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Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults.
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Factor Neurotrófico Derivado del Encéfalo , Factor I del Crecimiento Similar a la Insulina , Memoria a Corto Plazo , Tiempo de Reacción , Entrenamiento de Fuerza , Vibración , Humanos , Entrenamiento de Fuerza/métodos , Masculino , Femenino , Persona de Mediana Edad , Vibración/uso terapéutico , Anciano , Factor Neurotrófico Derivado del Encéfalo/sangre , Memoria a Corto Plazo/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cognición/fisiología , Norepinefrina/sangre , Flujo Sanguíneo Regional/fisiología , Encéfalo/fisiologíaRESUMEN
BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.
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Citocromos c , Exenatida , Agonistas Receptor de Péptidos Similares al Glucagón , Enfermedades Mitocondriales , Citocromos c/uso terapéutico , Enfermedades Mitocondriales/tratamiento farmacológico , Enfermedades Mitocondriales/metabolismo , Exenatida/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: In December 2022, the Taiwan National Health Insurance Administration (NHIA) announced the reimbursement of three dosages of pemigatinib 4.5 mg, 9 mg, and 13.5 mg for treating advanced intrahepatic cholangiocarcinoma (ICC) with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and set the reimbursement price for pemigatinib 4.5 mg at NT$6600. This study aims to analyze the cost-effectiveness of pemigatinib 13.5 mg as a second-line treatment compared to mFOLFOX and 5-FU chemotherapy for advanced ICC patients with FGFR2 fusions/rearrangements from the perspective of Taiwan's NHIA. METHODS: This study used a 3-state partitioned survival model to analyze the 5 year cost-effectiveness of pemigatinib as a second-line treatment for advanced ICC patients in whom first-line gemcitabine-based chemotherapy failed and to compare the results with those for the mFOLFOX and 5-FU chemotherapy regimens. Overall survival and progression-free survival were estimated from the FIGHT-202 trial (pemigatinib), ABC-06 trial (mFOLFOX), and NIFTY trial (5-FU). The price of pemigatinib 13.5 mg was set at the potentially highest listing price (NT$17,820). Other parameters of utility, disutility, and costs related to advanced ICC were obtained from the published literature. The willingness-to-pay threshold was three times the forecasted gross domestic product per capita in 2022 (NT$2,928,570). A 3% discount rate was applied to quality-adjusted life-years (QALYs) and costs. Several scenario analyses were performed, including a gradual price reduction for pemigatinib. Deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA), and value of information were performed to assess uncertainty. RESULTS: Pemigatinib was not cost-effective compared to mFOLFOX or 5-FU in the base-case analysis. When the price of pemigatinib was reduced by 50% or more, pemigatinib gained a positive net monetary benefit (mFOLFOX: NT$55,374; 5-FU: NT$92,437) and a 72% (mFOLFOX) and 77.1% (5-FU) probability of being cost-effective. Most of the uncertainty came from the medication cost of pemigatinib, health state utility, and the overall survival associated with pemigatinib. CONCLUSIONS: According to the NCCN guidelines, the daily use of pemigatinib 13.5 mg at the hypothesized NHIA price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU. The price reduction scenario suggested a 50% price reduction, NT$8910 per 13.5 mg, for advanced ICC patients with FGFR2 fusions/rearrangements.
This study performed a cost-effectiveness analysis on the use of targeted therapy pemigatinib 13.5 mg daily in second-line treatment for Taiwanese patients with intrahepatic cholangiocarcinoma (ICC) harboring FGFR2 fusions/rearrangements. This regimen was approved by the U.S. Food and Drug Administration in 2020 and recommended by the National Comprehensive Cancer Network (NCCN). Taiwan's National Health Insurance Administration (NHIA) has announced the reimbursement of three pemigatinib dosages of 4.5 mg, 9 mg, and 13.5 mg to be listed in the NHI coverage in 2022. However, as of the middle of April 2023, only the listing price for pemigatinib 4.5 mg has been determined, while pricing for the other two dosages remains pending. Based on a hypothesized NHIA price of NT$17,820/13.5 mg, this study evaluated the cost-effectiveness of pemigatinib 13.5 mg as a second-line treatment for advanced ICC with FGFR2 fusions/rearrangements compared to mFOLFOX (a regimen recommended by NCCN) and 5-FU (a regimen fully covered by Taiwan NHIA) and recommended a listing price for NHIA as reference. Our study showed that the hypothesized price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU. The price reduction scenario suggested a 50% reduction (NT$8910) in the hypothesized NHIA price for advanced ICC patients with FGFR2 fusions/rearrangements.
