Applicability of oculomics for individual risk prediction: Repeatability and robustness of retinal Fractal Dimension using DART and AutoMorph

Purpose: To investigate whether Fractal Dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness. Methods: We used two datasets: Caledonia, healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 colour fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE, thus it provides a pessimistic lower-bound as vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and Intraclass Correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter {\lambda} which is within-eye Standard Deviation (SD) of FD measurements in units of between-eyes SD. Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all p<0.0001). Median {\lambda} in Caledonia without exclusions was 3.55\% for DART and 12.65\% for AutoMorph, and improved to up to 1.67\% and 6.64\% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with {\lambda} (Pearson 0.5350-0.7550, depending on dataset and method, all p<0.0001). Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods

Galanin (1-15) enhances the behavioral effects of fluoxetine in the forced swimming test: a new therapeutic strategy against depression

The selective serotonergic (5- HT) reuptake inhibitors, including Fluoxetine (FLX), are the most commonly used for treatment of major depression. However, the understanding of the mechanism of action of FLX beyond its effect of elevating 5-HT is limited. The interaction between 5-HT system and neuropeptides signaling could be a key aspect. The neuropeptide Galanin(1-15) [GAL(1-15)], induced a strong depression-like and anxiogenic-like effects in the forced swimming test (FST), the tail suspension test, the open field and the light/dark test. The GALR1-GALR2 heteroreceptor complexes in the dorsal hippocampus and in the dorsal raphe were involved in these effects. We have analyzed the effect of GAL(1–15) on FLX-mediated responses in the FST. We tested the involvement of GALR in the GAL(1–15) effect with the selective GALR2 antagonist M871 and using siRNA GALR2 or GALR1 knockdown rats. Groups of rats received three injections of sc FLX(2.5mg/Kg) or FLX(10mg/Kg) and a single icv injection of a threshold dose of GAL(1-15)(1nmol) 15 minutes before the FST. In a second set of experiments, we determined the involvement of GALR1 and GALR2 in the effect of GAL(1-15) on FLX-mediated action. Groups of rats received three injections of sc FLX(10mg/kg), a single icv injection of GAL(1-15) (1nmol) and the GALR2 antagonist M871 (3nmol) icv alone or in combination. Also, in siRNA GALR1 or GALR2 knockdown rats we coadministered FLX(10mg/Kg) and GAL(1-15)(1nmol). The coadministration of sc FLX(2.5mg/Kg) and icv injection of GAL(1-15)(1nmol) induced antidepressant-like effects with a significant decrease in the immobility (p<0.05). Moreover, an increase in the swimming time (p <0.05) was also observed. The strong enhancement by GAL(1-15) of the antidepressant-like effects mediated by FLX was validated using the effective dose of FLX 10mg/kg. Icv GAL(1-15) significantly decreased the immobility time induced by the effective dose of FLX(10mg/kg) by 50% in the FST (p<0.05). Moreover, an increase of the swimming time by about 40% versus FLX(10mg/kg) group was also observed (p<0.01). The GALR2 antagonist M871 3nmol significantly blocked the GAL(1–15)-induced reduction of the immobility time (p<0.05), and increase in the swimming time (p<0.01) found after coadministration of icv injection of GAL(1-15) and sc FLX(10mg/kg) in the FST. The coadministration of sc FLX(10mg/kg) and icv injection of GAL(1-15) in siRNA GALR1 or GALR2 knockdown animals did not produce a further reduction of the immobility time and a further increase in the swimming time compared to FLX alone. In the current study we describe for the first time that GAL(1-15) enhances the antidepressant-like effects induced by FLX in the FST. Indications were also obtained for the involvement of a GALR1/GALR2 heteroreceptor complex in the GAL (1-15)-mediated actions based on the use of the specific GALR2 antagonist M871 and icv injections of GALR1 siRNA or GALR2 siRNA producing a reduction of GALR1 or GALR2, respectively. The results open up the possibility to use GAL(1-15) as for a combination therapy with FLX as a novel strategy for treatment of depression. This work was supported by grants awarded by Spanish Ministry of Economy (SAF2016-79008-P),Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The potent vasodilator ethyl nitrite is formed upon reaction of nitrite and ethanol under gastric conditions

By acting as a bioreactor, affording chemical and mechanical conditions for the reaction between dietary components, the stomach may be a source of new bioactive molecules. Using gas chromatography-mass spectrometry we here demonstrate that, under acidic gastric conditions, ethyl nitrite is formed in µM concentrations from the reaction of red wine or distilled alcoholic drinks with physiological amounts of nitrite. Rat femoral artery rings and gastric fundus strips dose-dependently relaxed upon exposure to nitrite:ethanol mixtures. In contrast, when administered separately in the same dose ranges, nitrite evoked only minor vasorelaxation while ethanol actually caused a slight vasoconstriction. Mechanistically, the relaxation effect was assigned to generation of nitric oxide (-NO) as supported by direct demonstration of -NO release from ethyl nitrite and the absence of relaxation in the presence of the soluble guanylyl cyclase inhibitor, ODQ. In conclusion, these results suggest that ethanol in alcoholic drinks interacts with salivary-derived nitrite in the acidic stomach leading to the production of the potent smooth muscle relaxant ethyl nitrite. These findings reveal an alternative chemical reaction pathway for dietary nitrate and nitrite with possible impact on gastric physiology and pathophysiology.http://www.sciencedirect.com/science/article/B6T38-4SCDB0R-4/1/5f2ae4cd1ef8af7eca3f5d4ee8f353a

