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Background: We previously demonstrated the validity of a regression model that included ethnicity as a novel predictor for predicting normative brain volumes in old age. The model was optimized using brain volumes measured with a standard tool FreeSurfer. Objective: Here we further verified the prediction model using newly estimated brain volumes from Neuro I, a quantitative brain analysis system developed for Korean populations. Methods: Lobar and subcortical volumes were estimated from MRI images of 1,629 normal Korean and 786 Caucasian subjects (age range 59-89) and were predicted in linear regression from ethnicity, age, sex, intracranial volume, magnetic field strength, and scanner manufacturers. Results: In the regression model predicting the new volumes, ethnicity was again a substantial predictor in most regions. Additionally, the model-based z-scores of regions were calculated for 428 AD patients and the matched controls, and then employed for diagnostic classification. When the AD classifier adopted the z-scores adjusted for ethnicity, the diagnostic accuracy has noticeably improved (AUCâ=â0.85, ΔAUCâ=â+â0.04, Dâ=â4.10, pâ<â0.001). Conclusions: Our results suggest that the prediction model remains robust across different measurement tool, and ethnicity significantly contributes to the establishment of norms for brain volumes and the development of a diagnostic system for neurodegenerative diseases.
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Doença de Alzheimer , Encéfalo , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/etnologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico , Povo Asiático , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Tamanho do Órgão , População Branca , População do Leste AsiáticoRESUMO
Age is the primary risk factor for Parkinson's disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD postmortem midbrain samples. Combined multiomic analysis along a pseudopathogenesis trajectory reveals that all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We present evidence for a disease-associated oligodendrocyte subtype and identify genes lost over the aging and disease process, including CARNS1, that may predispose healthy cells to develop a disease-associated phenotype. Surprisingly, we found that chromatin accessibility changed little over aging or PD within the same cell types. Peak-gene association patterns, however, are substantially altered during aging and PD, identifying cell-type-specific chromosomal loci that contain PD-associated single-nucleotide polymorphisms. Our study suggests a previously undescribed role for oligodendrocytes in aging and PD.
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Doença de Parkinson , Humanos , Idoso , Doença de Parkinson/genética , Multiômica , Mesencéfalo/metabolismo , Microglia/metabolismo , Núcleo Solitário/metabolismo , CromatinaRESUMO
The epigenome, consisting of chemical modifications to DNA and histone proteins, can alter gene expression. Clustered regularly interspaced short palindromic repeats/dead CRISPR-associated protein 9 (CRISPR/dCas9) systems enable precise target gene-specific gene modulation by attaching different "effector" domains to the dCas9 protein to activate or repress specific genes. CRISPR/dCas9-SunTag is an improved system version, allowing more efficient and precise gene activation or repression by recruiting multiple copies of the protein of interest. A CRISPR/dCas9-SunTag-based modular epigenetic toolkit was developed, enabling gene-specific epigenetic architecture modulation. This protocol generated a stable SH-SY5Y cell line expressing the CRISPR/dCas9-SunTag-JARID1A system to study H3K4Me3-mediated promoter regulation at a 200-400 bp of fine resolution. The procedure involved designing sgRNAs, subcloning dCas9-5XGCN4 into pLvx-DsRed, validating epigenetic mark changes with ChIP, and validating gene expression changes with RT-qPCR. This epigenetic toolkit is valuable for researchers to understand the relationship between gene-specific epigenetic modifications and gene expression.
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Sistemas CRISPR-Cas , Neuroblastoma , Humanos , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , RNA Guia de Sistemas CRISPR-Cas , Neuroblastoma/genética , Epigênese GenéticaRESUMO
PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).
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Sobreviventes de Câncer , Neoplasias , Humanos , Sobreviventes de Câncer/psicologia , Fadiga/etiologia , Fadiga/terapia , Força Muscular , Neoplasias/complicações , Neoplasias/psicologia , Qualidade de Vida , Sobreviventes/psicologiaRESUMO
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.
