Synthesis, In Silico Studies, Antiprotozoal and Cytotoxic Activities of Quinoline‐Biphenyl Hybrids

This is the pre-peer reviewed version of the following article: Synthesis, In Silico Studies, Antiprotozoal and Cytotoxic Activities of Quinoline‐Biphenyl Hybrids, which has been published in final form at https://doi.org/10.1002/slct.201903835. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe synthesis, in silico studies, antiprotozoal and cytotoxic activities of eleven quinoline‐biphenyl hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against Plasmodium falciparum, and amastigotes forms both Leishmania (V) panamensis and Trypanosoma cruzi. Cytotoxicity was evaluated against human U‐937 macrophages. 8‐phenylquinoline (4 a) showed similar activity than meglumine antimoniate and 4‐(quinolin‐8‐yl)phenol (4 b) exhibited an activity similar to that of benznidazole. 8‐(3,4‐dimethoxyphenyl) quinoline (4 k) showed the best activity against P. falciparum. Although these compounds were toxic for mammalian U‐937 cells, however they may still have potential to be considered as candidates for drug development because of their antiparasite activity. Molecular docking was used to determine the in silico inhibition of some of the designed compounds against PfLDH and cruzipain, two important pharmacological targets involved in antiparasitic diseases. All hybrids were docked to the three‐dimensional structures of PfLDH and T. cruzi cruzipain as enzymes using AutoDock Vina. Notably, the docking results showed that the most active compounds 4‐(quinolin‐8‐yl)phenol (4 b, CE50: 11.33 μg/mL for T. cruzi) and 8‐(3,4‐dimethoxyphenyl) quinoline (4 k, CE50: 8.84 μg/mL for P. falciparum) exhibited the highest scoring pose (−7.5 and −7.7 kcal/mol, respectively). This result shows a good correlation between the predicted scores with the experimental data profile, suggesting that these ligands could act as competitive inhibitors of PfLDH or T. cruzi cruzipain enzymes, respectively. Finally, in silico ADME studies of the quinoline hybrids showed that these novel compounds have suitable drug‐like properties, making them potentially promising agents for antiprotozoal therapy

Effectiveness of different methods for delivering tailored nutrition education to low income, ethnically diverse adults

<p>Abstract</p> <p>Background</p> <p>Computer-tailored written nutrition interventions have been shown to be more effective than non-tailored materials in changing diet, but continued research is needed. Your Healthy Life/Su Vida Saludable (YHL-SVS) was an intervention study with low income, ethnically diverse, English and Spanish-speaking participants to determine which methods of delivering tailored written nutrition materials were most effective in lowering fat and increasing fruit and vegetable (F&V) intake.</p> <p>Methods</p> <p>YHL-SVS was a randomized controlled trial with four experimental conditions: 1) Nontailored (NT) comparison group; 2) Single Tailored (ST) packet; 3) Multiple Tailored (MT) packet mailed in four installments; 4) Multiple Re-Tailored (MRT) MT packets re-tailored between mailings via brief phone surveys. A baseline telephone survey collected information for tailoring as well as evaluation. Follow-up evaluation surveys were collected 4- and 7-months later. Primary outcomes included F&V intake and fat related behaviors. Descriptive statistics, paired t-test and ANOVA were used to examine the effectiveness of different methods of delivering tailored nutrition information.</p> <p>Results</p> <p>Both the ST and MT groups reported significantly higher F&V intake at 4-months than the NT and MRT groups. At 7 months, only the MT group still had significantly higher F&V intake compared to the NT group. For changes in fat-related behaviors, both the MT and MRT groups showed more change than NT at 4 months, but at 7 months, while these differences persisted, they were no longer statistically significant. There was a significant interaction of experimental group by education for change in F&V intake (P = .0085) with the lowest educational group demonstrating the most change.</p> <p>Conclusion</p> <p>In this study, tailored interventions were more effective than non-tailored interventions in improving the short-term dietary behaviors of low income, ethnically diverse participants. Delivery of information in multiple smaller doses over time appeared to improve effectiveness. Future studies should determine which variables are mediators of dietary change and whether these differ by participant demographics. Moreover, future research should differentiate the effects of tailoring vs. cultural adaptation in ethnically diverse populations and study the dissemination of tailored interventions into community-based settings.</p> <p>Trial registration</p> <p>Current Controlled Trials # NCT00301691.</p

La cuenta fisica del agua mediante modelación hidrológica distribuida.

