Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

<p>Abstract</p> <p>Background</p> <p>Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux.</p> <p>Methods/design</p> <p>The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study.</p> <p>Discussion</p> <p>The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol.</p> <p>Trial registration number</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031667">NCT01031667</a></p

A strategy to obtain axenic cultures of Arthrospira spp. cyanobacteria

A strategy to obtain axenic cultures of the cyanobacterium Arthrospira sp. (‘platensis’) Lefevre 1963/M-132-1 strain, consisting of a series of physical and chemical procedures, and the application of an optimized pool of antibiotics, is described in this paper. This strategy, which is an inexpensive and fast way to obtain axenic cultures, can be applied to Arthrospira spp. from culture collections or samples from their natural habitats to eliminate a wide spectrum of contaminants. A high alkaline treatment (pH 12, using KOH) of 72 h is a determinant initial procedure applied to eliminate protozoa and Microcystis sp. Bacteria were eliminated by an optimal antibiotic pool treatment, and Chroococcus sp. residuals were discarded by serial dilution. Optimal concentrations of the antibiotics composing the pool were obtained by a 24 factorial central composite rotatable design (CCRD) and Response Surface Methodology (RSM), resulting in: ampicillin 61.6 μg/ml, penicillin 85.8 μg/ml, cefoxitin 76.9 μg/ml, and meropenem 38.9 μg/ml. The results also indicate that cefoxitin was the most effective antibiotic of this pool. After obtaining the axenic culture, identification of Lefevre 1963/M-132-1 strain was performed using amplification and sequencing of the ITS region (including part of 16S rRNA, tRNA Ile, ITS, tRNA Ala and part of 23S rRNA region) and fatty acid composition data. Data base comparison revealed that Lefevre strain is closely related to A. platensis species (99% identity), while fatty acid composition data suggested A. maxima. These seemingly contradictory results are discussed

ДИЭЛЕКТРИЧЕСКИЕ ХАРАКТЕРИСТИКИ КОНДЕНСАТОРНЫХ СТРУКТУР НА ОСНОВЕ ПЛЕНОК ТИТАНАТА СТРОНЦИЯ, СФОРМИРОВАННЫХ ЗОЛЬ-ГЕЛЬ МЕТОДОМ

The thin film capacitors were formed on silicon. The capacitor is based on the strontium titanate multi-layer which was fabricated using the sol-gel method after heat treatment at the temperature 750 or 800 °C. The lower and upper electrodes were made from platinum and nickel accordingly. The average values of the dielectric permittivity, ε, and the loss factor, tg δ, were found between 150-190 and 0,06-0,1 respectively. The standard deviation values of the mentioned characteristics were calculated.Сформированы тонкопленочные конденсаторы на подложках кремния. Основу конденсатора составляет многослойная пленка титаната стронция, полученная золь-гель методом при температурах отжига 750-800 °С. Нижний электрод сформирован из платины, верхний - из никеля. Средние значения диэлектрической проницаемости и тангенса угла диэлекрических потерь лежат в пределах 150-190 и 0,06-0,1 соответственно. Приведены значения среднеквадратического отклонения указанных величи

Low-Frequency Noise in N-GaN with High Electron Mobility

We report on the results of measurements of low frequency noise in n-type gallium nitride (GaN) grown on sapphire with 300 K electron mobility of 790 cm2/V s. The noise spectra have the form of 1/f noise with a Hooge parameter α of approximately 5×10−2. This value of α is two orders of magnitude smaller than that observed before in n-GaN. The obtained results show that the level of flicker noise in GaN, just like that in GaAs and Si, strongly depends on the structural perfection of the material (the amplitude of the 1/f noise is much smaller in material with high mobility). The effects of band-to-band illumination on the low-frequency noise show that 1/f noise in GaN might be caused by the occupancy fluctuations of the tail states near the band edges. This mechanism of the 1/f noise is similar to that in GaAs and Si