Wnt/ß-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium.

ß-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent Müller glia.

Retinal progenitor cells (RPCs) divide in limited numbers to generate the cells comprising vertebrate retina. The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Müller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of Tsc1-deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of hypoxia-induced factor 1-alpha (Hif1a), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.

Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium.

In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity.

A 9-Year Comparison of Dementia Prevalence in Korea: Results of NaSDEK 2008 and 2017.

BACKGROUND: In many high-income Western countries, the prevalence of dementia had been reduced over the past decades. OBJECTIVE: We investigated whether the prevalence of all-cause dementia, Alzheimer's disease, vascular dementia, and mild cognitive impairment (MCI) had changed in Korea from 2008 to 2017. METHODS: Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2017 was conducted on representative elderly populations that were randomly sampled across South Korea. Both surveys employed a two-stage design (screening and diagnostic phases) and diagnosed dementia and MCI according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the consensus criteria from the International Working Group, respectively. The numbers of participants aged 65 years or older in the screening and diagnostic phases were 6,141 and 1,673 in the NaSDEK 2008 and 2,972 and 474 in the NaSDEK 2017, respectively. RESULTS: The age- and sex-standardized prevalence of all-cause dementia and Alzheimer's disease showed nonsignificant decrease (12.3% to 9.8%, odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.54-1.48 for all-cause dementia; 7.6% to 6.8%, OR [95% CI] = 0.91 [0.58-1.42] for Alzheimer's disease). Vascular dementia decreased in the young-old population aged less than 75 years (2.7% to 0.001%, OR [95% CI] = 0.04 [0.01-0.15]) and in women (1.9% to 0.5%, OR [95% CI] = 0.27 [0.10-0.72]) while MCI remained stable (25.3% to 26.2%, OR [95% CI] = 1.08 [0.67-1.73]). CONCLUSION: We found that the prevalence of dementia in Korea showed a nonsignificant decrease between 2008 and 2017.

A Systematic Review and Meta-Analysis of Nonpharmacological Interventions for Moderate to Severe Dementia.

OBJECTIVE: Due to limited efficacy of medications, non-pharmacological interventions (NPI) are frequently co-administered to people with moderate to severe dementia (PWMSD). This systematic review and meta-analysis investigated the effects of NPI on activities of daily living (ADL), behavioral and psychological symptoms of dementia (BPSD), and cognition and quality of life (QoL) of PWMSD. METHODS: A literature search was conducted in the following databases: Cochrane CENTRAL, EMBASE, Medline, CIHNAL, PsycINFO, KoreaMED, KMbase, and KISS. We conducted a meta-analysis on randomized controlled trials and used the generic inverse variance method with a fixed-effects model to calculate the standardized mean difference (SMD). The protocol had been registered (CRD42017058020). RESULTS: Ten randomized controlled trials met the inclusion criteria of the current meta-analysis. NPI were effective in improving ADL [SMD=0.28, 95% confidence interval (CI)=0.11-0.45] and reducing depression (SMD=-0.44, 95% CI=-0.70- -0.19). However, NPI were not effective in reducing agitation, anxiety, or overall, or improving cognitive function. In a subgroup analysis, music therapy was effective in reducing overall BPSD (SMD=-0.52, 95% CI=-0.90- -0.13). CONCLUSION: Albeit the number of studies was limited, NPI improved ADL and depression in PWMSD.

A Systematic Review of Nonpharmacological Interventions for Moderate to Severe Dementia: A Study Protocol for a Systematic Review and Meta-Analysis.

The study is designed as a systematic review on nonpharmacological interventions for patients with moderate to severe dementia. This review will be conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The following databases will be searched: Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, KoreaMED, KMbase, and KISS. The primary outcome will include the effect of the interventions on activities of daily living and behavioral and psychological symptoms of dementia. The literature search will be conducted based on search strategies designed for each database. The reviewers will independently assess the identified studies and extract the data. The risk of bias will be assessed and a meta-analysis will be conducted in accordance with the methodology for meta-analysis described in the Cochrane handbook. This systematic review will provide clinicians and policy makers with reliable evidence for developing and implementing nonpharmacological interventions for moderate to severe patients with dementia.

Cognitive Stimulation as a Therapeutic Modality for Dementia: A Meta-Analysis.

OBJECTIVE: Although cognitive stimulation (CS) is one of the most popular non-pharmacological interventions for people with dementia, its efficacy is still debatable. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of CS in people with dementia. METHODS: Data sources were identified by searching PubMed, MEDLINE, Embase, psychINFO, and Cochrane Reviews Library. A total of 7,354 articles were identified, and of these, 30 RCTs were selected based on the selection criteria. Of these 30 RCTs, 14 were finally included in our meta-analysis [731 participants with dementia; 412 received CS (CS group) and 319 received usual care (control group)]. RESULTS: We found that the people with dementia had a moderate benefit from CS. The mean difference between the CS and control groups was 2.21 [95% CI (0.93, 3.49), Z=3.38, p=0.00007] in the Alzheimer's Disease Assessment Scale-Cognition and 1.41 [95% CI (0.98, 1.84), Z=6.39, p<0.00001] in the Mini-Mental State Examination. CS also improved quality of life in people with dementia [95% CI (0.72, 3.38), Z=3.02, p=0.003]. CONCLUSION: CS is effective for improving cognition and quality of life in people with dementia; however, its effects were small to moderate.

Prevalence Rates of Dementia and Mild Cognitive Impairment Are Affected by the Diagnostic Parameter Changes for Neurocognitive Disorders in the DSM-5 in a Korean Population.

AIM: To examine the impact of the revised diagnostic criteria for neurocognitive disorders (NCDs) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) on the prevalence of dementia and mild cognitive impairment (MCI). METHODS: A total of 755 participants aged 65 years or older in the Nationwide Survey on Dementia Epidemiology in Korea 2012 were rediagnosed according to the DSM-5 criteria. RESULTS: The estimated age-, gender-, education-, and urbanicity-standardized prevalence rates of major and mild NCDs were 8.35 and 11.10%, respectively, and those of dementia and MCI were 8.74 and 31.85%, respectively. Cohen's κ for dementia and major NCD was 0.988, and that for MCI and mild NCD was 0.273. CONCLUSION: Diagnostic discrepancies between major/mild NCDs and dementia/MCI might depend on the operationalization of neuropsychological performance criteria.

An International Comparative Study on Driving Regulations on People with Dementia.

Over 40% of people with dementia drive, with a two to five times greater accident risk than controls. This has fueled public concerns about the risk of traffic accidents by drivers with dementia (DWD). We compared driving regulations on seniors and DWD between ten European and Asia-Pacific countries to identify key implications for national strategies. Moderate to severe dementia was a reason for driver's license revocation in all countries. However, regulations on mild dementia varied considerably, with most basing their decisions on severity, rather than simply the presence of dementia. Most used validated assessments, but responsibility for triggering the administrative process fell on drivers in some countries and on physicians in others. Administrations should consider the following when developing driving policies: 1) ideal regulations on DWD should ensure that restrictions are implemented only when needed; 2) fitness to drive should be assessed using validated instruments; 3) the use of processes that automatically initiate driving competency examinations following a diagnosis of dementia should be explored; and 4) restrictions should be delicately tailored to a range of driving competence levels, and assistive incentives compensating for lost driving privileges should be provided.

Incidence of and risk factors for Alzheimer's disease and mild cognitive impairment in Korean elderly.

BACKGROUND/AIMS: Knowledge of incidence rates and risk factors is essential for the development of strategies to treat patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: A subpopulation of the Nationwide Survey on Dementia Epidemiology (460 Korean subjects aged ≥65 years from 2 rural and 2 urban districts) was followed up for 3.5 years. The age-specific incidence was estimated and risk factors were identified. RESULTS: The age-standardized incidence of AD and MCI was 7.9 and 28.1 cases per 1,000 person-years, respectively. MCI was associated with a 6-fold increased risk of AD. Depression was a risk factor for AD with MCI. Age, lack of formal education, illiteracy, rural residence, and marital status were associated with the risk of AD. CONCLUSION: Strategies to control modifiable risk factors should be implemented to decrease the incidence of AD.

Prevalence and trends of dementia in Korea: a systematic review and meta-analysis.

