Functional brain connectivity in children with focal epilepsy: A systematic review of functional MRI studies.

Epilepsy is increasingly recognised as a brain network disorder and many studies have investigated functional connectivity (FC) in children with epilepsy using functional MRI (fMRI). This systematic review of fMRI studies, published up to November 2023, investigated profiles of FC changes and their clinical relevance in children with focal epilepsy compared to healthy controls. A literature search in PubMed and Web of Science yielded 62 articles. We categorised the results into three groups: 1) differences in correlation-based FC between patients and controls; 2) differences in other FC measures between patients and controls; and 3) associations between FC and disease variables (for example, age of onset), cognitive and seizure outcomes. Studies revealed either increased or decreased FC across multiple brain regions in children with focal epilepsy. However, findings lacked consistency: conflicting FC alterations (decreased and increased FC) co-existed within or between brain regions across all focal epilepsy groups. The studies demonstrated overall that 1) interhemispheric connections often displayed abnormal connectivity and 2) connectivity within and between canonical functional networks was decreased, particularly for the default mode network. Focal epilepsy disrupted FC in children both locally (e.g., seizure-onset zones, or within-brain subnetworks) and globally (e.g., whole-brain network architecture). The wide variety of FC study methodologies limits clinical application of the results. Future research should employ longitudinal designs to understand the evolution of brain networks during the disease course and explore the potential of FC biomarkers for predicting cognitive and postsurgical seizure outcomes.

Impact of age and gender differences in the prevalence and patterns of multimorbidity in the Thai Cohort Study.

BACKGROUND: The study aims to identify the common patterns of multimorbidity and their distribution by age and gender. METHOD: This cross-sectional study collected self-reported data from 42 785 Thai Cohort Study members through mailed questionnaires. Employing prevalence-based analysis, it identified common multimorbidity (coexistence of two or more chronic conditions) patterns, analysing the three most common patterns stratified by age and sex. P for trend (p-trend) was used to test the linear trend for associations between age and prevalence of these chronic conditions in the multimorbidity patterns. RESULTS: Chronic conditions with the highest prevalence were related to metabolic syndromes: obesity (28.5%), hyperlipidaemia (13.2%) and hypertension (7.2%). A positive linear age-multimorbidity association was observed (p-trend = 0.0111). The 60+ participants averaged 1.20 diseases, with 33.7% multimorbidity prevalence. Hyperlipidaemia + obesity was most prevalent in the under-40 multimorbid group (38.7%). Men exhibited a higher prevalence of multimorbidity and associated patterns involving hypertension, hyperlipidaemia and obesity than women. CONCLUSION: Metabolic syndrome components were the prominent factors driving multimorbidity. Significant age and gender differences were also revealed in multimorbidity prevalence. People aged 60+ faced high risk of multimorbidity, while younger individuals tended towards the multimorbidity pattern of obesity and hyperlipidaemia. Men were more susceptible to multimorbidity patterns associated with metabolic syndromes. Future studies for metabolic-related multimorbidity should consider these differences, addressing age and gender issues.

The Impact of Multimorbidity on All-Cause Mortality: A Longitudinal Study of 87,151 Thai Adults.

Objectives: To investigate associations between multimorbidity, socio-demographic and health behaviour factors, and their interactions (multimorbidity and these factors) with all-cause mortality among Thai adults. Methods: Associations between multimorbidity (coexistence of two + chronic diseases) and mortality between 2005 and 2019 were investigated among Thai Cohort Study (TCS) participants (n = 87,151). Kaplan-Meier survival curves estimated and compared survival times. Multivariate Cox proportional hazards models examined associations between risk factors, and interactions between multimorbidity, these factors, and survival. Results: 1,958 cohort members died between 2005 and 2019. The risk of death was 43% higher for multimorbid people. In multivariate Cox proportional hazard models, multimorbidity/number of chronic conditions, age, long sleep duration, smoking and drinking were all independent factors that increased mortality risk. Women, urbanizers, university education, over 20,000-baht personal monthly income and soybean products consumption lowered risk. The interactions between multimorbidity and these variables (except for female, urbanizers and soybeans intake) also had significant (p < 0.05) impact on all-cause mortality. Conclusion: The results emphasise the importance of healthy lifestyle and reduced intake of alcohol and tobacco, in reducing premature mortality, especially when suffering from multimorbidity.

The association between educational level and multimorbidity among adults in Southeast Asia: A systematic review.

BACKGROUND: In Southeast Asia, the prevalence of multimorbidity is gradually increasing. This paper aimed to investigate the association between educational level and multimorbidity among over 15-years old adults in Southeast Asia. METHODS: We conducted a systematic review of published observational studies. Studies were selected according to eligibility criteria of addressing definition and prevalence of multimorbidity and associations between level of education and multimorbidity in Southeast Asia. The Newcastle-Ottawa Scale (NOS) was used to measure the quality and risk of bias. The methodology has been published in PROSPERO with registered number ID: CRD42021259311. RESULTS: Eighteen studies were included in the data synthesis. The results are presented using narrative synthesis due to the heterogeneity of differences in exposures, outcomes, and methodology. The prevalence of multimorbidity ranged from 1.7% to 72.6% among over 18 years-old adults and from 1.5% to 51.5% among older people (≥ 60 years). There were three association patterns linking between multimorbidity and education in these studies: (1) higher education reducing odds of multimorbidity, (2) higher education increasing odds of multimorbidity and (3) education having no association with multimorbidity. The association between educational attainment and multimorbidity also varies widely across countries. In Singapore, three cross-sectional studies showed that education had no association with multimorbidity among adults. However, in Indonesia, four cross-sectional studies found higher educated persons to have higher odds of multimorbidity among over 40-years-old persons. CONCLUSIONS: Published studies have shown inconsistent associations between education and multimorbidity because of different national contexts and the lack of relevant research in the region concerned. Enhancing objective data collection such as physical examinations would be necessary for studies of the connection between multimorbidity and education. It can be hypothesised that more empirical research would reveal that a sound educational system can help people prevent multimorbidity.

Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin.

BACKGROUND: Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated. METHODS: To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O + S), or vehicle (control) for 5 weeks. RESULTS: Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O + S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O + S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O + B. CONCLUSIONS: Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.

Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα-SREBP Pathway in 3T3-L1 Cells.

The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1), fatty acid synthase (FAS), peroxisome proliferator activated receptor-γ (PPARγ), SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα), which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1%) compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication.