Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
1.
BMC Med Ethics ; 25(1): 68, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858731

RESUMO

BACKGROUND: Q-CEP (Qualificação dos Comitês de Ética em Pesquisa que compõem o Sistema CEP/Conep) is a nationwide project resulting from a partnership between the Brazilian National Research Ethics Commission (Conep), the Ministry of Health and Hospital Moinhos de Vento (HMV). It was developed to consolidate policy for ethical review of research with human beings in all members of the CEP/Conep System, Brazil's national system of institutional review boards. The aim of this study was therefore to report on the experience and results of the Q-CEP project. METHODS: An observational, retrospective study includes data from the Q-CEP, obtained from visits to all the institutional research ethics committees (RECs) in the country. The actions implemented by Q-CEP were part of a two-step process: (i) training visits to each REC; (ii) development of distance learning modules on strategic topics pertaining to research ethics evaluation. The data presented herein cover step one (training visits), defined by Q-CEP as the diagnostic stage of the project. For a country with social and economics inequalities such as Brazil, this is a particularly important stage; an accurate picture of reality is needed to inform planning of quality improvement strategies. RESULTS: In 2019-2021, Q-CEP visited 832 RECs and trained 11,197 people. This sample covered almost all active RECs in the country; only 4 (0.5%) were not evaluated. Of the 94 items evaluated, 62% did not reach the target of at least 80% compliance and around 1/4 (26%) were below 50% compliance. The diagnostic stage of the process revealed inadequacies on the part of the RECs in their ethical reviews. The analysis of informed consent forms showed compliance in only 131 RECs (15.74%). The description of pending issues made by RECs in their reports was compliant in 19.33% (n = 161). Administrative and operational aspects were also considered inadequate by more than half of the RECs. CONCLUSIONS: Overall, Brazilian RECs showed poor compliance in several aspects of their operation, both in ethics evaluation and in other processes, which justifies additional training. The Q-CEP project is part of a quality improvement policy promoted by the Brazilian Ministry of Health. The data obtained in the diagnostic step of the project have contributed to the qualification and consolidation of one of the world's largest research ethics evaluation systems.


Assuntos
Pesquisa Biomédica , Comitês de Ética em Pesquisa , Ética em Pesquisa , Melhoria de Qualidade , Brasil , Humanos , Pesquisa Biomédica/ética , Estudos Retrospectivos
2.
Ann Hepatol ; 29(4): 101477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38360269

RESUMO

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.


Assuntos
Técnicas de Imagem por Elasticidade , Lipase , Cirrose Hepática , Proteínas de Membrana , Psoríase , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Lipase/genética , Proteínas de Membrana/genética , Estudos Transversais , Cirrose Hepática/genética , Psoríase/genética , Adulto , Idoso , Estudos Prospectivos , Fígado Gorduroso/genética , Prevalência , Predisposição Genética para Doença , Fatores de Risco , Síndrome Metabólica/genética , Síndrome Metabólica/complicações , Polimorfismo Genético , Genótipo , Aciltransferases , Fosfolipases A2 Independentes de Cálcio
3.
Liver Int ; 44(4): 1042-1050, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38293718

RESUMO

BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Cirrose Hepática/genética , Fibrose , Prognóstico , Hepatopatia Gordurosa não Alcoólica/genética , Genótipo , Proteínas de Membrana/genética
4.
G3 (Bethesda) ; 12(7)2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35511163

RESUMO

Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are the result of complex demographic history, such as 2 or 3-way admixing events, bottlenecks and/or expansions, and adaptive events unique to the American continent. To explore the impact of these events on the genetic structure of Latino populations, we evaluated the following haplotype features: linkage disequilibrium, shared identity by descent segments, runs of homozygosity, and extended haplotype homozygosity (integrated haplotype score) in Latinos represented in the 1000 Genome Project along with array data from 171 Brazilians sampled in the South and Southeast regions of Brazil. We found that linkage disequilibrium decay relates to the amount of American and African ancestry. The extent of identity by descent sharing positively correlates with historical effective population sizes, which we found to be steady or growing, except for Puerto Ricans and Colombians. Long runs of homozygosity, a particular instance of autozygosity, was only enriched in Peruvians and Native Americans. We used simulations to account for random sampling and linkage disequilibrium to filter positive selection indexes and found 244 unique markers under selection, 26 of which are common to 2 or more populations. Some markers exhibiting positive selection signals had estimated time to the most recent common ancestor consistent with human adaptation to the American continent. In conclusion, Latino populations present highly divergent haplotype characteristics that impact genetic architecture and underlie complex phenotypes.