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Pais , Smartphone , Adolescente , Criança , Humanos , Inquéritos e Questionários , República da Coreia , EstudantesRESUMO
With the upsurge in the use of disposable masks during the coronavirus disease pandemic, improper disposal of discarded masks and their negative impact on the environment have emerged as major issues. Improperly disposed of masks release various pollutants, particularly microplastic (MP) fibers, which can harm both terrestrial and aquatic ecosystems by interfering with the nutrient cycling, plant growth, and the health and reproductive success of organisms. This study assesses the environmental distribution of polypropylene (PP)-containing MPs, generated from disposable masks, using material flow analysis (MFA). The system flowchart is designed based on the processing efficiency of various compartments in the MFA model. The highest amount of MPs (99.7 %) is found in the landfill and soil compartments. A scenario analysis reveals that waste incineration significantly reduces the amount of MP transferred to landfills. Therefore, considering cogeneration and gradually increasing the incineration treatment rate are crucial to manage the processing load of waste incineration plants and minimize the negative impact of MPs on the environment. The findings provide insights into the potential environmental exposure associated with the improper disposal of waste masks and indicate strategies for sustainable mask disposal and management.
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Ecossistema , Máscaras , Microplásticos , Plásticos , PolipropilenosRESUMO
BACKGROUND: Demand for urban forest programs for the healing of cancer survivors is increasing. To develop a forest healing program for the integrated care of cancer patients, it is necessary to analyze the experiences of forest healing instructors who have conducted programs for cancer patients. METHODS: This qualitative study applied focus group interviews (FGIs; four interviews with sixteen participants) to describe and understand the experiences of forest healing instructors who run forest healing programs for cancer patients. RESULTS: Four themes were identified: "prepared encounters and unexpected encounters," "yearning for healing," "people who need special care," and "things to prepare for cancer patient programs." CONCLUSION: Forest healing instructors had difficulty facilitating programs for cancer patients owing to prejudice and a lack of knowledge about the characteristics of cancer patients. Moreover, differentiated programs and places that align with the specific needs of cancer patients are needed. It is necessary to develop an integrated care forest healing program for cancer patients and educate forest healing instructors about the needs of cancer patients.
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Neoplasias , Humanos , Pesquisa Qualitativa , Grupos Focais , PreconceitoRESUMO
AIM: The aim of this study is to examine nursing students' experiences of alternative and nonstandard practicum methods used during the Coronavirus Disease 19 (COVID-19) pandemic and the associations between these experiences and nursing students' anxiety with clinical decision-making. BACKGROUND: Nursing students experiencing alternative clinical practice methods during the COVID19 pandemic have expressed regrets about being unable to experience direct nursing care and doubts about their clinical decision-making in actual clinical settings as a nurse in the future. METHODS: Online surveys were distributed to 239 third-year nursing students through a link in an email. Data were collected from December 2020 to January 2021. RESULTS: Approximately 80% of participants in the Fall 2020 semester experienced an alternative clinical practice method. The extent of time spent experiencing alternative clinical practice methods and satisfaction with the clinical practicum were associated with anxiety about clinical decision-making. CONCLUSIONS: Although the pandemic continues, nursing students' clinical practice is needed in a clinical setting as much as possible to reduce the anxiety about clinical decision-making. During the pandemic, clinical nurse educators and clinical managers should work and communicate more closely to facilitate the students' clinical practice.
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COVID-19 , Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Pandemias , Bacharelado em Enfermagem/métodos , COVID-19/epidemiologia , Ansiedade/epidemiologiaRESUMO
It is important to manage the health of cancer survivors who have returned to their daily lives. An increasing number of cancer survivors are undertaking health care in forests near their residences. This cross-sectional study aimed to determine the perceptions of forest healing and the program preferences of adult cancer survivors. Data were collected from 388 female cancer survivors through an online survey. Breast cancer survivors comprised 66.2%, and 63.6% of the study participants were diagnosed with cancer within 2 to 5 years prior to the study. The subjective health status was 2.68 ± 0.61 out of 4 points. Of the participants, 62.1% had heard of forest healing and 65.7% intended to participate in the forest healing program. Participants who frequently visited the forest were more likely to participate in the forest healing program in the future than those who rarely visited the forest. A survey among 255 people on specific preferences for the program found that the regular visit type was preferred over the one-time visit type. These results are meaningful because they can be used as a basis for the development of a forest treatment program that reflects the needs of cancer survivors.
