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1.
Eur J Neurosci ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34614247

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is diagnosed subjectively based on an individual's behaviour and performance. The clinical community has no objective biomarker to inform the diagnosis and subtyping of ADHD. This study aimed to explore the potential diagnostic biomarkers of ADHD among surface values, volumetric metrics, and radiomic features that were extracted from structural MRI images. Public data of New York University and Peking University were downloaded from the ADHD-200 consortium. MRI T1-weighted images were pre-processed using CAT12. We calculated surface values based on the Desikan-Killiany atlas. The volumetric metrics (mean grey matter volume and mean white matter volume) and radiomic features within each AAL brain area were calculated using DPABI and IBEX, respectively. The differences among three groups of participants were tested using ANOVA or Kruskal-Wallis test depending on the normality of the data. We selected discriminative features and classified typically developing controls (TDCs) and ADHD patients as well as two ADHD subtypes using least absolute shrinkage and selection operator and support vector machine algorithms. Our results showed that the radiomics-based model outperformed the others in discriminating ADHD from TDC as well as classifying ADHD subtypes (area under curve [AUC]: 0.78 and 0.94 in training test; 0.79 and 0.85 in testing set). Combining grey matter volumes, surface values, and clinical factors with radiomic features can improve the performance for classifying ADHD patients and TDCs with training and testing AUCs of 0.82 and 0.83, respectively. This study demonstrates that MRI T1-weighted features, especially radiomic features, are potential diagnostic biomarkers of ADHD.

2.
Hum Resour Health ; 19(1): 109, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496893

RESUMO

BACKGROUND: Village clinic doctors (VCDs) are part of the health service force in rural China. VCDs' job satisfaction (JS) is important to the stability of the three-tiered health service system. Since 2009, the Chinese government launched a new health care system reform (NHCSR) which affected VCDs significantly. This study aimed to analysing the effect of NHCSR on JS among VCDs. METHODS: All the data came from three surveys in Shandong Province conducted in 2012, 2015 and 2018. In 2012, an originally designed questionnaire was used to conduct a baseline survey of 405 VCDs from 27 townships in nine counties. In 2015 and 2018, 519 and 223 VCDs in the same counties were surveyed with the same questionnaire. Descriptive analysis and ANOVA were used to analyse the level and changes in VCDs' JS. RESULTS: The mean scores of VCDs' total JS were 2.664 ± 1.069, 3.121 ± 0.931 and 2.676 ± 1.044 in 2012, 2015 and 2018, respectively, with a significant difference (F = 28.732, P < 0.001). The mean scores of the medical practice environment and the job itself showed a continuous downward trend. The trends of the mean scores for job reward, internal work environment and organizational management were consistent with the trend for total JS. CONCLUSION: The NHCSR had a partly negative impact on VCDs' JS. Policy-makers should pay more attention to VCDs' job reward and medical practice environment. With the implementation of new reform policies, VCDs' JS should be the subject of more systematic and detailed research.

3.
ISA Trans ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34482954

RESUMO

This paper aims to tackle the controller design issue of highly nonlinear and stochastic inflatable robotic arms (IRAs). A novel control scheme, i.e., hybrid adaptive disturbance rejection control (HADRC), is devised to handle the challenging tracking control of hard-to-model IRAs. The model-free adaptive control (MFAC) that linearizes the dynamics by leveraging solely the online input and output (I/O) data of plants is analytically enhanced for superlinear convergence. Both internal and external disturbances are rejected via the active disturbance rejection control (ADRC) that requires little prior model information. The fuzzy logic control (FLC) is subsequently implemented to correlate the two sub-controllers and contribute to attaining smooth motions. The superiority of the proposed scheme is demonstrated by the comparative simulations and experiments on a 2-degree-of-freedom (DOF) IRA.