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(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: -0.29 ± 0.44 vs. -0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = -0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies.
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BACKGROUND: To identify the risk factors for postoperative hydrocephalus and the need for ventriculoperitoneal (VP) shunt after posterior fossa tumor (PFT) resection in pediatric patients and establish a predictive model. METHODS: A total of 217 pediatric patients (≤14 years old) with PFTs who underwent tumor resection from November 2010 to December 2020 were divided into a VP shunt group (n = 29) and non-VP shunt group (n = 188). Univariate and multivariate logistic regression were performed. A predictive model was established based on the independent predictors. Receiver operating characteristic curves were generated to determine the cutoff values and areas under the curve (AUCs). The Delong test was performed to compare the AUCs. RESULTS: Age less than three years (P = 0.015, odds ratio [OR] = 3.760), blood loss (BL) (P = 0.002, OR = 1.601), and locations at fourth ventricle (P < 0.001, OR = 7.697) were the independent predictors. The predictive model was as follows: total score = age (<3; yes = 2, no = 0) + BL + tumor locations (fourth ventricle; yes = 5, no = 0). The AUC of our model was higher than those of age less than three years, BL, locations at the fourth ventricle, and compound factors (age <3 + locations) (0.842 vs 0.609, 0.734, 0.732, and 0.788, respectively). The cutoff values of the model and BL were 7.5 points and 2.75 U, respectively. CONCLUSIONS: BL, age less than three years, and tumors at the fourth ventricle were independent predictors. Model scores over 7.5 points predict a high risk.
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Neoplasias Encefálicas , Hidrocefalia , Neoplasias Infratentoriales , Niño , Humanos , Preescolar , Adolescente , Derivación Ventriculoperitoneal/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/complicaciones , Neoplasias Infratentoriales/cirugía , Neoplasias Infratentoriales/complicaciones , Hidrocefalia/cirugía , Hidrocefalia/etiología , Hemorragia/complicacionesRESUMEN
OBJECTIVE: To construct and verificate an RNA-binding protein (RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis. METHODS: RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas database (CGGA) were downloaded. The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database. We then identified prognosis related hub genes and constructed a prognostic model. This model was further validated in the CGGA-693 and CGGA-325 cohorts. RESULTS: Totally 174 differently expressed genes-encoded RBPs were identified, containing 85 down-regulated and 89 up-regulated genes. We identified five genes-encoded RBPs (ERI1, RPS2, BRCA1, NXT1, and TRIM21) as prognosis related key genes and constructed a prognostic model. Overall survival (OS) analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup. The area under the receiver operator characteristic curve (AUC) of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset, demonstrating a favorable prognostic model. Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings. A nomogram was constructed based on the five genes and validated in the TCGA cohort, confirming a promising discriminating ability for gliomas. CONCLUSION: The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.
