New Multicomponent Forms of the Antiretroviral Nevirapine with Improved Dissolution Performance

In the pharmaceutical area, some drugs exhibit physicochemical properties that adversely affect the formulation processes for bioavailability and effectiveness. Nevirapine (NVP) is an antiretroviral drug that presents low aqueous solubility, which directly impacts its bioavailability. Among all possible modifications, multicomponent crystals, such as cocrystals and eutectic compositions, have been successfully used to improve the solubility of drugs. In this work, the propensity of the formation of multicomponent systems of NVP with seven possible coformers were predicted and tested: salicylic acid (SA), 3-hydroxybenzoic acid (3HBZC), 4-hydroxybenzoic acid (4HBZC), saccharin (SAC), theophylline (THEO), caffeine (CAF), and urea (URE). Results indicate that NVP-SA, NVP-SAC, NVP-3HBZC, and NVP-4HBZC are cocrystals, whereas NVP-THEO and NVP-CAF are eutectic materials, and NVP-URE is a solid physical mixture. A temperature-dependent disorder behavior was identified for NVP-SA cocrystal. Dissolution studies for the eutectic materials are reported, evidencing that these materials exhibit a significant increase in NVP dissolution kinetics.Fil: Costa, Rogeria Nunes. Universidade Federal de Sao Paulo; BrasilFil: Reviglio, Ana Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Siedler, Sana. Universidade Federal de Santa Catarina; BrasilFil: Cardoso, Simone G.. Universidade Federal de Santa Catarina; BrasilFil: Garro Linck, Yamila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Monti, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Carvalho, Alexandre Magnus G.. Centro Nacional de Pesquisa em Energia e Materiais; BrasilFil: Resende, Jackson A. L. C.. Universidade Federal do Mato Grosso do Sul; BrasilFil: Chaves, Marcelo H. C.. Fundación Oswaldo Cruz; BrasilFil: Rocha, Helvético Vinícius Antunes. Fundación Oswaldo Cruz; BrasilFil: Choquesillo Lazarte, Duane. Consejo Superior de Investigaciones Científicas; España. Universidad de Granada; EspañaFil: Infantes, Lourdes. Consejo Superior de Investigaciones Científicas; España. Instituto de Química Física Rocasolano; EspañaFil: Cuffini, Silvia Lucia. Universidade de Sao Paulo; Brasi

Room temperature chiral magnetic skyrmion in ultrathin magnetic nanostructures

Magnetic skyrmions are chiral spin structures with a whirling configuration. Their topological properties, nanometer size and the fact that they can be moved by small current densities have opened a new paradigm for the manipulation of magnetisation at the nanoscale. To date, chiral skyrmion structures have been experimentally demonstrated only in bulk materials and in epitaxial ultrathin films and under external magnetic field or at low temperature. Here, we report on the observation of stable skyrmions in sputtered ultrathin Pt/Co/MgO nanostructures, at room temperature and zero applied magnetic field. We use high lateral resolution X-ray magnetic circular dichroism microscopy to image their chiral N\'eel internal structure which we explain as due to the large strength of the Dzyaloshinskii-Moriya interaction as revealed by spin wave spectroscopy measurements. Our results are substantiated by micromagnetic simulations and numerical models, which allow the identification of the physical mechanisms governing the size and stability of the skyrmions.Comment: Submitted version. Extended version to appear in Nature Nanotechnolog

Skin color and severe maternal outcomes: evidence from the brazilian network for surveillance of severe maternal morbidity

Taking into account the probable role that race/skin color may have for determining outcomes in maternal health, the objective of this study was to assess whether maternal race/skin color is a predictor of severe maternal morbidity. This is a secondary analysis of the Brazilian Network for Surveillance of Severe Maternal Morbidity, a national multicenter cross-sectional study of 27 Brazilian referral maternity hospitals. A prospective surveillance was performed to identify cases of maternal death (MD), maternal near miss (MNM) events, and potentially life-threatening conditions (PLTC), according to standard WHO definition and criteria. Among 9,555 women with severe maternal morbidity, data on race/skin color was available for 7,139 women, who were further divided into two groups: 4,108 nonwhite women (2,253 black and 1,855 from other races/skin color) and 3,031 white women. Indicators of severe maternal morbidity according to WHO definition are shown by skin color group. Adjusted Prevalence Ratios (PRadj - 95%CI) for Severe Maternal Outcome (SMO=MNM+MD) were estimated according to sociodemographic/obstetric characteristics, pregnancy outcomes, and perinatal results considering race. Results. Among 7,139 women with severe maternal morbidity evaluated, 90.5% were classified as PLTC, 8.5% as MNM, and 1.6% as MD. There was a significantly higher prevalence of MNM and MD among white women. MNMR (maternal near miss ratio) was 9.37 per thousand live births (LB). SMOR (severe maternal outcome ratio) was 11.08 per 1000 LB, and MMR (maternal mortality ratio) was 170.4 per 100,000 LB. Maternal mortality to maternal near miss ratio was 1 to 5.2, irrespective of maternal skin color. Hypertension, the main cause of maternal complications, affected mostly nonwhite women. Hemorrhage, the second more common cause of maternal complication, predominated among white women. Nonwhite skin color was associated with a reduced risk of SMO in multivariate analysis. Nonwhite skin color was associated with a lower risk for severe maternal outcomes. This result could be due to confounding factors linked to a high rate of Brazilian miscegenation.2019CNPQ - Conselho Nacional de Desenvolvimento Científico e Tecnológico402702/2008-

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity