RESUMO
Recent studies indicate that differences in cognition among individuals may be partially attributed to unique brain wiring patterns. While functional connectivity (FC)-based fingerprinting has demonstrated high accuracy in identifying adults, early studies on neonates suggest that individualized FC signatures are absent. We posit that individual uniqueness is present in neonatal FC data and that conventional linear models fail to capture the rapid developmental trajectories characteristic of newborn brains. To explore this hypothesis, we employed a deep generative model, known as a variational autoencoder (VAE), leveraging two extensive public datasets: one comprising resting-state functional MRI (rs-fMRI) scans from 100 adults and the other from 464 neonates. VAE models trained on rs-fMRI from both adults and newborns produced superior age prediction performance (with r between predicted- and actual age â¼ 0.7) and individual identification accuracy (â¼45 %) compared to models trained solely on adult or neonatal data. The VAE model also showed significantly higher individual identification accuracy than linear models (=10â¼30 %). Importantly, the VAE differentiated connections reflecting age-related changes from those indicative of individual uniqueness, a distinction not possible with linear models. Moreover, we derived 20 latent variables, each corresponding to distinct patterns of cortical functional network (CFNs). These CFNs varied in their representation of brain maturation and individual signatures; notably, certain CFNs that failed to capture neurodevelopmental traits, in fact, exhibited individual signatures. CFNs associated with neonatal neurodevelopment predominantly encompassed unimodal regions such as visual and sensorimotor areas, whereas those linked to individual uniqueness spanned multimodal and transmodal brain regions. The VAE's capacity to extract features from rs-fMRI data beyond the capabilities of linear models positions it as a valuable tool for delineating cognitive traits inherent in rs-fMRI and exploring individualized imaging phenotypes.
Assuntos
Encéfalo , Conectoma , Aprendizado Profundo , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/crescimento & desenvolvimento , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologiaRESUMO
Background: Recent research has focused on a new group called the "weekend warriors". These individuals accumulate their recommended moderate to vigorous physical activity (MVPA) over just 1-2 days, often during weekends, while remaining relatively inactive during the rest of the week. However, the effects of engaging in low-frequency MVPA on the risk of metabolic syndrome (MetS) are not well understood. This study investigated the association between physical activity patterns and the risk of MetS among Korean adults. Methods: This study included 26,197 participants (11,804 male and 14,393 female) aged ≥ 20 years from the Korea National Health and Nutrition Examination Survey. MVPA was measured using a global physical activity questionnaire. MetS was defined as the presence of more than three risk factors. Results: The odds ratio (OR) for MetS was 0.60 (95% confidence interval [CI] = 0.52, 0.70) in the "regularly active" group and 0.82 (95% CI = 0.69, 0.98) in the "weekend warrior" group compared to that in the inactive group (reference), which controlled for all covariates. For sensitivity analyses, the results across all subgroups exhibited similar patterns, with more pronounced effects observed in women, middle-aged individuals, and non-drinkers/light drinkers. Conclusions: Our findings suggest that concentrated bouts of moderate to vigorous physical activity, even if undertaken infrequently, confer health benefits that align with the recommended guidelines. This study contributes to the growing evidence on the relationship between physical activity patterns and MetS risk in Korean adults. The study also emphasizes the potential of different activity patterns in mitigating metabolic risk.