4.
Biomater Sci ; 9(15): 5160-5174, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34312627

RESUMO

Lack of long-term patency has hindered the clinical use of small-diameter prosthetic vascular grafts with the majority of these failures due to the development of neointimal hyperplasia. Previous studies by our laboratory revealed that small-diameter expanded polytetrafluoroethylene (ePTFE) grafts coated with antioxidant elastomers are a promising localized therapy to inhibit neointimal hyperplasia. This work is focused on the development of poly(diol-co-citrate-co-ascorbate) (POCA) elastomers with tunable properties for coating ePTFE vascular grafts. A bioactive POCA elastomer (@20 : 20 : 8, [citrate] : [diol] : [ascorbate]) coating was applied on a 1.5 mm diameter ePTFE vascular graft as the most promising therapeutic candidate for reducing neointimal hyperplasia. Surface ascorbate density on the POCA elastomer was increased to 67.5 ± 7.3 ng mg-1 cm-2. The mechanical, antioxidant, biodegradable, and biocompatible properties of POCA demonstrated desirable performance for in vivo use, inhibiting human aortic smooth muscle cell proliferation, while supporting human aortic endothelial cells. POCA elastomer coating number was adjusted by a modified spin-coating method to prepare small-diameter ePTFE vascular grafts similar to natural vessels. A significant reduction in neointimal hyperplasia was observed after implanting POCA-coated ePTFE vascular grafts in a guinea pig aortic interposition bypass graft model. POCA elastomer thus offers a new avenue that shows promise for use in vascular engineering to improve long-term patency rates by coating small-diameter ePTFE vascular grafts.


Assuntos
Elastômeros , Politetrafluoretileno , Animais , Prótese Vascular , Citratos , Ácido Cítrico , Células Endoteliais/patologia , Cobaias , Hiperplasia/prevenção & controle
5.
Adv Healthc Mater ; 10(13): e2100302, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34061473

RESUMO

Pulmonary hypertension is a highly morbid disease with no cure. Available treatments are limited by systemic adverse effects due to non-specific biodistribution. Self-assembled peptide amphiphile (PA) nanofibers are biocompatible nanomaterials that can be modified to recognize specific biological markers to provide targeted drug delivery and reduce off-target toxicity. Here, PA nanofibers that target the angiotensin I-converting enzyme and the receptor for advanced glycation end-products (RAGE) are developed, as both proteins are overexpressed in the lung with pulmonary hypertension. It is demonstrated that intravenous delivery of RAGE-targeted nanofibers containing the targeting epitope LVFFAED (LVFF) significantly accumulated within the lung in a chronic hypoxia-induced pulmonary hypertension mouse model. Using 3D light sheet fluorescence microscopy, it is shown that LVFF nanofiber localization is specific to the diseased pulmonary tissue with immunofluorescence analysis demonstrating colocalization of the targeted nanofiber to RAGE in the hypoxic lung. Furthermore, biodistribution studies show that significantly more LVFF nanofibers localized to the lung compared to major off-target organs. Targeted nanofibers are retained within the pulmonary tissue for 24 h after injection. Collectively, these data demonstrate the potential of a RAGE-targeted nanomaterial as a drug delivery platform to treat pulmonary hypertension.


Assuntos
Hipertensão Pulmonar , Nanofibras , Animais , Hipertensão Pulmonar/tratamento farmacológico , Pulmão , Camundongos , Receptor para Produtos Finais de Glicação Avançada , Distribuição Tecidual
6.
Biomaterials ; 274: 120862, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975274

RESUMO

Smoke inhalation injury is associated with significant mortality and current therapies remain supportive. The purpose of our study was to identify proteins upregulated in the lung after smoke inhalation injury and develop peptide amphiphile nanofibers that target these proteins. We hypothesize that nanofibers targeted to angiotensin-converting enzyme or receptor for advanced glycation end products will localize to smoke-injured lungs. METHODS: Five targeting sequences were incorporated into peptide amphiphile monomers methodically to optimize nanofiber formation. Nanofiber formation was assessed by conventional transmission electron microscopy. Rats received 8 min of wood smoke. Levels of angiotensin-converting enzyme and receptor for advanced glycation end products were evaluated by immunofluorescence. Rats received the targeted nanofiber 23 h after injury via tail vein injection. Nanofiber localization was determined by fluorescence quantification. RESULTS: Peptide amphiphile purity (>95%) and nanofiber formation were confirmed. Target proteins were increased in smoke inhalation versus sham (p < 0.001). After smoke inhalation and injection of targeted nanofibers, we found a 10-fold increase in angiotensin-converting enzyme-targeted nanofiber localization to lung (p < 0.001) versus sham with minimal localization of non-targeted nanofiber (p < 0.001). CONCLUSIONS: We synthesized, characterized, and evaluated systemically delivered targeted nanofibers that localized to the site of smoke inhalation injury in vivo. Angiotensin-converting enzyme-targeted nanofibers serve as the foundation for developing a novel nanotherapeutic that treats smoke inhalation lung injury.


