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1.
Pediatr Allergy Immunol ; 35(1): e14065, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284919

RESUMO

As a potential link between genetic predisposition, environmental exposures, and food allergy outcomes, epigenetics has been a molecular variable of interest in ongoing efforts to understand food allergy mechanisms and outcomes. Here we review population-based investigations of epigenetic loci associated with food allergy, focusing on established clinical food allergy. We first provide an overview of epigenetic mechanisms that have been studied in cohorts with food allergy, predominantly DNA methylation but also microRNA. We then discuss investigations that have implemented epigenome-wide approaches aimed at genome-wide profiling and discovery. Such epigenome-wide studies have collectively identified differentially methylated and differentially regulated loci associated with T cell development, antigen presentation, reaction severity, and causal mediation in food allergy. We then discuss candidate-gene investigations that have honed in on Th1, Th2, T regulatory, and innate genes of a priori interest in food allergy. These studies have highlighted methylation changes in specific candidate genes as associated with T regulatory cell activity as well as differential methylation of Type 1 and Type 2 cytokine genes associated with various food allergies. Intriguingly, epigenetic loci associated with food allergy have also been explored as potential biomarkers for the clinical management of food allergy. We conclude by highlighting several priority directions for advancing population-based epigenomic and epigenetic understandings of food allergy.


Assuntos
Hipersensibilidade Alimentar , MicroRNAs , Humanos , Epigenômica , Hipersensibilidade Alimentar/genética , Diferenciação Celular , Epigênese Genética
2.
Sci Rep ; 13(1): 22078, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087008

RESUMO

High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation.


Assuntos
Proteínas de Choque Térmico HSP27 , Heme Oxigenase-1 , Animais , Ratos , Células Cultivadas , Proteínas de Choque Térmico HSP27/genética , Hiperplasia , Lipoproteínas HDL/farmacologia , Neointima/tratamento farmacológico
3.
Food Chem X ; 20: 100889, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38144845

RESUMO

This study aimed to evaluate umami taste in Hanwoo with different feed by chemical analysis, sensory evaluation and an electronic tongue system. Hanwoo cattle were divided into three groups: control group (fed only total mixed ration [TMR]), T1 (fed soybean meal + TMR), and T2 (fed soybean meal + corn-dried distiller's grain with solubles [Corn DDGS] + TMR). The three most abundant fatty acids (C18:1n-9, C16:0, and C18:0) in the T1, T2, and control groups accounted for 83.63%, 86.07%, and 85.52% of the total fatty acid content, respectively. Umami taste-related glutamic acid levels were significantly high in T1 (109.89 mg/kg), followed by T2 (66.66 mg/kg) and control (47.27 mg/kg). Fatty acid levels showed a high correlation with umami taste. The results of this study showed that the amino acid and fatty acid levels had been affected by feed types and soybean- or Corn DDGS-based feed potentially enhanced Hanwoo's umami flavor.

4.
Pediatr Neurol ; 141: 118-132, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36812698

RESUMO

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, validity, feasibility, and predictive utility. A total of 48 outcome measures were included and were rated by experts based on the available evidence within the literature supporting the strengths of their psychometric properties and practical use. Only three measures were found to be validated for use in pediatric stroke: the Pediatric Stroke Outcome Measure, the Pediatric Stroke Recurrence and Recovery Questionnaire, and the Pediatric Stroke Quality of Life Measure. However, multiple additional measures were deemed to have good psychometric properties and acceptable utility for assessing pediatric stroke outcomes. Strengths and weaknesses of commonly used measures including feasibility are highlighted to guide evidence-based and practicable outcome measure selection. Improving the coherence of outcome assessment will facilitate comparison of studies and enhance research and clinical care in children with stroke. Further work is urgently needed to close the gap and validate measures across all clinically significant domains in the pediatric stroke population.


Assuntos
Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Criança , Consenso , Reprodutibilidade dos Testes , Avaliação de Resultados em Cuidados de Saúde , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Psicometria
5.
Int J Mol Sci ; 25(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38203294

RESUMO

Ketone bodies (KBs), such as acetoacetate and ß-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.


Assuntos
Lesões Encefálicas , Dieta Cetogênica , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Humanos , Corpos Cetônicos , Neuroproteção , Fármacos Neuroprotetores/uso terapêutico , Infarto Cerebral
6.
Psychiatry Investig ; 19(11): 958-964, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36444159

RESUMO

OBJECTIVE: This study aimed to reveal the relationship between social capital, the happiness of others, and the happiness of Korean adults. METHODS: Data from 4,890 participants (2,092 males [42.78%] and 2,798 females [57.22%]) aged 19 to 79 years were used. Data used in the analysis were provided by the Survey on Koreans' Happiness and Quality of Life (2019) conducted by the Korea Institute for Health and Social Affairs. RESULTS: First, age, education, marital status, and subjective economic level were found to be significantly related to individual happiness. Second, social capital, which including trust and social participation, was positively related to individual happiness. Third, the key result of this study was that the happiness of close people was positively associated with individual happiness. Fourth, belonging showed a significant moderating effect on the relationship between the happiness of others and individual happiness. CONCLUSION: This study contributes by examining the relationship between the happiness of others and individual happiness after controlling for social capital and demographic variables and examining the moderating effect of social capital on the relationship between the happiness of self and others. These results are expected to help understand the factors that determine the happiness of Korean adults.

7.
Exp Mol Med ; 54(4): 531-541, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35478209

RESUMO

Aptamers are widely used as binders that interact with targets with high affinity or as inhibitors of the function of target molecules. However, they have also been used to modulate target protein function, which they achieve by activating the target or stabilizing its conformation. Here, we report a unique aptamer modulator of the insulin receptor (IR), IR-A62. Alone, IR-A62 acts as a biased agonist that preferentially induces Y1150 monophosphorylation of IR. However, when administered alongside insulin, IR-A62 shows variable binding cooperativity depending on the ligand concentration. At low concentrations, IR-A62 acts as a positive allosteric modulator (PAM) agonist that enhances insulin binding, but at high concentrations, it acts as a negative allosteric modulator (NAM) agonist that competes with insulin for IR. Moreover, the concentration of insulin affects the binding of IR-A62 to IR. Finally, the subcutaneous administration of IR-A62 to diabetic mice reduces blood glucose levels with a longer-lasting effect than insulin administration. These findings imply that aptamers can elicit various responses from receptors beyond those of a simple agonist or inhibitor. We expect further studies of IR-A62 to help reveal the mechanism of IR activation and greatly expand the range of therapeutic applications of aptamers.


Assuntos
Diabetes Mellitus Experimental , Receptor de Insulina , Regulação Alostérica , Animais , Insulina/metabolismo , Ligantes , Camundongos , Receptor de Insulina/metabolismo
9.
J Neurosci Methods ; 365: 109383, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634283

RESUMO

BACKGROUND: Single-element focused transducers applied in blood-brain barrier (BBB) disruption experiments to optimize intravascular therapies in CNS diseases have the advantage of low cost and portability. Most of the in vivo studies on non-human primates report the use of single-element transducers with an annular spherical shape and a central frequency of 500 kHz. High-frequency ultrasound has smaller focal area and less standing-wave effect but lower transcranial penetration efficiency. Our study reports the feasibility and safety concerns of BBB opening by single-element spherical transducers with central frequencies of 300, 650 and 800 kHz on two rhesus macaques. METHODS: Pulsed ultrasound exposure (3-minute duration, 0.5-1% duty cycle) combined with microbubble injection (SonoVue, 0.2uL/g) was used to disrupt the BBB of the monkeys under the magnetic resonance imaging (MRI) guidance. Gadolinium contrast-enhanced MRI was used to confirm and evaluate the BBB opening after sonication. T2-weighted fast spin echo and T2 * -weighted gradient echo sequences were used to check the post-sonication complications, such as edema and micro-bleeding. RESULTS: Contrast enhancement was found on the post-sonication T1 weighted images for all experiments, showing that the BBB was successfully opened under all the three frequencies on both monkeys. The enhanced area was largest at the lowest frequency. No obvious hypo-intensity or hyper-intensity was observed on either the T2 * weighted gradient echo images or T2-weighted fast-spin echo images, implying the safety of the opening procedure. However, signal enhancement was also observed in the subarachnoid space of the sulci for all frequencies, indicating that the BBB was also disrupted in the propagation path outside the focal area. CONCLUSIONS: The feasibility of BBB opening with single-element transducer under frequencies ranging from 300 kHz to 800 kHz was confirmed by experiments in two non-human primates in vivo. Further investigation into the off-target effects and transducer configurations is needed for safety optimization.


