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Neurodegenerative diseases (NDDs) are age-related disorders characterized by progressive neurodegeneration and neuronal cell loss in the central nervous system. Neuropathological conditions such as the accumulation of misfolded proteins can cause neuroinflammation, apoptosis, and synaptic dysfunction in the brain, leading to the development of NDDs including Alzheimer’s disease (AD) and Parkinson’s disease (PD). MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression post-transcriptionally via RNA interference. Recently, some studies have reported that some miRNAs play an important role in the development of NDDs by regulating target gene expression. MiRNA-485 (miR-485) is a highly conserved brain-enriched miRNA. Accumulating clinical reports suggest that dysregulated miR-485 may be involved in the pathogenesis of AD and PD. Emerging studies have also shown that miR-485 plays a novel role in the regulation of neuroinflammation, apoptosis, and synaptic function in the pathogenesis of NDDs. In this review, we introduce the biological characteristics of miR-485, provide clinical evidence of the dysregulated miR-485 in NDDs, novel roles of miR-485 in neuropathological events, and discuss the potential of targeting miR-485 as a diagnostic and therapeutic marker for NDDs.

This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea.A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high-sensitivity C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and adiponectin. A summary z-score was calculated by summing up the z-scores of each biomarker. The least-square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model.Participants with a BMI ≥27.5 kg/mA high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers.

Backgrounds/Aims: Unfavorable lipid profiles may be associated with prognosis among breast cancer survivors. We aimed to examine the association between physical activity levels and subclasses of lipoprotein among breast cancer survivors. Methods: We included a total of 378 women diagnosed with primary breast cancer and survived for ≥6 months since the surgery. Physical activity levels were presented as the metabolic equivalent of task (MET) hours/week from a structured questionnaire. High-throughput proton nuclear magnetic resonance (NMR) metabolomics platform was used to quantify plasma levels of specific lipid biomarkers and particle sizes. The multivariable adjusted least-square means (LS-means) and 95% confidence intervals (CIs) of lipid profile markers across physical activity (quartile) were estimated by using generalized linear models. Results: We observed inverse associations of physical activity levels with circulating levels of total triglycerides (TG), TG in very low-density lipoprotein (VLDL), and TG in high-density lipoprotein (HDL) among breast cancer survivors. LS-means (95% CIs) for 1st and 4th quartiles of physical activity were 1.07 (0.99-1.17) and 0.96 (0.88-1.04; p for trend=0.048) for total TG (nmol/L), 0.68 (0.62-0.74) and 0.60 (0.54-0.66; p for trend=0.045) for TG in VLDL (nmol/L), and 0.14 (0.13-0.15) and 0.12 (0.11-0.13; p for trend=0.045) for TG in HDL (nmol/L). These associations were limited to breast cancer survivors with stage II or III. We also found a smaller VLDL size with high physical activity among those with stage II or III. Among participants with a BMI of ≥25 kg/m2, we found that high physical activity was associated with decreased levels of TG in VLDL and small VLDL size; according to subsequent quartiles of physical activity, LS-means (95% CIs) were 0.73 (0.62-0.87), 0.88 (0.72-1.08), 0.74 (0.61-0.89), and 0.56 (0.44-0.71) for TG in VLDL (nmol/L), respectively (p for trend=0.047); and 38.67 (38.34-39.00), 38.75 (38.36-39.15), 38.65 (38.28-39.01), and 37.98 (37.52-38.45) for VLDL size (nm), respectively (p for trend=0.024). Conclusions: We found that high physical activity was associated with lower circulating levels of subclasses of TG and smaller VLDL size among breast cancer survivors with stage II or III or those with a BMI of ≥25 kg/m2. Further prospective or randomized controlled studies are warranted to confirm the significance of physical activity associated with favorable lipid profiles among breast cancer survivors. Funding Information: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT, MSIT) (No. 2014R1A2A2A01007794, 2019R1F1A1061017, and 2021R1F1A1062476) and K-BIO KIURI Center program (NRF2020M3H1A107330413). Citation Format: Hyun Jeong Cho, Minji Kang, Zisun Kim, Hyun Jo Youn, Jihyoung Cho, Jun Won Min, Yoo Seok Kim, Jung Eun Lee. Association between physical activity and lipid profile among breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 743.

