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.

Development and application of artificial intelligence-based facial skin image diagnosis system: Changes in facial skin characteristics with ageing in Korean women.

OBJECTIVE: To develop and validate an artificial intelligence (AI)-based diagnostic system for analysing facial skin images using expert judgements and explore its feasibility for skin ageing research, specifically by evaluating facial skin changes in Korean women of various ages. METHODS: Our AI-based facial skin diagnosis system (Dr. AMORE®) uses facial images of Korean women to analyse wrinkles, pigmentation, skin pores, and other skin red spots. The system is trained using clinical expert evaluations and deep learning. We assessed the system's precision and sensitivity by analysing the correlation between the diagnoses by the AI system and those of the experts. We used 120 images of Korean women aged 10-60 years to evaluate the changes in various facial skin characteristics with ageing. RESULTS: The precision and sensitivity of the developed system were excellent (>0.9%), and the diagnosis scores using the detected area and intensity of each item were correlated significantly higher with the visual evaluation results of the clinical experts (>0.8, p < 0.001). We also analysed facial images of Korean women aged 10-60 years to quantify changes in the scores of wrinkles, pigmentation, and skin pores with age. We identified the age group with the most significant changes as 20s to 30s. Analysis of the detailed skin characteristics of each item showed that wrinkles and pigmentation changed significantly in the 20s-30s, and skin pores increased significantly in the 10s-20s. There was no significant correlation with age or change according to the age group for skin red spots. CONCLUSION: Developed AI-based facial skin diagnosis system can automatically diagnose skin conditions based on clinical expert judgement using only photographic images and analyse various items in detail, quantitatively, and visually. This AI system can provide new and useful approaches in research areas that require a lot of resources and different characterizations, such as the study of facial skin ageing.

OBJECTIF: Développer et valider un système de diagnostic basé sur l'intelligence artificielle (IA) pour analyser les images de la peau du visage à l'aide de jugements d'experts et explorer sa faisabilité pour la recherche sur le vieillissement de la peau, en particulier en évaluant les changements de la peau du visage chez les femmes Coréennes de différents âges. MÉTHODES: Notre système de diagnostic de la peau du visage basé sur l'intelligence artificielle (Dr. AMORE®) utilise des images du visage de femmes Coréennes pour analyser les rides, la pigmentation, les pores de la peau et d'autres taches rouges de la peau. Le système est entraîné à l'aide d'évaluations d'experts cliniques et de l'apprentissage profond. Nous avons évalué la précision et la sensibilité du système en analysant la corrélation entre les diagnostics du système d'IA et ceux des experts. Nous avons utilisé 120 images de femmes coréennes âgées de 10 à 60 ans pour évaluer les changements de diverses caractéristiques de la peau du visage avec le vieillissement. RÉSULTATS: la précision et la sensibilité du système développé étaient excellentes (>0.9%), et les scores de diagnostic utilisant la zone détectée et l'intensité de chaque élément étaient corrélés de manière significativement plus élevée avec les résultats de l'évaluation visuelle des experts cliniques (>.8, p < 0.001). Nous avons également analysé des images du visage de femmes coréennes âgées de 10 à 60 ans afin de quantifier les changements dans les scores des rides, de la pigmentation et des pores de la peau avec l'âge. Nous avons identifié le groupe d'âge présentant les changements les plus significatifs comme étant celui des 20­30 ans. L'analyse des caractéristiques détaillées de la peau pour chaque élément a montré que les rides et la pigmentation changeaient de manière significative chez les 20­30 ans, et que les pores de la peau augmentaient de manière significative chez les 10­20 ans. Il n'y avait pas de corrélation significative avec l'âge ou de changement en fonction du groupe d'âge pour les taches rouges de la peau. CONCLUSION: Le système de diagnostic de la peau du visage basé sur l'IA peut diagnostiquer automatiquement les affections cutanées sur la base d'un jugement d'expert clinique en utilisant uniquement des images photographiques et analyser divers éléments en détail, quantitativement et visuellement. Ce système d'IA peut fournir des approches nouvelles et utiles dans des domaines de recherché qui nécessitent beaucoup de ressources et de caractérisations différentes, comme l'étude du vieillissement de la peau du visage.

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.

Epithelial Endoplasmic Reticulum Stress Enhances the Risk of Muc5b-associated Lung Fibrosis.

The gain-of-function minor allele of the MUC5B (mucin 5B, oligomeric mucus/gel-forming) promoter (rs35705950) is the strongest risk factor for idiopathic pulmonary fibrosis (IPF), a devastating fibrotic lung disease that leads to progressive respiratory failure in adults. We have previously demonstrated that Muc5b overexpression in mice worsens lung fibrosis after bleomycin exposure and have hypothesized that excess Muc5b promotes endoplasmic reticulum (ER) stress and apoptosis, stimulating fibrotic lung injury. Here, we report that ER stress pathway members ATF4 (activating transcription factor 4) and ATF6 coexpress with MUC5B in epithelia of the distal IPF airway and honeycomb cyst and that this is more pronounced in carriers of the gain-of-function MUC5B promoter variant. Similarly, in mice exposed to bleomycin, Muc5b expression is temporally associated with markers of ER stress. Using bulk and single-cell RNA sequencing in bleomycin-exposed mice, we found that pathologic ER stress-associated transcripts Atf4 and Ddit3 (DNA damage inducible transcript 3) were elevated in alveolar epithelia of SFTPC-Muc5b transgenic (SFTPC-Muc5bTg) mice relative to wild-type (WT) mice. Activation of the ER stress response inhibits protein translation for most genes by phosphorylation of Eif2α (eukaryotic translation initiation factor 2 alpha), which prevents guanine exchange by Eif2B and facilitates translation of Atf4. The integrated stress response inhibitor (ISRIB) facilitates interaction of phosphorylated Eif2α with Eif2B, overcoming translation inhibition associated with ER stress and reducing Atf4. We found that a single dose of ISRIB diminished Atf4 translation in SFTPC-Muc5bTg mice after bleomycin injury. Moreover, ISRIB resolved the exaggerated fibrotic response of SFTPC-Muc5bTg mice to bleomycin. In summary, we demonstrate that MUC5B and Muc5b expression is associated with pathologic ER stress and that restoration of normal translation with a single dose of ISRIB promotes lung repair in bleomycin-injured Muc5b-overexpressing mice.

Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction.

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.

Neuropsychological, neuroimaging and autopsy findings of butane encephalopathy.

BACKGROUND: Butane is an aliphatic hydrocarbon used in various commercial products. While numerous reports of sudden cardiac-related deaths from butane inhalation have been described, butane-associated acute encephalopathy has rarely been reported. CASE PRESENTATION: A 38-year-old man presented with cognitive dysfunction after butane gas inhalation. Neuropsychological test results showed impairments in verbal and visual memory, and frontal executive function. Diffusion weighted MRI revealed symmetric high-signal changes in the bilateral hippocampus and globus pallidus. FDG-PET demonstrated decreased glucose metabolism in the bilateral precuneus and occipital areas and the left temporal region. At the 8-month follow-up, he showed still significant deficits in memory and frontal functions. Diffuse cortical atrophy with white matter hyperintensities and extensive glucose hypometabolism were detected on follow-up MRI and FDG-PET, respectively. Brain autopsy demonstrated necrosis and cavitary lesions in the globus pallidus. CONCLUSIONS: Only a few cases of butane encephalopathy have been reported to date. Brain lesions associated with butane encephalopathy include lesions in the bilateral thalamus, insula, putamen, and cerebellum. To the best of our knowledge, this is the first report on bilateral hippocampal and globus pallidal involvement in acute butane encephalopathy. The pathophysiology of central nervous system complications induced by butane intoxication is not yet fully understood. However, the direct toxic effects of butane or anoxic injury secondary to cardiac arrest or respiratory depression have been suggested as possible mechanisms of edematous changes in the brain after butane intoxication.

Influence of Sociodemographic Factors, Health Conditions, and Activity on Participation in People With Spinal Cord Injury in South Korea.

