Plasma Amyloid-ß Oligomerization Tendency Predicts Amyloid PET Positivity.

PURPOSE: Among other emerging amyloid-targeting blood-based biomarkers, Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) measures dynamic changes in concentration of oligomeric amyloid-ß (OAß), which is considered the main pathogenic culprit of Alzheimer's disease (AD), in plasma after spiking with synthetic amyloid-ß (Aß). We aimed to investigate the predictability of MDS-OAß on amyloid positron emission tomography (PET) positivity. PATIENTS AND METHODS: A total of 96 subjects who visited Seoul National University Bundang Hospital for medical check-up complaining of cognitive decline and had undergone extensive medical assessment were recruited. Amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid PET. Plasma OAß concentration was measured by MDS-OAß. In the previous validation study, 0.78ng/mL was established as the cut-off value and the plasma OAß concentration higher than or equal to the cut-off value was defined as MDS-OAß positive. RESULTS: MDS-OAß positivity could discriminate amyloid PET positivity with the AUC value of 0.855 (95% CI 0.776-0.933). Adding MDS-OAß positivity to prediction models including age, MMSE score, and APOE ε4 status improved performance up to the AUC value of 0.926 (95% CI 0.871-0.980). CONCLUSION: The Aß oligomerization tendency in plasma could predict amyloid PET positivity with high performance, and, when it is combined with age, MMSE score, and APOE ε4 status, predictability was improved substantially. This suggests the potential of MDS-OAß as a useful initial stage test in the clinical and research fields of AD.

Endogenous Aß peptide promote Aß oligomerization tendency of spiked synthetic Aß in Alzheimer's disease plasma.

Alzheimer's disease (AD) is the most common form of age-associated dementia. Several studies have predicted that AD is caused by the production and deposition of the ß-amyloid peptide (Aß) in the brain, which is one of pathologic hallmarks of AD. In particular, Aß oligomers are reportedly the most toxic and pathogenic of other peptide forms. We previously developed Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß), a technique for measuring Aß oligomerization in plasma to diagnose AD. Here, we clarified the molecular sizes of oligomers that can be detected by the MDS and investigated differences in plasma spiking with a synthetic Aß peptide in the plasma of AD patients and individuals with non-AD neurological conditions. To determine Aß oligomer sizes detectable by MDS, size exclusion chromatography (SEC) was first performed on incubated samples of synthetic Aß42 peptides. As a result, no MDS signals were observed for the Aß42 monomer fractions, but strong signals were found for oligomers of 7-35-mers long. Also, an amplified luminescent proximity homogeneous assay-linked immunoassay (AlphaLISA) was used to confirm that synthetic Aß peptides not only recruited endogenous Aß in plasma but also induced significantly stronger seeding in AD plasma than in healthy control plasma. In addition, the absence of the MDS signals in Aß-depleted plasma confirmed that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aß in plasma. Therefore, the MDS-OAß measurement of oligomerization differences in plasma after incubation with spiked synthetic Aß peptides has significant potential in AD diagnosis.

Blood Amyloid-ß Oligomerization as a Biomarker of Alzheimer's Disease: A Blinded Validation Study.

BACKGROUND: Oligomeric amyloid-ß (Aß) is one of the major contributors to the pathomechanism of Alzheimer's disease (AD); Aß oligomerization in plasma can be measured using a Multimer Detection System-Oligomeric Aß (MDS-OAß) after incubation with spiked synthetic Aß. OBJECTIVE: We evaluated the clinical sensitivity and specificity of the MDS-OAß values for prediction of AD. METHODS: The MDS-OAß values measured using inBlood™ OAß test in heparin-treated plasma samples from 52 AD patients in comparison with 52 community-based subjects with normal cognition (NC). The inclusion criterion was proposed by the NINCDS-ADRDA and additionally required at least 6 months of follow-up from the initial clinical diagnosis in the course of AD. RESULTS: The MDS-OAß values were 1.43±0.30 ng/ml in AD and 0.45±0.19 (p < 0.001) in NC, respectively. Using a cut-off value of 0.78 ng/ml, the results revealed 100% sensitivity and 92.31% specificity. CONCLUSION: MDS-OAß to measure plasma Aß oligomerization is a valuable blood-based biomarker for clinical diagnosis of AD, with high sensitivity and specificity.

Factors Influencing Self-Care Competence in Korean Women With Rheumatoid Arthritis.

