Assessing Health and Economic Benefits of Omega-3 Fatty Acid Supplementation on Cardiovascular Disease in the Republic of Korea.

BACKGROUND: Cardiovascular disease (CVD) is the primary cause of mortality worldwide and imposes a significant social burden on many countries. METHODS: This study assessed the health and economic benefits of omega-3 associated with CVD. The meta-analysis estimated the risk ratio (RR) and absolute risk reduction (ARR), and the economic impact was calculated using direct and indirect costs related to CVD treatments in Korean adults. RESULTS: A total of 33 studies were included in the meta-analysis on CVD outcomes, with 80,426 participants in the intervention group and 80,251 participants in the control group. The meta-analysis determined a significant reduction in omega-3 in CVD (RR = 0.92, 95% CI: 0.86~0.97) and ARR (1.48%). Additionally, the subgroup analysis indicated that higher doses and the long-term consumption of omega-3 could further enhance these effects. After applying ARR from meta-analysis to the target population of about 1,167,370 in 2021, the Republic of Korea, it was estimated that omega-3 consumption could result in an economic benefit of KRW 300 billion by subtracting the purchase expenses of omega-3 supplements from the total social cost savings. CONCLUSION: Omega-3 supplements can help to reduce the risk of CVD and subsequent economic benefits in the Republic of Korea.

Targeting IKKß Activity to Limit Sterile Inflammation in Acetaminophen-Induced Hepatotoxicity in Mice.

The kinase activity of inhibitory κB kinase ß (IKKß) acts as a signal transducer in the activating pathway of nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death in the development of numerous hepatocellular injuries. However, the importance of IKKß activity on acetaminophen (APAP)-induced hepatotoxicity remains to be defined. Here, a derivative of caffeic acid benzylamide (CABA) inhibited the kinase activity of IKKß, as did IMD-0354 and sulfasalazine which show therapeutic efficacy against inflammatory diseases through a common mechanism: inhibiting IKKß activity. To understand the importance of IKKß activity in sterile inflammation during hepatotoxicity, C57BL/6 mice were treated with CABA, IMD-0354, or sulfasalazine after APAP overdose. These small-molecule inhibitors of IKKß activity protected the APAP-challenged mice from necrotic injury around the centrilobular zone in the liver, and rescued the mice from hepatic damage-associated lethality. From a molecular perspective, IKKß inhibitors directly interrupted sterile inflammation in the Kupffer cells of APAP-challenged mice, such as damage-associated molecular pattern (DAMP)-induced activation of NF-κB activity via IKKß, and NF-κB-regulated expression of cytokines and chemokines. However, CABA did not affect the upstream pathogenic events, including oxidative stress with glutathione depletion in hepatocytes after APAP overdose. N-acetyl cysteine (NAC), the only FDA-approved antidote against APAP overdose, replenishes cellular levels of glutathione, but its limited efficacy is concerning in late-presenting patients who have already undergone oxidative stress in the liver. Taken together, we propose a novel hypothesis that chemical inhibition of IKKß activity in sterile inflammation could mitigate APAP-induced hepatotoxicity in mice, and have the potential to complement NAC treatment in APAP overdoses.

Treatment strategies for Lennox-Gastaut syndrome: outcomes of multimodal treatment approaches.

