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Quantification of chaos is a challenging issue in complex dynamical systems. In this paper, we discuss the chaotic properties of generalized Lotka-Volterra and May-Leonard models of biodiversity, via the Hamming distance density. We identified chaotic behavior for different scenarios via the specific features of the Hamming distance and the method of q-exponential fitting. We also investigated the spatial autocorrelation length to find the corresponding characteristic length in terms of the number of species in each system. In particular, the results concerning the characteristic length are in good accordance with the study of the chaotic behavior implemented in this work.
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Biodiversidade , Dinâmica não Linear , Modelos BiológicosRESUMO
OBJECTIVE: This study investigated the associations of occupational physical activity and active transport with depressive symptoms, stratified by income range, among Brazilian working adults. STUDY DESIGN: This cross-sectional study drew on data from the 2019 Brazilian National Health Survey. METHODS: We used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms in working adults aged 18-65 years, with physical activities (occupational physical activity and active transport) self-reported through a specially developed questionnaire. Crude and adjusted logistic regression models were fitted. RESULTS: Individuals at the highest level of occupational physical activity (odds ratio [OR] 1.35; 95% confidence interval [95% CI] 1.19-1.53) and at the moderate level of active transport to work (OR 1.66; 95% CI 1.24-2.22) returned increased odds of depressive symptoms as compared with those who were inactive in these domains. Stratified by income group, light active transport to work (OR 0.57; 95% CI 0.34-0.95) in the lower income group (Range 1) was associated with lower odds of depressive symptoms. On the other hand, individuals at the highest level of active transport to work returned higher odds of depressive symptoms in the low- and intermediate-income groups, Ranges 3 and 4 (OR 1.92; 95% CI 1.22-3.00 and OR 2.91; 95% CI 1.71-4.95, respectively). CONCLUSION: Our results suggest that occupational physical activity and active transport may be a risk factor for depressive symptoms. They also point to differences in this relationship by income range. Further studies are needed to pursue the analysis of how specific domains of physical activity contribute to depressive symptoms.
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Depressão , Exercício Físico , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Exercício Físico/psicologia , Estudos Transversais , Brasil/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Adulto Jovem , Adolescente , Idoso , Meios de Transporte/estatística & dados numéricos , Renda/estatística & dados numéricos , Inquéritos EpidemiológicosRESUMO
With the increasing data rate requirements on short-reach links, the recent standardization of unamplified coherent optical systems is paving the way for a cost and power-effective solution, targeting a massive deployment in the near future. However, unamplified systems are introducing new challenges. Particularly, the performance is highly dependent on the peak-to-average power ratio (PAPR) of the transmitted signal, which puts at question the use of the typical constellation formats. In this work, we use an end-to-end deep learning framework to optimize the geometry of different constellation sizes, ranging from 8- to 128-ary constellations. In general, it is shown that the performance of these systems is maximized with constellations whose outer symbols are disposed in a square shape, owing to the minimization of the real-valued PAPR. Following this premise, we experimentally demonstrate that odd-bit constellations can be significantly optimized for unamplified coherent links, achieving power budget gains in the range of 0.5-3 dB through the geometric optimization of 8-, 32- and 128-ary constellations.
