Easy dual-mode ambient mass spectrometry with Venturi self-pumping, canned air, disposable parts and voltage-free sonic-spray ionization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)An exceptionally easy to assemble source for ambient mass spectrometry is described. Based on Venturi easy ambient sonic-spray ionization (V-EASI), the source was further simplified by the use of a can of compressed air which simultaneously provides solution or solvent Venturi self-pumping and continuous, stable and abundant low-noise ion signal via voltage-free sonic-spraying. Further simplification was also attained by the use of inexpensive and readily commercially available parts: a surgical 2-way catheter, an aerosol can of compressed air, a 30 cm long fused-silica capillary and a hypodermic needle. This 'Spartan' V-EASI source seems to offer one of the easiest and cheapest ways to make ions for ambient desorption/ionization mass spectrometry analysis of both liquid and solid samples.1371125372540Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Brazilian Science Foundation's FINEPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Mental health screening using the MINI test in medical students

Introducción: Los trastornos de salud mental constituyen un problema prevalente en alumnos de educación superior, siendo los estudiantes de medicina una población especialmente vulnerable. Objetivos: Determinar la frecuencia de trastornos de salud mental en los alumnos de una escuela de medicina. Diseño: Estudio descriptivo, transversal. Institución: Escuela de Medicina, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo, Lambayeque, Perú. Participantes: Alumnos de una escuela de medicina. Intervenciones: En el semestre académico 2010-I, se evaluó la frecuencia de trastornos de salud mental en los alumnos utilizando el test Mini International Neuropsychiatric Interview (MINI), validado en español, como método de tamizaje. Principales medidas de resultados: Frecuencia de problemas de salud mental. Resultados: Se evaluó 159 estudiantes, 94 del sexo femenino (59,1%) y 65 de sexo masculino (40,8%); la media de la edad fue de 18,6+/- 2,1 años; 35 alumnos (22%) tuvieron al menos un trastorno mental. Los diagnósticos más frecuentes fueron: episodio hipomaniaco pasado (16 alumnos; 10,2%), riesgo suicida (11; 6,9%), trastorno depresivo actual (9; 5,6%), trastorno de angustia actual (8; 5%), agorafobia (8; 5%). En 20 (12,6%) y 11 estudiantes (6,9%), respectivamente, algún profesional de la salud le había diagnosticado previamente ansiedad y depresión. Conclusiones: Los problemas de salud mental fueron frecuentes en esta población de estudiantes, siendo el episodio hipomaniaco pasado, el riesgo suicida y el episodio depresivo actual los más frecuentes.Introduction: Mental health disorders are prevalent in higher education students and medical students are especially vulnerable. Objectives: To determine mental health problems frequency in students of Medicine. Design: Descriptive, transversal study. Setting: School of Medicine, Universidad Catolica Santo Toribio de Mogrovejo, Chiclayo, Lambayeque, Peru. Participants: Medical students. Interventions: During the 2010-I academic semester, frequency of mental health problems were determined using the Mini International Neuropsychiatric Interview (MINI) test, validated in Spanish, as a screening test for mental health. Main outcome measures: Frequency of mental health problems. Results: From 159 students interviewed, 94 were women (59,1%) and 65 men (40,8%). Average age was 18,7+/- 2,1 years; 35 students (22%) had at least one mental disorder. There were 16 (10,2%) students with history of hypomania episode, 11 with suicide risk (6,9%), 9 with current depressive disorder (5,6%), 8 with agoraphobia (4,8%), 8 with current anxiety disorder (4,8%); 20 (12,6%) and 11 (6,9%) students respectively mentioned that a health care provider had previously diagnosed anxiety and depression. Conclusions: Mental health disorders were frequent in these medical students; past hypomania episode, suicidal risk and current depressive disorder were the most frequently diagnosed mental health disorders

From non-symmetric particle systems to non-linear PDEs on fractals

We present new results and challenges in obtaining hydrodynamic limits for non-symmetric (weakly asymmetric) particle systems (exclusion processes on pre-fractal graphs) converging to a non-linear heat equation. We discuss a joint density-current law of large numbers and a corresponding large deviations principle.Comment: v2: 10 pages, 1 figure. To appear in the proceedings for the 2016 conference "Stochastic Partial Differential Equations & Related Fields" in honor of Michael R\"ockner's 60th birthday, Bielefel

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.Methods The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (394 cases, 1,606 controls). Benign breast biopsy slides were reviewed by pathologists and CCL presence assessed. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between CCL and breast cancer risk. Results: Women with CCL (140 cases, 448 controls) had an increased risk of breast cancer compared with those without CCL (OR = 1.44, 95% CI: 1.14 to 1.83), although this was attenuated and became non-significant after adjustment for the histologic category of BBD (OR = 1.20, 95% CI: 0.94 to 1.54). CCL presence was associated with the greatest risk of breast cancer for those with nonproliferative BBD (OR = 1.36, 95% CI: 0.79 to 2.37) and the lowest risk for those with atypical hyperplasia (AH) (OR = 1.10, 95% CI: 0.65 to 1.87); however, this apparent heterogeneity in risk across BBD categories was not significant (P for interaction between CCL presence and BBD category = 0.77). Conclusions: These results provide evidence that CCL may be an important marker of breast cancer risk in women with BBD but suggest that CCL do not increase breast cancer risk independently of concurrent proliferative changes in the breast