BACKGROUND: The incidence of many chronic diseases is increasing rapidly in South Korea. Rheumatoid arthritis is a chronic disease for which treatment by both doctors and long-term self-care by patients is deemed very important for successful disease management. PURPOSE: This study is designed to examine and identify the factors influencing self-care competence in Korean women with rheumatoid arthritis. METHODS: A cross-sectional descriptive design was employed. Participants included 132 women aged 20 years or older who were visiting rheumatoid arthritis outpatient clinics at hospitals in Seoul and Gyeonggi-do, South Korea. Measures included a demographics form, Self-as-Carer Inventory, Korean Activities of Daily Living scale, Visual Analogue Scale, Mishel Uncertainty in Illness Scale-Community Form, and Self-esteem Scale. RESULTS: The analyses illustrated the significance of the prediction model (F = 21.744, p < .001). The value of the adjusted R was set at .401, corresponding to 40.1% explanatory power. Uncertainty (ß = -.43) and self-esteem (ß = .26) were identified as having the most influence on self-care competence in Korean women with rheumatoid arthritis. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This cross-sectional study yielded preliminary evidence that nursing interventions that reduce uncertainty and improve self-esteem in Korean women with rheumatoid arthritis are necessary to promote the self-care competence of this vulnerable population. Healthcare professionals should recognize uncertainty and self-esteem as factors that influence self-care competence in Korean women with rheumatoid arthritis.

Development of a Community-Based Palliative Care Model for Advance Cancer Patients in Public Health Centers in Busan, Korea.

PURPOSE: A feasible palliative care model for advance cancer patients is needed in Korea with its rapidly aging population and corresponding increase in cancer prevalence. This study describes the process involved in the development of a community-based palliative care (CBPC) model implemented originally in a Busan pilot project. MATERIALS AND METHODS: The model development included steps I and II of the pilot project, identification of the service types, a survey exploring the community demand for palliative care, construction of an operational infrastructure, and the establishment of a service delivery system. Public health centers (including Busan regional cancer centers, palliative care centers, and social welfare centers) served as the regional hubs in the development of a palliative care model. RESULTS: The palliative care project included the provision of palliative care, establishment of a support system for the operations, improvement of personnel capacity, development of an educational and promotional program, and the establishment of an assessment system to improve quality. The operational infrastructure included a service management team, provision teams, and a support team. The Busan Metropolitan City CBPC model was based on the principles of palliative care as well as the characteristics of public health centers that implemented the community health projects. CONCLUSION: The potential use of the Busan CBPC model in Korea should be explored further through service evaluations.

The inhibitory effect of Duchesnea chrysantha extract on the development of atopic dermatitis-like lesions by regulating IgE and cytokine production in Nc/Nga mice.

Duchesnea chrysantha belongs to the Rosaceae family and has been used traditionally for the treatment of various diseases in Korea and other parts of East Asia. This study examined the antiinflammatory effect of Duchesnea chrysantha extract (DcE) on atopic dermatitis in vitro and in vivo. DcE inhibited the production of IL-6, IL-8 and MCP-1 in THP-1 cells and the release of IL-6 and MCP-1 in EoL-1 cells after treatment with house dust mite extract. In the in vivo experiment, Nc/Nga mice were sensitized to DNCB and then orally and dorsally administered DcE (50 mg/kg in PBS) for 3 weeks. The DcE administration significantly reduced the skin severity score when compared with the control group and inhibited the thickening of the epidermis and infiltration of inflammatory cells into the dermis. In addition, the serum IgE levels decreased markedly in the DcE-treated mice when compared with the control group. The synthesis of IL-5, IL-13, MCP-1 and eotaxin was also decreased in splenocytes of the DcE-treated group, while IFN-γ was increased in the Dc-administered group. These results may indicate that DcE attenuates the development of atopic dermatitis-like lesions by lowering the IgE and inflammatory cytokine levels, and that it is useful in drug development for the treatment of atopic dermatitis.

House dust mite, Dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human monocytic THP-1 cells.

