Pathophysiology and Treatment of Lipid Abnormalities in Cerebrotendinous Xanthomatosis: An Integrative Review.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.

Effect of subgingival periodontal therapy on glycaemic control in type 2 diabetes patients: Meta-analysis and meta-regression of 6-month follow-up randomized clinical trials.

BACKGROUND: Periodontitis worsens the hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). Subgingival instrumentation, with or without surgical access, is the gold-standard treatment for periodontitis. The aim was to summarize the evidence on the effect of subgingival instrumentation (with or without open flap) on the reduction of glycosylated haemoglobin (HbA1c). METHODS: Nine electronic databases were searched up to 15 February 2023. Twelve randomized controlled trials with at least 6 months of follow-up were included. Studies using systemic or local-delivery antimicrobial therapies were excluded. Meta-analyses were performed using the random-effects model. The sources of heterogeneity were assessed by applying linear meta-regression. Risk of bias was assessed by RoB 2, and certainty of evidence by GRADE. RESULTS: Eleven studies were included in the quantitative analyses (1374 patients). Subgingival instrumentation resulted in 0.29% lower HbA1c (95% confidence interval: 0.10-0.47; p = .03) compared with non-active treatment. DISCUSSION: None of the 12 studies were assessed as having low risk of bias. The percentage of females and the time of diabetes diagnosis significantly explained the high level of heterogeneity. Subgingival periodontal therapy results in a significant and clinically relevant improvement in glycaemic control over 6 months in patients with T2DM and periodontitis. The grade of evidence was moderate.

Identifying congenital generalized lipodystrophy using deep learning-DEEPLIPO.

Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease characterized by near complete absence of functional adipose tissue from birth. CGL diagnosis can be based on clinical data including acromegaloid features, acanthosis nigricans, reduction of total body fat, muscular hypertrophy, and protrusion of the umbilical scar. The identification and knowledge of CGL by the health care professionals is crucial once it is associated with severe and precocious cardiometabolic complications and poor outcome. Image processing by deep learning algorithms have been implemented in medicine and the application into routine clinical practice is feasible. Therefore, the aim of this study was to identify congenital generalized lipodystrophy phenotype using deep learning. A deep learning approach model using convolutional neural network was presented as a detailed experiment with evaluation steps undertaken to test the effectiveness. These experiments were based on CGL patient's photography database. The dataset consists of two main categories (training and testing) and three subcategories containing photos of patients with CGL, individuals with malnutrition and eutrophic individuals with athletic build. A total of 337 images of individuals of different ages, children and adults were carefully chosen from internet open access database and photographic records of stored images of medical records of a reference center for inherited lipodystrophies. For validation, the dataset was partitioned into four parts, keeping the same proportion of the three subcategories in each part. The fourfold cross-validation technique was applied, using 75% (3 parts) of the data as training and 25% (1 part) as a test. Following the technique, four tests were performed, changing the parts that were used as training and testing until each part was used exactly once as validation data. As a result, a mean accuracy, sensitivity, and specificity were obtained with values of [90.85 ± 2.20%], [90.63 ± 3.53%] and [91.41 ± 1.10%], respectively. In conclusion, this study presented for the first time a deep learning model able to identify congenital generalized lipodystrophy phenotype with excellent accuracy, sensitivity and specificity, possibly being a strategic tool for detecting this disease.

Evaluation of the anti-diabetic drug sitagliptin as a novel attenuate to SARS-CoV-2 evidence-based in silico: molecular docking and molecular dynamics.

