RESUMO
OBJECTIVES: The aim of this study was to analyse the spatial patterns and factors associated with the incidence of tuberculosis-diabetes (TB-DM) in Brazil, from 2001 to 2019. STUDY DESIGN: Ecological study. METHODS: Brazilian municipalities were used as the units of analysis. The local empirical Bayesian rate and the spatial autocorrelation test were calculated. Moran and Getis-Ord Gi∗ were used to identify spatial clusters, and spatially weighted regression was conducted. RESULTS: In total, 75,021 new cases of TB associated with DM were reported in Brazil during the study period. Most Brazilian municipalities had an average TB-DM incidence of 1.0-2.0/100,000 inhabitants. The regression showed that the Gini index (ß = 0.85) and family health strategy coverage (ß = -0.26) were the two indicators that had the most influence on TB-DM incidence in Brazil. CONCLUSIONS: This study identified spatial clusters of TB-DM in Brazil. The results also indicated that social inequalities played a key role in the incidence of TB.
Assuntos
Diabetes Mellitus , Análise Espacial , Tuberculose , Humanos , Brasil/epidemiologia , Incidência , Tuberculose/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores Socioeconômicos , Teorema de Bayes , Fatores de Risco , Masculino , FemininoRESUMO
The emergence of infections caused by Acinetobacter baumannii, a multidrug-resistant bacterium, has been a concern worldwide. This bacterium is an important hospitalacquired pathogen that causes several diseases including ventilator-associated pneumonia, bloodstream infections, and meningitis. This study aimed to determine antibioticresistant mechanisms in the pathogenesis of A. baumannii and the alternative treatment strategies against it. The combined actions of outer membrane protein A, formation of a biofilm on biotic and abiotic surfaces, phospholipases C and D, metal homeostatic system, lipopolysaccharides, and verotoxins are relevant for virulence and pathogenesis. A. baumannii resists the broad-spectrum antibiotics by its mechanisms of resistance, such as ß-lactamases, efflux pump, aminoglycoside modifying enzymes, permeability changes, and alternation of targets. In an attempt to overcome the resistance mechanisms, plant-derived compounds and a combination of the antibiotics and the plant phytocompounds have been focused. Nanoparticles synthesised with the plant extract have been studied extensively. Furthermore, we projected modern methods, including multi-omics analysis, to study insight into mechanisms of actions of antibiotics. The information suggested that the potential antibiotic mechanisms of A. baumannii could lead to an alternative treatment against A. baumannii infections.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , beta-LactamasesRESUMO
The objective of this study was to analyse the dynamics of spatial dispersion of the coronavirus disease 2019 (COVID-19) in Brazil by correlating them to socioeconomic indicators. This is an ecological study of COVID-19 cases and deaths between 26 February and 31 July 2020. All Brazilian counties were used as units of analysis. The incidence, mortality, Bayesian incidence and mortality rates, global and local Moran indices were calculated. A geographic weighted regression analysis was conducted to assess the relationship between incidence and mortality due to COVID-19 and socioeconomic indicators (independent variables). There were confirmed 2 662 485 cases of COVID-19 reported in Brazil from February to July 2020 with higher rates of incidence in the north and northeast. The Moran global index of incidence rate (0.50, P = 0.01) and mortality (0.45 with P = 0.01) indicate a positive spatial autocorrelation with high standards in the north, northeast and in the largest urban centres between cities in the southeast region. In the same period, there were 92 475 deaths from COVID-19, with higher mortality rates in the northern states of Brazil, mainly Amazonas, Pará and Amapá. The results show that there is a geospatial correlation of COVID-19 in large urban centres and regions with the lowest human development index in the country. In the geographic weighted regression, it was possible to identify that the percentage of people living in residences with density higher than 2 per dormitory, the municipality human development index (MHDI) and the social vulnerability index were the indicators that most contributed to explaining incidence, social development index and the municipality human development index contributed the most to the mortality model. We hope that the findings will contribute to reorienting public health responses to combat COVID-19 in Brazil, the new epicentre of the disease in South America, as well as in other countries that have similar epidemiological and health characteristics to those in Brazil.