Alzheimer’s disease (AD), an age-dependent, progressive neurodegenerative disorder, is the most common type of dementia, accounting for 50–70% of all dementia cases. Due to the increasing incidence and corresponding socioeconomic burden of dementia, it has rapidly emerged as a challenge to public health worldwide. The characteristics of AD include the development of extracellular amyloid-beta plaques and intracellular neurofibrillary tangles, vascular changes, neuronal inflammation, and progressive brain atrophy. However, the complexity of the biology of AD has hindered progress in elucidating the underlying pathophysiological mechanisms of AD, and the development of effective treatments. MicroRNAs (miRNAs, which are endogenous, noncoding RNAs of approximately 22 nucleotides that function as posttranscriptional regulators of various genes) are attracting attention as powerful tools for studying the mechanisms of diseases, as they are involved in several biological processes and diseases, including AD. AD is a multifactorial disease, and several reports have suggested that miRNAs play an important role in the pathological processes of AD. In this review, the basic biology of miRNAs is described, and the function and physiology of miRNAs in the pathological processes of AD are highlighted. In addition, the limitations of current pharmaceutical therapies for the treatment of AD and the development of miRNA-based next-generation therapies are discussed.

Alzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.

The innate immune system plays key roles in controlling Alzheimer's disease (AD), while secreting cytokines to eliminate pathogens and regulating brain homeostasis. Recent research in the field of AD has shown that the innate immune-sensing ability of pattern recognition receptors on brain-resident macrophages, known as microglia, initiates neuroinflammation, Aβ accumulation, neuronal loss, and memory decline in patients with AD. Advancements in understanding the role of innate immunity in AD have laid a strong foundation to elucidate AD pathology and devise therapeutic strategies for AD in the future. In this review, we highlight the present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion in AD. We also discuss how the AD pathology influences these biological processes.

Calcium, one of the most abundant minerals in the human body, has a pivotal role in human physiology. However, only a few studies have examined the association of dietary calcium intake with mortality in a population with low calcium intake.The aim of this study was to examine the association of dietary calcium intake with risk of all-cause and cause-specific mortality among Korean adults with low calcium intake.This study was a prospective cohort study.The analysis was conducted using data from 44,327 eligible Korean adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey 2007-2015. Dietary calcium intake was assessed using 1-day 24-hour recall data.The main outcomes of this study were mortality from all causes, cancer, cardiovascular disease, respiratory disease, and all other causes combined. The outcome was ascertained through linkage to the death registry compiled by Statistics Korea with the use of the resident registration number.Weighted Cox proportional hazard models were used to estimate the hazard ratios and 95% CIs of the all-cause and cause-specific mortality according to dietary calcium intake.During a mean follow-up of 7.28 person-years, 1,889 deaths were ascertained. After multivariable adjustment, the hazard ratios for all-cause mortality for the second quintile to the highest quintile of dietary calcium intake, respectively, compared with the first quintile were 0.86 (95% CI 0.73 to 1.00), 0.82 (95% CI 0.69 to 0.98), 0.85 (95% CI 0.69 to 1.03), and 0.78 (95% CI 0.64 to 0.96) (P for trend from the lowest to the highest quintile = .04). There were no statistically significant associations between dietary calcium intake and risk of mortality from cancer, cardiovascular, or respiratory disease.In this large prospective cohort study of Korean adults, lower dietary calcium intake was associated with a higher risk of all-cause mortality.

Background Alzheimer`s disease (AD) is a progressive neurodegenerative disease worldwide. Accumulation of amyloid-β (Aβ), neurofibrillary tangles and neuroinflammation play the important neuro-pathology in patients with AD. miRNA is multifunctional and involved in physiological and pathological processes. Recently, microRNAs have been linked to neurodegenerative diseases. However, it is little known whether miRNA dysregulation contributes to AD pathology progression such as Aβ processing, phagocytosis and neuroinflammation. Here, we identify miR485-3p as a novel modulator of AD pathology in 5XFAD mice. Methods To study the role of miR485-3p in AD, we used in control or miR485-3p antisense oligonucleotides (miR485-3p ASO) injected 5XFAD mouse model. Changes of Aβ processing and clearance and inflammation were analyzed by biochemical method in vitro and in vivo. Result This study suggests that miR485-3p, a novel miRNA targeting SIRT1 may contribute to pathogenesis in an AD mouse. We found SIRT1 is significantly reduced in the precentral gyrus of Alzheimer patient`s and in 5XFAD mice. To determine whether the inhibition of miRNA 485-3p would affect AD pathology, we studied the effect of the antisense oligo in the brain of 5XFAD mice through direct intracerebral ventricular injection with miR485-3p ASO. We demonstrated that miR485-3p ASO significantly reduced Aβ plaque and amyloid biosynthetic enzyme. Importantly, the attenuation of Aβ plaques through miR485-3p ASO was mediated through Aβ phagocytic activity of glial cells, by which it can directly target CD36. MiR485-3p ASO also decreased inflammatory responses. Collectively, these responses inhibited neuronal loss caused by Aβ lead to improvements of cognitive impairment. Conclusion Our data provide evidence for the molecular mechanisms which underlie the miR485-3p ASO responses in an AD mouse model. These results suggest that attenuating miRNA 485-3p levels might represent a novel therapeutic approach in AD.