The current outbreak of COVID-19 cases worldwide has been responsible for a significant number of deaths, especially in hospitalized patients suffering from comorbidities, such as obesity, diabetes, hypertension. The disease not only has prompted an interest in the pathophysiology, but also it has propelled a massive race to find new anti-SARS-CoV-2 drugs. In this scenario, known drugs commonly used to treat other diseases have been suggested as alternative or complementary therapeutics. Herein we propose the use of sitagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP4) used to treat type-II diabetes, as an agent to block and inhibit the activity of two proteases, 3CLpro and PLpro, related to the processing of SARS-CoV-2 structural proteins. Inhibition of these proteases may possibly reduce the viral load and infection on the host by hampering the synthesis of new viruses, thus promoting a better outcome. In silico assays consisting in the modeling of the ligand sitagliptin and evaluation of its capacity to interact with 3CLpro and PLpro through the prediction of the ligand bioactivity, molecular docking, overlapping of crystal structures, and molecular dynamic simulations were conducted. The experiments indicate that sitagliptin can interact and bind to both targets. However, this interaction seems to be stronger and more stable to 3CLpro (ΔG = -7.8 kcal mol-1), when compared to PLpro (ΔG = -7.5 kcal mol-1). This study suggests that sitagliptin may be suitable to treat COVID-19 patients, beyond its common use as an anti-diabetic medication. In vivo studies may further support this hypothesis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03406-w.

Qualidade da dieta e risco cardiometabólico em crianças e adolescentes com excesso de peso / Diet quality and cardiometabolic risk in children and adolescents with excess weight / Calidad de la dieta y el riesgo cardiometabolico de niños y adolescentes con exceso de peso

Objetivo: Avaliar a qualidade da dieta de crianças e adolescentes com excesso de peso e determinar a relação com fatores de risco cardiometabólico. Métodos: Estudo quantitativo, transversal e analítico, realizado entre dezembro de 2016 e agosto de 2018, com crianças e adolescentes. Coletaram-se variáveis comportamentais (prática de atividade física e tempo de tela), antropométricas (peso, altura, índice de massa corporal, circunferência abdominal e do pescoço) e dietéticas (recordatório de 24 horas) e os dados bioquímicos foram consultados nos prontuários. Avaliou-se a resistência à insulina (RI), usando Homeostasis Model Assessment ­ Insulin Resistance (HOMA-IR), e a qualidade da dieta, por meio do Índice de Qualidade da Dieta Revisado (IQD-R). Análises realizadas pelos testes de Spearman e Mann-Whitney U, com nível de significância de 5%. Resultados: A amostra incluiu 100 crianças e adolescentes, sendo 71 (71%) do sexo feminino, média de idade de 9,42 ± 2,89 anos. IQD-R apresentou valor médio de 61,16 (IC 95%: 59,14 ­ 63,19) e nenhum participante apresentou dieta de boa qualidade. Não foram encontradas associações entre o escore do IQD-R e marcadores cardiometabólicos. Observaram-se associações negativas entre os componentes "vegetais totais e leguminosas" e HOMA-IR (r= -0,290), "vegetais verde-escuros, alaranjados e leguminosas" e HOMA-IR (r= -0,333) e "vegetais verde-escuros, alaranjados e leguminosas" com insulina de jejum (r= -0,291). Participantes com mais de três fatores de risco cardiometabólico tiveram pontuação significativamente maior do componente "gordura sólida e açúcar de adição". Conclusão: Nenhum participante investigado apresentou dieta qualitativamente adequada. A baixa ingestão de vegetais e leguminosas foi associada com marcadores de RI. Descritores: Promoção da Saúde, Obesidade Pediátrica; Consumo de Alimentos; Resistência à Insulina; Doenças Cardiovasculares.

