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BACKGROUND: Interprofessional education (IPE) has the potential to shape students' collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. METHODS: Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson's correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. RESULTS: Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p < .001) after participating in IPE. The positive relationship between collaboration perception and interprofessional identity strengthened after participating in IPE, as evident from the correlation (Time 1: r = .69; p < .001; Time 2: r = .79; p < .001). Furthermore, collaboration perception in Time 1 significantly predicted the variance in interprofessional identity at Time 2 (ß = 0.347, p < .001). Qualitative findings indicated that 85.2% of students expressed that IPE played a role in promoting their interprofessional identity and collaboration attitudes. CONCLUSIONS: Incorporating the IPE program into the curriculum can effectively enhance students' collaboration perception and interprofessional identity, ultimately preparing them for collaborative practice in the healthcare system. By engaging students in interprofessional teamwork, communication, and joint decision-making processes, the IPE program provides a valuable context for students to develop a sense of belonging and commitment to interprofessional collaboration.
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Comportamento Cooperativo , Educação Interprofissional , Relações Interprofissionais , Identificação Social , Humanos , Feminino , Masculino , Estudantes de Ciências da Saúde/psicologia , Atitude do Pessoal de Saúde , Adulto Jovem , Adulto , CurrículoRESUMO
Learning 2D sectional anatomy facilitates the comprehension of 3D anatomical structures, anatomical relationships, and radiological anatomy. However, the efficacy of technology-enhanced collaborative instructional activities in sectional anatomy remains unclear, especially if theoretical frameworks, namely the Cognitive Theory of Multimedia Learning (CTML), are applied in instructional design. Thus, this study compared the educational impact of distinct 45-min-long technology-enhanced collaborative learning tasks in sectional anatomy. A sample of 115 first-year medical students was randomly divided into three experimental groups that used different supporting technologies to learn the sectional anatomy of the chest: IMAIOS e-learning platform and Microsoft Surface Hub (n = 37); anatomage table (n = 38); anatomage table with CTML-based presets (n = 40). Prelearning and postlearning tests revealed that significant knowledge gains in sectional anatomy were obtained by all groups even though no inter-group differences were found. Moreover, a five-point Likert scale questionnaire showed that the learning session was highly valued by all participants and that users of the anatomage with CTML-based presets reported higher enjoyment than users of the IMAIOS system (mean difference = 0.400; p = 0.037). In addition, students using the IMAIOS system and the anatomage with CTML-based presets provided System Usability Scale (SUS) scores of 67.64 and 67.69, respectively, reaching the benchmark of usability. By contrast, students using the anatomage table without presets awarded a SUS score of 64.14. These results suggest that the integration of multimedia technologies in anatomy teaching and learning should be grounded on CTML principles of instructional design. Otherwise, students' perceptions of ed-tech usability are potentially hindered.
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The shift in the way how health care is delivered from exclusive (disciplinary) to a more collective and inclusive (interprofessional) has recently been gaining traction in health care. The need for this shift is even magnified when the health care system face unprecedented challenges that single expertise is no more enough. The promise of transformative power of collaboration in health care suggests that collective intelligence achieves tasks more effectively than a single expertise could achieve.
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Atenção à Saúde , Relações Interprofissionais , Ocupações em Saúde , Humanos , Equipe de Assistência ao PacienteRESUMO
BACKGROUND: Team cohesiveness and collective efficacy have been construed as important characteristics of a high-functioning team. However, the psychological mechanism through which they promote positive outcomes remains unknown. Understanding this psychological process is important to teachers and programme implementers to yield actionable interventions that can be used to craft effective practices for optimizing team outcomes. This is especially true in interprofessional education (IPE) in medical education, where a team-based approach to patient management is promoted. Drawing from the social-cognitive theory, we examined a hypothesized model where team cohesiveness predicts collaboration outcomes (teamwork satisfaction, overall satisfaction with the team experience, and IPE goal attainment) via collective efficacy. METHODS: We used data from Chinese medicine, medicine, nursing, and social work students in Hong Kong (n = 285) who were enrolled in IPE. They were invited to respond to scales in two time points. We performed mediation analysis using structural equations modelling to test the indirect effect model: team cohesiveness â collective efficacy â outcomes. RESULTS: Results of structural equation modelling revealed that collective efficacy fully mediated the relationships between team cohesiveness and all three team outcomes, providing support for the hypothesised model [RMSEA = 0.08, NFI = 0.90, CFI = 0.93, IFI = 0.93, TLI = 0.93]. Team cohesiveness predicted the achievement of collaboration outcomes via collective efficacy. CONCLUSION: The findings demonstrated the important roles of team cohesiveness and collective efficacy in promoting successful team collaboration. Team cohesiveness predicted collective efficacy, and collective efficacy, in turn, predicted collaboration outcomes. This study contributed to theorising the pathways towards successful team collaboration outcomes.
