Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure ...in the Brazilian Amazon.
In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan–Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed.
Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0–77·6) with tafenoquine, 73·4% (71·9–75·0) with 7-day primaquine, and 82·1% (77·7–86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2–89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8–87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49–0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76–120) in those treated with tafenoquine and 68 days (52–94) in those treated with 7-day primaquine.
In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America.
Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government.
For the Portuguese translation of the abstract see Supplementary Materials section.
Shrimp residues generated by the seafood industrial processing are generally discarded in the environment without any further treatment, leading to a loss of nutritional value such as proteins, ...lipids, chitin, carotenoids, and minerals. This practice can lead to environmental problems due to the decomposition of these substances in the air. The objective of this study was to extract astaxanthin-rich materials from shrimp (Litopenaeus vannamei) industrial residue (WO) and smaller-scale residue meal (MO) in processing shrimp with soybean oil to evaluate their physicochemical characteristics, fatty acid content, and antioxidant potential. WO and MO were found to contain 27.48 and 33.34 µg g-1 of astaxanthin, respectively. The physicochemical properties of pigmented oils are established by legislation. The MO material showed significantly higher antioxidant activity compared to the soybean oil (control), especially when based on the oxygen radical absorbance capacity (ORAC) test, which showed antioxidant activity of 0.484 and 0.264 µmol eq Trolox g-1 for the MO and soybean oil (control), respectively, possibly accompanying their respective astaxanthin contents in the MO sample. The pigmented oils from both the shrimp residues showed significant potential for being used in the food industry due to their affordability and their high antioxidant activity.
Cancer is one of the most urgent problems in medicine. In recent years, cancer is the second leading cause of death globally. In search for more effective and less toxic treatment against cancer, ...natural products are used as prototypes in the synthesis of new anticancer drugs. The aim of this study was to investigate the in vivo toxicity and the mechanism of antitumor action of 7-isopentenyloxycoumarin (UMB-07), a coumarin derivative with antitumor activity. The toxicity was evaluated in vitro (hemolysis assay), and in vivo (micronucleus and acute toxicity assays). Ehrlich ascites carcinoma model was used to evaluate in vivo antitumor activity of UMB-07 (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.), after 9 days of treatment, as well as toxicity. UMB-07 (2000 μg/mL) induced only 0.8% of hemolysis in peripheral blood erythrocytes of mice. On acute toxicity assay, LD
50
(50% lethal dose) was estimated at around 1000 mg/kg (i.p.), and no micronucleated erythrocytes were recorded after UMB-07 (300 mg/kg, i.p.) treatment. UMB-07 (25 and 50 mg/kg) reduced tumor volume and total viable cancer cells. In the mechanism action investigation, no changes were observed on the cell cycle analysis; however, UMB-07 reduced peritumoral microvessels density and CCL2 chemokine levels. In addition, UMB-07 showed weak toxicity on biochemical, hematological, and histological parameters after 9 days of antitumor treatment. The current findings suggest that UMB-07 has low toxicity and exerts antitumor effect by inhibit angiogenesis via CCL2 chemokine decrease.
The present study investigated the use of choline chloride:glycerol deep eutectic solvent as an adjuvant for tuning the ethanol extraction of astaxanthin from Litopenaeus vannamei processing ...residues. The adjuvant concentration did not show a clear trend on the total carotenoid, however, the addition of adjuvant proved to be advantageous in the ultrasound-assisted experiments. In order to establish a balance between total carotenoid and productivity, an operational condition with ultrasound, 5% (m/v) choline chloride:glycerol and 10 min of incubation was selected, which provided 737.69 μg g-1 total carotenoids and 32.71 μg g-1 astaxanthin. When compared to the astaxanthin standard, the shrimp residue extract obtained greater antioxidant activity in free radical scavenging tests. In addition, the shrimp residue extract dramatically reduced the dosage of norfloxacin (up to 87.5%) and gentamicin (up to 75.0%) antibiotics in tests to inhibit the growth of gram-negative bacteria.
Inhibition of arginase blocks the first step of the synthesis of polyamines that are essential for the multiplication and maintenance of the antioxidant mechanism through synthesis of trypanothione. ...Display omitted
► Cecropia pachystachya contains anti-leishmanial flavonoids. ► Flavonoids altered mitochondrial DNA arrangements. ► Flavonoids are strong inhibitors of arginase. ► Orientin (luteolin-8-C-glucoside) show an IC50 of 16μM for arginase inhibition.
The plant Cecropia pachystachya Trécul is widely used in Brazilian ethnomedicine to treat hypertension, asthma, and diabetes. Arginase is an enzyme with levels that are elevated in these disorders, and it is central to Leishmania polyamine biosynthesis. The aims of this study were to evaluate antileishmanial activity and inhibition of the arginase enzyme by C. pachystachya extracts, and to study changes in cellular organization using electron microscopy. The ethanol extract of C. pachystachya was tested on Leishmania (Leishmania) amazonensis promastigote survival/proliferation and arginase activity in vitro. Qualitative ultrastructural analysis was also used to observe changes in cell organization. The major bioactive molecules of the ethanol extract were characterized using liquid chromatography–electrospray ionization-mass spectrometry (LC–ESI-MS). The ethyl acetate fraction of the ethanol extract diminished promastigote axenic growth/survival, inhibited arginase activity, and altered a mitochondrial kinetoplast DNA (K-DNA) array. The bioactive compounds of C. pachystachya were characterized as glucoside flavonoids. Orientin (9) (luteolin-8-C-glucoside) was the main component of the methanol-soluble ethyl acetate fraction obtained from the ethanol extract and is an arginase inhibitor (IC50 15.9μM). The ethyl acetate fraction was not cytotoxic to splenocytes at a concentration of 200μg/mL. In conclusion, C. pachystachya contains bioactive compounds that reduce the growth of L. (L.) amazonensis promastigotes, altering mitochondrial K-DNA arrangement and inhibiting arginase.
