Markers of mitochondrial energy metabolism and their potential relationships with fatigue in human adults: a scoping review

This scoping review aimed to synthesize the best available evidence of the associations between molecular and genetic markers of mitochondrial metabolism and fatigue in human adults. The research question guiding this review was, "Are there potential relationships between mitochondrial metabolism markers and fatigue?" The literature search used three terms (mitochondria; fatigue; energy metabolism), which yielded 263 manuscripts and 22 theses/dissertations. The studies included in the review had to meet three criteria: (1) Include adult participants (≥18 years of age); (2) Show a relationship between mitochondrial energy metabolism and fatigue; (3) Be published in English, Spanish, or Portuguese. Of the 17 articles included for a full-text review, some had a cross-sectional design (6/17, 35%), and more than half (12/17, 70%) were published between 2015 and 2020. The predominant population studied were patients diagnosed with chronic fatigue syndrome (9/17, 53%). Most studies (15/17, 88%) assessed fatigue with validated instruments. Mitochondrial markers associated with fatigue are a) mitochondrial transport pathways and respiratory chain, b) mutations in mitochondrial DNA, and c) energy disorders in cells of the immune system, such as natural killer cells. Mitochondrial metabolic activities, such as the production and transport of ATP, are significant components that may help understand the etiology of fatigue. Future directions should include longitudinal study designs, characterization of fatigue phenotypes, and the identification of markers involved in production and transport pathways. The clinical relevance in this field can lead to interventions targeting mitochondrial markers to reduce or prevent fatigue.

Polymorphisms of the GSTT1 and GSTM1 genes in polycystic ovary syndrome

SUMMARY BACKGROUND: This study aimed to investigate the deletion polymorphisms of the genes of the glutathione S-transferase family GSTT1 and GSTM1 in patients with Polycystic Ovarian Syndrome (PCOS), comparing them with a control population. METHODS: Blood was collected from 219 women (110 with PCOS and 109 controls) and genomic DNA was extracted. For the analysis of polymorphisms, the technique used was multiplex PCR. In the statistical analysis, the chi-square test and multiple logistic regression were used. RESULTS: There is no association between the GSTM1 null and GSTT1 null genotypes with PCOS when analyzed separately (P = 0.616 and P = 0.188). The analysis of the combined genotypes showed differences between the groups (P < 0.05), evidencing that the genotypic combination GSTT1 positive and GSTM1 negative is more frequent among patients. In the multivariate analysis, smoking was more frequent in the control group (OR = 0.22; 95% CI - 0.87-0.57; P = 0.002) while the presence of a family history of PCOS (OR = 2, 96; 95% CI - 1.54-5.68; P = 0.001) was more frequent in women with PCOS. CONCLUSIONS: In the studied sample, the deletion polymorphisms of the GSTT1 and GSTM1 genes isolated are not associated with PCOS, but in combination, they may be implicated in the etiology of the condition.

RESUMO OBJETIVO: Este estudo teve como objetivo investigar os polimorfismos de deleção dos genes da família glutationa S-transferase GSTT1 e GSTM1 em pacientes com síndrome dos ovários policísticos (SOP), comparando-as com uma população controle. MÉTODOS: Foi colhido sangue de 219 mulheres (110 com SOP e 109 controles) e extraído o DNA genômico. Para análise dos polimorfismos, a técnica empregada foi PCR multiplex. Na análise estatística foi utilizado o teste do qui-quadrado e regressão logística múltipla. RESULTADOS: Não há associação dos genótipos GSTM1 nulo e GSTT1 nulo com SOP quando analisados isoladamente (p=0,616 e p=0,188). A análise dos genótipos combinados mostrou diferenças entre os grupos (p<0,05), evidenciando que a combinação genotípica GSTT1 positivo e GSTM1 negativo é mais frequente entre as pacientes. Na análise multivariada, o hábito tabagista foi mais frequente no grupo controle (OR=0,22; IC 95% - 0,87-0,57; p=0,002), enquanto que a presença do histórico de SOP familiar (OR=2,96; IC 95% - 1,54-5,68; p=0,001) foi mais frequente nas mulheres com SOP. CONCLUSÕES: Na casuística estudada, os polimorfismos de deleção dos genes GSTT1 e GSTM1 isolados não estão associados a SOP, mas em combinação podem estar implicados na etiologia da condição.

