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BACKGROUND: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. METHODS: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed. RESULTS: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates. CONCLUSION: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis.
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BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
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Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons , Hormônios Tireóideos , Proteínas tau , Humanos , Masculino , Feminino , Idoso , Proteínas tau/sangue , Proteínas tau/metabolismo , Estudos Transversais , Hormônios Tireóideos/sangue , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/sangue , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Tiroxina/sangue , Tireotropina/sangue , Estudos de CoortesRESUMO
Morning glory disc anomaly is a rare congenital anomaly affecting the optic disc and is frequently associated with retinal detachment. This report presents a unique case of a 10-year-old boy with morning glory disc anomaly and serous retinal detachment, treated with oral acetazolamide. Remarkably, half of the retina exhibiting bullous detachment was reattached leading to full recovery of vision within a few days after starting acetazol-amide treatment. There was no recurrence after discontinuation of medication. Oral acetazolamide can be considered an alternative treatment option for retinal detachment associated with morning glory disc anomaly of non-rhegmatogenous origin. [Ophthalmic Surg Lasers Imaging Retina 2024;55:415-417.].
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Acetazolamida , Inibidores da Anidrase Carbônica , Disco Óptico , Descolamento Retiniano , Tomografia de Coerência Óptica , Humanos , Acetazolamida/uso terapêutico , Acetazolamida/administração & dosagem , Masculino , Criança , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/tratamento farmacológico , Descolamento Retiniano/etiologia , Administração Oral , Disco Óptico/anormalidades , Inibidores da Anidrase Carbônica/uso terapêutico , Inibidores da Anidrase Carbônica/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Angiofluoresceinografia/métodosRESUMO
Background: Application of visual scoring scales for regional atrophy in Alzheimer's disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets.
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Background: This study aims to report the midterm outcomes after surgical treatment of Hawkins Classification III Talar neck fractures. Methods: From March 2010 to April 2022, among a total of 155 patients who visited our hospital with talus fractures, 31 patients underwent surgical treatment for Hawkins classification III talar neck fractures. The inclusion criteria comprised patients with a symptom duration of over 1 year who were available for outpatient follow-up and underwent magnetic resonance imaging (MRI) follow-up 2 months after surgery. Exclusion criteria included patients without preoperative ankle periarticular arthritis, and a total of 27 patients were enrolled. Traffic accidents and falls accounted for 86% of 23 cases, open fractures were 8 cases, and the mean follow-up period was 34.10 months (range, 12-80 months). Clinical outcomes were measured by American Orthopaedic Foot and Ankle Society (AOFAS) score and Foot function index (FFI), and radiological results were obtained using simple radiographs before and after surgery and MRI at 2 months postoperatively to confirm bone union and complications. Results: Complete bone union was achieved in all cases, and the mean duration of union was 4.9 months (range, 4-6 months) and there were no nonunion and varus malunion. At the final follow-up, the mean AOFAS score was 80.18 points (range, 36-90 points) and the mean FFI score was 31.43 points (range, 10-68 points), showing relatively good clinical outcomes. There were 15 cases of avascular necrosis, 6 cases of traumatic arthritis of the ankle joint, 6 cases of irritation of the posterior tibial nerve, and 4 cases of wound problems. Conclusions: Hawkins classification III talar neck fractures are mostly caused by high-energy injuries and have a relatively poor prognosis due to the high incidence of complications such as avascular necrosis or posttraumatic arthritis. However, if correct anatomical reduction and rigid internal fixation are performed within a short time after the injury, good results can be expected.
