Chitosan and hyaluronic acid nanoparticles as vehicles of epoetin beta for subconjunctival ocular delivery

Research Areas: Pharmacology & PharmacyNeuroprotection in glaucoma using epoetin beta (EPOβ) has yielded promising results. Our team has developed chitosan-hyaluronic acid nanoparticles (CS/HA) designed to carry EPOβ into the ocular globe, improving the drug’s mucoadhesion and retention time on the ocular surface to increase its bioavailability. In the present in vivo study, we explored the possibility of delivering EPOβ to the eye through subconjunctival administration of chitosan-hyaluronic acid-EPOβ (CS/HA-EPOβ) nanoparticles. Healthy Wistar Hannover rats (n = 21) were split into 7 groups and underwent complete ophthalmological examinations, including electroretinography and microhematocrit evaluations before and after the subconjunctival administrations. CS/HA-EPOβ nanoparticles were administered to the right eye (OD), and the contralateral eye (OS) served as control. At selected timepoints, animals from each group (n = 3) were euthanized, and both eyes were enucleated for histological evaluation (immunofluorescence and HE). No adverse ocular signs, no changes in the microhematocrits (≈45%), and no deviations in the electroretinographies in both photopic and scotopic exams were observed after the administrations (p < 0.05). Intraocular pressure remained in the physiological range during the assays (11–22 mmHg). EPOβ was detected in the retina by immunofluorescence 12 h after the subconjunctival administration and remained detectable until day 21. We concluded that CS/HA nanoparticles could efficiently deliver EPOβ into the retina, and this alternative was considered biologically safe. This nanoformulation could be a promising tool for treating retinopathies, namely optic nerve degeneration associated with glaucoma.info:eu-repo/semantics/publishedVersio

Usefulness of genetic characterization of narcolepsy and hypersomnia on phenotype definition: a study in Portuguese patients

The determination of human leukocyte antigen (HLA) class II genotype is widely used to confirm the diagnosis of narcolepsy with or without cataplexy. The HLA genotyping is reliable, easy to perform and reassures the clinician. It is also less invasive than other methodologies and is in accordance with the autoimmune hypothesis for the origin of narcolepsy. AIM. To assess the usefulness of genetic markers (HLA) in the differential diagnosis between different sleep disorders and their relevance in the context of our population

Green manure legumes affect seasonal soil and leaf CO2 exchange rates in an olive rainfed orchard

Management methods that decrease requirement for agricultural chemicals are needed to reduce adverse environmental impacts. Moreover, they can play an important role in atmospheric C02 emission and fixation. We propose green manure legumes to reduce erosion, soil compaction and nitrate pollution, to improve biodiversity, soil carbon sink and fertility, to save fossil fuels and to increase yield and the nutritional value of food products. The research was carried out near Mirandela, Northeast Portugal, on a 15- year commercial olive orchard (Olea europaea L. cv. Cobrançosa), grown under rainfed conditions

Analysis of new high-precision transit light curves of WASP-10 b: starspot occultations, small planetary radius, and high metallicity

The WASP-10 planetary system is intriguing because different values of radius have been reported for its transiting exoplanet. The host star exhibits activity in terms of photometric variability, which is caused by the rotational modulation of the spots. Moreover, a periodic modulation has been discovered in transit timing of WASP-10 b, which could be a sign of an additional body perturbing the orbital motion of the transiting planet. We attempt to refine the physical parameters of the system, in particular the planetary radius, which is crucial for studying the internal structure of the transiting planet. We also determine new mid-transit times to confirm or refute observed anomalies in transit timing. We acquired high-precision light curves for four transits of WASP-10 b in 2010. Assuming various limb-darkening laws, we generated best-fit models and redetermined parameters of the system. The prayer-bead method and Monte Carlo simulations were used to derive error estimates. Three transit light curves exhibit signatures of the occultations of dark spots by the planet during its passage across the stellar disk. The influence of stellar activity on transit depth is taken into account while determining system parameters. The radius of WASP-10 b is found to be no greater than 1.03 Jupiter radii, a value significantly smaller than most previous studies indicate. We calculate interior structure models of the planet, assuming a two-layer structure with one homogeneous envelope atop a rock core. The high value of the WASP-10 b's mean density allows one to consider the planet's internal structure including 270 to 450 Earth masses of heavy elements. Our new mid-transit times confirm that transit timing cannot be explained by a constant period if all literature data points are considered. They are consistent with the ephemeris assuming a periodic variation of transit timing...Comment: Accepted for publication in A&

Clinical experience with the integrase inhibitors Dolutegravir and Elvitegravir in HIV-infected patients: efficacy, safety and tolerance