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AIM: To compare microcrack formation in roots of extracted teeth after the shaping of straight and curved root canals with hand, rotary and reciprocating files using micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Thirty straight mandibular incisors and 30 severely curved mesial roots of mandibular molars were randomly divided into 6 experimental groups (n = 10) according to the systems used for the root canal preparation and the root canal curvature: ProTaper Universal for Hand Use (Dentsply Sirona, Ballaigues, Switzerland), HyFlex EDM (Coltene-Whaledent, Altstätten, Switzerland) and Reciproc Blue (VDW, Munich, Germany) files used in mandibular incisors (straight canals) and mesial roots of mandibular molars (curved canals). The roots were imaged with micro-CT scanning at an isotropic resolution of 14 µm before and after root canal preparation, and the cross-sectional images generated were assessed to detect microcracks. RESULTS: All dentinal defects identified after root canal preparation were already present before instrumentation, and no new microcracks were detected. Dentinal microcracks were present in 19% (ProTaper Universal for Hand Use), 11% (Hyflex EDM) and 23% (Reciproc Blue) of the cross-sections when the instrumentation was performed in mandibular incisors. Instrumentation of mandibular molars revealed microcracks in 15% (ProTaper Universal for Hand Use), 16% (Hyflex EDM) and 17% (Reciproc Blue) of the cross-sections. CONCLUSIONS: Preparation of straight and curved root canals with ProTaper Universal for Hand Use, HyFlex EDM and Reciproc Blue systems did not produce microcracks in extracted teeth when evaluated with micro-CT.
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Cavidade Pulpar , Preparo de Canal Radicular , Estudos Transversais , Cavidade Pulpar/diagnóstico por imagem , Alemanha , Microtomografia por Raio-XRESUMO
BACKGROUND: Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. METHODS: Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 µg twice daily + budesonide/formoterol 200/6 µg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. RESULTS: Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. CONCLUSIONS: Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.
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Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Brônquios/patologia , Adulto , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/fisiologia , Asma/complicações , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêuticoRESUMO
Autoantibodies of the IgG class against N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) were first described in anti-NMDAR encephalitis and seen as disease indicators. Recent work on together over 5000 individuals challenged this exclusive view by showing age-dependently up to >20% NMDAR1-autoantibody seroprevalence with comparable immunoglobulin class and titer distribution across health and disease. The key question therefore is to understand the properties of these autoantibodies, also in healthy carriers, in order to assess secondary complications and possible contributions to neuropsychiatric disease. Here, we believe we provide for human NMDAR1-autoantibodies the first comprehensive analysis of their target epitopes and functionality. We selected sera of representative carriers, healthy or diagnosed with very diverse conditions, that is, schizophrenia, age-related disorders like hypertension and diabetes, or anti-NMDAR encephalitis. We show that all positive sera investigated, regardless of source (ill or healthy donor) and immunoglobulin class, provoked NMDAR1 internalization in human-induced pluripotent stem cell-derived neurons and reduction of glutamate-evoked currents in NR1-1b/NR2A-expressing Xenopus oocytes. They displayed frequently polyclonal/polyspecific epitope recognition in the extracellular or intracellular NMDAR1 domains and some additionally in NR2A. We conclude that all circulating NMDAR1-autoantibodies have pathogenic potential regarding the whole spectrum of neuronal NMDAR-mediated effects upon access to the brain in situations of increased blood-brain-barrier permeability.
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Autoanticorpos/sangue , Epitopos/metabolismo , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Receptores de N-Metil-D-Aspartato/imunologia , Idoso , Animais , Endocitose/fisiologia , Feminino , Fibroblastos/imunologia , Ácido Glutâmico/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Masculino , Potenciais da Membrana/fisiologia , Transtornos Mentais/sangue , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/imunologia , Neurônios/imunologia , Oócitos , Xenopus laevisRESUMO
BACKGROUND AND OBJECTIVE: Elevated levels of matrix metalloproteinase-7 (MMP7) have been observed in serum samples of subjects with type 2 diabetes mellitus (T2DM) and in gingival tissues of subjects with periodontitis. The aim of the present study was to collect in vivo and in silico evidence on the role of MMP7 in the interplay between T2DM and generalized periodontitis (GP). MATERIAL AND METHODS: The extent of MMP7 expression and localization were immunohistochemically analyzed in gingival tissues of patients with GP with T2DM (T2DM/GP, n = 11), systemically healthy patients with GP (n = 7), and systemically and periodontally healthy controls (n = 11). An in silico network model was built to determine the interactions between MMP7 and T2DM pathways. Regulation of neutrophil transmigration by MMP7 was analyzed in a knock-out mice model. RESULTS: In human gingival tissues, the proportion of cells with robust MMP7 expression was elevated in patients with T2DM/GP in comparison to controls (P = .014). According to the in silico analysis, "hydroxyl radical" and "hydrogen peroxide" compounds were among the most central nodes of the network, and were within the shortest paths connecting "glucose" to "MMP7." In MMP7 knock-out mice, an intense accumulation of neutrophils was observed in the gingival epithelium as compared to wild-type mice (P = .0001). CONCLUSION: Elevated MMP7 expression in gingival tissues of patients with T2DM/GP is related to the activation of reactive oxygen species by hyperglycemia. Suppression of MMP7 expression results in impaired neutrophil transmigration in gingiva.
