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1.
Sci Adv ; 6(19): eaaz8011, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494716

RESUMO

Development of new approaches to biomimetically reconstruct vasculature networks remains challenging in regenerative medicine. We introduce a particle-based artificial stem cell spheroid (ASSP) technology that recapitulates paracrine functions of three-dimensional (3D) SSPs for vasculature regeneration. Specifically, we used a facile method to induce the aggregation of stem cells into 3D spheroids, which benefited from hypoxia microenvironment-driven and enhanced secretion of proangiogenic bioactive factors. Furthermore, we artificially reconstructed 3D spheroids (i.e., ASSP) by integration of SSP-secreted factors into micro-/nanoparticles with cell membrane-derived surface coatings. The easily controllable sizes of the ASSP particles provided superior revascularization effects on the ischemic tissues in hindlimb ischemia models through local administration of ASSP microparticles and in myocardial infarction models via the systemic delivery of ASSP nanoparticles. The strategy offers a promising therapeutic option for ischemic tissue regeneration and addresses issues faced by the bottlenecked development in the delivery of stem cell therapies.

2.
Mol Pharm ; 17(6): 2072-2082, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32352301

RESUMO

Reports on the comprehensive factors for design considerations of hypoxia-activated prodrugs (HAPs) are rare. We introduced a new model system composed of a series of highly water-soluble HAPs, providing a platform to comprehensively understand the interaction between HAPs and hypoxic biosystems. Specifically, four kinds of new HAPs were designed and synthesized, containing the same biologically active moiety but masked by different bioreductive groups. Our results demonstrated that the activity of the prodrugs was strongly dependent on not only the molecular structure but also the hypoxic tumor microenvironment. We found the presence of a direct linear relationship between cytotoxicity of the HAPs and the reduction potential of whole molecule/oxygen concentration/reductase expression. Moreover, limited blood vasculature in hypoxic regions was also a critical barrier for effective activation of the HAPs. This study offers a comprehensive insight into understanding the design factors required for HAPs.

4.
ACS Nano ; 14(4): 4014-4026, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32212674

RESUMO

Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) have exhibited regenerative capability in animal models of ischemia-reperfusion (I/R) acute kidney injury (AKI) and are considered as potential alternatives to direct MSC therapy. However, real-time in vivo imaging of MSC-EVs in renal I/R injury has yet to be established. Renal intracellular targets of MSC-EVs responsible for their regenerative effects also remain elusive. Here, we report that we real-time observed MSC-EVs specifically accumulated in the injured kidney and were taken up by renal proximal tubular epithelia cells (TECs) via DPA-SCP with aggregation-induced emission (AIE) characteristics. DPA-SCP precisely tracked the fate of MSC-EVs in a renal I/R injury mouse model for 72 h and exhibited superior spatiotemporal resolution and tracking ability to popular commercially available EV tracker PKH26. Further analysis revealed that the accumulated MSC-EVs stimulated mitochondrial antioxidant defense and ATP production via activating the Keap1-Nrf2 signaling pathway, which protected TECs against oxidative insult by reducing mitochondrial fragmentation, normalizing mitochondrial membrane potential, and increasing mitochondrial DNA copy number. Increased microRNA-200a-3p expression in renal TECs induced by MSC-EVs was identified as a regulatory mechanism contributing to the protective actions on mitochondria as well as stimulating the renal signal transduction pathways. In conclusion, MSC-EVs accumulated in the renal tubules during renal I/R injury and promoted the recovery of kidney function via activating the Keap1-Nrf2 signaling pathway and enhancing mitochondrial function of TECs. DPA-SCP with AIE characteristics allows noninvasive and precise in vivo visualization of MSC-EVs in kidney repair.