Nitrogen fertilization can provide greater nutritional support and mitigate salt stress in the millet crop. The aim of this study was to evaluate the physiological responses and agronomic performance ...of millet crop subjected to nitrogen fertilization and irrigation water salinity. The study was carried out in a greenhouse, using a completely randomized design in a 5 × 2 factorial scheme, with four replications, with five doses of nitrogen (40; 60; 80; 100 and 120 kg ha−1 of N), and two levels of electrical conductivity for the irrigation water: 0.3 and 4.0 dS m−1. We concluded that salt stress increased leaf sodium levels and had a negative impact on stalk and panicle dry mass, leaf gas exchange, mineral element concentrations (K, P, and Ca), and water use efficiency. The use of lower-salinity water associated with increased nitrogen fertilization provides greater stalk and panicle dry mass, photosynthesis, water use efficiency, chlorophyll index, leaf potassium concentration, and biomass production. The adverse effects of salt stress were evident in decreased transpiration and stomatal conductance, alongside reductions in leaf phosphorus and calcium levels, coupled with elevated leaf sodium concentrations, particularly as nitrogen fertilization rates increased in potted millet plants. These findings offer insights for devising strategies aimed at mitigating the detrimental effects of salt stress on millet plant nutrition through targeted nitrogen fertilization approaches.
Managing and evolving a chatbot's content is a laborious process and there is still a lack of standardization. In this context of standardization, the absence of a management process can lead to bad ...user experiences with a chatbot. This work proposes the Chatbot Management Process, a methodology for content management on chatbot systems. The proposed methodology is based on the experiences acquired with the development of Evatalk, the chatbot for the Brazilian Virtual School of Government. The focus of this methodology is to evolve the chatbot content through the analysis of user interactions, allowing a cyclic and human-supervised process. We divided the proposed methodology into three distinct phases, namely, manage, build, and analyze. Moreover, the proposed methodology presents a clear definition of the roles of the chatbot team. We validate the proposed methodology along with the creation of the Evatalk chatbot, whose amount of interactions was of 22,771 for the 1,698,957 enrolled attendees in the Brazillian Virtual School of Government in 2020. The application of the methodology on Evatalk's chatbot brought positive results: we reduced the chatbot's human hand-off rate from 44.43% to 30.16%, the chatbot's knowledge base examples increased by 160% whilst maintaining a high percentage of confidence in its responses and keeping the user satisfaction collected in conversations stable.
Resumo Este ensaio propõe apontamentos sobre as especificidades da leitura de textos literários como experiência potencialmente formadora de novos sentidos para o leitor e subversiva à linguagem do ...poder, com seus discursos normatizados e normatizadores do cotidiano. Foi realizada uma revisão narrativa de literatura sobre a temática, e dividiu-se este texto em quatro eixos centrais: o primeiro, em que se apresenta algumas concepções sobre literatura, texto literário e leitura literária; o segundo, em que se discorre sobre a leitura individual e de escuta, partindo do pressuposto de que tal modalidade possibilita ao leitor uma experiência criativa e crítica a partir da produção de sentidos derivada do encontro com o texto. Este ponto encontra-se intimamente relacionado ao terceiro, a leitura literária como experiência; e por fim, apresentam-se interpretações sobre a leitura literária como experiência de subversão à palavra de ordem e à linguagem do poder. Tal diálogo nos levou a concluir que a leitura literária pode representar uma resistência às naturalizações do instituído cotidiano, uma vez que ela se revela como um âmbito de produção de singularidades, instigando no leitor a interrogação sobre o mundo concreto ao seu redor e seus discursos hegemônicos.
ABSTRACT The development and the use of new technologies in agriculture contribute to significant advances in research with practical applications in several fields, such as image analytical ...techniques, which are simple, fast, and objective analyses. This work aimed to evaluate rice seeds’ quality using X-ray, multispectral, and chlorophyll fluorescence image analytical techniques and relate this information with the photosynthetic efficiency of seedlings. Initially, the seeds were identified and enumerated, then X-ray images were obtained, and the void space (area between the endosperm + embryo and the glumes) was calculated. Next, the same seeds were used in the X-rays, multispectral, and chlorophyll fluorescence images. Afterward, the seeds were placed to germinate in polyethylene cups with a capacity of 250 mL, and evaluations of the photochemical yield of photosynthesis photosystem II (FSII) and of the seedling fluorescence chlorophyll were carried out seven, nine, and 11 days after the emergence of the seedlings. The reflectance of seeds in the spectral bands between 365 nm and 780 nm showed a positive correlation with the chlorophyll fluorescence. Furthermore, the higher photosynthetic efficiency of rice seedlings at 11 days after emergence is directly related to the reflectance of the seeds at spectral bands between 365 nm and 780 nm.
To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis.
Fifteen Swiss ...mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day.
The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces.
L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.
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