Background School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. Methods A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. Results The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. Conclusion This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.

Background Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment. Methods This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months. Results The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months. Conclusions Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.

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