5.
Nanomaterials (Basel) ; 10(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085453

RESUMO

Understanding the dispersivity and migration of cellulose nanocrystals (CNCs) in porous media is important for exploring their potential for soil and water remediation. In this study, a series of saturated column experiments were conducted to investigate the coupled effects of ionic strength, iron oxides (hematite), and soil colloids on the transport of CNCs through quartz sand and natural soils (red earth and brown earth). Results showed that CNCs had high mobility in oxide-free sand and that iron oxide coating reduced the mobility of CNCs. An analysis of Derjaguin-Landau-Verwey-Overbeek interactions indicated that CNCs exhibited a deep primary minimum, nonexistent maximum repulsion and secondary minimum on hematite-coated sand, favorable for the attachment of CNCs. The maximum effluent percentage of CNCs was 96% in natural soils at 5 mM, but this value decreased to 4% at 50 mM. Soil colloids facilitated the transport of CNCs in brown earth with larger effect at higher ionic strength. The ionic strength effect was larger in natural soils than sand and in red earth than brown earth. The study showed that CNCs can travel 0.2 m to 72 m in porous media, depending on soil properties, solution chemistry, and soil colloids.

6.
Sci Total Environ ; 713: 136644, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31955105

RESUMO

Release of antibiotics into the environment has caused ecological and human health concerns in recent years. However, little is known about their transport behaviors in chemically heterogeneous porous media. In this study, we investigated the coupled effects of surface chemistry and soil colloids on the transport of ciprofloxacin and tetracycline through sand under steady state saturated flow conditions. Both antibiotics had a much higher capacity of adsorption on soil colloids (17,500 mg/kg for ciprofloxacin and 8600 mg/kg for tetracycline) than on sand (5.11 mg/kg for ciprofloxacin and 2.80 mg/kg for tetracycline). However, ciprofloxacin adsorption increased to 8.91 mg/kg after the sand was coated with iron oxide and to 8.73 mg/kg after the sand was coated with humic acid. Tetracycline, adsorption increased to 7.99 mg/kg after sand was coated with iron oxide coated sand and to 8.35 mg/kg after the sand was coated with humic acid coated The high adsorption capacity of ciprofloxacin led to a recovery rate of <4% in the effluents of the columns containing 0%, 20% and 50% of iron oxide/humic acid coated sand. The surface coating decreased the recovery rates of tetracycline from 35.4% (in uncoated sand) to 12.0% (in column containing 50% iron oxide coated sand) and 0.010% (in column containing 50% humic acid coated sand), respectively. Once adsorbed to soil colloids, the recovery rate of ciprofloxacin increased by 26.7% in uncoated sand column, 21.1% in iron oxide coated sand column, and 32.7% in humic acid coated sand column. Similarly, the presence of the colloids increased the recovery rate of tetracycline from 13.8% to 33.2% after the sand was coated with humic acid. Colloids did not significantly influence the transport and recovery of tetracycline in the uncoated sand and iron oxide coated sand due likely to its lower adsorption affinity.


Assuntos
Antibacterianos/química , Adsorção , Coloides , Substâncias Húmicas , Porosidade , Dióxido de Silício
7.
Pharmacogenomics ; 21(1): 43-53, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769341

RESUMO

Aim: To assess the cost-effectiveness of CYP2D6*10 genetic testing for the management of Chinese women with hormone receptor-positive (HR+) breast cancer treated with selective estrogen receptor modulator. Methods: A Markov model was developed to evaluate a total expected cost and an incremental cost-effectiveness ratio (ICER). Robustness of the model was addressed in one-way analyses and probabilistic sensitivity analysis. Results: The cost of strategies of tamoxifen, toremifene without genotyping and the strategy base on CYP2D6*10 genotype were $63,879.19, $90,156.60 and $95,021.41, and the quality-adjusted life years gained are 8.1588, 12.89687 and 13.85911, respectively. The incremental cost-effectiveness ratio of the CYP2D6*10 testing versus toremifene were 5,055.74221/quality-adjusted life year, respectively. Conclusion: CYP2D6*10 pharmacogenetic-guided selective estrogen receptor modulator can be a cost-effective strategy in the Chinese patients with hormone receptor-positive breast cancer.

