Data-Driven Modeling of the Cellular Pharmacokinetics of Degradable Chitosan-Based Nanoparticles

Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale processes. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between controlling processes. We demonstrate data simulation techniques to reproduce the time-dependent dose of trimethyl chitosan nanoparticles in an ND7/23 neuronal cell line, used as an in vitro model of native peripheral sensory neurons. Derived analytical expressions of the mean dose per cell accurately capture the pharmacokinetics by including a declining delivery rate and an intracellular particle degradation process. Comparison with experiment indicates a supply time constant, τ = 2 h. and a degradation rate constant, b = 0.71 h−1. Modeling the dose heterogeneity uses simulated data distributions, with time dependence incorporated by transforming data-bin values. The simulations mimic the dynamic nature of cell-to-cell dose variation and explain the observed trend of increasing numbers of high-dose cells at early time points, followed by a shift in distribution peak to lower dose between 4 to 8 h and a static dose profile beyond 8 h

The evolution of the density of galaxy clusters and groups: denser environments at higher redshifts

We show that, observationally, the projected local density distribution in high-z clusters is shifted towards higher values compared to clusters at lower redshift. To search for the origin of this evolution, we analyze a sample of haloes selected from the Millennium Simulation and populated using semi-analytic models, investigating the relation between observed projected density and physical 3D density, using densities computed from the 10 and 3 closest neighbours. Both observationally and in the simulations, we study the relation between number of cluster members and cluster mass, and number of members per unit of cluster mass. We find that the observed evolution of projected densities reflects a shift to higher values of the physical 3D density distribution. In turn, this must be related with the globally higher number of galaxies per unit of cluster volume N/V in the past. We show that the evolution of N/V is due to a combination of two effects: a) distant clusters were denser in dark matter (DM) simply because the DM density within R_{200} (~the cluster virial radius) is defined to be a fixed multiple of the critical density of the Universe, and b) the number of galaxies per unit of cluster DM mass is remarkably constant both with redshift and cluster mass if counting galaxies brighter than a passively evolving magnitude limit. Our results highlight that distant clusters were much denser environments than today's clusters, both in galaxy number and mass, and that the density conditions felt by galaxies in virialized systems do not depend on the system mass.Comment: accepted for publication in MNRA

The Role of Gender Inequality and Health Expenditure on the Coverage of Demand for Family Planning Satisfied by Modern Contraceptives: A Multilevel Analysis of Cross-Sectional Studies in 14 LAC Countries

BACKGROUND: Despite international efforts to improve reproductive health indicators, little attention is paid to the contributions of contextual factors to modern contraceptive coverage, especially in the Latin America and the Caribbean (LAC) region. This study aimed to identify the association between country-level Gender Inequality and Health Expenditure with demand for family planning satisfied by modern contraceptive methods (DFPSm) in Latin American sexually active women. METHODS: Our analyses included data from the most recent (post-2010) Demographic and Health Survey or Multiple Indicator Cluster Survey from 14 LAC countries. Descriptive analyses and multilevel logistic regressions were performed. Six individual-level factors were included. The effect of the country-level factors Gender Inequality Index (GII) and Current Health Expenditure on DFPSm was investigated. FINDINGS: DFPSm ranged from 41.8% (95% CI: 40.2-43.5) in Haiti to 85.6% (95% CI: 84.9-86.3) in Colombia, with an overall median coverage of 77.8%. A direct association between the odds of DFPSm and woman\u27s education, wealth index, and the number of children was identified. Women from countries in the highest GII tertile were less likely (OR: 0.32, 95% CI: 0.13-0.76) to have DFPSm than those living in countries in the lowest tertile. INTERPRETATION: Understanding the contribution of country-level factors to modern contraception may allow macro-level actions focused on the population\u27s reproductive needs. In this sense, country-level gender inequalities play an important role, as well as individual factors such as wealth and education. FUNDING: Bill and Melinda Gates Foundation and Associação Brasileira de Saúde Coletiva (ABRASCO)

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D—a randomised multicentre international clinical trial

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 )

Physical Activity Patterns of the Spanish Population Are Mostly Determined by Sex and Age: Findings in the ANIBES Study

Background Representative data for the Spanish population regarding physical activity (PA) behaviors are scarce and seldom comparable due to methodological inconsistencies. Aim Our objectives were to describe the PA behavior by means of the standardized self-reported International Physical Activity Questionnaire (IPAQ) and to know the proportion of the Spanish population meeting and not meeting international PA recommendations. Material and Methods PA was assessed using the IPAQ in a representative sample of 2285 individuals (males, 50.4%) aged 9–75 years and living in municipalities of at least 2,000 inhabitants. Data were analyzed according to: age groups 9–12, 13–17, 18–64, and 65–75 years; sex; geographical distribution; locality size and educational levels. Results Mean total PA was 868.8±660.9 min/wk, mean vigorous PA 146.4±254.1 min/wk, and mean moderate PA 398.1±408.0 min/wk, showing significant differences between sexes (p<0.05). Children performed higher moderate-vigorous PA than adolescents and seniors (p<0.05), and adults than adolescents and seniors (p<0.05). Compared to recommendations, 36.2%of adults performed <150 min/week of moderate PA, 65.4% <75 min/week of vigorous PA and 27.0%did not perform any PA at all, presenting significant differences between sexes (p<0.05). A total of 55.4%of children and adolescents performed less than 420 min/week of MVPA, being higher in the later (62.6%) than in the former (48.4%). Highest non-compliance was observed in adolescent females (86.5%). Conclusion Sex and age are the main influencing factors on PA in the Spanish population. Males engage in more vigorous and light PA overall, whereas females perform more moderate PA. PA behavior differs between age groups and no clear lineal increase with age could be observed. Twenty-seven percent of adults and 55.4% of children and adolescents do not meet international PA recommendations. Identified target groups should be addressed to increase PA in the Spanish populationCoca-Cola Iberia through Spanish Nutrition Foundation (FEN)Coca-Cola Iberi