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Fixação Interna de Fraturas , Fraturas Ósseas , Tálus , Humanos , Tálus/cirurgia , Tálus/lesões , Tálus/diagnóstico por imagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Adulto Jovem , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Adolescente , Imageamento por Ressonância MagnéticaRESUMO
Importance: Many epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood. Objective: To examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aß) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults. Design, Setting, and Participants: This was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aß deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aß deposition were included. Exposure: Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Main Outcomes and Measures: Baseline levels and longitudinal changes of global Aß and AD-signature region tau deposition measured by PET scans. Results: Among the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aß deposition (ß = -0.04; 95% CI, -0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (ß = -0.02; 95% CI, -0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (ß = -0.06; 95% CI, -0.11 to -0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aß deposition (ß = 0.006; 95% CI, 0.00-0.02; P = .27). Conclusions and Relevance: The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aß and tau deposition.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Leptina , Proteínas tau , Humanos , Leptina/sangue , Feminino , Masculino , Idoso , Doença de Alzheimer/sangue , Estudos Longitudinais , Estudos Transversais , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Tomografia por Emissão de Pósitrons , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , República da Coreia/epidemiologia , Idoso de 80 Anos ou mais , Disfunção Cognitiva/sangue , Biomarcadores/sangue , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. METHODS: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. RESULTS: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). CONCLUSIONS: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.
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This study aimed to explore the predictors of posttraumatic stress disorder (PTSD) in women who have recently experienced sexual assault, by examining psychological and neurophysiological factors using a prospective design with resting-state electroencephalogram (EEG) functional connectivity. The study enrolled 33 women who had been recently traumatized by sexual assault and conducted assessments within a month of the trauma. These survivors were evaluated for PTSD three months later and were classified into two groups: PTSD positive (n = 12) and PTSD negative (n = 21). They were compared to two control groups comprising women who had not experienced any extremely traumatic events: 25 with depression and 25 healthy controls. The evaluation focused on resting-state EEG functional connectivity within default mode network (DMN) using small-worldness (SW), based on graph theory. We also assessed self-reported levels of depression, anxiety, anger, and executive functions. The findings indicated that survivors who developed PTSD three months post-trauma exhibited higher anxiety levels and reduced DMN SW in the beta 3 frequency, compared to those who did not develop PTSD. Contrary to expectations, survivors without PTSD showed decreased executive functioning and lower prefrontal centrality compared to those with PTSD. This study underscores the importance of early assessment and intervention for sexual assault survivors at risk of developing PTSD.
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Rede de Modo Padrão , Eletroencefalografia , Delitos Sexuais , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Feminino , Adulto , Estudos Prospectivos , Adulto Jovem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagemRESUMO
BACKGROUND: Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses. METHODS: In this study, 750 older adults with mild cognitive impairment and Alzheimer's disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion. RESULTS: The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions. DISCUSSION: Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Delusões , Disfunção Cognitiva/diagnóstico por imagem , Cognição , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.
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Linfócitos T CD8-Positivos , Interleucina-7 , Neoplasias , Proteínas Recombinantes de Fusão , Humanos , Animais , Camundongos , Microambiente Tumoral , Receptor de Morte Celular Programada 1 , Fatores ImunológicosRESUMO
Although injuries are a leading cause of death and affect the life expectancy of individuals who live with disabilities globally, the potential role of air pollution exposure on injuries due to external causes has received little scientific attention, especially compared with that given to the association of air pollution and non-external causes of morbidity and mortality. We investigated the association between emergency department visits for externally caused injuries and short-term exposure to major ambient air pollutants, with focus on the intentions and mechanisms of injuries. We identified 2,049,855 injured patients in Seoul, South Korea between 2008 and 2016 using the National Emergency Database. Daily short-term exposure to air pollution including particles <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) was estimated based on hourly concentrations. We employed a time-stratified case-crossover study design using a conditional Poisson regression model adjusted for meteorological variables, influenza epidemics, and holidays. Immediate exposure (lag 0) to most pollutants significantly increased the risk of total injuries (PM2.5, 0.42 %; NO2, 0.68 %; SO2, 1.05 %; CO, 0.57 %; O3, 1.86 % per interquartile range increment), and the associations differed according to the intention and mechanism of injury. Unintentional and assault injuries were significantly associated with air pollution exposure, whereas self-harm injuries showed no association. In mechanism-specific analyses, injuries caused by falls, blunt objects, penetration, traffic accidents, machinery, and slips were associated with specific air pollutants, even in the co-pollutant models. The associations were stronger in injured patients aged <15 years, and in males than in their counterparts. Our results suggest that short-term air pollution exposure might play a role in the risk of externally caused injuries and the association may differ depending on the intention and mechanism of injury, which provide important evidence for injury prevention and air quality strategies.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Ozônio , Humanos , Masculino , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos Cross-Over , Exposição Ambiental/análise , Poluentes Ambientais/análise , Intenção , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Dióxido de Enxofre/análise , Feminino , AdolescenteRESUMO
BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/complicações , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/complicações , Proteínas Amiloidogênicas , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Texture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with svPPA and AD. METHODS: We enrolled all participants from three university hospitals in Korea. We obtained T1-weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying svPPA, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis. RESULTS: Compared to the AD group, the svPPA group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture- and volume-based models were good and comparable in classifying svPPA from normal cognition (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture-based model achieved a good level of performance in classifying svPPA and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume). CONCLUSION: Texture may be a useful neuroimaging marker for early detection of svPPA in older adults and its differentiation from AD.