Assuntos
COVID-19/diagnóstico , Pandemias/estatística & dados numéricos , Teorema de Bayes , Brasil/epidemiologia , COVID-19/epidemiologia , Cidades/epidemiologia , Humanos , Incidência , Modelos Lineares , Pandemias/prevenção & controle , Fatores de Risco , Fatores Socioeconômicos , Análise EspacialRESUMO
This study aims to identify the risk factors associated with mortality and survival of COVID-19 cases in a state of the Brazilian Northeast. It is a historical cohort with a secondary database of 2070 people that presented flu-like symptoms, sought health assistance in the state and tested positive to COVID-19 until 14 April 2020, only moderate and severe cases were hospitalised. The main outcome was death as a binary variable (yes/no). It also investigated the main factors related to mortality and survival of the disease. Time since the beginning of symptoms until death/end of the survey (14 April 2020) was the time variable of this study. Mortality was analysed by robust Poisson regression, and survival by Kaplan-Meier and Cox regression. From the 2070 people that tested positive to COVID-19, 131 (6.3%) died and 1939 (93.7%) survived, the overall survival probability was 87.7% from the 24th day of infection. Mortality was enhanced by the variables: elderly (HR 3.6; 95% CI 2.3-5.8; P < 0.001), neurological diseases (HR 3.9; 95% CI 1.9-7.8; P < 0.001), pneumopathies (HR 2.6; 95% CI 1.4-4.7; P < 0.001) and cardiovascular diseases (HR 8.9; 95% CI 5.4-14.5; P < 0.001). In conclusion, mortality by COVID-19 in Ceará is similar to countries with a large number of cases of the disease, although deaths occur later. Elderly people and comorbidities presented a greater risk of death.
Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , COVID-19 , Doenças Cardiovasculares/complicações , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/complicações , Complicações do Diabetes/complicações , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Nefropatias/complicações , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Pandemias , Pneumonia Viral/complicações , Distribuição de Poisson , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Chagas disease (CD) is a neglected disease and endemic in Brazil. In the Brazilian Northeast Region, it affects millions of people. Therefore, it is necessary to identify the spatiotemporal trends of CD mortality in the Northeast of Brazil. This ecological study was designed, in which the unit of analysis was the municipality of the Brazilian northeast. The data source was the Information System of Mortality. It was calculated relative risk from socioeconomic characteristics. Mortality rates were smoothed by the Local Empirical Bayes method. Spatial dependency was analysed by the Global and Local Moran Index. Scan spatial statistics were also used. A total of 11 287 deaths by CD were notified in the study. An expressive parcel of this number was observed among 70-year-olds or more (n = 4381; 38.8%), no schooling (n = 4381; 38.8%), mixed-race (n = 4381; 62.3%), male (n = 6875; 60.9%). It was observed positive spatial autocorrelation, mostly in municipalities of the state of Bahia, Piauí (with high-high clusters), and Maranhão (with low-low clusters). The spatial scan statistics has presented a risk of mortality in 24 purely spatial clusters (P < 0.05). The study has identified the spatial pattern of CD mortality mostly in Bahia and Piauí, highlighting priority areas in planning and control strategies of the health services.
Assuntos
Doença de Chagas/mortalidade , Doenças Endêmicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Espaço-Temporal , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the length of CAG repeat expansions in ATXN3 shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA3/MJD carriers from distinct origins and developed population-specific models to predict AO. METHODS: This was a parametric survival modelling study. RESULTS: The European formula (EF) was tested in 739 independent SCA3/MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population-specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population-specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azorean patients. Hence, specific prediction models were required for each SCA3/MJD ethnic group. CONCLUSIONS: Our data strongly support the existence of as yet unknown factors that modulate AO in SCA3/MJD in a population-dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA3/MJD carriers from distinct geographical origins.
Assuntos
Idade de Início , Doença de Machado-Joseph/fisiopatologia , Adulto , Algoritmos , Povo Asiático , Brasil , Portador Sadio , Estudos de Coortes , Feminino , Humanos , Doença de Machado-Joseph/genética , Masculino , Pessoa de Meia-Idade , População , Portugal , Valor Preditivo dos Testes , Taiwan , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the pathogenesis of several neurodegenerative disorders, including Machado-Joseph disease (MJD), an autosomal dominant late-onset polyglutamine ataxia that results from an unstable expansion of a CAG tract in the ATXN3 gene. The size of the CAG tract only partially explains age at onset (AO), highlighting the existence of disease modifiers. Mitochondrial DNA (mtDNA) haplogroups have been associated with clinical presentation in other polyglutamine disorders, constituting potential modifiers of MJD phenotype. METHODS: A cross-sectional study, using 235 unrelated patients from Portugal, Brazil, India and Japan, was performed to investigate if mtDNA haplogroups contribute to AO of MJD. mtDNA haplogroups were obtained after sequencing the mtDNA hypervariable region I. Patients were classified in 15 phylogenetically related haplogroup clusters. RESULTS: The AO was significantly different among populations, implying the existence of other non-CAG factors, which seem to be population specific. In the Portuguese population, patients classified as belonging to haplogroup JT presented the earliest onset (estimated onset 34.6 years of age). Haplogroups W and X seem to have a protective effect, causing a delay in onset (estimated onset 47 years of age). No significant association between haplogroup clusters and AO was detected in the other populations or when all patients were pooled. Although haplogroup JT has already been implicated in other neurodegenerative disorders, no previous reports of an association between haplogroups W and X and disease were found. CONCLUSIONS: These findings suggest that haplogroups JT, W and X modify AO in MJD. Replication studies should be performed in European populations, where the frequency of the candidate modifiers is similar.
