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IMPORTANCE: Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes.
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Evolução Molecular , Duplicação Gênica , Vírus Gigantes , Genoma Viral , Vírus Gigantes/genética , FilogeniaRESUMO
BODIPYs have a well-established role in biological sciences as chemosensors and versatile biological markers due to their chemical reactivity, which allows for fine-tuning of their photophysical characteristics. In this work, we combined the unique reactivity of arylazo sulfones with the advantages of a "sunflow" reactor to develop a fast, efficient, and versatile method for the photochemical arylation of BODIPYs and other chromophores. This approach resulted in red-shifted emitting fluorophores due to extended electronic delocalization at the 3- and 5-positions of the BODIPY core. This method represents an advantageous approach for BODIPY functionalization compared to existing strategies.
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BACKGROUND: Antineutrophil cytoplasmatic antibodies (ANCA) have been detected in patients with systemic lupus erythematosus (SLE). In this study, we investigated the presence of ANCA in a sample of Brazilian SLE patients and its possible associations with clinical and serological outcomes. Additionally, we reviewed the literature of on ANCA in SLE. RESULTS: The presence of ANCA was detected in 130 patients using indirect immunofluorescence (IIF). The test was positive in 29.9% of the cases (17.6% pANCA and 11.5% cANCA). Male sex and peripheral vasculitis were more prevalent in the ANCA-positive sample. cANCA was associated with lupus anticoagulant and pANCA had a positive association with peripheral vasculitis and a negative association with anti- SSB/La antibodies. In the 22 studies included in the literature review, a wide range of ANCA positivity was found (13% to 81.1% by IIF and 0 to 22.2% by ELISA). ANCA was associated with renal damage in the Asian population. Although other associations have been found in isolated studies, they were not consistently reported. CONCLUSIONS: The ANCA prevalence found in this Brazilian sample was within the range reported in the literature and these autoantibodies were more frequent in males and in patients with vasculitis. The literature showed controversial results on the association between ANCA and SLE disease activity or clinical characteristics.
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Lúpus Eritematoso Sistêmico , Vasculite , Humanos , Masculino , Anticorpos Anticitoplasma de Neutrófilos , Anticorpos Antinucleares , Brasil/epidemiologia , Estudos Transversais , Lúpus Eritematoso Sistêmico/complicações , Mieloblastina , Vasculite/complicações , FemininoRESUMO
Traditional theories of the nuclear magnetic resonance (NMR) autocorrelation function for intra-molecular dipole pairs assume a single-exponential decay, yet the calculated autocorrelation of realistic systems displays a rich, multi-exponential behavior, resulting in anomalous NMR relaxation dispersion (i.e., frequency dependence). We develop an approach to model and interpret the multi-exponential intra-molecular autocorrelation using simple, physical models within a rigorous statistical mechanical development that encompasses both rotational diffusion and translational diffusion in the same framework. We recast the problem of evaluating the autocorrelation in terms of averaging over a diffusion propagator whose evolution is described by a Fokker-Planck equation. The time-independent part admits an eigenfunction expansion, allowing us to write the propagator as a sum over modes. Each mode has a spatial part that depends on the specified eigenfunction and a temporal part that depends on the corresponding eigenvalue (i.e., correlation time) with a simple, exponential decay. The spatial part is a probability distribution of the dipole pair, analogous to the stationary states of a quantum harmonic oscillator. Drawing inspiration from the idea of inherent structures in liquids, we interpret each of the spatial contributions as a specific molecular mode. These modes can be used to model and predict the NMR dipole-dipole relaxation dispersion of fluids by incorporating phenomena on the molecular level. We validate our statistical mechanical description of the distribution in molecular modes with molecular dynamics simulations interpreted without any relaxation models or adjustable parameters: the most important poles in the Padé-Laplace transform of the simulated autocorrelation agree with the eigenvalues predicted by the theory.