[Abstract] Two integrase inhibitors (INSTIs), dolutegravir (DTG) and elvitegravir/cobicistat (EVG/COBI), have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in north-western Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. A total of 542 DTG (n = 275)- or EVG/COBI (n = 267)-based therapies were initiated during the study period. Overall, more than 90% of naïve and pre-treated patients had virological suppression in both groups after 48 weeks of initiation of treatment per-protocol snapshot analysis. During follow-up, 10.2% of patients were treated with DTG and 4.5% of those treated with EVG discontinued due to adverse events (AE). In the case of DTG mainly related to neuropsychiatric disturbances (70.4%) and for EVG/COBI with gastrointestinal discomfort (50%). Female sex [HR 2.255 (95%CI 1.121–4.535), p = 0.023] and DTG treatment [HR 2.453 (95%CI 1.221–4.931), p = 0.012] were associated with AE discontinuations. Specifically for neuropsychiatric events, DTG treatment [HR 5.906 (95%CI 1.954–17.846), p = 0.002] and receiving abacavir/lamivudine/DTG [HR 4.380 (95%CI 1.348–14.233), p = 0.014] were identified as predictive risk factors for treatment discontinuations in two different multivariate analyses. A high percentage of AE discontinuations not previously described in clinical trials has been observed, especially with DTG. Female gender and DTG treatment were identified as risk factors for AE discontinuation. DTG-based therapies, especially in combination with abacavir/lamivudine, were associated with an increased risk of treatment discontinuation due to neuropsychiatric AE.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; PI16/0215

The AGN content in luminous IR galaxies at z\sim2 from a global SED analysis including Herschel data

We use Herschel-PACS far-infrared data, combined with previous multi-band information and mid-IR spectra, to properly account for the presence of an active nucleus and constrain its energetic contribution in luminous infrared (IR) sources at z\sim2. The sample is composed of 24 sources in the GOODS-South field, with typical IR luminosity of 10^{12} Lo. Data from the 4 Ms Chandra X-ray imaging in this field are also used to identify and characterize AGN emission. We reproduce the observed spectral energy distribution (SED), decomposed into a host-galaxy and an AGN component. A smooth-torus model for circum-nuclear dust is used to account for the direct and re-processed contribution from the AGN. We confirm that galaxies with typical L_{8-1000um}\sim10^{12}Lo at z\sim2 are powered predominantly by star-formation. An AGN component is present in nine objects (\sim35% of the sample) at the 3sigma confidence level, but its contribution to the 8-1000 um emission accounts for only \sim5% of the energy budget. The AGN contribution rises to \sim23% over the 5-30 um range (in agreement with Spitzer IRS results) and to \sim60% over the narrow 2-6 um range. The presence of an AGN is confirmed by X-ray data for 3 (out of nine) sources, with X-ray spectral analysis indicating the presence of significant absorption, i.e. NH\sim10^{23}-10^{24} cm^{-2}. An additional source shows indications of obscured AGN emission from X-ray data. The comparison between the mid-IR--derived X-ray luminosities and those obtained from X-ray data suggests that obscuration is likely present also in the remaining six sources that harbour an AGN according to the SED-fitting analysis.Comment: 12 pages, including 5 figures. Accepted for publication in MNRA

Modelling the Spectral Energy Distribution of Compact Luminous Infrared Galaxies: Constraints from High Frequency Radio Data

We have performed 23 GHz VLA observations of 7 compact, luminous infrared galaxies, selected to have evidence of starburst activity. New and published multi-frequency data are combined to obtain the spectral energy distributions of all 7 galaxies from the near-infrared to the radio (at 1.4 GHz). These SEDs are compared with new models, for dust enshrouded galaxies, which account for both starburst and AGN components. In all 7 galaxies the starburst provides the dominant contribution to the infrared luminosity; in 4 sources no contribution from an AGN is required. Although AGN may contribute up to 50 percent of the total far--infrared emission, the starbursts always dominate in the radio. The SEDs of most of our sources are best fit with a very high optical depth of (>=50) at 1 micron. The scatter in the far-infrared/radio correlation, found among luminous IRAS sources, is due mainly to the different evolutionary status of their starburst components. The short time-scale of the star formation process amplifies the delay between the far-infrared and radio emission. This becomes more evident at low radio frequencies (below about 1 GHz) where synchrotron radiation is the dominant process. In the far-infrared (at wavelengths shorter than 100 micron) an additional source of scatter is provided by AGN, where present. AGN may be detected in the near-infrared by the absence of the knee, typical of stellar photospheres. However, near-infrared data alone cannot constrain the level at which AGN contribute because the interpretation of their observed properties, in this wave-band, depends strongly on model parameters.Comment: 14 pages, accepted for publication in Astronomy and Astrophysic