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Diabetes Mellitus Tipo 2/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Periodontite/metabolismo , Adulto , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Periodontite/diagnóstico por imagem , Radiografia Panorâmica , TurquiaRESUMO
The aim of this work was to investigate associations between individual cow Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity, 305-d corrected milk production, and somatic cell count during 5 lactations lifespan in Portuguese dairy herds using multilevel mixed models. We used MAP serum ELISA (Idexx MAP Ac, Idexx Laboratories Inc., Westbrook, ME) results (n = 23,960) from all the 20,221 adult cows present in 329 farms and corresponding 47,586 lactation records from the National Dairy Improvement Association. Cows and farms were classified as positive or negative. Multilevel mixed models were used to investigate the association of cow MAP status with variation in milk production and somatic cell count. Cow MAP status, farm status, and lactation number were considered as independent variables. A quadratic function of lactation number was used to mimic the effect of lactation order on milk production. The models considered 3 levels: measurement occasion (level 1) within cow (level 2) and cow within farm (level 3). Four final models were produced, including all herds and cows, to address the effect of farm status (models 1 and 2) or the effect of cow status (models 3 and 4) on the outcome variables. Our results show that MAP status affects milk production. Losses are detectable from third lactation onward. During the first 5 lactations, positive cows accumulated an average loss of 1,284.8 kg of milk when compared with the negative cows. We also observed that somatic cell counts were higher in positive cows and a positive interaction occurs between cow status and lactation number, suggesting a positive association between MAP infection and increased somatic cell counts. Our results are in line with previous studies, suggesting a possible positive relation between cow milk production and susceptibility to MAP infection.
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Doenças dos Bovinos/fisiopatologia , Bovinos , Contagem de Células/veterinária , Lactação/fisiologia , Paratuberculose/fisiopatologia , Animais , Doenças dos Bovinos/microbiologia , Feminino , Leite , Paratuberculose/epidemiologiaRESUMO
The emerging inverse electron demand Diels-Alder (IEDDA) reaction stands out from other bioorthogonal reactions by virtue of its unmatchable kinetics, excellent orthogonality and biocompatibility. With the recent discovery of novel dienophiles and optimal tetrazine coupling partners, attention has now been turned to the use of IEDDA approaches in basic biology, imaging and therapeutics. Here we review this bioorthogonal reaction and its promising applications for live cell and animal studies. We first discuss the key factors that contribute to the fast IEDDA kinetics and describe the most recent advances in the synthesis of tetrazine and dienophile coupling partners. Both coupling partners have been incorporated into proteins for tracking and imaging by use of fluorogenic tetrazines that become strongly fluorescent upon reaction. Selected notable examples of such applications are presented. The exceptional fast kinetics of this catalyst-free reaction, even using low concentrations of coupling partners, make it amenable for in vivo radiolabelling using pretargeting methodologies, which are also discussed. Finally, IEDDA reactions have recently found use in bioorthogonal decaging to activate proteins or drugs in gain-of-function strategies. We conclude by showing applications of the IEDDA reaction in the construction of biomaterials that are used for drug delivery and multimodal imaging, among others. The use and utility of the IEDDA reaction is interdisciplinary and promises to revolutionize chemical biology, radiochemistry and materials science.
