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Recent evidence shows that the curvature of porous scaffold plays a significant role in guiding tissue regeneration. However, the underlying mechanism remains controversial to date. In this study, we developed an in silico model to simulate the effect of surface curvature on the osteoconduction of scaffold implants, which comprises the primary aspects of bone regeneration. Selective laser melting was used to manufacture a titanium scaffold with channels representative of different strut curvatures for in vivo assessment. The titanium scaffold was implanted in the femur condyles of rabbits to validate the mathematical model. Simulation results suggest that the curvature affected the distribution of growth factors and subsequently induced the migration of osteoblast lineage cells and bone deposition to the locations with higher curvature. The predictions of the mathematical model are in good agreement with the in vivo assessment results, in which newly formed bone first appeared adjacent to the vertices of the major axes in elliptical channels. The mechanism of curvature-guided osteoconduction may provide a guide for the design optimization of scaffold implants to achieve enhanced bone ingrowth.
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Regeneração Óssea/fisiologia , Osteoblastos , Alicerces Teciduais/química , Animais , Movimento Celular , Fêmur/citologia , Fêmur/cirurgia , Masculino , Osteoblastos/citologia , Osteoblastos/fisiologia , Porosidade , Coelhos , Propriedades de Superfície , Titânio/químicaRESUMO
It is important to overcome different types of uncertainties for the safe and reliable navigation of mobile robots. Uncertainty sources can be categorized into recognition, motion, and environmental sources. Although several challenges of recognition uncertainty have been addressed, little attention has been paid to motion uncertainty. This study shows how the uncertainties of robot motions can be quantitatively modeled through experiments. Although the practical motion uncertainties are affected by various factors, this research focuses on the velocity control performance of wheels obtained by encoder sensors. Experimental results show that the velocity control errors of practical robots are not negligible. This paper proposes a new motion control scheme toward reliable obstacle avoidance by reflecting the experimental motion uncertainties. The presented experimental results clearly show that the consideration of the motion uncertainty is essential for successful collision avoidance. The presented simulation results show that a robot cannot move through narrow passages owing to a risk of collision when the uncertainty of motion is high. This research shows that the proposed method accurately reflects the motion uncertainty and balances the collision safety with the navigation efficiency of the robot.
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The international community, under the auspices of the World Health Organization, developed the landmark Framework Convention on Tobacco Control (FCTC) to curb the global tobacco epidemic. As an internationally binding convention about global best practices on tobacco control, the FCTC has become an overriding source of policy transfer for developing countries in the fight against smoking. However, since its ratification of the first global norm over tobacco governance and against the grim background of the widespread tobacco-induced public health devastation within its borders, China has failed to genuinely pursue FCTC policies because of domestic political and social factors. The empirical findings of this article point to the dominance of political-social dynamics for China's nontransfer of FCTC policies, arguing that the government's GDPism, its sovereignty-first mentality, and hostility to NGOs as well as widespread social acceptability of tobacco consumption and high smoking prevalence are fundamental causes of China's nontransfer of FCTC policies. The article explicates how these variables correspond to FCTC policies in an analytic framework of policy transfer.
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Política de Saúde , Cooperação Internacional , Política , Indústria do Tabaco/organização & administração , China , Humanos , Prevalência , Saúde Pública , Fumar/epidemiologia , Fumar/legislação & jurisprudência , Meio Social , Indústria do Tabaco/legislação & jurisprudência , Organização Mundial da SaúdeRESUMO
The COVID-19 pandemic has wreaked havoc on global economy and human communities. Promoting the accessibility and affordability of vaccine via diplomacy is the key to mitigating the pandemic crisis. China has been accused of seeking geopolitical objectives by launching vaccine diplomacy. The definition of vaccine diplomacy is neutral by nature. China's vaccine diplomacy is based on its holistic approach to national security and the importance China attaches to the "Belt and Road" Initiative. With a whole-of-government approach on both the bilateral and multilateral levels and marketization of vaccines, China's vaccine diplomacy has immense implications for global health governance, in that it helps to narrow the global immunization vaccination gap and to promote human-right-based approach to global health governance. However, the sustainability of China's vaccine diplomacy is questionable because of the Sino-American geopolitical competition and doubts over the efficacy of China's vaccines. The escalation of power rivalry between China and the U.S. and the concerns over the efficacy of China's vaccines forebode the gloomy future of China's vaccine diplomacy.
