Objectives: ：To describe the differences in long-term outcomes in Alzheimer’s disease (AD) patients according to initial dementia severity. Methods: ：A retrospective chart review of AD patients from a dementia clinic at the University Hospital in Korea was conducted from April 2010 to March 2017. There were 168 patients enrolled, who were divided into three groups based on initial Clinical Dementing Rating (CDR). There were 55 in the very mild group (CDR=0.5 ; mean age 80.64±6.57), 93 in the mild group (CDR=1 ; mean age 80.57±7.28) and 20 in the moderate group (CDR=2 ; mean age 83.00±9.07). Participants were treated with donepezil±memantine. The observation period was 2.44±0.50 years. Cognitive function and severity of dementia were initially assessed by the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) and were annually assessed by Mini-Mental State Exam (MMSE), CDR and CDR-Sum of boxes (CDR-SB). Results: ：The annual decline rate of MMSE score was -0.82 and those of very mild, mild, moderate groups were -0.63, -0.80, -1.96 respectively, while the annual change in CDR-SB score was 0.98, very mild group 0.86, mild group 1.03, moderate group 1.26. Education level, male, initial CDR were found to be significant potential factors in the annual change in MMSE, while initial CDR was a significant potential factor in the annual change in CDR-SB. Conclusion ：It is meaningful that we studied long-term outcomes of anti-dementia medications in real-world clinical setting. The higher the initial severity of AD, the higher the cognitive decline rate.

Objective: To analyze the rheological and biochemical properties of saliva in healthy adults. Methods: The subjects were seven healthy young adults (20-39 years). The whole saliva was collected by the spitting method between 9:00 am and 12:00 am. Unstimulated saliva was collected first, which was followed by the collection of stimulated saliva using citric acid was collected. The viscosity was measured using a capillary viscometer to examine the rheological properties. The MUC5B concentration was analyzed using an enzyme-linked immunosorbent assay (ELISA) for the biochemical properties. Results: Ten and five minutes were required on average for unstimulated saliva and stimulated saliva, respectively, to collect the minimum amount needed for analysis (8 ml). The flow rate increased from 1.037±0.323 ml/min to 1.823± 0.660 ml/min after stimulation (P=0.018). Citric acid stimulation also increased the MUC5B concentration in the saliva from 3.706±3.575 μg/ml to 6.928±2.03 μg/ml (P=0.028). The viscosity of saliva, however, did not show a significant difference between with (1.1±0.164 cSt) or without (1.019±0.08 cSt) stimulation (P=0.128). A positive correlation was observed between the flow rate and MUC5B concentration (Spearman’s rho=0.547, P=0.043). On the other hand, there was no significant correlation between the MUC5B concentration and viscosity both in the unstimulated and stimulated saliva (P=0.939 and 0.819, respectively). Conclusion No significant correlation was observed between the MUC5B concentration and viscosity. Considering the time required to collect samples, an analysis of the stimulated saliva appears feasible in various research settings.The feasibility of these analysis methods should be examined in a patient population.

Objective: To investigate the clinical and swallowing characteristics related to respiratory infection in patients with parkinsonism. Methods: One hundred and forty-two patients with parkinsonism who underwent videofluoroscopic swallowing studies (VFSS) were enrolled in this study. The initial clinical and VFSS characteristics were compared between patients with and without a history of respiratory infection in the past year. A multivariate logistic regression model was applied to identify clinical and swallowing characteristics related to respiratory infections. Results: Patients with respiratory infections were older (74.75±10.20 years vs. 70.70±8.83 years, p=0.037), had a higher Hoehn and Yahr (H&Y) stage (stage IV–V, 67.9% vs. 49.1%; p=0.047), and were more likely to have a diagnosis of idiopathic Parkinson’s disease (IPD) (67.9% vs. 41.2%, p=0.011) than those without respiratory infections. Among VFSS findings, bolus formation, premature bolus loss, oral transit time, pyriform sinus residues, pharyngeal wall coatings, and penetration/aspiration were significantly worse in patients with respiratory infections (p<0.05). Regarding clinical characteristics, higher H&Y stage (odds ratio [OR], 3.174; 95% confidence interval [CI], 1.226–8.216; p=0.017) and diagnosis of IPD (OR, 0.280, 95% CI, 0.111–0.706; p=0.007) were significantly related to respiratory infections in the multivariate analysis. Among VFSS findings, pyriform sinus residue (OR, 14.615; 95% CI, 2.257–94.623; p=0.005) and premature bolus loss (OR, 5.151; 95% CI, 1.047–25.338; p=0.044) were also significantly associated with respiratory infection. Conclusion This study suggests that disease severity, diagnosis, pyriform sinus residue, and premature bolus loss observed in VFSS are associated with respiratory infection in patients with parkinsonism.

PURPOSE: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. MATERIALS AND METHODS: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients. RESULTS: Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01). CONCLUSION: We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.
6-Mercaptopurine ; Alleles ; Computational Biology ; Cytochrome P-450 CYP1A1 ; Cytoprotection ; DNA Damage ; Genotype ; Humans ; Incidence ; Neutropenia* ; Pediatrics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma*

OBJECTIVES: Rare disease research requires a broad range of disease-related information for the discovery of causes of genetic disorders that are maladies caused by abnormalities in genes or chromosomes. A rarity in cases makes it difficult for researchers to elucidate definite inception. This knowledge base will be a major resource not only for clinicians, but also for the general public, who are unable to find consistent information on rare diseases in a single location. METHODS: We design a compact database schema for faster querying; its structure is optimized to store heterogeneous data sources. Then, clinicians at Seoul National University Hospital (SNUH) review and revise those resources. Additionally, we integrated other sources to capture genomic resources and clinical trials in detail on the Korean Rare Disease Knowledge base (KRDK). RESULTS: As a result, we have developed a Web-based knowledge base, KRDK, suitable for study of Mendelian diseases that commonly occur among Koreans. This knowledge base is comprised of disease summary and review, causal gene list, laboratory and clinic directory, patient registry, and so on. Furthermore, database for analyzing and giving access to human biological information and the clinical trial management system are integrated on KRDK. CONCLUSIONS: We expect that KRDK, the first rare disease knowledge base in Korea, may contribute to collaborative research and be a reliable reference for application to clinical trials. Additionally, this knowledge base is ready for querying of drug information so that visitors can search a list of rare diseases that is relative to specific drugs. Visitors can have access to KRDK via http://www.snubi.org/software/raredisease/.
Databases, Genetic ; Humans ; Information Storage and Retrieval ; Knowledge Bases ; Korea ; Online Systems ; Rare Diseases

Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.
Animals ; Body Weight ; Coronary Vessels ; Humans ; Iliac Artery ; Models, Animal ; Rabbits ; Research Personnel ; Stents* ; Tissue and Organ Harvesting