Assuntos
Nanofibras , Lesão por Inalação de Fumaça , Animais , Pulmão , Peptídeos , Ratos , Fumaça
7.
Brief Bioinform ; 22(5)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-33822848

RESUMO

Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.

8.
Hum Resour Health ; 19(1): 20, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588888

RESUMO

BACKGROUND: General practitioners are the gatekeepers of the health of the residents. This study aims to evaluate the trend and equity of general practitioners' allocation from 2012 to 2017 in China and provide a reference for regional health planning and rational distribution of general practitioners. METHODS: We extracted the data of general practitioners from 22 provinces, 5 autonomous regions, and 4 municipalities of mainland China. The population and geographical area were taken from the China Statistical Yearbook. The general practitioners' data were taken from the China Health Statistical Yearbook. Lorenz curve, Gini coefficient, and agglomeration degree were used to analyze the data. RESULTS: The number of general practitioners was 252,717 in 2017, which equates to 1.82 per 10,000 residents, and accounts for 7.45% of the total number of practicing (assistant) doctors. From 2012 to 2017, the population-based Gini coefficient for general practitioners reduced from 0.31 to 0.24, while the geographical area-based Gini coefficient remained unchanged at 0.73. The agglomeration degree based on population increased from 0.72 to 0.73 in the western region including Tibet (0.403) and Shaanxi (0.513). Moreover, in the eastern region the agglomeration degree reduced from 1.477 to 1.329. In the middle region it rose from 0.646 to 0.802. The agglomeration degree based on the geographical area in the western region increased from 0.270 to 0.277 while the values in Tibet, Qinghai, Xinjiang were less than 0.1. In the eastern region, it reduced from 1.447 to 1.329. It increased from 1.149 to 1.423 in the middle region. CONCLUSIONS: The number of general practitioners has increased significantly in China. It has a fair allocation based on population. However, the equity based on geographical area is low and uneven in different regions with large regional differences. In the western region, there is an allocation shortage with respect to population and geographical area. Concerned departments should establish and improve the incentive and performance appraisal mechanisms of general practitioners. The Internet + should be used to empower their service capacity and efficiency. The educational input should be increased for the western region and government should encourage the eastern region to support the western region.

9.
Nucleic Acids Res ; 49(4): 2027-2043, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33476374

RESUMO

Dysfunction of splicing factors often result in abnormal cell differentiation and apoptosis, especially in neural tissues. Mutations in pre-mRNAs processing factor 31 (PRPF31) cause autosomal dominant retinitis pigmentosa, a progressive retinal degeneration disease. The transcriptome-wide splicing events specifically regulated by PRPF31 and their biological roles in the development and maintenance of retina are still unclear. Here, we showed that the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed in prpf31 knockout zebrafish when compared with other tissues at an early embryonic stage. At the cellular level, significant mitotic arrest and DNA damage were observed. These defects could be rescued by the wild-type human PRPF31 rather than the disease-associated mutants. Further bioinformatic analysis and experimental verification uncovered that Prpf31 deletion predominantly causes the skipping of exons with a weak 5' splicing site. Moreover, genes necessary for DNA repair and mitotic progression are most enriched among the differentially spliced events, which may explain the cellular and tissular defects in prpf31 mutant retinas. This is the first time that Prpf31 is demonstrated to be essential for the survival and differentiation of RPCs during retinal neurogenesis by specifically modulating the alternative splicing of genes involved in DNA repair and mitosis.


Assuntos
Processamento Alternativo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Retina/embriologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Apoptose , Sistemas CRISPR-Cas , Sobrevivência Celular , Dano ao DNA , Reparo do DNA , Éxons , Técnicas de Inativação de Genes , Pontos de Checagem da Fase M do Ciclo Celular , Células-Tronco Neurais/citologia , Neurônios Retinianos/citologia , Neurônios Retinianos/metabolismo , Fuso Acromático/ultraestrutura , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
10.
Am J Physiol Lung Cell Mol Physiol ; 319(3): L471-L480, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32697601