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Doença de Alzheimer , Afasia Primária Progressiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Semântica , Afasia Primária Progressiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.
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Artérias , Canais Iônicos , Contração Isométrica , Humanos , Canais Iônicos/fisiologia , Nifedipino/farmacologia , Artéria Uterina , Artérias/fisiologiaRESUMO
Facial expressions play a crucial role in the diagnosis of mental illnesses characterized by mood changes. The Facial Action Coding System (FACS) is a comprehensive framework that systematically categorizes and captures even subtle changes in facial appearance, enabling the examination of emotional expressions. In this study, we investigated the association between facial expressions and depressive symptoms in a sample of 59 older adults without cognitive impairment. Utilizing the FACS and the Korean version of the Beck Depression Inventory-II, we analyzed both "posed" and "spontaneous" facial expressions across six basic emotions: happiness, sadness, fear, anger, surprise, and disgust. Through principal component analysis, we summarized 17 action units across these emotion conditions. Subsequently, multiple regression analyses were performed to identify specific facial expression features that explain depressive symptoms. Our findings revealed several distinct features of posed and spontaneous facial expressions. Specifically, among older adults with higher depressive symptoms, a posed face exhibited a downward and inward pull at the corner of the mouth, indicative of sadness. In contrast, a spontaneous face displayed raised and narrowed inner brows, which was associated with more severe depressive symptoms in older adults. These findings suggest that facial expressions can provide valuable insights into assessing depressive symptoms in older adults.
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Depressão , Expressão Facial , Idoso , Humanos , Povo Asiático/psicologia , Depressão/diagnóstico , Depressão/psicologia , EmoçõesRESUMO
BACKGROUND: Despite the high prevalence of alcohol use disorders (AUDs) in Korea, few studies have been conducted on the temporal priority with comorbid mental disorders. We investigated the temporal priority of lifetime AUDs and comorbid mood and anxiety disorders among the general population of Korea. METHODS: Data of 18,807 respondents aged 18 years or older, collected from three national epidemiological surveys comprising face-to-face interviews using the Korean version of the Composite International Diagnostic Interview for DSM-IV mental disorders. For each mood or anxiety disorder, the extent to which one mental disorder precedes another was investigated by calculating the proportion of primary AUDs by that of primary mood or anxiety disorder. RESULTS: Regarding alcohol dependence, dysthymic disorder is 5.6 times more likely to occur before alcohol dependence. Moreover, generalized anxiety disorder, social phobia, and specific phobia are 3.6 times, 4.5 times, and 6.3 times more likely to occur before, respectively. Regarding alcohol abuse, specific phobia is 6.3 times more likely to occur before, whereas major depressive disorder is two times more likely to occur after. Moreover, the lag times between primary alcohol abuse and subsequent mood or anxiety disorders were longer than those between primary alcohol dependence and the latter. LIMITATIONS: The age of onset might be subject to recall bias. The presence of non-respondents could have influenced the results. CONCLUSION: We need to recognize that one of the mental disorders could lead to another and consider it in the management of people with AUDs or mood and anxiety disorders.