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BACKGROUND: Cognitive dysfunction (CD) is frequently found in patients with systemic lupus erythematosus (SLE) and contributes to impairment in the patient's quality of life. AIM: To study CD in a sample of patients and the possible associations with cumulative damage, disease activity, clinical/serological profile, and cumulative glucocorticoid dose. METHODS: Included in this study are 103 patients with SLE and 95 controls for cognitive performance through MoCA (Montreal Cognitive Assessment) and MMSE (Mini-Mental State Examination). Disease activity was measured by SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and cumulative organ damage by SLICC/ACR/DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). CES-D (Center for Epidemiological Studies-Depression) scale was used to evaluate depression. Data on clinical and serological profile, treatment, and cumulative glucocorticoid dose were also collected. RESULTS: Patients with SLE had worse performance in the MoCA (p = 0.009) and MMSE (p = 0.01) than controls. The MoCA results showed that visuospatial and abstraction domains (p = 0.03 and p = 0.002, respectively) were impaired, and the MMSE results showed that language and spatial orientation were reduced (p = 0.002 and p = 0.01, respectively) when compared to controls. Both questionnaires (MoCA with r = -0.29 and MMSE r = -0.21) correlated negatively with SLICC/ACR/DI and the MoCA with SLEDAI (r = -0.22). No associations were found with cumulative glucocorticoid dose, degree of depression, and clinical or serological profile. CONCLUSIONS: According to the MoCA, visuospatial cognition and abstraction were impaired, and according to the MMSE, spatial orientation and language were impaired in patients with SLE. The CD was correlated with cumulative damage and disease activity. These findings demonstrate that both disease-activity and disease-injury associated CD is found broadly in SLE patients in a Brazilian population, supporting the prior reports of CD in other regional SLE populations.
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Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Humanos , Estudos Transversais , Qualidade de Vida , Brasil/epidemiologia , Glucocorticoides/efeitos adversos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Índice de Gravidade de DoençaRESUMO
Gadolinium-based contrast agents are key in clinical MRI for enhancing the longitudinal NMR relativity (r1) of hydrogen nuclei (1H) in water and improving the contrast among different tissues. The importance of MRI in clinical practice cannot be gainsaid, yet the interpretation of MRI relies on models with severe assumptions, reflecting a poor understanding of the molecular-scale relaxation processes. In a step towards building a clearer understanding of the relaxation processes, here we investigate thermal and concentration effects on r1 of the Gd3+-aqua complex using both semi-classical molecular dynamics (MD) simulations and measurements. We follow the MD simulation approach recently introduced by [Singer et al., Phys. Chem. Chem. Phys., 2021, 23, 20974], in which no NMR relaxation model or free-parameter is assumed to predict r1, thereby bringing new insights into the physics of r1 on a molecular scale. We expand the autocorrelation function G(t) in terms of molecular modes and determine the thermal activation energies of the two largest modes, both of which are consistent with the range of literature values for rotational diffusion. We also determine the activation energies for translational diffusion and low-field electron-spin relaxation, both of which are consistent with the literature. Furthermore, we validate the MD simulations at human body temperature and concentrations of the paramagnetic ion used in clinical MRI, and we quantify the uncertainties in both simulations and measurements.
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Imageamento por Ressonância Magnética , Simulação de Dinâmica Molecular , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Meios de Contraste/químicaRESUMO
OBJECTIVE: To provide the prevalence and an overview of cleft lip and palate (CL/P) in the period of 2008 to 2017, as well as the profile of care provided for this condition in Brazil. DESIGN: Cross-sectional study of epidemiological character. SETTING: Brazilian government website. PARTICIPANTS: National Live Birth and Hospital Information System. INTERVENTION: Organization of the end databases and performance-based statistical analysis. MAIN OUTCOME MEASURE(S): Analysis of the prevalence of CL/P in newborns, sociodemographic condition of the mothers, surgical procedures and hospitalizations, and specialized hospitals in Brazil within a 10-year period. RESULTS: The average prevalence of CL/P in Brazil was â¼52 children per 100â 000 live births in the covered period, corresponding to 1 per 1924 newborns. The presence of cleft was associated with preterm birth, being underweight, and the male gender. The highest prevalence was found in the South region, while the lowest was found in the Northeast region, with increasing rates in the North region of Brazil. The states with the highest prevalence were not those with a great number of hospitalizations and surgical procedures for live births with CL/P. CONCLUSION: In the 10-year study period, the prevalence of CL/P was 0.52 newborns per 1000 live births, a result which differs among the states of Brazil. The need to reinforce the national monitoring of the prevalence and surgical procedures of cleft patients have also emphasized the need to improve public medical care for CL/P subjects.