Diagnosis of current Alzheimer’s disease (AD) is difficult even for medical specialists, and there is no clear biomarker. Also, aging is highly related to the onset of AD. The purpose of this study is to screen miRNA as an aging-considered biomarker for AD treatment and diagnosis. The patient group for this study was divided into a young normal, old normal, or AD group. We developed a method of discovering sequentially expressed miRNAs to distinguish miRNAs that were sequentially expressed in the three groups. Sequentially expressed miRNAs correlated highly with the patient’s age, and most showed expression patterns that distinguished young, old, and AD. Specifically, the miRNA expression we found showed similar patterns in the brains of patients with AD. Among the selected miRNAs, one set derived from the same precursor: The expression of miR-150 was a disease- and age-specific downregulation in both 3p and 5p forms, and the precursor also had the same pattern. We named that triple matching. Also, the found miR-150 precursor had AD-specific miRNA-imbalance characteristics. We developed a novel AD diagnostic method using triple matching and miRNA-imbalance. The triple matching and miRNA imbalance-based relative ratio diagnosis method we developed will be very powerful in resolving the challenges of absolute diagnostic quantification based on biomarker expression. Also, our research results suggest the possibility of a treatment target for AD.

The authors wish to make the following corrections to this paper [1]. In the Affiliations: Dr. SangJoon Lee has been requested by Ulsan National Institutes of Science and Technology (UNIST) that his affiliation of UNIST be removed from the Affiliations, because Dr. Lee’s position was not officially assigned by UNIST when the paper was published. The corrected affiliation section should be: SangJoon Lee2: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, Japan. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated.

Background The development of natural cosmetic materials without side effects to protect skin from heat shock is necessary. We recently reported that advanced cooling composition (ACC) has anti-inflammatory effect in RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and strong anti-microbial effect against Pseudomonas aeruginosa, Staphylococcus aureus, MRSA (Methicillin-resistant Staphylococcus aureus), Candida albicans, and Streptococcus mutans. Aims To further investigate whether advanced anti-inflammation composition (AAIC), newly developed from existing ACC has beneficial effects in heat shock-induced immortalized human keratinocytes (HaCaT cells), HaCaT cells were pretreated with AAIC before heat shock treatment. Methods Cell viability for heat shock treatment and different concentrations of AAIC in HaCaT cells were assessed by MTT assay. Anti-oxidative activity of AAIC was measured using the DPPH assay. The protein expression in heat shock-induced HaCaT cells treated with AAIC was evaluated by immunofluorescence staining and western blot analysis. Results AAIC, which is effective at 100 µg/mL concentration, was nontoxic in HaCaT cells and had an anti-oxidative effect demonstrated by scavenging DPPH free radicals. AAIC treatment significantly attenuated the aberrant levels of pro-inflammatory and pro-apoptotic signaling molecules in heat shock-induced HaCaT cells compared with control cells. Conclusion AAIC potentially includes effective anti-oxidative activity, anti-inflammatory, and anti-apoptotic properties against heat shock-induced keratinocytes, suggesting that it can be provided as a raw material for imparting skin health.

Background: Glycoprotein IIb/IIIa (αIIb/β3) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to αIIb/β3. Methods: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to αIIb/β3, and its final reaction, clot retraction. Results: We found that G-Ro dose-dependently inhibited thrombin-induced platelet aggregation and attenuated the binding of fibrinogen to αIIb/β3 by phosphorylating cyclic adenosine monophosphate (cAMP)-dependently vasodilator-stimulated phosphoprotein (VASP; Ser157). In addition, G-Ro strongly abrogated the clot retraction reflecting the intensification of thrombus. Conclusion: We demonstrate that G-Ro is a beneficial novel compound inhibiting αIIb/β3-mediated fibrinogen binding, and may prevent platelet aggregation-mediated thrombotic disease.

We recently demonstrated that advanced cooling composition (ACC) has effective ingredients that exhibit anti-inflammatory effects in RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and exhibit strong antimicrobial effects on Pseudomonas aeruginosa, Staphylococcus aureus, MRSA (methicillin-resistant Staphylococcus aureus), Candida albicans, and Streptococcus mutans. To further investigate whether ACC has beneficial effects in ultraviolet B (UVB)-irradiated human keratinocytes (HaCaT cells), HaCaT cells were pretreated with ACC prior to UVB irradiation. Our data showed that ACC, which is effective at 100 &micro, g/mL, is nontoxic and has an antioxidative effect against UVB-induced intracellular reactive oxygen species (ROS) in HaCaT cells. In addition, ACC exerts cytoprotective effects against UVB-induced cytotoxicity in HaCaT cells by inhibiting abnormal inflammation and apoptosis through the regulation of mitogen-activated protein kinase (MAPK) signals, such as jun-amino-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). Therefore, these results indicate that ACC is a potentially beneficial raw material that possesses antioxidative, anti-inflammatory, and antiapoptotic effects against UVB-induced keratinocytes and may have applications in skin health.