Photometric redshift accuracy in AKARI Deep Surveys

We investigate the photometric redshift accuracy achievable with the AKARI infrared data in deep multi-band surveys, such as in the North Ecliptic Pole field. We demonstrate that the passage of redshifted policyclic aromatic hydrocarbons and silicate features into the mid-infrared wavelength window covered by AKARI is a valuable means to recover the redshifts of starburst galaxies. To this end we have collected a sample of ~60 galaxies drawn from the GOODS-North Field with spectroscopic redshift 0.5<~z_spec<~1.5 and photometry from 3.6 to 24 micron, provided by the Spitzer, ISO and AKARI satellites. The infrared spectra are fitted using synthetic galaxy Spectral Energy Distributions which account for starburst and active nuclei emission. For ~90% of the sources in our sample the redshift is recovered with an accuracy |z_phot-z_spec|/(1+z_spec)<~10%. A similar analysis performed on different sets of simulated spectra shows that the AKARI infrared data alone can provide photometric redshifts accurate to |z_phot-z_spec|/(1+z_spec)<~10% (1-sigma) at z<~2. At higher redshifts the PAH features are shifted outside the wavelength range covered by AKARI and the photo-z estimates rely on the less prominent 1.6 micron stellar bump; the accuracy achievable in this case on (1+z) is ~10-15%, provided that the AGN contribution to the infrared emission is subdominant. Our technique is no more prone to redshift aliasing than optical-uv photo-z, and it may be possible to reduce this aliasing further with the addition of submillimetre and/or radio data.Comment: 27 pages, 12 figures, 4 tables. Accepted for publication on MNRA

The evolution of the dust and gas content in galaxies

We use deep Herschel observations taken with both PACS and SPIRE imaging cameras to estimate the dust mass of a sample of galaxies extracted from the GOODS-S, GOODS-N and the COSMOS fields. We divide the redshift–stellar mass (M star )–star formation rate (SFR) parameter space into small bins and investigate average properties over this grid. In the first part of the work we investigate the scaling relations between dust mass, stellar mass and SFR out to z = 2.5. No clear evolution of the dust mass with redshift is observed at a given SFR and stellar mass. We find a tight correlation between the SFR and the dust mass, which, under reasonable assumptions, is likely a consequence of the Schmidt-Kennicutt (S-K) relation. The previously observed correlation between the stellar content and the dust content flattens or sometimes disappears when considering galaxies with the same SFR. Our finding suggests that most of the correlation between dust mass and stellar mass obtained by previous studies is likely a consequence of the correlation between the dust mass and the SFR combined with the main sequence, i.e., the tight relation observed between the stellar mass and the SFR and followed by the majority of star-forming galaxies. We then investigate the gas content as inferred from dust mass measurements. We convert the dust mass into gas mass by assuming that the dust-to-gas ratio scales linearly with the gas metallicity (as supported by many observations). For normal star-forming galaxies (on the main sequence) the inferred relation between the SFR and the gas mass (integrated S-K relation) broadly agrees with the results of previous studies based on CO measurements, despite the completely different approaches. We observe that all galaxies in the sample follow, within uncertainties, the same S-K relation. However, when investigated in redshift intervals, the S-K relation shows a moderate, but significant redshift evolution. The bulk of the galaxy population at z ∼ 2 converts gas into stars with an efficiency (star formation efficiency, SFE = SFR/M gas , equal to the inverse of the depletion time) about 5 times higher than at z ∼ 0. However, it is not clear what fraction of such variation of the SFE is due to an intrinsic redshift evolution and what fraction is simply a consequence of high-z galaxies having, on average, higher SFR, combined with thesuper-linear slope of the S-K relation (whileother studies finda linear slope). We confirm that the gas fraction (f gas = M gas /(M gas + M star )) decreases with stellar mass and increases with the SFR. We observe no evolution with redshift once M star and SFR are fixed. We explain these trends by introducing a universal relation between gas fraction, stellar mass and SFR that does not evolve with redshift, at least out to z ∼ 2.5. Galaxies move across this relation as their gas content evolves across the cosmic epochs. We use the 3D fundamental f gas –M star –SFR relation, along with the evolution of the main sequence with redshift, to estimate the evolution of the gas fraction in the average population of galaxies as a function of redshift and as a function of stellar mass: we find that M star > ∼ 10 11 M ? galaxies show the strongest evolution at z > ∼ 1.3 and a flatter trend at lower redshift, while f gas decreases more regularly over the entire redshift range probed in M star < ∼ 10 11 Mo galaxies, in agreement with a downsizing scenario

ABC 2 -SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hospitalitzacions; MortalitatCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hospitalizaciones; MortalidadCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hospitalizations; MortalityObjectives The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. Methods Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March–July, 2020. The model was validated in the 1054 patients admitted during August–September, as well as in an external cohort of 474 Spanish patients. Results Median (25–75th percentile) age of the model-derivation cohort was 60 (48–72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO 2 /FiO 2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829–0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833–0.885]) and Spanish (0.894 [95% CI 0.870–0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.This study was supported in part by Minas Gerais State Agency for Research and Development ( Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG ) [grant number APQ-00208-20], National Institute of Science and Technology for Health Technology Assessment ( Instituto de Avaliação de Tecnologias em Saúde – IATS )/ National Council for Scientific and Technological Development ( Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq ) [grant number 465518/2014-1], and CAPES Foundation ( Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ) [grant number 88887.507149/2020-00]. AS was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from Instituto de Salud Carlos III through the Ministry of Economy and Competitiveness, Spain