Background: Multimodal treatment approaches are often considered for patients with Lennox-Gastaut syndrome (LGS). Creating an algorithm that can guide healthcare providers in selecting treatment options for patients with LGS remains a challenge. Herein, we assessed the long-term seizure-free and neurodevelopmental outcomes of stepwise multimodal treatment in patients with LGS. Objective: Herein, we assess the long-term seizure-free and neurodevelopmental outcomes of stepwise multimodal treatment in patients with LGS. Methods: We retrospectively examined the data of 371 patients with LGS who underwent stepwise multimodal treatment, including antiseizure medication (ASM) therapy, dietary therapy (DT), resective epilepsy surgery (R-ES), and palliative epilepsy surgery (P-ES). The seizure-free outcome was considered to be the effect of the final treatment according to the treatment algorithm, and the percentage of patients who remained seizure-free in each treatment group was calculated. ASM treatment, DT, R-ES, and P-ES were applied to 371 (100%), 201 (54.2%), 112 (30.2%), and 115 (31.0%) patients with LGS, respectively. We evaluated the stepwise multimodal treatment outcomes in these patients. Results: One hundred sixty-eight patients (45.3%) remained seizure-free for at least 1 year (seizure-free-for-1-year group), 61 of whom (16.5%) remained seizure-free for more than 5 years (remained-seizure-free group). Among the patients treated with ASM therapy, DT, R-ES, and P-ES, 41 (11.1%), 53 (14.3%), 56 (15.1%), and 29 (7.8%), respectively, remained seizure-free for 1 year. In addition, 15 (4.1%), 15 (4.1%), 19 (5.1%), and 12 (3.2%) patients in the ASM, DT, R-ES, and P-ES treatment groups, respectively, remained seizure-free for more than 5 years. Both the seizure-free-for-1-year and remained-seizure-free groups showed significant improvement in electroencephalography findings and neurodevelopmental status following treatment. Conclusion: This study provides an update on the long-term seizure outcomes and neurodevelopmental improvements in a large cohort of patients with LGS following comprehensive multimodal treatment. We emphasize that the active combination of multiple ASMs, DT, and surgical treatment could provide long-term seizure-free outcomes and significant neurological benefits to patients with LGS.

Association of Cerebral Blood Flow and Brain Tissue Relaxation Time With Neurodevelopmental Outcomes of Preterm Neonates: Multidelay Arterial Spin Labeling and Synthetic MRI Study.

OBJECTIVES: Both cerebral blood flow (CBF) and brain tissue relaxation times are known to reflect maturation in the neonatal brain. However, we do not yet know if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire CBF and relaxation time in preterm neonates, using multidelay arterial spin labeling and synthetic magnetic resonance imaging (MRI), and show their association with later neurodevelopmental outcomes. MATERIALS AND METHODS: In this prospective study, preterm neonates were recruited, and multidelay arterial spin labeling and synthetic MRI were performed between September 2017 and December 2018. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age, and both cognitive and motor outcome scores were measured. Transit time-corrected CBF and T1 and T2 relaxation time values were measured for different brain regions. The measured values were correlated with gestational age (GA) at birth and corrected GA at the MRI scan. Simple and multiple linear regression analyses were performed for the measured values and neurodevelopmental outcome scores. RESULTS: Forty-nine neonates (median [interquartile range] GA, 30 [2] weeks, 209 [17] days; 28 boys) underwent MRI scans at or near term-equivalent age (median [interquartile range] corrected GA, 37 [2] weeks, 258 [14] days). Transit time-corrected CBF (coefficient, 0.31-0.59) and relaxation time (coefficient, -0.39 to -0.86) values showed significant correlation with corrected GA but not with GA. After controlling for GA, the frontal white matter CBF in preterm neonates showed a negative relationship with cognitive outcome scores (ß = -0.97; P = 0.029). Frontal white matter T1 relaxation times showed a positive relationship with cognitive outcome scores (ß = 0.03; P = 0.025) after controlling for GA. CONCLUSIONS: Higher CBF values and lower T1 relaxation times in frontal white matter were associated with poorer cognitive outcomes. As quantitative neuroimaging markers, CBF and relaxation times may help predict neurodevelopmental outcomes in preterm neonates.

Extrahippocampal Radiomics Analysis Can Potentially Identify Laterality in Patients With MRI-Negative Temporal Lobe Epilepsy.