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Neoplasias da Mama , Sobreviventes de Câncer , Adulto , Humanos , Feminino , Estudos Transversais , Intenção , Sobreviventes , Neoplasias da Mama/terapiaRESUMO
PURPOSE: Deregulation of SNCA encoding α-synuclein (α-SYN) has been associated with both the familial and sporadic forms of Parkinson disease (PD). Epigenetic regulation plays a crucial role in PD. The intron1 of SNCA harbors a large unmethylated CpG island. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), a CpG island binding protein, can repress gene expression by occupying hypomethylated CpG-rich promoters, and therefore SNCA could be a target for TET1. We investigated whether TET1 binds to SNCA-intron1 and regulates gene expression. METHODS: The dopaminergic neuronal cell line, ReNcell VM, was used. Reverse transcription-polymerase chain reaction (RT-PCR), real time-quantitative PCR, Western blot, dot-blot, and Chromatin immunoprecipitation were conducted. The substantia nigra tissues of postmortem PD samples were used to confirm the level of TET1 expression. RESULTS: In the human dopaminergic cell line, ReNcell VM, overexpression of the DNA-binding domain of TET1 (TET1-CXXC) led to significant repression of α-SYN. On the contrary, knocking down of TET1 led to significantly higher expression of α-SYN. However, overexpression of the DNA-hydroxymethylating catalytic domain of TET1 failed to change the expression of α-SYN. Altogether, we showed that TET1 is a repressor for SNCA, and a CXXC domain of TET1 is the primary mediator for this repressive action independent of its hydroxymethylation activity. TET1 levels in PD patients are significantly lower than that in the controls. CONCLUSION: We identified that TET1 acts as a repressor for SNCA by binding the intron1 regions of the gene. As a high level of α-SYN is strongly implicated in the pathogenesis of PD, discovering a repressor for the gene encoding α-SYN is highly important for developing novel therapeutic strategies for the disease.
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The diagnosis of Alzheimer's disease (AD) needs to be improved. We investigated if hippocampal subfield volume measured by structural imaging, could supply information, so that the diagnosis of AD could be improved. In this study, subjects were classified based on clinical, neuropsychological, and amyloid positivity or negativity using PET scans. Data from 478 elderly Korean subjects grouped as cognitively unimpaired ß-amyloid-negative (NC), cognitively unimpaired ß-amyloid-positive (aAD), mild cognitively impaired ß-amyloid-positive (pAD), mild cognitively impaired-specific variations not due to dementia ß-amyloid-negative (CIND), severe cognitive impairment ß-amyloid-positive (ADD+) and severe cognitive impairment ß-amyloid-negative (ADD-) were used. NC and aAD groups did not show significant volume differences in any subfields. The CIND did not show significant volume differences when compared with either the NC or the aAD (except L-HATA). However, pAD showed significant volume differences in Sub, PrS, ML, Tail, GCMLDG, CA1, CA4, HATA, and CA3 when compared with the NC and aAD. The pAD group also showed significant differences in the hippocampal tail, CA1, CA4, molecular layer, granule cells/molecular layer/dentate gyrus, and CA3 when compared with the CIND group. The ADD- group had significantly larger volumes than the ADD+ group in the bilateral tail, SUB, PrS, and left ML. The results suggest that early amyloid depositions in cognitive normal stages are not accompanied by significant bilateral subfield volume atrophy. There might be intense and accelerated subfield volume atrophy in the later stages associated with the cognitive impairment in the pAD stage, which subsequently could drive the progression to AD dementia. Early subfield volume atrophy associated with the ß-amyloid burden may be characterized by more symmetrical atrophy in CA regions than in other subfields. We conclude that the hippocampal subfield volumetric differences from structural imaging show promise for improving the diagnosis of Alzheimer's disease.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Atrofia/patologia , Peptídeos beta-Amiloides , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologiaRESUMO
Parkinson's disease (PD) is a neurodegenerative disease characterized by inclusions of aggregated α-synuclein (α-Syn). Oxidative stress plays a critical role in nigrostriatal degeneration and is responsible for α-Syn aggregation in PD. Vitamin C or ascorbic acid acts as an effective antioxidant to prevent free radical damage. However, vitamin C is easily oxidized and often loses its physiological activity, limiting its therapeutic potential. The objective of this study was to evaluate whether NXP031, a new compound we developed consisting of Aptamin C and Vitamin C, is neuroprotective against α-synucleinopathy. To model α-Syn induced PD, we stereotactically injected AAV particles overexpressing human α-Syn into the substantia nigra (SN) of mice. One week after AAV injection, NXP031 was administered via oral gavage every day for eight weeks. We found that oral administration of NXP031 ameliorated motor deficits measured by the rotarod test and prevented the loss of nigral dopaminergic neurons caused by WT-α-Syn overexpression in the SN. Also, NXP031 blocked the propagation of aggregated α-Syn into the hippocampus by alleviating oxidative stress. These results indicate that NXP031 can be a potential therapeutic for PD.