Background Intracellular Ca 2+ ([Ca 2+ ] i ) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of [Ca 2+ ] i mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the Ca 2+ -antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS). Methods We investigated the Ca 2+ -antagonistic effect of KRG-TS on cyclic nucleotides-associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I (IP 3 RI) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation. Results The inhibition of [Ca 2+ ] i mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-Br-cAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) (Thr 197 ) by KRG-TS. The phosphorylation of IP 3 RI (Ser 1756 ) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-Br-cGMPS. These results suggest that the inhibitory effect of [Ca 2+ ] i mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation. Conclusion These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits [Ca 2+ ] i mobilization in thrombin–platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease.

We interviewed special educators (a) whose students with disabilities (SWDs) were proficient on the 2008 general education assessment but were assigned to the 2009 alternate assessment based on modified achievement standards (AA-MAS), and (b) whose students with mild disabilities took the 2008 alternate assessment based on alternate achievement standards (AA-AAS) and then the 2009 AA-MAS. We explored teachers’ rationales for test-type assignment, student characteristics, and quality of instruction to determine the test-type decisions’ appropriateness. All teachers based their decisions on combinations of factors in the guidelines plus subjective and noninstructional factors. Findings raised concerns about the subjectivity of the assessment assignment system and the inappropriate grade-level instruction for SWDs. Future research, implications of these findings, and limitations are discussed.

Effects of ginkgolide A (GA) from Ginkgo biloba leaves in collagen (10 μg/mL)-stimulated platelet aggregation were investigated. Zymographic analysis confirmed that pro-matrix metalloproteinase-9 (MMP-9) (92 kDa) was activated by GA to form an activated MMP-9 (86-kDa) on gelatinolytic activities. GA concentration-dependently inhibited platelet aggregation, intracellular Ca2+ mobilization, and thromboxane A2 (TXA2) formation by inhibiting the cyclooxygenase-1 (COX-1) activity in collagen-stimulated platelets. In addition, GA increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have an anti-platelet function in both resting and collagen-stimulated platelets. On the other hand, GA did not prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT) associated with the extrinsic and intrinsic coagulation pathways on human plasma, respectively. Therefore, we suggest that the inhibitory effect of GA on platelet aggregation might involve the following pathway. GA may increase the MMP-9 activity and intracellular cAMP and cGMP production, inhibit intracellular Ca2+ mobilization, and decrease TXA2 production by down-regulating the COX-1, thereby leading to inhibition of platelet aggregation without cytotoxicity. These results strongly indicate that GA is a potent inhibitor of collagen-stimulated platelet aggregation. It may play an important role as a negative regulator during platelet activation.

Korean general and special educators (n = 229) and American general and special educators (n = 348) were surveyed to explore (a) their perceptions of the importance of self-determination for students with disabilities, (b) how frequently they teach it, (c) the relationship between their perception of the importance of teaching self-determination and how often they teach it, and (d) the barriers they perceive that inhibit them from teaching it. American general and special educators attached higher importance to self-determination instruction than their Korean counterparts, but Korean educators taught self-determination skills to their students with disabilities more often than American educators did. There was greater incongruence between the value American educators placed on promoting self-determination and the time they devoted to teaching it than there was for Korean educators. Educators of both countries shared some perceived barriers to promoting self-determination (e.g., communication difficulty, students were too young, and other more urgent instructional needs), but each group cited barriers the other did not (e.g., teacher lacked sufficient skill, difficult to empathize with student, and no instructional latitude). Limitations and implications are discussed along with suggestions for future research.

ObjectivesTo estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea.DesignRetrospective cohort study.SettingThe Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service.ParticipantsAdult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded.Main outcome measuresHealthcare resource utilisation and costs related to DME in the 12-month postindex period.ResultsDuring the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (pConclusionThe average annual eye-related medical cost of the DEX-implant group was significantly lower than that of the anti-VEGF group during the study period, which was mainly due to decreased utilisation of eye care-related injections. Further long-term studies are needed.