Objective: The objective of the study was to investigate whether radiomics features of extrahippocampal regions differ between patients with epilepsy and healthy controls, and whether any differences can identify patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Methods: Data from 36 patients with hippocampal sclerosis (HS) and 50 healthy controls were used to construct a radiomics model. A total of 1,618 radiomics features from the affected hippocampal and extrahippocampal regions were compared with features from healthy controls and the unaffected side of patients. Using a stepwise selection method with a univariate t-test and elastic net penalization, significant predictors for identifying TLE were separately selected for the hippocampus (H+) and extrahippocampal region (H-). Each model was independently validated with an internal set of MRI-negative adult TLE patients (n = 22) and pediatric validation cohort with MRI-negative TLE (n = 20) from another tertiary center; diagnostic performance was calculated using area under the curve (AUC) of the receiver-operating-characteristic curve analysis. Results: Forty-eight significant H+ radiomic features and 99 significant H- radiomic features were selected from the affected side of patients and used to create a hippocampus model and an extrahippocampal model, respectively. Texture features were the most frequently selected feature. Training set showed slightly higher accuracy between hippocampal (AUC = 0.99) and extrahippocampal model (AUC = 0.97). In the internal validation and external validation sets, the extrahippocampal model (AUC = 0.80 and 0.92, respectively) showed higher diagnostic performance for identifying the affected side of patients than the hippocampus model (AUC = 0.67 and 0.69). Significance: Radiomics revealed extrahippocampal abnormality in the affected side of patients with TLE and could potentially help to identify MRI-negative TLE. Classification of Evidence: Class IV Criteria for Rating Diagnostic Accuracy Studies.

Long-term results of vagus nerve stimulation in children with Dravet syndrome: Time-dependent, delayed antiepileptic effect.

OBJECTIVE: This study aimed to assess the long-term outcomes of vagus nerve stimulation (VNS) in children with pharmaco-resistant Dravet syndrome (DS). METHODS: We enrolled 22 patients with pharmaco-resistant DS who underwent VNS implantation at Severance Children's Hospital from March 2005 to October 2020. Efficacy and tolerability were assessed at 3, 6, 12, 18, 24, 30, and 36 months after VNS implantation. Efficacy was measured as the percentage reduction in seizure frequency at each follow-up compared with the baseline (pre-implantation) values. RESULTS: Median patient age at VNS implantation was 10.0 years (interquartile range 7.7-13.3). The median follow-up period was 4.3 years (interquartile range 3.0-6.5) after VNS implantation. All cases were followed up for ≥2 years after VNS implantation. Three (13.6 %) patients maintained seizure freedom for ≥1 year. Among them, one achieved seizure freedom after 30 months of VNS. More than 50 % reduction in seizure frequency was observed in 36.4 % (8/22), 54.5 % (12/22), and 63.2 % (12/19) of the patients at 12, 24, and 36 months, respectively. The median percent reduction in seizure frequency was 18.8 %, 50.6 %, and 60.0 % at 12, 24, and 36 months, respectively. Compared with the baseline value, the seizure frequency was significantly lower at 24, 30, and 36 months, as well as at the longest follow-up period (p < 0.05, Wilcoxon signed-rank test). The symptom that was mostly associated with adverse events was hoarseness (4/22, 18.2 %); however, they had temporary or minimal effects on activities of daily living. CONCLUSIONS: Our findings demonstrate that VNS therapy allows long-term, progressive, and time-dependent improvement in seizure control for pharmaco-resistant DS. Clinicians should be aware of the delayed VNS efficacy over the years and should encourage long-term VNS maintenance by patients.

Utility of 7 Tesla Magnetic Resonance Imaging in Patients With Epilepsy: A Systematic Review and Meta-Analysis.