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Educação Médica , Pessoal de Educação , Medicina , Humanos , Educação Interprofissional , Hong KongRESUMO
Students' attitudes toward interprofessional teamwork can be linked to successful interprofessional education. This points to the importance of identifying a scale that may be useful in keeping track of the change in students' attitudes over time. In response to this, using a combination of within- and between-network approaches to construct validity, we examined the psychometric acceptability of the Interprofessional Attitude Scale (IPAS) involving 274 Chinese healthcare and social care pre-licensure students in Hong Kong. Overall results indicated that IPAS had good internal consistency. Results of the confirmatory factor analysis provided support to the overall five-factor solution although one negatively worded item obtained non-significant factor loading. Results of the between-network analysis suggest that various subscales of IPAS correlated systematically with other theoretically relevant variables: teamwork attitudes, communication, and team effectiveness. The IPAS is a valid measure to examine predominantly Chinese healthcare and social care students' interprofessional attitudes in online interprofessional education.
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Atitude do Pessoal de Saúde , Relações Interprofissionais , Hong Kong , Humanos , Equipe de Assistência ao Paciente , Psicometria/métodos , Inquéritos e QuestionáriosRESUMO
The Students' Perceptions of Physician-Pharmacist Interprofessional Clinical Education and its revision (SPICE, SPICE-R) were designed to understand medicine and pharmacy students' perceptions of interprofessional education and collaborative practice in managing complex health problems. The SPICE-R authors, however, suggested for additional items for subscales "roles and responsibilities for collaborative care" and "patient outcomes from collaborative practice". We added two items and introduced SPICE-R3 to differentiate it from the 10-item SPICE-R2 and to adapt the scale to a wider range of healthcare members. We administered the SPICE-R3 to healthcare students at the height of the COVID-19 outbreak in Hong Kong in February 2020. Using data from 225 students from Chinese medicine, medicine, nursing, and pharmacy, confirmatory factor analysis indicated nine items having acceptable item coefficients. Our data obtained a good fit to the three-factor, nine-item model suggesting construct validity. Results of the between-network analysis suggest that the three subscales of SPICE-R3 correlated systematically with other theoretically relevant variables in the nomological network suggesting convergent validity. The SPICE-R3 is a valid measure to examine Hong Kong healthcare students' interprofessional attitudes in online interprofessional education even during the pandemic. Implications and directions for future research are provided.
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COVID-19 , Estudantes de Farmácia , Atitude do Pessoal de Saúde , Análise Fatorial , Humanos , Educação Interprofissional , Relações Interprofissionais , SARS-CoV-2RESUMO
PURPOSE: To investigate the novel molecular mechanisms of the antioxidant and anti-inflammatory properties of S-allylmercaptocysteine (SAMC) based on a transcriptomic study in a nonalcoholic steatohepatitis (NASH) rat model METHODS: NASH was induced in Sprague-Dawley rats by feeding with a high fat diet (HFD) for 12 weeks. 200 mg/kg SAMC was fed by oral gavage for 4 weeks from 9 to 12 week. RESULTS: SAMC co-administration attenuated HFD-induced liver injury, including the increased serum ALT, hepatic oxidative stress and inflammation. Transcriptomic analysis revealed that SAMC dramatically induced the XRE- and ARE-driven drug metabolising enzymes (DMEs) including Akr7a3, Akr1b8, and Nqo1. The nuclear translocation of the upstream regulator of xenobiotics metabolism, AHR, and regulator of antioxidant responses, NRF2, were significantly increased by SAMC treatment. Furthermore, SAMC counteracted the effects of HFD on NF-κB/IκB and NLRP3/6 pathways with decreasing protein levels of ASC, cleaved caspase-1, IL-18, and IL-1ß. These results were further verified in another mice NASH model induced by an MCD diet with SAMC co-administration. CONCLUSION: We propose that SAMC triggers AHR/NRF2-mediated antioxidant responses which may further suppress the NLRP3/6 inflammasome pathway and NF-κB activation, contributing to the improvement of NASH.