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Glioma , Humanos , Pronóstico , Nomogramas , Algoritmos , Proteínas de Unión al ARNRESUMEN
BACKGROUND AND OBJECTIVES: The National Comprehensive Cancer Network recommends a second-line treatment of pemigatinib for patients with intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and modified FOLFOX (mFOLFOX) for those without FGFR2 alterations. However, these regimens are not yet covered by Taiwa's National Health Insurance. This cost-effectiveness analysis evaluated the cost-effectiveness of the pemigatinib/mFOLFOX regimen as the second-line treatment for advanced intrahepatic cholangiocarcinoma based on FGFR2 status in comparison with the regimen of fluorouracil chemotherapy and provided a cost-effectiveness analysis-based reference price for pemigatinib. METHODS: A three-state partitioned survival model with a 5-year time horizon was constructed for patients with advanced intrahepatic cholangiocarcinoma who did not respond to first-line therapy. Overall and progression-free survival functions of pemigatinib, mFOLFOX, and fluorouracil were estimated from the FIGHT-202, ABC-06, and NIFTY trials, respectively. The utility of health states and disutility of adverse events were obtained from the literature. The genetic testing fee and price of pemigatinib were set as the market price. Other costs related to advanced intrahepatic cholangiocarcinoma were calculated using National Health Insurance claims data. The willingness-to-pay threshold was three times the gross domestic product per capita in 2021 (NT$2,889,684). A 3% discount rate was applied to quality-adjusted life-years and costs. Scenario analyses included a gradual price reduction of pemigatinib, alternative survival models, application of a National Health Insurance payment conversion factor to non-medication costs, and consideration of life-years as effectiveness. A deterministic sensitivity analysis, probabilistic sensitivity analysis, and a value of information analysis were performed. RESULTS: The new regimen provided an incremental 0.13 quality-adjusted life-years, with incremental costs of NT$459,697, yielding an incremental cost-effectiveness ratio of NT$3,411,098 per quality-adjusted life-year and an incremental net monetary benefit of - NT$70,268. The new regimen was found to be 53.2% cost effective in the probabilistic sensitivity analysis. The expected value of uncertainty measured by the expected value of perfect information was NT$80,695/person. In scenario analyses, the incremental net monetary benefit was positive when the price of pemigatinib was reduced by 40% or more. When applying a conversion factor to non-medical costs, the probability of the new regimen being cost effective was slightly increased from 53.2 to 56.5% compared with the base-case analysis. The utility and the cost of the new regimen were the main drivers of uncertainty. CONCLUSIONS: Although the new second-line genetic-based and biomarker-driven regimen of pemigatinib/mFOLFOX appears not cost effective for patients with advanced intrahepatic cholangiocarcinoma in the base-case analysis, our analysis suggests it is highly likely to be cost effective in the case of a 40% price reduction on pemigatinib.
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Colangiocarcinoma , Análisis de Costo-Efectividad , Humanos , Fluorouracilo/uso terapéutico , Colangiocarcinoma/tratamiento farmacológico , Biomarcadores , Análisis Costo-Beneficio , Años de Vida Ajustados por Calidad de VidaRESUMEN
There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism identification with/without antibiotic stewardship team (AST) and the clinical outcome of patients with bloodstream infections (BSI). In a systematic review and meta-analysis, we evaluated the effectiveness of rapid microbial identification by MALDI-TOF MS with and without AST on clinical outcomes. We searched PubMed and EMBASE databases from inception to 1 February 2022 to identify pre-post and parallel comparative studies that evaluated the use of MALDI-TOF MS for microorganism identification. Pooled effect estimates were derived using the random-effects model. Twenty-one studies with 14,515 patients were meta-analysed. Compared with conventional phenotypic methods, MALDI-TOF MS was associated with a 23% reduction in mortality (RR = 0.77; 95% CI: 0.66; 0.90; I2 = 35.9%; 13 studies); 5.07-h reduction in time to effective antibiotic therapy (95% CI: -5.83; -4.31; I2 = 95.7%); 22.86-h reduction in time to identify microorganisms (95% CI: -23.99; -21.74; I2 = 91.6%); 0.73-day reduction in hospital stay (95% CI: -1.30; -0.16; I2 = 53.1%); and US$4140 saving in direct hospitalization cost (95% CI: $-8166.75; $-113.60; I2 = 66.1%). No significant heterogeneity sources were found, and no statistical evidence for publication bias was found. Rapid pathogen identification by MALDI-TOF MS with or without AST was associated with reduced mortality and improved outcomes of BSI, and may be cost-effective among patients with BSI.
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Sepsis , Antibacterianos/uso terapéutico , Costos y Análisis de Costo , Humanos , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Factores de TiempoRESUMEN
Septins play important roles in regulating development and differentiation. Septin 7 (SEPT7) is a crucial component in orchestrating the septin core complex into highly ordered filamentous structures. Here, we showed that genetic depletion of SEPT7 or treatment with forchlorfenuron (FCF; a compound known to affect septin filament assembly) led to reduced the S phase entry in cell models and zebrafish embryos. In addition to colocalizing with actin filaments, SEPT7 resided in the centrosome, and SEPT7 depletion led to aberrant mitotic spindle pole formation. This mitotic defect was rescued in SEPT7-deficient cells by wild-type SEPT7, suggesting that SEPT7 maintained mitotic spindle poles. In addition, we observed disorganized microtubule nucleation and reduced cell migration with SEPT7 depletion. Furthermore, SEPT7 formed a complex with and maintained the abundance of p150glued , the component of centriole subdistal appendages. Depletion of p150glued resulted in a phenotype reminiscent of SEPT7-deficient cells, and overexpression of p150glued reversed the defective phenotypes. Thus, SEPT7 is a centrosomal protein that maintains proper cell proliferation and microtubule array formation via maintaining the abundance of p150glued .