Objective: 7 Tesla magnetic resonance imaging (MRI) enables high resolution imaging and potentially improves the detection of morphologic abnormalities in patients with epilepsy. However, its added value compared with conventional 1.5T and 3.0T MRI is unclear. We reviewed the evidence for the use of 7 Tesla MRI in patients with epilepsy and compared the detection rate of focal lesions with clinical MRI. Methods: Clinical retrospective case studies were identified using the indexed text terms "epilepsy" AND "magnetic resonance imaging" OR "MR imaging" AND "7T" OR "7 Tesla" OR "7T" in Medline (2002-September 1, 2020) and Embase (1999-September 1, 2020). The study setting, MRI protocols, qualitative, and quantitative assessment were systematically reviewed. The detection rate of morphologic abnormalities on MRI was reported in each study in which surgery was used as the reference standard. Meta-analyses were performed using a univariate random-effects model in diagnostic performance studies with patients that underwent both 7T MRI and conventional MRI. Results: Twenty-five articles were included (467 patients and 167 healthy controls) consisting of 10 case studies, 10 case-control studies, 4 case series, and 1 cohort study. All studies included focal epilepsy; 12 studies (12/25, 48%) specified the disease etiology and 4 studies reported focal but non-lesional (MRI-negative on 1.5/3.0T) epilepsy. 7T MRI showed superior detection and delineation of morphologic abnormalities in all studies. In nine comparative studies, 7T MRI had a superior detection rate of 65% compared with the 22% detection rate of 1.5T or 3.0T. Significance: 7T MRI is useful for delineating morphologic abnormalities with a higher detection rate compared with conventional clinical MRI. Most studies were conducted using a case series or case study; therefore, a cohort study design with clinical outcomes is necessary. Classification of Evidence: Class IV Criteria for Rating Diagnostic Accuracy Studies.

Brain MRI radiomics analysis may predict poor psychomotor outcome in preterm neonates.

OBJECTIVES: This study aimed to apply a radiomics approach to predict poor psychomotor development in preterm neonates using brain MRI. METHODS: Prospectively enrolled preterm neonates underwent brain MRI near or at term-equivalent age and neurodevelopment was assessed at a corrected age of 12 months. Two radiologists visually assessed the degree of white matter injury. The radiomics analysis on white matter was performed using T1-weighted images (T1WI) and T2-weighted images (T2WI). A total of 1906 features were extracted from the images and the minimum redundancy maximum relevance algorithm was used to select features. A prediction model for the binary classification of the psychomotor developmental index was developed and eightfold cross-validation was performed. The diagnostic performance of the model was evaluated using the AUC with and without including significant clinical and DTI parameters. RESULTS: A total of 46 preterm neonates (median gestational age, 29 weeks; 26 males) underwent brain MRI (median corrected gestational age, 37 weeks). Thirteen of 46 (28.3%) neonates showed poor psychomotor outcomes. There was one neonate among 46 with moderate to severe white matter injury on visual assessment. For the radiomics analysis, twenty features were selected for each analysis. The AUCs of prediction models based on T1WI, T2WI, and both T1WI and T2WI were 0.925, 0.834, and 0.902. Including gestational age or DTI parameters did not improve the prediction performance of T1WI. CONCLUSIONS: A radiomics analysis of white matter using early T1WI or T2WI could predict poor psychomotor outcomes in preterm neonates. KEY POINTS: • Radiomics analysis on T1-weighted images of preterm neonates showed the highest diagnostic performance (AUC, 0.925) for predicting poor psychomotor outcomes. • In spite of 45 of 46 neonates having no significant white matter injury on visual assessment, the radiomics analysis of early brain MRI showed good diagnostic performance (sensitivity, 84.6%; specificity, 78.8%) for predicting poor psychomotor outcomes. • Radiomics analysis on early brain MRI can help to predict poor neurodevelopmental outcomes in preterm neonates.

Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats.

Sarcopenia- or cachexia-related muscle atrophy is due to imbalanced energy metabolism and oxidative stress-induced muscle dysfunction. Monoterpenes play biological and pharmacological reactive oxygen species (ROS) scavenging roles. Hence, we explored the effects of camphene, a bicyclic monoterpene, on skeletal muscle atrophy in vitro and in vivo. We treated L6 myoblast cells with camphene and then examined the ROS-related oxidative stress using Mito TrackerTM Red FM and anti-8-oxoguanine antibody staining. To investigate lipid metabolism, we performed real-time polymerase chain reactions, holotomographic microscopy, and respiratory gas analysis. Rat muscle atrophy in in vivo models was observed using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and immunocytochemistry. Camphene reversed the aberrant cell size and muscle morphology of L6 myoblasts under starvation and in in vivo models. Camphene also attenuated E3 ubiquitin ligase muscle RING-finger protein-1, mitochondrial fission, and 8-oxoguanine nuclear expression in starved myotubes and hydrogen peroxide (H2O2)-treated cells. Moreover, camphene significantly regulated lipid metabolism in H2O2-treated cells and in vivo models. These findings suggest that camphene may potentially affect skeletal muscle atrophy by regulating oxidative stress and lipid metabolism.