Visible neutrino decay in the light of appearance and disappearance long-baseline experiments

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESWe investigate the present constraints from MINOS and T2K experiments for the neutrino decay scenario induced by non-diagonal couplings of Majorons to neutrinos. As novelty, on top of the typical invisible decay prescription, we add the contribution of visible decay, where final products can be observed. This new effect depends on the nature of the neutrino-Majoron coupling, which can be of scalar or pseudoscalar type. Using the combination of disappearance data from MINOS and disappearance and appearance data from T2K, for normal ordering, we constrain the decay para alpha E Gamma for the heaviest neutrino, where E and are the neutrino energy and width, respectively. We find that when considering visible decay within appearance data, alpha < O (10(-5))eV(2), at 90% C.L., for both kinds of couplings, which is better by one order of magnitude compared to previous bounds.11129FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES014/19164-62015/20129-3311980/2013-9461147/2014-9Sem informaçãoA.M.G. and J.J.P. acknowledge funding by the Direccion de Gestion de la Investigacion at PUCP, through grant DGI-2015-3-0026. They would also like to thank S. Sanchez for discussions on the use of GENIE, as well as O.A. Diaz in the Direccion de Tecnologias de Informacion at PUCP, for implementing our code within the LEGION system. A.M.G is thankful for the Unicamp hospitality and for the support of the FAPESP funding grant 2015/20129-3. A.M.G and O.L.G.P are also thankful to the Oficina de Internacionalizacion de la Investigacion at PUCP. A.L.G. G. is supported by CAPES, and R.A.G. would like to thanks CNPq grants 461147/2014-9 and 311980/2013-9. O.L.G.P. is thankful for the PUCP hospitality and partial support under the Programa Latino Americano de Fisica (PLAF) from Brazilian Physics Society. He is also thankful for the support of FAPESP funding grant 2014/19164-6 and CNPq research fellowship 307269/2013-2 and 304715/2016-6 and partial funding from ICTP

Order enhancement and coarsening of self-organized silicon nanodot patterns induced by ion-beam sputtering

3 pages, 3 figures.-- PACS nrs.: 81.05.Cy, 81.07.-b, 68.47.Fg, 81.16.Rf, 79.20.Rf, 68.35.Bs.The temporal evolution of the characteristic wavelength (λ) and ordering range (ξ) of self-organized nanodot patterns induced during Ar+ ion beam sputtering on Si(001) and Si(111) surfaces is studied by atomic force microscopy and grazing incidence x-ray diffraction. The patterns exhibit initial coarsening of λ (up to 54–60 nm) and increase in ξ (up to 400–500 nm) after which both features stabilize. The pattern formation is only weakly controlled by the crystallographic surface orientation, Si(111) surfaces showing a faster evolution into a proper stationary state. This trend is attributed to a higher sputtering rate at this orientation, as confirmed by theoretical simulations.This work has been supported by grants BFM2003- 07749-C05-01, BFM2003-07749-C05-02, and BFM2003- 07749-C05-05 from the Spanish Ministerio de Educación y Ciencia (MEC). Two of the authors (R.G. and J.M.-G.) acknowledge financial support from MEC through the “Ramón y Cajal” and FPU programs, respectively.Publicad

Avaliação da toxicidade das lamas de cal sobre o ouriço-do-mar Paracentrotus lividus (Lamark, 1816). Perspetivas para novas aplicações destes resíduos industriais

Através da utilização do ouriço-do-mar Paracentrotus lividus como bioindicador, neste estudo avaliou-se a potencialidade de utilização de um resíduo das indústrias do papel, as lamas de cal, em duas vertentes. A primeira consistia em aproveitar a característica alcalina das lamas de cal como redutiva da crescente acidificação dos oceanos. Nos bioensaios realizados obteve-se um aumento significativo na percentagem de malformações das larvas pluteus de P. lividus que foram cultivadas em águas com concentrações superiores a 0,1 mg/L de lamas de cal, o que coloca em causa esta primeira potencialidade. A segunda baseava-se no elevado teor em cálcio presente nas lamas de cal que desta forma poderiam servir como matéria-prima deste macronutriente em rações para adultos P. lividus. Após 6 meses de cultivo em que os ouriços-do-mar foram alimentados com 4 rações diferentes que diferiam na concentração de lamas de cal utilizadas, os resultados obtidos para as variáveis biométricas analisadas, para o índice gonadossomático, para a concentração de Ca, Hg, Pb e Cd nas gónadas e parede do corpo, e para os ensaios ecotoxicológicos, parecem viabilizar esta segunda potencialidade.Through the use of the sea urchin Paracentrotus lividus as bioindicator, this study evaluated the potential to use the waste of paper mills, lime sludge, on two perspectives. The first was to take advantage of the lime sludge alkaline character as a deterrent of increasing ocean acidification. In bioassay testing, a significant increase in the percentage of plutei larvae malformations was obtained when they were cultured at lime sludge concentrations above 0.1 mg/L. This result undermines this first perspective. The second relied on the lime sludge high calcium concentration which could thereby serve as raw material for P. lividus feeds. After 6 months of captive period in which adult sea urchins were fed 4 diets that differed in lime sludge addition, the results obtained for the biometric variables analyzed, for the GSI, for the concentration of Ca, Hg, Pb and Cd in the gonads and in the body wall, and for larvae ecotoxicological testing, appear to support this second potential