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Hepatopatia Gordurosa não Alcoólica , Preparações Farmacêuticas , Animais , Cisteína/análogos & derivados , Inflamação/tratamento farmacológico , Fígado , Camundongos , Fator 2 Relacionado a NF-E2/genética , Inibidor de NF-kappaB alfa , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: In response to the observations that interprofessional education (IPE) is seemingly atheoretical or under-theorised, this quantitative research seeks to uncover students' motivational mechanisms which could explain their behavioural and collaborative outcomes using self-determination theory (SDT). While SDT has been studied in various contexts, its applicability to IPE remains underexplored. This study aims to integrate a new perspective in understanding students' motivation in IPE by exploring how the fulfilment of a need for sense of autonomy, competence and relatedness is linked to desirable IPE outcomes. METHODS: Utilising quantitative methods, we involved 255 health care students in Hong Kong from the medical, nursing and pharmacy disciplines enrolled in IPE anticoagulation therapy module. They were invited to respond to the Psychological Need Satisfaction Questionnaire and other measures as part of the post-test. RESULTS: Sense of autonomy emerged as the strongest positive predictor of behavioural (collective dedication, behavioural engagement) and collaboration outcomes (team effectiveness, goal achievement). There were no significant program-level differences across these outcomes except for behavioural engagement for which nursing students had a higher perception than medicine students. CONCLUSIONS: We were able to demonstrate that SDT is a meaningful framework in understanding behavioural and collaboration outcomes in IPE. The major theoretical contribution of this study refers to the ability of students' motivation to explain variance in their behavioural outcomes. That is, sense of autonomy consistently predicted team effectiveness, collective dedication, behavioural engagement and goal achievement. Autonomous motivation among a sample of health care students can explain behavioural outcomes. Theoretical, methodological and practical implications are discussed.
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Estudantes de Medicina , Estudantes de Enfermagem , Hong Kong , Humanos , Educação Interprofissional , Relações Interprofissionais , MotivaçãoRESUMO
BACKGROUND: This study compares median nerve cross-sectional area (CSA) measurements at the wrist obtained with ultrasound (US) and magnetic resonance imaging (MRI) using cadaveric measurements as the gold standard. METHODS: Median nerve CSA was measured using US and MRI in 9 cadaveric wrists obtained from 5 subjects at 5 locations: distal forearm, proximal to tunnel inlet, at tunnel inlet, at tunnel outlet, and distal to tunnel outlet and then on identical cadaveric transverse sections obtained with a bandsaw. All US, MRI, and cadaveric measurements were repeated to determine reliability. Median nerves of 10 patients with clinical carpal tunnel syndrome (CTS) were measured with US and MRI using an identical method US. RESULTS: Median nerve CSA MRI measurements correlated better (Pearson correlation: 0.80-0.95, P < .05) with cadaveric measurements than with US measurements (Pearson correlation: 0.61-0.79, P < .05). Median nerve CSA US measurements (8.6-12.5 mm2 , P < .05) were smaller at all levels than MRI (11.3-14.7 mm2 ) or cadaveric (11.0-14.9 mm2 ) measurements while MRI and cadaver measurements were similar at all levels. Median nerve CSA MRI measurements in CTS patients were larger than US measurements at all levels. CONCLUSION: Median nerve CSA measurements by MRI are larger than US measurements and correlated better with cadaveric measurements. Median nerve CSA criteria used for diagnosing CTS on US are not likely to be applicable to MRI.
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Imageamento por Ressonância Magnética/métodos , Nervo Mediano/diagnóstico por imagem , Ultrassonografia/métodos , Punho/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Cadáver , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Reprodutibilidade dos Testes , Articulação do PunhoRESUMO
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. METHODS: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. RESULTS: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3ß in HCC. CONCLUSION: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Carcinoma Hepatocelular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas/genética , Masculino , Espectrometria de Massas , Camundongos , Camundongos Nus , RNA Longo não Codificante/genética , Inibidores da Topoisomerase II/farmacologiaRESUMO
Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O2 for 14 days. Levels of markers for oxidative stress (malondialdhyde) and inflammation (tumor necrosis factor-α (TNFα), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and the expressions of total endothelial NO synthase (eNOS) and phosphorylated eNOS at serine1177 (ser1177) were determined in the lung tissue. We found that the RVSP and the thickness of the arteriolar wall were significantly increased in the vehicle-treated hypoxic animals with elevated levels of malondialdhyde and mRNA expressions of the inflammatory mediators, when compared with the normoxic control. In addition, the phosphorylated eNOS (ser1177) level was significantly decreased, despite an increased eNOS expression in the vehicle-treated hypoxic group. Melatonin treatment significantly attenuated the levels of RVSP, thickness of the arteriolar wall, oxidative and inflammatory markers in the hypoxic animals with a marked increase in the eNOS phosphorylation in the lung. These results suggest that melatonin attenuates pulmonary hypertension by antagonizing the oxidative injury and restoration of NO production.