OBJECTIVE: To verify the causal relationship between sociodemographic factors, health conditions, and activities that influence the participation of people with spinal cord injury (SCI) using International Spinal Cord Injury (InSCI) Survey data and to investigate the moderation effects of environmental restrictions and health care system concerns. DESIGN: Cross-sectional community survey and structural equation model. SETTING: SCI databases of the Korea National Rehabilitation Center and Korea Spinal Cord Injury Association. PARTICIPANTS: Community-dwelling adults (N=890) with SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The InSCI questionnaire domains included sociodemographic factors, health conditions, activity, participation, environmental restrictions, and health system concerns. Sociodemographic factors included age, education, and income. Health conditions included bowel dysfunction, respiratory problems, and pain, among others. Activity included "daily routine" and "using hands," among others. Participation included "interacting with people" and "intimate relationships," among others. Environmental restrictions included "public places" and "negative attitudes," among others. Health care system concerns included "nursing care" and "experience of being treated," among others. RESULTS: The hypothesis that health conditions would have a significant effect on activity was supported because 51% of the total variance in activity factors was explained by health condition factors. The hypothesis that activity would have a significant effect on participation was also supported because 63.4% of total variance in participation factors was explained by activity factors. The moderation effect tests supported the hypotheses that health conditions, activity, and participation would differ depending on the extent of environmental restrictions as well as the extent of health system concerns. CONCLUSIONS: When formulating policies and recommendations to promote the participation of people with SCI living in the South Korean community, the influence of environmental restrictions and health systems as well as the causal influence of health conditions and activity should be considered.

Predicting cognitive stage transition using p-tau181, Centiloid, and other measures.

BACKGROUND: A combination of plasma phospho-tau (p-tau), amyloid beta (Aß)-positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE-V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aß-PET and brain imaging data were analyzed. RESULTS: Older age, increased plasma p-tau181, Aß-PET positivity, and decreased semantic fluency were independently associated with cognitive stage transitions. Combining age, p-tau181, the Centiloid scale, semantic fluency, and hippocampal volume produced high predictive value in predicting future cognitive stage transition (area under the curve = 0.879). CONCLUSIONS: Plasma p-tau181 and Centiloid scale alone or in combination with other biomarkers, might predict future cognitive stage transition in non-dementia patients. HIGHLIGHTS: -Plasma p-tau181 and Centiloid scale might predict future cognitive stage transition. -Combining them or adding other biomarkers increased the predictive value. -Factors that independently associated with cognitive stage transition were demonstrated.

Latent classes of smartphone dependency trajectories and predictors of classes among middle school students in South Korea.

PURPOSE: With widespread use of smartphones, side effects of smartphone dependency among adolescents are emerging as a social problem. Screening high-risk groups is important for appropriate interventions to prevent smartphone dependency in early adolescence. This study thus aimed to identify latent classes of smartphone dependency trajectories and predictors of classes among South Korea's middle school students. DESIGN AND METHODS: We used data from 2164 middle school students from the Korean Children and Youth Panel Survey (2018-2020). Latent growth curve modeling (LGCM) was performed to confirm the longitudinal trajectory, and latent class growth modeling (LCGM) was performed to identify latent classes of middle school students' smartphone dependency. Then, multinomial logistic regression analysis was conducted to explore predictors of the classes. RESULTS: The LGCM showed that the trajectory of all middle school students' smartphone dependency increased (intercept 30.65, slope = 1.09). However, the LCGM identified three latent classes: (1) low-stable (intercept 23.01, nonsignificant slope), (2) medium-increasing (intercept 30.37, significant increasing slope), and (3) high-increasing (intercept 37.79, significant increasing slope). Predictors of each latent class included gender, aggressive behavior, self-esteem, parental smartphone dependency, parenting attitude, and negative peer relationships. CONCLUSION: The results indicate that the smartphone dependency trajectory of all adolescents is not the same, and there are latent classes with different trajectory patterns. PRACTICAL IMPLICATIONS: These findings may contribute to the development of nursing interventions for the smartphone dependency of adolescents. Such interventions should encourage positive factors and eliminate negative factors and, especially, involve parents.

