Optimizing Lane Departure Warning System towards AI-Centered Autonomous Vehicles.

The operational efficacy of lane departure warning systems (LDWS) in autonomous vehicles is critically influenced by the retro-reflectivity of road markings, which varies with environmental wear and weather conditions. This study investigated how changes in road marking retro-reflectivity, due to factors such as weather and physical wear, impact the performance of LDWS. The study was conducted at the Yeoncheon SOC Demonstration Research Center, where various weather scenarios, including rainfall and transitions between day and night lighting, were simulated. We applied controlled wear to white, yellow, and blue road markings and measured their retro-reflectivity at multiple stages of degradation. Our methods included rigorous testing of the LDWS's recognition rates under these diverse environmental conditions. Our results showed that higher retro-reflectivity levels significantly improve the detection capability of LDWS, particularly in adverse weather conditions. Additionally, the study led to the development of a simulation framework for analyzing the cost-effectiveness of road marking maintenance strategies. This framework aims to align maintenance costs with the safety requirements of autonomous vehicles. The findings highlight the need for revising current road marking guidelines to accommodate the advanced sensor-based needs of autonomous driving systems. By enhancing retro-reflectivity standards, the study suggests a path towards optimizing road safety in the age of autonomous vehicles.

Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients.

Bipolar disorder (BD) is a psychiatric condition characterized by depressive and manic episodes that affect 2% of the world population. The first-line long-term treatment for mood stabilization is lithium (Li). Induced pluripotent stem cell modeling of BD using hippocampal dentate gyrus-like neurons derived from Li-responsive (LR) and Li-non-responsive (NR) patients previously showed neuronal hyperexcitability. Li treatment reversed hyperexcitability only on the LR neurons. In this study we searched for specific targets of Li resistance in NR neurons and found that the activity of Wnt/ß-catenin signaling pathway was severely affected, with a significant decrease in expression of LEF1. Li targets the Wnt/ß-catenin signaling pathway by inhibiting GSK-3ß and releasing ß-catenin that forms a nuclear complex with TCF/LEF1, activating the Wnt/ß-catenin transcription program. Therefore, we propose that downregulation of LEF1 may account for Li resistance in NR neurons. Our results show that valproic acid (VPA), a drug used to treat NR patients that also acts downstream of GSK-3ß, upregulated LEF1 and Wnt/ß-catenin gene targets, increased transcriptional activity of complex ß-catenin/TCF/LEF1, and reduced excitability in NR neurons. In addition, decreasing LEF1 expression in control neurons using shLEF1 caused hyperexcitability, confirming that the impact of VPA on excitability in NR neurons was connected to changes in LEF1 and in the Wnt/ß-catenin pathway. Our results suggest that LEF1 may be a useful target for the discovery of new drugs for BD treatment.

Dibutyl phthalate exposure during gestation and lactation in C57BL/6 mice: Maternal behavior and neurodevelopment in pups.

OBJECTIVES: Neurotoxic effects of phthalate during pregnancy on immature brain of the offspring or mature brains of the mothers remain unclear. We examined the effect of dibutyl phthalate (DBP) exposure during gestation and lactation on the maternal behavior of mother mice and neurodevelopment in pups. METHODS: Pregnant mice were treated orally with DBP (0, 50 and 100 mg/kg/day, N = 20 per group) from gestational day 13 to postnatal day (PND) 15. Maternal behavior was measured using pup retrieval and nest shape test at postpartum day 4. For the pups, the neurodevelopment was measured using negative geotaxis, cliff avoidance at PND 7, swimming test and olfactory orientation at PND 14. RNA and protein expressions in the brain cortex of 50 mg/kg/day and control group (0 mg/kg/day) were analyzed using microarray and Western blot analysis. Nissl-stained sections at the coronal level of interaural 2.56 mm, bregma -1,23 mm, were used for counting of dark cortical neurons in mother and pup mice. RESULTS: DBP treated mother mice (50 and 100 mg/kg/day) showed poor maternal behavior, poor nesting and retrieval behavior compared to the control group (0 mg/kg/day). In brain cortex, DBP-treated mothers showed decrease in protein expression of Nr4a3, Egr1, Arc, BDNF and phosphorylation of AKT and CREB, were also decreased in cortex of DBP-treated mothers. Pups exposed to DBP showed significantly decreased scores in negative geotaxis at PND 7 and swimming scores and olfactory orientation tests at PND 14. The cortex of the DBP exposed pups showed increase in expression of dopamine receptor D2 gene. Nissl staining showed that the dark neurons were increased in cortex of DBP treated mothers and DBP exposed pups. Suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain. CONCLUSION: DBP exposure during gestation and lactation cause impairment in maternal behaviors and downregulation of neuronal plasticity and survival signals. Pups of mothers with exposed to DBP, showed delayed neurodevelopment and dark neurons increase in brain cortex, suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain.