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Doenças Neurodegenerativas , Doença de Parkinson , Animais , Ácido Ascórbico/farmacologia , Modelos Animais de Doenças , Dopamina/farmacologia , Neurônios Dopaminérgicos/metabolismo , Humanos , Camundongos , Estresse Oxidativo , Substância Negra/metabolismo , alfa-Sinucleína/metabolismoRESUMO
The purpose of the study was to explore factors associated with glaucomatous deterioration in eyes with primary angle closure (PAC) after lens extraction, including PAC suspect (PACS), PAC, and PAC glaucoma (PACG). We retrospectively analyzed data of 77 eyes with PACS, PAC, and PACG that underwent lens extraction with more than 2 years postoperative follow-up. Postoperative glaucoma progression was analyzed by either structural (optic disc/retinal nerve fiber layer (RNFL) photographs or optical coherent tomography (OCT)) or functional (visual field (VF)) criterion. Cox proportional hazard analysis (hazard ratio (HR)) was used to determine risk factors for progression using uni-and multivariate analysis. The analysis was conducted in groups with or without glaucomatous optic neuropathy (PACS/PAC vs. PACG). Forty-one eyes with PACS/PAC and 36 eyes with PACG were included. The mean postoperative follow-up period was 3.5 ± 1.4 years. Intraocular pressure (IOP) was reduced postoperatively from 23.1 ± 14.4 to 13.4 ± 2.1 mmHg. In the PACS/PAC group, seven eyes (17.0%) showed structural progression, but none showed progression in VF. Preoperative RNFL thickness was the only risk factor for structural progression (HR = 0.928, p = 0.002) in the PACS/PAC group. In the PACG group, 24 eyes (66.7%) showed structural progression and 12 eyes (33.3%) showed VF progression. Thinner preoperative RNFL thickness (HR = 0.964, p = 0.043) and high postoperative IOP fluctuation (HR = 1.296, p = 0.011) were significantly associated with VF progression; none of the factors were associated with structural progression. Angle closure eyes with thinner baseline RNFL thickness and higher postoperative IOP fluctuation may require careful follow-up for glaucoma progression after lens extraction.
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This study aimed to identify the priority of educational needs to strengthen the competency of forest healing instructors who operate forest healing programs for cancer survivors. A survey was conducted with 91 forest healing instructors using a questionnaire. The average perceived importance of the forest healing program for cancer survivors of forest healing instructors was higher compared to the average knowledge of the forest healing instructors. The Borich needs assessment model showed the highest educational need in the domains of "Cancer survivors' overview" and "Health status screening method". In addition, deriving the priority of educational needs using the Borich needs assessment model and the focus trajectory model revealed that the highest priority was for "Health status screening method" and "Effective communication with cancer survivors". These results can be used as basic data for developing a forest healing instructors training program for cancer survivors that reflects the instructors' needs and the characteristics of cancer survivors.
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Sobreviventes de Câncer , Neoplasias , Escolaridade , Florestas , Humanos , Avaliação das Necessidades , Neoplasias/terapia , Inquéritos e QuestionáriosRESUMO
Low social capital has been reported to be associated with depression in adolescents. In general, adolescents with immigrant backgrounds lack social capital. By employing a latent profile analysis (LPA) for the specification of social capital among multicultural adolescents, depression interventions can be explored through the framework of social capital. The purpose of this study was to identify distinct latent profiles of social capital and explore the depressive symptoms of multicultural adolescents in those profiles. Data of 1,244 adolescents from the Multicultural Adolescents Panel Survey (MAPS) were used, which was conducted for 3rd-year middle school students in 2016. An LPA was used to identify profiles by different social capital classes and Quade's non-parametric ANCOVA was used to confirm the differences in depressive symptoms between profiles. Latent profile analysis indicated four classes. Analysis revealed that there were differences in the level of depressive symptoms according to the social capital sub-profiles (F = 44.42, p < 0.001). Class 1 had the lowest level of depressive symptoms (13.91 ± 4.43) and Class 4 had the highest level (18.07 ± 5.25). The depressive symptoms scores of Classes 2 and 3 were 16.49 ± 5.27 and 16.74 ± 4.95, respectively. These findings provide insight into the interplay between social capital and depressive symptoms among multicultural adolescents. Support in consideration of differences in social capital is needed to reduce depression among multicultural adolescents.