Propriedades psicométricas da Genetic Counseling Outcome Scale (GCOS-24) para o idioma Português-Brasileiro / Psychometric properties of Genetic Counseling Outcome Scale (GCOS24) for Portuguese-Brazilian language

Medidas robustas de desfechos são necessárias para fornecer evidências, a fim de apoiar o desenvolvimento de serviços de aconselhamento genético (AG). O empoderamento do paciente tem sido identificado como um desfecho essencial no processo de aconselhamento genético e em uma medida de desfecho relatado pelo paciente (PROM- patient reported outcome measure), que foi desenvolvida para medir o empoderamento em serviços de genética: a Genetic Counselling Outcome Scale (GCOS-24). O objetivo desse estudo foi investigar as propriedades psicométricas da Genetic Counselling Outcome Scale (GCOS-24) para o português brasileiro. As propriedades psicométricas da GCOS-24, na língua portuguesa, foram avaliadas em uma amostra aleatória de 278 adultos, com idade entre 18 e 70 anos, atendidos em um ambulatório de genética clínica de um serviço de referência em genética, localizado em um hospital escola no interior do estado de São Paulo. A dimensionalidade e a estrutura fatorial foram avaliadas por meio da Análise Fatorial Exploratória (AFE) e da Análise Fatorial Confirmatória (AFC). A confiabilidade foi avaliada por dois indicadores: alfa de Cronbach e Omega do McDonald's. AFE e AFC demonstraram que a GCOS com 24 itens não apresentou um ajuste adequado do modelo, comprometendo sua validade. Além disso, os valores de confiabilidade de alfa de Cronbach 0,79 e de Ômega do McDonald's 0,78 estavam muito próximos da taxa mínima aceitável de 0,70. Como não foi encontrada solução para a estrutura original, decidimos realizar a retirada dos itens individualmente e realizamos as reanálises até que os indicadores do modelo fossem ajustados em um instrumento menor. Uma nova estrutura com 10 itens produziu um instrumento com duas dimensões: conhecimento e esperança, com melhor qualidade de ajuste do que a do instrumento original. Os valores do índice de confiabilidade Alfa e Ômega aumentaram para 0,85 e todos os escores foram melhores na GCOS com 10 itens do que no instrumento com 24 itens. Assim, a análise psicométrica mostrou evidências de validade do construto da GCOS, empoderamento, porém em sua versão mais curta. Desse modo, este estudo contribui para o processo de validação internacional da GCOS, com a meta final de utilizar esse instrumento como uma PROM, com o empoderamento como medida de desfecho, para avaliar e melhorar a qualidade do AG, em vários cenários de genética clínica

Robust outcome measures of outcomes are needed to provide evidence to support the development of genetic counseling services. Patient empowerment has been identified as an essential outcome in the genetic counseling process and in a patient reported outcome measure (PROM) that has been developed to measure empowerment in genetic services: the Genetic Counselling Outcome Scale (GCOS-24). The main goal of this study was to investigate the psychometric properties of Genetic Counselling Outcome Scale (GCOS-24) for the PortugueseBrazilian language. The psychometric properties of GCOS-24 were evaluated in a random sample of 278 Brazilian adults, aged between 18 and 70 years, attended at a genetics outpatient clinic of a referral service in genetics, located in a teaching hospital in the state of São Paulo. Dimensionality and factorial structure were evaluated through Exploratory Factor Analysis (AFE) and Confirmatory Factor Analysis (AFC). Reliability was assessed by two indicators: Cronbach's Alpha and McDonald's Omega. AFE and AFC demonstrated that the GCOS with 24 items did not present an adequate adjustment of the model, compromising its validity. In addition, Cronbach's alpha reliability values 0.79 and McDonald's Omega 0.78 were very close to the minimum acceptable rate of 0.70. As no solution was found for the original structure, we decided to proceed with the removal of the individual items and perform the reanalysis of the model until the model indicators were adjusted in a smaller instrument. A new structure with 10 items produced an instrument with two dimensions: knowledge and hope, with a better quality of fit than the original instrument. Alpha and Omega reliability index values increased to 0.85 and all scores were better in the GCOS with 10 items than in the 24 item instrument. Thus, the psychometric analysis showed evidence of GCOS construct validity, empowerment, however in its shorter version. This study contributes to the international validation process of the GCOS, with the ultimate goal of using this instrument as a PROM, with empowerment as an outcome measure, to assess and improve the quality of genetic counseling in various clinical genetics scenarios