Adverse effects of prenatal mercury exposure on neurodevelopment during the first 3 years of life modified by early growth velocity and prenatal maternal folate level.

BACKGROUND AND AIMS: Previous studies have suggested that mercury exposure and folate levels during pregnancy may influence early childhood neurodevelopment. Rapid catch-up growth in children is associated with an increased risk of pathological nervous system development. We evaluated whether the association between prenatal folate and mercury-related neuropsychological dysfunction was modified by growth velocity during childhood. METHODS: The Mothers and Children's Environmental Health (MOCEH) birth cohort study began in 2006 and by 2010, 1751 women had been enrolled before the second trimester of their pregnancy along with their partners. Participants visited the research center at birth and 6, 12, 24, and 36 months. We measured mercury levels in maternal and cord blood and folate in maternal serum. Questionnaires to evaluate the environment and health of their child were administered and anthropometric factors including body weight and height were measured. Certified investigators used the Bayley test to measure neurobehavioral outcomes. We calculated postnatal growth change as the change in infant weight for-age z-score between birth and 3 years. Multiple linear regression and mixed models were used to examine the association between mercury exposure and children's neurodevelopment as well as the modifying effects of folate and growth velocity. RESULTS: A total of 30.6% of children experienced rapid growth during the first 3 years of life. Median values of mercury in the low folate group were significantly higher in rapid growers (3.41 µg/L in maternal blood and 5.63 µg/L in cord blood) than in average/slow growers (3.05 µg/L in maternal blood and 5.19 µg/L in cord blood). Rapid growers were also significantly associated with decreased psychomotor development scores during the first 3 years of life and with having mothers who had low prenatal folate levels, even after adjusting for potential confounders. CONCLUSION: Prenatal mercury exposure adversely affects infant neurodevelopment and is associated with rapid growth during the first 3 years of life. This effect was limited to children whose mothers had low prenatal folate levels, suggesting a protective effect of folate against developmental neurotoxicity due to mercury exposure and rapid catch-up growth.

Exposure to prenatal secondhand smoke and early neurodevelopment: Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: The association between exposure to secondhand smoke (SHS) during pregnancy and a child's neurodevelopment has not been established yet. We explored the association between prenatal exposure to SHS and neurodevelopment at 24 months of age considering genetic polymorphism and breastfeeding in 720 mothers and their offspring enrolled in the Korean multicenter birth cohort study (Mothers and Children Environmental Health, MOCEH). METHODS: We quantified urine cotinine concentrations in mothers once from 12th to 20th gestational weeks and excluded those whose urine cotinine levels exceeded 42.7 ng/ml to represent SHS exposure in early pregnancy. Mental developmental index (MDI) and psychomotor developmental index (PDI) values were measured using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II) at 24 months of age. A general linear model was used to assess the relationship between maternal urinary cotinine level and neurodevelopment. RESULTS: MDI scores were inversely associated with cotinine [ß = - 2.73; 95% confidence interval (CI): - 5.32 to - 0.15] in children whose mothers had early pregnancy urinary cotinine levels >1.90 ng/ml. No association was evident in children whose mothers had cotinine levels ≤1.90 ng/ml. This negative association was more pronounced in children whose mothers had both Glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1) null type [ß = - 5.78; 95% CI: -10.69 to - 0.87], but not in children whose mothers had any present type of GSTM1/GSTT1 [ß = - 1.64; 95% CI: -4.79 to 1.52]. The association was no longer significant when children received breast milk exclusively for up to 6 months [ß = - 0.24; 95% CI: -4.69 to 4.20] compared to others [ß = - 3.75; 95% CI: -7.51 to 0.00]. No significant association was found for PDI. CONCLUSIONS: Maternal exposure to SHS during pregnancy may result in delayed MDI in early childhood. This effect might be modified by genetic polymorphism and breastfeeding behavior.

