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According to World Health Organization, the number of people with blindness due to infectious diseases has reduced in the last 20 years whereas 80% of all visual impairment can be prevented or cured. Despite of that, 285 million people are estimated to be visually impaired worldwide as about 90% are from low-income society. Considering this scenario, it is still necessary to think about this public and know how to teach them disciplines such as Mathematics that are important to their lives as citizens. The Mathematics concepts are always in need for living in our society as we have to pay bills and considering that Mathematics knowledge is demanded all time from health to payment. In this article, we briefly discuss the blindness and the Mathematics universe, pointing this educational area as one that should be more educational developed. The article also intends to stimulate and contribute for the production of new strategies and didactical materials for teaching Mathematics to this public with special needs. [ABSTRACT FROM AUTHOR]

Dengue is the leading cause of viral death worldwide. The vector Aedes aegypti mosquito is also responsible for Zika and Chincungunha transmission, another very compromising viral diseases. As the understanding of the vector life cycle and its habitat is important for preventing and fighting against these diseases, we propose to use a mathematic concept, graphos, and a problem-based situation (the removal of potential breeding sites for mosquitoes in the player city) to design a computational game that may help on spreading information and to stimulate a players proactive virtual and real behavior. Thus this paper describes the design and construction of an educational computer game called "Graphos against mosquitos," based on graphos, a mathematics theoretical concept. We designed the Graphos game using as the main elements: a child, twelve neighborhood blocks, mosquitoes, streets and containers where mosquitoes lay eggs (tires, cans, bottles, plants with water deposits). In the game, the player (Avatar) is the main element that should "walk in" the streets (edges) of the city, removing the potential breeding grounds for mosquitoes in each block (vertices). As this game is based on the mathematics theoretical concept graphos using two dimensions, the city has two distinct vertices that are the beginning and end of it, which discriminate the beginning and end of the game. The player should remove all containers of each street, avoiding mosquitoes growth and passing only one time for each of them. As containers are removed, the player gains points and is prevented to return to the previous street. In this game the removal of all containers that pose risk of becoming mosquito breeding sites, without coming back to the previous street but only forward, is translatable into " graphos language". When finishing the game properly, it opens a final screen where the player is awarded with a medal. On this screen, the player can write his/her name, being invited to act as a "health worker" no longer in virtual form, but in the real life. Through teaching by using computational material ruled by mathematical concepts such as graphos, we hope to stimulate and contribute for fighting and controlling the vector of these serious viral diseases. [ABSTRACT FROM AUTHOR]

In Argentine grazing systems, additional supply of energy and protein is needed to balance the diet during periods of pasture shortage in winter. Three protein meal sources were evaluated, in terms of milk yield and composition, for grazing dairy cows receiving a supplementary PMR. Thirty three multiparous cows, averaging 75 ± 15 DIM, and over 7000 L/cow in previous lactations, were randomly assigned to 3 treatments: SM= soybean meal, L-SuM= sunflower meal-low-protein and CM= canola meal, in a continuous split-plot design with covariance analysis. The diets were isoenergetic (1.82 Mcal NEL) and isonitrogenous (17% CP), and were formulated (DM basis) with 17 % pasture and 83% of a PMR containing corn silage, alfalfa hay, corn grain, minerals and vitamins premix and the corresponding protein meal. The CP concentrations were 28, 35 and 41% for L-SuM, CM and SM, and represented 25, 20 and 15% total diet DM, respectively. Table 1 shows milk yield and composition for all treatments. The L-SM had the lowest response in terms of milk yield, but the highest in milk fat percentage, thus suggesting concentration effects. On the other hand, CM produced the lowest protein concentrations, probably because of differences in dietary amino acid supply to the mammary gland. Milk urea concentration was lowest for CM. [ABSTRACT FROM AUTHOR]