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AIMS: Cardiac tissue engineering has been proposed as an appropriate method to repair myocardial infarction (MI). Evidence suggests that a cell with scaffold combination was more effective than a cell-only implant. Nevertheless, to date, there has been no research into elastic biodegradable poly(lactide-co-epsilon-caprolactone) (PLCL) scaffolds. The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) with elastic biodegradable PLCL scaffold transplants in a rat MI model. METHODS AND RESULTS: Ten days after inducing MI through the cryoinjury method, a saline control, MSC, PLCL scaffold, or MSC-seeded PLCL scaffold was transplanted onto the hearts. Four weeks after transplantation, cardiac function and histology were evaluated. Transplanted MSCs survived and differentiated into cardiomyocytes in the injured region. Left ventricular ejection fraction in the MSC+PLCL group increased by 23% compared with that in the saline group; it was also higher in the MSC group. The infarct area in the MSC+PLCL group was decreased by 29% compared with that in the saline group; it was also reduced in the MSC group. CONCLUSION: Mesenchymal stem cells plus PLCL should be an excellent combination for cardiac tissue engineering.
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Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Poliésteres , Engenharia Tecidual , Alicerces Teciduais , Função Ventricular Esquerda , Animais , Ecocardiografia , Masculino , Proteínas Musculares/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Ratos , Ratos Endogâmicos LewRESUMO
Dipeptidyl peptidase-4 (DPP4) is one of the most potent mammalian serine proteases participated in the pathogenesis of subclinical atherosclerosis. Here we investigated whether the plasma soluble form of DPP4 is associated with the prevalence of coronary artery disease (CAD) with and without diabetes mellitus (DM). A cross-sectional study was conducted of 496 aged 26-81 years with (n = 362) and without (n = 134) CAD. Plasma DPP4 activity, high sensitive C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein levels were measured. The coronary atherosclerotic plaques were evaluated by coronary angiography. The CAD patients with (n = 84) and without (n = 278) DM had significantly higher DPP4 levels (11.8 ± 3.1 vs. 6.9 ± 3.5 ng/mL, P<0.01) than the nonCAD subjects. The acute coronary syndrome patients (n = 299) had elevated DPP4 levels than those with stable angina patients (n = 83). CAD patients even without DM had increased plasma DPP4 activities as compared with nonCAD subjects (10.9 ± 4.9 vs. 6.4 ± 3.1, ng/L, P< 0.01). A linear regression analysis revealed that overall, the DPP4 levels were positively associated with LCL-C and hs-CRP levels as well as syntax scores. A multiple logistic regression analysis demonstrated that plasma DPP4 activity was independent predictor of CAD (odds ratio, 1.56; 95% CI, 1.19-1.73; P<0.01). Our study shows that increased DPP4 activity levels are associated with the presence of CAD and that the plasma DPP4 level serves as a novel biomarker for CAD even without DM.
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Effective treatment of diabetic neuropathy (DN) remains unsolved. We serendipitously observed dramatic relief of pain in several patients with painful DN receiving granulocyte-colony stimulating factor (G-CSF). The aim of this study was to determine if G-CSF could treat DN in an animal model and to ascertain its mechanism of action. In a rodent model of DN, G-CSF dramatically recovered nerve function, retarded histological nerve changes and increased the expression of neurotrophic factors within nerve. A sex-mismatched bone marrow transplantation (BMT) study revealed that G-CSF treatment increased the abundance of bone marrow (BM)-derived cells in nerves damaged by DN. However, we did not observe evidence of transdifferentiation or cell fusion of BM-derived cells. The beneficial effects of G-CSF were dependent on the integrity of BM. In conclusion, G-CSF produced a therapeutic effect in a rodent model of DN, which was attributed, at least in part, to the actions of BM-derived cells.
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Potenciais de Ação/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Animais , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Neuropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Masculino , Fatores de Crescimento Neural/efeitos dos fármacos , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , RatosRESUMO
Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the "lowLVEF" group) and the 90 patients showing LVEF values ≥ 40% (the "highLVEF" group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = -0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84-0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.