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Capital Social , Adolescente , Diversidade Cultural , Depressão/epidemiologia , Humanos , República da Coreia/epidemiologia , Classe SocialRESUMO
This study aimed to classify cancer survivors' latent profile analysis (LPA) according to the problem list and identify the differences in distress between subgroups. Furthermore, this study identified differences between subgroups based on their demographic and clinical characteristics. A self-reported cross-sectional survey was administered to 446 adult cancer survivors in Korea. A distress thermometer and problem list were used, and four domains of the problem list were used to perform LPA and create subgroups. Quade's non-parametric analysis of covariance was used to determine the difference in distress between the profiles. The three identified subgroups of the problem list were: "low problem group" (36.7%), "high problem group" (49.1%), and "family only low problem group" (14.2%). The analysis showed that there was a difference in the distress level according to the sub-profile of the problem list (F = 43.69, p < 0.001). In interventions for distress, integrative interventions that are not limited to one area are necessary, and cultural characteristics as well as the problem list relevant to cancer survivors should be considered.
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Sobreviventes de Câncer , Neoplasias , Adulto , Estudos Transversais , Humanos , Neoplasias/epidemiologia , Qualidade de Vida , República da Coreia/epidemiologia , Autorrelato , Estresse Psicológico , Inquéritos e QuestionáriosRESUMO
Aging is a neurodegenerative disease that leads to cognitive impairment, and an increase in oxidative stress as a major cause is an important factor. It has been reported that aging-related cognitive impairment is associated with increased oxidative damage in several brain regions during aging. As a powerful antioxidant, vitamin C plays an important role in preventing oxidative stress, but due to its unstable chemical properties, it is easily oxidized and thus the activity of antioxidants is reduced. In order to overcome this easily oxidized vulnerability, we developed NXP032 (vitamin C/DNA aptamer complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. We developed NXP032 (vitamin C/DNA Aptamin C320 complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. In the present study, we evaluated the neuroprotective effects of NXP032 on aging-induced cognitive decline, oxidative stress, and neuronal damage in 17-month-old female mice. NXP032 was orally administered at 200 mg/kg of ascorbic acid and 4 mg/kg of DNA aptamer daily for eight weeks. Before the sacrifice, a cognitive behavioral test was performed. Administration of NXP032 alleviated cognitive impairment, neuronal damage, microglia activity, and oxidative stress due to aging. We found that although aging decreases the Nrf2-ARE pathway, NXP032 administration activates the Nrf2-ARE pathway to increase the expression of SOD-1 and GSTO1/2. The results suggest that the new aptamer complex NXP032 may be a therapeutic intervention to alleviate aging-induced cognitive impairment and oxidative stress.
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Potential biomarkers for Alzheimer's disease (AD) include amyloid ß1-42 (Aß1-42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aß1-42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aß1-42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson's correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aß1-42 concentrations decreased. The plasma and CSF NFL/Aß1-42 were strongly correlated (r = 0.558). Plasma NFL/Aß1-42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aß1-42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aß1-42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aß1-42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.
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PRCIS: Long-term prognosis of primary angle-closure was assessed after lens extraction (LE) according to different mechanisms of angle closure (AC). Patients with pupillary block (PB) had a higher probability of glaucomatous progression than patients with plateau iris configuration (PIC). PURPOSE: The aim was to investigate and compare the clinical characteristics and long-term prognosis of primary angle-closure disease (PACD) after LE according to different mechanisms of AC. METHODS: In this retrospective observational cohort study, 118 eyes with PACD that underwent LE (mean follow-up; 6.0±3.5 y after surgery) were included. PACD eyes were categorized into three subgroups according to their dominant AC mechanisms, determined by anterior segment optic coherent tomography obtained before LE; PB, PIC, and exaggerated lens vault (ELV). Postoperative glaucomatous progression was determined according to functional (visual field) or structural (optic disc photographs or optic coherent tomography measured retinal nerve fiber layer thickness) criteria. Univariate and multivariate logistic regression analysis was performed to determine the risk factors associated with glaucomatous progression. RESULTS: Fifty-two, 51, and 15 eyes with PB, PIC, and ELV, respectively, were included. All eyes showed significant intraocular pressure reduction, with a greater reduction in the ELV group than in the PB group after LE (27.0% vs. 12.5%, P=0.018). Lower baseline retinal nerve fiber layer thickness [odds ratio (OR): 0.966, P=0.004] and thinner central corneal thickness (OR: 0.985, P=0.021), and the PB group (OR: 2.891, P=0.022, reference to PIC group) were significantly associated with glaucomatous progression after LE. CONCLUSIONS: In eyes with PACD, glaucoma progression was observed following LE despite reduced intraocular pressure. The probability of progression was highest in eyes with pupil block as a mechanism of AC. Close monitoring of glaucoma in these patients is suggested.