Environmental Tobacco Smoke Exposure at Home and Attributable Problem Behaviors in Korean Children and Adolescents for 2012-2014 in a Nationally Representative Survey.

BACKGROUND: This study aimed to examine the environmental tobacco smoke (ETS) exposure at home and associated problem behaviors in Korean children and adolescents. METHODS: Approximately 2,167 children aged 3-18 years were included in the study after excluding 163 active smokers from the Korean Environmental Health Survey in Children and Adolescents (2012-2014). ETS data were obtained using a questionnaire; problem behaviors were measured using the Child Behavior Checklist administered to parents. The relationship between ETS exposure and problem behavior was evaluated using a survey regression model adjusted for region, age, sex, income, and father's education. The population-attributable fraction (PAF%) was calculated based on problem behaviors related to ETS exposure at home. RESULTS: The rates of ETS exposure at home were 20%, 28%, and 39% in children aged 3-5, 6-11, and 12-18 years, respectively; ETS exposure at home was associated with behavioral problems: the exposed group having higher total behavioral problem score (95% confidence interval [CI]) than the non-exposed by 2.46 (0.60-4.32) and 2.74 (0.74-4.74) in children aged 6-11 and 12-18 years, respectively, with no significant association in those aged 3-5 years. The PAF% (95% CI) of total problem behaviors for ETS exposure at home were 2.68 (-10.11-17.78), 10.66 (3.25-17.55), and 11.62 (3.03-18.96) in children aged 3-5, 6-11, and 12-18 years, respectively. Children with externalizing problems had higher PAF% than those with internalizing problems. CONCLUSION: In Korea, ETS exposure at home is associated with problem behaviors in children and adolescents with about more than 10% population attributable fraction.

Association between maternal intake of n-6 to n-3 fatty acid ratio during pregnancy and infant neurodevelopment at 6 months of age: results of the MOCEH cohort study.

BACKGROUND & AIMS: Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for infant neurodevelopment. The nutritional adequacy of dietary LC-PUFAs depends not only on the LC-PUFAs intake but also on the n-6 to n-3 fatty acid ratio (n-6/n-3 PUFAs). This study aimed to identify the association between the maternal dietary n-6/n-3 PUFAs and motor and cognitive development of infants at 6 months of age. METHODS: We used data from 960 participants in the Mothers and Children's Environmental Health (MOCEH) study, which is a multi-center prospective cohort study. Dietary intake of pregnant women was assessed by a one-day 24-h recall method. Food consumption of infants was estimated based on the volume of breast milk and weaning foods. The duration of each feed was used to estimate the likely volume of milk consumed. Dietary intake of infants at 6 months was also assessed by a 24-h recall method. Cognitive and motor development of infants at 6 months of age was assessed by the Korean Bayley scales of infant development edition II (BSID-II) including the mental developmental index (MDI) and the psychomotor developmental index (PDI). RESULTS: Maternal intakes of n-6/n-3 PUFAs and linoleic acid (LA)-to-α-linolenic acid (ALA) ratio (LA/ALA) were 9.7 ± 6.3 and 11.12 ± 6.9, respectively. Multiple regression analysis, after adjusting for covariates, showed that n-6/n-3 PUFAs was negatively associated with both the MDI (ß = -0.1674, P = 0.0291) and PDI (ß = -0.1947, P = 0.0380) at 6 months of age. These inverse associations were also observed between LA/ALA and both the MDI and PDI (MDI; ß = -0.1567; P = 0.0310, PDI; ß = -0.1855; P = 0.0367). Multiple logistic regression analysis, with the covariates, showed that infants whose mother's LA/ALA were ranked in the 2nd, 3rd, and 4th quartile were at approximately twice the risk with more than twice the risk of delayed performance on the PDI compared to the lowest quartile (1st vs. 2nd; OR = 2.965; 95% CI = 1.376 - 6.390, 1st vs. 3rd; OR = 3.047; 95% CI = 1.374 - 6.756 and 1st vs. 4th; OR = 2.551; 95% CI = 1.160 - 5.607). CONCLUSIONS: Both the maternal dietary n-6/n-3 PUFAs and LA/ALA intake were significantly associated with the mental and psychomotor development of infants at 6 months of age. Thus, maintaining low n-6/n-3 PUFAs and LA/ALA is encouraged for women during pregnancy.