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Catepsina K/sangue , Insuficiência Cardíaca/sangue , Hipertensão/sangue , Disfunção Ventricular Esquerda/sangue , Idoso , Proteína C-Reativa/metabolismo , Ecocardiografia , Matriz Extracelular/genética , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Lipoproteínas , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Análise de Regressão , Troponina I/sangue , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
PURPOSE: Cathepsin K is a potent collagenase implicated in human and animal atherosclerosis-based vascular remodeling. This study examined the hypothesis that serum CatK is associated with the prevalence of coronary artery disease (CAD). MATERIALS AND METHODS: Between January 2011 and December 2012, 256 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. A total of 129 age-matched subjects served as controls. RESULTS: The subjects' serum cathepsin K and high sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher serum cathepsin K levels compared to the controls (130.8±25.5 ng/mL vs. 86.9±25.5 ng/mL, p<0.001), and the patients with acute coronary syndrome had significantly higher serum cathepsin K levels compared to those with stable angina pectoris (137.1±26.9 ng/mL vs. 102.6±12.9 ng/mL, p<0.001). A linear regression analysis showed that overall, the cathepsin K levels were inversely correlated with the high-density lipoprotein levels (r=-0.29, p<0.01) and positively with hs-CRP levels (r=0.32, p<0.01). Multiple logistic regression analyses shows that cathepsin K levels were independent predictors of CAD (odds ratio, 1.76; 95% confidence interval, 1.12 to 1.56; p<0.01). CONCLUSION: These data indicated that elevated levels of cathepsin K are closely associated with the presence of CAD and that circulating cathepsin K serves a useful biomarker for CAD.
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Catepsina K/sangue , Doença da Artéria Coronariana/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use.
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Tecido Adiposo/citologia , Âmnio/citologia , Células Epiteliais/citologia , Sangue Fetal/citologia , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Animais , Diferenciação Celular , Ecocardiografia , Células Epiteliais/transplante , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Cadeias Pesadas de Miosina/metabolismo , Tomografia por Emissão de Pósitrons , Radiografia , Ratos , Ratos NusRESUMO
The threat posed by infectious diseases has been increasingly framed as a security issue. The UN Security Council's Resolution 1308, which designated HIV/AIDS as a threat to international security, evidenced the securitization process. Using securitization theory as a theoretical tool, this article explores the securitization of infectious diseases in the World Health Organization (WHO). While WHO has tended to securitize infectious diseases since 2000, it has encountered a dilemma in the process because of the inherent asymmetry of interest between developed and developing countries. The act of securitization in WHO currently remains mostly a rhetorical device, since WHO's norms emblematic of securitization have not been backed by operational measures for verification or enforcement due to these asymmetric interests.
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Controle de Doenças Transmissíveis , Países Desenvolvidos , Países em Desenvolvimento , Vigilância da População , Medidas de Segurança/organização & administração , Organização Mundial da Saúde/organização & administração , Bioterrorismo/prevenção & controle , Doenças Transmissíveis Emergentes/prevenção & controle , Política de Saúde , Humanos , Pandemias/prevenção & controle , PolíticaRESUMO
We hypothesized that delaying the timing of intra-coronary infusion of G-CSF mobilized stem cell until at least 4 weeks after coronary stenting should avoid the stimulation of vascular smooth muscle cells during the early active cellular proliferative phase, thus decreases in-stent restenosis while preserving the beneficial effect of stem cell therapy on cardiac function in patients with myocardial infarction (MI). 25 patients with ST-elevation myocardial infarction (STEMI) treated with stenting were enrolled in this pilot study. The ages of MI at the time of cell treatment were from 1 month to 59 months. At 6 months follow-up, the left ventricular ejection fraction (LVEF) increased from 32% to 37.7% and the stress thallium perfusion defect decreased from 31.4% to 28.1%. Cell treatment-related complications such as arrhythmias were not observed. 9 patients who underwent cell treatment less than 3 months after coronary stenting were evaluated for in-stent restenosis; it was found in only 1 patient. This pilot study shows that delayed more than 4 weeks after coronary stenting but less than 3 months after MI, intra-coronary infusion of G-CSF mobilized PBSCs may improve cardiac function without triggering in-stent restenosis.