Assuntos
Barreira Hematoencefálica , Microbolhas , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Meios de Contraste , Estudos de Viabilidade , Humanos , Macaca mulatta , Imageamento por Ressonância Magnética/métodos , Transdutores
10.
J Exp Med ; 218(10)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34491266

RESUMO

Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease.


Assuntos
Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Antituberculosos/uso terapêutico , Evolução Biológica , Busca de Comunicante , Feminino , Expressão Gênica , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Análise de Sequência de RNA , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico
11.
Int J Hyperthermia ; 38(1): 1322-1332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34477032

RESUMO

INTRODUCTION: The radiofrequency ablation (RFA) of liver cancer is a desirable treatment option, as it is minimally invasive. An accurate numerical simulation can greatly help physicians better plan their surgical protocols. Previously, the displacement current in the RFA process was considered negligible, and therefore RFA simulation was modeled as a direct current (DC) system instead of an alternating current (AC) system. Our study investigated the hypothesis that the displacement current in the RFA process should not always be considered negligible. METHODS: AC measurements of ex vivo bovine liver ablation were performed, and numerical simulations were also conducted to test the hypothesis that the relative permittivity would significantly decrease after the liver tissue reached a high temperature. RESULTS: The displacement current was observed to be a sizable fraction of the conduction current, especially before the onset of the first pause. The simulation results indicated that the relative permittivity is likely to decrease to several hundred or lower at elevated temperatures. CONCLUSIONS: Our study results suggest that the DC model may be inadequate, especially before the first roll-off and that additional information could be available during RFA treatment by considering the AC nature of RFA, which could lead to improved numerical simulation. Additional measurements of tissue parameters are needed to reach the full potential of the AC model for further development of ablation control.


Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Animais , Bovinos , Simulação por Computador , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia
12.
NMR Biomed ; 34(12): e4598, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34396597

RESUMO

Magnetic resonance acoustic radiation force imaging (MR-ARFI) is a promising tool for transcranial neurosurgery planning and monitoring. However, the ultrasound dose during ARFI is quite high due to the high intensity required and the repetitive ultrasound sonication. To reduce the ultrasound deposition and prevent unwanted neurological effects, undersampling in k-space data acquisition is adopted in the current study. Three reconstruction methods, keyhole, k-space hybrid and temporal differences (TED) compressed sensing, the latter two of which were initially proposed for MR thermometry, were applied to the in vivo transcranial focus localization based on MR-ARFI data in a retrospective way. The accuracies of the three methods were compared with the results from the fully sampled data as reference. The results showed that the keyhole method tended to smooth the displacement map and underestimate the peak displacement. The K-space hybrid method was better at recovering the displacement map and was robust to the undersampling pattern, while the TED method was more time efficient under a higher image resolution. For an image of a lower resolution, the K-space hybrid and TED methods were comparable in terms of accuracy when a high undersampling rate was applied. The results reported here facilitate the choice of appropriate undersampled reconstruction methods in transcranial focal localization based on MR-ARFI.