Prevalence, correlates, and associated psychological problems of substance use in Korean adolescents.

BACKGROUND: Substance use among Korean adolescents has been increasing, but little is known about the correlates of substance use in this population. Identification of the correlates is required for development of preventive approaches that aim to reduce or eliminate risk. Therefore, we examined the prevalence and correlates of substance use including psychological problems in a nationwide sample of Korean adolescents. METHODS: Data from the 2014 Korean Youth Risk Behavior Web-Based Survey, collected from 72,060 adolescents aged 12-18 years (mean age 14.94 ± 1.75 years), were analyzed. Participants' lifetime experiences with substances (alcohol, tobacco, and illicit drugs) were assessed. Participants' perceived stress, depressive mood, and suicidality during the previous 12 months were also investigated. RESULTS: The lifetime prevalence estimates of alcohol, tobacco, and illicit drug use were 43.0, 19.9, and 0.4 % of the participants, respectively. The most commonly used illicit drugs were inhalants. Older age, male gender, non-residence with family, low parental educational level and socio-economic status, and low academic achievement were positively and significantly associated with substance use. Substance (alcohol, tobacco, and illicit drug) use was positively and significantly associated with severe stress, depressive mood, and suicidality during the previous 12 months, with the highest odds ratios obtained from illicit drug use. CONCLUSIONS: These results indicate that the use of substances (alcohol, tobacco, and illicit drugs) among Korean adolescents is associated with socially disadvantaged families, psychological problems, and risky behavior. Health education including dependency prevention programs is needed for these high-risk groups.

Evaluating subjective domains of antipsychotic-induced adverse effects using heart rate variability.

AIMS: Antipsychotic-induced autonomic dysregulation may lead to a wide range of subjective side-effects in schizophrenia patients. Using heart rate variability (HRV) measures, we prospectively examined the relationship between subjective side-effects and cardiac autonomic regulation in unmedicated schizophrenia patients. METHODS: Forty-five unmedicated schizophrenia patients were assessed for antipsychotic-associated side-effects and HRV parameters at baseline and after 6 weeks of treatment. Psychiatric symptoms and subjective side-effects were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Liverpool University Neuroleptic Side-effect Rating Scale (LUNSERS). RESULTS: Correlations between subjective adverse effects and HRV measures at baseline and at week 6 varied. Nonetheless, the changes in the psychic side-effects domain were significantly correlated with the changes in time-domain HRV measures and sample entropy (SampEn). In addition, the change in SampEn was significantly associated with that in the scores of extrapyramidal, anticholinergic, miscellaneous, and red herring domains as well as the mean total LUNSERS score. CONCLUSION: Baseline HRV measures may predict clinical response and adverse events associated with treatment adherence. Also, subjective side-effects may correspond well with the changes in neurocardiac dynamics, and the changes in SampEn may effectively reflect subjective discomfort in patients receiving antipsychotic treatment.

Parental quality of life and depressive mood following methylphenidate treatment of children with attention-deficit hyperactivity disorder.