The effect of monensin on milk production was evaluated in 58 lactating Holstein cows (48 multiparous; 10 primiparous) grazing a mixed-alfalfa pasture and supplemented with a partial mixed ration in a completely randomized design with repeated measurements. Cows were paired by calving date, lactation number, previous lactation milk production, body weight, and body condition score and were assigned to one of 2 treatments: control or monensin. Cows on the monensin treatment received 2 monensin controlled-release capsules (335 mg/d for 90 d), one 30 d before the expecting calving date and the other 60 d after calving. Short-term (0 to 150 d in milk) and long-term (305-d adjusted lactation) effects ofmonensin were evaluated. Pasture (measured by difference between pre- and postgrazing pasture mass), supplements, and total dry matter intake did not differ between treatments and averaged 8.7, 14.1, and 22.9 kg/d, respectively. In the short-term, monensin increased milk production (27.7 vs. 26.6 kg/d) and milk protein yield (0.890 vs. 0.860 kg/d); milk fat yield was not affected (0.959 kg/d). Monensin decreased milk fat content (3.51 vs. 3.60%) with no changes in milk protein content (3.25%). In the long term, milk production and milk protein yield were also increased by monensin: 214 and 7 kg, respectively. Monensin reduced the loss of body condition score and increased percentage of pregnancy at first service (44.8 vs. 20.7%). Monensin improves production and reproduction performance of dairy cows grazing a mixed-alfalfa pasture and supplemented with a partial mixed ration. [ABSTRACT FROM AUTHOR]

Lectins are ubiquitous proteins involved in the immune defenses of different organisms and mainly responsible for non-self-recognition and agglutination reactions. This work describes molecular and biological characterization of a rhamnose-binding lectin (RBL) from Rhodnius prolixus, which possesses a 21 amino acid signal peptide and a mature protein of 34.6 kDa. The in-silico analysis of the primary and secondary structures of RpLec revealed a lectin domain fully conserved among previous insects studied. The three-dimensional homology model of RpLec was similar to other RBL-lectins. Docking predictions with the monosaccharides showed rhamnose and galactose-binding sites comparable to Latrophilin-1 and N-Acetylgalactosamine-binding in a different site. The effects of RpLec gene silencing on levels of infecting Trypanosoma cruzi Dm 28c and intestinal bacterial populations in the R. prolixus midgut were studied by injecting RpLec dsRNA into the R. prolixus hemocoel. Whereas T. cruzi numbers remained unchanged compared with the controls, numbers of bacteria increased significantly. The silencing also induced the up regulation of the R. prolixus defC (defensin) expression gene. These results with RpLec reveal the potential importance of this little studied molecule in the insect vector immune response and homeostasis of the gut bacterial microbiota., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1β release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: Platelets plays a central role in hemostatic processes and consequently are similarly involved in pathological processes, such as arterial thrombosis and atherosclerosis. Herein we described the synthesis, antiplatelet profile and structure-activity relationship (SAR) of a new series of N'-substitutedphenylmethylene-1H-pyrazolo[3,4-b]pyridine-carbohydrazide derivatives (3a-3k)., Methods: These compounds were synthesized in good yield and tested in platelet aggregation assays using collagen, ADP and arachidonic acid as agonists. We also performed a SAR studies using SPARTAN' 08 program, in silico ADMET screening and the Lipinski " rule of five " using Osiris Property Explorer and molinspiration on-line programs., Results: Interestingly, the new compounds were active against collagen and arachidonic acid (AA) with the two most actives compounds (3a and 3c - IC(50)=61 microM and 68 microM respectively) almost 5-fold more potent than aspirin (IC(50)=300 microM). These derivatives showed low theoretical toxicity risks in in silico ADMET screening and fulfilled the Lipinski rule of five, suggesting good oral biodisponibility., Conclusion: This work showed carbohydrazide group as potential for designing new antiplatelets. On that purpose, 3a and 3c may act as prototypes to generate more efficient and safe molecules for treating thrombotic diseases.

Chagas disease is an endemic parasitic infection caused by Trypanosomacruzi that affects 18-20 million people in Central and South America. Recently we described the Epoxy-alpha-Lap, an oxyran derivative of alpha-lapachone, which presents a low toxicity profile and a high inhibitory activity against T.cruzi epimastigotes forms, the non-infective form of this parasite. In this work we described the trypanocidal effects of Epoxy-alpha-Lap on extracellular (trypomastigote) and intracellular (amastigote) infective forms of two T. cruzi strains (Y and Colombian) known by their different infective profile. Our results showed that Epoxy-alpha-Lap is lethal to trypomastigote Y and Colombian strains (97% and 84%, respectively). Interestingly, Epoxy-alpha-Lap also showed a trypanocidal effect in human macrophage infected with T. cruzi Y (85.6%) and Colombian (71.9%) strains amastigote forms. Similar effects were observed on T. cruzi amastigote infected Vero cells (96.4% and 95.0%, respectively). Our results pointed Epoxy-alpha-Lap as a potential candidate for Chagas disease chemotherapy since it presents trypanocidal activity on all T. cruzi forms with low) toxicity profile.