Assuntos
Encéfalo/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Terapia por Ultrassom/métodos , Algoritmos , Animais , Humanos , Macaca mulatta , Estudos Retrospectivos
13.
Quant Imaging Med Surg ; 11(6): 2415-2427, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079712

RESUMO

BACKGROUND: Opening the blood-brain barrier (BBB) with focused ultrasound and microbubbles (MBs) has potential use in non-invasive targeted therapy for central nervous system (CNS) diseases. Rapid short-pulse (RaSP) ultrasound with a microsecond sequence has been proposed as a minimally disruptive and efficient method for opening the BBB. This work aimed to test the feasibility and safety of BBB opening in a non-human primate model using combined RaSP ultrasound sequence and MBs. METHODS: The BBB of 2 rhesus macaques were opened with RaSP and the commonly used 10 millisecond long pulse (LP), combined with microbubble (SonoVueTM, 0.2 µL/g) injection in a bolus. The transducer's central frequency was 300 kHz, and the acoustic pressure was set to 0.56 MPa calibrated in water. The BBB opening procedure was guided and evaluated with contrast-enhanced magnetic resonance imaging. The relative signal enhancement was compared between RaSP and LP sonication. T2-weighted fast-spin echo (FSE) and T2*-weighted gradient echo (GRE) sequences were scanned to evaluate edema and micro-bleeding at the end of the procedure. RESULTS: The relative signal enhancement was significantly higher (P<0.01) in the focal area compared to a similar area of the opposite hemisphere at all time points after sonication in each monkey, indicating the successful opening of the BBB. The relative signal enhancement in RaSP reached more than 60% of that with LP in our experiment, while the energy deposition was only 6% of LP. No edema or hemorrhage was found on magnetic resonance images after RaSP. CONCLUSIONS: Combined RaSP ultrasound and MBs for the BBB opening is a practical method in large animal models.

14.
IEEE Trans Biomed Eng ; 68(12): 3659-3670, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34014817

RESUMO

OBJECTIVE: The purpose of this work was to enable simultaneous head and spine Magnetic Resonance imaging (MRI) in children at 3T by using a dedicated multichannel radiofrequency coil array system. METHODS: A 24-channel head and spine pediatric coil system was developed and constructed. The coil's performance was compared with a commercially available 24-channel adult head-neck coil and a spine coil (1-4 spine of 16-channel were selected). Signal-to-noise ratio (SNR) and parallel imaging capability were quantitatively evaluated by phantom studies and in vivo imaging experiments. With Institutional Review Board and Ethics Committee approval, the designed coil was used to acquire head and spine images on 27 children in clinical settings. RESULTS: The pediatric coil provided substantial SNR improvements with an increase of 32% to 40% in the brain region and up to a two-fold increase in the surface. SNR increased by at least 18% in the spine region. The coil enabled higher resolution and a faster imaging speed, owing to significantly improved SNR. Extensive coverage of the coil enabled high-quality fast imaging from head-neck to the whole spine. Good image quality with an average score 4.63 out of 5 was achieved using the developed pediatric coil in clinical studies. CONCLUSION: Simultaneous head and spine MRI with superior performance have been successfully acquired in children subjects at 3T using the dedicated 24-channel head and spine pediatric coil system. SIGNIFICANCE: The 24-channel pediatric coil system potentially can enhance pediatric head and spine MRI in clinical research and diagnosis.


Assuntos
Imageamento por Ressonância Magnética , Coluna Vertebral , Adulto , Criança , Desenho de Equipamento , Humanos , Imagens de Fantasmas , Ondas de Rádio , Razão Sinal-Ruído , Coluna Vertebral/diagnóstico por imagem
15.
Artigo em Inglês | MEDLINE | ID: mdl-33807420

RESUMO

Endometriosis is an inflammatory and estrogen-dependent gynecological disease associated with exposure to environmental endocrine disruptors. n-Butyl benzyl phthalate (BBP), a ubiquitous plasticizer, has weak estrogenic activity, and exposure to BBP is associated with endometriosis. We aimed to elucidate the immunomodulatory effect of BBP on endometriosis development. We previously established a surgery-induced endometriosis-like murine model. In the present study, we exposed those mice to BBP 10 days prior to surgery and 4 weeks after surgery at physiologically relevant doses to mimic human exposure. Chronic exposure to BBP did not promote the growth of endometriotic lesions; however, the lesion survival rate in BBP-treated mice did increase significantly compared with control mice. Multiparametric flow cytometry showed that BBP exposure did not affect the homeostasis of infiltrated immune subsets in lesions but did enhance CD44 (adhesion marker) expression on plasmacytoid dendritic cells (pDCs). Blocking CD44 interactions locally inhibited endometriotic lesion growth. Immunofluorescence results further confirmed that CD44 blocking inhibited pDC infiltration and reduced the frequency of CD44+ pDCs in endometriotic tissues. BBP also disrupted the estrus cycle in these mice. This study suggests that chronic exposure to low-dose BBP may promote survival of endometriotic tissue through CD44-expressing pDCs.