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Reação de Cicloadição , Cicloparafinas/química , Elétrons , Corantes Fluorescentes/química , Animais , Sistemas de Liberação de Medicamentos , Cinética , Imagem MolecularRESUMO
The objective of this study was to evaluate the effect of Moquiniastrum polymorphum ssp floccosum ethanolic extract (MPEE) on 1,2 dimethylhydrazine (DMH)-induced colorectal carcinogenesis in mice. Forty-two male Swiss mice (Mus musculus) were subdivided into six groups (N = 7/group): negative control, DMH, MPEE, pre-treatment, simultaneous, and post-treatment. Results showed that MPEE has antigenotoxic potential on the tested protocols pre- and silmultaneous treatment, and the percent damage reductions (%DRs) were 81.88 and 93.12%, respectively. The micronucleus test demonstrated that MPEE has great antimutagenic activity, with %DRs higher than 77.09 in the associated groups. The aberrant crypt focus assay demonstrated anticarcinogenic potential of MPEE as the associated groups showed %DRs that ranged from 62.13 to 95.14%. The study shows that MPEE is nontoxic and has chemopreventive and anticarcinogenic activity, thus it may prove to be a promising medicinal plant in view of its demonstrated properties.
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1,2-Dimetilidrazina/toxicidade , Focos de Criptas Aberrantes/tratamento farmacológico , Asteraceae/química , Neoplasias Colorretais/tratamento farmacológico , Etanol/administração & dosagem , Focos de Criptas Aberrantes/prevenção & controle , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Etanol/farmacologia , Masculino , Camundongos , Testes para Micronúcleos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
STUDY DESIGN: Quasi-experimental translational study with pre- and post-measures. OBJECTIVES: To determine the effects of the Spinal Cord Injury and Physical Activity in the Community (SCIPA Com) intervention on leisure-time physical activity (LTPA) and associated outcomes among participants with spinal cord injury (SCI). SETTING: Young Men's Christian Associations and community fitness centers, Australia and New Zealand. METHODS: SCIPA Com consisted of three stages: (i) training exercise professionals via the Train the Trainers Spinal Cord Injury course; (ii) implementation of supervised physical activity programs twice a week for 30 to 60 min for 8 to 12 weeks; and (iii) follow-up assessments on health outcomes over 9 months. Participants with SCI were classified as active or inactive by baseline LTPA levels and linear mixed methods compared LTPA between groups over time. RESULTS: Sixty-four community-dwelling participants with SCI completed customized physical activity programs. Compared with baseline, there were significant improvements in LTPA (26 min per day, 95% confidence interval (CI): 16.6-35.4; P<0.001), functional goals (2, 95% CI: 1.72-2.37; P<0.001), self-esteem (1.5, 95% CI: 0.72-2.27; P<0.001) and overall quality of life (P<0.05). Over time, LTPA participation was greater among the active compared with the inactive group, although LTPA levels among the inactive improved compared with baseline. CONCLUSIONS: Significant improvements in LTPA participation and health outcomes were observed, especially among inactive individuals with SCI. SCIPA Com is an ecologically valid intervention based on training and support provided to community exercise professionals who, although new to adapted training, delivered effective physical activity programs for those at risk of inactivity. SPONSORSHIP: Transport Accident Commission (Project Number DP172) and the International Postgraduate Research Scholarship (IPRS), Curtin University.