Backgrounds: Gastric cancer, the fifth most common cancer, is the third most common cause of death from cancer with more than half of the cases occurring in Eastern Asia. The World Cancer Research Fund proposed “foods preserved by salting” as probable risk factors of gastric cancer, as evidenced from epidemiological studies addressing high salt foods and gastric cancer. Methods: We conducted a pooled analysis of Korean cohorts, The Korean Genome Epidemiology Study (KoGES) and Korean Multi-center Cancer Cohort Study (KMCC) to investigate the association between salted food intake and gastric cancer mortality among Korean population. We used cox proportional hazard models adjusted for potential confounding factors. We also reviewed global observational studies published until October 2018 and conducted a dose-response and a categorical meta-analysis. We used either a random effect model or a fixed effect model depending on the heterogeneity of the studies. We further categorized salted food into salted vegetable, fish, and soup to examine the relative risk (RR) of gastric cancer for specific salted foods. Results: The pooled RRs (95% confidence intervals, CIs) of gastric cancer among KoGES and KMCC were 0.99 (0.95-1.04) per 50g increase in salted food intake and 0.98(0.94-1.03), 1.79(1.05-3.06), 1.17(0.95-1.43) per 50g increase in intake of salted vegetable, fish, and soup, respectively. The pooled RR (95% CI) of gastric cancer, compared with the lowest category of salted food intake, was 0.95(0.63-1.27) for the highest category of intake. For the dose-response meta-analysis, we included 35 studies (15 cohort and 20 case-control), and the combined global RRs (95% CIs) of gastric cancer per 50g increase in intake were 1.07 (1.02-1.12) for salted food and 1.11(1.03-1.20), 2.10(1.27-3.46), 1.00(0.99-1.01) for salted vegetable, fish, and soup, respectively. When we analyzed prospective studies only, the RRs (95% CIs) per 50g increase in intake were 1.02(0.99-1.06) for salted food and 1.05(0.98-1.13), 1.26(1.01-1.59), 1.00(0.99-1.01) for salted vegetable, fish, and soup, respectively. For the categorical meta-analysis, 69 studies (23 cohort and 46 case-control) were included; the combined RRs (95% CIs) of the highest intake category, compared to the lowest intake category, were 1.19(1.11-1.27), 1.30(1.19-1.40), 1.06(0.95-1.16), and 1.03(0.92-1.14) for salted food, vegetable, fish, and soup, respectively. Conclusions: The pooled analysis showed a statistically significant association between risk of gastric cancer and salted fish intake among Korean population. The global meta-analyses also showed a significant association between intake of salted food and risk of gastric cancer. Acknowledgements: This study was funded by the Korean Foundation for Cancer Research (Grant Number. CB-2017-A-2) Citation Format: Jin Young Yoo, Hyun Jeong Cho, Sungji Moon, Inah Kim, Kwang-Pil Ko, Sue Kyung Park, Jung Eun Lee. Salted food intake and risk of gastric cancer: A pooled analysis of Korean cohorts and a global meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 636.

AIM In this study, we investigated the effects of caffeic acid (CAFA), a phenolic acid, on Ca(2＋)-antagonistic cyclic nucleotides associated with the phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP) and the thromboxane A2 (TXA2)-associated microsomal cyclooxygenase-1 (COX-1) activity in collagen (10 μg/mL)-stimulated platelet aggregation. METHODS Washed platelets (10(8)/mL) obtained from Sprague-Dawley rats (6-7 weeks old, male) were preincubated for 3 minutes at 37℃ in the presence of 2 mM exogenous CaCl2 with or without CAFA or other materials, stimulated with collagen (10 μg/mL) for 5 minutes, then used to determine the levels of intracellular cytosolic Ca(2＋) ([Ca(2＋)]i), TXA2, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), COX-1 activity, VASP and IP3R phosphorylation. RESULTS CAFA dose-dependently inhibited collagen-induced platelet aggregation and suppressed the production of TXA2, an aggregation-inducing autacoid associated with the strong inhibition of COX-1 in platelet microsomes exhibiting cytochrome C reductase activity. CAFA dose-dependently inhibited collagen-elevated [Ca(2＋)]i mobilization, which was increased by a cAMP-dependent protein kinase (A-kinase) inhibitor, Rp-8-Br-cAMPS, but not a cGMP-dependent protein kinase (G-kinase) inhibitor, Rp-8-Br-cGMPS. In addition, CAFA significantly increased the formation of cAMP and cGMP, intracellular Ca(2＋)-antagonists that function as aggregation-inhibiting molecules. CAFA increased IP3R (320 kDa) phosphorylation, indicating the inhibition of IP3-mediated Ca(2＋) release from internal stores (i.e. the dense tubular system) via the IP3R on collagen-activated platelets. Furthermore, CAFA-induced IP3R phosphorylation was strongly inhibited by an A-kinase inhibitor, Rp-8-Br-cAMPS, but only mildly inhibited by a G-kinase inhibitor, Rp-8-Br-cGMPS. These results suggest that the inhibition of [Ca(2＋)]i mobilization by CAFA is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CAFA elevated the phosphorylation of VASP-Ser(157), an A-kinase substrate, but not the phosphorylation of VASP-Ser(239), a G-kinase substrate. We demonstrate that CAFA increases cAMP and subsequently phosphorylates both IP3R and VASP-Ser(157) through A-kinase activation to inhibit [Ca(2＋)]i mobilization and TXA2 production via the inhibition of the COX-1 activity. CONCLUSIONS These results strongly indicate that CAFA is a potent beneficial compound that elevates the level of cAMP-dependent protein phosphorylation in collagen-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic diseases.