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Fenda Labial , Fissura Palatina , Nascimento Prematuro , Gravidez , Feminino , Criança , Recém-Nascido , Humanos , Masculino , Fenda Labial/epidemiologia , Fenda Labial/cirurgia , Fissura Palatina/epidemiologia , Nascido Vivo/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Seguimentos , PrevalênciaRESUMO
BACKGROUND: The natural abundance of stable isotope 15 N (δ15 N) in production systems has emerged as an alternative to distinguish organic products from conventional ones. This study evaluated the use of δ15 N values recorded for nitrogen fertilizers, soil and plant tissue in order to set the differences between organic and conventional agricultural production systems applied to rice, potatoes, apple and banana crops. RESULTS: Values of δ15 N recorded for N sources ranged from +5.58 to +18.27 and from -3.55 to +3.19 in organic and synthetic fertilizers, respectively. Values recorded for δ15 N in food from organic rice, potatoes and banana farms were higher than values recorded for δ15 N in conventional farms; the same was observed for values recorded for δ15 N in leaves from the four crops. CONCLUSION: Results have allowed for differentiation between production systems due to values of δ15 N recorded in leaves of all crops and food, for rice, potatoes and banana trees. © 2021 Society of Chemical Industry.
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Alimentos Orgânicos/análise , Alimentos Orgânicos/normas , Isótopos de Nitrogênio/análise , Certificação , Qualidade dos Alimentos , Malus/química , Musa/química , Oryza/química , Solanum tuberosum/químicaRESUMO
A thermally stable carbocationic covalent organic network (CON), named RIO-70 was prepared from pararosaniline hydrochloride, an inexpensive dye, and triformylphloroglucinol in solvothermal conditions. This nanoporous organic material has shown a specific surface area of 990â m2 g-1 and pore size of 10.3â Å. The material has CO2 uptake of 2.14â mmol g-1 (0.5â bar), 2.7â mmol g-1 (1â bar), and 6.8â mmol g-1 (20â bar), the latter corresponding to 3 CO2 molecules adsorbed per pore per sheet. It is shown to be a semiconductor, with electrical conductivity (σ) of 3.17×10-7 â S cm-1 , which increases to 5.26×10-4 â S cm-1 upon exposure to I2 vapor. DFT calculations using periodic conditions support the findings.
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BACKGROUND: Systemic lupus erythematosus (SLE) may have a different serological and clinical profile according to age of disease onset. AIM: To compare clinical presentation and serological data from patients with SLE onset in childhood (cSLE) with disease onset in adulthood (aSLE) in a sample of Brazilian patients. METHODS: Retrospective study of 614 SLE patients from a single Rheumatology Unit from Brazil: 77 (12.5%) cSLE and 537 (87.4%) aSLE. Clinical and serological data were obtained from the charts. Comparisons of cSLE with aSLE in general and according to patient's gender were made. RESULTS: The comparison of whole sample showed that children had more malar rash (p = 0.04), seizures (p < 0.0001), psychosis (p = 0.02), glomerulonephritis (p = 0.001), anti-dsDNA (p = 0.008), anticardiolipin IgM (p = 0.04) but less discoid lesions (p = 0.01), anti-Ro (p < 0.0001) and anti-La antibodies (p = 0.007). When only the male sample was compared, no differences in glomerulonephritis and anti-dsDNA frequencies were found. CONCLUSION: Children had a higher frequency of severe manifestations (glomerulonephritis and central nervous system) than adults. The difference in glomerulonephritis occurrence disappeared when only males were compared.
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Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Adolescente , Adulto , Idade de Início , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Exantema/diagnóstico , Exantema/epidemiologia , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/epidemiologia , Humanos , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Prevalência , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/epidemiologia , Índice de Gravidade de DoençaRESUMO
We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives.