AIM: This naturalistic study investigated the associations between quality of life and depressive mood in parents and symptom changes in attention-deficit hyperactivity disorder (ADHD) children. METHODS: At baseline and at weeks 4 and 8, the parents evaluated their children, who were receiving treatment with osmotic-release oral system methylphenidate (mean dosage 36.3 ± 15.5 mg/day), using the Swanson, Nolan, and Pelham - Fourth Edition (SNAP-IV-18) scale. The parents evaluated themselves using the Beck Depression Inventory (BDI) and the World Health Organization Quality of Life Assessment, Brief Version (WHOQOL-BREF). RESULTS: A significant reduction in SNAP-IV-18 scores and improvements in parental BDI scores and parental WHOQOL-BREF scores were observed. The decrease in BDI scores from baseline to 8 weeks was significantly associated with increases in WHOQOL-BREF sub-domain scores from baseline to 8 weeks, with a greater decrease at 4 weeks and after. The decrease in the SNAP-IV-18 hyperactivity-impulsivity score was significantly associated with increases in WHOQOL social sub-domain scores from baseline to 8 weeks. For those patients who showed a 25% or greater decrease in the SNAP-IV-18 total scores from baseline to 8 weeks, the decreases in the SNAP-IV-18 total score and in the inattention and hyperactivity-impulsivity scores were significantly associated with a decrease in BDI scores from baseline to 8 weeks. CONCLUSION: Methylphenidate treatment for ADHD was associated with both symptom alleviation in children with ADHD and improvement in parental depressive mood and quality of life, suggesting that the effects of treatment could go beyond symptom improvement in ADHD.

Multifaceted Approach to Addressing Problem Behaviors in Developmentally Challenged Children.

Parents of children with autism spectrum disorder (ASD) often encounter unique challenges when attempting to understand their children's challenging behaviors such as self-injury, aggression, noncompliance, and stereotypies. In this study, we aimed to analyze and clarify the definition of challenging behaviors in individuals with ASD, identify the variables associated with challenging behaviors, and determine the function of these behaviors. Systematic observation and data collection are crucial to understand the functions of specific behaviors exhibited by individuals with ASD based on their antecedents and consequences. Knowledge regarding these will enable clinicians to develop and implement effective interventions. Additionally, the treatment approach should aim for generalization to improve the quality of lives of both children with ASD and their caregivers.

Relationship between blood manganese levels and children's attention, cognition, behavior, and academic performance--a nationwide cross-sectional study.

Manganese (Mn) is neurotoxic at high concentrations. However, Mn is an essential element that can protect against oxidative damage; thus, extremely low levels of Mn might be harmful. Our aim was to examine whether either high or low environmental Mn exposure is related to academic and attention function development among school-aged children. This cross-sectional study included 1089 children 8-11 years of age living in five representative areas in South Korea. Blood Mn, blood lead, and urine cotinine were measured. We assessed IQ with the Wechsler Abbreviated Scale of Intelligence; attention with a computerized continuous performance test called the Attention-deficit/hyperactivity disorder (ADHD) Diagnostic System (ADS), the Korean version of the Stroop Color-Word Test, the Children's Color Trails Test (CCTT), and the ADHD Rating Scale; academic functions with the Learning Disability Evaluation Scale (LDES); and emotional and behavioral problems with the Korean version of the Child Behavior Checklist (CBCL). We further assessed the presence of ADHD using a highly structured diagnostic interview, the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The median blood concentration of Mn was 14.14 µg/L. We observed a nonlinear association between the CCTT2 completion time and the CPT commission error (F=3.14, p=0.03 and F=4.05, p=0.01, respectively). We divided the data into three groups: lower (<8.154 µg/L), and upper 5th percentile (>21.453 µg/L) and middle 90th percentile to determine whether a lack or overload of Mn could cause adverse effects. After adjusting for urine cotinine, blood lead, children's IQ, and other potential confounders, the high Mn group showed lower scores in thinking (B=-0.83, p=0.006), reading (B=-0.93, p=0.004), calculations (B=-0.72, p=0.005), and LQ (B=-4.06, p=0.006) in the LDES and a higher commission error in the CPT (B=8.02, p=0.048). The low Mn group showed lower color scores in the Stroop test (B=-3.24, p=0.040). We found that excess Mn in children is associated with lower scores of thinking, reading, calculation, and LQ in the LDES and higher scores of commission error in the ADS test. In contrast, lower Mn in children is associated with lower color scores in the Stroop test. The findings of this cross-sectional study suggest that excess exposure or deficiency of Mn can cause harmful effects in children.

Examination of categorical approach to symptom assessment: cross-validation of foulds' Delusions-Symptoms-States Inventory with Korean non-patient and patient groups.