Assuntos
Disruptores Endócrinos , Endometriose , Ácidos Ftálicos , Animais , Feminino , Humanos , Camundongos , Plastificantes/toxicidade
16.
Artigo em Inglês | MEDLINE | ID: mdl-33086759

RESUMO

Background: Health literacy has become the best predictor of healthcare status. However, two-thirds of health providers are unaware of patients' health literacy. Thus, the aim of the study is to investigate factors related to Chinese-speaking nurses' knowledge and experience of health literacy. Methods: This cross-sectional study used a web-based survey. A total of 430 nurses were recruited by stratified sampling from different levels of hospitals and community health centers in Taiwan. Primary outcome measure by Health Literacy Knowledge and Experience. Results: The participants' overall health literacy knowledge was limited; the correct responses were 51%. The education level of the participants, job category, working years, and having attended in-service patient education programs were the predictors of knowledge of health literacy (p < 0.05); Institute, job category, and having attended in-service patient education programs were the predictors of experience of health literacy (p < 0.01). Conclusions: Participants' education levels and In-service patient education programs are beneficial factors to improve nurses' knowledge of health literacy. Furthermore, nursing education should emphasize on how to identify individuals' health literacy and using readable healthcare materials to improve health education.


Assuntos
Letramento em Saúde , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Povo Asiático , Estudos Transversais , Feminino , Humanos , Conhecimento , Masculino , Inquéritos e Questionários , Taiwan
17.
IEEE Trans Med Imaging ; 39(12): 4401-4412, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32833632

RESUMO

The phased-array radio frequency (RF) coil plays a vital role in magnetic resonance-guided focused ultrasound (MRgFUS) neuromodulation studies, where accurate brain functional stimulations and neural circuit observations are required. Although various designs of phased-array coils have been reported, few are suitable for ultrasound stimulations. In this study, an MRgFUS neuromodulation system comprised of a whole brain coverage non-human primate (NHP) RF coil and an MRI-compatible ultrasound device was developed. When compared to a single loop coil, the NHP coil provided up to a 50% increase in the signal-to-noise ratio (SNR) in the brain and acquired better anatomical image-quality. The NHP coil also demonstrated the ability to achieve higher spatial resolution and reduce distortion in echo-planer imaging (EPI). Ultrasound beam characteristics and transcranial magnetic resonance acoustic radiation force (MR-ARF) were measured for simulated positions, and calculated B0 maps were employed to establish MRI-compatibility. The differences between focused off and on ultrasound techniques were measured using SNR, g-factors, and temporal SNR (tSNR) analyses and all deviations were under 2.3%. The EPI images quality and stable tSNR demonstrated the suitability of the MRgFUS neuromodulation system to conduct functional MRI studies. Last, the time course of the blood oxygen level dependent (BOLD) signal of posterior cingulate cortex in a focused ultrasound neuromodulation study was detected and repeated with MR thermometry.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Animais , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas , Razão Sinal-Ruído
18.
Neurol Clin Pract ; 10(3): 232-244, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32642325