8.
Clin Drug Investig ; 40(1): 25-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31559573

RESUMO

BACKGROUND: A CYP2D6 gene polymorphism is related to the effect of tamoxifen treatment in patient with estrogen-receptor positive (ER) positive breast cancer and CYP2D6*10 T/T can lead to a poor prognosis in Asian patients. Although one-off pharmacogenetic testing may optimize adjuvant endocrine therapy, testing prior to tamoxifen initiation incurs additional costs. AIM: We conducted a study to assess the cost-effectiveness of CYP2D6*10 pharmacogenetic testing to guide the adjuvant endocrine therapy compared with tamoxifen without CYP2D6*10 testing in China. METHODS: A semi-Markov model was developed to evaluate costs and health outcomes represented as quality adjusted life year (QALY) gained. Input data were obtained from the public literature. The results were expressed as incremental cost per QALY gained. A one-way deterministic sensitivity analysis explored the impact of uncertainty in the model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. RESULTS: In the base-case analysis, in the CYP2D6*10 testing and alternative adjuvant endocrine therapy group, the incremental total cost was US$17,966.95 and the incremental QALY was 3.582. Thus, the incremental cost-effectiveness ratio was US$5015.693 per QALY gained. Compared with a willingness-to-pay threshold of US$26,508/QALY in China, the CYP2D6*10 testing is the dominant strategy in postmenopausal women with ER-positive breast cancer in China, and the increased cost of genetic testing was completely worthwhile. The sensitivity analyses showed that the model we built was quite stable. CONCLUSION: From the perspective of the Chinese healthcare system, CYP2D6*10 pharmacogenetic testing was cost effective for postmenopausal women with ER-positive early breast cancer.

9.
Mol Genet Genomics ; 295(2): 391-407, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31797032

RESUMO

Rice is a major dietary source of essential mineral nutrients and toxic elements (aka ionome) for humans. However, the genetic basis underlying the variation in ionome is still largely unknown. Here, we mapped 51 and 61 quantitative trait loci (QTLs) controlling the concentrations of 13 and 15 elements in rice (Oryza sativa L.) grain and straw, respectively, using a recombinant inbred lines (RILs) that were grown at three different field sites in 3 years. Several QTLs were repeatedly detected in both grain and straw or in multiple years; the resulting 87 unique QTLs with 17 of them (20%) were co-localized with previously reported corresponding QTLs and 70 were novel ionomic QTLs. At least, 14 genomic clusters that controlled the concentrations of multiple elements were identified. Furthermore, we identified a molybdate transporter gene OsMOT1;1 as the putative causal gene for a QTL controlling molybdenum concentration in both straw and grain. QTL analyses based on the concentrations of multiple elements in both grain and straw of RIL population grown in three field sites in 3 years allow us to identify tissue common QTLs and reproducible QTLs that were validated in multiple years. The identification of ionomic QTLs will be useful in revealing the molecular mechanisms underlying the accumulation of elements in rice and providing the opportunity to reduce the accumulation of toxic elements and enrich the accumulation of beneficial elements in rice grain.


Assuntos
Proteínas de Transporte de Ânions/genética , Molibdênio/metabolismo , Oryza/genética , Locos de Características Quantitativas/genética , Proteínas de Transporte de Ânions/metabolismo , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Grão Comestível/genética , Grão Comestível/metabolismo , Oryza/metabolismo
10.
Health Commun ; 35(6): 707-715, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822154

RESUMO

While breastfeeding seems to be widely accepted in the United States, extended breastfeeding (defined as breastfeeding beyond 12 months of age) tends to be stigmatized. Healthcare professionals are assumed to play a significant role in supporting women who desire to practice extended breastfeeding; however, how healthcare professionals react to extended breastfeeding has not been well understood. This research surveyed 116 healthcare students, who majored in nursing and human medicine, and examined their perceived advantages and disadvantages, emotional responses to, and advice that they would provide to future mothers regarding extended breastfeeding. The results indicated that students responded predominantly with negative emotions and neutral responses to extended breastfeeding, with a small number of participants responding with positive emotions. Many participants believed that it would bring benefits to the child and that it would be burdensome to the mother. Participants displayed a variety of behavioral responses when asked about advice that they would provide to future mothers with whom they will interact in a clinical setting. Practical implications are discussed.