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Proteínas de Ciclo Celular/metabolismo , Centrosoma/metabolismo , Complejo Dinactina/metabolismo , Microtúbulos/metabolismo , Fase S , Septinas/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Centrosoma/efectos de los fármacos , Complejo Dinactina/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Microtúbulos/efectos de los fármacos , Microtúbulos/genética , Compuestos de Fenilurea/farmacología , Piridinas/farmacología , Fase S/efectos de los fármacos , Puntos de Control de la Fase S del Ciclo Celular , Septinas/genética , Transducción de Señal , Pez Cebra/embriología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
To explore the phenotype spectrum of DEPDC5 variants and the possible mechanisms underlying phenotypical variation, we performed targeted next-generation sequencing in 305 patients with focal epilepsies and 91 patients with generalized epilepsies. Protein modeling was performed to predict the effects of missense mutations. All previously reported epilepsy-related DEPDC5 variants were reviewed. The genotype-phenotype correlations with molecular sub-regional implications were analyzed. We identified a homozygous DEPDC5 mutation (p.Pro1031His) in a case with focal cortical dysplasia and eight heterozygous mutations in 11 families with mild focal epilepsies, including 13 patients in eight families with focal epilepsy with febrile seizures plus/febrile seizures (FEFS + /FS). The mutations included one termination codon mutation (p.Ser1601_Ter1604del_ext133), three truncating mutations (p.Val151Serfs∗27, p.Arg239∗, and p.Arg838∗), and four missense mutations (p.Tyr7Cys, p.Tyr836Cys, p.Pro1031His, and p.Gly1545Ser) that were predicted to affect hydrogen bonds and protein stability. Analysis on epilepsy-related DEPDC5 variants revealed that malformations of cortical development (MCDs) had a tendency of higher frequency of null mutations than those without MCD. MCD-associated heterozygous missense mutations were clustered in structural axis for binding arrangement (SABA) domain and close to the binding sites to NPRL2/NPRL3 complex, whereas those associated with FEFS + /FS were a distance away from the binding sites. Evidence from four aspects and one possible evidence from sub-regional implication suggested MCD and FEFS + /FS as phenotypes of DEPDC5 variants. This study suggested that the phenotypes of DEPDC5 variants vary from mild FEFS + /FS to severe MCD. Heterozygous DEPDC5 mutations are generally less pathogenic and commonly associated with mild phenotypes. Bi-allelic mutations and second hit of somatic mutations, together with the genotype-phenotype correlation and sub-regional implication of DEPDC5 variants, explain severe phenotypes.
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In this study, spatial atomic layer deposition (sALD) is employed to prepare titanium dioxide (TiO2) thin films by using titanium tetraisopropoxide and water as metal and water precursors, respectively. The post-annealing temperature is varied to investigate its effect on the properties of the TiO2 films. The experimental results show that the sALD TiO2 has a similar deposition rate per cycle to other ALD processes using oxygen plasma or ozone oxidant, implying that the growth is limited by titanium tetraisopropoxide steric hindrance. The structure of the as-deposited sALD TiO2 films is amorphous and changes to polycrystalline anatase at the annealing temperature of 450 °C. All the sALD TiO2 films have a low absorption coefficient at the level of 10-3 cm-1 at wavelengths greater than 500 nm. The annealing temperatures of 550 °C are expected to have a high compactness, evaluated by the refractive index and x-ray photoelectron spectrometer measurements. Finally, the 550 °C-annealed sALD TiO2 film with a thickness of ~8 nm is applied to perovskite solar cells as a compact electron transport layer. The significantly enhanced open-circuit voltage and conversion efficiency demonstrate the great potential of the sALD TiO2 compact layer in perovskite solar cell applications.