Recent studies have raised concerns about the vagueness of alternate assessment eligibility guidelines, specifically, that students with mild disabilities (SWMD) have been inappropriately assigned to alternate assessment–alternate achievement standards (AA-AAS). In this study, special education teachers ( N = 317) were surveyed about SWMD in vignettes to explore (a) perceptions of the clarity of eligibility guidelines, (b) teachers’ test-type decisions, (c) factors considered when making test-type decisions, and (d) teachers’ priority rankings of these factors. Teachers’ test-type decisions varied by state, subjectivity, and noninstructional factors. Findings raise concerns about the inconsistency and lack of specificity of the current state guidelines, their vulnerability to subjective interpretation of eligibility, and states’ different alternate assessment systems. Directions for future research, implications of the current findings, and limitations are discussed.

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 μM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

Definition of estuary and its administrative boundaries is needed for the practical management of estuarine environment. However, the majority of Korean estuaries are lack of scientific data required for defining the administrative boundaries. For this reason, a systematic way to set the boundaries has not been developed so far. This study proposed adaptive and comprehensive criteria in defining the boundary of an estuary based on the available data which includes physiochemical, geographical and topographical characteristics and regional data such as land uses and socio-economic conditions. An estuary boundary is defined with a sequential manner. First of all, according to the estuarine circulation pattern, 463 estuaries in Korea were classified into open estuaries and closed estuaries. Then an individual belonging to each type of estuary is defined an water zone boundary considering the physiochemical, geographical and topographical characteristics and land uses. Finally, a land zone boundary is set along the catchment. According to the proposed criteria, we have delineated 274 estuarine management zones in Korea on a trial basis and found that it was possible to set a boundary reasonably considering the difference of level of available data and regional characteristics in each estuary.

The purpose of this study was to establish an analytical framework and quantitative methodologies to analyze 'the cognitive effects of web map use' and to empirically test it. This experimental design was established based on the literature about spatial cognition. Accuracy, reaction time, and confidence within each participant were compared to measure the cognitive effects of web map use for wayfinding. Geometric accuracy of the cognitive maps was estimated and calculated based on the bidimensional regression. The experimental results showed that characteristics of map users and repetition of map use rather than types of map representation did significantly affect accuracy and reaction time of spatial cognition by using web maps. And confidence appeared to be low when the participants referred to both 2D and 3D maps for wayfinding tasks on the web maps. Understanding spatial cognition of web map users, which was suggested in the study, will help cartographers make more effectively-communicated maps.

This study examined the validity of test accommodation in third–eighth graders using differential item functioning (DIF) and mixture IRT models. Two data sets were used for these analyses. With the first data set (N = 51,591) we examined whether item type (i.e., story, explanation, straightforward) or item features were associated with item difficulty, item discrimination, or DIF. The second data set (N = 3,452) was used to investigate whether observed DIF was related to students' accommodation status, gender, race, disability, or latent academic ability. Item types and features were significantly related to item difficulty but not to DIF. Story items were not always more difficult than explanation or straightforward items. Observed DIF was partially explained by an interaction of accommodation use and academic ability. Limitations and implications of this study are discussed, and suggestions for future research are offered.

The purpose of this case study was to determine teachers’ rationales for assigning students with mild disabilities to alternate assessment based on alternate achievement standards (AA-AAS). In interviews, special educators stated that their primary considerations in making the assignments were low academic performance, student use of extended standard modifications, and the inflexible 1% cap. None of the teachers provided their students with grade-level content or appropriate modifications. Some students were competent in grade-level reading, but were assigned to the 2010 AA-AAS because read-aloud accommodation is not permitted in the reading passages of the general assessment. Findings raised concerns about the susceptibility of eligibility guidelines to lead to subjective decisions. Future research, implications of these findings, and limitations of the study are discussed.