11.
Breastfeed Med ; 15(1): 35-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859523

RESUMO

Background: Breastfeeding has become the recognized standard for good parenting, with social costs for not breastfeeding, but not every mother wants to or is able to breastfeed. Objectives: This study investigated social and personal costs with no breastfeeding. Materials and Methods: An in-depth survey was conducted with 250 mothers with infants who were not breastfeeding. Situated in the Framework Integrating Normative Influences on Stigma model for stigma, the study analyzed internalized stigma and perception of stigma from others, maternal feelings of warmth for the infant, and hiding formula use. Results: Mothers who chose not to breastfeed reported little personal or public stigma. In comparison, mothers who were unable to breastfeed experienced relatively more internalized stigma and perceived that other people saw them as failures. Mothers who experienced more internalized and perceived social network stigma were likely to hide use of infant formula from others and had lower feelings of warmth for their infants. Knowledge about formula use and availability of support resulted in less stigma and more warmth for the infant. Conclusions: These results suggest that public responses causing a mother to feel guilty for using infant formula result in negative feelings of self-worth and dysfunctional maternal behaviors.

12.
Methods Mol Biol ; 2081: 53-65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31721118

RESUMO

Bioimaging instrumentation can be used to observe environmental phenomena such as the transport, retention, and distribution of bacteria in soils in situ in a real-time, nondestructive manner. Bacteria designed to emit bioluminescence light signals are injected into a transparent column packed with soils, and then the column is placed into a bioimaging instrument, such as a PerkinElmer IVIS Spectrum, while it is connected through thin teflon tubes to other parts of the column system located outside of the imaging chamber, including a fraction collector for collecting effluent solution and a pump for introducing bacterial suspension or experimental solution. After self-correction of soil autofluorescence and bioluminescence and setup of required imaging parameters, the transport experiment is initiated by introducing the bacterial suspension to the soil column while the spatiotemporal distribution of bioluminescent bacteria in the entire soil column is imaged. Finally, the images are processed to analyze bacterial migration in the soil under various environmental conditions in comparison with the breakthrough and elution curves of the bacteria obtained by analyzing the effluent samples.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31671717

RESUMO

In the United States, more than 200 communities are designated by the U.S. Environmental Protection Agency as areas of concern for dioxins. Informing the public about potential risks associated with dioxins and delivering information about how to avoid such risks are essential activities. News coverage of environmental and health problems affects how members of the public assess those problems in terms of both severity and how they are understood, as well as the extent of attention given to the problem by policy-makers. To contextualize public and institutional responses to dioxin contamination and remediation in a dioxin-affected community, we assessed 176 newspaper articles published over 30 years concerning dioxin contamination in Midland, Michigan, in terms of risk, trust in institutions, environmental stigma, and citizen participation. Articles about dioxin contamination and remediation in Midland appeared in both domestic and international newspapers. Domestically, both national and local newspapers covered this issue. The risks for human health and the environment caused by exposure to dioxins were widely covered, with much less media attention given to the trustworthiness of the organizations responsible for managing the risk, environmental stigma, and citizen participation. News coverage of these four themes also changed significantly overtime. Overall, our findings highlight the important role of local news media in communicating risk information, guiding safe behaviors, and facilitating community-level decision-making.


Assuntos
Dioxinas , Poluentes Ambientais , Poluição Ambiental , Meios de Comunicação de Massa , Jornais como Assunto , Atitude Frente a Saúde , Participação da Comunidade , Dioxinas/análise , Dioxinas/toxicidade , Saúde Ambiental , Política Ambiental , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Poluição Ambiental/efeitos adversos , Poluição Ambiental/análise , Poluição Ambiental/prevenção & controle , Poluição Ambiental/estatística & dados numéricos , Humanos , Meios de Comunicação de Massa/estatística & dados numéricos , Michigan , Jornais como Assunto/estatística & dados numéricos , Risco , Estigma Social , Confiança
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1069-1072, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753086