The First Reported Case of Infant Botulism in Korea: Treatable Infantile Neuromuscular Disease.

Botulism is a rare neuromuscular disorder caused by neurotoxins produced by Clostridium botulinum. The diagnosis of infant botulism may be obscured or delayed, as its presentation is similar to that of infantile neuromuscular disorders. We report the first Korean case of infant botulism in an acute progressive floppy infant with poor sucking and a weak cry. No abnormalities were found in all blood, cerebrospinal fluid, genetic test, nerve conduction study, and imaging studies. A stool-toxin test was finally performed under suspicion of infant botulism, and the result was positive. The patient was immediately treated with heptavalent botulism antitoxin. Follow-up after 3 months showed normal development with a complete resolution of all symptoms. Therefore, clinical suspicion of infant botulism, which is a treatable infantile neuromuscular disease, is essential for early diagnosis and prompt treatment in the differential diagnosis of a floppy infant.

Maternal, neonatal, and child health systems under rapid urbanization: a qualitative study in a suburban district in Vietnam.

BACKGROUND: Vietnam has been successful in increasing access to maternal, neonatal, and child health (MNCH) services during last decades; however, little is known about whether the primary MNCH service utilization has been properly utilized under the recent rapid urbanization. We aimed to examine current MNCH service utilization patterns at a district level. METHODS: The study was conducted qualitatively in a rural district named Quoc Oai. Women who gave a birth within a year and medical staff at various levels participated through 43 individual in-depth interviews and 3 focus group interviews. RESULTS: Primary MNCH services were underutilized due to a failure to meet increased quality needs. Most of the mothers preferred private clinics for antenatal care and the district hospital for delivery due to the better service quality of these facilities compared to that of the commune health stations (CHSs). Mothers had few sociocultural barriers to acquiring service information or utilizing services based on their improved standard of living. A financial burden for some services, including caesarian section, still existed for uninsured mothers, while their insured counterparts had relatively few difficulties. CONCLUSIONS: For the improved macro-efficiency of MNCH systems, the government needs to rearrange human resources and/or merge some CHSs to achieve economies of scale and align with service volume distribution across the different levels.

Understanding the immunopathogenesis of autoimmune diseases by animal studies using gene modulation: A comprehensive review.

Autoimmune diseases are clinical syndromes that result from pathogenic inflammatory responses driven by inadequate immune activation by T- and B-cells. Although the exact mechanisms of autoimmune diseases are still elusive, genetic factors also play an important role in the pathogenesis. Recently, with the advancement of understanding of the immunological and molecular basis of autoimmune diseases, gene modulation has become a potential approach for the tailored treatment of autoimmune disorders. Gene modulation can be applied to regulate the levels of interleukins (IL), tumor necrosis factor (TNF), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), interferon-γ and other inflammatory cytokines by inhibiting these cytokine expressions using short interfering ribonucleic acid (siRNA) or by inhibiting cytokine signaling using small molecules. In addition, gene modulation delivering anti-inflammatory cytokines or cytokine antagonists showed effectiveness in regulating autoimmunity. In this review, we summarize the potential target genes for gene or immunomodulation in autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel diseases (IBD) and multiple sclerosis (MS). This article will give a new perspective on understanding immunopathogenesis of autoimmune diseases not only in animals but also in human. Emerging approaches to investigate cytokine regulation through gene modulation may be a potential approach for the tailored immunomodulation of some autoimmune diseases near in the future.

Stem Cell Factor-Inducible MITF-M Expression in Therapeutics for Acquired Skin Hyperpigmentation.

