Soowon Park

N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes.

Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the cytoplasm, plasma membrane, and both plasma membrane and presynaptic terminals, respectively. The N-terminal 20 amino acids of the long form of apPDE4 were involved in presynaptic terminal targeting by binding to several lipids. In addition, the N terminus of the short form of apPDE4 bound to several lipids including phosphoinositols, thereby targeting the plasma membrane. Overexpression of the long and the short forms, but not the supershort form attenuated 5-HT-induced membrane hyperexcitability. Finally, the knockdown of apPDE4s in sensory neurons impaired both short-term and long-term facilitation. Thus, these results suggest that apPDE4s can participate in the regulation of cAMP signaling through specific subcellular localization by means of lipid binding activities.

spatial memory impairments in amnestic mild cognitive impairment in a virtual radial arm maze

Objective This study aims to apply the virtual radial arm maze (VRAM) task to find spatial working memory and reference memory impairments in patients of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Spatial memory functions between aMCI converters and nonconverters are also compared using VRAM results. Methods We assessed the spatial memory in 20 normal controls, 20 aMCI, and 20 mild AD subjects using VRAM. The Mini-Mental State Examination, Clinical Dementia Rating scale, and other neuropsychological tests were given to the subjects in conjunction with the VRAM test. Scores in working memory errors and reference memory errors were compared among the three groups using repeated measures analysis of variance. In addition, aMCI patients were followed-up after 5 years and surveyed for AD conversion rate. Results In AD patients, both spatial working and reference memory were impaired. However, in aMCI subjects, only spatial reference memory was impaired. Significant spatial reference memory impairment was found in the aMCI converter group when compared to the nonconverter group. Conclusion Spatial working memory is less impaired in aMCI while reference memory is similarly damaged in AD. In aMCI patients, more severe spatial reference memory deficit is a neuropsychological marker for AD conversion. VRAM may be well utilized in humans to assess spatial memory in normal aging, in aMCI, and in AD.

Daily skin care habits and the risk of skin eruptions and symptoms in cancer patients

BACKGROUND Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.

Factors affecting stigma toward suicide and depression: A Korean nationwide study:

Background: Suicide attempts and depression are considerably misunderstood by Korean society. Studies regarding factors should provide basic information concerning the factors that should be considered when examining stigmatization. Aim: This study aimed to investigate sociodemographic factors related to the social stigma toward people with a history of suicide attempts or depression in a Korean nationwide community sample. Method: Face-to-face interviews were conducted with participants selected via a multi-stage cluster sampling method; 779 respondents completed Link’s Perceived Devaluation and Discrimination (PDD) scale to assess the social stigma they attached to suicide attempts, and another 743 completed PDD scale to assess the social stigma they attached to depression. Multiple regression analysis, including socioeconomic and psychiatric variables, was performed to identify the factors predictive of social stigma. Results: Results of multiple regressions revealed that age (β = .12, p = .018), sex (β = .08, p = .038), years of education (β = −.31, p = .006) and history of suicide attempts (β = −.11, p = .009) significantly predicted the degree of stigma toward people who had made suicide attempts, whereas age (β = .15, p = .003) and education (β = −.40, p = .001) also predicted the social stigma toward people with depression, sex and history of a depressive episode did not. Conclusion: Older men with less education and no experience with suicide perceived suicide attempts more negatively. Similarly, older people with less education placed a greater stigma on people suffering from depression. These results suggest that greater access to higher education may reduce stigma toward people with mental illness.

Development and validation of the Pictorial Cognitive Screening Inventory for illiterate people with dementia

Purpose The purpose of this study was to develop and validate a tool called the Pictorial Cognitive Screening Inventory (PCSI), which consists of pictorial memory and attention tests that are not influenced by literacy level. Patients and methods PCSI, Mini Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) questionnaires were administered to 80 elderly participants (20 illiterate normal, 20 illiterate with dementia, 20 literate normal, and 20 literate with dementia). Results PCSI scores were highly correlated with those of the MMSE (r 0.51) and the CDR (r −0.71). In addition, the PCSI scores differed significantly between the normal group and the dementia group (mean difference 1.71, standard error [SE] 0.14, P<0.001), while no such difference was observed between the illiterate group and the literate group (mean difference 0.00, SE 0.24, P=0.997). Diagnostic validity of the PCSI is excellent, with a sensitivity of 90% and a specificity of 98% for screening dementia, whereas the MMSE has a sensitivity of 85% and a specificity of 60%. Conclusion These results indicate that the PCSI is a sensitive and reliable test for screening dementia, regardless of an individual’s literacy skills. The PCSI meets the increasing needs for screening of dementia in illiterate elderly populations in developing countries.