RESUMO

OBJECTIVE: To study the long-term prognosis of vesicoureteral reflux in children. METHODS: A retrospective analysis was performed for the clinical data of 138 children (218 ureters with reflux) who were diagnosed with vesicoureteral reflux for the first time from November 2005 to March 2017 and received medical treatment and regular follow-up. According to the initial grade of reflux, the ureters with reflux were divided into a low-grade group (141 ureters, grade I-III) and a high-grade group (77 ureters, grade IV-V), and the two groups were compared in terms of clinical data and follow-up results. RESULTS: Among the 138 children, there were 82 boys and 56 girls. Their age ranged from 31 days to 10 years at the time of confirmed diagnosis, with a median age of 8 months. The follow-up time ranged from 8 months to 7 years, with a median follow-up time of 1.4 years. At the time of confirmed diagnosis, the high-grade group had significantly higher levels of urinary N-acetyl-ß-D-glucosaminidase, urinary microalbumin and urinary immunoglobulin G than the low-grade group (P<0.05). Among the 218 ureters with reflux, 132 (60.6%) achieved a reduction in the grade of reflux (among which 74 achieved complete disappearance of reflux), 43 had no change in the grade of reflux, and 43 had an increase in the grade of reflux. Compared with the high-grade group, the low-grade group had a significantly higher complete remission rate (41.1% vs 19.5%, P=0.001) and a significantly shorter time to complete remission of reflux (P=0.002). CONCLUSIONS: Most children with vesicoureteral reflux can achieve a reduction in the grade of reflux or even complete disappearance of reflux during follow-up, and the children with low-grade reflux have better prognosis than those with high-grade reflux.


Assuntos
Refluxo Vesicoureteral , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31618820

RESUMO

Loss of property value is a major concern in communities faced with the toxic byproducts of industrial practices. Even after site remediation, stigma may persist and negatively affect market values of residential properties. To study the effects of contamination and of remediation on property values in Midland, Michigan, where dioxins have been released into the environment through the incineration of contaminated waste and the discharge of contaminated water for many years, records of assessed value were obtained for 229 homes within the same neighborhood for the previous 18 years. A multilevel, longitudinal analysis was conducted to determine if there was a relationship between level of dioxin and assessed value after controlling for housing characteristics. Remediated and un-remediated properties saw increases in value at a similar rate over time. However, a property's level of dioxin was found to have a small, significant, and negative relationship with assessed value, and this negative effect was present regardless if a home had been remediated or not. These results suggest that while environmental remediation may be effective at removing the contamination, its economic effects may persist for a longer period of time.


Assuntos
Dioxinas/análise , Recuperação e Remediação Ambiental/métodos , Monitoramento Ambiental/métodos , Habitação , Incineração , Michigan
16.
BMJ Open ; 9(9): e028869, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515419

RESUMO

INTRODUCTION: Qigong exercise offers a potentially safe, low-cost and effective mind-body rehabilitative intervention for mitigating the problem of gait interruption among patients with Parkinson's disease (PD) who have frequent freezing of gait (FOG) episodes. However, its clinical effects have not been established. This paper describes the trial protocol of evaluating the clinical efficacy of a newly developed Integrated Qigong in improving gait among patients with PD who have FOG. METHODS AND ANALYSIS: A single-blind randomised controlled trial is designed to compare Integrated Qigong and balance training with an attention control. Participants will be patients with mild to moderate PD who experience FOG and are recruited from local communities in Shanghai, China. Participants will be randomly allocated to one of the three groups: Integrated Qigong group, a balance exercise intervention group, or control group. The total number of participants will be 126, and masked assessments will be made at baseline, 12 weeks (end of intervention) and 12-week follow-up. Both Integrated Qigong group and balance training group will receive a group-based exercise intervention that meets three times per week, 60 min in duration, for 12 weeks. The control group will receive a 60 min weekly group session and monthly health education. The primary outcomes are gait parameters (stride length, gait velocity, stride time variability) and occurrence of FOG. The secondary outcomes are postural instability, walking disability, falling, fear of falling and quality of life. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Shanghai University of Sport and registered at China Clinical Trial Registry. Participants will sign informed consent prior to the participation of the trial. The findings of the study will be published in peer-reviewed academic journals and disseminated to PD support groups, medical community and media. TRIAL REGISTRATION NUMBER: ChiCTR1800016570.

