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BACKGROUND: Coffee and tea consumption has been linked to dementia. However, it remained unknown how sex and vascular risk factors modify the association. We aimed to investigate the association of coffee and tea consumption with dementia and whether sex and vascular comorbidities modified the association. METHODS: We included 278 elderly patients with Alzheimer's disease (AD) and 102 patients with vascular dementia (VaD) from three hospitals; controls (N = 468) were recruited during the same period. We collected the frequency and amount of coffee and tea consumption and the presence of vascular comorbidities. The multinomial logistic regression model was utilized to evaluate the association of coffee and tea consumption with dementia, stratified by sex and vascular comorbidities. RESULTS: Different combinations and quantities of coffee and tea consumption protected against AD and VaD. Consumption of ≥3 cups of coffee or tea per day was protective against AD [adjusted odds ratio (aOR) = 0.42; 95% confidence interval (CI) = 0.22-0.78)] and VaD (aOR = 0.42; 95% CI = 0.19-0.94). Stratified analyses showed that the protective effects of a higher quantity of coffee and tea against AD were more pronounced among females and individuals with hypertension. Consumption of either coffee or tea was associated with a decreased risk of VaD among diabetic participants (aOR = 0.23; 95% CI = 0.06-0.98). Hyperlipidemia modified the association of coffee or tea consumption on the risk of AD and VaD (both Pinteraction < 0.01). CONCLUSION: The risk of AD and VaD was lower with increased consumption of coffee and tea; the impact differed by sex and vascular comorbidities including hypertension, hyperlipidemia, and diabetes.
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Data-independent acquisition (DIA) mass spectrometry has grown in popularity in recent years, because of the reproducibility and quantitative rigor of a systematic tandem mass spectrometry (MS/MS) sampling method. However, traditional DIA methods may spend valuable instrument time acquiring MS/MS spectra with no usable information in them, affecting sensitivity and quantitative performance. We developed a DIA strategy that dynamically adjusts the MS/MS windows during the chromatographic separation. The method focuses MS/MS acquisition on the most relevant mass range at each point in timeâincreasing the quantitative sensitivity by increasing the time spent on each DIA window. We demonstrate an improved lower limit of quantification, on average, without sacrificing the number of peptides detected.
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Péptidos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Péptidos/análisisRESUMEN
An Orbitrap-based ion analysis procedure determines the direct charge for numerous individual protein ions to generate true mass spectra. This individual ion mass spectrometry (I2MS) method for charge detection enables the characterization of highly complicated mixtures of proteoforms and their complexes in both denatured and native modes of operation, revealing information not obtainable by typical measurements of ensembles of ions.
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Espectrometría de Masas/métodos , Proteínas/química , Proteómica/métodos , HumanosRESUMEN
BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5â¯cm3 had a lower incidence of initial enlargement (pâ¯= 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8⯱ 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (pâ¯= 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5â¯cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.
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Neuroma Acústico , Radiocirugia , Humanos , Radiocirugia/métodos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Estudios Retrospectivos , Imagen por Resonancia Magnética , Aceleradores de Partículas , Estudios de Seguimiento , Resultado del TratamientoRESUMEN
In this study, the plausible role of trimethylamine N-oxide (TMAO), a microbiota metabolite, was investigated as a link between peripheral inflammation and the inflammation of the central nervous system using different cell lines. TMAO treatment favored the differentiation of adipocytes from preadipocytes (3T3-L1 cell line). In macrophages (RAW 264.7 cell line), which infiltrate adipose tissue in obesity, TMAO increased the expression of pro-inflammatory cytokines. The treatment with 200 µM of TMAO seemed to disrupt the blood-brain barrier as it induced a significant decrease in the expression of occludin in hCMECs. TMAO also increased the expression of pro-inflammatory cytokines in primary neuronal cultures, induced a pro-inflammatory state in primary microglial cultures, and promoted phagocytosis. Data obtained from this project suggest that microbial dysbiosis and increased TMAO secretion could be a key link between peripheral and central inflammation. Thus, TMAO-decreasing compounds may be a promising therapeutic strategy for neurodegenerative diseases.