Aged wild-type littermates and APPswe+PS1/ΔE9 mice present similar deficits in associative learning and spatial memory independent of amyloid load

APPswe+PS1/ΔE9 transgenic (Tg) mice with Aβ plaque formation in neocortex and hippocampus were evaluated in tests measuring exploratory activity, anxiety, and memory ability using open field test (OFT), Y-maze, contextual fear conditioning (CFC), and Morris water maze (MWM). Wild type (WT) and Tg mice over eight months old showed same locomotion activity and anxiety level in novel stimulation, open field, and Y-maze contexts. In other experiments that measured associative memory and spatial memory in Tg mice and their littermates, the subjects also presented similar deficiencies in memory acquisition. These two aged groups showed abnormal freezing level variance especially in CFC test. In comparison to that in non-transgenic 8-week-old mice group, the acquisition of spatial memory in MWM task was impaired in aged WT and bigenic Tg mice. Taken together, aged wild-type littermates and Tg mice present similar deficits in associative learning and spatial memory independent of amyloid plaques.

Differences in prefrontal, limbic, and white matter lesion volumes according to cognitive status in elderly patients with first-onset subsyndromal depression.

The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs) in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI) and Alzheimers disease (AD). We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59), MCI (n = 27), and AD (n = 27), adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.

Neural predictors of cognitive improvement by multi-strategic memory training based on metamemory in older adults with subjective memory complaints

Previous studies have indicated that memory training may help older people improve cognition. However, evidence regarding who will benefit from such memory trainings has not been fully discovered yet. Understanding the clinical and neural inter-individual differences for predicting cognitive improvement is important for maximizing the training efficacy of memory-training programs. The purpose of this study was to find the individual characteristics and brain morphological characteristics that predict cognitive improvement after a multi-strategic memory training based on metamemory concept. Among a total of 49 older adults, 39 participated in the memory-training program and 10 did not. All of them underwent brain MRIs at the entry of the training and received the neuropsychological tests twice, before and after the training. Stepwise regression analysis showed that lower years of education predicted cognitive improvement in the training group. In MRI, thinner cortices of precuneus, cuneus and posterior cingulate gyrus and higher white matter anisotropy of the splenium of corpus callosum predicted cognitive improvement in the training group. Old age, lower education level and individual differences in cortical thickness and white matter microstructure of the episodic memory network may predict outcomes following multi-strategic training.

Interpersonal trauma moderates the relationship between personality factors and suicidality of individuals with posttraumatic stress disorder

Individuals with posttraumatic stress disorder (PTSD) are more prone to suicidal ideation and behavior. While those who have experienced interpersonal trauma exhibit more suicidality than those who have experienced non-interpersonal trauma, it is unclear how the traumatic effects are related to an individual’s personality characteristics. This study examined the association between interpersonal trauma and personality factors with suicidality, and elucidated the moderating role of interpersonal trauma in individuals with PTSD. The study included 6,022 participants from the Korean Epidemiologic Catchment Area Study 2011. The Korean Version of Composite International Diagnostic Interview was used for the survey, including the participants’ history of suicidality, the traumas they have experienced, and their PTSD symptoms. The 11-item version of the Big Five Inventory (BFI-11) was used to assess the participants’ personality factors. 76 individuals were diagnosed with PTSD, while 810 had been exposed to trauma but were not diagnosed with any DSM-IV mental disorder. Among the individuals with PTSD, those who had experienced interpersonal trauma were more likely to have suicidal ideation than those who had experienced non-interpersonal trauma (p = .020; odds ratio [OR] = 3.643; 95% confidence interval of OR = [1.226, 10.825]). High agreeableness and conscientiousness predicted less suicidality in those exposed to non-interpersonal trauma, while predicting more suicidality in those exposed to interpersonal trauma. Clinicians examining individuals with PTSD should pay closer attention to the trauma that they have experienced, as well as their personality factors, to provide appropriate treatment.

Development and Validation of the Rappel Indicé-24: Behavioral and Brain Morphological Evidence.

The primary goals of the present study were to develop and validate the Rappel Indicé 24 (RI-24), a shorter version of the original Rappel Indicé, which includes 48 items (RI-48), and to identify the specific brain regions that were correlated with scores on the RI-24. Using these clinical scales, the present study evaluated 91 elderly Korean participants who were classified into 3 groups: normal control (NC; n = 34), patients with mild cognitive impairment (MCI; n = 29), and patients with Alzheimer disease (AD; n = 28). Of the 91 participants, 77 also underwent magnetic resonance imaging scans. The RI-24 delayed cued recall (DCR) scores significantly differed among the NC, MCI, and AD groups. A receiver–operating characteristic curve analysis revealed that the RI-24 was very sensitive (89%) and specific (91%) for the detection of AD. Furthermore, although the time needed to administer the RI-24 was half that needed for the RI-48, the 24-item version showed a high correlation (r = .85 for the DCR score) with the 48-item version. In terms of brain morphological characteristics, voxel-based morphometry analyses revealed a significant positive correlation between DCR score and gray matter volume in the parahippocampal gyrus (r = .468), which plays a role in cued recall. Taken together, the present findings indicate that the RI-24 is a sensitive and reliable test for the detection of memory impairments in patients with MCI and AD despite its brief administration time.