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Magnésio , Quinolinas , Indicadores e Reagentes , Lítio , ZincoRESUMO
Atomistic molecular dynamics simulations are used to predict 1H NMR T1 relaxation of water from paramagnetic Gd3+ ions in solution at 25 °C. Simulations of the T1 relaxivity dispersion function r1 computed from the Gd3+-1H dipole-dipole autocorrelation function agree within ≃8% of measurements in the range f0 ≃ 5 â 500 MHz, without any adjustable parameters in the interpretation of the simulations, and without any relaxation models. The simulation results are discussed in the context of the Solomon-Bloembergen-Morgan inner-sphere relaxation model, and the Hwang-Freed outer-sphere relaxation model. Below f0 â² 5 MHz, the simulation overestimates r1 compared to measurements, which is used to estimate the zero-field electron-spin relaxation time. The simulations show potential for predicting r1 at high frequencies in chelated Gd3+ contrast-agents used for clinical MRI.
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PURPOSE: Clinicopathological features and chemotherapy can influence the quality of life (QOL), women with ovarian cancer. This study aimed to evaluate the physical and functional well-being, and ovarian cancer-specific effects scores reported from QOL questionnaire among women with ovarian cancer at the time of in their initial diagnosis and access the scores trajectory of women receiving neoadjuvant and adjuvant chemotherapy. METHODS: This prospective study used cross-sectional analysis at baseline and longitudinal analysis from baseline to 12-month post-chemotherapy. QOL was evaluated at the baseline, at sixth cycle and 12-month post-chemotherapy using FACT-O questionnaire. Clinicopathological features and chemotherapy regime were evaluated and tested for associations with QOL measures. RESULTS: Of the 38 women enrolled in this study, 27 (80.1%) completed the questionnaire for 12 months. The multivariate linear regression results suggest, at the baseline, women with advance stage and presence of post-surgery residual disease showed lower scores in physical and functional well-being, ovarian cancer-specific effects, and FACT-O TOI domains (p < 0.05). Longitudinal analysis spanning over 12 months showed an improvement in mean physical well-being, functional well-being, and ovarian cancer-specific effects scores, independent of chemotherapy received (p < 0.05). CONCLUSIONS: At the baseline, the clinicopathological features such as stage, presence of post-surgery residual disease, and type of chemotherapy correlated with on QOL scores. At one-year follow-up, women who underwent chemotherapy showed improvement in QOL regardless of the type of chemotherapy they received. Future prospective study with a larger group is recommended.
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Neoplasias Ovarianas , Qualidade de Vida , Estudos Transversais , Feminino , Seguimentos , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Estudos ProspectivosRESUMO
Bovine mastitis is an infectious disease that affects the mammary gland of dairy cattle with considerable economic losses. Staphylococcus aureus is the main microorganism involved in this highly contagious process, and the treatment is only using antibiotics. Currently, the search for new treatment and/or compounds is still in need due to microbial resistance. In this work, we evaluated the potential of eugenol and thymol derivatives against S. aureus strains from bovine mastitis. On that purpose, nine derivatives were synthesized from eugenol and thymol (1-9), and tested against 15 strains of S. aureus from subclinical bovine mastitis. Initially, the strains were evaluated for the biofilm production profile, and those with strong adherence were selected to the antimicrobial sensitivity determination in the Minimum Inhibitory Concentration (MIC) assays. Herein the compounds toxicity was also evaluated by in silico analysis using Osiris DataWarrior® software. The results showed that 60% of the strains were considered strongly adherent and three strains (S. aureus 4271, 4745 and 4746) were selected for the MIC tests. Among the nine eugenol and thymol derivatives tested, four were active against the evaluated strains (MIC = 32 µg mL-1) within CLSI standard values. In silico analysis showed that all derivatives had cLopP < 5, cLogS > - 4 and TPSA < 140 Å2, and similar theoretical toxicity parameters to some antibiotics currently on the market. These molecules also showed negative drug-likeness values, pointing to the originality of these structures and theoretical feasibility on escaping of resistance mechanism and act against resistant strains. Thus, these eugenol derivatives may be considered as promising for the development of new treatments against bovine mastitis and future exploring on this purpose.