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Polyglycolic acid (PGA) is a promising polymer in the packaging field owing to its excellent hydrolysis, heat resistance, and gas barrier properties, but it is limited in application due to its poor toughness. For this reason, a covalently bonded chain extender is introduced to increase compatibility with flexible polymers. However, covalent bonds are unfavorable for application to degradable plastics because of the energy required for reverse reactions. Therefore, we intended to effectively control the ductility of blending plastics by using a novel ionic chain extender with a relatively weaker non-covalent bond than the existing covalent bond. Polycaprolactone (PCL), which has biodegradability and flexibility, was selected as a blending polymer. For comparison, a covalently reactive chain extender (G-CE) and a non-covalently ionic chain extender (D-CE) were synthesized and compounded with blending plastics. Each chain extender improved the compatibility between PGA and PCL, and the ductility of the PGA/PCL blending plastics was more greatly enhanced with non-covalently bonded D-CE than with covalently bonded G-CE. At this time, the ductility of the PGA/PCL(90/10) blending plastic without CE was 7.2%, the ductility of blending plastic with D-CE (10D) was 26.6%, and the ductility of blending plastic with G-CE (10G) was 18.6%. Therefore, it was confirmed that the novel ionic chain extender inducing non-covalent bonds improves the compatibility between PGA and PCL and is more advantageous in enhancing ductility through a reversible reaction.
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Introduction: The study aims to test whether an increase in memory load could improve the efficacy in detection of Alzheimer's disease and prediction of the Mini-Mental State Examination (MMSE) score. Methods: Speech from 45 mild-to-moderate Alzheimer's disease patients and 44 healthy older adults were collected using three speech tasks with varying memory loads. We investigated and compared speech characteristics of Alzheimer's disease across speech tasks to examine the effect of memory load on speech characteristics. Finally, we built Alzheimer's disease classification models and MMSE prediction models to assess the diagnostic value of speech tasks. Results: The speech characteristics of Alzheimer's disease in pitch, loudness, and speech rate were observed and the high-memory-load task intensified such characteristics. The high-memory-load task outperformed in AD classification with an accuracy of 81.4% and MMSE prediction with a mean absolute error of 4.62. Discussion: The high-memory-load recall task is an effective method for speech-based Alzheimer's disease detection.
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OBJECTIVES: Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-ß (Aß) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aß deposition in the brain has not been observed. DESIGN & METHODS: Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aß positron emission tomography (Aß-PET) positivity in patients with AD. RESULTS: Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aß-PET-positive participants compared to Aß-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aß-PET-positive AD patients vs. Aß-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aß-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. CONCLUSION: These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aß deposition in the brain and had high diagnostic accuracy for predicting Aß-PET positivity.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Exossomos , MicroRNAs , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Exossomos/genética , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , MicroRNAs/genéticaRESUMO
BACKGROUND: Low body mass index (BMI) or underweight status in late life is associated with an increased risk of dementia or Alzheimer's disease (AD). However, the relationship between late-life BMI and prospective longitudinal changes of in-vivo AD pathology has not been investigated. METHODS: This prospective longitudinal study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). A total of 194 cognitive normal older adults were included in the analysis. BMI at baseline was measured, and two-year changes in brain Aß and tau deposition on PET imaging were used as the main outcomes. Linear mixed-effects (LME) models were used to examine the relationships between late-life BMI and longitudinal change in AD neuropathological biomarkers. RESULTS: A lower BMI at baseline was significantly associated with a greater increase in tau deposition in AD-signature region over 2 years (ß, -0.018; 95% CI, -0.028 to -0.004; p = .008), In contrast, BMI was not related to two-year changes in global Aß deposition (ß, 0.0002; 95% CI, -0.003 to 0.002, p = .671). An additional exploratory analysis for each sex showed lower baseline BMI was associated with greater increases in tau deposition in males (ß, -0.027; 95% CI, -0.046 to -0.009; p = 0.007), but not in females. DISCUSSION: The findings suggest that lower BMI in late-life may predict or contribute to the progression of tau pathology over the subsequent years in cognitively unimpaired older adults.