The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 ...December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
To analyze the perceptions of professionals, caregivers, children, and adolescents with disabilities regarding the implementation of the My Abilities First (MAF) tool in Specialized Child ...Rehabilitation Centers (CERs).
This is a qualitative research based on Reflexive Thematic Analysis (RTA). The study involved twenty-seven intentionally selected individuals, comprising 12 physiotherapists, 4 occupational therapists, 11 caregivers, 9 children and 2 adolescents. Participants completed sociodemographic and clinical questionnaires and took part in semi-structured online interviews, focusing on two themes: Positive health approaches and the MAF tool. The study was approved by the local ethics committee (opinion 4.779.175).
Reflexive Thematic Analysis of the interviews resulted in two themes: (1) Perceptions regarding the MAF tool as an educational and contributory process to enhance the inclusion and participation of children and adolescents with disabilities, and (2) Barriers and facilitators for the implementation process of the MAF tool. The implementation of MAF was identified as a driving factor in promoting equity and increased participation of children and adolescents with disabilities in various settings, including health, education, and leisure. Interviewees highlighted the need to confront attitudinal, communication, and social barriers that may hinder the implementation of the tool.
The implementation of the MAF tool was perceived as an innovation due to its focus on the abilities of individuals with disabilities. However, there is a need to restructure it to broaden its scope and access to different contexts in order to confront barriers and enhance the inclusion and participation of children and adolescents with disabilities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Understanding the role of 3CLpro protease for SARS-CoV-2 replication and knowing the potential of flavonoid molecules like rutin, myricetin, and baicalein against 3CLpro justify an investigation into ...their inhibition. This study investigates possible bonds and reactivity descriptors of rutin, myricetin, and baicalein through conformational and electronic properties. Density functional theory was used to determine possible interactions. Analyses were carried out through the molecular electrostatic potential, electron localization function, Fukui function descriptors based on frontier orbitals, and non-covalent interactions. A docking study was performed using a resolution of 1.55 Å for 3CLpro to analyze the interactions of rutin, myricetin, and baicalein. Scores of structures showed that rutin is the best ligand, followed by myricetin and baicalein. Docking studies showed that baicalein and rutin can establish effective interactions with residues of the catalytic dyad (Cys145 and His41), but just rutin forms a hydrogen bond. Myricetin, in turn, could not establish an effective interaction with Cys145. Baicalein interaction arose with active residues such as Arg188, Val186, Gln189, and Gln192. Interactions of rutin and myricetin with Arg188 and Gln189 were also found. A critical interaction was observed only for rutin with the hydroxyls of ring A with His41, and also for Cys145 with rings B and C, which is probably related to the highest score of rutin.
The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known ...archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant. Across the basin, the relative abundance and richness of domesticated species increase in forests on and around archaeological sites. In southwestern and eastern Amazonia, distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples.
Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use ...of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC50 values ranging from 1.4 to 46 μm. None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound (11).
Chloroquine (CQ) is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ‐resistant strains. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone with IC50 values ranging from 1.4 to 46 µm.
Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are ...enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells.
Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease ...progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
Abstract Cowpea is a leguminous plant belonging to the fabaceae family cultivated in the North and Northeast regions of Brazil, with productive potential. Among the abiotic factors, water deficiency ...is one of the main environmental limitations that influence agricultural production in the world. The objective of this work was to study the relative water content and osmoregulators of cowpea plants subjected to water stress. The experiment was carried out in a greenhouse at the Universidade Federal Rural da Amazônia (UFRA, Belém, PA), cowpea plants BR-17 Gurguéia Vigna unguiculata (L.) Walp were used. The experimental design was completely randomized (DIC) in a 2 × 2 factorial scheme, two water conditions (control and water deficit) and two times of stress (four and six days of water suspension), with 7 replications, totaling 28 experimental units. The water deficit affected plants, causing a reduction in relative water content (69.98%), starch (12.84% in leaves and 23.48% in roots) and carbohydrates (84.34%), and an increase in glycine-betaine, sucrose (114.11% in leaves and 18.71% in roots) and proline (358.86%) at time 2. The relative water content was negatively affected by water conditions, with a decrease in relation to the interaction of the aerial part and the root system. Therefore, greater metabolic responses were noted in plants that were subjected to stress treatment at time 2 (6 days).
Resumo O feijão-caupi é uma planta leguminosa pertencente à família das Fabaceae cultivada nas regiões Norte e Nordeste do Brasil, com potencial produtivo. Entre os fatores abióticos, a deficiência hídrica é uma das principais limitações ambientais que influenciam a produção agrícola no mundo. O objetivo do trabalho foi estudar o conteúdo relativo de água e os osmorreguladores de plantas de feijão-caupi submetidas ao estresse hídrico. O experimento foi conduzido em casa de vegetação da Universidade Federal Rural da Amazônia (UFRA, Belém, PA), foram utilizadas plantas de feijão-caupi BR-17 Gurguéia Vigna unguiculata (L.) Walp. O delineamento experimental foi inteiramente casualizado (DIC) em esquema fatorial 2 × 2, duas condições hídricas (controle e déficit hídrico) e dois tempos de estresse (quatro e seis dias de suspensão hídrica), com 7 repetições, totalizando 28 unidades experimentais. O estresse hídrico afetou as plantas, provocando redução no conteúdo relativos de água (69,98%), amido (12,84% nas folhas e 23,48% nas raízes) e carboidratos (84,34%), e aumento na glicina-betaína, sacarose (114,11% nas folhas e 18,71% nas raízes) e prolina (358,86%) no tempo 2. O conteúdo relativo de água foi afetado negativamente pelas condições hídricas, com diminuição em relação à interação da parte aérea e do sistema radicular. Diante disso, notou-se maiores respostas metabólicas nas plantas que foram submetidas ao tratamento de estresse no tempo 2 (6 dias).
Agroecological production represents a new reality in vegetable farming. Thus, the study aimed to search for the presence of pesticides in agroecological samples and microbiological and ...parasitological contamination in Lactuca sativa L. of agroecological and conventional fairs in Alagoas. Thirty-two samples were collected, a hygienic-sanitary checklist was performed, along with coliform, Salmonella spp., Staphylococcus aureus research and Gas Chromatography with Mass Spectrometer (GC-MS) for pesticide research; using two methodologies for parasitological studies. Thirty-two samples were analyzed, with a sanitary adequacy level at 45% and 38% for fairs (agroecological and conventional) respectively, with three samples (9.4%) in total, being adequate to the microbiological pattern according to RDC no. 12/2001. Among the 23 samples which were tested positive for parasites, 69.5% originated from samples extracted at conventional fairs, and 53% of every positive samples presented Entamoeba coli as the main contaminant. All together, no traces of deltamethrin were detected, but in two of the samples a peak retention for diphenoconazole was detected. In conclusion, the fairs represent an adequate environment for human pathogens and indicators. Therefore greater hygiene training of vegetable traders and consumers in the state of Alagoas is required, especially in conventional fairs, which presented more critical microbiological and parasitological indexes comparing to fairs with agroecological products; however, the presence of difenoconazole in two samples of agricultural fairs suggests accidental contamination or indiscriminate use of this chemical in the production of Lactuca sativa, however, products with agroecological origin represents a better choice for the consumers.
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