaline (alpha-adrenoceptor agonist) increased the frequency of pelvic thrusting in mount and intromission responses, whereas both the alpha 2-adrenoceptor agonist clonidine (25 micrograms) and the beta-adrenoceptor agonist isoproterenol (40 micrograms) reduced the frequency of pelvic thrusting in these responses as compared to values obtained under the intrathecal administration of saline. On the other hand, the duration of the thrusting trains and the potency or vigor of pelvic thrusting in mounts and intromissions did not differ from values obtained under saline treatment. These findings indicate a possible participation of noradrenaline in the modulation of the spinal mechanisms involved in the generation of rhythmic pelvic thrusting performed by the male rat during copulation.     

New species of Aeromonas isolated in Cuba

One hundred and fifty-five strains of Aeromonas isolated in the stools of children under 5 years presenting with acute diarrheal disease were studied. Using the Aerokey II system for the identification of species, 47 strains were identified as Aeromonas caviae, 58 as Aeromonas hydrophila, 23 as Aeromonas veronii biovar sobria, 14 as Aeromonas trota, 9 as Aeromonas veronii biovar veronii, 2 as Aeromonas jandaei and 2 as Aeromonas shubertii, Emphasis is placed on the advantages of this method which allowed for the classification of new species not identified previously in our country.     

Improving sub-pixel accuracy for long range stereo

Dense stereo algorithms are able to estimate disparities at all pixels including untextured regions. Typically these disparities are evaluated at integer disparity steps. A subsequent sub-pixel interpolation often fails to propagate smoothness constraints on a sub-pixel level.We propose to increase the sub-pixel accuracy in low-textured regions in four possible ways: First, we present an analysis that shows the benefit of evaluating the disparity space at fractional disparities. Second, we introduce a new disparity smoothing algorithm that preserves depth discontinuities and enforces smoothness on a sub-pixel level. Third, we present a novel stereo constraint (gravitational constraint) that assumes sorted disparity values in vertical direction and guides global algorithms to reduce false matches, especially in low-textured regions. Finally, we show how image sequence analysis improves stereo accuracy without explicitly performing tracking. Our goal in this work is to obtain an accurate 3D reconstruction. Large-scale 3D reconstruction will benefit heavily from these sub-pixel refinements.Results based on semi-global matching, obtained with the above mentioned algorithmic extensions are shown for the Middlebury stereo ground truth data sets. The presented improvements, called ImproveSubPix, turn out to be one of the top-performing algorithms when evaluating the set on a sub-pixel level while being computationally efficient. Additional results are presented for urban scenes. The four improvements are independent of the underlying type of stereo algorithm.     

HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EV_MSC-T-HIF^c). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EV_MSC-T-HIF^c suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.     

Low-Thermal-Conductivity Rare-Earth Zirconates for Potential Thermal-Barrier-Coating Applications

Rare-earth zirconates have been identified as a class of low-thermal-conductivity ceramics for possible use in thermal barrier coatings (TBCs) for gas-turbine engine applications. To document and compare the thermal conductivities of important rare-earth zirconates, we have measured the thermal conductivities of the following hot-pressed ceramics: (i) Gd₂Zr₂O₇ (pyrochlore phase), (ii) Gd₂Zr₂O₇ (fluorite phase), (iii) Gd_2.58Zr_1.57O₇ (fluorite phase), (iv) Nd₂Zr₂O₇ (pyrochlore phase), and (v) Sm₂Zr₂O₇ (pyrochlore phase). We have also measured the thermal conductivity of pressureless-sintered 7 wt% yttria-stabilized zirconia (7YSZ)—the commonly used composition in current TBCs. All rare-earth zirconates investigated here showed nearly identical thermal conductivities, all of which were ∼30% lower than the thermal conductivity of 7YSZ in the temperature range 25°–700°C. This finding is discussed qualitatively with reference to thermal-conductivity theory.     

Nafcillin release from poly(acrylic acid–co–methyl methacrylate) hydrogels

Summary Copolymeric poly(acrylic acid-co-methyl methacrylate) hydrogels for three different compositions: (90/10), (80/20) and (60/40), have been studied. Drug release has been examined as a function of the hydrogel composition by HPLC (High Pressure Liquid Cromatography). The release experiments were carried out at 37 °C. The fraction of available drug release was linear in t^1/2. The values of the diffusional coefficient (0.50<n<1.0) indicate that the nafcillin release mechanism from the hydrogels in study is non-Fickian. The diffusion coefficients for this drug release have been calculated. The molecular diffusion of nafcillin through hydrogels is controlled by the swelling.     

Responses by amphisbaenianBlanus cinereus to chemicals from prey or potentially harmful ant species

We tested the ability of amphisbaenians (Blanus cinereus) to discriminate between odors of ant species selected as prey (Pheidole pallidula) and odors of potentially harmful ant species (Messor barbarus) that are avoided. Tongue-flick rate to swabs impregnated with ant odors, cologne, or deionized water differed among treatments, showing that amphisbaenians were able to discriminate ant species odors. Amphisbaenians showed an aggressive response and bit applicators bearing the odor of harmful ants, while the odor of prey ants did not elicit bites to swabs. The possible evolutionary advantage of identifying and avoiding harmful ants is discussed in relation to the fossoriality of amphisbaenians.