RESUMO

Smoke inhalation injury increases morbidity and mortality. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. The goal of our research was threefold: 1) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous mouse model, 2) to validate the rat smoke inhalation injury model using a variety of laboratory techniques, and 3) to compare and contrast our rat model with both the well-established mouse model and previously published rat models to highlight our improvements on smoke delivery and lung injury. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. Lung sections were hematoxylin and eosin stained, lung edema was assessed with wet-to-dry (W/D) ratio, and inflammatory cell infiltration and cytokine elevation were evaluated using flow cytometry, immunohistochemistry, and ELISA. We confirmed that our mouse and rat models of smoke inhalation injury mimic the injury seen after human burn inhalation injury with evidence of pulmonary edema, neutrophil infiltration, and inflammatory cytokine elevation. Interestingly, rats mounted a more severe immunological response compared with mice. In summary, we successfully validated a reliable and clinically translatable survival model of lung injury and immune response in rats and mice and characterized the extent of this injury. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic.


Assuntos
Lesão Pulmonar Aguda/mortalidade , Líquido da Lavagem Broncoalveolar/imunologia , Lesão por Inalação de Fumaça/mortalidade , Fumaça/efeitos adversos , Lesão Pulmonar Aguda/imunologia , Animais , Modelos Animais de Doenças , Pulmão/imunologia , Pulmão/fisiopatologia , Camundongos , Infiltração de Neutrófilos/fisiologia , Ratos , Lesão por Inalação de Fumaça/tratamento farmacológico , Lesão por Inalação de Fumaça/imunologia
11.
Exp Ther Med ; 20(1): 591-598, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32537017

RESUMO

Severe burns may lead to intestinal inflammation and oxidative stress, resulting in intestinal barrier damage and gut dysfunction. Loganin, an iridoid glycoside compound, has been isolated from Cornus officinalis Sieb. et Zucc; however, its role in the treatment of burn injury is yet to be fully elucidated. Therefore, the present study examined the effect of loganin administration on burn-induced intestinal inflammation and oxidative stress after severe burns in male Sprague-Dawley rats. Histological injury was assessed by hematoxylin and eosin staining. Furthermore, cytokine expression in intestinal tissues was measured by ELISA and reverse transcription-quantitative PCR. Antioxidative activities were assessed by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). Apoptosis was detected by flow cytometry. Apoptosis-related proteins, toll-like receptor 4 (TLR4) protein and NF-κB translocation were examined by western blotting. Immunohistochemical staining was used to observe TLR4 and NF-κB p65 expression in intestinal tissues. The present study suggested that loganin administration significantly reduced burn injury-induced intestinal histological changes, tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß production and oxidative stress, evidenced by decreased ROS levels and MDA content (P<0.05). Furthermore, loganin increased SOD, CAT and GSH-Px levels and intestinal epithelial cell apoptosis. Loganin treatment also significantly inhibited activation of the TLR4/NF-κB signaling pathway in the intestine of severely burned rats (P<0.05). In conclusion, loganin reduced burns-induced intestinal inflammation and oxidative stress, potentially by regulating the TLR4/NF-κB signaling pathway.

12.
Sheng Li Xue Bao ; 72(2): 255-261, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328620

RESUMO

Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABAB receptor agonist, is the only specific GABAB receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABAB receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 µL/side or 0.12 nmol/0.2 µL/side), rather than vehicle or BLF (0.01 nmol/0.2 µL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABAB receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.


Assuntos
Baclofeno/administração & dosagem , Condicionamento Clássico , Morfina , Núcleo Accumbens/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Animais , Agonistas dos Receptores de GABA-B/administração & dosagem , Locomoção , Masculino , Memória , Camundongos , Camundongos Endogâmicos C57BL , Recompensa
13.
Chem Commun (Camb) ; 55(40): 5693-5696, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31025688

RESUMO

The durability issue of a carbon supported PtNi3 alloy catalyst (PtNi3/C) under acidic conditions has been solved by introducing an N-doped graphitic carbon (NGC) layer to coat the surface of the PtNi3/C catalyst. The as-prepared PtNi3/C@NGC catalyst exhibits superior durability, being able to undergo 10 000 voltage cycles with negligible activity decay.

