Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Metformin Prevents Tumor Cell Growth and Invasion of Human Hormone Receptor-Positive Breast Cancer (HR+ BC) Cells via FOXA1 Inhibition.

Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.

Classifying Studies on Workplace Violence for Visiting Nurses Using the Social-Ecological Model: A Scoping Review.

PURPOSE: To prevent workplace violence (WV) against visiting nurses (VNs), understanding the influencing factors is crucial. To better comprehend potential violence prevention strategies, the U.S. Centers for Disease Control and Prevention has presented the four-level social-ecological model (SEM) at the 1) individual, 2) relationship, 3) community, and 4) societal levels. This study aims to quantify WV studies against VNs, examine the influencing factors, identify gaps based on SEM levels, and propose future research and policy directions. DESIGN: A scoping review was conducted following the five-stage protocol proposed by Arksey and O'Malley in 2005. METHODS: Systematic searches, including manual searches, were performed using English and Korean databases. Published journal articles including editorials on WV against VNs were included, irrespective of the publication date. FINDINGS: Sixty journal articles were finally selected. Until the 1990s, most of the literature comprised editorials, with empirical research emerging after the 2000s. Classifying studies by SEM level, many studies have focused on individual (86.7%) and community (66.7%) factors, but fewer have addressed relationship (21.7%) and societal (16.7%) factors. CONCLUSIONS: The study revealed that much research has focused on individual-centered training, with gaps in risk assessment tool development, training incorporating relational aspects, standardized protocols, and understanding of the impact of legal rights and policies. This article advocates a comprehensive approach that considers all SEM levels to address WV against VNs. CLINICAL EVIDENCE: The findings confirm a research gap, which suggests the direction for future research and policies. Stakeholders should be urged to implement evidence-based strategies that contribute to safer work environments for VNs.

Evaluating the effects of action learning on the research competency of undergraduate nursing students: A mixed-methods study.

BACKGROUND: Research skills in nursing are crucial for guiding evidence-based practice and enhancing health care. However, undergraduate nursing students often encounter challenges in skill development because of curriculum constraints that prioritize clinical education. Bridging this skill gap is imperative for preparing students for evidence-based practice and nursing scholarship. AIM: This study aimed to investigate the impact of incorporating action learning into undergraduate nursing research classes to improve the quality of nurse education. DESIGN: A mixed-methods approach was employed using pre- and post-online surveys for quantitative analysis and reflective journals for qualitative analysis. SETTINGS: The study was conducted at a college of nursing in Seoul, South Korea. PARTICIPANTS: A convenience sample of 19 fourth-year nursing students participated in the study. METHODS: Action learning-based nursing research classes were implemented over ten sessions, integrating lectures and team activities. Pre- and post-assessment data on communication skills, critical thinking tendencies, and problem-solving abilities were analyzed using paired t-tests. The qualitative analysis involved content analysis of individual and team reflective journals. RESULTS: Participants in action learning-based nursing research classes showed significant improvements in their communication skills (t = 3.46, p = 0.002), critical thinking tendencies (t = 3.80, p = 0.001), and problem-solving abilities (t = 1.82, p = 0.043). From the analysis of reflective journals four main themes were developed: organized team projects, dynamics of learning goal achievement, extended application of learning outcomes, and recommendations for better action learning-based classes. CONCLUSIONS: This study highlights action learning as an effective educational method that integrates theory and practice in nurse education, helping students prepare for their future roles as nursing professionals. The findings underscore the effectiveness of action learning in improving undergraduate nursing students' research competency and support the need for continued development of such pedagogical approaches.

Effect and mechanisms of Gambi-jung against high-fat diet-induced cardiac apoptosis in mice.

Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, optic atrophy protein 1, and fission protein 1. Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.

Case report: Neuronal intranuclear inclusion disease initially mimicking reversible cerebral vasoconstriction syndrome: serial neuroimaging findings during an 11-year follow-up.

Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder known for its diverse clinical manifestations. Although episodic neurogenic events can be associated with NIID, no reported cases have demonstrated concurrent clinical features or MRI findings resembling reversible cerebral vasoconstriction syndrome (RCVS). Here, we present the inaugural case of an adult-onset NIID patient who initially displayed symptoms reminiscent of RCVS. The 59-year-old male patient's initial presentation included a thunderclap headache, right visual field deficit, and confusion. Although his brain MRI appeared normal, MR angiography unveiled left posterior cerebral artery occlusion, subsequently followed by recanalization, culminating in an RCVS diagnosis. Over an 11-year period, the patient encountered 10 additional episodes, each escalating in duration and intensity, accompanied by seizures. Simultaneously, cognitive impairment progressed. Genetic testing for NIID revealed an abnormal expansion of GGC repeats in NOTCH2NLC, with a count of 115 (normal range, <60), and this patient was diagnosed with NIID. Our report highlights that NIID can clinically and radiologically mimic RCVS. Therefore, in the differential diagnosis of RCVS, particularly in cases with atypical features or recurrent episodes, consideration of NIID is warranted. Additionally, the longitudinal neuroimaging findings provided the course of NIID over an 11-year follow-up period.

Influence of short-lived radioiodines other than 131I on screening direct thyroid measurements with TCS-172 NAI(TL) survey meters.

In a nuclear emergency, one of the actions taken for the sake of public is to monitor thyroid exposure to radioiodines. Japan's Nuclear Regulation Authority recently published a report on such monitoring and proposed direct thyroid measurements with conventional NaI(Tl) survey meters (e.g. Hitachi model TCS-172) as a primary screening method. A previous study proposed screening levels (SLs) used in these simplified measurements as the net reading values of the TCS-172 device. Age-specific SLs were derived from a thyroid equivalent dose of 100 mSv due to the inhalation intake of 131I. This study addressed the possible influence of short-lived iodine isotopes other than 131I on the simplified measurements. In preparation for such measurements, the responses of the device for 132I as an ingrowth component from 132Te, 133I, 134I and 135I in the thyroid were evaluated by numerical simulations using age-specific stylized phantoms in addition to those obtained for 131I in the previous study. The radioactivity ratios of the relevant isotopes were taken from the inventory data of the Fukushima Daiichi Nuclear Power Plant. The results were used to predict the net readings of the device when 132Te-132I and 133I as well as 131I were inhaled at 24 or 72 h after the shutdown of a nuclear power plant. In these cases, the signals from 132Te-132I and 133I become undetectable a couple of days after intake, which could lead to underestimations of the thyroid dose. To estimate the thyroid dose accurately from the simplified measurements, it is necessary to identify the exact time of intake after the shutdown and the actual physiochemical property of 132Te that affects the thyroid uptake of 132I.

Generation of an induced pluripotent stem cell line (PNUYHi002-A) from a patient with Alzheimer's disease carrying PRNP M232R variant.

We generated a human induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells isolated from a 59-year-old male patient with Alzheimer's disease (AD). The iPSC line was meticulously characterized to confirm its pluripotency, absence of transgenes, and normal karyotype. The unexpected discovery of the M232R variant in PRNP makes this cell line a valuable resource for investigating AD pathogenesis.

Effect of Dietary Habits on Alzheimer's Disease Progression.

PURPOSE: Research on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer's disease dementia (ADD). MATERIALS AND METHODS: This study included 705 patients with mild-to-moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB), Seoul-Instrumental Activities of Daily Living, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and neuropsychological test battery (NTB) z-scores, which were evaluated annually over 3 years. RESULTS: In Q10 (eat all food evenly without being picky), the 3-year mean differences in CDR-SB (increases in scores represent worsening) compared to the "rarely" group were -1.86 [95% confidence interval (CI)=-3.64 - -0.09, p=0.039] for the "usually" group and -2.23 (95% CI=-4.40 - -0.06, p=0.044) for the "always" group. In Q7 (add salt or soy sauce to food when eating), the 3-year mean differences in CDR-SB compared to the "always" group were -2.47 (95% CI=-4.70 - -0.24, p=0.030) for the "usually" group and -3.16 (95% CI=-5.36 - -0.96, p=0.005) for the "rarely" group. The "rarely" and "usually" groups in Q7 showed significantly less decline in NTB z-score and CGA-NPI compared to the "always" group. CONCLUSION: Eating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.