Study for skin gloss perception using computer modulation and frequency separation on surface reflection.

OBJECTIVE: Skin gloss is a parameter of beauty and health and is used to evaluate the efficacy of makeup or skin care products. Skin gloss is a perception-based characteristic, which yet needs to be evaluated quantitatively and objectively. This study aimed to investigate the factors affecting the perception of matte, glossiness and greasiness on Korean women's skin, focusing on the effect of surface reflection. METHODS: In this study, a visual evaluation of skin gloss was performed using modulated images that combined facial reference (normal) images with images characterized by 64 different levels of surface reflection to investigate factors that might affect the perception of matte, glossy and greasy skin. Fifteen participants classified the respective images into three categories (matte, glossy and greasy), and the intensity of each image was rated using a three-point scale (weak, moderate or strong). A multinomial logistic regression analysis was performed using 960 data points (n = 64 × 15). A high-frequency average + 1 standard deviation (SD = 4) was set as the criterion for a highly glossy object. RESULTS: A significant difference was found between the three categories considering four parameters: low-frequency mean (LFM) and SD (LFSD) and high-frequency mean (HFM) and SD (HFSD). The results of the multinomial logistic regression analysis showed that LFM and HFSD were significant influencing factors for perceiving matte, glossiness and greasiness. As the LFM and HFSD of the images increased, perception changed from matte, to glossy and greasy. Further, the total number and total area of highly glossy objects were significantly different among the three categories. CONCLUSION: We identified four different factors related to perceiving matte, glossiness and greasiness on the faces of Korean women, including the LFM and HFSD of surface reflection, as well as the number of highly glossy objects and the area of surface reflection. Furthermore, we identified evenness of shine as a key factor for the perception of greasiness. These parameters could be useful for distinguishing skin gloss and for a quantitative evaluation of greasiness.

OBJECTIF: L'éclat de la peau est un paramètre de beauté et de santé, et est utilisé pour évaluer l'efficacité des produits de maquillage ou de soins de la peau. L'éclat de la peau est une caractéristique basée sur la perception, qui doit pourtant être évaluée quantitativement et objectivement. Cette étude visait à examiner les facteurs affectant la perception de la matité, de l'éclat et du caractère graisseux sur la peau de femmes coréennes, en se concentrant sur l'effet de la réflexion de surface. MÉTHODES: Dans cette étude, une évaluation visuelle de l'éclat de la peau a été réalisée à l'aide d'images modulées combinant des images de référence du visage (normales) et des images caractérisées par 64 niveaux différents de réflexion de surface afin d'étudier les facteurs susceptibles d'affecter la perception d'une peau mate, brillante et grasse. Quinze participants ont classé les images respectives en trois catégories (peau mate, brillante et grasse), et l'intensité de chaque image a été évaluée sur une échelle de trois points (faible, modérée ou forte). Une analyse de régression logistique multinomiale a été réalisée à partir de 960 points de données (n = 64 x 15). Une moyenne de haute fréquence + 1 écart type (ET = 4) a été définie comme critère pour un objet très brillant. RÉSULTATS: Une différence significative a été constatée entre les trois catégories en tenant compte de quatre paramètres : la moyenne des basses fréquences (MBF) et l'ET (ETBF), et la moyenne des hautes fréquences (MHF) et l'ET (ETHF). Les résultats de l'analyse de régression logistique multinomiale ont montré que la MBF et l'ETHF étaient des facteurs d'influence significatifs pour percevoir la matité, l'éclat et le caractère graisseux. Au fur et à mesure que la MBF et l'ETHF des images augmentaient, la perception passait de « mate ¼ à « brillante ¼ et « grasse ¼. En outre, le nombre total et la surface totale des objets très brillants étaient significativement différents dans les trois catégories. CONCLUSION: Nous avons identifié quatre facteurs différents liés à la perception de la matité, de l'éclat et du caractère graisseux sur le visage de femmes coréennes, notamment la MBF et l'ETHF de la réflexion de surface, ainsi que le nombre d'objets très brillants et la zone de la réflexion de surface. En outre, nous avons identifié l'uniformité de l'éclat comme un facteur clé de la perception du caractère graisseux. Ces paramètres pourraient être utiles pour distinguer l'éclat de la peau et pour une évaluation quantitative du caractère graisseux.