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PURPOSE: TPP1 mutations have been identified in patients with variable phenotypes such as late infantile neuronal ceroid lipofuscinosis (LINCL), juvenile neuronal ceroid lipofuscinosis (JNCL), and spinocerebellar ataxia 7. However, the mechanism underlying phenotype variation is unknown. We screened TPP1 mutations in patients with epilepsies and analyzed the genotype-phenotype correlation to explain the phenotypic variations. METHODS: We performed targeted next-generation sequencing in a cohort of 330 patients with epilepsies. All previously reported TPP1 mutations were systematically retrieved from the PubMed and NCL Mutation Database. RESULTS: The homozygous missense TPP1 mutation c.646 G > A/ p.Val216Met was identified in a family with two affected siblings. The proband presented with seizures from three years of age, while no ataxia, cognitive regression, or visual abnormalities were observed. Further analysis of all reported TPP1 mutations revealed that the LINCL group had a significantly higher frequency of truncating and invariant splice-site mutations than the JNCL group. In contrast, the JNCL group had a higher frequency of variant splice-site mutations than LINCL. There was a significant correlation between phenotype severity and the frequency of destructive mutation. CONCLUSION: This study suggested that the phenotype of mainly epilepsy can be included in the phenotypic spectrum of TPP1 mutations, which are candidate targets for genetic screening in patients with epilepsy. With the development of therapy techniques, early genetic diagnosis may enable the improvement of etiology-targeted treatments. The relationship between phenotype severity and the genotype of TPP1 mutations may help explain the phenotypic variations.
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Aminopeptidasas/genética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Mutación Missense , Lipofuscinosis Ceroideas Neuronales/genética , Serina Proteasas/genética , Tripeptidil Peptidasa 1 , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Epilepsia/complicaciones , Epilepsia/genética , Epilepsia/fisiopatología , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Lipofuscinosis Ceroideas Neuronales/complicaciones , Lipofuscinosis Ceroideas Neuronales/fisiopatología , Fenotipo , Índice de Severidad de la Enfermedad , Hermanos , Tripeptidil Peptidasa 1/genéticaRESUMEN
To perform photothermal therapy (PTT) and luminescence imaging by a single wavelength NIR light irradiation, we have designed and prepared a novel nanocomposite incorporating the IR806 photothermal sensitizers (PTS) into the core-shell-shell NaYF4:Yb,Er@ NaYF4:Yb@NaYF4:Yb,Nd up-conversion nanoparticles (UCNPs). Irradiation with the 793 nm near-infrared (NIR) laser, the Nd3+ ions in the UCNPs were sensitized to up-convert energy via Yb3+ to the Er3+ ions to emit visible light at 540 nm and 654 nm, as well as to down-convert energy to the Yb3+ ions to emit NIR light at 980 nm. For luminescence imaging, the 793 nm NIR radiation is more suitable to use for deeper-tissue penetration and to reduce overheating problem due to water absorption as compared to 980 nm radiation. Additionally, the same 793 nm NIR radiation could also excite the IR806 dye for effective PTT. Surface modifications of the UCNPs with mesoporous silica (mSiO2) and polyallylamine (PAH) allow stable loading of IR806 dye and further derivatization with polyethylene glycol-folic acid (PEG-FA) for tumor targeting. Preliminary in vitro studies demonstrated that the final UCNP@mSiO2/IR806@PAH-PEG-FA nanocomposites (UCNC-FAs) could be uptaken by the MDA-MB-231 cancer cells and were "dark" viable, and when irradiated with the 793 nm laser, the MDA-MB-231 cell viability was effectively reduced. This indicated that the UCNC-FAs nanocomposites could be potentially useful for targeted photothermal therapy and up-conversion luminescence imaging by a single wavelength NIR light irradiation.
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The aim of this study was to investigate the role of self-regulation of cerebrum in the executive impairment. 22 subjects were enrolled were assessed by a neuropsychological test of executive function using attentional networks test and the cerebral activity was evaluated by functional magnetic resonance imaging. The patients with TLE had a longer reaction time than controls (P < 0.05). Moreover, the healthy controls showed more right hemisphere lateralized activation in incongruent tasks. Finally, both positively and negatively correlated cerebral areas were found in the healthy controls but only negatively correlated cerebral areas were found in the TLE patients. Reduced cerebral lead to areas and lack of activation of right midline positively self-regulatory cerebral areas may executive impairment in TLE patients.