Monitoring and evaluation of provincial classical swine fever immunization implementation with an E2 subunit vaccine in Jeju Island, South Korea.

Purpose: Accidental vaccination with a live attenuated low-virulence strain of Miyagi (LOM) vaccine led to the reemergence of classical swine fever virus (CSFV) in Jeju province, South Korea in 2014. To control the continual outbreaks of LOM-derived CSFV, the provincial government launched a provincial mass vaccination project using a CSF-E2 subunit vaccine. We conducted this study to assess the herd immunity level and outcomes of E2 vaccine-based immunization in breeding and growing herds on Jeju Island during 2020-2021. Materials and Methods: A large-scale vaccination trial using the Bayovac CSF-E2 vaccine investigated its efficacy in breeding and growing herds under farm application conditions (10 CSFV-affected and three CSFV-naïve swine farms). Results: The level of herd immunity in each farm was classified into three (S1-S3) and six (G1-G6) profiles in breeding and growing herds, respectively. Immunity monitoring revealed a remarkable improvement in the herd immunity status in all farms. The majority (10/13) of farms, including CSFV-free farms, showed the S1G1 immunity profile in 2021, indicating the appropriate implementation of the advised vaccination regime. Moreover, there were significant decreases in Erns seropositivity from 100% to 50% and 25.9% to 4.3% at farm and pig levels, respectively. In particular, all farms were confirmed as CSFV free in the growing-finishing herds. Conclusion: Our large-scale trial demonstrated the effectiveness of the E2 subunit vaccine in establishing herd immunity stabilization and eliminating CSFV circulation in the affected farms and highlighted the need for a provincial vaccination policy to regain the CSF-free status on Jeju Island.

Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells.

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activationmediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells. [BMB Reports 2024; 57(6): 299-304].

Relationship between the Residual Cesium Body Contents and Individual Behaviors among Evacuees from Municipalities near the Fukushima Daiichi Nuclear Power Plant.

ABSTRACT: To support estimations of early individual internal doses to residents who suffered from the 2011 accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), we have sought to use whole-body counter (WBC) measurement results of subjects who lived in municipalities neighboring the FDNPP at the time of the accident. These WBC measurements started several months after the accident; the targeted radionuclides were 134Cs and 137Cs. Our previous study had analyzed the relationship between the residual Cs contents of individuals and evacuation behaviors in the period immediately after the accident for residents of Namie-town, one of the most radiologically affected municipalities. Those results suggested that the first major release event at the FDNPP on 12 March 2011 caused significant exposure, particularly to those who delayed evacuation on that day. The present study expanded its scope to include subjects from four towns neighboring the FDNPP (Namie, Futaba, Okuma, and Tomioka) to gather additional evidence of the exposure that took place on 12 March 2011. Additionally, we investigated the relationship between individual cesium doses and subjects' destinations following the largest release event on 15 March 2011. The study population was 1,145 adults. We first divided the subjects into two evacuation groups depending on the distance from the FDNPP and their evacuation whereabouts (25-km boundary) as of 15:00 on 12 March 2011: the G1 group (≥25 km) and the G2 group (<25 km). We further divided these two subject groups into seven subgroups based on the subjects' destinations as of 0:00 on 16 March 2011. Our four main findings are as follows. (1) The 137Cs detection rate was significantly different between the G1 and G2 groups of Namie-town and Futaba-town but not for those of Okuma-town and Tomioka-town. This result corresponds to the plume passage (flowing toward the northwest to the north) in the afternoon of 12 March 2011 and supports our previous study. (2) The upper-percentile committed effective doses (CEDs) of the G2 groups were higher than those of the G1 groups for all four towns, although the between-group difference varied with the town. The highest CEDs were found in the G2 group of Futaba-town, and the lowest CEDs were in the Namie-town G1 group: 0.16 mSv and 0.04 mSv at the 90th percentile, respectively. The CEDs for both the G1 and G2 groups were relatively high for Okuma-town and Tomioka-town compared to those of the G1 group of Namie-town, although the former subjects were expected to be less exposed on 12 March 2011 and then evacuated to remote places, as did the residents of the other towns. (3) The CEDs of the G1 subgroup that evacuated outside Fukushima Prefecture were extremely low, suggesting that these subjects were little exposed on both 12 and 15 March 2011. However, the CEDs of the same G1 subgroup were rather higher than those of the corresponding G2 subgroup for Futaba-town and Okuma-town. We thus speculate that the WBC measurements were likely to have been affected by the contamination occurring in the second-round temporary re-entry (except for the Namie-town residents). (4) The analyses of the Namie-town evacuees indicated that the area including the middle and northern parts of Fukushima Prefecture was relatively more affected by the major release event on 15 March 2011. In conclusion, the early cesium intake due to the FDNPP accident remained detectable in the WBC measurements of certain present subjects; however, further analyses of the available data are necessary for a full understanding of the WBC measurement results.

