Modeling of coastal water contamination in Fortaleza (Northeastern Brazil)

An important tool in environmental management projects and studies due to the complexity of environmental systems, environmental modeling makes it possible to integrate many variables and processes, thereby providing a dynamic view of systems. In this study the bacteriological quality of the coastal waters of Fortaleza (Brazil) was modeled considering multiple contamination sources. Using the software SisBaHiA, the dispersion of thermotolerant coliforms and Escherichia coli from three sources of contamination (rivers, storm drains and submarine outfall) was analyzed. The models took into account variations in bacterial decay due to solar radiation and other environmental factors. Fecal pollution discharged from rivers and storm drains is transported westward by coastal currents, contaminating strips of beach water to the left of each storm drain or river. Exception to this condition only occurs on beaches protected by the breakwater of the harbor, where counterclockwise vortexes reverse this behavior. The results of the models were consistent with field measurements taken during the dry and the rainy season. Our results show that the submarine outfall plume was over 2 km from the nearest beach. The storm drains and the Maceió stream are the main factors responsible for the poor water quality on the waterfront of Fortaleza

Exploring the anti-proliferative activity of Pelargonium sidoides DC with in silico target identification and network pharmacology

Pelargonium sidoides DC (Geraniaceae) is a medicinal plant indigenous to Southern Africa that has been widely evaluated for its use in the treatment of upper respiratory tract infections. In recent studies, the anti-proliferative potential of P. sidoides was shown, and several phenolic compounds were identified as the bioactive compounds. Little, however, is known regarding their anti-proliferative protein targets. In this study, the anti-proliferative mechanisms of P. sidoides through in silico target identification and network pharmacology methodologies were evaluated. The protein targets of the 12 phenolic compounds were identified using the target identification server PharmMapper and the server for predicting Drug Repositioning and Adverse Reactions via the Chemical–Protein Interactome (DRAR-CPI). Protein–protein and protein–pathway interaction networks were subsequently constructed with Cytoscape 3.4.0 to evaluate potential mechanisms of action. A total of 142 potential human target proteins were identified with the in silico target identification servers, and 90 of these were found to be related to cancer. The protein interaction network was constructed from 86 proteins involved in 209 interactions with each other, and two protein clusters were observed. A pathway enrichment analysis identified over 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with the protein targets and included several pathways specifically related to cancer as well as various signaling pathways that have been found to be dysregulated in cancer. These results indicate that the anti-proliferative activity of P. sidoides may be multifactorial and arises from the collective regulation of several interconnected cell signaling pathways.https://link.springer.com/journal/110302018-11-18hj2017AnatomyBiochemistr

Determination of optimal ultrasound planes for the initialisation of image registration during endoscopic ultrasound-guided procedures

Purpose Navigation of endoscopic ultrasound (EUS)-guided procedures of the upper gastrointestinal (GI) system can be technically challenging due to the small fields-of-view of ultrasound and optical devices, as well as the anatomical variability and limited number of orienting landmarks during navigation. Co-registration of an EUS device and a pre-procedure 3D image can enhance the ability to navigate. However, the fidelity of this contextual information depends on the accuracy of registration. The purpose of this study was to develop and test the feasibility of a simulation-based planning method for pre-selecting patient-specific EUS-visible anatomical landmark locations to maximise the accuracy and robustness of a feature-based multimodality registration method. Methods A registration approach was adopted in which landmarks are registered to anatomical structures segmented from the pre-procedure volume. The predicted target registration errors (TREs) of EUS-CT registration were estimated using simulated visible anatomical landmarks and a Monte Carlo simulation of landmark localisation error. The optimal planes were selected based on the 90th percentile of TREs, which provide a robust and more accurate EUS-CT registration initialisation. The method was evaluated by comparing the accuracy and robustness of registrations initialised using optimised planes versus non-optimised planes using manually segmented CT images and simulated (n=9) or retrospective clinical (n=1) EUS landmarks. Results The results show a lower 90th percentile TRE when registration is initialised using the optimised planes compared with a non-optimised initialisation approach (p value <0.01). Conclusions The proposed simulation-based method to find optimised EUS planes and landmarks for EUS-guided procedures may have the potential to improve registration accuracy. Further work will investigate applying the technique in a clinical setting

Potent Trivalent Inhibitors of Thrombin through Hybridization of Salivary Sulfopeptides from Hematophagous Arthropods