14.
PLoS One ; 12(11): e0187668, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29121640

RESUMO

BACKGROUND: The association between physical activity, sedentary behavior and health-related quality of life in children and adolescents has been mostly investigated in those young people with chronic disease conditions. No systematic review to date has synthesized the relationship between physical activity, sedentary behavior and health-related quality of life in the general healthy population of children and adolescents. The purpose of this study was to review systematically the existing literature that evaluated the relations between physical activity, sedentary behavior and health-related quality of life in the general population of children and adolescents. METHODS: We conducted a computer search for English language literature from databases of MEDLINE, EMBASE, PSYCINFO and PubMed-related articles as well as the reference lists of existing literature between 1946 and the second week of January 2017 to retrieve eligible studies. We included the studies that assessed associations between physical activity and/or sedentary behavior and health-related quality of life among the general population of children and adolescents aged between 3-18 years. The study design included cross-sectional, longitudinal and health intervention studies. We excluded the studies that examined associations between physical activity, sedentary behavior and health-related quality of life among children and adolescents with specific chronic diseases, and other studies and reports including reviews, meta-analyses, study protocols, comments, letters, case reports and guidelines. We followed up the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement in the reporting of this review. The risk of bias of the primary studies was assessed by the Newcastle-Ottawa Scale. We synthesized the difference in health-related quality of life scores between different levels of physical activity and sedentary time. RESULTS: In total, 31 studies met the inclusion criteria and were synthesized in the review. Most of the included studies used a cross-sectional design (n = 21). There were six longitudinal studies and three school-based physical activity intervention studies. One study used both cross-sectional and longitudinal designs. We found that higher levels of physical activity were associated with better health-related quality of life and increased time of sedentary behavior was linked to lower health-related quality of life among children and adolescents. A dose-response relation between physical activity, sedentary behavior and health-related quality of life was observed in several studies suggesting that the higher frequency of physical activity or the less time being sedentary, the better the health-related quality of life. CONCLUSIONS: The findings in this study suggest that school health programs promoting active lifestyles among children and adolescents may contribute to the improvement of health-related quality of life. Future research is needed to extend studies on longitudinal relationships between physical activity, sedentary behavior and health-related quality of life, and on effects of physical activity interventions on health-related quality of life among children and youth.


Assuntos
Exercício Físico , Qualidade de Vida , Comportamento Sedentário , Adolescente , Criança , Humanos
15.
J Vis Exp ; (124)2017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28715373

RESUMO

The sense of taste allows animals to detect chemicals in the environment, giving rise to behaviors critical for survival. When Gustatory Receptor Neurons (GRNs) detect tastant molecules, they encode information about the identity and concentration of the tastant as patterns of electrical activity that then propagate to follower neurons in the brain. These patterns constitute internal representations of the tastant, which then allow the animal to select actions and form memories. The use of relatively simple animal models has been a powerful tool to study basic principles in sensory coding. Here, we propose three new methods to study gustatory coding using the moth Manduca sexta. First, we present a dissection procedure for exposing the maxillary nerves and the subesophageal zone (SEZ), allowing recording of the activity of GRNs from their axons. Second, we describe the use of extracellular electrodes to record the activity of multiple GRNs by placing tetrode wires directly into the maxillary nerve. Third, we present a new system for delivering and monitoring, with high temporal precision, pulses of different tastants. These methods allow the characterization of neuronal responses in vivo directly from GRNs before, during and after tastants are delivered. We provide examples of voltage traces recorded from multiple GRNs, and present an example of how a spike sorting technique can be applied to the data to identify the responses of individual neurons. Finally, to validate our recording approach, we compare extracellular recordings obtained from GRNs with tetrodes to intracellular recordings obtained with sharp glass electrodes.


Assuntos
Paladar/fisiologia , Animais , Manduca
16.
BMC Infect Dis ; 17(1): 164, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222680