Objective: To assess the quality of the diet of children and adolescents with excess weight and determine its relationship with cardiometabolic risk factors. Methods: This quantitative descriptive cross-sectional study was carried out from December 2016 to August 2018 with children and adolescents. Behavioral (regular physical activity, screen time), anthropometric (weight, height, Body Mass Index, abdominal circumference, neck circumferences) and dietary (24-hour recalls) data were collected, and biochemical data were retrieved from medical records. Insulin resistance (IR) was measured using the Homeostasis Model Assessment ­ Insulin Resistance (HOMA-IR) and diet quality was assessed using the Revised Diet Quality Index (Índice de Qualidade da Dieta Revisado ­ IQD-R). Analyses using Spearman's and Mann-Whitney U tests were performed with a significance threshold set at 5%. Results: The sample consisted of 100 children and adolescents, 71 (71%) of whom were girls, and the mean age was 9.42±2.89 years. The mean IQD-R was 61.16 (95%CI: 59.14 ­ 63.19) and none of the participants presented a good quality diet. No associations were found between the IQD-R score and cardiometabolic markers. However, negative associations were observed between "total vegetables and legumes" and HOMA-IR (r=-0.290), "dark green and orange vegetables and legumes" and HOMA-IR (r=-0.333) and "dark green and orange vegetables and legumes" and fasting insulin (r=-0.291). The participants who presented more than three cardiometabolic risk factors had a significantly higher score on the "solid fat and added sugar" component. Conclusion: None of the participants had a qualitatively adequate diet. The low intake of vegetables and legumes was associated with IR markers. Descriptors: Health Promotion, Pediatric Obesity; Food Intake; Insulin Resistance; Cardiovascular Diseases.

Objetivo: Evaluar la calidad de la dieta de niños y adolescentes con exceso de peso y determinar la relación con los factores de riesgo cardiometabolico. Métodos: Estudio cuantitativo, transversal y analítico realizado entre diciembre de 2016 y agosto de 2018 con niños y adolescentes. Se recogieron las variables de conducta (práctica de actividad física y tiempo de pantalla), antropométricas (peso, altura, índice de masa corporal, circunferencia abdominal y del cuello) y dietéticas (recordatorio de 24 horas) y los datos bioquímicos han sido consultados de los historiales clínicos. Se evaluó la resistencia a la insulina (RI) usando el Homeostasis Model Assessment ­ Insulin Resistance (HOMA-IR) y la calidad de la dieta a través del Índice de Calidad de la Dieta Revisado (ICD-R). Los análisis han sido realizados por las pruebas de Spearman y Mann-Whitney U con el nivel de significancia del 5%. Resultados: La muestra ha sido de 100 niños y adolescentes de los cuales 71 (71%) era del sexo femenino con la media de edad de 9,42 ± 2,89 años. El ICD-R presentó el valor medio de 61,16 (IC 95%: 59,14 - 63,19) y ningún participante presentó dieta de buena calidad. No se ha encontrado asociaciones entre la puntuación del ICD-R y los marcadores cardiometabolicos. Se ha observado asociaciones negativas entre los componentes "vegetales totales y leguminosas" y el HOMA-IR (r= -0,290), "vegetales verde-oscuros, anaranjados y leguminosas" y el HOMA-IR (r= -0,333) y "vegetales verde-oscuros, anaranjados y leguminosas" y la insulina de ayuno (r= - 0,291). Los participantes con más de tres factores de riesgo cardiometabolico tuvieron la puntuación significativamente mayor en el componente "grasa sólida y azúcar de adición". Conclusión: Ningún participante investigado presentó la dieta cualitativamente adecuada. La baja ingesta de vegetales y leguminosas se ha asociado con los marcadores de RI Descriptores: Promoción de la Salud, Obesidad Pediátrica; Consumo de Alimentos; Resistencia a la Insulina; Enfermedades Cardiovasculares.

Comparação antropométrica e do perfil glicêmico de idosos diabéticos praticantes de atividade física regular e não praticantes / Anthropometric comparison and the glycemic profile in ederly diabetics practitioners and non-practitioners of regular physical activity