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Terapia por Exercício/métodos , Exercício Físico/fisiologia , Características de Residência , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Resultado do Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Seguimentos , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Atividade Motora , Nova Zelândia , Adulto JovemRESUMO
Dulce de leche samples available in the Brazilian market were submitted to sensory profiling by quantitative descriptive analysis and acceptance test, as well sensory evaluation using the just-about-right scale and purchase intent. External preference mapping and the ideal sensory characteristics of dulce de leche were determined. The results were also evaluated by principal component analysis, hierarchical cluster analysis, partial least squares regression, artificial neural networks, and logistic regression. Overall, significant product acceptance was related to intermediate scores of the sensory attributes in the descriptive test, and this trend was observed even after consumer segmentation. The results obtained by sensometric techniques showed that optimizing an ideal dulce de leche from the sensory standpoint is a multidimensional process, with necessary adjustments on the appearance, aroma, taste, and texture attributes of the product for better consumer acceptance and purchase. The optimum dulce de leche was characterized by high scores for the attributes sweet taste, caramel taste, brightness, color, and caramel aroma in accordance with the preference mapping findings. In industrial terms, this means changing the parameters used in the thermal treatment and quantitative changes in the ingredients used in formulations.
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Comportamento de Escolha , Comportamento do Consumidor , Laticínios , Preferências Alimentares , Brasil , Doces , Carboidratos , Análise por Conglomerados , Cor , Humanos , Análise dos Mínimos Quadrados , Modelos Logísticos , Odorantes , Análise de Componente Principal , Olfato , PaladarRESUMO
UNLABELLED: Sound evidence on the effectiveness of fluoride varnishes (FV) to reduce caries incidence in preschool children is lacking. OBJECTIVE: To assess whether the application of FV in preschool children at 6-month intervals decreases the incidence of caries and produces any adverse effects. METHODS: A randomized, examiner- and patient-blind, placebo-controlled, parallel-group design, clinical trial, comprising 1- to 4-year-old children, 100 in each group (FV or placebo varnish, PV), was conducted in Rio de Janeiro, Brazil. Two trained pediatric dentists performed the clinical examinations (kappa = 0.85). Dental caries was recorded at the d2 (cavitated enamel) and d3 (dentine) levels using the International Caries Diagnosis and Assessment System. RESULTS: At baseline, the mean age of the participants was 2.4 years (SD 0.9) and the mean d3mfs was 0.8 (SD 1.9). Most of the children brushed their teeth with fluoride toothpaste and consumed fluoridated tap water. After 24 months, 89 and 92 children of the test and the control groups were analyzed, respectively. A total of 32 (35.9%) children in the FV group and 43 (46.7%) in the PV group presented new dentine caries lesions (χ(2) test; p = 0.14), showing relative and absolute risk reductions of 23% (95% CI: -9.5 to 45.9) and 11% (95% CI: -3.5 to 25.0). The mean caries increment differences between the test and control groups were -0.8 (95% CI: -2.0 to 0.4) at the d2 level and -0.7 (95% CI: -1.9 to 0.4) at the d3 level. Only 2 minor complaints regarding the intervention were reported. CONCLUSION: Although safe and well accepted, twice-yearly professional FV application, during 2 years, did not result in a significant decrease in caries incidence.
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Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Fluoretos Tópicos/uso terapêutico , Cariostáticos/administração & dosagem , Pré-Escolar , Índice CPO , Esmalte Dentário/patologia , Dentina/patologia , Feminino , Fluoretos Tópicos/administração & dosagem , Seguimentos , Humanos , Lactente , Análise de Intenção de Tratamento , Masculino , Higiene Bucal/educação , Placebos , Estudos Prospectivos , Medição de Risco , Comportamento de Redução do Risco , Método Simples-Cego , Classe Social , Dente Decíduo/patologia , Escovação Dentária/métodos , Cremes Dentais/uso terapêutico , Resultado do TratamentoRESUMO
Although twin, adoption, and family studies demonstrate that genetic factors are involved in the origins of stuttering, the mode of transmission of the disorder in families is not well defined and stuttering is considered a genetically complex trait. We performed a genome-wide linkage scan in a group of 43 Brazilian families, each containing multiple cases of persistent developmental stuttering. Linkage analysis under a dominant model of inheritance generated significant evidence of linkage in two Brazilian families, with a combined maximum single-point LOD score of 4.02 and a multipoint LOD score of 4.28 on chromosome 10q21. This demonstrated the presence of a novel variant gene at this locus that predisposes individuals to stuttering, which provides an opportunity to identify novel genetic mechanisms that underlie this disorder.
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Cromossomos Humanos Par 10 , Ligação Genética , Locos de Características Quantitativas , Gagueira/genética , Brasil , Mapeamento Cromossômico , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Repetições de Microssatélites , LinhagemRESUMO
Ultrasonographic imaging of the diaphragm is a non-invasive alternative for respiratory function evaluation in horses. This study aimed to measure diaphragm thickness, thickening (change in thickness with contraction) and thickening fraction in healthy adult horses during tidal breathing and forced vital capacity. Correlation between body weight (≤400 kg and >400 kg) and diaphragm thickness was investigated. To that purpose, 20 adult horses, weight 409±50 kg, height 1.47±0.05 m, and age 16±6 years were included in the study. Diaphragm thickness was measured at end-inspiration and end-expiration using B-mode and M-mode. The transducer was placed in the 10th, 11th and 12th intercostal spaces of both hemithoraces. Measurements obtained at end inspiration using M-mode during forced vital capacity were greater than for tidal breathing for diaphragm thickness (P=0.006), diaphragm thickening (P<0.001) and thickening fraction (P<0.001). The same was found for thickening (P<0.001) and thickening fraction (P<0.001). Diaphragm thickness at end-inspiration was greater in horses weighing >400kg than those ≤400kg at the inspiration (0.93±0.2 cm and 0.74±0 0.02 cm, P<0.001) and at the end of expiration (0.77±0.02 cm and 0.63±0, 02 cm, P<0.001). There was no difference in thickening fraction between horses weighing ≤400kg and >400kg (tidal breathing: 18±2 % and 16±2 %, P=0.609; forced vital capacity: 39±6 % and 31±5 %, P=0.301). Diaphragm assessment in horses is possible using both B-mode and M-mode. Breathing workload has a positive correlation between breathing workload and diaphragm contraction. Due to the relationship demonstrated between diaphragm thickness and weight, it is recommended that diaphragm thickening fraction is used to compare diaphragm measurements between horses.
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Diafragma , Ultrassonografia , Cavalos/fisiologia , Animais , Diafragma/diagnóstico por imagem , Diafragma/fisiologia , Ultrassonografia/métodos , Ultrassonografia/veterinária , Masculino , FemininoRESUMO
CONTEXT: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. METHODS: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å.
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Antimaláricos , Glutationa Redutase , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Plasmodium falciparum , Antimaláricos/química , Antimaláricos/farmacologia , Plasmodium falciparum/enzimologia , Plasmodium falciparum/efeitos dos fármacos , Glutationa Redutase/antagonistas & inibidores , Glutationa Redutase/química , Glutationa Redutase/metabolismo , Ligação Proteica , Domínio Catalítico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , HumanosRESUMO
The aim of the study was to compare and correlate levels of ferritin, transferrin, iron and APPs in healthy horses and those surgically treated for strangulating colic. On admission, measurements of inflammatory markers related to iron and total protein, fibrinogen, albumin, haptoglobin and ceruloplasmin were made. The study comprised 22 horses, divided into a control group (CG) of healthy horses (n = 10) and horses with surgically treated acute abdomen (n = 12), obstruction group (OG). The OG was subdivided according to the affected intestinal segment (small vs. large) and according to outcome (survivors vs. non survivors). The OG had higher haptoglobin (34.8±14.2 mg/dL vs 20.8±7.21 mg/dL) and transferrin (487±161 mg/dL vs 369±71.4 mg/dL) values and lower iron (96.9±65 µg/dL vs 218±105 µg/dL) values than the CG. The OG horses with large intestine obstruction had lower values of transferrin (374.6±130 mg/dL) than horses with small intestinal obstruction (598.6±98.9 mg/dL). There was no difference in outcome between horses with large and small intestinal obstruction. Ferritin levels were moderately correlated with total protein (r = 0.594; P = 0.042) and albumin (r = 0.584; P = 0.046) in OG. In the multivariate exploratory analysis, fibrinogen levels were higher in animals that did not survive. In conclusion, haptoglobin, transferrin and iron were useful inflammatory markers for colic in horses. The correlation of ferritin with other APPs shows a possible role of ferritin as an APP in horses. Fibrinogen levels are higher in horses with greater risk of death from strangulating obstructions.