RESUMO

BACKGROUND: Current diagnostic methods for Schistosoma japonicum infection are insensitive for low-density infections. Therefore, a new diagnostic assay based on recombinase polymerase amplification (RPA) technology was established and assessed for field applification. METHODS: The S.japonicum RPA assay was developed to target highly repetitive retrotransposon SjR2 gene of S japonicum, and its sensitivity and specificity were assessed by serial dilution of S. japonicum genomic DNA and other related worm genomic DNA respectively. The RPA diagnostic validity was first evaluated in 60 fecal samples from healthy people and patients, and then compared with other diagnostic tests in 200 high-risk individuals living in endemic areas. RESULTS: The real time RPA assay could detect 0.9 fg S. japonicum DNA within 15 min and distinguish S. japonicum from other worms. The validity analysis of RPA for the detection of S. japonicum in stool samples from 30 S. japonicum-infected patients and 30 healthy persons indicated 100% sensitivity and specificity. When testing 200 fecal or serum samples from a high-risk population, the percentage sensitivity of RPA was 100%, whereas that of indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) were 80.3% and 85.2% respectively. In addition, the RPA presented better consistency with the stool-based tests than IHA and ELISA. Overall, the RPA was superior to other detection methods with respect to detection time, sensitivity, and convenience. CONCLUSIONS: This is the first time we applied the RPA technology to the field evaluation of S. japonicum infection. And the results suggest that RPA-based assays can be used as a promising point-of-care test for the diagnosis of schistosomiasis.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/diagnóstico , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , China/epidemiologia , DNA de Helmintos/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Testes de Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Recombinases , Schistosoma japonicum/genética , Sensibilidade e Especificidade , Adulto Jovem
17.
Parasit Vectors ; 9: 476, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27577576

RESUMO

BACKGROUND: With the continuous decline in prevalence and intensity of Schistosoma japonicum infection in China, more accurate and sensitive methods suitable for field detection become much needed for schistosomiasis control. Here, a novel rapid and visual detection method based on the combination of recombinase polymerase amplification (RPA) and lateral flow dipstick (LFD) was developed to detect S. japonicum DNA in fecal samples. RESULTS: The LFD-RPA assay targeting SjR2 could detect 5 fg S. japonicum DNA, which was identical to qPCR and real-time RPA assay, and showed no cross-reaction with other parasites. The detection could be finished within 15-20 min at a wide temperature range (25-45 °C), and the results could be visualized by naked eye. The diagnostic validity of LFD-RPA assay was further assessed with 14 fecal samples of infected patients diagnosed by Kato-Katz method and 31 fecal samples of healthy persons, and compared with that of Enzyme-linked immunosorbent assay (ELSIA) and Indirect Hemagglutination Assay (IHA). The LFD-RPA assay showed 92.68 % sensitivity, 100 % specificity and excellent diagnostic agreement with the gold standard Kato-Katz test (k = 0.947, Z = 6.36, P < 0.001), whereas ELISA showed 85.71 % sensitivity, 93.55 % specificity, and substantial diagnostic agreement (k = 0.793, Z = 5.31, P < 0.001), and IHA showed 78.57 % sensitivity, 83.87 % specificity, and moderate diagnostic agreement (k = 0.600, Z = 4.05, P < 0.001), indicating that the LFD-RPA was much better than the traditional methods. CONCLUSIONS: The LFD-RPA assay established by us is a sensitive, specific, rapid and convenient method for the diagnosis of schistosomiasis, and shows a great potency in field application.


Assuntos
DNA de Helmintos/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/diagnóstico , Esquistossomose Japônica/urina , Animais , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Recombinases , Esquistossomose Japônica/parasitologia , Sensibilidade e Especificidade
18.
Vaccine ; 34(24): 2656-62, 2016 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-27113166

RESUMO

BACKGROUND AND AIMS: To evaluate immunogenicity and efficacy of a 10µg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns. METHODS: Overall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10µg Hep-KSC, 10µg Engerix-B or 5µg Hep-KSC and those in PM group received 10µg Hep-KSC or 10µg Engerix-B at 0, 1 and 6 months, with an additional 200IU HBIG at birth for the latter. RESULTS: For NM Group, 10µg Hep-KSC paralleled 10µg Engerix-B but outperformed 5µg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p=0.0077) and anti-HBs geometric mean concentration (GMC) (798.87mIU/ml vs 790.16mIU/ml vs 242.04mIU/ml, p<0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000mIU/ml was higher in 10µg Hep-KSC than 5µg Hep-KSC group (45.77% vs 11.93%, p<0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10µg Hep-KSC and 10µg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10µg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10µg Engerix-B group. The anti-HBs GMC was comparable between 10µg Hep-KSC and 10µg Engerix-B group at 7 and 12 months (575.31mIU/ml vs 559.64mIU/ml; 265.79mIU/ml vs 264.48mIU/ml). CONCLUSIONS: 10µg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.