BACKGROUND: Foulds' Delusions-Symptoms-State Inventory (DSSI) has been purported to be a reliable, systematic categorical measure to assess the patients with schizophrenia according to the degree of illness. However, further cross-validations using other clinical measures and diverse samples from other cultures have not been advanced recently. We aimed to examine the validity of the DSSI hierarchical class model using both Korean non-patient and patient (schizophrenia and depression) groups. METHOD: The hypothesis of inclusive, non-reflexive relationships among the DSSI classes was tested. The power of DSSI to detect presence of symptoms was assessed via cross-validation with other clinical measures, and the differences between the clinical features among the DSSI classes were examined using the Minnesota Multiphasic Personality Inventory (MMPI). RESULTS: The high rate of model conformity (91.1%) across the samples and cross-validation with other criterion measures provided further support for the validity of DSSI. CONCLUSIONS: DSSI is a reliable self-report measure that can be applied to both patient and non-patients to assess the presence and severity of psychiatric illness. Future studies that include more diverse clinical groups are necessary to lend further support for its utility in clinical practice.

Methylphenidate-osmotic-controlled release oral delivery system treatment reduces parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of the current study was to investigate the effect of methylphenidate-osmotic release oral delivery system (MPH-OROS) treatment on parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Four hundred and ninety-five children and adolescents (391 boys and 104 girls), aged 7 to 18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for ADHD, were recruited at 48 psychiatric outpatient clinics across South Korea. Children's symptoms, parenting stress, and parental depression were assessed at baseline, week 4, and week 8 of MPH-OROS treatment using the Korean version of the DuPaul's ADHD Rating Scale (ARS), the Beck's Depression Inventory (BDI), and the Parenting Stress Index, Short Form (PSI-SF). RESULTS: We found significantly decreased scores of ARS, parental BDI, and PSI-SF from baseline to week 4 and from week 4 to week 8. Also, there were positive correlations among baseline PSI-SF, ARS, and BDI scores. The changes in BDI and ARS scores were significantly associated with the PSI score changes, accounting for 20.1% and 10.0%, respectively. CONCLUSIONS: We suggest that the increased parenting stress and depression in parents of children and adolescents with ADHD can be improved following the treatment with MPH-OROS.

Deterioration of Mental Health in Children and Adolescents During the COVID-19 Pandemic.

This paper reviews the global effect of the coronavirus disease 2019 (COVID-19) pandemic on the mental health of children and adolescents in South Korea, the U.S., Japan, and China. We reviewed research on deteriorated mental health, including increased suicide, suicidal thoughts, and self-harm. Various studies have shown that students' mental health issues, such as depression and anxiety, have worsened during the COVID-19 pandemic. Furthermore, the number of students who committed suicide has significantly increased in the U.S. and Japan. Factors such as prior mental health status, change in daily routine, reduced physical activity, excessive screen time, overuse of electronic devices, and reduced social support have been reported to have a significant effect. The chain of deteriorating mental health among the youth began at the onset of COVID-19, social distancing, and school closure. As youths began to stay at home instead of going to school, they lost opportunities to connect with their friends or teachers, who could provide support outside of their homes. Young people spent less time on physical activity and more time online, which damaged their sleeping schedule and daily routine. In preparing for the post-pandemic phase, we should thoroughly analyze the long-term effects of the pandemic on youth mental health, while simultaneously tackling current imminent issues.

Identifying the Unmet Medical Needs of HIV-Positive Subjects in Korea: Results of a Nationwide Online Survey.

An online survey was conducted in Korea to identify the unmet medical needs of people living with human immunodeficiency virus (HIV) (PLWH). Participants (n = 105) were mostly male (93.3%), aged >40 years (75.2%), and treated for ≥6 years post-diagnosis (61.9%). Most PLWH (71.4%) were very satisfied/satisfied with their HIV management. Areas of concern were quality of life (QoL) and mental health. Characteristics of a long-term therapeutic agent were 'low risk of resistance', 'high long-term viral suppression efficacy', and 'high degree of safety'. Pre-consultation QoL and mental health screening would be beneficial for the long-term success of HIV management.

Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells.

OBJECTIVE: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. METHODS: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase ß (CaMKKß) using immunoblotting and CPT1 enzymatic activity measures. RESULTS: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30-60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKß inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKß phosphorylation. CONCLUSION: These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKß in human SH-SY5Y and U-87 MG cells.

The effect of residential greenness during pregnancy on infant neurodevelopment using propensity score weighting: A prospective mother-infant paired cohort study.