O objetivo do estudo foi comparar os parâmetros antropométricos e perfil glicêmico de idosos diabéticos tipo 2 praticantes de atividade física regular e não praticantes. Métodos: O estudo, do tipo transversal, envolveu 70 idosos com diabetes mellitus tipo 2, com idade entre 60 e 80 anos. A coleta de dados foi através de questionário estruturado abordando: a) características demográficas dos pacientes (idade e nível de escolaridade) e b) características do padrão de atividade física (frequência, duração (min) e tempo (meses) da prática de exercícios físicos). Foram realizadas medidas antropométricas e verificação do perfil glicêmico (glico-hemoglobina). Os dados foram analisados no programa STATA versão 9.0. Foram calculados a média e desvio padrão da média (DP) e realizado o teste de análise de variância (ANOVA). Para verificar a associação de variáveis qualitativas, utilizou-se o teste exato de Fisher e as associações entre as variáveis quantitativas foram estimadas através do coeficiente de correlação de Pearson, com uma confiança de 95%. O nível de significância foi de p<0,05. Resultados: Em relação ao nível de escolaridade, não houve influência na realização da prática de atividade física. Nos PAF observa-se uma diminuição do IMC e do perfil glicêmico, quando comparados aos NPAF. A caminhada foi a atividade física mais realizada pelos idosos (51,5%). A partir dos resultados obtidos na análise dos dados, foi possível mostrar os benefícios que a atividade física proporciona aos indivíduos no processo de envelhecimento e no bom controle glicêmico.

Capacidade funcional e atividade física de idosos com diabetes tipo 2 / Functional capacity and physical activity among elderly with type 2 diabetic

Os objetivos do estudo foram: a) avaliar a capacidade funcional de idosos diabéticos tipo 2 comparando-os com idosos não diabéticos e b) comparar o nível da capacidade funcional com a prática de atividade física. A amostra foi constituída por 114 idosos, sendo 70 diabéticos, com média de idade de 67,67 ± 5,3 anos e 44 não-diabéticos, com média de idade de 72,84 ± 6,2 anos. O estudo foi baseado em informações obtidas a partir de entrevista direta nas quais os idosos foram avaliados quanto à capacidade funcional através de aplicação da escala de atividades da vida diária (AVDs) proposta por Matsudo (2000). Os dados foram analisados pelo Teste Qui-quadrado com p<0,05. Na realização das atividades da vida diária (AVDs), 45,7% (n=32) dos idosos diabéticos e 54,5% (n=24) dos idosos não diabéticos informaram realizar facilmente e sem ajuda a tarefa subir e descer escadas, na tarefa lavar e passar roupas, 62,8% (n=44) dos idosos diabéticos e 72,7% (n=32) dos não diabéticos relataram realizar facilmente e sem ajuda. Não houve diferença significativa entre o nível de capacidade funcional e a prática de atividade física dos idosos diabéticos comparados com os não diabéticos (X2=1,59). Conclui-se que os idosos diabéticos e não diabéticos eram independentes nas realizações das AVDs e AIVDs, aqueles que realizavam atividade física apresentaram um nível de capacidade funcional melhor. É fundamental a implementação de programas sociais e de atividades físicas para melhorar a qualidade de vida dessa população.

The objectives of the study were: a) to evaluate the functional capacity of elderly type 2 diabetic, comparing them with non diabetic elderly and b) compare the level of functional capacity with practice of physical activity. The sample consisted of 114s elderly, 70 diabetic, with mean age of 67.67 ± 5.3 years old and 44 non-diabetics, with mean age of 72.84 ± 6.2 years old. This study was based on information obtained from direct interview in which the elderly were evaluated as to the functional capacity through application of the scale of activities of daily living (AVDs), by Matsudo (2000). The data were analyzed using the Qui-square test with p<0.05. In carrying out activities of daily living (AVDs), 45.7% (n=32) of elderly diabetic and 54.5% (n=24) non-diabetic elderly easily make informed and without help the task up and down stairs, and task wash and clothes, 62.8% (n=44) of elderly diabetic and 72.7% (n=32) non-diabetic elderly easily make informed. There was no significant difference between the level of functional capacity and physical activity of elderly diabetic compared with non-diabetic (X2=1.59). It was concluded that the elderly diabetics were independent of the achievements AVD and AIVDs, those who performed physical activity showed a level of functional capacity better. It is essential to implementation of social programs and physical activities to improve the quality of life of the population.