RESUMO
OBJECTIVES: To evaluate whether deep learning-based detection algorithms (DLD)-based triaging can reduce outpatient chest radiograph interpretation workload while maintaining noninferior sensitivity. METHODS: This retrospective study included patients who underwent initial chest radiography at the outpatient clinic between June 1 and June 30, 2017. Readers interpreted radiographs with/without a commercially available DLD that detects nine radiologic findings (atelectasis, calcification, cardiomegaly, consolidation, fibrosis, nodules, pneumothorax, pleural effusion, and pneumoperitoneum). The reading order was determined in a randomized, crossover manner. The radiographs were classified into negative and positive examinations. In a 50% worklist reduction scenario, radiographs were sorted in descending order of probability scores: the lower half was regarded as negative exams, while the remaining were read with DLD by radiologists. The primary analysis evaluated noninferiority in sensitivity between radiologists reading all radiographs and simulating a 50% worklist reduction, with the inferiority margin of 5%. The specificities were compared using McNemar's test. RESULTS: The study included 1964 patients (median age [interquartile range], 55 years [40-67 years]). The sensitivity was 82.6% (195 of 236; 95% CI: 77.5%, 87.3%) when readers interpreted all chest radiographs without DLD and 83.5% (197 of 236; 95% CI: 78.8%, 88.1%) in the 50% worklist reduction scenario. The difference in sensitivity was 0.8% (95% CI: - 3.8%, 5.5%), establishing noninferiority of 50% worklist reduction (p = 0.01). The specificity increased from 86.7% (1498 of 1728) to 90.4% (1562 of 1728) (p < 0.001) with DLD-based triage. CONCLUSION: Deep learning-based triaging may substantially reduce workload without lowering sensitivity while improving specificity. CLINICAL RELEVANCE STATEMENT: Substantial workload reduction without lowering sensitivity was feasible using deep learning-based triaging of outpatient chest radiograph; however, the legal responsibility for incorrect diagnoses based on AI-standalone interpretation remains an issue that should be defined before clinical implementation. KEY POINTS: ⢠A 50% workload reduction simulation using deep learning-based detection algorithm maintained noninferior sensitivity while improving specificity. ⢠The CT recommendation rate significantly decreased in the disease-negative patients, whereas it slightly increased in the disease-positive group without statistical significance. ⢠In the exploratory analysis, the noninferiority of sensitivity was maintained until 70% of the workload was reduced; the difference in sensitivity was 0%.
Assuntos
Inteligência Artificial , Aprendizado Profundo , Humanos , Pessoa de Meia-Idade , Radiografia , Radiografia Torácica , Radiologistas , Estudos Retrospectivos , Sensibilidade e Especificidade , Triagem , Carga de Trabalho , Adulto , IdosoRESUMO
The human brain begins to develop in the third gestational week and rapidly grows and matures over the course of pregnancy. Compared to fetal structural neurodevelopment, less is known about emerging functional connectivity in utero. Here, we investigated gestational age (GA)-associated in vivo changes in functional brain connectivity during the second and third trimesters in a large dataset of 110 resting-state functional magnetic resonance imaging scans from a cohort of 95 healthy fetuses. Using representational similarity analysis, a multivariate analytical technique that reveals pair-wise similarity in high-order space, we showed that intersubject similarity of fetal functional connectome patterns was strongly related to between-subject GA differences (r = 0.28, P < 0.01) and that GA sensitivity of functional connectome was lateralized, especially at the frontal area. Our analysis also revealed a subnetwork of connections that were critical for predicting age (mean absolute error = 2.72 weeks); functional connectome patterns of individual fetuses reliably predicted their GA (r = 0.51, P < 0.001). Lastly, we identified the primary principal brain network that tracked fetal brain maturity. The main network showed a global synchronization pattern resembling global signal in the adult brain.
Assuntos
Conectoma , Adulto , Gravidez , Feminino , Humanos , Recém-Nascido , Idade Gestacional , Conectoma/métodos , Feto , Encéfalo , Terceiro Trimestre da Gravidez , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). METHODS: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. RESULTS: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2-3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time. CONCLUSION: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.
Assuntos
Bronquiectasia , Bronquiolite , Infecções por Mycobacterium não Tuberculosas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Bronquiolite/diagnóstico por imagem , Bronquiolite/microbiologia , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
Reliability and robustness of resting state functional connectivity MRI (rs-fcMRI) relies, in part, on minimizing the influence of head motion on measured brain signals. The confounding effects of head motion on functional connectivity have been extensively studied in adults, but its impact on newborn brain connectivity remains unexplored. Here, using a large newborn data set consisting of 159 rs-fcMRI scans acquired in the Developing Brain Institute at Children's National Hospital and 416 scans from The Developing Human Connectome Project (dHCP), we systematically investigated associations between head motion and rs-fcMRI. Head motion during the scan significantly affected connectivity at sensory-related networks and default mode networks, and at the whole brain scale; the direction of motion effects varied across the whole brain. Comparing high- versus low-head motion groups suggested that head motion can impact connectivity estimates across the whole brain. Censoring of high-motion volumes using frame-wise displacement significantly reduced the confounding effects of head motion on neonatal rs-fcMRI. Lastly, in the dHCP data set, we demonstrated similar persistent associations between head motion and network connectivity despite implementing a standard denoising strategy. Collectively, our results highlight the importance of using rigorous head motion correction in preprocessing neonatal rs-fcMRI to yield reliable estimates of brain activity.