Background: The study RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) demonstrated that Losartan was more effective lo reduce the progression of kidney disease in diabetic patients with proteinuria and a reduction in glomerular filtration rate., Aim: To perform a cost benefit analysis of Losartan use from provider and payer points of view., Material and Methods: Published data of the RENAAL study was analyzed. The costs of the use or not use of Losartan in patients with diabetic nephropathy were compared in terms of total costs of the disease including medications, hospital admissions for myocardial infarction, cerebrovascular accidents and congestive cardiac failure and the costs of chronic hemodialysis., Results: The reduction in antihypertensive medication use, hospital admissions, and the delay in dialysis requirement from a mean of 65 to 79 months induced by Losartan use, results in net savings of $7,576,135 per patient, at 3.5 years of intervention. The figure does not change using different sensitivity scenarios., Conclusions: The eventual use of Losartan in type 2 diabetic patients results in important savings.

Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) is one of the most important targets for treatment of Acquired Immune Deficiency Syndrome (AIDS). It catalyzes the reverse transcription of HIV-RNA into a double stranded DNA, and the knowledge of its substrate specificity and catalytic mechanism has guided the development of several inhibitors widely used on current HIV/AIDS therapy. However, mutations in HIV-1 RT structure can lead to the emergence of drug-resistant virus strains. The goal of this review is to summarize relevant structural features of HIV-1 RT and its inhibitors in such a way that this cost-effective target in the development of new antiretroviral drugs is particularly highlighted.

The Lachesis muta thrombin-like enzyme (LM-TL) is a single chain serine protease that shares 38% sequence identity with the serine protease domain of thrombin and also displays similar fibrinogen-clotting activity. In addition, the 228 amino acid residue LM-TL is 52% identical to trypsin, and cleaves chromogenic substrates with similar specificity. Herein we report a three-dimensional (3D) model validated experimentally for LM-TL based on these two homologous proteins of known 3D structure. Spatial modeling of LM-TL reveals a serine protease with a chymotrypsin fold presenting a hydrophobic pocket on its surface, involved in substrate recognition, and an important 90's loop, involved in restricting the LM-TL catalytic site cleft. Docking analysis showed that LM-TL would not form a stable complex with basic pancreatic trypsin inhibitor and wild-type ecotin since its 90's loop would restrict the access to the catalytic site. LM-TL formed acceptable interactions with fibrinopeptide A and a variant of ecotin; ecotin-TSRR/R in which both the primary and secondary binding sites are mutated Val81Thr, Thr83Ser, Met84Arg, Met85Arg and Asp70Arg. Furthermore, analysis of the primary structures of LM-TL and of the seven snake venom thrombin-like enzymes (SVTLEs) family reveals a subgroup formed by LM-TL, crotalase, and bilineobin, both closely related to thrombin. Therefore, LM-TL provides an initial point to compare SVTLEs with their counterparts, e.g. the mammalian serine proteases, and a basis for the localization of important residues within the little known SVTLEs family.

Many of the components of Bothrops jararaca venom are proteolytic enzymes. In the present work, we investigated the proteolytic action of B. jararaca venom upon its own constituents. Crude venom was reconstituted and incubated at pH 5.0 or 8.5 for up to 48h at room temperature. Aliquots taken at 0, 24 and 48h of incubation were then tested for proteolytic activity and several biological activities, as well as electrophoretic migration pattern and antibody recognition. Rate of hydrolysis of azocasein by venom samples was not changed by the incubation, but hemagglutinating activity decreased by 93% after 24h of incubation at pH 8.5, with no detectable changes at pH 5.0. Incubation of venom samples caused a progressive increase in phospholipase A(2) and procoagulant activities that was more evident in samples incubated at pH 5.0. The electrophoretic migration pattern showed no significant change for venom samples incubated at pH 5.0, whereas in samples incubated at pH 8.5 bands in the region between 66 and 45kDa gradually disappeared. The addition of a mixture of protease inhibitors (EDTA, PMSF, PPACK and benzamidine) effectively protected against venom degradation at pH 8.5. The cocktail of inhibitors also reduced the changes in phospholipase A(2) activity found in venom samples incubated at pH 5.0. Recognition of venom samples by polyclonal antibodies raised against crude venom was progressively lost during incubation at both pH 5.0 and 8.5; again the addition of protease inhibitors protected against loss of antibody recognition. We conclude that prolonged manipulation of B. jararaca venom at an acidic or alkaline pH can produce significant changes in its biological properties.