Through a systematic review and meta-analysis of epidemiological studies on dementia, we assessed the prevalence of dementia and its subtypes-Alzheimer' disease (AD) and vascular dementia (VaD)-in Korea. We searched for epidemiological studies on dementia published in 1990-2013 using PubMed, Scopus, EMBASE, KoreaMed, KISS, and RiCH. Dementia prevalence in elderly patients (aged≥65 yr) was 9.2% (95% confidence interval [CI], 8.2%-10.4%) from 11 studies, which was higher than those from Western and other Asian countries. AD was the most prevalent dementia type, with a prevalence of 5.7% (95% CI, 5.0%-6.4%) from 10 studies compared with 2.1% (95% CI, 1.6%-2.7%) for VaD from 9 studies. The age-specific prevalence of dementia approximately doubled with each 5.8-yr increase of age. Although a significant increasing trend of dementia prevalence was not observed, it increased slightly from 7.3% to 8.7% after 2005; AD prevalence increased after 1995 and VaD prevalence decreased after the early 2000s. The AD/VaD ratio increased from 1.96 in the early 1990s to 4.13 in the 2010s, similar to the worldwide ratio. Owing to this high prevalence in the aging population, dementia will impose significant economic burdens to Korean society.

Association between measures of obesity and colorectal adenoma.

BACKGROUND: Few studies have used body mass index (BMI), waist-to-hip ratio (WHR) and waist circumference (WC) at the same time to investigate the association between obesity and colorectal adenoma. This study examined the strength of association between colorectal adenoma and obesity using not only BMI, but also WHR and WC. METHODS: Subjects of this study included 1322 asymptomatic patients who underwent colonoscopy for cancer screening from January 2006 to June 2008. Anthropometric measurements, blood test results, and a self-administered questionnaire from each subject were analyzed. RESULTS: Four hundred and fourteen adenoma cases were identified in 1322 subjects. Using univariate analysis, the prevalence of adenoma was associated with BMI and WHR and was higher among the abdominal obesity group using WC guidelines of the Korean Society for the Study of Obesity, but not using WC guidelines of the International Diabetes Federation. In multiple Logistic regression analysis, general obesity (BMI ≥ 25 kg/m(2)) increased the risk of colorectal adenoma (odds ratio (OR), 1.43; 95% confidence interval (CI), 1.05 - 1.94). Also, abdominal obesity by the WC cutoffs and the highest WHR percentile group (WHR ≥ 0.95) were significantly associated with adenoma. Among three measures of obesity, however, only BMI had a persistent association with adenoma after adjusting reciprocally for BMI, WC, and WHR (OR, 1.30; 95%CI, 1.02 - 1.80; and 1.49; 1.06 - 2.10, adjusted for WC and WHR, respectively). CONCLUSION: The data suggest that general obesity is associated with an increased risk of colorectal adenoma.

Zinc increases the phagocytic capacity of canine peripheral blood phagocytes in vitro.

Zinc is a trace element that plays a central role in the immune system. In the present study, the effect of zinc on the phagocytic capacity of canine peripheral blood phagocytes was examined in vitro by flow cytometry. Zinc was used at a concentration of 100 microM, which preserved cell viability. Treatment with zinc did not directly affect the phagocytic capacity of peripheral blood polymorphonuclear neutrophils (PMN) and mononuclear cells (PBMC). However, it did directly enhance the phagocytic capacity of peripheral blood monocyte-rich cells. Moreover, the phagocytic capacity of PMN and monocyte-rich cells but not PBMC was remarkably enhanced by culture supernatants from PBMC but not PMN treated with zinc. Anti-recombinant canine (rc) tumor necrosis factor-alpha (TNF-alpha) polyclonal antibody (pAb) neutralized the enhancing effect of the culture supernatant from zinc-treated PBMC and this supernatant had higher TNF-alpha levels than the culture supernatant of untreated PBMC. Thus, zinc may stimulate canine PBMC to produce TNF-alpha, which enhances the phagocytic capacity of canine peripheral blood phagocytes.

Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action.