Assuntos
Mapeamento Encefálico , Conectoma , Adulto , Criança , Recém-Nascido , Humanos , Mapeamento Encefálico/métodos , Reprodutibilidade dos Testes , Artefatos , Encéfalo/diagnóstico por imagem , Conectoma/métodos , Movimento (Física) , Imageamento por Ressonância Magnética/métodosRESUMO
Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months-to-years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI-related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate-severe TBI who had primarily high-velocity and high-impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post-injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post-injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post-injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post-injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Lesão Encefálica Crônica , Substância Branca , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas/patologia , Substância Branca/patologia , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
BACKGROUND: Infants born very and extremely premature (V/EPT) are at a significantly elevated risk for neurodevelopmental disorders and delays even in the absence of structural brain injuries. These risks may be due to earlier-than-typical exposure to the extrauterine environment, and its bright lights, loud noises, and exposures to painful procedures. Given the relative underdeveloped pain modulatory responses in these infants, frequent pain exposures may confer risk for later deficits. METHODS: Resting-state fMRI scans were collected at term equivalent age from 148 (45% male) infants born V/EPT and 99 infants (56% male) born at term age. Functional connectivity analyses were performed between functional regions correlating connectivity to the number of painful skin break procedures in the NICU, including heel lances, venipunctures, and IV placements. Subsequently, preterm infants returned at 18 months, for neurodevelopmental follow-up and completed assessments for autism risk and general neurodevelopment. RESULTS: We observed that V/EPT infants exhibit pronounced hyperconnectivity within the cerebellum and between the cerebellum and both limbic and paralimbic regions correlating with the number of skin break procedures. Moreover, skin breaks were strongly associated with autism risk, motor, and language scores at 18 months. Subsample analyses revealed that the same cerebellar connections strongly correlating with breaks at term age were associated with language dysfunction at 18 months. CONCLUSIONS: These results have significant implications for the clinical care of preterm infants undergoing painful exposures during routine NICU care, which typically occurs without anesthesia. Repeated pain exposures appear to have an increasingly detrimental effect on brain development during a critical period, and effects continue to be seen even 18 months later.
Assuntos
Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento , Lactente , Recém-Nascido , Humanos , Masculino , Feminino , Transtornos do Neurodesenvolvimento/etiologia , Imageamento por Ressonância Magnética , Cognição , Dor/etiologiaRESUMO
3D concrete printing (3DCP) is an emerging additive manufacturing technology in the construction industry. Its challenges lie in the development of high-performance printable materials and printing processes. Recently developed carbon-based nanomaterials (CBNs) such as graphene, graphene oxide, graphene nanoplatelets, and carbon nanotubes, have various applications due to their exceptional mechanical, chemical, thermal, and electrical characteristics. CBNs also have found potential applications as a concrete ingredient as they enhance the microstructure and modify concrete properties at the molecular level. This paper focuses on state-of-the-art studies on CBNs, 3DCP technology, and CBNs in conventional and 3D printable cement-based composites including CBN dispersion techniques, concrete mixing methods, and fresh and hardened properties of concrete. Furthermore, the current limitations and future perspectives of 3DCP using CBNs to produce high-quality composite mixtures are discussed.
RESUMO
Three-dimensional (3D) geopolymer printing (3DGP) technology is a rapidly evolving digital fabrication method used in the construction industry. This technology offers significant benefits over 3D concrete printing in terms of energy saving and reduced carbon emissions, thus promoting sustainability. 3DGP technology is still evolving, and researchers are striving to develop high-performance printable materials and different methods to improve its robustness and efficiency. Carbon-based nanomaterials (CBNs) with beneficial properties have a wide range of applications in various fields, including as concrete/geopolymer systems in construction. This paper comprehensively reviews the research progress on carbon-based nanomaterials (CBNs) used to develop extrusion-based 3D geopolymer printing (3DGP) technology, including dispersion techniques, mixing methods, and the materials' performance. The rheological, mechanical, durability, and other characteristics of these materials are also examined. Furthermore, the existing research limitations and the prospects of using 3DGP technology to produce high-quality composite mixtures are critically evaluated.
