Age-related macular degeneration (AMD) is a leading cause of blindness in people over 65 years old. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular AMD (nAMD); however, fibrosis remains an unmet medical need due to the lack of effective medications. This study evaluated eight natural products from Celastrus orbiculatus, which has been reported to have anti-inflammatory effects, for their effects on the fibrotic pathological process as well as choroidal neovascularization (CNV). We investigated the half-maximal inhibitory concentration (IC 50) values of these compounds on VEGF and alphasmooth muscle actin (α-SMA, a fibrosis marker) expression-induced by human acute monocytic cell (THP-1) conditioned media in retinal pigment epithelium cells (ARPE-19). Four compounds reduced both VEGF and α-SMA at 10 μM, with three—Celafolin A-1, COFH5645, and COFH543435—showing the highest potency. Intravitreal injections of the compound in a mouse model of CNV induced by laser photocoagulation confirmed its efficacy. Celafolin A-1 significantly reduced α-SMA and VEGF expression and decreased hyper-reflective lesions and CNV areas. Binding affinity measurements using biolayer interferometry identified an interaction between Celafolin A-1 and crystallin alpha B (Cryab), a protein involved in stress responses and fibrosis. Celafolin A-1 reduced the expression levels of Cryab as well as its phosphorylated form at Ser45, indicating that its mechanism involves the regulation of Cryab phosphorylation. Taken together, Celafolin A-1 exhibits dual inhibitory effects on VEGF and fibrosis, suggesting it as a candidate for the treatment of nAMD.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Objectives: This study aimed to identify the effectiveness of treatment programs for children with reading (RD) or mathematics disorders (MD). Structured treatment programs were developed to improve phonological awareness and number sense among children and adolescents with RD or MD, respectively, and the effectiveness of the learning disorder treatment programs were evaluated. Methods: We used standardized, objective diagnostic, and evaluation tools not only to recruit participants with RD, MD, or comorbid attention deficit and hyperactivity disorder, but also to assess the effectiveness of the treatments regarding both improved core neurocognitive deficits of RD or MD and academic achievement. Forty children with RD or MD received one-on-one treatments from therapists. Results: In the RD group, treatment effects were observed in all subtests. In the word and paragraph reading tests, the accuracy rates and fluency improved. The results of the phonological working memory test, word–sound correspondence test, and rapid automatic naming tests also improved. In the MD group, the accuracy rate and fluency on the arithmetic test improved. An increase in the accuracy rate in the size and distance comparison tests and a decrease in the error rate in the estimation test were also observed. However, there were no improvements in reaction time in these subtests. Conclusion Learning disorder treatment programs that focus on improving phonological awareness or number sense in children with RD or MD improved achievement, phonological awareness, and number sense.

Objectives: This study investigated the effectiveness of the intervention program for elementary school students with reading disorders. Methods: The intervention program focused on phonological awareness, phonics, and decoding training applied individually to 25 children with a reading disorder by the teachers in charge for four months. To measure the efficacy, this study evaluated the word reading accuracy, fluency, and the related cognitive functions, including phonemic awareness, phonics, and rapid automatized naming using the Computerized Comprehensive Learning Test-Reading before and after the program. Results: After the intervention, improvements were observed in the following: the reading fluency score and fluency percentile in the word attack test; reading accuracy rate, fluency score, and fluency percentile in the nonword decoding test; fluency score and fluency percentile in the rapid automatized naming tests; accuracy rate in the letter-sound matching test; accuracy rate in the nonword repetition test. On the other hand, there was no significant difference in the paragraph reading fluency test. According to the subtypes of reading disabilities, children with dyslexic or mixed types improved after the intervention. Conclusion Reading accuracy and fluency of school-aged children with reading disorders improved through the intervention program by the schoolteachers.

Objectives: This study investigated the effectiveness of the intervention program for elementary school students with reading disorders. Methods: The intervention program focused on phonological awareness, phonics, and decoding training applied individually to 25 children with a reading disorder by the teachers in charge for four months. To measure the efficacy, this study evaluated the word reading accuracy, fluency, and the related cognitive functions, including phonemic awareness, phonics, and rapid automatized naming using the Computerized Comprehensive Learning Test-Reading before and after the program. Results: After the intervention, improvements were observed in the following: the reading fluency score and fluency percentile in the word attack test; reading accuracy rate, fluency score, and fluency percentile in the nonword decoding test; fluency score and fluency percentile in the rapid automatized naming tests; accuracy rate in the letter-sound matching test; accuracy rate in the nonword repetition test. On the other hand, there was no significant difference in the paragraph reading fluency test. According to the subtypes of reading disabilities, children with dyslexic or mixed types improved after the intervention. Conclusion Reading accuracy and fluency of school-aged children with reading disorders improved through the intervention program by the schoolteachers.

No abstract available.
Brain

OBJECTIVES: This study investigated the prevalence of reading and mathematical learning disabilities of students at primary schools in Jeju Island, South Korea. We examined major causes of learning disabilities including reading disorder, mathematical disorder, attention deficit, and other causes including socioemotional factors. METHODS: We conducted screening processes to 659 participants (340 male, 51%) in 4 elementary schools in Jeju Island. To identify the causes of learning problems, 84 children were administered tests such as the Korean-Wechsler Intelligence Scale for Children-fourth edition, the Comprehensive Learning Test-Reading/Math, and the Comprehensive Attention Test. RESULTS: This study found that 13% of elementary school students in the Jeju region had learning disabilities. Among learning disabilities, specific reading and mathematical disorders accounted for 9% of study subjects. In addition, 2% of participants had intellectual impairment and 1% had other causes such as socioemotional factors. 65% of children with learning disabilities and 74% of children with reading or mathematic disorders had concurrent attention deficit disorder. 68% of children with reading disorders also had comorbid mathematical disorder. CONCLUSION: The prevalence, causes, and comorbidity of reading and mathematical learning disabilities of students in Jeju Island, South Korea did not differ from those in foreign countries. Because most learning disabilities are complex, comprehensive evaluations and tailored interventions are necessary to help children with learning disabilities.
Attention Deficit Disorder with Hyperactivity ; Child* ; Comorbidity ; Dyscalculia ; Dyslexia ; Epidemiology ; Humans ; Intelligence ; Korea ; Learning Disorders* ; Learning* ; Male ; Mass Screening ; Mathematics ; Prevalence*

OBJECTIVES: This study was conducted in order to develop a computerized test to measure the level of mathematic achievement and related cognitive functions in children and adolescents in South Korea. METHODS: The computerized Comprehensive Learning Test-Mathematic (CLT-M) consists of the whole number computation test, enumeration of dot group test, number line estimation test, numeral comparing test (magnitude/distance), rapid automatized naming test, digit span test, and working memory test. To obtain the necessary data and to investigate the reliability and validity of this test, 399 children and adolescents from kindergarten to middle school were recruited. RESULTS: The internal consistency reliability of the CLT-M was high (Cronbach's alpha=0.76). Four factors explained 66.4% of the cumulative variances. In addition, the data for all of the CLT-M subtests were obtained. CONCLUSION: The computerized CLT-M can be used as a reliable and valid tool to evaluate the level of mathematical achievement and associated cognitive functions in Korean children and adolescents. This test can also be helpful to detect mathematical learning disabilities, including specific learning disorder with impairment in mathematics, in Korea.
Adolescent* ; Child* ; Cognition ; Dyscalculia ; Humans ; Korea ; Learning ; Learning Disorders ; Mathematics* ; Memory, Short-Term ; Reproducibility of Results ; Specific Learning Disorder