Maternal Serologic Screening to Prevent Congenital Toxoplasmosis: A Decision-Analytic Economic Model

We constructed a decision-analytic and cost-minimization model to compare monthly maternal serological screening for congenital toxoplasmosis, prenatal treatment, and post-natal follow-up and treatment according to the current French protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. We use sensitivity analysis to evaluate robustness of results. We find that universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French (Paris) protocol, leads to savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, incidence of primary T. gondii infection during pregnancy, and to bivariate analysis of test costs and incidence of primary T. gondii infection. Given the parameters in this model and a maternal screening test cost of$12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities

The macroecology of chemical communication in lizards: do climatic factors drive the evolution of signalling glands?

Chemical communication plays a pivotal role in shaping sexual and ecological interactions among animals. In lizards, fundamental mechanisms of sexual selection such as female mate choice have rarely been shown to be influenced by quantitative phenotypic traits (e.g., ornaments), while chemical signals have been found to potentially influence multiple forms of sexual and social interactions, including mate choice and territoriality. Chemical signals in lizards are secreted by glands primarily located on the edge of the cloacae (precloacal glands, PG) and thighs (femoral glands), and whose interspecific and interclade number ranges from 0 to >100. However, elucidating the factors underlying the evolution of such remarkable variation remains an elusive endeavour. Competing hypotheses suggest a dominant role for phylogenetic conservatism (i.e., species within clades share similar numbers of glands) or for natural selection (i.e., their adaptive diversification results in deviating numbers of glands from ancestors). Using the prolific Liolaemus lizard radiation from South America (where precloacal glands vary from 0-14), we present one of the largest-scale tests of both hypotheses to date. Based on climatic and phylogenetic modelling, we show a clear role for both phylogenetic inertia and adaptation underlying gland variation: (i) solar radiation, net primary productivity, topographic heterogeneity and precipitation range have a significant effect on number of PG variation, (ii) humid and cold environments tend to concentrate species with a higher number of glands, (iii) there is a strong phylogenetic signal that tends to conserve the number of PG within clades. Collectively, our study confirms that the inertia of niche conservatism can be broken down by the need of species facing different selection regimes to adjust their glands to suit the demands of their specific environments

Impact of Human Management on the Genetic Variation of Wild Pepper, Capsicum annuum var. glabriusculum

Management of wild peppers in Mexico has occurred for a long time without clear phenotypic signs of domestication. However, pre-domestication management could have implications for the population's genetic richness. To test this hypothesis we analysed 27 wild (W), let standing (LS) and cultivated (C) populations, plus 7 samples from local markets (LM), with nine polymorphic microsatellite markers. Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele number was higher in W, and 15 and 40% less in LS and C populations, respectively. Genetic variation had a significant population structure. In W populations, structure was associated with ecological and geographic areas according to isolation by distance. When LM and C populations where included in the analysis, differentiation was no longer apparent. Most LM were related to distant populations from Sierra Madre Oriental, which represents their probable origin. Historical demography shows a recent decline in all W populations. Thus, pre-domestication human management is associated with a significant reduction of genetic diversity and with a loss of differentiation suggesting movement among regions by man. Measures to conserve wild and managed populations should be implemented to maintain the source and the architecture of genetic variation in this important crop relative

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

<p>Abstract</p> <p>Background</p> <p>Microglial activation is an important histologic characteristic of the pathology of Alzheimer’s disease (AD). One hypothesis is that amyloid beta (Aβ) peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Aβ stimulation of microglia may prove to be an important therapeutic strategy for AD.</p> <p>Methods</p> <p>Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Aβ1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Aβ stimulated signaling response and subsequent increase in TNFα secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Aβ plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis.</p> <p>Results</p> <p>Aβ fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFα levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Aβ plaque load, or the related tyrosine kinase, Lyn. These anti-inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals.</p> <p>Conclusions</p> <p>These data suggest that amyloid dependent microgliosis may be Src kinase dependent <it>in vitro</it> and <it>in vivo.</it> This study defines a role for Src kinase in the microgliosis characteristic of diseased brains and suggests that particular tyrosine kinase inhibition may be a valid anti-inflammatory approach to disease. Dasatinib is an FDA-approved drug for treating chronic myeloid leukemia cancer with a reported ability to cross the blood-brain barrier. Therefore, this suggests a novel use for this drug as well as similar acting molecules.</p