Blood feeding arthropods, such as leeches, ticks, flies and mosquitoes, provide a privileged source of peptidic anticoagulant molecules. These primarily operate through inhibition of the central coagulation protease thrombin by binding to the active site and either exosite I or exosite II. Herein, we describe the rational design of a novel class of trivalent thrombin inhibitors that simultaneously block both exosites as well as the active site. These engineered hybrids were synthesized using tandem diselenide-selenoester ligation (DSL) and native chemical ligation (NCL) reactions in one-pot. The most potent trivalent inhibitors possessed femtomolar inhibition constants against alpha-thrombin and were selective over related coagulation proteases. A lead hybrid inhibitor possessed potent anticoagulant activity, blockade of both thrombin generation and platelet aggregation in vitro and efficacy in a murine thrombosis model at 1 mg kg(-1). The rational engineering approach described here lays the foundation for the development of potent and selective inhibitors for a range of other enzymatic targets that possess multiple sites for the disruption of protein-protein interactions, in addition to an active site

Trial-based cost-effectiveness analysis comparing surgical and endoscopic drainage in patients with obstructive chronic pancreatitis

Objective: Published evidence indicates that surgical drainage of the pancreatic duct was more effective than endoscopic drainage for patients with chronic pancreatitis. This analysis assessed the cost-effectiveness of surgical versus endoscopic drainage in obstructive chronic pancreatitis. Design: This trial-based cost-utility analysis (ISRCTN04572410) was conducted from a UK National Health Service (NHS) perspective and during a 79-month time horizon. During the trial the details of the diagnostic and therapeutic procedures, and pancreatic insufficiency were collected. The resource use was varied in the sensitivity analysis based on a review of the literature. The health outcome was the Quality-Adjusted Life Year (QALY), generated using EQ-5D data collected during the trial. There were no pancreas-related deaths in the trial. All-cause mortality from the trial was incorporated into the QALY estimates in the sensitivity analysis. Setting: Hospital. Participants: Patients with obstructive chronic pancreatitis. Primary and secondary outcome measures: Costs, QALYs and cost-effectiveness. Results: The result of the base-case analysis was that surgical drainage dominated endoscopic drainage, being both more effective and less costly. The sensitivity analysis varied mortality and resource use and showed that the surgical option remained dominant in all scenarios. The probability of cost-effectiveness for surgical drainage was 100% for the base case and 82% in the assessed most conservative case scenario. Conclusions: In obstructive chronic pancreatitis, surgical drainage is highly cost-effective compared with endoscopic drainage from a UK NHS perspective

Activity-guided isolation and identification of the major antioxidant and anticancer compounds from a commercial Pelargonium sidoides tincture

Extracts prepared from the roots of Pelargonium sidoides (DC) are commercially available for the treatment of respiratory related conditions. Recently, a commercial radix mother tincture of this plant was shown to have both antioxidant and anticancer effects especially related to the G0/G1 block in the Jurkat E6.1 cell line (unpublished results). Fractions were prepared by semi-preparative HPLC, and their antioxidant and anticancer activities were determined. The more hydrophilic fractions isolated namely F6-F12 were all found to have strong reducing capacities and were able to scavenge peroxyl radicals. In the human lung cell line, NCI-H460, significant cellular antioxidant effects were observed. Anticancer activity was evaluated in the NCI-pre-screen panel (NCI-H460, MCF-7 and SF-268) and the Jurkat E6.1 cell line. Fractions F7, F9 and F12 were found to inhibit the cell growth of these four cell-lines (p < 0.05), especially the Jurkat E6.1 cell line with the sulforhodamine B assay. Mass spectrometry analysis revealed that these active fractions contained several polyphenolic compounds such as gallic acid, trihydroxycoumarin, dihydroxycoumarin sulfates, proanthocyanidins and phenolic glycosides. A phenolic acid glycoside sulfate not previously shown in Pelargonium sidoides extracts was also isolated. In conclusion, the antioxidant and/or anticancer activity of the Pelargonium sidoides tincture may be attributed to the presence of these polyphenolics.National Research Foundation of South Africahttp://link.springer.com/journal/442016-11-30hb201

Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G(0)/G(1) arrest and apoptosis in Jurkat leukaemia cells

