Objective: Apolipoprotein E (APOE) genotype is associated with risk of Alzheimer’s disease (AD), but the association ofAPOE ε4 allele with longitudinal medial temporal lobe atrophy (MTA) has been controversial. This study aims to evaluate the effect of APOE genotype on longitudinal MTA over a 2-year period in cognitively impaired patients with amyloid deposition. Methods: This retrospective longitudinal study included 65 cognitively impaired subjects with amyloid deposition (subjective memory impairment, mild cognitive impairment, and mild AD). Participants were divided into carriers (n=27) and non-carriers (n=38) of the ε4 allele. The main outcome is longitudinal reduction of medial temporal lobe (hippocampus, entorhinal cortex, and parahippocampal gyrus) over 2 years. Analysis of covariance was conducted to compare the differences in longitudinal MTA between groups, controlling for covariates. Results: At baseline, hippocampal volume was 4.6% smaller (6.38±1.13 vs. 6.69±0.83, p=0.026) and entorhinal thickness was6.4% thinner (3.51±0.57 vs. 3.75±0.52, p=0.033) in APOE ε4 carriers than non-carriers. Furthermore, APOE ε4 carriers had significantly 72% greater longitudinal hippocampal atrophy compared to non-carriers (-0.43±0.30 vs. -0.25±0.31, p=0.041). Conclusion Our findings of baseline or longitudinal MTA in APOE ε4 carriers suggest that APOE ε4 genotype may contrib-ute to underlying pathophysiology of medial temporal lobe in AD.

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic noncancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dosereducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

Objective: The purpose of this study is to investigate the association of the apolipoprotein E (APOE) e4 genotype with cognition, brain volume, glucose metabolism, and amyloid deposition in patients with Alzheimer disease (AD). Methods: This is cross-sectional study of 69 subjects with AD. All subjects were divided into carriers and non-carriers of the e4 allele. Forty APOE e4 carriers and 29 APOE e4 non-carriers underwent neuropsychological, structural magnetic resonance imaging, [18F]fluorodeoxyglucose positron emission tomography scans (PET) and [18F]florbetaben amyloid PET. Analysis of co-variance was conducted to compare the differences on cognition, brain volume, glucose metabolism and amyloid deposition between APOE e4 carriers and non-carriers after controlling demographics. Results: APOE e4 carriers had 50% lower scores of Seoul Verbal Learning Test (delayed recall) compared to non-carriers (0.88±1.65 vs. 1.76±1.75, p<0.05). However, APOE e4 carriers performed better on other cognitive tests than non-carriers (Korean version of Boston Naming Test [11.04±2.55 vs. 9.66±2.82, p<0.05], Rey Complex Figure Test [25.73±8.56 vs. 20.15±10.82, p<0.05], and Stroop test [color response] [48.28±26.33 vs. 31.56±27.03, p<0.05]). APOE e4 carriers had slightly smaller hippocampal volume than non-carriers (3.09±0.38 vs. 3.32±0.38, p<0.05), but greater total brain cortical thickness (1.45±1.55 vs. 1.37±1.24, p<0.05). Amyloid deposition did not differ significantly between APOE e4 carriers and non-carriers, and no signifi-cant difference in glucose metabolism was found between groups. Conclusion We found that APOE e4 genotype is associated with cognition, brain volume in AD, suggesting that APOE e4 genotype could play an important role in the underlying pathogenesis of AD.

BACKGROUND/OBJECTIVES: Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency.Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency.MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. RESULTS: The 2,2-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). CONCLUSIONS These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

Objective: This study examined the volume of choroid plexus across AD without delusion (AD-D), AD with paranoid delusion (AD+PD), and AD with misidentification delusion (AD+MD). Methods: This is a hospital based cross-sectional study of patients with AD. The main outcome measure is the volume of choroid plexus that were measured as regions of interest with magnetic resonance imaging and the FreeSurfer analysis at baseline. Analysis of covariance (ANCOVA) was conducted to compare the differences on the volume of choroid plexus across AD-D, AD+PD, and AD+MD after controlling demographics. Results: There was no volume difference in the both choroid plexus between AD-D and AD+D. However, the volumes of both cho-roid plexus were significantly reduced in AD+MD compared to AD+PD. Conclusion Our study demonstrates that AD+MD has significantly reduced volumes of choroid plexus compared to AD+PD. These findings suggest that AD+MD and AD+PD may have different pathophysiological mechanisms related to neuroimmune re-sponses in the choroid plexus.