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Inflamación , Metilaminas , Humanos , Inflamación/metabolismo , Metilaminas/farmacología , Metilaminas/metabolismo , Citocinas , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is associated with brain injury in newborns and may lead to disability or death. Mild therapeutic hypothermia (TH) is an effective neuroprotective intervention and an established standard of care in western countries. The gut microbiome, the genomic and physicochemical contribution of the gut microbiota, serves important functions and is increasingly recognized as a major influencer on development. The impact of HIE and TH on the evolving gut microbiota of the newborn remains to be elucidated. OBJECTIVE: The objective of this study was to carry out an exploratory study on the effects of HIE and TH on the gut microbiome in term neonates. METHODS AND RESULTS: Stool samples were obtained from 28 newborns with HIE (median age 68 h) undergoing TH on the neonatal unit (HIE TH group), with a follow-on stool sample available for 20 of these babies (median age 151 h). For comparison, a single stool specimen was obtained from 19 healthy newborns on the postnatal ward (median age 34 h). The microbiota composition was determined using established microbial DNA extraction and 16S rRNA gene sequencing methodology. There was no difference in the mode of delivery or the method of feeding the newborns, once established, between the 2 groups. All the infants in the HIE TH group had received antibiotics compared to only one of the controls. A lower α-diversity, quantified by the Shannon diversity index, was noted in the microbiota of the HIE TH group in comparison to the control group. The HIE TH group had a higher mean relative abundance (MRA) of facultative anaerobes and aerobes such as Staphylococcus species and a lower MRA of strict anaerobes, such as members of the Bacteroides genus, compared to the control. Also, there was a significant reduction in the MRA of the genus Bifidobacterium in the HIE TH group. Although the mode of delivery exerts a profound influence on the gut microbiota of the newborn, distance-based redundancy analysis showed that TH may exert an independent influence. This study could not determine the independent contribution of the use of antibiotics or the neonatal intensive care unit environment. CONCLUSION: In this study, we demonstrate an alteration in the microbiota composition in newborns undergoing TH for HIE.
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Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Microbiota , Adulto , Anciano , Antibacterianos , Humanos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Lactante , Recién Nacido , ARN Ribosómico 16SRESUMEN
Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCMHR: 1.05, CI: 1.01−1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.
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Esclerosis Amiotrófica Lateral , Biomarcadores , Progresión de la Enfermedad , Humanos , Leucocitos Mononucleares , Monocitos , Estudios RetrospectivosRESUMEN
Purpose Alzheimer disease (AD) is an irreversible neurodegenerative disease that causes progressive cognitive decline. Co-existing thymoma should be considered when rapid deterioration of cognition was noted in AD patients and removal of thymoma may improve cognition in AD. Case report We report a 72-year-old woman with initial complaints of memory impairment for 2 years. After detailed history taking, neuropsychological tests, brain magnetic resonance imaging, and positive amyloid positron emission tomography, she was diagnosed as having dementia of the Alzheimer type. At the time of diagnosis, her dementia condition was mild (clinical dementia rating [CDR] is equal to 1, CDR sum of boxes [CDR-sb] = 4.5, Mini-Mental State Examination (MMSE) is equal to 21 divided by 30). She needed moderate assistance in performing daily life activities. One year after AD diagnosis, her condition deteriorated drastically, and she experienced frequent falls and severe weakness apart from cognitive symptoms. Concurrent myasthenia gravis (MG) with thymoma was found later, and thymectomy was performed. Her symptoms related to MG alleviated after the operation. Notably, her cognitive symptoms also improved 4 months after the operation, and her dementia reversed to mild cognitive impairment. Conclusion Although the role of neuroinflammation in AD has been widely discussed, it remains elusive. Removal of the co-existing thymoma not only alleviated the patient's MG symptoms but also improved her cognitive performance. We supposed that this effect may have been a direct result of the decrease in acetylcholine receptor antibody or reduction in the degree of neuroinflammation. Keywords Alzheimer disease, thymoma, neuroinflammation, central cholinergic effects, acetylcholine receptor antibody.