Assuntos
DNA Mitocondrial/genética , Haplótipos , Doença de Machado-Joseph/genética , Adulto , Idade de Início , Brasil , Estudos Transversais , Feminino , Humanos , Índia , Japão , Masculino , Pessoa de Meia-Idade , PortugalRESUMO
The present study aimed to evaluate the effects of ~45â¯nm nanoplastics (NPs) on the marine fish Dicentrarchus labrax after a short-term exposure. Animals were exposed to a concentration range of NPs for 96â¯h and liver, plasma and skin mucus were sampled. Assessed endpoints included biochemical biomarkers and expression of genes related to lipid metabolism, immune system and general cell stress. Abundance of mRNA transcripts related to lipid metabolism, pparα and pparγ, were significantly increased after exposure to NPs. Biochemical endpoints revealed decreased esterase activity levels in plasma, suggesting that the immune system of fish might be compromised by exposure to NPs. Moreover, significantly lower levels of alkaline phosphatase were found in the skin mucus of animals exposed to NPs. The present results suggest that NPs may represent a hazard to this marine fish, potentially interfering with the metabolism of lipids and the correct function of the immune response.
Assuntos
Bass/metabolismo , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Polimetil Metacrilato/farmacologia , Pele/efeitos dos fármacos , Estresse Fisiológico , Animais , Bass/genética , Bass/imunologia , Bass/fisiologia , Regulação da Expressão Gênica , Sistema Imunitário , Fígado/metabolismo , Polimetil Metacrilato/toxicidade , Pele/metabolismoRESUMO
BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 10 is a neurodegenerative disorder that is due to an expanded ATTCT repeat tract in the ATXN10 gene. Our aim was to describe clinical characteristics and intragenic haplotypes of patients with spinocerebellar ataxia type 10 from Brazil and Peru. METHODS: Expanded alleles were detected by repeat-primed polymerase chain reaction. Disease progression was measured by the Scale for the Assessment and Rating of Ataxia, and the Neurological Examination Score for Spinocerebellar Ataxias when possible. Haplotypes were constructed based on polymorphic markers within and outside the gene. RESULTS: Thirteen new families were diagnosed (three from Peru). Patients from three Brazilian families diagnosed previously were also reassessed. In total, 25 individuals (16 families) were evaluated. Mean (± SD) age at onset and disease duration were 34.8 ± 10.2 and 12 ± 8 years, respectively. Common findings were ataxia, dysarthria/dysphagia, nystagmus, pyramidal signs, ophthalmoparesis and seizures. No associations were found between clinical findings and geographical origins. Twelve patients living in remote regions were examined only once. In the remaining individuals, the Scale for the Assessment and Rating of Ataxia score, and Neurological Examination Score for Spinocerebellar Ataxias worsened by 0.444 (95% CI, -0.088 to 0.800) and 0.287 (95% CI, -0.061 to 0.635) points/year, respectively. A common haplotype, 19CGGC14, was found in 11/13 of Brazilian and in 1/3 of Peruvian families. CONCLUSIONS: The progression rate was slower than in other spinocerebellar ataxias. A consistently recurrent intragenic haplotype was found, suggesting a common ancestry for most, if not all, patients.