Aim: In this study, we investigated the effect of (−)-epigallocatechin-3-gallate (EGCG) on cyclic nucleotide production and vasodilator-stimulated phosphoprotein (VASP) phosphorylation in collagen (10 µg/mL)-stimulated platelet aggregation.Methods: Washed platelets (108/mL) from Sprague-Dawley rats (6-7 weeks old, male) were preincubated for 3 min at 37°C in the presence of 2 mM exogenous CaCl2 with or without EGCG or other materials, stimulated with collagen (10 µg/mL) for 5 min, and then used for the determination of intracellular cytosolic Ca2+ ([Ca2+]i), thromboxane A2 (TXA2), adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and VASP phosphorylation.Results: EGCG dose-dependently inhibited collagen-induced platelet aggregation by inhibiting both [Ca2+]i mobilization and TXA2 production. Of two aggregation-inhibiting molecules, cAMP and cGMP, EGCG significantly increased intracellular levels of cAMP, but not cGMP. EGCG-elevated cAMP level was decreased by SQ22536, an adenylate cyclase inhibitor, but not by etazolate, a cAMPspecific phosphodiesterase inhibitor. In addition, EGCG elevated the phosphorylation of VASP-Ser157, a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-Ser239, a cGMP-dependent protein kinase substrate, in intact platelets and collagen-induced platelets, and VASP-Ser157 phosphorylation by EGCG was inhibited by both an adenylate cyclase inhibitor SQ22536 and an A-kinase inhibitor Rp-8-Br-cAMPS. We have demonstrated that EGCG increases cAMP via adenylate cyclase activation and subsequently phosphorylates VASP-Ser157 through A-kinase activation to inhibit [Ca2+]i mobilization and TXA2 production on collagen-induced platelet aggregation.Conclusions: These results strongly indicate that EGCG is a beneficial compound elevating cAMP level in collagen-platelet interaction, which may result in the prevention of platelet aggregation-mediated thrombotic diseases.

Promoting the self-determination of students with disabilities as a means to access the general curriculum has been the subject of research in recent years, as has the importance of efforts to promote self-determination during elementary years. To examine the status of such efforts in the field, 203 elementary special educators were surveyed in 23 states to determine how (a) classroom instructional practices or strategies, (b) classroom ecological or setting variables, and (c) self-reported barriers to promoting self-determination affected their perceptions of the importance of teaching self-determination and the frequency with which they did so. Results indicated that special educators’ perceived importance of teaching self-determination was not impacted by classroom instructional factors, but was affected by classroom ecological factors. Classroom ecological factors were not, however, significant in the frequency with which teachers provided instruction on self-determination, but classroom instructional practices were. Limitations and implications are discussed, and suggestions for future research are offered.

Ginseng, the root of Panax ginseng Meyer, has been used frequently in traditional oriental medicine and is popular globally. Ginsenosides, which are the saponins in ginseng, are the major components having pharmacological and biological activities, including anti-diabetic and anti-tumor activities. In this study, we investigated the effects of total saponin from Korean red ginseng (TSKRG) on thrombin-produced thromboxane A2 (TXA2), an aggregating thrombogenic molecule, and its associated microsomal enzymes cyclooxygenase (COX)-1 and TXA2 synthase (TXAS). Thrombin (0.5 U/mL) increased TXA2 production up to 169 ng/10(8) platelets as compared with control (0.2 ng/10(8) platelets). However, TSKRG inhibited potently TXA2 production to the control level in a dose-dependent manner, which was associated with the strong inhibition of COX-1 and TXAS activities in platelet microsomes having cytochrome c reductase activity. The results demonstrate TSKRG is a beneficial traditional oriental medicine in platelet-mediated thrombotic diseases via suppression of COX-1 and TXAS to inhibit production of TXA2.

Estuaries have been used competitively and exploited for the past decades in Korea. To preserve the environment of the estuaries from the integrated perspective, new policies have started to change such exploitative development in 2000s. Due to the poor knowledge-base, however, there has been a lack of support system which enables to execute such policies effectively. The present study was conducted to figure out the limits of the estuarine management research projects in Korea, which is being performed to overcome these limitations. It was studied through Gap Analysis between domestic and foreign advanced practices as well as Analytical Hierarchy Process on expert survey in terms of the three aspects: how well the estuarine management research projects in Korea meets the demands of policy making and administration; raises the awareness of citizens about the merit of environmental preservation; and establishes knowledge-based support system. This project turned out to reflect adequately the development of programs for building estuarine management systems. But consideration of other ministries was relatively scarce. But the contents which directly support community-based activities and educational programs to improve citizens` awareness were judged to be insufficient. According to the results of Gap Analysis, research about the structure and function of estuarine ecosystems, which can support to develop policy alternatives in detail, was relatively more necessary. Therefore, to support estuarine policy management effectively, the development of a realistic plan, which can overcome fundamental issues inherent in the Korean environmental management system and the limitation of the estuarine management research projects in Korea itself, is needed.