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Microglial proliferation and activation and macrophage accumulation are implicated in neuropathic pain development. In this study, we aim to suppress microgliosis and macrophage accumulation by over-expressing a non-functional soluble colony stimulating factor-1 receptor (sCSF1R) using an adeno-associated virus 9 vector (AAV9). AAV9/sCSF1R and the control vector AAV9/GFP were intrathecally administered into the lumbar spine of adult C57BL/6 mice. Two weeks later, these mice underwent partial sciatic nerve ligation to induce neuropathic pain. GFP and sCSF1R were highly expressed in lumbar dorsal root ganglia (DRG) and spinal cord of AAV9-injected mice. A significant increase in microglia densities in the dorsal and ventral horns of lumbar spinal cords and macrophage densities in DRG and sciatic nerves were observed in the mice with either ligation alone or pre-treated with AAV9/GFP. In nerve-ligated mice pre-treated with AAV9/sCSF1R the microglia densities in the dorsal and ventral horns and macrophage densities in DRG and sciatic nerves were significantly lower compared to nerve-ligated mice pre-treated with AAV9/GFP. Behavioral tests showed that nerve-ligated mice pre-treated with AAV9/sCSF1R had a significantly higher paw withdrawal threshold, indicating the alleviation of neuropathic pain. The results implicate that viral vector-mediated expression of sCSF1R may represent a novel strategy in the alleviation of neuropathic pain.
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Factor Estimulante de Colonias de Macrófagos , Neuralgia , Animales , Ganglios Espinales/metabolismo , Hiperalgesia/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Neuralgia/metabolismo , Neuralgia/terapia , Receptor de Factor Estimulante de Colonias de Macrófagos , Médula Espinal/metabolismoRESUMEN
Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.
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Ácidos Docosahexaenoicos/uso terapéutico , MicroARNs/metabolismo , Microglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Contusiones/tratamiento farmacológico , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/farmacología , Femenino , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/citología , Microglía/metabolismo , Vaina de Mielina/metabolismo , Neuronas/metabolismo , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Células PC12 , Ratas , Ratas Sprague-DawleyRESUMEN
Native mass spectrometry involves transferring large biomolecular complexes into the gas phase, enabling the characterization of their composition and stoichiometry. However, the overlap in distributions created by residual solvation, ionic adducts, and post-translational modifications creates a high degree of complexity that typically goes unresolved at masses above â¼150 kDa. Therefore, native mass spectrometry would greatly benefit from higher resolution approaches for intact proteins and their complexes. By recording mass spectra of individual ions via charge detection mass spectrometry, we report isotopic resolution for pyruvate kinase (232 kDa) and ß-galactosidase (466 kDa), extending the limits of isotopic resolution for high mass and high m/z by >2.5-fold and >1.6-fold, respectively.
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Procesamiento Proteico-Postraduccional , Proteínas , Iones , Espectrometría de MasasRESUMEN
Movies can be an effective tool for increasing the depth and breadth of learning. In this era of continuously advancing knowledge and technology, it is essential to design curricula that shorten the learning time of RN-BSN nursing students and arouse and stimulate their interest and potential. Designing an in-service nursing curriculum that enhances the self-reflection capabilities of students is challenging. Cinema teaching and the development of the plots model facilitate student engagement with movies. Through emotional development and the setting of background contexts, cinema teaching helps transform and establish students' knowledge of mental and psychological healthcare and increases their understanding of patient behaviors. Mental and psychological education aims to enhance cognition and provide practical learning strategies for in-serving nursing students. By implementing the cinema teaching method, students come to empathize with the pain and helplessness of patients and their families and learn how to provide care and social support to these patients.
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Bachillerato en Enfermería , Estudiantes de Enfermería , Curriculum , Humanos , Películas Cinematográficas , Investigación en Educación de Enfermería , EnseñanzaRESUMEN
Targeted mass spectrometry methods produce high-quality quantitative data in terms of limits of detection and dynamic range, at the cost of a substantial compromise in throughput compared to methods such as data independent and data dependent acquisition. The logistical and experimental issues inherent to maintaining assays of even several hundred targets are significant. Prominent among these issues is the drift in analyte retention time as liquid chromatography (LC) columns wear, forcing targeted scheduling windows to be much larger than LC peak widths. If these problems could be solved, proteomics assays would be capable of targeting thousands of peptides in an hour-long experiment, enabling large cohort studies to be performed without sacrificing sensitivity and specificity. We describe a solution in the form of a new method for real-time chromatographic alignment and demonstrate its application to a 56 min LC-gradient HeLa digest assay with 1489 targets. The method is based on the periodic acquisition of untargeted survey scans in a reference experiment and alignment to those scans during subsequent experiments. We describe how the method enables narrower scheduled retention time windows to be used. The narrower scheduling windows enables more targets to be included in the assay or proportionally more time to be allocated to each target, improving the sensitivity. Finally, we point out how the procedure could be improved and how much additional target multiplexing could be gained in the future.