Assuntos
Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Adolescente , Adulto , Idade de Início , Alelos , Ataxina-10/genética , Brasil/epidemiologia , Criança , DNA/genética , Progressão da Doença , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Peru/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologia , Adulto JovemRESUMO
Fluorescent particles can be markers of bioaerosols and are therefore relevant to nosocomial infections. To date, little research has focused on fluorescent particles in occupied indoor environments, particularly hospitals. In this study, we aimed to determine the spatial and temporal variation of fluorescent particles in two large hospitals in Brisbane, Australia (one for adults and one for children). We used an Ultraviolet Aerodynamic Particle Sizer (UVAPS) to identify fluorescent particle sources, as well as their contribution to total particle concentrations. We found that the average concentrations of both fluorescent and non-fluorescent particles were higher in the adults' hospital (0.06×106 and 1.20×106 particles/m3 , respectively) than in the children's hospital (0.03×106 and 0.33×106 particles/m3 , respectively) (P<.01). However, the proportion of fluorescent particles was higher in the children's hospital. Based on the concentration results and using activity diaries, we were able to identify sources of particle production within the two hospitals. We demonstrated that particles can be easily generated by a variety of everyday activities, which are potential sources of exposure to pathogens. Future studies to further investigate their role in nosocomial infection are warranted.
Assuntos
Aerossóis/análise , Microbiologia do Ar , Poluição do Ar em Ambientes Fechados/análise , Infecção Hospitalar/transmissão , Fluorescência , Hospitais/classificação , Austrália , Monitoramento Ambiental , Fatores de TempoRESUMO
We aimed to present a systematic review on Huntington's disease (HD) in Latin America (LA). PubMed and LILACS were searched up to March 2015, reporting confirmed HD cases in LA. Case series, cross-sectional, case-control, and prospective studies were included. From 534 communications, 47 were eligible. Population-based studies were not found; minimal prevalence of 0.5-4/100,000 was estimated for Venezuela and Mexico. Geographical isolates were well characterized in Venezuela and in Peru. CAG repeats at HTT gene varied between 7-33 and 37-112 in normal and expanded alleles, respectively. Intermediate alleles were found in 4-10% of controls. Ages at onset and the expanded CAG repeats correlated with r from - 0.55 to -0.91. While haplotype patterns of Venezuelan and Brazilian chromosomes were similar to those observed in Europeans, haplotypes from Peruvian HD patients did not match the same pattern. The limited number of papers found suggests that HD is poorly diagnosed in LA. Minimal prevalence seemed to be halfway between those of Caucasians and Asians. Range of CAG repeats was similar to those of Europeans. Haplotype studies indicate that majority of HD patients might be of Caucasian descent; an Asian origin for some Peruvian patients was proposed.
Assuntos
Proteína Huntingtina/genética , Doença de Huntington/genética , Expansão das Repetições de Trinucleotídeos , Adolescente , Adulto , Idade de Início , Idoso , Povo Asiático/genética , Criança , Pré-Escolar , Haplótipos , Humanos , Doença de Huntington/epidemiologia , Doença de Huntington/etnologia , América Latina/etnologia , Pessoa de Meia-Idade , Prevalência , População Branca/genética , Adulto JovemRESUMO
Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta-CAGexp from parent-offspring pairs, and delta-CAGexp between siblings were obtained. One hundred and fifty-nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta-CAGexp among 115 direct parent-offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta-CAGexp between 269 siblings correlated with their delta-of-age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.
Assuntos
Ataxina-3/genética , Instabilidade Genômica , Padrões de Herança , Doença de Machado-Joseph/genética , Proteínas Repressoras/genética , Expansão das Repetições de Trinucleotídeos , Adolescente , Adulto , Fatores Etários , Idade de Início , Alelos , Doenças Assintomáticas , Segregação de Cromossomos , Feminino , Frequência do Gene , Heterozigoto , Humanos , Doença de Machado-Joseph/patologia , Masculino , Meiose , Linhagem , Índice de Gravidade de Doença , Fatores Sexuais , IrmãosRESUMO
The oral microbiome can alter the balance between health and disease, locally and systemically. Within the oral cavity, bacteria, archaea, fungi, protozoa, and viruses may all be found, each having a particular role, but strongly interacting with each other and with the host, in sickness or in health. A description on how colonization occurs and how the oral microbiome dynamically evolves throughout the host's life is given. In this chapter the authors also address oral and nonoral conditions in which oral microorganisms may play a role in the etiology and progression, presenting the up-to-date knowledge on oral dysbiosis as well as the known underlying pathophysiologic mechanisms involving oral microorganisms in each condition. In oral pathology, oral microorganisms are associated with several diseases, namely dental caries, periodontal diseases, endodontic infections, and also oral cancer. In systemic diseases, nonoral infections, adverse pregnancy outcomes, cardiovascular diseases, and diabetes are among the most prevalent pathologies linked with oral cavity microorganisms. The knowledge on how colonization occurs, how oral microbiome coevolves with the host, and how oral microorganisms interact with each other may be a key factor to understand diseases etiology and progression.
Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Doenças da Boca/microbiologia , Boca/microbiologia , Bactérias/classificação , Bactérias/genética , HumanosRESUMO
Exposure to lead may cause changes in the male reproductive system. We evaluated the effect of lead chloride (PbCl2) in vitro on semen quality from 31 individuals. Samples were incubated at room temperature for two exposure times (4 h and 8 h) and with two concentrations of PbCl2 (15 µg/ml or 30 µg/ml). Results showed that PbCl2 significantly inhibited rapid progressive motility and caused an increase in the percentage of tail anomalies in both times and concentrations assessed, as well as a decrease in vitality in the group exposed to 30 µg/ml PbCl2. A significant increase in immotile sperm was also observed between the group control and the groups submitted to lead. Total motility and DNA fragmentation also showed a significant decrease and increase, respectively, after 4 h of incubation in the group exposed to 30 µg/ml and in both groups after 8 h of incubation. In conclusion, PbCl2 affected sperm parameters and DNA integrity, which are essential for male fertility.
Assuntos
Fragmentação do DNA/efeitos dos fármacos , Chumbo/toxicidade , Espermatozoides/efeitos dos fármacos , Adulto , Animais , Membrana Celular/efeitos dos fármacos , Humanos , Masculino , Análise do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologiaRESUMO
AIM: To evaluate the frequent use of ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland) systems on shaping ability of root canal utilizing Solidworks (2014, Dassault Systemes) software. MATERIALS AND METHODS: Thirty-six root canals in clear resin blocks (Dentsply-Maillefer) were allocated into six experimental groups (n = 36). Six new sets of PTN instruments (Dentsply Maillefer, Ballaigues, Switzerland) were used six times to shape the resin blocks. A #15 K-file was inserted to the working length (WL), followed by ProGlider (PG) to create a glide path. Sequential use of PTN instrumentation in a crown-down technique was used to reach size (30/07) apically. Macroscopic photos of the blocks were taken before and after instrumentation, layered by Paint Shop Pro 9 from JascSoftware, and then canal transportation was measured using Solidwork 2014. The data were analyzed by SPSS software version 22. Multivariate statistical analysis general linear model (GLM) was also applied. Bonferroni correction test was used in multiple comparisons and the statistical significance was set to 0.05. RESULTS: There was no difference in canal transportation resulted from utilizing PTN files after six multiple uses; in addition, the PTN files showed ability to maintain the original canal anatomy, especially in the apical level, where lowest total mean value of canal center displacement was seen (3 mm level) (0.019 ± 0.017). CONCLUSION: ProTaper Next files can be used to prepare single and multiple canals in a single furcated tooth. CLINICAL SIGNIFICANCE: ProTaper Next nickel-titanium (NiTi) file system is a safe instrument that respects the canal shape, allows practitioners to treat difficult cases with good results, and low risk of separation.
Assuntos
Ligas Dentárias , Preparo de Canal Radicular , Cavidade Pulpar , Desenho de Equipamento , Humanos , Níquel , Titânio , Ápice DentárioRESUMO
The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.
Assuntos
Coreia/genética , Demência/genética , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Doença de Huntington/genética , Ataxias Espinocerebelares/genética , Adulto , Brasil , Coreia/diagnóstico , Coreia/epidemiologia , Coreia/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Demência/diagnóstico , Demência/epidemiologia , Demência/patologia , Feminino , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Transtornos Heredodegenerativos do Sistema Nervoso/epidemiologia , Transtornos Heredodegenerativos do Sistema Nervoso/patologia , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/epidemiologia , Doença de Huntington/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/patologia , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17ß-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development.
