CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1.

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson\u27s disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1(-/-) mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP(+))-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling

CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin αIIb. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1-/- mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP+)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP+-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP+-induced neurotoxicity by blocking ASK1-mediated signaling

MALT lymphoma at the base of tongue of a 29-year-old woman treated with radiation therapy alone

Mucosa-associated lymphoid tissue (MALT) lymphoma is frequently reported in the gastrointestinal tract (GIT), but the incidence is low in the upper aerodigestive tract. In particular, MALT lymphoma of the tongue is very rare. Only four cases have been reported in the English literature to date. We report a case of 29-year-old woman who had a past history of peripheral T cell lymphoma of the head and neck and a new mass at the right base of tongue 3 years later. An incisional biopsy of the base of tongue revealed a new pathology, one that of extranodal marginal zone B cell lymphoma (MALT lymphoma). After staging work-up, she was diagnosed to be at the Ann Arbor stage IE. She was treated with 30.6 Gy of radiation therapy alone and there was no recurrence after 3 years follow-up

Unmet healthcare needs of elderly people in Korea

Abstract Background Elderly people often have more complicated healthcare needs than younger adults due to additional functional decline, physical illness, and psychosocial needs. Unmet healthcare needs increase illness severity, complications, and mortality. Despite this, research on the unmet healthcare needs of elderly people is limited in Korea. This study analysed the effect of functional deterioration related to aging on unmet healthcare needs based on the Korea Health Panel Study. Methods This cross-sectional study used data from the 2011–2013 survey of 8666 baseline participants aged 65 years and older. Unmet healthcare needs were calculated using a complex weighted sample design. Group differences in categorical variables were analysed using the Rao-Scott Chi-square test. Using logistic regression analysis, the association between unmet healthcare needs and aging factors was analysed. Results The prevalence of unmet healthcare needs in Korean elderly was 17.4%. Among them, the leading reason was economic hardship (9.2%). Adjusting for sex, age, socioeconomic characteristics, and health-related characteristics, the group with depression syndrome was 1.45 times more likely to have unmet healthcare needs than that without depression syndrome (95% CI = 1.13–1.88). The group with visual impairment was 1.48 times more likely to have unmet healthcare needs than that without it (95% CI = 1.22–1.79). The group with hearing impairment was 1.40 times more likely to have unmet healthcare needs than that without it (95% CI = 1.15–1.72). The group with memory impairment was 1.74 times more likely to have unmet healthcare needs than that without it (95% CI = 1.28–2.36). Conclusions The unmet medical needs of the elderly are more diverse than those of younger adults. This is because not only socioeconomic and health-related factors but also aging factors that are important to the health of the elderly are included. All factors were linked organically; therefore, integrated care is needed to improve healthcare among the elderly. To resolve these unmet healthcare needs, it is necessary to reorganize the healthcare system in Korea to include preventive and rehabilitative services that address chronic diseases in an aged society and promote life-long health promotion

Validation of the Korean Quick Dementia Rating System (K-QDRS)

The Quick Dementia Rating System (QDRS) is a brief and rapid dementia staging tool that does not require a trained rater. The purpose of this study is to demonstrate the validity, reliability, and diagnostic usefulness of the Korean version of the QDRS (K-QDRS). We collected a total of 411 subject-informant dyads including cognitively unimpaired (CU, n = 22), mild cognitive impairment (MCI, n = 198), and dementia (n = 191). The Clinical Dementia Rating (CDR) scale, Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of instrumental activity of daily living (K-IADL), Short Form of the Geriatric Depression Scale, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and detailed neuropsychological tests were administered as gold standards of dementia staging, cognition, function, mood, and behavior. Internal consistency of the K-QDRS was excellent with Cronbach's alpha of 0.933. Concurrent validity was also satisfactory, with the K-QDRS correlating highly with the CDR Sum of Boxes (Pearson's r = 0.791), K-MMSE (Pearson's r = -0.518), K-IADL (Pearson's r = 0.727), and CGA-NPI (Pearson's r = 0.700). The K-QDRS was highly correlated with the global CDR, K-IADL, and CGA-NPI. We suggested two types of comparisons (for initial diagnosis and for follow-up evaluation). The cutoff scores for follow-up were 1.0 for MCI, 3.5 for very mild dementia, 6.5 for mild dementia, and 11.0 for moderate dementia. The K-QDRS is a valid and reliable dementia rating questionnaire and can be used, briefly and rapidly, in various settings like clinical practices, longitudinal cohort studies, and community primary care

Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells

Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis. Valproic acid (VPA) (1–5 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105. However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN). The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter. Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1. Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs. These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs

Validation of the Korean Version of the Lewy Body Composite Risk Score (K-LBCRS)

The Lewy body composite risk score (LBCRS) is a useful clinical screening tool to help determine whether the dementia is related to Lewy body pathology. The purpose of this study is to verify reliability, validity, and diagnostic usefulness of Korean version of LBCRS (K-LBCRS). CDR-sum of boxes, Mini-Mental State Examination, and standardized scales related to cognition, mood, behavior, and motor function were administered to a total of 107 subjects, including 30 dementia with Lewy bodies (DLB), 54 Alzheimer's disease (AD), and 23 cognitively normal elderly people and their collateral informants. Internal consistency of the K-LBCRS was good with Cronbach's alpha of 0.85, and concurrent validity was also satisfactory, with K-LBCRS correlating highly with CDR-SB and other scales. The test-retest reliability was very high with a Pearson correlation coefficient of 0.97. The mean scores of K-LBCRS were significantly different among three groups, with DLB (6.2 +/- 2.4), AD (1.4 +/- 1.3), and controls (0.3 +/- 0.6). We identified a cut-off score of 3 as best to differentiate between DLB and AD, having AUC of 0.97 (95% CI 0.94-1.00), sensitivity 97%, specificity 83%, positive predictive value 76%, negative predictive value 98%, which is the same score suggested in the original study. This study shows K-LBCRS as a new useful screening tool for Korean DLB patients in clinical settings