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Antioxidantes/uso terapêutico , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Melatonina/uso terapêutico , Animais , Doença Crônica , Hipertensão Pulmonar/patologia , Hipóxia/patologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models. METHODS: NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). RESULTS: Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. CONCLUSION: Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH.
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Proteínas de Transporte/metabolismo , Mel , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Animais , Proteínas de Transporte/genética , Proteínas de Ciclo Celular , Linhagem Celular , Dieta Hiperlipídica , Regulação para Baixo , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inflamassomos/genética , Inflamação/dietoterapia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Ácido Palmítico/administração & dosagem , Ácido Palmítico/toxicidade , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
Retinitis pigmentosa (RP) is a photoreceptor-degenerative disease caused by various mutations and is characterized by death of rod photoreceptor cell followed by gradual death of cone photoreceptors. The molecular mechanisms that lead to rod and cone death are not yet fully understood. Neuroinflammation contributes to the progression of many chronic neurodegenerative disorders. However, it remains to be determined how microglia contribute to photoreceptor disruption in RP. In this study, we explored the role of microglia as a contributor to photoreceptor degeneration in the rd10 mouse model of RP. First, we demonstrated that microglia activation was an early alteration in RP retinas. Inhibition of microglia activation by minocycline reduced photoreceptor apoptosis and significantly improved retinal structure and function and visual behavior in rd10 mice. Second, we identified that minocycline exerted its neuroprotective effects through both anti-inflammatory and anti-apoptotic mechanisms. Third, we found that Cx3cr1 deficiency dysregulated microglia activation and subsequently resulted in increased photoreceptor vulnerability in rd10 mice, suggesting that the Cx3cl1/Cx3cr1 signaling pathway might protect against microglia neurotoxicity. We concluded that suppression of neuroinflammatory responses could be a potential treatment strategy aimed at improving photoreceptor survival in human RP.
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Microglia/metabolismo , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Retina/fisiologia , Degeneração Retiniana/prevenção & controle , Retinose Pigmentar/complicações , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Receptor 1 de Quimiocina CX3C , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Minociclina/farmacologia , Mutação/genética , Fármacos Neuroprotetores/farmacologia , Pirazóis/farmacologia , Receptores de Quimiocinas/genética , Retina/efeitos dos fármacos , Degeneração Retiniana/etiologia , Retinose Pigmentar/genéticaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD. DATA SOURCE: We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. RESULTS: The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing intrahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptor gamma expression levels; (ii) decreasing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro-inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. CONCLUSION: Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.
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Exercício Físico/fisiologia , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Apoptose , Autofagia , Citocromos c/metabolismo , Regulação para Baixo , Hepatite/prevenção & controle , Humanos , Interleucina-1beta/antagonistas & inibidores , Gordura Intra-Abdominal , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The carotid body (CB) plays an important role in the alteration of cardiorespiratory activity in chronic intermittent hypoxia (IH) associated with sleep-disordered breathing, which may be mediated by local expression of the renin-angiotensin system (RAS). We hypothesized a pathogenic role for IH-induced RAS expression in the CB. The CB expression of RAS components was examined in rats exposed to IH resembling a severe sleep-apnoeic condition for 7 days. In situ hybridization showed an elevated expression of angiotensinogen in the CB glomus cells in the hypoxic group when compared with the normoxic control group. Immunohistochemical studies and Western blot analysis revealed increases in the protein level of both angiotensinogen and angiotensin II type 1 (AT1) receptors in the hypoxic group, which were localized to the glomic clusters containing tyrosine hydroxylase. RT-PCR studies confirmed that levels of the mRNA expression of angiotensinogen, angiotensin-converting enzyme, AT1a and AT2 receptors were significantly increased in the CBs of the hypoxic rats. Functionally, the [Ca(2+)]i response to exogenous angiotensin II was enhanced in fura-2-loaded glomus cells dissociated from hypoxic rats when compared with those of the normoxic control animals. Pretreatment with losartan, but not PD123319, abolished the angiotensin II-induced [Ca(2+)]i response, suggesting an involvement of AT1 receptors. Moreover, daily treatment of the IH group of rats with losartan attenuated the levels of oxidative stress, gp91(phox) expression and macrophage infiltration in the CB. Collectively, the upregulated local RAS expression could play a pathogenic role in the augmented CB activity and local inflammation via AT1 receptor activation during IH conditions in patients with sleep-disordered breathing.