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Mastite Bovina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Bovinos , Eugenol/farmacologia , Feminino , Mastite Bovina/tratamento farmacológico , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus aureus , Timol/farmacologiaRESUMO
BACKGROUND: Toxoplasma gondii causes toxoplasmosis and is controlled by activated macrophages. However, infection of macrophages by tachyzoites induces TGF-ß signaling (TGF-s) inhibiting nitric oxide (NO) production. NO inhibition may be a general escape mechanism of distinct T. gondii strains. OBJECTIVES: To evaluate in activated macrophages the capacity of T. gondii strains of different virulence and genetics (RH, type I; ME-49, type II; VEG, type III; P-Br, recombinant) to evade the NO microbicidal defense system and determine LC3 loading to the parasitophorous vacuole. METHODS: Activated peritoneal macrophages were infected with the different T. gondii strains, NO-production was evaluated by the Griess reagent, and inducible nitric oxide synthase expression, TGF-s, and LC3 localisation assayed by immunofluorescence. FINDINGS: Only RH persisted in macrophages, while VEG was more resistant than P-Br and ME-49. All strains induced TGF-s, degradation of inducible nitric oxide synthase, and NO-production inhibition from 2 to 24 h of infection, but only RH sustained these alterations for 48 h. By 24 h of infection, TGF-s lowered in macrophages infected by ME-49, and P-Br, and NO-production recovered, while VEG sustained TGF-s and NO-production inhibition longer. LC3 loading to parasitophorous vacuole was strain-dependent: higher for ME-49, P-Br and VEG, lower for RH. All strains inhibited NO-production, but only RH sustained this effect probably because it persisted in macrophages due to additional evasive mechanisms as lower LC3 loading to parasitophorous vacuole. MAIN CONCLUSIONS: These results support that T. gondii can escape the NO microbicidal defense system at the initial phase of the infection, but only the virulent strain sustain this evasion mechanism.
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Macrófagos Peritoneais/parasitologia , Macrófagos/parasitologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/biossíntese , Toxoplasma/fisiologia , Animais , Macrófagos/metabolismo , Camundongos , Toxoplasmose Animal/parasitologiaRESUMO
Using molecular hybridization, specific sulfonamide derivatives of eugenol were synthesized with subtle modifications in the allylic chain of the eugenol subunit (and also in the nature of the substituent group in the sulfonamide aromatic ring) which allowed us to study the influence of structural changes on the antimicrobial potential of the hybrids. Antimicrobial test results showed that most of the synthesized hybrid compounds showed good activity with better results than the parent compounds. Molecular docking studies of the hybrids with the essential bacterial enzyme DHPS showed complexes with low binding energies, suggesting that DHPS could be a possible target for the antibacterial sulfonamide-eugenol hybrids. Furthermore, most of the final compounds presented similar docking poses to that of the crystallographic ligand sulfamethoxazole. The results obtained allow us to conclude that these are promising compounds for use as new leads in the search for new antibacterial sulfonamides.
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Antibacterianos/farmacologia , Desenho de Fármacos , Eugenol/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Eugenol/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/químicaRESUMO
BACKGROUND: The combination of near-infrared (NIR) spectroscopy and chemometrics can be used to group or discriminate soils based on spectral response. In this study, we conducted discrimination and classification analyses on soils managed with different sources of fertilization and plant species grown in organic and conventional farming systems. RESULTS: Principal component analysis explained 96% (PC1) and 3% (PC2) of the data variability and separated the soil samples of organic and conventional management systems. The wavenumbers that contributed most to the separation of the management systems were in the range of 3600 and 7300 cm-1 , especially the absorption peaks of 3700 and 4600 cm-1 (characteristic of CH and NH combinations), and 5200 and 7000 cm-1 (typical of OH combinations). Machine learning analysis using k-nearest neighbor and random forest algorithms was efficient in classifying soil samples according to management system with an accuracy of 97.8% and can therefore be used for future classification studies. CONCLUSION: Based on the results, we strongly recommend the use of NIR spectroscopy associated with chemometrics for discriminating soils grown with Malus domestica, Musa spp., Oryza sativa and Solanum tuberosum L. under organic and conventional management systems through spectral response. © 2021 Society of Chemical Industry.
