The ameliorative effects of Averroha carambola on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice

AbstractObjectiveTo evaluated immunomodulatory and antioxidant activity of the methanol extract of Averrhoa carambola (A. carambola) leaves in mice.MethodsThe assessment of immunomodulatory activity on specific and non-specific immunity was studied by administration of test extract by oral feeding canula to the test groups. Hemagglutinating antibody (HA) titer, delayed type of hypersensitivity (DTH) response, hematological profile (Hb, WBC, RBC), lipid per oxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) were determined by in vivo experiments.ResultsThe evaluation of immunomodulatory potential of A. carambola (800 and 1 200 mg/kg, p.o.) evoked a dose-dependent increase in antibody titer values and DTH reaction induced by SRBC was also found significant (P<0.001). Also it caused increase in hematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed mice. Result shows that the extract treated animals showed up regulation of (IL-6 and TNF-α) cytokines.ConclusionsImmunomodulators are being used as an adjuvant in conditions of immunodeficiency in cancer and to a limited extent in acquired immunodeficiency syndrome. The results obtained in this study indicate that A. carambola possesses potential immunomodulatory and antioxidant activity

Challenges in laser cleaning of cultural heritage stained glass

Stained-glass windows play an important role in cultural heritage. Human and environmental factors have subjected these pieces to risks of damage. Mechanical and chemical- based cleaning methods have been used for their restoration and conservation. Additionally, short-pulse lasers have opened new opportunities for safe and controlled cleaning and restoration of these important materials. In this work, ultra-short pulsed lasers were used to clean an artificially applied coating from the surface of a contemporary colorless glass frequently used in the restoration of stained-glass windows. One of the objectives was to explore the applicability of using these types of lasers to safely clean historical stained-glass windows. It was observed that temperature rise and subsequent heat accumulation in the coating layer being removed was sufficient to generate significant thermal stresses on the underlying glass surface leading to damages even when the laser energies are lower than the damage thresholds. Some laser treatments that limit this heat accumulation were designed in this study. For laser systems operating at frequencies in the range of several hundreds of kHz, the option was to work in burst mode, limiting the number of pulses in each burst and selecting an adequate time lapse between two consecutive burst runs. A method to uniformly clean a given surface is proposed in this work. When lower frequencies are available, treatments using frequencies lower than 20 kHz are enough to safely clean the glass. When UV laser radiation is used, optical damage is also an important aspect to be considered. In this case, the cleaning protocol has to deal with both issues, to avoid heat accumulation and chemical damageEuropean Commission under Grant Agreement 766311 - H2020-MSCA-ITN-EJD ED-ARCHMAT Projec

Ultra-Short Pulse Laser Cleaning of Contaminated Pleistocene Bone: A Comprehensive Study on the Influence of Pulse Duration and Wavelength

The impact of wavelength and pulse duration in laser cleaning of hard blackish contaminants crust from archaeologically significant Pleistocene bone is investigated in this research. The objective is to determine the practical cleaning procedures and identify adequate laser parameters for cleaning archaeological bone from Sima de los Huesos (Spain) based on conservation and restoration perspectives. Bone surface cleaning was performed utilizing two Q-switched Nd:YAG lasers: sub-nanosecond pulsed lasers with emission wavelengths at 355 nm and 1064 nm, respectively, and a Yb:KGW femtosecond pulsed laser with an emission wavelength in the third harmonic at 343 nm. In all experiments, the laser beam scanning mode was applied to measure cleaning efficiency in removing contaminants and degradation products while assessing the underlying substrate surface damage. Several properties, including wavelength-dependent absorption, pulse repetition rate, and thermal properties of the material, are analyzed when evaluating the ability of these lasers to boost the cleaning efficiency of the deteriorated bone surface. Bone surface morphology and composition were studied and compared before and after laser irradiation, using Optical Microscopy, Scanning Electron Microscopy with Energy Dispersive X-ray Spectrometry (SEM-EDS), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS) characterization methods. The results indicate that 238-femtosecond UV laser irradiation with 2.37 TWcm−2 is significantly safer and more efficient toward surface contaminant desorption than sub-nanosecond laser irradiation. The results herein presented suggest that these types of fs lasers may be considered for realistic laser conservation of valuable historic and archaeological museum artifacts