Assuntos
Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Lactente , Saccharomyces cerevisiae , Vacinas Sintéticas/uso terapêutico
19.
J Neurosci ; 35(35): 12309-21, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26338341

RESUMO

UNLABELLED: Four of the five major sensory systems (vision, olfaction, somatosensation, and audition) are thought to use different but partially overlapping sets of neurons to form unique representations of vast numbers of stimuli. The only exception is gustation, which is thought to represent only small numbers of basic taste categories. However, using new methods for delivering tastant chemicals and making electrophysiological recordings from the tractable gustatory system of the moth Manduca sexta, we found chemical-specific information is as follows: (1) initially encoded in the population of gustatory receptor neurons as broadly distributed spatiotemporal patterns of activity; (2) dramatically integrated and temporally transformed as it propagates to monosynaptically connected second-order neurons; and (3) observed in tastant-specific behavior. Our results are consistent with an emerging view of the gustatory system: rather than constructing basic taste categories, it uses a spatiotemporal population code to generate unique neural representations of individual tastant chemicals. SIGNIFICANCE STATEMENT: Our results provide a new view of taste processing. Using a new, relatively simple model system and a new set of techniques to deliver taste stimuli and to examine gustatory receptor neurons and their immediate followers, we found no evidence for labeled line connectivity, or basic taste categories such as sweet, salty, bitter, and sour. Rather, individual tastant chemicals are represented as patterns of spiking activity distributed across populations of receptor neurons. These representations are transformed substantially as multiple types of receptor neurons converge upon follower neurons, leading to a combinatorial coding format that uniquely, rapidly, and efficiently represents individual taste chemicals. Finally, we found that the information content of these neurons can drive tastant-specific behavior.


Assuntos
Células Quimiorreceptoras/fisiologia , Órgãos dos Sentidos/citologia , Sinapses/fisiologia , Paladar/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiologia , Animais , Células Quimiorreceptoras/ultraestrutura , Relação Dose-Resposta a Droga , Eletrofisiologia , Feminino , Masculino , Manduca , Microscopia Eletrônica de Varredura , Tempo de Reação/fisiologia , Cloreto de Sódio/farmacologia , Estimulação Química , Sacarose/farmacologia , Sinapses/ultraestrutura , Fatores de Tempo
20.
Respir Physiol Neurobiol ; 219: 43-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26282788

RESUMO

OBJECTIVES: Transient receptor potential vanilloid 4 (TRPV4) calcium channels are known to promote endothelium-dependent relaxation of mouse mesenteric arteries but TRPV4's role in the pulmonary vasculature is uncertain. Thus, we characterized TRPV4 channel vascular tone regulation in mouse main pulmonary artery rings and in the isolated perfused pulmonary circulation and studied possible mechanisms behind these characterizations. METHODS AND RESULTS: Using myography and a TRPV4 specific agonist GSK1016790A in a C57BL/6 WT mouse model of isolated constant-flow lung perfusion, we studied vascular tone regulation in arterial rings from the main left and right pulmonary arteries and vascular resistance of the intra-pulmonary circulation beyond the second branches of the pulmonary arteries. Removal of the endothelium confirmed endothelial dependence. GSK1016790A relaxed the main pulmonary artery (EC50 4 × 10(-8)mol/L), which was inhibited by removal of the endothelium from main pulmonary artery rings. GSK1016790A significantly increased vascular resistance of the pulmonary circulation in isolated perfused lungs, but these effects were inhibited by a TRPV4 antagonist AB159908. A nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and K(+) channel blockers apamin plus charybdotoxin (ChTx) significantly inhibited GSK1016790A in the main pulmonary artery and in an isolated perfused lung in vitro. CONCLUSIONS: Activated TRPV4 channels increase pulmonary vascular resistance and vasodilate the main pulmonary artery.


Assuntos
Pulmão/irrigação sanguínea , Pulmão/fisiologia , Artéria Pulmonar/fisiologia , Canais de Cátion TRPV/metabolismo , Animais , Apamina/farmacologia , Fármacos Cardiovasculares/farmacologia , Charibdotoxina/farmacologia , Inibidores Enzimáticos/farmacologia , Leucina/análogos & derivados , Leucina/farmacologia , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Cardiovasculares , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Circulação Pulmonar/fisiologia , Sulfonamidas/farmacologia , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Técnicas de Cultura de Tecidos , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
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