Assuntos
Disruptores Endócrinos/toxicidade , Ovário/efeitos dos fármacos , Truta , Poluentes Químicos da Água/toxicidade , Androstatrienos/toxicidade , Animais , Aromatase/genética , Inibidores da Aromatase/toxicidade , Estradiol/metabolismo , Feminino , Fungicidas Industriais/toxicidade , Expressão Gênica/efeitos dos fármacos , Imidazóis/toxicidade , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Ovário/metabolismo , Testosterona/metabolismo , Compostos de Trialquitina/toxicidade , Truta/genética , Truta/metabolismoRESUMO
This study aimed to evaluate urea excretion, nitrogen balance and microbial protein synthesis in lactating goats fed with diets containing different protein sources in the concentrate (soybean meal, cottonseed meal, aerial part of cassava hay and leucaena hay). Four Alpine goats whose mean body weight was 42.6±6.1 kg at the beginning of the experiment, a mean lactation period of 94.0±9.0 days and a production of 1.7±0.4 kg of milk were distributed in a 4×4 Latin square with four periods of 15 days. Diets were formulated to be isonitrogenous, containing 103.0 g/kg of CP, 400 g/kg of Tifton 85 hay and 600 g/kg of concentrate. Diet containing cottonseed meal provided (p<0.05) increased excretion of urea and urea nitrogen in the urine (g/d and mg/kg of BW) when compared with leucaena hay. The diets affected the concentrations of urea nitrogen in plasma (p<0.05) and excretion of urea nitrogen in milk, being that soybean meal and cottonseed meal showed (p<0.05) higher than the average aerial part of the cassava hay. The use of diets with cottonseed meal as protein source in the concentrate in feeding of lactating goats provides greater nitrogen excretion in urine and negative nitrogen balance, while the concentrate with leucaena hay as a source of protein, provides greater ruminal microbial protein synthesis.
RESUMO
The recent synthesis of a two-dimensional quasi-hexagonal-phase monolayer network of C60 molecules, known as qHPC60, holds significant promise for future semiconductor applications. However, the mechanism behind charge transport in these networks remains unknown. In this study, we developed a Holstein-Peierls Hamiltonian model to investigate charge transport in qHPC60, incorporating both local and non-local electron-phonon couplings. Our computational approach involved identifying suitable semi-empirical parameters to realize the formation of stable polarons in this material. The results unveiled the formation of stable large polarons as the primary carriers in the charge transport throughout qHPC60. To explore polaron transport properties, we conducted dynamic simulations within the picosecond time scale while subjecting the system to an external electric field. Our analysis emphasized the substantial influence of anisotropy on shaping mobile polarons, with an anisotropy coefficient of at least 50%. The polarons exhibited velocities within the acoustic regime ranging from 0.5-1.5 nm ps-1. While these velocities are comparable to those observed in high-end organic molecular crystals, they are considerably lower than those in graphene and conducting polymers. With qHPC60 possessing a semiconducting band gap of approximately 1.6 eV, our findings shed light on its potential application in flat electronics, overcoming the null-gap predicament of graphene.
RESUMO
BACKGROUND: The impact of prion proteins in the rules that dictate biological reproduction is still poorly understood. Likewise, the role of prnt gene, encoding the prion-like protein testis specific (Prt), in ram reproductive physiology remains largely unknown. In this study, we assessed the effect of Prt in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization medium incubated with spermatozoa and oocytes. Moreover, a computational model was constructed to infer how the results obtained could be related to a hypothetical role for Prt in sperm-zona pellucida (ZP) binding. METHODS: Mature ovine oocytes were transferred to fertilization medium alone (control) or supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated with ovine spermatozoa and after 18 h, presumptive zygotes (n=142) were fixed to evaluate fertilization rates or transferred (n=374) for embryo culture until D6-7. Predicted ovine Prt tertiary structure was compared with data obtained by circular dichroism spectroscopy (CD) and a protein-protein computational docking model was estimated for a hypothetical Prt/ZP interaction. RESULTS: The fertilizing rate was lower (P=0.006) in APPA group (46.0+/-6.79%) when compared to control (78.5+/-7.47%) and CSerum (64.5+/-6.65%) groups. In addition, the cleavage rate was higher (P<0.0001) in control (44.1+/-4.15%) than in APPA group (19.7+/-4.22%). Prt CD spectroscopy showed a 22% alpha-helical structure in 30% (m/v) aqueous trifluoroethanol (TFE) and 17% alpha in 0.6% (m/v) TFE. The predominant alpha-helical secondary structure detected correlates with the predicted three dimensional structure for ovine Prt, which was subsequently used to test Prt/ZP docking. Computational analyses predicted a favorable Prt-binding activity towards ZP domains. CONCLUSIONS: Our data indicates that the presence of APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover, the CD analysis data reinforces the predicted ovine Prt trend towards an alpha-helical structure. Predicted protein-protein docking suggests a possible interaction between Prt and ZP, thus supporting an important role for Prt in ovine fertilization.