The house dust mite (Dermatophagoides pteronissinus) plays an important role in the pathogenesis of allergic diseases, including atopic dermatitis, and asthma. Monocyte chemotactic protein 1 (MCP-1/CCL2)/IL-6/IL-8 (CXCL8) plays a pivotal role in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The aim of this study was to investigate the effect of D. pteronissinus extract (DpE) on expression of MCP-1/IL-6/IL-8 mRNA and protein and the signal transduction in the human monocytic cell line, THP-1. The mRNA and protein expression of MCP-1/CCL2, IL-6, and IL-8 were elevated by DpE in a time and dose-dependent manner in THP-1 cells. The increased expression of MCP-1, IL-6, and IL-8 was not affected by aprotinin (serine protease inhibitor) or E64 (cysteine protease inhibitor). We found that MCP-1 and IL-6 expression due to DpE was related to Src, protein kinase C delta (PKC delta), extracellular-signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and IL-8 expression was involved in Src family tyrosine kinase, PKC delta, ERK. DpE increased the phosphorylation of ERK and p38 MAPK after 5min and peaked at 30min. The activation was significantly blocked by PP2, an inhibitor of Src family tyrosine kinase and rottlerin, an inhibitor of PKC delta (p<0.01). DpE increases MCP-1, IL-6, and IL-8 expression and transduces its signal via Src family tyrosine kinase, PKC, and ERK in a protease-independent manner. This finding may contribute to the elucidation of the pathogenic mechanism triggered by DpE .

Shewanella donghaensis sp. nov., a psychrophilic, piezosensitive bacterium producing high levels of polyunsaturated fatty acid, isolated from deep-sea sediments.

A Gram-negative, motile, rod-shaped, psychrophilic bacterium, LT17T, was isolated from deep-sea sediments (3300 m depth) of the East Sea (Sea of Japan). Optimal growth of LT17T requires the presence of 2.5 % (w/v) NaCl, a pH of 7.0-7.5 and a temperature of 17 degrees C. The isolate grows optimally under a hydrostatic pressure of 10 MPa and growth is possible between 0.1 and <30 MPa. The novel strain is positive in tests for catalase, oxidase, lipase, beta-glucosidase and gelatinase activities and reduces nitrate to nitrate. The predominant cellular fatty acids are iso-C13 : 0, iso-C15 : 0, C16 : 0, C16 : 1omega7 and C20 : 5omega3. The DNA G+C content of strain LT17T is 38.8 mol%. Phylogenetic analysis of 16S rRNA gene sequences places this bacterium in the class Gammaproteobacteria, within the genus Shewanella. The closest relatives of strain LT17T are Shewanella japonica (97.8 % gene sequence similarity), Shewanella pacifica (97.5 %), Shewanella olleyana (96.8 %), Shewanella frigidimarina (96.5 %) and Shewanella gelidimarina (95.4 %). The DNA-DNA hybridization levels between the novel isolate and its closest known phylogenetic relatives, S. japonica and S. pacifica, are lower than 14 %. On the basis of this polyphasic evidence, strain LT17T represents a novel species of the genus Shewanella, for which the name Shewanella donghaensis sp. nov. is proposed. The type strain is LT17T (=KCTC 10635BPT=JCM 12524T).

Spotted fever group and typhus group rickettsioses in humans, South Korea.

The presence of the nucleic acid of the spotted fever group (SPG) and typhus group (TG) rickettsiae was investigated in 200 serum specimens seropositive for SFG rickettsiae by multiplex-nested polymerase chain reaction with primers derived from the rickettsial outer membrane protein B gene. The DNA of SFG, TG, or both rickettsiae was amplified in the 24 serum specimens, and sequence analysis showed Rickettsia conorii, R. japonica, and R. felis in the specimens. R. conorii and R. typhi were found in 7 serum specimens, which indicated the possibility of dual infection in these patients. These findings suggest that several kinds of rickettsial diseases, including boutonneuse fever, rickettsialpox, R. felis infection, and Japanese spotted fever, as well as scrub typhus and murine typhus, are occurring in Korea.

Seroepidemiology of spotted fever group and typhus group rickettsioses in humans, South Korea.

The prevalence of spotted fever group (SFG) and typhus group (TG) rickettsioses was investigated in 3,362 sera by immunofluorescence assay. The serum samples were obtained from patients with acute febrile episodes in South Korea from December 1992 to November 1993. The number of polyvalent positive sera against SFG rickettsial agents at the level of 1: 40 dilution was 269 (8%) in Rickettsia sibirica, 482 (14.34%) in R. conorii, and 546 (16.24%) in R. akari. Many of the positive sera contained immunoglobulin (Ig) M antibodies rather than IgG antibodies. These results strongly suggest that SFG rickettsioses are prevalent in Korea. For TG rickettsial agents, the number of positive sera was 1,096 (32.60%) in R. typhi and 951 (28.29%) in R. prowazekii. Only a few epidemic typhus positive sera contained IgM antibodies. The result suggests that recent and/or primary infections of epidemic typhus were very rare in Korea during the said period. Among seven patients who had high titers (1:5,120) of IgG antibody to R. prowazekii, six were over 50 years old. The result suggests that Brill-Zinsser disease was prevalent in Korea.