17.
Proc Natl Acad Sci U S A ; 116(39): 19626-19634, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31488712

RESUMO

Doxorubicin is a widely used chemotherapeutic agent that causes dose-dependent cardiotoxicity in a subset of treated patients, but the genetic determinants of this susceptibility are poorly understood. Here, we report that a noncanonical tumor suppressor activity of p53 prevents cardiac dysfunction in a mouse model induced by doxorubicin administered in divided low doses as in the clinics. While relatively preserved in wild-type (p53 +/+ ) state, mice deficient in p53 (p53 -/- ) developed left ventricular (LV) systolic dysfunction after doxorubicin treatment. This functional decline in p53 -/- mice was associated with decreases in cardiac oxidative metabolism, mitochondrial mass, and mitochondrial genomic DNA (mtDNA) homeostasis. Notably, mice with homozygous knockin of the p53 R172H (p53 172H/H ) mutation, which like p53 -/- state lacks the prototypical tumor suppressor activities of p53 such as apoptosis but retains its mitochondrial biogenesis capacity, showed preservation of LV function and mitochondria after doxorubicin treatment. In contrast to p53-null state, wild-type and mutant p53 displayed distinct mechanisms of transactivating mitochondrial transcription factor A (TFAM) and p53-inducible ribonucleotide reductase 2 (p53R2), which are involved in mtDNA transcription and maintenance. Importantly, supplementing mice with a precursor of NAD+ prevented the mtDNA depletion and cardiac dysfunction. These findings suggest that loss of mtDNA contributes to cardiomyopathy pathogenesis induced by doxorubicin administered on a schedule simulating that in the clinics. Given a similar mtDNA protection role of p53 in doxorubicin-treated human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, the mitochondrial markers associated with cardiomyopathy development observed in blood and skeletal muscle cells may have prognostic utility.


Assuntos
Cardiotoxicidade/metabolismo , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/fisiologia , Cardiomiopatias/metabolismo , DNA Mitocondrial/genética , Proteínas de Ligação a DNA , Cardiopatias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias Cardíacas/metabolismo , Proteínas Mitocondriais , Mutação , Miócitos Cardíacos/metabolismo , Biogênese de Organelas , Cultura Primária de Células , Fatores de Transcrição , Proteína Supressora de Tumor p53/genética
18.
BMC Public Health ; 19(1): 1030, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370829

RESUMO

BACKGROUND: We examined the correlations between living arrangement and the physical activity (PA) levels of youth aged 9-19 years while accounting for demographic factors such as age, sex, and socioeconomic status in Shanghai, China. METHODS: Cross-sectional analyses of data from the 2014 Physical Activity and Fitness in Shanghai China-The Youth Study was conducted. Participants were 33,213 primary (9-11-year-olds; n = 13,237), junior middle (12-14-year-olds; n = 11,157), and junior high school students (15-19-year-olds; n = 8819). Youth (boys = 49%) and their guardians were randomly sampled from 17 districts in Shanghai, China. Youths' moderate-to-vigorous PA (MVPA) levels, information about living arrangement, and guardians' sociodemographic factors were collected via questionnaires. RESULTS: Only 17.8% of school-aged youths in Shanghai met MVPA recommendations, with significantly more boys (20.6%) meeting recommendations than girls (p < .001). Youths living in rural areas showed an overall significantly higher percentage of meeting MVPA recommendations (20.3%) than those living in urban areas (p < .001). Youths who lived with single parents showed an overall significantly lower percentage of meeting MVPA recommendations (15.3%) than those living with their grandparent(s) or with both parents (p < .001). A logistic regression analysis revealed that, among 9-11-year-olds, children who live with their grandparent(s) were less likely to meet MVPA recommendations than those who lived with both parents (boys: adjusted odds ratio (aOR) = 0.72, 95% confidence interval (CI) = 0.61-0.84; girls: aOR = 0.84, 95%CI = 0.72-0.98). CONCLUSIONS: Type of living arrangement was associated with the PA of youth in Shanghai, with no significant gender difference. Youth aged 9-19 years who lived with single parents had the lowest percentage of meeting MVPA recommendations. The probability of achieving 60 min/day MVPA recommendations was significantly lower among 9-11-year-old children living with their grandparent(s) than children living with both parents; however, no such difference was observed among adolescents. Our findings suggest that living arrangement may be an important consideration for promotion of PA among youth in China.