Parkinson's disease (PD) is a common, progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays an important role in the pathogenesis of PD. In this study, we used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether human mesenchymal stem cells (hMSCs) have a protective effect on the dopaminergic system through anti-inflammatory mechanisms. The hMSC treatment significantly decreased LPS-induced microglial activation, tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS) mRNA expression, and production of NO and TNF-alpha compared with the LPS-only treatment group. In co-cultures of microglia and mesencephalic dopaminergic neurons, hMSC treatment significantly decreased the loss of tyrosine hydroxylase-immunopositive (TH-ip) cells. The hMSC treatment in rats showed that TH-ip neuronal loss induced by LPS stimulation in the SN was considerably decreased and was clearly accompanied by a decrease in activation of microglia, as well as TNF-alpha and iNOS mRNA expression and production of TNF-alpha. These data suggest that hMSCs have a neuroprotective effect on dopaminergic neurons through anti-inflammatory actions mediated by the modulation of microglial activation. Along with various trophic effects and trans-differentiational potency, the anti-inflammatory properties of MSCs could have major therapeutic implications in the treatment of PD.

Prevalence of irritable bowel syndrome, influence of lifestyle factors and bowel habits in Korean college students.

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is considered to be prevalent in the general population, but there are little data on bowel habits and IBS in Korea. Because nurses are frequently called on to help this patient population with IBS and help manage their symptoms, it is very necessary to get some practical information about patients' experiences and to outline a multifaceted approach to the practical management of patient with IBS. So this study aims to describe the bowel habits and the prevalence of IBS in young university students in Korea and to investigate the influence of lifestyle factors, including dietary habits, on IBS prevalence. Finally, we discuss the nursing needs for an holistic approach. METHODS: A cross-sectional study, using the self-reported questionnaire based on previous studies done abroad and the Rome alpha criteria was applied with 1717 young university students. RESULTS: The answers of 747 men and 970 women were included in the study. The prevalence of IBS, as defined by the Rome alpha criteria, was 5.7% of the subjects. The proportion of women (70.7%) was significantly higher than the proportion of men in the IBS group as compared to that in the non-IBS group (odds ratio 2.07, 95% CI 1.2-3.7). Residential type (odds ratio 1.27, 95% 1.06-1.5) and frequency of meals (odds ratio 1.69, 95% CI 1.2-2.5) significantly differed between the IBS group and non-IBS group. There was a trend towards the higher prevalence of IBS with fewer hours of exercise (odds ratio 0.99, 95% CI 0.95-1.04). 90.6% of respondents reported stool frequencies between three times per day and three times per week. Characteristics of defecation differed significantly between men and women (p<0.05, to p<0.0001). CONCLUSION: The prevalence of IBS in healthy young people of Korea was lower compared with those reported in the West. This study shows that proportionately more women suffered from IBS than men and dietary factors and lifestyle were significantly related to IBS. From our study results, we found that there are multifaceted nursing aspects required to reduce symptoms, such as dietary education and encouragement to change lifestyle aimed at controlling stress.

[Effect of Helicobacter pylori on gastric epithelial cell kinetics and expression of apoptosis-related proteins in gastric carcinogenesis].

BACKGROUND/AIMS: We investigated apoptosis, cell proliferation and the expression of apoptosis-related proteins in the gastric epithelial cells of Helicobacter pylori (H. pylori)-negative and positive patients. METHODS: TUNEL staining, immunohistochemical staining for Ki-67, p53, Bcl-2, Bcl-X(L) and Bax were performed on paraffin-embedded specimens obtained from 11 H. pylori-negative controls, 20 H. pylori-positive chronic gastritis, 10 chronic gastritis with intestinal metaplasia (IM), 11 adenoma, and 7 adenocarcinoma patients. Apoptosis and proliferation were expressed as apoptosis index (AI) and proliferation index (PI). RESULTS: In H. pylori-positive groups, apoptosis and proliferation were increased compared with controls. However, an AI/PI ratio was highest in chronic gastritis cases and then gradually reduced according to the progress from IM to cancer. p53 was expressed in 28.6% of adenocarcinoma cases. Expression of Bax was significantly increased in chronic gastritis and IM patients compared with controls. CONCLUSIONS: H. pylori infection induces marked increase in apoptosis and proliferation of gastric mucosa. In the premalignant lesions, the balance between apoptosis and proliferation is altered, and this imbalance may play a key role in the gastric carcinogenesis.