Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression

Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves as a risk factor for multiple neurodevelopmental disorders including autism spectrum disorders and schizophrenia. Although alterations in the cortex and hippocampus of MIA offspring have been described, less evidence exists on the impact on the cerebellum. Here, we report altered expression of cytokines and chemokines in the cerebellum of MIA offspring, including increase in the neuroinflammatory cytokine TNFα and its receptor TNFR1. We also report reduced expression of the synaptic organizing proteins cerebellin-1 and GluRδ2. These synaptic protein alterations are associated with a deficit in the ability of cerebellar neurons to form synapses and an increased number of dendritic spines that are not in contact with a presynaptic terminal. These impairments are likely contributing to the behavioral deficits in the MIA exposed offspring

Maternal Immune Activation Causes Behavioral Impairments and Altered Cerebellar Cytokine and Synaptic Protein Expression

Emerging epidemiology studies indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as viral or bacterial infections during pregnancy serves as a risk factor for multiple neurodevelopmental disorders including autism spectrum disorders and schizophrenia. Although alterations in the cortex and hippocampus of MIA offspring have been described, less evidence exists on the impact on the cerebellum. Here, we report altered expression of cytokines and chemokines in the cerebellum of MIA offspring, including increase in the neuroinflammatory cytokine TNFα and its receptor TNFR1. We also report reduced expression of the synaptic organizing proteins cerebellin-1 and GluRδ2. These synaptic protein alterations are associated with a deficit in the ability of cerebellar neurons to form synapses and an increased number of dendritic spines that are not in contact with a presynaptic terminal. These impairments are likely contributing to the behavioral deficits in the MIA exposed offspring

Potential role of fibrosis-4 score in hepatocellular carcinoma screening:The Kangbuk Samsung Health Study

Aim: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD.Methods: Korean adults (n=340,825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods.Results: In 93 HCC cases, 71 were identified in G4, while 20 cases (21.5%) in G2 and G3 combined where ultrasound and fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, fibrosis-4 and ultrasound had the highest AUROC (0.93 [0.87–0.99]), whereas in G3, the combined screening methods had the highest AUROC (0.98 [0.95–1.00]). The positive predictive value was lower in G2 and G3 than in G4 but was &gt;5% when restricted to a high fibrosis-4 score.Conclusions: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the fibrosis-4 score in identifying individuals at high risk of HCC. KEYWORDS: alpha-fetoprotein, fatty liver disease, fibrosis-4, hepatocellular carcinoma, liver ultrasound<br/

The Effect of Depression on Serum VEGF Level in Alzheimer’s Disease

Objective. Growing evidence suggests that angiogenesis might represent a new pathogenic mechanism involved in the progression of Alzheimer’s disease (AD). Among angiogenic cytokines, vascular endothelial growth factor (VEGF) levels in AD patients have been evaluated, but the results are controversial among studies. We investigated serum levels of VEGF in AD patients with depression, AD patients without depression, and the controls, respectively. The aim of this study is to elucidate the relationship between VEGF, depression, and cognitive impairment in AD. Methods. The CDR (Clinical Dementia Rating), MMSE-KC (the Mini-Mental Status Examination-Korean version), and SGDS-K (the Korean version of the Geriatric Depression Scale-Short Form) were measured in the subjects. Serum VEGF levels were measured in 24 AD patients with depression, 25 AD patients without depression, and 26 controls, using an enzyme-linked immunosorbent assay kit. Results. Serum VEGF levels in AD patients with depression were significantly higher than AD patients without depression or the control. A correlation was observed between VEGF and scores on SGDS-K, but no correlation was detected between VEGF and MMSE-KC scores. Conclusion. Serum VEGF levels in AD patients with depression were higher than those without depression. Depression might be associated with changes in serum levels of VEGF in AD patients

Potential role of fibrosis-4 score in hepatocellular carcinoma screening: the Kangbuk Samsung Health Study

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Prediabetes diagnosis is associated with the progression of coronary artery calcification: the Kangbuk Samsung Health Study

Aims: the implications of prediabetes diagnosed by isolated glucose versus glycated hemoglobin (HbA1c) on subclinical atherosclerosis are uncertain. We investigated associations between prediabetes defined by different diagnostic criteria and coronary artery calcification (CAC) and its progression over time.Materials and methods: the cross-sectional study included 146,436 Korean adults without diabetes who underwent CAC estimation computed tomography (CT) during health examinations between 2011 and 2019. We used multinomial logistic regression models. The longitudinal study comprised 41,100 participants with at least one follow-up cardiac CT and annual CAC progression rates and ratios were estimated. Prediabetes was categorized into 3 groups: isolated glucose prediabetes (fasting blood glucose (FBG) 100–125 mg/dl, HbA1c &lt; 5.7%); isolated HbA1c prediabetes (FBG &lt; 100 mg/dl, HbA1c 5.7–6.4%), and prediabetes meeting both FBG and HbA1c criteria (FBG 100–125 mg/dl, HbA1c 5.7%–6.4%).Results: after adjusting for covariates, the prevalence ratios (95% CI) for CAC score&gt; 100 comparing isolated glucose prediabetes, isolated HbA1c prediabetes, and prediabetes fulfilling both criteria to those of normoglycemia were 1.12 (0.99–1.26), 1.24 (1.11–1.39), and 1.31 (1.18–1.45), respectively. The multivariable-adjusted ratio (CIs) of annual CAC progression rates comparing the corresponding groups to the normoglycemia group were 1.031 (1.023–1.039), 1.025 (1.019–1.032), and 1.054 (1.047–1.062), respectively.Conclusions: CAC risk and CAC progression were consistently highest in individuals meeting both glucose and HbA1c criteria, while all three prediabetes types showed significantly increased risk of CAC progression. Atherosclerosis risk reduction management is necessary for prediabetes, especially in patients meeting both criteria.<br/

Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome

Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human-based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human-based FXS model via differentiation of astrocytes from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca2+ signaling, impaired sterol biosynthesis, and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment

Fatty liver disease and changes in dense breasts in pre- and postmenopausal women: the Kangbuk Samsung health study

Purpose: while increased breast density is a risk factor for breast cancer, the effect of fatty liver disease on breast density is unknown. We investigated whether fatty liver is a risk factor for changes in breast density over ~4 years of follow-up in pre- and postmenopausal women.Methods: this study included 74,781 middle-aged Korean women with mammographically determined dense breasts at baseline. Changes in dense breasts were identified by more screening mammograms during follow-up. Hepatic steatosis (HS) was measured using ultrasonography. Flexible parametric proportional hazards models were used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), and a Weibull accelerated failure time model (AFT) was used to determine the time ratios (TRs) and 95% CIs.Results: during a median follow-up of 4.1 years, 4,022 women experienced resolution of the dense breasts. The association between HS and dense breast resolution differed by the menopause status (P for interaction&lt;0.001). After adjusting for body mass index and other covariates, the aHRs (95% CI) for dense breast resolution comparing HS to non-HS were 0.81 (0.70–0.93) in postmenopausal women, while the association was converse in premenopausal women with the corresponding HRs of 1.30 (1.18–1.43). As an alternative approach, the multivariable-adjusted TR (95% CI) for dense breast survival comparing HS to non-HS were 0.81 (0.75-0.87) and 1.19 (1.06-1.33) in premenopausal and postmenopausal women, respectively.Conclusion: the association between HS and changes in dense breasts differed with the menopause status. HS increased persistent dense breast survival in postmenopausal women but decreased it in premenopausal women. menopause status