CONTEXT : Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown root extracts rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. OBJECTIVE : This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). MATERIALS AND METHODS : The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukemia cell line at concentrations of 0-150 μg/mL. Effect on cell growth was determined with sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. Effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. RESULTS : Dihydroxycoumarin sulfates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 of 9.7 μg/mL). The PST arrested Jurkat cells at G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. CONCLUSION : We present evidence that Pelargonium sidoides has cancer cell type specific antiproliferative effects and may be a source of novel anticancer molecules.National Research Foundation of South Africa.http://www.tandfonline.com/loi/iphb202017-09-30hb2016AnatomyBiochemistr

Rotating metrics admitting non-perfect fluids in General Relativity

In this paper, by applying Newman-Janis algorithm in spherical symmetric metrics, a class of embedded rotating solutions of field equations is presented. These solutions admit non-perfect fluidsComment: LaTex, 39 page

Antioxidant and anti-inflammatory properties of Ilex guayusa tea preparations : a comparison to Camellia sinensis teas

Ilex guayusa tea preparations are now commercially available as Runa tea. Little is known regarding the antioxidant and anti-inflammatory bioactivities of this tea. The I. guayusa teas had a total polyphenolic content between 54.39 and 67.23 mg GAE/g dry mass and peroxyl radical scavenging capacities between 1773.41 and 2019 µmol TE/g dry mass, nearly half of that for the Camellia sinensis teas. The I. guayusa teas afforded 60-80% protection from oxidative stress in the Caco-2 cellular antioxidant assay, comparable to the C. sinensis teas. The anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells of I. guayusa teas was similarly comparable to the C. sinensis teas with nitric oxide production reduced by 10-30%. Major compounds identified by mass spectrometry were the phenolic mono- and dicaffeoylquinic acid derivatives. I. guayusa teas are a good source of dietary phenolic compounds with cellular antioxidant and anti-inflammatory properties.http://pubs.rsc.org/en/journals/journalissues/fo#!recentarticles&adv2018-12-13hj2017AnatomyBiochemistr

Evaluation of the anti-diabetic activity of some common herbs and spices : providing new insights with inverse virtual screening

Culinary herbs and spices are widely used as a traditional medicine in the treatment of diabetes and its complications, and there are several scientific studies in the literature supporting the use of these medicinal plants. However, there is often a lack of knowledge on the bioactive compounds of these herbs and spices and their mechanisms of action. The aim of this study was to use inverse virtual screening to provide insights into the bioactive compounds of common herbs and spices, and their potential molecular mechanisms of action in the treatment of diabetes. In this study, a library of over 2300 compounds derived from 30 common herbs and spices were screened in silico with the DIA-DB web server against 18 known diabetes drug targets. Over 900 compounds from the herbs and spices library were observed to have potential anti-diabetic activity and liquorice, hops, fennel, rosemary, and fenugreek were observed to be particularly enriched with potential anti-diabetic compounds. A large percentage of the compounds were observed to be potential polypharmacological agents regulating three or more anti-diabetic drug targets and included compounds such as achillin B from yarrow, asparasaponin I from fenugreek, bisdemethoxycurcumin from turmeric, carlinoside from lemongrass, cinnamtannin B1 from cinnamon, crocin from sa ron and glabridin from liquorice. The major targets identified for the herbs and spices compounds were dipeptidyl peptidase-4 (DPP4), intestinal maltase-glucoamylase (MGAM), liver receptor homolog-1 (NR5A2), pancreatic alpha-amylase (AM2A), peroxisome proliferator-activated receptor alpha (PPARA), protein tyrosine phosphatase non-receptor type 9 (PTPN9), and retinol binding protein-4 (RBP4) with over 250 compounds observed to be potential inhibitors of these particular protein targets. Only bay leaves, liquorice and thyme were found to contain compounds that could potentially regulate all 18 protein targets followed by black pepper, cumin, dill, hops and marjoram with 17 protein targets. In most cases more than one compound within a given plant could potentially regulate a particular protein target. It was observed that through this multi-compound-multi target regulation of these specific protein targets that the major anti-diabetic e ects of reduced hyperglycemia and hyperlipidemia of the herbs and spices could be explained. The results of this study, taken together with the known scientific literature, indicated that the anti-diabetic potential of common culinary herbs and spices was the result of the collective action of more than one bioactive compound regulating and restoring several dysregulated and interconnected diabetic biological processes.The National Research Foundation of South Africa, the Spanish Ministry of Economy and Competitiveness (CTQ2017-87974-R) and by the Fundación Séneca del Centro de Coordinación de la Investigación de la Región de Murcia under Project 20988/PI/18.http://www.mdpi.com/journal/moleculesam2020BiochemistryGeneticsMicrobiology and Plant Patholog