Assuntos
Genética Populacional , Hispânico ou Latino , Brasil , Demografia , Haplótipos , Hispânico ou Latino/genética , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único
5.
Br J Nutr ; 125(3): 241-250, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32693844

RESUMO

Excess body weight confers a high risk to human health. Body weight variation between subjects can be partially explained by genetic differences. The aim of the present study was to investigate the association of genetic variants in the ADIPOQ (rs2241766) and LEP (rs7799039) genes with body weight trajectories in children from birth to 6 years of age. This was a prospective cohort (PREDI Study). Socio-economic, biological and anthropometric data were collected at four time points: at birth in the maternity unit; 1-2, 4-5 and 6 years old at the participants' homes. Genotyping was performed by PCR-restriction fragment length polymorphism. Poisson regression and linear mixed-effect regression models were used to address the association of ADIPOQ and LEP genotypes with BMI. Excessive body weight at pre-pregnancy (ß = 0·339, P = 0·01) and excessive gestational weight gain (ß = 0·51, P < 0·001) were associated with children's BMI trajectory from birth to 6 years. The ADIPOQ-rs2241766 TG or GG genotype was associated with a higher risk of excess body weight in the first 6 years of life (both sexes relative risk 1·25, 95 % CI 1·01, 1·56; female relative risk 1·67, 95 % CI 1·20, 2·31). BMI increased over the years according to the presence of the TG or GG genotype (ß = 0·01, 95 % CI 0·01, 0·02), particularly in females (ß = 0·02, 95 % CI 0·01, 0·04). The ADIPOQ-rs2241766 TG and GG genotypes increased the risk of excess body weight in children from birth to 6 years of age and had a positive effect on body weight trajectories in girls. The LEP-rs7799039 genetic variant was not associated with body weight trajectory in children.


Assuntos
Adiponectina/genética , Trajetória do Peso do Corpo , Variação Genética , Genótipo , Leptina/genética , Adulto , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Ganho de Peso na Gestação , Humanos , Lactente , Modelos Lineares , Masculino , Obesidade/genética , Distribuição de Poisson , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Gravidez
6.
Am J Infect Control ; 47(2): 180-185, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30253905

RESUMO

BACKGROUND: Grouping patients who acquired resistant microorganisms within a single area (cohorting) has been used to prevent cross-transmission. We aimed to assess cohorting effectiveness in the absence of an outbreak. METHODS: An interrupted time series study was performed in a general hospital considering patients admitted to wards. In the first year, patients who acquired multidrug-resistant (MDR) bacteria were isolated without physical transfer. In the second year, cohorting was implemented, and patients with mixed MDR bacteria were transferred to individual rooms in a specific isolation unit. Cultures were requested upon clinician orders, and surveillance or routine cultures were not performed. The effect of cohorting on the incidence density of MDR bacteria acquisition was assessed using segmented regression analysis. RESULTS: In the first and second years, 2.0 and 2.8 cases per 1,000 patient-days acquired MDR bacteria. The length of hospitalization and mortality rate were similar between phases. There was a linear increase of the monthly incidence densities of MDR bacteria acquisition in the first year (ß1: 0.11; 95% confidence interval [CI]: -0.02 to 0.24), though without an immediate impact of cohorting (ß2: -1.32; 95% CI: -3.81 to 1.16) or a change in the temporal trend (ß3: 0.04; 95% CI: -0.14 to 0.23) from the first to second phase. CONCLUSION: Cohorting may not reduce the incidence density of MDR bacteria acquisition in the absence of an outbreak.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Isolamento de Pacientes/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/microbiologia , Infecções Bacterianas/transmissão , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Feminino , Hospitais Gerais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Am J Hum Biol ; 30(5): e23164, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30129237

RESUMO

OBJECTIVE: The aim of this study was to examine the influence of the FTO-rs9939609 polymorphism on excess body weight in women during the reproductive transition from pre- to post-pregnancy. METHODS: This was a prospective cohort study covering a period extending from before pregnancy to 2 and 4 years after pregnancy. A total of 435 women were first included in the study and, at last follow-up, 220 of them continued to participate in the study. The FTO-rs9939609 polymorphism was analyzed by the polymerase chain reaction/ restriction fragment length polymorphism (PCR/RFLP) method. RESULTS: The FTO-rs9939609 polymorphism was associated with increasing weight and body mass index (BMI) during the follow-up period. Women carrying at least 1 risk allele (A) were significantly heavier (P < .05, up to 4.24 kg) and had a 1.30 kg/m2 higher BMI. Although the AA genotype was significantly associated with a greater risk compared to the wild-type genotype in the cross-sectional analysis, the results did not differ significantly in the longitudinal analysis (AA genotype, ß = 1.20, 95% CI 0.85-1.68), even after adjustment for pre-pregnancy age, smoking before pregnancy, parity at pregnancy, and gestational weight gain. CONCLUSIONS: The FTO-rs9939609 polymorphism was associated with increased weight and BMI in mothers before and after pregnancy. However, we found no significant effect of the polymorphism on excess body weight of women during the reproductive trajectory.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Aumento de Peso/genética , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Índice de Massa Corporal , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Sobrepeso/epidemiologia , Polimorfismo de Fragmento de Restrição , Gravidez , Prevalência , Estudos Prospectivos , Adulto Jovem
8.
Pathol Res Pract ; 213(9): 1067-1071, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28843749

