The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures

How to minimise the effect of tumour cell content in detection of aberrant genetic markers in neuroblastoma

Background:Clinical heterogeneity reflects the complexity of genetic events associated with neuroblastoma (NB). To identify the status of all described genetic loci with possible prognostic interest, high-throughput approaches have been used, but only with tumour cell content >60%. In some tumours, necrotic, haemorrhagic and/or calcification areas influence the low amount of neuroblasts. We evaluated the effect of tumour cell content in the detection of relevant aberrant genetic markers (AGM) diagnosed by fluorescence in situ hybridisation (FISH) on tissue microarrays (TMA) in NB.Methods:Two hundred and thirty-three MYCN non-amplified primary NB included in 12 TMAs were analysed.Results:Presence of AGM reduced event-free survival (EFS) (P=0.004) as well as overall survival (OS) (P=0.004) of patients in the whole cohort. There were no differences in prognostic impact of presence of AGM according to tumour cell content.Conclusion:We propose the use of FISH to diagnose AGM of all NB samples having the above-mentioned areas to determine patient risk

Post-licensing safety of fosamprenavir in HIV-infected children in Europe

Purpose: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration. Methods: Retrospective analysis of individual patient data for all children aged 6–18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity. Results: Ninety-two HIV-infected children aged 6–18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1–11 years), and median age at start of FPV/r was 15 years (12–17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported. Conclusions: Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported

Virtual Blocks: a serious game for spatial ability improvement on mobile devices

This paper presents a novel spatial instruction system for improving spatial abilities of engineering students. A 3D mobile game application called Virtual Blocks has been designed to provide a 3D virtual environment to build models with cubes that help students to perform visualization tasks to promote the development of their spatial ability during a short remedial course. A validation study with 26 freshman engineering students at La Laguna University (Spain) has concluded that the training had a measurable and positive impact on students spatial ability. In addition, the results obtained using a satisfaction questionnaire show that Virtual Blocks is considered an easy to use and stimulating application.This work has been partially supported by the (Spanish) National Program for Studies and Analysis project "Evaluation and development of competencies associated to the spatial ability in the new engineering undergraduate courses" (Ref. EA2009-0025) and the (Spanish) National Science Project "Enhancing Spatial REasoning and VIsual Cognition with advanced technological tools (ESREVIC)" (Ref TIN2010-21296-C02-02)Martín Dorta, NN.; Sanchez Berriel, I.; Bravo, M.; Hernández, J.; Saorin, JL.; Contero, M. (2014). Virtual Blocks: a serious game for spatial ability improvement on mobile devices. Multimedia Tools and Applications. 73(3):1575-1595. https://doi.org/10.1007/s11042-013-1652-0S15751595733Baartmans BG, Sorby SA (1996) Introduction to 3-D spatial visualization. Prentice Hall, Englewood CliffsClements D, Battista M (1992) Geometry and spatial reasoning. In: Grouws DA (ed) Handbook of research on mathematics teaching and learning. New York, pp 420–464Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, HillsdaleDe Lisi R, Cammarano DM (1996) Computer experience and gender differences in undergraduate mental rotation performance. Comput Hum Behav 12:351–361Deno JA (1995) The relationship of previous experiences to spatial visualization ability. Eng Des Graph J 59(3):5–17Feng J, Spence I, Pratt J (2007) Playing an action video game reduces gender differences in spatial cognition. Psychol Sci 18(10):850–855French JW (1951) The description of aptitude and achievement tests in terms of rotated factors. Psychometric monograph 5Guilford JP, Lacy JI (1947) Printed classification tests, A.A.F. Aviation Psychological Progress Research Report, 5. US. Government Printing Office, Washington DCHalpern DF (2000) Sex differences and cognitive abilities. Erlbaum, MahwahHöfele C (2007) Mobile 3D graphics: learning 3D graphics with the Java Micro Edition. Editorial ThomsonKajiya JT, Kay TL (1989) Rendering fur with three dimensional textures. In Proceedings of the 16th Annual Conference on Computer Graphics and interactive Techniques SIGGRAPH ’89. ACM Press, New York pp 271–280Linn MC, Petersen AC (1985) Emergence and characterization of gender differences in spatial abilities: a meta-analysis. Child Dev 56:1479–1498Martin-Dorta N, Sanchez-Berriel I, Bravo M, Hernandez J, Saorin JL, Contero M (2010) A 3D educational mobile game to enhance student’s spatial skills, ICALT, pp.6–10, 2010 10th IEEE International Conference on Advanced Learning TechnologiesMartin-Dorta N, Saorin J, Contero M (2008) Development of a fast remedial course to improve the spatial abilities of engineering students. J Eng Educ 27(4):505–514Martin-Dorta N, Saorin JL, Contero M (2011) Web-based spatial training using handheld touch screen devices. Educ Technol Soc 14(3):163–177McGee MG (1979) Human spatial abilities: psychometric studies and environmental, genetic, hormonal, and neurological influences. Psychol Bull 86:889–918Noguera JM, Segura RJ, Ogayar CJ, Joan-Arinyo R (2011) Navigating large terrains using commodity mobile devices. Comput Geosci 37:1218–1233Okagaki L, Frensch PA (1994) Effects of video game playing on measures of spatial performance: gender effects in late adolescence. J Appl Dev Psychol 15(1):33–58Pulli K, Aarnio T, Miettinen V, Roimela K, Vaarala J (2007) Mobile 3D graphics with OpenGL ES and M3G. Editorial Morgan KaufmannQuaiser-Pohl C, Geiser C, Lehmann W (2005) The relationship between computer-game preference, gender, and mental-rotation ability. Personal Individ Differ 40(3):609–619Smith IM (1964) Spatial ability- its educational and social significance. The University of London Press, LondonSorby S (2007) Developing 3D spatial skills for engineering students. Australas Assoc Eng Educ 13(1):1–11Terlecki MS, Newcombe NS (2005) How important is the digital divide? The relation of computer and videogame usage to gender differences in mental rotation ability. Sex Roles 53(5/6):433–441Terlecki MS, Newcombe NS, Little M (2008) Durable and generalized effects of spatial experience on mental rotation: gender differences in growth patterns. Appl Cogn Psychol 22:996–1013Thurstone LL (1950) Some primary abilities in visual thinking (Tech. Rep. No. 59). IL University of Chicago Psychometric Laboratory, ChicagoThurstone LL, Thurstone TG (1941) Factorial studies of intelligence. Psychometric monographs. Chicago Press, ChicagoVanderberg S, Kuse A (1978) Mental Rotation, a group test of three dimensional spatial visualization. Percept Mot Skills 47:599–604Zimmerman WS (1954) Hypotheses concerning the nature of the spatial factors. Educ Psychol Meas 14:396–40

Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant

Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging. Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region). Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop. Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env. Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies. In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env. While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region. Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions

Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages

Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections

Metastasis to the breast from an adenocarcinoma of the lung with extensive micropapillary component: a case report and review of the literature

Breast metastasis from extra-mammary malignancy is rare. Based on the literature an incidence of 0.4-1.3% is reported. The primary malignancies most commonly metastasizing to the breast are leukemia-lymphoma, and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 73-year-old female presented with dyspnea and dry cough of 4 weeks duration and a massive pleural effusion was found on a chest radiograph. Additionally, on physical examination a poorly defined mass was noted in the upper outer quadrant of the left breast. The patient underwent bronchoscopy, excisional breast biopsy and medical thoracoscopy. By cytology, histology and immunohistochemistry primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Both the primary and metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient received chemotherapy but passed away within 7 months. Accurate differentiation of metastatic from primary carcinoma is of crucial importance because the treatment and prognosis differ significantly

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background\ud In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.\ud \ud Methods\ud We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings.\ud \ud Results\ud Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls).\ud \ud Conclusions\ud Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases

Carbon nanoparticles in lateral flow methods to detect genes encoding virulence factors of Shiga toxin-producing Escherichia coli

The use of carbon nanoparticles is shown for the detection and identification of different Shiga toxin-producing Escherichia coli virulence factors (vt1, vt2, eae and ehxA) and a 16S control (specific for E. coli) based on the use of lateral flow strips (nucleic acid lateral flow immunoassay, NALFIA). Prior to the detection with NALFIA, a rapid amplification method with tagged primers was applied. In the evaluation of the optimised NALFIA strips, no cross-reactivity was found for any of the antibodies used. The limit of detection was higher than for quantitative PCR (q-PCR), in most cases between 104 and 105 colony forming units/mL or 0.1–0.9 ng/μL DNA. NALFIA strips were applied to 48 isolates from cattle faeces, and results were compared to those achieved by q-PCR. E. coli virulence factors identified by NALFIA were in very good agreement with those observed in q-PCR, showing in most cases sensitivity and specificity values of 1.0 and an almost perfect agreement between both methods (kappa coefficient larger than 0.9). The results demonstrate that the screening method developed is reliable, cost-effective and user-friendly, and that the procedure is fast as the total time required is <1 h, which includes amplification