Development and evaluation of a problem-based learning simulation module for home-visit nursing.

OBJECTIVES: Although home-visit healthcare programs in Korea are expected to expand, providing hands-on experience to nursing students may be limited. This study aimed to develop and evaluate a problem-based learning (PBL) simulation module that reflects home-visit healthcare services provided by public health centers for pre-frail older adults. DESIGN AND SAMPLE: The simulation module, including PBL as prebriefing, was developed by the researchers and revised based on expert reviews. The module was evaluated using a mixed-method embedded one-group post-test-only design with focus group interviews (FGIs). Quantitative data (n = 29) were collected between April and June, 2021. FGIs (n = 10) were conducted twice in June 2021, and qualitative data were analyzed using an inductive content analysis approach. RESULTS: The average score of the Simulation Design Scale was 4.67 ± 0.36. The overall mean score of the Educational Practices Questionnaire was 4.75 ± 0.37. Three themes emerged from the FGIs: immersive learning experience, changes in perspective on nursing, and enhanced nursing competency. CONCLUSION: This PBL-based simulation module was evaluated as a systematic learning process in which nursing students could become self-directed learners, interacting and collaborating with colleagues, instructors, and environments. The module encourages them to practice home visit services.

Development of pediatric simulation-based education - a systematic review.

BACKGROUND: This systematic literature review explored the general characteristics, validation, and reliability of pediatric simulation-based education (P-SBE). METHODS: A literature search was conducted between May 23 and 28 using the PRISMA guidelines, which covered databases such as MEDLINE, EMBASE, CINAHL, and Cochrane Library. In the third selection process, the original texts of 142 studies were selected, and 98 documents were included in the final content analysis. RESULTS: A total of 109 papers have been published in the ten years since 2011. Most of the study designs were experimental studies, including RCT with 76 articles. Among the typologies of simulation, advanced patient simulation was the most common (92), and high-fidelity simulation was the second most common (75). There were 29 compatibility levels and professional levels, with 59 scenarios related to emergency interventions and 19 scenarios related to communication feasibility and decision making. Regarding the effect variable, 65 studies confirmed that skills were the most common. However, validity of the scenarios and effect variables was not verified in 56.1% and 67.3% of studies, respectively. CONCLUSION: Based on these findings, simulation based-education (SBE) is an effective educational method that can improve the proficiency and competence of medical professionals dealing with child. Learning through simulation provides an immersive environment in which learners interact with the presented patient scenario and make decisions, actively learning the attitudes, knowledge, and skills necessary for medical providers. In the future, it is expected that such research on SBE will be actively followed up and verified for its validity and reliability.

Experience of School Nurses During Public Health Crises: From 2009 H1N1 Influenza to the COVID-19 Pandemic.

PURPOSE: To elucidate the experiences of school nurses when responding to public health crises in Korea. DESIGN: Phenomenological research. METHODS: One-on-one online in-depth interviews were conducted (N = 10). FINDINGS: Major public health crises considerably affected schools, school nurses, and the revision of the School Health Act. CONCLUSIONS: The experiences of school nurses in responding to periodic public health crises over the few decades have contributed to the advancement of an infectious disease response system in schools. CLINICAL EVIDENCE: The activities of school nurses during public health crises could serve as a foundation to improve the system.

Community Health Nursing During the COVID-19 Pandemic in Korea: Consequences, Challenges, and Directions.

PURPOSE: To explore the consequences, challenges, and future directions based on community health nurses' experiences during COVID-19. DESIGN: Qualitative study. Four focus group interviews were conducted with 27 community health nurses. FINDINGS: Three major themes emerged: 1) Coordination of roles and duties, 2) Identifying deterioration of patients' health and increasing demand for visits, and 3) Changing service delivery strategies: a testing ground for new services. CONCLUSIONS: Community health nurses were essential public healthcare providers during the pandemic. The findings are informative for nurses and policy makers who can develop and suggest different services in the post-COVID era.