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Fertilizantes/análise , Solo/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Agricultura , Algoritmos , Produtos Agrícolas/crescimento & desenvolvimento , Análise Discriminante , Análise de Componente PrincipalRESUMO
Microwave-mediated N-arylation of 4-chloroquinazolines in THF/H2O rapidly and efficiently afforded a library of novel 6-halo-2-phenyl-substituted 4-anilinoquinazolines. The methodology was compatible with numerous ortho-, meta-, and para-substituted N-methylanilines as well as substituted anilines and furnished the corresponding 4-anilinoquinazolines in good yields. Preliminary screening of the synthesized compounds against tumor cells (HCT-116 and T98G) showed promising antiproliferative properties.
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BACKGROUND: Dating violence has an alarming prevalence among Brazilian adolescents. School-based preventive programs have been implemented, but remain isolated initiatives with low reach. Health communication strategies based on innovative technologies with a high potential of diffusion are urgent. This study aimed to develop a computer-tailored intervention to prevent victimization and perpetration of dating violence among Brazilian youth. METHODS: The intervention, called Dating SOS (SOS Namoro), is based on the I-Change Model and attachment theory and is a comprehensive preventive program targeted to young people with a current partner. The intervention design included the stages of needs assessment; definition of objectives of change; development of the library of messages; elaboration of a questionnaire for tailoring feedbacks according to the relevant variables; integration of the content in the software Tailor Builder; pre-testing; and usability and efficacy evaluation planning. Dating SOS is composed of four online sessions. The first session gives a tailored orientation on attachment style and risk perception of violence. The second session addresses knowledge on conflict management, positive and negative social models of intimate relationships and an action plan to improve everyday interactions. The third session covers social norms, self-efficacy and an action plan to cope with conflicts. The fourth session discusses attitudes, social support and an action plan to protect from violence. Improvements on the interface and tailoring refinement was done after pre-testing to improve attractiveness and decrease risk of iatrogenic effects. DISCUSSION: The principal merit of the present study resides in the development of an innovative strategy based on the qualified use of the internet for education surrounding romantic relationships and the prevention of dating violence among adolescent and young Brazilians, a hitherto unaddressed need in the field. The intervention usability and efficacy should be investigated in further studies. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials. RBR-9frj8q. Prospectively registered on July 25, 2019. http://www.ensaiosclinicos.gov.br/rg/RBR-9frj8q/.
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Comunicação em Saúde/métodos , Internet , Violência por Parceiro Íntimo/prevenção & controle , Serviços Preventivos de Saúde/métodos , Adolescente , Adulto , Brasil , Vítimas de Crime/estatística & dados numéricos , Difusão de Inovações , Feminino , Humanos , Violência por Parceiro Íntimo/estatística & dados numéricos , Masculino , Teoria Psicológica , Inquéritos e Questionários , Adulto JovemRESUMO
It is known that the current treatment for toxoplasmosis causes side effects. Thus, it is essential to develop new therapies with reduced adverse effects while concurrently maintaining broad coverage and prophylactic therapy. Melatonin is a hormone that participates in the circadian cycle in vertebrates and has antioxidant, immunomodulatory, and antitumoral functions. In addition, it has been shown that melatonin can modulate immune responses and parasitic development during infection by Trypanosoma cruzi and Leishmania spp. Furthermore, studies indicate that melatonin increases the number of lymphocytes in rats infected by Toxoplasma gondii. However, there is no information on the possible effects of melatonin in T. gondii-infected host cells in vitro. This study analyzed the effects of melatonin treatment in the monkey kidney cell epithelial cell line, LLC-MK2, after infection with T. gondii. LLC-MK2 cells were infected and treated/not treated with melatonin, and the infection index was then quantified. Melatonin treatment did not alter host cell viability and was able to reduce parasite proliferation in LLC-MK2 cells at 24 and 48 h and at 6 days. Analysis by scanning electron microscopy confirmed reduction of parasite proliferation and alterations of tachyzoite shapes. Transmission electron microscopy images showed parasites with ruptured plasma membranes and cytoplasmic leakage. After treatment, parasites showed positive staining for apoptotic-like cell death. These results suggest that the use of melatonin as the lead compound for the synthesis of new compounds may constitute an alternative treatment for toxoplasmosis.