Rationale: Microphthalmia-associated transcription factor M (MITF-M) plays important roles in the pigment production, differentiation and survival of melanocytes. Stem cell factor (SCF) and its receptor KIT stimulate MITF-M activity via phosphorylation at the post-translation level. However, the phosphorylation shortens half-life of MITF-M protein over the course of minutes. Here, we investigated novel hypotheses of (i) whether SCF/KIT can regulate MITF-M activity through gene expression as the alternative process, and (ii) whether chemical inhibition of KIT activity can mitigate the acquired pigmentation in skin by targeting the expression of MITF-M. Methods: We employed melanocyte cultures in vitro and pigmented skin samples in vivo, and applied immunoblotting, RT-PCR, siRNA-based gene knockdown and confocal microscopy. Results: The protein and mRNA levels of MITF-M in epidermal melanocytes and the promoter activity of MITF-M in B16-F0 melanoma cells demonstrated that SCF/KIT could trigger the expression of MITF-M de novo, following the phosphorylation-dependent proteolysis of pre-existing MITF-M protein. SCF/KIT regulated the transcription abilities of cAMP-responsive element-binding protein (CREB), CREB-regulated co-activator 1 (CRTC1) and SRY-related HMG-box 10 (SOX10) but not ß-catenin at the MITF-M promoter. Meanwhile, chemical inhibition of KIT activity abolished SCF-induced melanin production in epidermal melanocyte cultures, as well as protected the skin from UV-B-induced hyperpigmentation in HRM2 mice or brownish guinea pigs, in which it down-regulated the expression of MITF-M de novo at the promoter level. Conclusion: We propose the targeting of SCF/KIT-inducible MITF-M expression as a strategy in the therapeutics for acquired pigmentary disorders.

Short- and long-term seizure-free outcomes of dietary treatment in infants according to etiology.

PURPOSE: It is important to determine whether specific etiology is more effective to dietary treatment so that the diet can be started earlier for infants. We evaluated etiology-specific, seizure-free outcomes of dietary treatment in infants <1 year of age. METHODS: We conducted a 10-year, retrospective, longitudinal observational study of 115 infants treated with ketogenic diet (KD) or modified Atkins diet (MAD). RESULTS: Most patients (70%) received classical KD; 30% received MAD. During follow-up, 90%, 73%, and 61% of the patients remained on the diet at 3, 6, and 12 months, respectively. Seizure-free outcomes were reported in 50%, 44%, and 50% of the patients at 3, 6, and 12 months, respectively. Long-term seizure-free outcomes over 12 months were reported in 43 (74%) of 58 infants who were seizure-free at 3 months. Etiologies were mostly symptomatic (structural brain abnormalities, genetic, or metabolic) in 83 (72%) of 115 patients. According to underlying etiology, long-term seizure-free outcomes were observed in 14 (33%) of 42 patients with structural brain abnormalities, 7 (33%) of 21 with genetic etiologies, 7 (35%) of 20 with metabolic etiologies, and 15 (47%) of 32 with unknown etiologies. There were no etiology-based differences with respect to long-term seizure-free outcomes (P = 0.63). CONCLUSION: The high rate of long-term seizure-free outcomes can be predicted based on the seizure freedom at 3 months regardless of etiology. Early dietary treatment is beneficial, even in infants <1 year of age with specific symptomatic etiologies such as genetic, structural brain abnormalities, and metabolic etiology.

Nuclear Entry of CRTC1 as Druggable Target of Acquired Pigmentary Disorder.