BACKGROUND: While prior studies have suggested an association between green spaces and infant neurodevelopment, the causal effect of green space exposure during pregnancy has not been fully investigated. This study aimed to identify with causal inference the effect of exposure to residential greenness during pregnancy on infants' mental-psychomotor development and the role of maternal education in modifying this association. METHODS: We prospectively collected data of pregnant women and their infants from Mothers and Children Environmental Health cohort study. Based on residential addresses, we compiled information on the percent of green space using different buffer distances (100 m, 300 m, and 500 m) and air pollution (PM2.5). Infant neurodevelopment was measured at 6 months of age using the Korean Bayley Scales of Infant Development II Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Generalized propensity scores (GPSs) were estimated from machine-learning (ML) algorithms. We deduced causal inference through GPS adjustment and weighting approaches. Further analyses confirmed whether the association was altered by maternal academic background. RESULTS: A total of 845 mother-infant pairs from the cohort study were included. We found that exposure to green spaces was robustly associated with infants' mental development. For example, an increase in % green space within 300 m increased the MDI by 14.32 (95 % confidence interval [CI], 3.44-25.2) in the weighting approach. Additionally, the association was even more noticeable for mothers with college degrees or above: an increase in % green space within 300 m increased the MDI by 23.69 (95 % CI, 8.53-38.85) and the PDI by 22.45 (95 % CI, 2.58-42.33) in the weighting approach. This association did not appear in mothers without college degrees. CONCLUSION: Exposure to green spaces during pregnancy showed a beneficial relationship with infant mental development. Maternal academic background could modify the impact of green space exposure on infant neurodevelopment.

Heterotrimeric stimulatory GTP-binding proteins inhibit cisplatin-induced apoptosis by increasing X-linked inhibitor of apoptosis protein expression in cervical cancer cells.

Treatment with cisplatin (cis-dichlorodiammineplatinum (II)) induces DNA double-stranded breaks and apoptosis in many human cancer cells. We have reported that heterotrimeric stimulatory GTP-binding proteins (Gαs) can modulate the apoptotic response of several cancer cells. This study investigated the effect of Gαs on apoptosis triggered by cisplatin and its underlying molecular mechanism in cervical cancer cells. Stable expression of constitutively active Gαs (GαsQL) decreased the release of cytochrome c from the mitochondria to the cytosol and cleavage of caspase-3 and poly(ADP-ribose) polymerases in HeLa cells treated with 30 µM cisplatin, indicating that Gαs inhibited cisplatin-induced apoptosis. Treatment with forskolin also inhibited apoptosis of C33A and CaSKi cervical cancer cells. Expression of GαsQL increased the expression of the X-linked inhibitor of apoptosis protein (XIAP) and partially maintained increased XIAP after cisplatin treatment. Knockdown of XIAP by siRNA augmented apoptosis. Expression of GαsQL increased XIAP mRNA; this increase was inhibited by a protein kinase A inhibitor and cAMP response element (CRE) decoy. A cAMP response element (CRE)-like element at -1396 bp in the XIAP promoter was found to mediate the induction of XIAP by Gαs. In addition, expression of GαsQL protected against the ubiquitin/proteasome-dependent degradation of the XIAP protein. This study shows that Gαs inhibits cisplatin-induced apoptosis by increasing transcription of XIAP and by decreasing degradation of XIAP protein in HeLa cervical cancer cells.

The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells.

In this study, we investigated the antitumor effects of the tricyclic antidepressant 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (imipramine) on glioma cells. We found that exposure of U-87MG cells to imipramine resulted in the inhibition of PI3K/Akt/mTOR signaling, reduction of clonogenicity, and induction of cell death. Imipramine stimulated the formation of acidic vesicular organelles, the conversion of LC3-I to LC3-II, and the redistribution of LC3 to autophagosomes, suggesting that it stimulates the progression of autophagy. It did not, however, induce apoptosis. We further showed that knockdown of Beclin-1 using siRNA abrogated imipramine-induced cell death. These results suggest that imipramine exerts antitumor effects on PTEN-null U-87MG human glioma cells by inhibiting PI3K/Akt/mTOR signaling and by inducing autophagic cell death.