RESUMO
BACKGROUND: The risk of gadolinium (Gd)-based contrast agent (GBCA)-induced nephrogenic systemic fibrosis (NSF) in patients with end-stage renal disease (ESRD) and the efficacy of prophylactic hemodialysis (HD) for protection against NSF are not well understood or summarized in the literature. PURPOSE: To determine the risk for NSF related to frequency and time per dialysis session after Gd-magnetic resonance imaging (MRI) by emphasizing the safety of Gd-MRI in patients with ESRD. MATERIAL AND METHODS: This retrospective observational study identified all GBCA injections for MRI examinations performed at two tertiary referral hospitals between 2005 and 2020. All clinical data, including dialysis records and medical history, were investigated for each patient through 2021. The end of follow-up coincided with the last hospital visit. RESULTS: Overall, 1129 patients with ESRD underwent 1461 Gd-MRI scans (41.5% gadoterate, 39.4% gadobutrol, and 7.7% gadoxetate); a total of 958 patients with 1229 (84.1%) examinations underwent HD on the day of the MRI study, within 2.1 ± 2.0 h (range = 0.2-15.7 h) immediately after Gd exposure. In 53.4% of scans, frequent HD had been performed urgently and then twice more on consecutive days to prophylactically avoid NSF. No cases of NSF were identified during the follow-up period (mean = 81.7 ± 50.5 months) regardless of dose of HD. CONCLUSION: No cases of NSF were reported in 1461 Gd-MRI examinations of 1129 inpatients with ESRD on HD. Our findings support the lack of benefit of frequent prophylactic HD being performed urgently within 4 h of the receipt of GBCA.
Assuntos
Falência Renal Crônica , Dermopatia Fibrosante Nefrogênica , Humanos , Meios de Contraste/efeitos adversos , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Dermopatia Fibrosante Nefrogênica/prevenção & controle , Gadolínio/efeitos adversos , Fatores de Risco , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: The primary purpose of this study was to determine radiation exposure of the surgeon during transforaminal endoscopic lumbar foraminotomy (TELF). Secondary purpose of this study was to compare clinical and radiologic outcomes between TELF under C-arm fluoroscopic guidance (C-TELF) and O-arm navigation-guided TELF (O-TELF). METHODS: The author reviewed patients' medical records who underwent TELF at our institute from June 2015 to November 2022. A total of 40 patients were included (18 patients with C-TELF and 22 with O-TELF). Basic demographic data were collected. Preoperative/postoperative visual analog scale (VAS) and Oswestry Disability Index (ODI) were recorded at the outpatient clinic. Radiologic features were compared on X-rays at each follow-up. The degree of foraminal expansion was measured/compared through MRI. In the C-TELF group, the amount of exposure was calculated with a dosimeter. RESULTS: Average surgeon's effective dose in the C-TELF group was 0.036 mSv. In the case of the O-TELF group, there was no radiation exposure during operation. However, the operation time in the O-TELF group was about 37 min longer than that in the C-TELF group. There were significant improvements in VAS/ODI after operation in both groups. Complications were identified in three patients. CONCLUSION: O-TELF showed similarly favorable clinical and radiologic outcomes to C-TELF in lumbar foraminal stenosis, including complication rate. Compared to C-TELF, O-TELF has an advantage of not wearing a lead apron since the operator is not exposed to radiation. However, the operation time was longer with O-TELF due to O-arm setting time. Because there are pros and cons, the choice of surgical method depends on the surgeon's preference.