RESUMO

AIM: Malignant melanoma is an aggressive disease and its incidence is increasing worldwide. Genetic predisposition and exposure to environmental factors, especially sunlight, are risk factors. Histopathologic distinction between nevi and melanomas can be difficult. It is anticipated that the evaluation of the immunohistochemical expression of some genes could contribute to the differential diagnosis of questionable histologically lesions. The objective of this study was to investigate wether the evaluation of the immunohistochemical expression of genes CADM1, TWIST1 and CDH1 (E-cadherin), that take part in mechanisms of cell adhesion and epithelial-mesenchymal transition, contributes to the differential diagnosis of melanocytic lesions difficult to diagnose. MATERIALS AND METHODS: Retrospective cross-sectional study based on immunohistochemistry analysis of samples of 30 dysplastic compound melanocytic nevi, 30 melanomas less than 1.0mm thick and 30 melanomas more than 1.0mm thick, diagnosed between 2013 and 2016. A score was used to evaluate color intensity and percentage of cells stained. RESULT: There were significant reductions in the expression of the genes CADM1 and CDH1 in melanomas (below and above 1.00mm of thickness) and in melanomas more than 1.0mm thick, respectively, compared to dysplastic compund melanocytic nevi. There was also lower expression of the genes CADM1 and CDH1 in melanomas greater than 1.0mm thick compared to melanomas less than 1.0mm. The gene TWIST1 showed no significant difference in expression between groups. CONCLUSION: These findings allow us to conclude that the immunohistochemical expression of CADM1 has the potential to contribute as an auxiliary tool to the differential diagnosis between nevi and melanomas.


Assuntos
Biomarcadores Tumorais/análise , Caderinas/biossíntese , Molécula 1 de Adesão Celular/biossíntese , Proteínas Nucleares/biossíntese , Proteína 1 Relacionada a Twist/biossíntese , Adulto , Idoso , Antígenos CD , Caderinas/análise , Molécula 1 de Adesão Celular/análise , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma , Pessoa de Meia-Idade , Nevo Pigmentado/diagnóstico , Proteínas Nucleares/análise , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Proteína 1 Relacionada a Twist/análise , Melanoma Maligno Cutâneo
9.
Photomed Laser Surg ; 35(1): 18-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27617768

RESUMO

OBJECTIVE AND BACKGROUND: The aim of this in vitro study was to compare the efficiency of a photodynamic therapy (PDT) technique employing rose bengal (RB) and methylene blue (MB) as photosensitizers (PSs) to reduce the viability of Enterococcus faecalis, a well-known pathogen found in root canal systems. Currently, in several clinical applications, including in the field of endodontics, MB is employed in association with a red laser source for the photoinactivation of pathogenic bacteria. METHODS: In this study, MB was used at 0.01% (31.2 mol/L) in association with a red (660 nm) laser as the excitation source in the MB group (MBG). Alternatively, the same test was performed with RB (25 mol/L) that was associated with a green (532 nm) light laser source in the RB group (RBG). A saline solution (0.9%) was used in the control group. The colony-forming units per milliliter (CFU/mL) were calculated after 24 h of incubation at 37°C, and the statistical analysis was performed using ANOVA. RESULTS: The results showed a significant reduction in the CFU/mL in the RBG group (0.12 × 108) compared with the control (2.82 × 108) and MBG groups (2.66 × 108). For the concentration and laser intensity employed in the experiments, the MBG group repeatedly showed no significant reduction in bacterial counts compared with the control. Therefore, the best result regarding the reduction of E. faecalis viable cells was obtained with RB as the PS. CONCLUSIONS: PDT may be improved if RB is used in association with a green light laser source for the inactivation of E. faecalis.


Assuntos
Enterococcus faecalis/efeitos dos fármacos , Azul de Metileno/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Rosa Bengala/farmacologia , Viabilidade Microbiana
10.
World J Gastroenterol ; 19(42): 7399-404, 2013 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-24259970

RESUMO

AIM: To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians. METHODS: A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients. RESULTS: SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07). CONCLUSION: The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.


Assuntos
Hepatite C Crônica/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antivirais/uso terapêutico , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Frequência do Gene , Predisposição Genética para Doença , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interferons , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Fenótipo , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
J Virol Methods ; 184(1-2): 93-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22664181

RESUMO

A sustained virological response is not achieved by a significant proportion of chronic hepatitis C patients treated with interferon-based regimens. Due to the associated side effects and high costs, therapy response markers have been thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and rs8099917, which are located upstream from the IL28B gene, have been remarkably described to have a strong association with treatment efficacy. The aim of this study was to develop a straightforward method for genotyping such polymorphisms. A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons was established for SNPs genotyping. Online computation resources were employed for retrieving reference sequences, such as the selection of oligonucleotides and restriction enzymes. Two pairs of primers were designed and validated for the amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp) with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were selected and used for allelic discrimination related to rs12979860 (C/T) and rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for all possible genotypes in 75 blood samples. In addition, the results were validated by sequencing. The method constitutes a simple and reliable assay, which may be readily available for genotyping of rs12979860 and rs8099917 in laboratories that support hepatitis C treatment centers.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferons/administração & dosagem , Interleucinas/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Primers do DNA/genética , Genótipo , Humanos , Prognóstico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...