Aberrant Multiciliogenesis in Idiopathic Pulmonary Fibrosis.

We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in the pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis models. Importantly, conditional deletion of a cilium gene, Ift88 (intraflagellar transport 88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis, whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

Kaempferol antagonizes adipogenesis by repressing histone H3K4 methylation at PPARγ target genes.

We previously demonstrated that kaempferol, a flavonoid present in various herbs, inhibits adipogenesis by repressing peroxisome proliferator-activated receptor γ (PPARγ) activity. Here, we focused on elucidation of the underlying mechanism using genome-wide tools. First, RNA sequencing (RNA-seq) analysis showed downregulation of genes involved in adipogenesis in response to kaempferol. Subsequent ChIP assays revealed that kaempferol regulates the expression of adipogenic (Adipoq, Fabp4, Lpl) genes by modulating enrichment of active H3K4me3 and repressive H3K27me3 histone codes on target promoters. Second, we performed ChIP sequencing analysis of active H3K4me3, and co-analysis with RNA-seq identified PPARγ responsive sites in genes downregulated by kaempferol, in terms of expression and H3K4me3 deposition. Third, direct kaempferol binding to PPARγ, for which the KD value was 44.54 µM, was determined by microscale thermophoresis. Further RT-qPCR and GST pull-down assays demonstrated that kaempferol antagonizes rosiglitazone-induced PPARγ activation and impairs the rosiglitazone-dependent interaction between PPARγ and its coactivator CBP. Overall, our data suggest that kaempferol, as a PPARγ antagonist, mediates epigenetic repression of lipid accumulation by regulating histone methylation, and could serve as a candidate epigenetic drug to treat obesity-related diseases.

Semantic variant primary progressive aphasia with a pathogenic variant p.Asp40Gly in the ANXA11 gene.

We report a patient with right-predominant semantic variant primary progressive aphsia linked with p.Asp40Gly variant of ANXA11, which is the first description of frontotemporal dementia without clinical and electrophysiological evidences of amyotrophic lateral sclerosis associated with a known pathogenic variant of ANXA11.

Atypical Young-onset Dementia in Cerebral Thromboangiitis Obliterans: A Case Report.

Young-onset dementia (YOD, age at onset below 45 y) has a broad differential diagnosis. We describe a 41-year-old man with atypical manifestations of YOD syndrome in cerebral thromoboangiitis obliterans (CTAO). Extensive antemortem workup including clinical assessment, laboratory investigations, neuroimaging, and genetic testing did not elucidate a diagnosis. Postmortem neuropathologic examination revealed cortical sickle-shaped granular atrophy, resulting from numerous remote infarcts and cortical microinfarcts that mainly affected the bilateral frontal and parietal lobe, confirming CTAO. Although CTAO is a rare cause of vascular dementia, it should be considered as one of the differentials in patients with YOD with a history of heavy smoking and presence of symmetric damages of watershed-territory on neuroimaging.

Improving the robustness of a catalyzed hairpin assembly with a three-arm nanostructure for nonenzymatic signal amplification.

Kinetically trapped hairpin DNA has great potential to dynamically build nanostructures, which can be initiated by sequence-specific nucleic acids. The branched junction, which has a multi-arm structure, is a representative nanostructure of DNA. In this study, we report a nonenzymatic and isothermal signal amplification accompanied by building a 3-arm structure based on a catalyzed hairpin DNA assembly (3-CHA). We improved the signal-to-background ratio of the 3-CHA by suppressing the leakage pathway of 3-CHA, thus eliminating unfavorable reaction sites exposed in the single-stranded region of hairpin DNAs. Background and amplified signals were analyzed with gel electrophoresis and real-time fluorescence monitoring. The limit of detection of the developed 3-CHA was estimated to be 29.3 pM for catalyst DNA at room temperature. Supported by the reduced leakage signal, the implemented 3-CHA showed great potential for detecting low concentrations of target DNA.