Assuntos
Foraminotomia , Cirurgia Assistida por Computador , Humanos , Foraminotomia/métodos , Imageamento Tridimensional , Cirurgia Assistida por Computador/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do TratamentoRESUMO
Precipitate generation is a challenging issue during the production of herbal decoction as it affects the stability and bioavailability of active compounds. Here we explored the composition of the natural precipitate formed from and its effect on drug release of Scutellariaâ baicalensis-Coptisâ chinensis paired extract (SCPE). Furthermore, the surface morphology of the SCPE precipitate was also investigated. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to chemical component analysis and field emission scanning electron microscope (FE-SEM) was performed to particle observation. Baicalin (BA), berberine (BBR) and starch-arginine-rich polymers were abundant in the SCPE precipitate. FE-SEM micrographs showed spheroidal shaped particles in the SCPE supernatant, while spherical and porous tissue-shaped particles in the SCPE precipitate. In vitro drug release of baicalin and berberine contained in the precipitate may increase as the polymer is removed. The presence of polymer-related interactions were confirmed by the greater increase in solubility of baicalin upon addition of arginine and polymer. This was also supported by the solubility decrease of the BA-BBR complex in polymer solution and the gelation of the BA-BBR complex in arginine solution. Our results provide a scientific basis for elucidating the pharmaceutical properties of the decoction of S.â baicalensis-C.â chinensis-based herbal medicine.
Assuntos
Berberina , Coptis , Medicamentos de Ervas Chinesas , Arginina , Berberina/análise , Berberina/química , Cromatografia Líquida , Coptis/química , Coptis chinensis , Liberação Controlada de Fármacos , Flavonoides/química , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais , Polímeros , Scutellaria baicalensis/química , Espectrometria de Massas em TandemRESUMO
Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<-6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.
Assuntos
Dermatite de Contato , Fraxinus , Animais , Camundongos , NF-kappa B/metabolismo , Fraxinus/metabolismo , Ciclo-Oxigenase 2/metabolismo , Casca de Planta/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dermatite de Contato/tratamento farmacológico , Interleucina-6 , Lipopolissacarídeos/farmacologia , Óxido NítricoRESUMO
Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network-wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been relatively limited. In this study, we propose a novel connectomic measure that we call network normality score (NNS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate-to-severe TBI patients, we demonstrate that structural network topology of patients is more heterogeneous and significantly different than that of healthy controls at 3 months postinjury, where dissimilarity further increases up to 12 months. We also show that NNS captures injury burden as quantified by posttraumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally, we compare NNS to major graph theory measures used in TBI literature and demonstrate the superiority of NNS in characterizing the disease.
Assuntos
Lesões Encefálicas Traumáticas , Transtornos Cognitivos , Conectoma , Substância Branca , Encéfalo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Humanos , Substância Branca/diagnóstico por imagemRESUMO
Age-related macular degeneration (AMD) is a chronic and progressive disease characterized by degeneration of the retinal pigment epithelium (RPE) and retina that ultimately leads to loss of vision. The pathological mechanisms of AMD are not fully known. Cellular senescence, which is a state of cell cycle arrest induced by DNA-damage or aging, is hypothesized to critically affect the pathogenesis of AMD. In this study, we examined the relationship between cellular senescence and RPE/retinal degeneration in mouse models of natural aging and accelerated aging. We performed a bulk RNA sequencing of the RPE cells from adult (8 months old) and naturally-aged old (24 months old) mice and found that common signatures of senescence and AMD pathology - inflammation, apoptosis, and blood vessel formation - are upregulated in the RPE of old mice. Next, we investigated markers of senescence and the degree of RPE/retinal degeneration in Zmpste24-deficient (Zmpste24-/-) mice, which is a model for progeria and accelerated aging. We found that Zmpste24-/- mice display markedly greater level of senescence-related markers in RPE and significant RPE/retinal degeneration compared to wild-type mice, in a manner consistent with natural aging. Overall, these results provide support for the association between cellular senescence of RPE and the pathogenesis of AMD, and suggest the use of Zmpste24-/- mice as a novel senescent RPE model of AMD.