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Cromatografía Liquida/métodos , Péptidos/química , Proteómica/métodos , HumanosRESUMEN
Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 µM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.
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Ácidos Docosahexaenoicos/uso terapéutico , Proyección Neuronal/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Técnicas de Cultivo de Célula , Portadores de Fármacos/química , Liberación de Fármacos , Embrión de Mamíferos , Fenómenos Mecánicos , Nanofibras/química , Neuronas/patología , Poliésteres/química , Ratas , Ratas Sprague-DawleyRESUMEN
Traumatic brain injury (TBI) could result in edema and cause an increase in intracranial pressure of the brain resulting in mortality and morbidity. Although there is hyperosmolarity therapy available for this pathophysiological event, it remains controversial. Recently, several groups have shown docosahexaenoic acid (DHA) to improve functional and histological outcomes following brain injury based on reduction of neuroinflammation and apoptosis. However, the effect of DHA on blood-brain barrier (BBB) dysfunction after brain injury has not been fully studied. Here, a controlled cortical impact rat model was used to test the effect of a single dose of DHA administered 30 min post injury. Modified neurological severity score (mNSS) and forelimb asymmetry were used to determine the functional outcomes. Neuroimaging and histology were used to characterize the edema and BBB dysfunction. The study showed that DHA-treated TBI rats had better mNSS and forelimb asymmetry score than vehicle-treated TBI rats. Temporal analysis of edema using MRI revealed a significant reduction in edema level with DHA treatment compared to vehicle in TBI rats. Histological analysis using immunoglobulin G (IgG) extravasation showed that there was less extravasation, which corresponded with a reduction in aquaporin 4 and astrocytic metalloprotease 9 expression, and greater endothelial occludin expression in the peri-contusional site of the TBI rat brain treated with DHA in comparison to vehicle treatment. In conclusion, the study shows that DHA can exert its functional improvement by prevention of the edema formation via prevention of BBB dysfunction after TBI.
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Barrera Hematoencefálica/efectos de los fármacos , Edema Encefálico/prevención & control , Lesiones Traumáticas del Encéfalo/complicaciones , Permeabilidad de la Membrana Celular , Ácidos Docosahexaenoicos/farmacología , Animales , Barrera Hematoencefálica/metabolismo , Edema Encefálico/etiología , Imagen por Resonancia Magnética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice. Immunohistochemical studies demonstrated that CSF1 was expressed in astrocytes and neurons in normal mouse spinal cord. In acute EAE, CSF1 expression was significantly increased, especially in astrocytes in peripheral white matter and large motoneurons. High density of activated microglia was observed in the gray matter where motoneurons expressed high-level CSF1 in acute EAE. Significant large motoneuron loss was seen in chronic EAE and the remaining motoneurons with high-level CSF1 were enwrapped by microglia. Viral vector mediated over-expression of CSF1 in spinal neurons induced profound proliferation and activation of microglia at the injection site and microglia enwrapped CSF1-transduced neurons and their neurites. Significant loss of large CSF1-transduced neurons was seen at 2 and 3 weeks post-viral injection. Demyelination in the CSF1-transduced areas was also significant. These results implicate that CSF1 upregulation in CNS may play an important role in the proliferation and activation of microglia in EAE, contributing to neuroinflammation and neurodegeneration. © 2018 Wiley Periodicals, Inc.