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OBJECTIVES: Studies have provided evidence regarding the pathology of the thalamus in patients with temporal lobe epilepsy (TLE). The thalamus, particularly the right thalamus, is one of the subcortical structures that are most uniformly accepted as being significantly involved in alertness. Moreover, alertness impairment in epilepsy has been reported. This study aimed to investigate alterations in thalamic resting-state functional connectivity (FC) and their relationships with alertness performance in patients with TLE; an issue that has not yet been addressed. METHODS: A total of 15 patients with right TLE (rTLE) and 16 healthy controls were recruited for the present study. All of the participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and the attention network test (ANT). Whole-brain voxel-wise FC analyses were applied to extract the thalamic resting-state functional networks in the patients with rTLE and healthy controls, and the differences between the two groups were evaluated. Correlation analyses were employed to examine the relationships between alterations in thalamic FC and alertness performance in patients with rTLE. RESULTS: Compared to the healthy controls, the FC within and between the bilateral thalamus was decreased in the patients with rTLE. Moreover, in the patient group, the bilateral anterior cingulate cortex (ACC) and subcortical regions, including the bilateral brainstem, cerebellum, putamen, right caudate nucleus, and amygdala, exhibited decreased FC with the ipsilateral thalamus (p<0.05, AlphaSim corrected, cluster size>44) but not with the contralateral thalamus (p<0.05, AlphaSim corrected, cluster size>43). The intrinsic and phasic alertness performances of the patients were impaired (p=0.001 and p<0.001, respectively) but not correlated with decreased thalamic FC. Meanwhile, the alertness performance was not altered in right TLE but was negatively correlated with decreased thalamic FC with ACC (p<0.05). CONCLUSIONS: Our findings highlight the functional importance of the thalamus in TLE pathology and suggest that damage to the thalamic resting-state functional networks, particularly ipsilateral to the epileptogenic focus, is present in patients with TLE.
Asunto(s)
Atención , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/psicología , Desempeño Psicomotor , Tálamo/fisiopatología , Adulto , Tronco Encefálico/fisiopatología , Cerebelo/fisiopatología , Femenino , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/fisiopatología , Pruebas Neuropsicológicas , Tiempo de Reacción , Adulto JovenRESUMEN
PURPOSE: This study aimed to investigate the resting-state brain network related to visuospatial working memory (VSWM) in patients with right temporal lobe epilepsy (rTLE). The functional mechanism underlying the cognitive impairment in VSWM was also determined. METHOD: Fifteen patients with rTLE and 16 healthy controls matched for age, gender, and handedness underwent a 6-min resting-state functional MRI session and a neuropsychological test using VSWM_Nback. The VSWM-related brain network at rest was extracted using multiple independent component analysis; the spatial distribution and the functional connectivity (FC) parameters of the cerebral network were compared between groups. Behavioral data were subsequently correlated with the mean Z-value in voxels showing significant FC difference during intergroup comparison. RESULTS: The distribution of the VSWM-related resting-state network (RSN) in the group with rTLE was virtually consistent with that in the healthy controls. The distribution involved the dorsolateral prefrontal lobe and parietal lobe in the right hemisphere and the partial inferior parietal lobe and posterior lobe of the cerebellum in the left hemisphere (p<0.05, AlphaSim corrected). Between-group differences suggest that the group with rTLE had a decreased FC within the right superior frontal lobe (BA8), right middle frontal lobe, and right ventromedial prefrontal lobe compared with the controls (p<0.05, AlphaSim corrected). The regions of increased FC in rTLE were localized within the right superior frontal lobe (BA11), right superior parietal lobe, and left posterior lobe of the cerebellum (p<0.05, AlphaSim corrected). Moreover, patients with rTLE performed worse than controls in the VSWM_Nback test, and there were negative correlations between ACCmeanRT (2-back) and the mean Z-value in the voxels showing decreased or increased FC in rTLE (p<0.05). CONCLUSION: The results suggest that the alteration of the VSWM-related RSN might underpin the VSWM impairment in patients with rTLE and possibly implies a functional compensation by enlarging the FC within the ipsilateral cerebral network.