Assuntos
Degeneração Macular , Degeneração Retiniana , Epitélio Pigmentado da Retina , Animais , Camundongos , Envelhecimento/patologia , DNA/metabolismo , Degeneração Macular/genética , Degeneração Macular/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Fenótipo , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/metabolismoRESUMO
Absract In developed countries, age-related macular degeneration (AMD) is a leading cause of irreversible blindness in adults. The key pathways of AMD are suggested to be excessive oxidative stress and inflammation in the central retina. Because air pollution has been found capable of inducing oxidative stress and inflammation, it may play a role in development of AMD. This study investigated the association between ambient air pollution and AMD in 15,115 middle-aged and older adults (≥40 years) from Korean National Health and Nutrition Examination Survey 2008-2012. After controlling for important confounders, ambient NO2 and CO in current-to-5 prior years and PM10 in 2-to-5 prior years were significantly associated with higher prevalence of early AMD, while O3 in current-to-5 prior years was significantly associated with lower prevalence of early AMD. When modeled air pollution within administrative division units, its ORs with an IQR increase in NO2, CO, and O3 at current year were 1.24 (95% CI: 1.05-1.46), 1.22 (95% CI: 1.09-1.38), and 0.80 (95% CI: 0.70-0.92), respectively. Overall, results from air pollution at local/town units were consistent with those at administrative division units. Long-term exposures to ambient air pollution may play a role in the risk of AMD in middle-aged and older adults.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Degeneração Macular , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/epidemiologia , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Inquéritos Nutricionais , Material Particulado/análiseRESUMO
BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. METHODS: We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. RESULTS: Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1-82) months. The median age was 55 (range, 33-75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. CONCLUSIONS: The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.
Assuntos
Pneumonias Intersticiais Idiopáticas/diagnóstico , Pneumonias Intersticiais Idiopáticas/epidemiologia , Adulto , Idoso , Biópsia/métodos , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/patologia , Pneumonias Intersticiais Idiopáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Atractylodes plants have been used in traditional herbal medicine to treat gastrointestinal diseases and contain various chemical compounds. Sesquiterpenoids are the most important therapeutic compounds in Atractylodes rhizomes. Based on studies reported from 2000 to 2022, we classified sesquiterpenoids by their chemical skeletons and original resources. Moreover, we discussed their biosynthesis and physicochemical and pharmacological features. We reported sesquiterpenoids with skeletal moieties, such as monocyclic sesquiterpenes (bisabolene- and elemene-type), bicyclic sesquiterpenes (eudesmane-, isopterocarpolone-, hydroxycarissone-, eremophilane-, bisesquiterpenoid-, guaiane- and spirovetivane-type and eudesmane lactones) and tricyclic sesquiterpenes (cyperene- and patchoulene-type), with their biosynthetic pathways, chemical modifications and inâ vivo metabolites. The pharmacological activities of sesquiterpenoids as anti-inflammatory, anti-tumor, anti-diabetic and anti-microbial and for treating gastrointestinal disorders have been reported for this genus.
Assuntos
Atractylodes , Sesquiterpenos de Eudesmano , Sesquiterpenos , Rizoma/química , Atractylodes/química , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/químicaRESUMO
The roots of Peucedanum japonicum (Apiaceae) have been used as an alternative to the roots of Saposhnikovia divaricata (Apiaceae) to treat common cold-related symptoms in Korea. However, a variety of Peucedanum species, including the roots of P. praeruptorum or Angelica decursiva (=P. decursivum), have been used to treat phlegm-heat-induced symptoms in China. Hence, as there are differences in the medicinal application of P. japonicum roots between Korea and China, chemotaxonomic classification of P. japonicum was evaluated. Sixty samples derived from P. japonicum, P. praeruptorum, A. decursiva, and S. divaricata were phylogenetically identified using DNA barcoding tools, and chemotaxonomic correlations among the samples were evaluated using chromatographic profiling with chemometric analyses. P. japonicum samples were phylogenetically grouped into the same cluster as P. praeruptorum samples, followed by S. divaricata samples at the next cluster level, whereas A. decursiva samples were widely separated from the other species. Moreover, P. japonicum samples showed higher chemical correlations with P. praeruptorum samples or A. decursiva samples, but lower or negative chemical correlations with S. divaricata samples. These results demonstrate that P. japonicum is more genetically and chemically relevant to P. praeruptorum or A. decursiva and, accordingly, the medicinal application of P. japonicum might be closer to the therapeutic category of these two species than that of S. divaricata.