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Corpo Carotídeo/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Sistema Renina-Angiotensina/genética , Regulação para Cima/genética , Angiotensina II/genética , Angiotensina II/metabolismo , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Cálcio/metabolismo , Fura-2/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo/genética , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Síndromes da Apneia do Sono/genética , Síndromes da Apneia do Sono/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
PURPOSE: To investigate the protective mechanisms of an 85 % pure extract of (-) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD). METHODS: Female Sprague-Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses. RESULTS: Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats. CONCLUSIONS: Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.
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Antioxidantes/farmacologia , Catequina/análogos & derivados , Fígado Gorduroso/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Catequina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dieta Hiperlipídica , Regulação para Baixo , Fígado Gorduroso/patologia , Feminino , Fibrose , Fatores de Transcrição Forkhead/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Hepatopatia Gordurosa não Alcoólica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Smad/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Difficulty in visualizing anatomical structures has been identified as a challenge in anatomy learning and the emergence of three-dimensional printed models (3DPMs) offers a potential solution. This study evaluated the effectiveness of 3DPMs for learning the arterial supply of the head and neck region. One hundred eighty-four undergraduate medical students were randomly assigned to one of four learning modalities including wet specimen, digital model, 3DPM, and textbook image. Posttest scores indicated that all four modalities supported participants' knowledge acquisition, most significantly in the wet specimen group. While the participants rated 3DPMs lower for helping correct identification of structures than wet specimens, they praised 3DPMs for their ability to demonstrate topographical relationships between the arterial supply and adjacent structures. The data further suggested that the biggest limitation of the 3DPMs was their simplicity, thus making it more difficult for users to recognize the equivalent structures on the wet specimens. It was concluded that future designs of 3DPMs will need to consider the balance between the ease of visualization of anatomical structures and the degree of complexity required for successful transfer of learning. Overall, this study presented some conflicting evidence of the favorable outcomes of 3DPMs reported in other similar studies. While effective for anatomy learning as a standalone modality, educators must identify the position 3DPM models hold relative to other modalities in the continuum of undergraduate anatomy education in order to maximize their advantages for students.
Assuntos
Anatomia , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Anatomia/educação , Educação de Graduação em Medicina/métodos , Imageamento Tridimensional/métodos , Modelos Anatômicos , Pescoço/diagnóstico por imagem , Impressão TridimensionalRESUMO
Background: Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease, this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells (MSCs) for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes. Methods: Human adipose mesenchymal stem cells (hADMSCs) were subjected to transfer, either with or without the nuclear factor erythroid 2-related factor 2 (Nrf2)/Dickkopf1 (DKK1) genes, followed by exposure to TNF-α/H2O2. Mouse models were subjected to acute chronic liver failure (ACLF) and subsequently injected with either transfected or untransfected MSCs. These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4 (CKAP4). Results: Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro. In a murine model of ACLF, transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults, boosted MSC transplantation efficacy, and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-γ/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver. Importantly, the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4, which interacts with DKK1, was specifically removed from recipient hepatocytes. However, the removal of the another receptor low-density lipoprotein receptor-related protein 6 (LRP6) had no impact on the effectiveness of MSC transplantation. Moreover, in long-term observations, no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs. Conclusions: Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.
RESUMO
BACKGROUND: Interprofessional education (IPE) incorporates healthcare students from various disciplines to learn with, about, and from one another, aiming to foster effective collaboration. However, the factors that promote these collaboration outcomes remain elusive. Recognizing this knowledge gap, this study utilizes self-determination theory applied in a ten-day IPE programme. The study aims are twofold: to clarify the potential influence of personal factors (autonomy, competence, and relatedness) and environmental factors (clear goals and technology support) on collaboration outcomes (team goal achievement and team effectiveness) and to examine the effect of the IPE on these outcomes. METHODOLOGY: The study utilized an IPE programme that integrated asynchronous and synchronous learning methods across two institutions in Hong Kong and the United Kingdom. This involved 147 students from diverse healthcare disciplines who were enrolled in the IPE programme. A pre- and post-test design was employed to examine programme effects. Multiple regression analysis was conducted to explore the factors influencing these outcomes, while paired samples t-tests were used to evaluate the effect of the IPE programme on collaboration outcomes. RESULTS: Among the personal factors, a sense of relatedness emerged as an important predictor of team effectiveness and goal achievement. Clear goals and technology support positively influenced collaboration outcomes. A paired samples t-test indicated significant improvements in collaboration outcomes after the IPE simulation. CONCLUSION: These findings highlight the importance of designing a large IPE programme that meets basic psychological needs (especially the sense of relatedness) and provides clear goals and adequate technology support in the IPE context. This study is helpful to understand how personal and environmental factors promote the collaboration outcomes in medical education and provide insights for future IPE curriculum development.