This study examined the learner characteristics and performance scores of students in the 2009 alternate assessment-modified achievement standard for one Midwestern state. Comparing performance differences by disability category for each content area from the students' 2008 test type assignments and performance scores facilitated examining the appropriateness of the 2009 test type assignment. The results raise concerns because some students with disabilities seemed to have been inappropriately assigned to test type. Students with intellectual disabilities had the lowest performances across grade level and subject area. Limitations and implications of this study are discussed and suggestions for future research are offered.

In this study, we investigated the effect of spinach saponin-enriched lipophilic fraction (SSEF) on collagen (10 μg/mL)-stimulated platelet aggregation in vivo. Dietary SSEF dose-dependently inhibited collagen-induced platelet aggregation by decreasing thromboxane A₂ production and intracellular Ca²⁺ agonist activity as an aggregation-inducing autacoidal molecule. In addition, SSEF significantly increased the formation of cyclic AMP and cyclic GMP, intracellular Ca²⁺ antagonists that are aggregation-inhibiting molecules in collagen-stimulated platelets. These results suggest that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation in vivo. Prothrombin time and activated partial thromboplastin time, indicators of blood coagulation, were potently prolonged by dietary SSEF in vivo. These findings suggest that SSEF prolongs the interval time between the conversion of fibrinogen to fibrin. Dietary SSEF also inhibited 0.4 M sucrose-induced hemolysis. Accordingly, our data demonstrate that SSEF might be a useful tool for inhibiting platelet activation and blood coagulation in thrombotic diseases.

In this study, we investigated the effect of spinach saponin-enriched fraction (SSEF) on collagen (10 μg/ml)-stimulated platelet aggregation. SSEF inhibited collagen-induced platelet aggregation, and which was involved in the inhibition of thromboxane A2 (TXA 2 ) production, an intracellular Ca 2+ -agonist as an aggregation-inducing autacoidal molecule. In addition, SSEF signifi cantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular Ca 2+ -antagonists as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that SSEF might inhibit Ca 2+ -elevation and TXA2 formation by increasing the production of Ca 2+ -antagonistic molecules cAMP and cGMP. These mean that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation. On the other hand, prothrombin time (PT) and activated partial thromboplastin time (APTT) were potently prolonged by SSEF. These fi ndings suggest that SSEF prolongs the internal time between the conversion of fi brinogen to fi brin. Accordingly, our data demonstrate that SSEF may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

Neutrophils are the first-line defense against microbes. Enhancing the microbicidal activity of neutrophils could complement direct antimicrobial therapy for controlling intractable microbial infections. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances neutrophil bactericidal activity (Yan et al. 2004. Nat. Med. 10: 161–167). In this study we show that LPC enhancement of neutrophil bactericidal activity is dependent on glycine, and is mediated by translocation of intracellularly located glycine receptor (GlyR) α2 to the plasma membrane, and subsequent increase in azurophil granule-phagosome fusion/elastase release. LPC induced GlyRα2-mediated [Cl−]i increase, leading to transient receptor potential melastatin (TRPM)2-mediated Ca2+ influx. Studies using human embryonic kidney 293 cells heterologously expressing TRPM2 and neutrophils showed that TRPM2 channel activity is sensitive to [Cl−]i. Finally, LPC induced p38 MAPK phosphorylation in an extracellular calcium/glycine dependent manner. SB203580, a p38 MAPK inhibitor, blocked LPC-induced enhancement in Lucifer yellow uptake, azurophil granule-phagosome fusion, and bactericidal activity. These results propose that enhancement of azurophil granule-phagosome fusion via GlyRα2/TRPM2/p38 MAPK signaling is a novel target for enhancement of neutrophil bactericidal activity.

The No Child Left Behind Act (2001) and the Individuals with Disabilities Education Improvement Act (2004) emphasize accountability to improve student academic achievement. Promoting self-determination has been proposed as a means to achieving this outcome. Elementary teachers in 30 states were surveyed to measure (a) their perceived importance of self-determination, (b) to what extent they teach it, and (c) the barriers that inhibit them from teaching it. Both general and special educators assigned considerable importance to self-determination instruction and reported at least occasionally providing such instruction. The authors found a lack of congruence between the value teachers place on promoting self-determination and the time they devote to teaching it. Limitations and implications are discussed, and suggestions for future research are offered.