Assuntos
Exercício Físico/fisiologia , Características de Residência/estatística & dados numéricos , Adolescente , Fatores Etários , Criança , China , Estudos Transversais , Feminino , Humanos , Masculino , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
19.
Acta Biochim Biophys Sin (Shanghai) ; 51(9): 960-968, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31389995

RESUMO

Nα-acetylation is a universal protein modification related to a wide range of physiological processes in eukaryotes and prokaryotes. RimI, an Nα-acetyltransferase in Mycobacterium tuberculosis, is responsible for the acetylation of the α-amino group of the N-terminal residue in the ribosomal protein S18. Despite growing evidence that protein acetylation may be correlated with the pathogenesis of tuberculosis, no structural information is yet available for mechanistically understanding the MtRimI acetylation. To enable structural studies for MtRimI, we constructed a serial of recombinant MtRimI proteins and assessed their biochemical properties. We then chose an optimal construct MtRimIC21A4-153 and expressed and purified the truncated high-quality protein for further biophysical and functional characterizations. The 2D 1H-15N heteronuclear single quantum coherence spectrum of MtRimIC21A4-153 exhibits wider chemical shift dispersion and favorable peak isolation, indicating that MtRimIC21A4-153 is amendable for further structural determination. Moreover, bio-layer interferometry experiments showed that MtRimIC21A4-153 possessed similar micromolar affinity to full-length MtRimI for binding the hexapeptide substrate Ala-Arg-Tyr-Phe-Arg-Arg. Enzyme kinetic assays also exhibited that MtRimIC21A4-153 had almost identical enzymatic activity to MtRimI, indicating insignificant influence of the recombinant variations on enzymatic functions. Furthermore, binding sites of the peptide were predicted by molecular docking approach, suggesting that this substrate binds to MtRimI primarily through electrostatic and hydrogen bonding interactions. Our results lay a foundation for the further structural determination and dynamics detection of MtRimI.


Assuntos
Acetiltransferases/química , Proteínas de Bactérias/química , Mycobacterium tuberculosis/enzimologia , Proteínas Recombinantes/química , Acetilação , Sítios de Ligação , Simulação de Acoplamento Molecular , Processamento de Proteína Pós-Traducional , Proteínas Ribossômicas/metabolismo , Especificidade por Substrato
20.
JMIR Med Inform ; 7(3): e13562, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31322132

RESUMO

BACKGROUND: Early identification of knee osteoarthritis (OA) can improve treatment outcomes and reduce medical costs. However, there are major limitations among existing classification or prediction models, including abstract data processing and complicated dataset attributes, which hinder their applications in clinical practice. OBJECTIVE: The aim of this study was to propose a Bayesian network (BN)-based classification model to classify people with knee OA. The proposed model can be treated as a prescreening tool, which can provide decision support for health professionals. METHODS: The proposed model's structure was based on a 3-level BN structure and then retrained by the Bayesian Search (BS) learning algorithm. The model's parameters were determined by the expectation-maximization algorithm. The used dataset included backgrounds, the target disease, and predictors. The performance of the model was evaluated based on classification accuracy, area under the curve (AUC), specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV); it was also compared with other well-known classification models. A test was also performed to explore whether physical fitness tests could improve the performance of the proposed model. RESULTS: A total of 249 elderly people between the ages of 60 and 80 years, living in the Kongjiang community (Shanghai), were recruited from April to September 2007. A total of 157 instances were adopted as the dataset after data preprocessing. The experimental results showed that the results of the proposed model were higher than, or equal to, the mean scores of other classification models: .754 for accuracy, .78 for AUC, .78 for specificity, and .73 for sensitivity. The proposed model provided .45 for PPV and .92 for NPV at the prevalence of 20%. The proposed model also showed a significant improvement when compared with the traditional BN model: 6.3% increase in accuracy (from .709 to .754), 4.0% increase in AUC (from .75 to .78), 6.8% increase in specificity (from .73 to .78), 5.8% increase in sensitivity (from .69 to .73), 15.4% increase in PPV (from .39 to .45), and 2.2% increase in NPV (from .90 to .92). Furthermore, the test results showed that the performance of the proposed model could be largely enhanced through physical fitness tests in 3 evaluation indices: 10.6% increase in accuracy (from .682 to .754), 16.4% increase in AUC (from .67 to .78), and 30.0% increase in specificity (from .60 to .78). CONCLUSIONS: The proposed model presents a promising method to classify people with knee OA when compared with other classification models and the traditional BN model. It could be implemented in clinical practice as a prescreening tool for knee OA, which would not only improve the quality of health care for elderly people but also reduce overall medical costs.

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