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Encefalomielitis Autoinmune Experimental/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Microglía/metabolismo , Neuronas/metabolismo , Médula Espinal/metabolismo , Enfermedad Aguda , Animales , Proliferación Celular/fisiología , Enfermedad Crónica , Encefalomielitis Autoinmune Experimental/patología , Femenino , Regulación de la Expresión Génica , Sustancia Gris/metabolismo , Sustancia Gris/patología , Células HEK293 , Humanos , Interleucinas/metabolismo , Masculino , Ratones , Microglía/patología , Neuronas/patología , Médula Espinal/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patologíaRESUMEN
In the present study, an innovative top-down liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the identification of clinically relevant fungi is tested using a model set of dermatophyte strains. The methodology characterizes intact proteins derived from Trichophyton species, which are used as parameters of differentiation. To test its resolving power compared to that of traditional Sanger sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), 24 strains of closely related dermatophytes, Trichophyton rubrum, T. violaceum, T. tonsurans, T. equinum, and T. interdigitale, were subjected to this new approach. Using MS/MS and different deconvolution algorithms, we identified hundreds of individual proteins, with a subpopulation of these used as strain- or species-specific markers. Three species, i.e., T. rubrum, T. violaceum, and T. interdigitale, were identified correctly down to the species level. Moreover, all isolates associated with these three species were identified correctly down to the strain level. In the T. tonsurans-equinum complex, eight out of 12 strains showed nearly identical proteomes, indicating an unresolved taxonomic conflict already apparent from previous phylogenetic data. In this case, it was determined with high probability that only a single species can be present. Our study successfully demonstrates applicability of the mass spectrometric approach to identify clinically relevant filamentous fungi. Here, we present the first proof-of-principle study employing the mentioned technology to differentiate microbial pathogens. The ability to differentiate fungi at the strain level sets the stage to improve patient outcomes, such as early detection of strains that carry resistance to antifungals.
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Arthrodermataceae/química , Arthrodermataceae/clasificación , Dermatomicosis/microbiología , Técnicas de Tipificación Micológica/métodos , Espectrometría de Masas en Tándem , Dermatomicosis/diagnóstico , Proteínas Fúngicas/análisis , Humanos , Especificidad de la Especie , Trichophyton/química , Trichophyton/clasificaciónRESUMEN
BACKGROUND/PURPOSE: Screening of dementia can help to initiate proper management of the disorder. The use of the Ascertain Dementia 8-item Questionnaire (AD8) in screening has been promoted in Taiwan recently. The purpose of this study was to compare the psychometric properties and appropriateness of informant-reported and self-rated AD8 in cognitive impairment screening in Taiwan. METHODS: The AD8 were administered to 153 participants and their informants recruited from two neurology out-patient clinics. The discriminative abilities for early cognitive impairment [Clinical Dementia Rating scale (CDR) 0.5 and 1] of informant-based and self-rating AD8 were determined and compared with their areas under the receiver operating curve. κ coefficients representing the agreement between self-rated and informant-reported AD8 scores were also calculated. RESULTS: Participants and their informants were aged 76.9 years and 56.0 years on average, respectively. Only informant-reported AD8 was significantly associated with CDR level (Spearman ρ=0.469, p<0.001) and Cognitive Abilities Screening Instrument score (Spearman ρ=-0.458, p<0.001). The item-by-item agreements between self-rated and informant-reported AD8 were poor (κ coefficients: -0.030 to 0.206). The area under the receiver-operator characteristic curve was 0.59 for self-rated AD8 scores, and 0.77 for informant-reported AD8 scores, indicating that the discriminating ability of AD8 scores between CDR 0 and CDR 0.5 or greater is better when reported by informant than when rated by self. CONCLUSION: Informant-rated AD8 gave more accurate screening results than self-reported AD8 in an out-patient clinic setting.
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Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Tamizaje Masivo/métodos , Pruebas Neuropsicológicas , Autoinforme , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Curva ROC , Sensibilidad y Especificidad , TaiwánRESUMEN
BACKGROUND: The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. METHODS: From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). RESULTS: Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. CONCLUSIONS: Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.
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Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Lenguaje , Conducta Verbal , Anciano de 80 o más Años , Escolaridad , Femenino , Evaluación Geriátrica , Humanos , Japón , Masculino , Pruebas Neuropsicológicas , Estudios Prospectivos , Factores SocioeconómicosRESUMEN
BACKGROUND: Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. METHODS: We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. RESULTS: Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. CONCLUSIONS: Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.