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Cólica , Doenças dos Cavalos , Obstrução Intestinal , Animais , Cavalos , Haptoglobinas/metabolismo , Ferro/metabolismo , Cólica/veterinária , Fibrinogênio/metabolismo , Inflamação/veterinária , Obstrução Intestinal/veterinária , Ferritinas , Albuminas/metabolismo , Transferrinas , Doenças dos Cavalos/metabolismoRESUMO
Health literacy (HL) is defined as a cognitive and social skill that determines the motivation and ability of individuals to understand and use information to promote and maintain proper health. Inadequate HL has been associated with worse outcomes in diabetes control, poor self-care, and higher hospitalization rates for some chronic diseases. We hypothesized that HL influences the prevalence of diabetic retinopathy (DR) among individuals with type 2 diabetes mellitus (T2DM) and that inadequate glycemic control would mediate this association. This was a cross-sectional study carried out with 288 participants of the "Brazilian Diabetes Study" cohort. Inclusion criteria were people diagnosed with T2DM aged between 40 and 70 years and ability to read and write. In the adequate HL group, DR was found in 16.5% of participants and in the inadequate HL group, it was found in 32.8% (P=0.0081). Individuals with inadequate HL had a higher risk of having DR, and this association was still statistically significant after adjusting for HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure. In conclusion, HL is related to DR without the mediation of classical clinical variables.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Letramento em Saúde , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Transversais , BrasilRESUMO
Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.
Assuntos
Suplementos Nutricionais , Óleos de Peixe , Síndrome Metabólica , Obesidade , Ratos Wistar , Animais , Síndrome Metabólica/dietoterapia , Óleos de Peixe/administração & dosagem , Obesidade/dietoterapia , Obesidade/metabolismo , Masculino , Ratos , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Interleucina-6/sangue , Modelos Animais de Doenças , FemininoRESUMO
Oral squamous cell carcinoma (OSCC) is a worldwide health problem because it is a great cause of cancer morbidity and mortality. The transforming growth factor-ß1 (TGF-ß1) is involved in the regulation of numerous immunomodulatory processes. Thus, the aim of this case-control study was to investigate the possible association between the TGF-ß1T869C polymorphism and oral cancer. The genomic DNA extracted from peripheral blood of 62 male smoker patients diagnosed with OSCC and 62 smokers without cancer was analysed. The C allele was significantly more prevalent in the oral cancer group than in the controls, and individuals carrying this allele had an estimated 2.73-fold greater relative risk of developing cancer compared with C allele noncarriers (OR = 2.73, 95% CI = 1.19-6.28). Although T allele was not statistically significant among the controls, considering the genotypic analysis, the TT homozygous genotype showed a protector effect in relation to oral cavity cancer (OR = 0.37, 95% CI = 0.16-0.84). Some clinicopathological features were also analysed for genotype distribution, and no significant differences were observed: tumour size (P > 0.70), nodal status (P > 0.10) and tumour stage (P > 0.70). This is the first report of a study assessing the importance of T869C TGF-ß polymorphism in oral cancer. It is known that the TGF-ß T869C variation results in a Leu10Pro substitution in the signal peptide sequence. Our results suggested that the C allele could increase TGF-ß secretion which suppresses antitumour immune responses and may affect the OSCC risk.