Bayesian estimates of linkage disequilibrium

[Background] The maximum likelihood estimator of D' – a standard measure of linkage disequilibrium – is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes. [Results] This paper proposes a Bayesian estimation of D' to address this problem. The reduction of the bias is achieved by using a prior distribution on the pair-wise associations between single nucleotide polymorphisms (SNP)s that increases the likelihood of equilibrium with increasing physical distances between pairs of SNPs. We show how to compute the Bayesian estimate using a stochastic estimation based on MCMC methods, and also propose a numerical approximation to the Bayesian estimates that can be used to estimate patterns of LD in large datasets of SNPs. [Conclusion] Our Bayesian estimator of D' corrects the bias toward disequilibrium that affects the maximum likelihood estimator. A consequence of this feature is a more objective view about the extent of linkage disequilibrium in the human genome, and a more realistic number of tagging SNPs to fully exploit the power of genome wide association studies.Research supported by NIH/NHLBI grant R21 HL080463-01, NIH/NIDDK 1R01DK069646-01A1 and the Spanish research program [projects TIN2004-06204-C03-02 and TIN2005-02516]

An Extension Study of PF-05280586, a Potential Rituximab Biosimilar, versus Rituximab in Subjects with Active Rheumatoid Arthritis

Objective; This extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF‐05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF‐05280586 after transition from a licensed rituximab product to PF‐05280586, and followup of biomarker and efficacy assessments. Methods; Subjects were offered ≤3 additional courses of treatment of PF‐05280586, with or without a single transition from rituximab EU (rituximab‐EU) or US (rituximab‐US) to PF‐05280586. Each course comprised 2 IV infusions (1,000 mg on Days 1 and 15, separated by 24 weeks [±8 weeks)]. Results; Of 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B‐cells between groups, and no apparent relationship between infusion‐related reactions and antidrug antibodies with or without single transition from licensed rituximab to PF‐05280586. Long‐term safety and tolerability of PF‐05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment‐emergent adverse events independent of single drug transition. The percentage of subjects with low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study. Conclusions; This study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from licensed rituximab to PF‐05280586, without increased immunogenicity on single transition

Ultrashort pulsed Femtosecond UV laser for selective cleaning of significant Cretaceous flints

This work reports on studies aimed to evaluate the utilization of ultrashort 238 fs (fs) pulsed UV laser emission at 343 nm for eliminating colored crusts and surface deposits on significant Cretaceous flint surfaces, in an attempt to safeguard its aesthetic appearance and archaeological value. The results indicate that fs UV lasers may be an ideal, non-contact tool for selective surface cleaning of sensitive archaeological artefacts, since they enable contaminant desorption while avoiding photothermal damage

Evolución de las enfermedades transmisibles en pacientes extranjeros en la ciudad de Valencia. 2001-2010.

El impacto del fenómeno migratorio iniciado en la última década del siglo XX, nos ha llevado de una población extranjera de 801.329 individuos en 1.999 a cifras de 791.232 en 2.009. Ello ha dado lugar a la publicación de numerosos estudios sobre la utilización de recursos sanitarios, la problemática psicológica, la fecundidad del colectivo y, principalmente, las patologías infecciosas dada la creencia de que las enfermedades transmisibles suponían un riesgo importado para la población española. En 2003 publicamos la frecuentación hospitalaria y el impacto de las enfermedades infecciosas en inmigrantes, el objeto de este trabajo ha sido determinar la frecuentación hospitalaria debida a enfermedades infecciosas y/o parasitarias, tras 10 años del primer estudio. Se desarrolló un estudio observacional longitudinal retrospectivo de motivos de ingreso y diagnósticos al alta de la población inmigrante hospitalizada en la ciudad de Valencia para el periodo 01/01/2006 a 31/12/2010. Se recuperaron 7.212 altas de procesos infecciosos 13.07%), 2.995 enfermedades transmisibles (5,43%). Los pacientes por origen fueron americano (35,83%), europeo (28,55%) y africano (21,60%), lo que representa un aumento importante de la población de África subsahariana con respecto al año 2001. El primer diagnóstico nos permitió ordenar los procesos como tuberculosis (27,62%), paludismo (13,58%), el VIH (10,86%) y la hepatitis (7,81%).Los procesos infecciosos y las enfermedades transmisibles han disminuido en valores absolutos a lo largo de la década 2001-2010, posiblemente por el descenso de las diferencias en el patrón cultural de la población a lo largo de los años de permanencia en España. No obstante, han aumentado en valores absolutos los pacientes del África subsahariana en los que las enfermedades infecciosas representan el 11,43% de las altas