Se presentan una comparación entre los modelos hidrológicos de agregación, tradicionalmente utilizados en el estudio de la cuenta física del agua en la cuenca y los modelos hidrológicos distribuidos. Se proponen estos últimos como instrumento de gestión apropiado para la planificación del recurso hídrico.A comparison between aggregation modls used in traditional physical count of water and distributed hydrological modeis is presented. The use of distributed hydrological modeis as a better water management tool is purposed

Dengue en el embarazo: efectos en el feto y el recién nacido.

The risk of dengue virus infection during pregnancy has increased due to the current rash of frequent and severe dengue epidemics. The effects of dengue virus in the fetus and newborn children have been studied only superficially and with contradictory results. Therefore, a retrospective cohort study was conducted in Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus infection acquired during pregnancy. Twenty-two babies born from mothers who suffered dengue during the epidemics of 1998 were compared with babies from non-infected mothers. In the exposed cohort, three premature births occurred, three children suffered from fetal anomalies and four children were born with low weight. In the non-exposed children, none of these problems were found. Psychomotor development was normal in both groups. Only the low weight subgroup was statistically significant (Fisher test, p = 0.045). These results suggested that the children from women with dengue during pregnancy present low weight, greater frequency of premature birth and increased fetal distress. A larger sample is necessary to confirm these results.El riesgo de infección por el virus del dengue durante el embarazo se está incrementando ante mayores y más severas epidemias, y las consecuencias sobre el feto y el recién nacido han sido poco estudiadas y, en otros casos, los resultados han sido contradictorios. Por esta razón, se realizó en Medellín un estudio de cohorte retrospectiva, cuyo objetivo fue determinar los efectos que produce el dengue durante el embarazo sobre el feto y el recién nacido. En dicho estudio se evaluaron 22 recién nacidos hijos de mujeres que presentaron dengue durante la epidemia de 1998 y se compararon con 24 recién nacidos, hijos de mujeres embarazadas sin dengue. En la cohorte con dengue se encontraron 3 niños prematuros, 3 niños con sufrimiento fetal y 4 niños con bajo peso al nacer. En la cohorte no expuesta no se encontraron niños con estos problemas. El desarrollo psicomotor fue normal en ambos grupos. De las observaciones anteriores, sólo fue estadísticamente significativa la frecuencia de niños con bajo peso al nacer (prueba exacta de Fisher, p=0,045). Estos resultados preliminares muestran que los recién nacidos de madres que sufrieron dengue durante la gestación tuvieron riesgo de bajo peso al nacer y presentaron con mayor frecuencia prematurez y sufrimiento fetal, aunque se requiere aumentar el tamaño de la muestra para confirmar estos resultados. Sin embargo, es necesario estrechar la vigilancia a las madres embarazadas con dengue dados los efectos nocivos sobre la evolución del recién nacido

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

Background Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. Methods This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). Results Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). Interpretation Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. Funding National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme)

Sobre la comprensión

Given the fact that the word "Understanding" has become to be part of the philosophical vocabulary of our times, this article pretends to develop a theoretical reflection about how such concept has achieve conceptual status in four German authors, namely, Dilthey, Husserl, Heidegger y Gadamer. The differences between them on his conceptions will be also presented and two point of concurrence will be tried to sustain, namely, the fact that his respective meditations goes against the tradition of thought behind them, and the fact that each one of this, in his ways, cannot avoid to imply the phenomena of language at the time while consider the human phenomena of understanding

Comprensión y lenguaje

El presente artículo pretende exponer,respecto de las posturas hermenéuticas de Gadamer y Ricoeur, el modo como ambos pensadores parecen responder al problema que interroga por el papel que desempeña el lenguaje en la actividad human