Rationale: SOX10 (SRY-related HMG-box 10) and MITF-M (microphthalmia-associated transcription factor M) restrict the expression of melanogenic genes, such as TYR (tyrosinase), in melanocytes. DACE (diacetylcaffeic acid cyclohexyl ester) inhibits melanin production in α-MSH (α-melanocyte stimulating hormone)-activated B16-F0 melanoma cells. In this study, we evaluated the antimelanogenic activity of DACE in vivo and elucidated the molecular basis of its action. Methods: We employed melanocyte cultures and hyperpigmented skin samples for pigmentation assays, and applied chromatin immunoprecipitation, immunoblotting, RT-PCR or siRNA-based knockdown for mechanistic analyses. Results: Topical treatment with DACE mitigated UV-B-induced hyperpigmentation in the skin with attenuated expression of MITF-M and TYR. DACE also inhibited melanin production in α-MSH- or ET-1 (endothelin 1)-activated melanocyte cultures. As a mechanism, DACE blocked the nuclear import of CRTC1 (CREB-regulated co-activator 1) in melanocytes. DACE resultantly inhibited SOX10 induction, and suppressed the transcriptional abilities of CREB/CRTC1 heterodimer and SOX10 at MITF-M promoter, thereby ameliorating facultative melanogenesis. Furthermore, this study unveiled new issues in melanocyte biology that i) KPNA1 (Impα5) escorted CRTC1 as a cargo across the nuclear envelope, ii) SOX10 was inducible in the melanogenic process, and iii) CRTC1 could direct SOX10 induction at the transcription level. Conclusion: We propose the targeting of CRTC1 as a unique strategy in the treatment of acquired pigmentary disorders.

The Reliability and Validity of the Korean Version of the Autism-Spectrum Quotient.

OBJECTIVE: This study was conducted to investigate the reliability and validity of the Korean version of Autism-Spectrum Quotient (AQ). METHODS: 20 participants with high-functioning autism (HFA) and 99 normal participants were recruited. All participants were completed the AQ and Empathy Quotient (EQ), and parents of the HFA group completed the parent-report AQ. For testing the reliability, we examined Cronbach's alpha, performed item analysis, and compared self versus parent report score of HFA participants. For testing the validity, we compared the difference of the score of AQ among HFA and control group using independent t-tests, and performed correlation analysis between AQ and EQ. The receiver operation characteristic curve analysis was performed to determine a cut-off. RESULTS: The Korean version of the AQ exhibited adequate internal consistency, and in most items, the HFA group scored higher in comparison to the control group. It was demonstrated that AQ has good discriminant validity through the confirmation of the significant difference in the AQ score between two groups. The concurrent validity was established through the significant correlation between AQ and EQ in the HFA group. The best estimate cut-off score of AQ for screening was 23. CONCLUSION: The Korean version of the AQ was determined as a reliable and valid instrument to assess HFA in Korean population.

Protective Role of Parenting Attitude on the Behavioral and Neurocognitive Development of the Children from Economically Disadvantaged Families.

OBJECTIVE: Association between home environment and the behavioral and neurocognitive development of children from a community childcare center for low-income families was examined (aged 6 to 12 years, n=155). METHODS: The parents performed a questionnaire on home environment (K-HOME-Q) to assess home environment including parenting attitude and the Child Behavior Checklist (K-CBCL). The children performed the Wechsler Intelligence (IQ) Scale, Stroop interference test (Stroop), word fluency test (WF), and design fluency test (DF) to assess their neurocognitive development. RESULTS: 'Nurturing of Development' and 'Variety of Language Interaction' scores from the K-HOME-Q, were inversely associated with total behavior problems, externalization, rule-breaking, and aggressive behavior subscales of K-CBCL, and 'Emotional atmosphere' and 'Tolerance toward the child' scores showed inverse associations with the total behavior problems, rule-breaking, aggressive behavior, and withdrawn/depressed subscales. Despite economic hardship, the mean scores of the neurocognitive tests were comparable to the average level of Korean children's normative sample. However, 'Nurturing of Development' and 'Tolerance toward the Child' score of K-HOME-Q were associated with better executive function (IQ, WF, DF). CONCLUSION: These results suggest that parental stimulation of development and tolerant parenting attitude may offer protection against the negative effects of suboptimal economic environment on children's behavior and neurocognitive development.

Radiation Dose Reduction without Compromise to Image Quality by Alterations of Filtration and Focal Spot Size in Cerebral Angiography.

OBJECTIVE: Different angiographic protocols may influence the radiation dose and image quality. In this study, we aimed to investigate the effects of filtration and focal spot size on radiation dose and image quality for diagnostic cerebral angiography using an in-vitro model and in-vivo patient groups. MATERIALS AND METHODS: Radiation dose and image quality were analyzed by varying the filtration and focal spot size on digital subtraction angiography exposure protocols (1, inherent filtration + large focus; 2, inherent + small; 3, copper + large; 4, copper + small). For the in-vitro analysis, a phantom was used for comparison of radiation dose. For the in-vivo analysis, bilateral paired injections, and patient cohort groups were compared for radiation dose and image quality. Image quality analysis was performed in terms of contrast, sharpness, noise, and overall quality. RESULTS: In the in-vitro analysis, the mean air kerma (AK) and dose area product (DAP)/frame were significantly lower with added copper filtration (protocols 3 and 4). In the in-vivo bilateral paired injections, AK and DAP/frame were significantly lower with filtration, without significant difference in image quality. The patient cohort groups with added filtration (protocols 3 and 4) showed significant reduction of total AK and DAP/patient without compromise to the image quality. Variations in focal spot size showed no significant differences in radiation dose and image quality. CONCLUSION: Addition of filtration for angiographic exposure studies can result in significant total radiation dose reduction without loss of image quality. Focal spot size does not influence radiation dose and image quality. The routine angiographic protocol should be judiciously investigated and implemented.

Association of current phthalate exposure with neurobehavioral development in a national sample.

BACKGROUND: Previous studies have indicated that phthalate exposure may influence the development of children, but the current data are limited, and controversy remains regarding the sex-specific and age-specific effects of phthalate exposure. METHODS: We investigated the sex- and age-specific associations of current phthalate exposure with neurobehavioral development scores in a nationally representative sample of 6-18-year-olds participating in the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C). Neurobehavioral development was assessed using the Korean Child Behavior Checklist (CBCL, N=1723) and the Korean Attention Deficit Hyperactivity Disorder Rating Scale (ARS, N=867). We measured the concentrations of phthalate metabolites in urine samples using high-performance liquid chromatography tandem mass spectrometry. The associations between urine phthalate metabolite concentrations and neurobehavioral development were examined by survey regression analysis for complex sampling and penalized regression splines using a generalized additive model. RESULTS: Survey regression analysis revealed that a higher mono-n-butyl phthalate (MnBP) level was associated with social (ß=0.60; 95% confidence interval=0.15-1.05), thought (0.55; 0.08-1.03), and attention (0.68; 0.21-1.14) problems on the CBCL. A significant association was found between the MnBP level and the ARS hyperactivity subscale score (0.42; 0.05-0.58). Higher levels of MnBP (0.87; 0.20-1.54), mono-2-ethyl-5-oxohexyl phthalate (MEOHP, 0.61; 0.11-1.11) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP, 0.51; 0.04-0.97) were associated with an increase in thought problems among the girls. Among the younger children aged 6-11 years, significant positive associations between the MnBP (0.71; 0.09-1.33), MECPP (0.74, 0.14-1.34), MEOHP (0.65; 0.10-1.20), and MEHHP (0.71; 0.21-1.21) levels and social problems and between the MnBP (1.11; 0.37-1.84), MEOHP (0.64; 0.13-1.15), and MEHHP (0.66; 0.18-1.14) levels and attention problems were observed. The penalized regression splines for the age-specific relationships between the urinary MnBP, MEOHP, and MEHHP levels and social and attention problems exhibited positive supralinear relationships with downward curvature in the 6-11 year age group. In contrast, the score for social problems exhibited nearly linear relationships with these levels in the 12-18 year age group. CONCLUSIONS: In this national sample, increased phthalate exposure exhibited supralinear associations with social, thought and attention problems in children aged 6-11 years, who showed greater vulnerability to phthalate exposure. The results highlight the need for the environmental regulation of phthalate exposure in younger children, even at low dosages.