RESUMO

OBJECTIVE: To test our hypothesis that anticoagulation is associated with better neurologic outcomes in childhood cerebral sinovenous thrombosis (CSVT), we analyzed treatment and outcomes in a population of 410 children from the International Pediatric Stroke Study (IPSS). METHODS: We included patients enrolled in the IPSS registry with a diagnosis of CSVT at age >28 days with radiologic confirmation, in isolation or with concomitant arterial ischemic stroke. The primary outcome was the neurologic status at discharge. We defined unfavorable outcome as severe neurologic impairment or death at discharge. The Pediatric Stroke Outcome Measure was used for long-term outcome in those with follow-up. Predictors of anticoagulation use and outcome were analyzed by logistic regression. RESULTS: Most children (95%) had identifiable risk factors, and 82% received anticoagulation. Shift analysis demonstrated better outcomes at discharge in children who were anticoagulated, and this persisted with longer-term outcomes. In multivariable analysis, anticoagulation was significantly associated with favorable outcomes (adjusted odds ratio [aOR] unfavorable 0.32, p = 0.007) whereas infarct was associated with unfavorable outcome (aOR unfavorable 6.71, p < 0.001). The trauma/intracranial surgery was associated with a lower odds of anticoagulation use (aOR 0.14, p < 0.001). CONCLUSIONS: Within the IPSS registry, children with risk factors of trauma or intracranial surgery were less likely to receive anticoagulation for CSVT. Anticoagulation was associated with a lower odds of severe neurologic impairment or death at hospital discharge, but this finding is limited and needs further confirmation in randomized, controlled, prospective studies.

19.
Mol Hum Reprod ; 26(8): 601-614, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497202

RESUMO

Endometriosis is an estrogen-dependent chronic inflammatory disease and is associated etiologically with environmental endocrine disruptor (EED) exposure. 4-nonylphenol (NP), a widely found EED, has weak estrogenic activity and modulates plasmacytoid dendritic cell (pDC) function in vitro and in vivo. We aimed to elucidate the immunomodulatory effect of NP on the development of endometriosis, particularly focusing on pDCs. This study established a surgically induced endometriosis murine model (C57BL/6) under conditions of NP treatment that are relevant to the level and route of human exposure. Multi-parametric flow cytometry was used for analysis of infiltrated immune cell subsets in lesions. The results showed that NP exposure significantly promoted endometriotic lesion growth, survival and angiogenesis development of lesions as well as pDC accumulation in the lesions in mice. Adoptive transfer of NP-conditioned pDCs into mice significantly enhanced lesion development and local pDC infiltration, whereas NP-conditioned conventional dendritic cells did not affect lesion growth. In vitro functional analysis showed that NP-conditioned pDCs in lesions expressed high levels of CD36, a scavenger receptor and NP-conditioned splenic pDCs secreted an enhanced level of IL-10 in response to apoptotic cell recognition in a CD36-dependent manner. Furthermore, we observed that local treatment with blocking antibodies against IL-10 and CD36 on the day of surgery significantly inhibited lesion development. NP exposure also altered the estrous cycle in mice. The results suggest that chronic and low-dose exposure to NP enhances endometriotic lesion growth by altering pDC homeostasis and function. This study has important implications for understanding the environment-innate immunity interaction in human endometriosis.


Assuntos
Endometriose/metabolismo , Fenóis/toxicidade , Animais , Western Blotting , Antígenos CD36/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Disruptores Endócrinos/metabolismo , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
20.
Phys Chem Chem Phys ; 22(15): 7962-7968, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32232299

RESUMO

We investigated the multiferroic properties of a hydrogenated graphene bilayer using first-principles calculations. The proposed material is composed of one fully hydrogenated and one semi-hydrogenated graphene monolayer. Inside the van der Waals gap, hydrogen atoms are only adsorbed on either the top or the bottom layer of graphene, thus breaking the centrosymmetry. The calculated electric polarization is 0.137 × 10-10 C m-1, with the transition barrier of switching the polarization being 393 meV per formula unit. We showed that ferroelectricity can be preserved down to atomic thickness. We also studied the domain wall energy and its migration for various domain wall densities, and our results indicate a robust polarization configuration against room temperature thermal fluctuation. As graphene is known to be able to sustain large strain, we further explored ferroelectricity tuning via strain, and found that the polarization can be effectively tuned up to 20% without perturbing the polarization switching barrier. Our results suggest a realizable multiferroic two-dimensional material using the most used two-dimensional material, graphene.

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