Association between osteoporosis and the rate of telomere shortening.

A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial. This study aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort. The KBASE study is an independent multicenter prospective cohort in South Korea, which began in 2014. We compared the LTL values for each participant at baseline and over a 2-year follow-up period. Boxplots were used to demonstrate the differences in the change in LTL over a 2-year follow-up according to osteoporosis. Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study. We observed that the LTL decreased by approximately 1.2 kbp over 2 years. While the LTL decreased as age increased, the rate of LTL shortening did not increase with age. Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038). We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort. We found that participants with osteoporosis had significantly faster LTL shortening over 2 years than those without osteoporosis. We hope this study will help elucidate the underlying mechanisms in the relationship between LTL and osteoporosis in the future.

Advancing ecological validity and clinical utility in virtual reality-based continuous performance test: exploring the effects of task difficulty and environmental distractors.

Introduction: Researchers have highlighted concerns regarding the limited diagnostic utility and ecological validity of the Continuous Performance Test (CPT). Recent advancements in VR-based CPTs have attempted to address these concerns by simulating real-life scenarios and enhancing attention deficit hyperactivity disorder (ADHD) diagnosis; however, certain areas require improvement for obtaining reliable data from both healthy individuals and those with ADHD. To tackle these issues, we developed an enhanced VR-based CPT program featuring four distinct difficulty levels, advancing toward home-based assessment. Method: Our feasibility study involved subjects without ADHD to establish a normative profile for VR-based CPT before extending it to ADHD assessment. Our sample included 20 Korean adults. They received a VR device with the VR-based CPT program installed and were asked to perform 1-2 blocks per day at home. Participants were instructed to complete 12 blocks over the subsequent 2 weeks. Psychological assessments and electroencephalograms (EEGs) were administered before and after the program. Post-study usability measures were also collected. Result: Higher commission errors were notably evident in the "very high" difficulty level which featured complex stimuli and increased distraction. A notable correlation emerged between the overall distraction level and CPT accuracy, along with a significant link between intensity scores and commission errors. No significant differences were found in psychological assessment and there were no significant changes in the Theta-Beta Ratio (TBR) index before and after the program. The usability of our program was fair. Discussion: The study reveals that the newly designed VR-CPT program, simulating diverse real-life environments and offering varying task difficulty levels, proved acceptable and feasible. The key point of our study was that the adjustment and segmentation of difficulty levels in the VR-based CPT were achieved, and that this effort was validated by examining the impact of different levels of difficulty on CPT measures. Implementing this experimental setup in a home-based environment increased ecological validity, as well as clinical utility. Limitations and suggested directions for further investigation are described in detail.