Ecological factors related to the widespread distribution of sylvatic Rhodnius ecuadoriensis populations in southern Ecuador

<p>Abstract</p> <p>Background</p> <p>Chagas disease transmission risk is a function of the presence of triatomines in domestic habitats. <it>Rhodnius ecuadoriensis </it>is one of the main vectors implicated in transmission of <it>Trypanosoma cruzi </it>in Ecuador. This triatomine species is present in domestic, peridomestic and sylvatic habitats in the country. To determine the distribution of sylvatic populations of <it>R. ecuadoriensis </it>and the factors related to this distribution, triatomine searches were conducted between 2005 and 2009 in southern Ecuador.</p> <p>Methods</p> <p>Manual triatomine searches were conducted by skilled bug collectors in 23 communities. Sylvatic searched sites were selected by a) directed sampling, where microhabitats were selected by the searchers and b) random sampling, where sampling points where randomly generated. Domiciliary triatomine searches were conducted using the one man-hour method. Natural trypanosome infection was determined by microscopic examination and PCR. Generalized linear models were used to test the effect of environmental factors on the presence of sylvatic triatomines.</p> <p>Results</p> <p>In total, 1,923 sylvatic individuals were collected representing a sampling effort of 751 man-hours. Collected sylvatic triatomines were associated with mammal and bird nests. The 1,219 sampled nests presented an infestation index of 11.9%, a crowding of 13 bugs per infested nest, and a colonization of 80% of the nests. Triatomine abundance was significantly higher in squirrel (<it>Sciurus stramineus</it>) nests located above five meters from ground level and close to the houses. In addition, 8.5% of the 820 examined houses in the same localities were infested with triatomines. There was a significant correlation between <it>R. ecuadoriensis </it>infestation rates found in sylvatic and synanthropic environments within communities (<it>p </it>= 0.012). Parasitological analysis revealed that 64.7% and 15.7% of the sylvatic bugs examined (n = 300) were infected with <it>Trypanosoma cruzi </it>and <it>T. rangeli </it>respectively, and 8% of the bugs presented mixed infections.</p> <p>Conclusions</p> <p>The wide distribution of sylvatic <it>R. ecuadoriensis </it>populations may jeopardize the effectiveness of control campaigns conducted to eliminate domestic populations of this species. Also, the high <it>T. cruzi </it>infection rates found in sylvatic <it>R. ecuadoriensis </it>populations in southern Ecuador could constitute a risk for house re-infestation and persistent long-term Chagas disease transmission in the region.</p

Statins in unconventional secretion of insulin-degrading enzyme and degradation of the amyloid-β peptide.

Population-based studies demonstrated that statins might decrease the risk of developing Alzheimer's disease (AD). Statins inhibit the 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase and thereby de novo synthesis of cholesterol. Cell culture and animal studies indicated that cholesterol affects the proteolytic processing of the amyloid precursor protein and the generation of amyloid-β (Aβ). Recently, we have demonstrated that statins can also stimulate the degradation of Aβ. The statin-induced clearance of Aβ could be attributed to increased release of the insulin-degrading enzyme (IDE) via an exosome-related unconventional secretory pathway. Interestingly, this statin-induced secretion of exosome-associated IDE was independent of cellular cholesterol concentrations, but rather caused by impairment of isoprenoid biosynthesis and protein prenylation. We further identified a new hexapeptide sequence in the C-terminal region of IDE, named the SlyX motif that is critically involved in IDE secretion. Taken these findings together, the increased clearance of Aβ by stimulated secretion of IDE might contribute to the protective effects of statins against AD