Objective: Although previous studies have shown association between anterior corpus callosum (ACC) and various psychotic disorder, the effect of ACC on development on psychotic symptoms in Alzheimer’s disease (AD) is still unclear. The purpose of this study is to investigate the association of ACC with the development of psychosis in patients with AD. Methods: This is a hospital based cross-sectional study of 241 AD patients. The main outcome measure is the volume of ACC that were measured as regions of interest with magnetic resonance imaging and the FreeSurfer analysis at baseline. Analysis of covariance and Logistic regression analysis conducted to assess the association between the volume of ACC and the presence of psychosis in AD, adjusting for age, education, Clinical Dementia Rating-Sum of Boxes, and total intracranial volume. Results: We found that the volume of ACC is significantly reduced in AD with psychosis (AD+P) compared to AD without psychosis (AD-P) (774.27±142.96 vs. 833.09±142.04, p=0.005). The volume of ACC associated with the presence of psychosis in AD (odds ratio=0.995; 95% confidence interval=0.993-0.997; p=0.006). Conclusion We have found that reduced volume of ACC in AD+P, suggesting that ACC might play an important role in the underlying pathogenesis of development of psychotic symptoms in AD.

Objective: Though anger was highly associated with eveningness in general population, there is no study on the relationship between chronotype and anger-related characteristics in bipolar or depressive disorders. This study aimed to investigate the difference of anger-related characteristics according to chronotypes in bipolar or depressive disorders. Methods: Patients with bipolar or depressive disorders (n=238) were included in this study. Their chronotypes and anger-related characteristics were assessed with a self-evaluation of the Composite Scale of Morningness (CSM), the State Trait Anger Expression Inventory (STAXI) and the Anger Coping Scale (ACS). Results: The eveningness group in patients with mood disorders showed the highest scores of anger-trait (p<0.001), anger-expression (p=0.002) and anger-in (p<0.001) in STAXI subscales, verbal aggression (p=0.010) in ACS subscales among three groups, but the morningess group showed the lowest scores of these subscales among three groups. However, there were no significant differences in all subscales of the STAXI and ACS according to diagnostic subtypes in the Friedman test. Conclusion The results of this study suggested that eveningness in patients with mood disorders might be related to anger proneness and maladaptive anger coping. To manage anger emotion in the patients with mood disorders, therapeutic interventions to modulate eveningness might be helpful.

Over the last two decades, several tissue clearing methodologies have been established that render tissues optically transparent and allow imaging of unsectioned tissues of significant volumes, thus improving the capacity to study the relationships between cell and 3D tissue architecture. Despite these technical advances, the important unsolved challenges that these methods face include complexity, time, consistency of tissue size before and after clearing, and ability to immunolabel various antibodies in cleared tissue. Here, we established very simple and fast tissue clearing protocol, FxClear, which involves acrylamide-free electrophoretic tissue clearing (ETC). By removal of the acrylamide infusion step, we were able to achieve fast reaction time, smaller tissue expansion, and higher immunoreactivity. Especially, immunoreactivity and fluorescence intensity were increased in FxClear-processed tissues compared to un-cleared tissues. Our protocol may be suitable for small-sized biopsy samples for 3D pathological examinations.
Acrylamide ; Antibodies ; Biopsy ; Fluorescence ; Immunohistochemistry ; Methods ; Reaction Time ; Tissue Engineering ; Tissue Expansion

OBJECTIVES: The objective of this study is to investigate differences in clinical characteristics between female panic disorder (PD) patients with abortion history (PD+A) and without abortion history (PD−A).METHODS: We examined data from 341 female patients diagnosed with PD. We divided the patients with PD into PD+A (82 patients) and PD−A (259 patients) to compare demographic and clinical characteristics. The following instruments were applied : stress coping strategies, NEO-neuroticism, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Depression Inventory, the Beck Anxiety Inventory (BAI) and the Sheehan Disability Scale.RESULTS: Compared to the PD−A, the PD+A group showed no significant difference in coping strategies. However, significantly higher scores in neuroticism, the ASI-R, the APPQ and the BAI were observed. In terms of health-related disability, the PD+A group did not show significant difference.CONCLUSIONS: Our results suggest that the PD+A group may differ from the PD−A group in trait markers such as neuroticism and anxiety sensitivity, and abortion history may be associated with panic-related symptom severity. Our study suggests that further consideration is needed on such clinical characteristics in PD patients with abortion history.
Abortion, Induced ; Anxiety ; Depression ; Female ; Humans ; Panic Disorder ; Panic ; Phobic Disorders

This case report aimed to describe cyclic patterns of residual mood symptoms in partially remitted bipolar I patient. In a 24-year-old woman with bipolar I disorder, residual mood symptoms measured by self-rated daily mood chart for 18 months were analyzed using wavelet analysis. A 146-day periodicity was prominent for the first 100 days after discharge. Between 100–200 days, 146-day periodicity was progressively diminished and 21- and 8-day periodicity was prominent. Between 200–516 days, 21-day periodicity was diminished and 85-day periodicity became prominent. This case suggest that bipolar patients might have cyclic residual symptoms with specific frequencies.
Bipolar Disorder ; Female ; Humans ; Periodicity ; Wavelet Analysis ; Young Adult