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1.
Sci Rep ; 11(1): 20346, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645876

RESUMO

High levels of sedentary behaviour are associated with poor health outcomes in people with multiple sclerosis (MS). Identifying modifiable correlates of sedentary behaviour for people with MS is essential to design effective intervention strategies to minimise sedentary time. This study aimed to quantify patterns and identify correlates of sedentary behaviour among adults with MS. Fatigue, self-efficacy, walking capability, the physical and psychological impact of MS, health-related quality of life, and participation and autonomy were assessed by questionnaire. Participants wore an activPAL monitor. Total (min/day), prolonged bouts (≥ 30 min) and breaks in sedentary time were calculated. Associations were examined using regression analysis adjusted for demographic and clinical confounders. Fifty-six adults with MS participated (mean ± SD age: 57.0 ± 9.25 years; 66% female). Self-efficacy for control over MS was associated with sedentary time (ß = 0.16, 95% CI 0.01, 0.30). Self-efficacy in function maintenance (ß = 0.02, 95% CI 0.00, 0.04), health-related quality of life (EuroQol-5D) (ß = 31.60, 95% CI 7.25, 55.96), and the autonomy indoors subscale of the Impact on Participation and Autonomy Questionnaire (ß = - 5.11, 95% CI - 9.74, - 0.485) were associated with breaks in sedentary time. Future studies should consider self-efficacy, health-related quality of life and participation and autonomy as potential components of interventions to reduce sedentary behaviour.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34590504

RESUMO

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King's Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.


Assuntos
Esclerose Amiotrófica Lateral , COVID-19 , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico , Teorema de Bayes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Capacidade Vital
3.
BMJ Open ; 10(12): e041425, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33371036

RESUMO

INTRODUCTION: The transition from child to adult health services is a challenging and complex process for young people with cerebral palsy (CP). Poorly managed transition is associated with deterioration in health, increased hospitalisations and reduced quality of life. While international research identifies key practices that can improve the experience and outcomes of transition, there is a paucity of data in the Irish context. This research study aims to gain an insight into the experience of transition for young people with CP in Ireland. METHODS AND ANALYSIS: A convergent parallel mixed-methods design will be used to collect, analyse and interpret quantitative and qualitative data. Participants will be young people aged 16-22 years with CP, their parent(s)/carer(s) and service providers. Quantitative and qualitative data will be collected through questionnaires and interviews, respectively. Quantitative data will be reported using descriptive statistics. Where sufficient data are collected, we will examine associations between the experience of transition practices and sociodemographic and CP-related factors, respectively, using appropriate regression models. Associations between service provider characteristics and provision of key transition practices may also be explored using appropriate regression models. Qualitative data will be analysed using the Framework Method. A coding matrix based on key transitional practices identified from the literature will be used to identify convergence and divergence across study components at the integration stage. ETHICS AND DISSEMINATION: The study has been approved by the RCSI University of Medicine and Health Sciences Research Ethics Committee (REC201911010). Results will be presented to non-academic stakeholders through a variety of knowledge translation activities. Results will be published in open access, peer-reviewed journals and presented at national and international scientific conferences.


Assuntos
Paralisia Cerebral , Transição para Assistência do Adulto , Adolescente , Adulto , Paralisia Cerebral/terapia , Criança , Humanos , Irlanda , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
4.
HRB Open Res ; 3: 61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33215059

RESUMO

Background: The transition from child-centred to adult-oriented healthcare is a challenging time for young people with neurodisability. As the prevalence of neurodisability increases, greater numbers of young people will eventually transfer to the adult healthcare system. While there is a growing recognition of the importance of providing quality, transitional care, little is known about how to manage and optimise this process for young people with neurodisability. The objective of this scoping review is to examine and map existing literature related to the transition from child-centred to adult-oriented healthcare systems for young people with neurodisability. Methods: Systematic literature searches of OVID MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library and Web of Science will be conducted from inception to present. A structured iterative search of grey literature will be conducted. This review will consider all study designs examining the transition from child to adult health services in neurodisability. Two reviewers will independently screen each retrieved title and abstract and assess full-text articles against the inclusion criteria to determine eligibility. Data will be extracted and synthesised quantitatively and qualitatively. The process and reporting will follow PRISMA-ScR guidelines. Conclusion: This review will provide a broad and systematically mapped synthesis of the extent and nature of the available published and unpublished literature on transition from child-centred to adult-oriented healthcare systems in neurodisability. The results will be used to determine gaps in the current evidence base in order to prioritise areas for future research.

5.
Disabil Rehabil ; : 1-7, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515233

RESUMO

Purpose: Self-monitoring may represent a mechanism to enhance physical activity among people with multiple sclerosis. To optimise activity monitoring as a behavioural tool to increase physical activity, user experience must be understood. This study evaluated user experience of the Yamax SW-200 Digi-walker pedometer in a group of people with MS.Methods: Semi-structured interviews were conducted with 15 adults who participated in a 12-week pedometer-supported behavioural change intervention, the iStep-MS trial. Interviews were audio-recorded and transcribed verbatim. Data were analysed using the Framework Method.Results: An overarching theme Pedometers, the frustrating motivators captures the complex and often contradictory experience of the pedometer. Sub-themes include: Increasing activity awareness, which describes the pedometer's utility in raising activity consciousness; Numeric motivation provides insight into dual motivating and demotivating experiences of using an objective feedback device; (Un) usability focuses on practical concerns encountered in the day-to-day use of the monitor.Conclusion: The Yamax SW-200 Digi-walker raised awareness and enhanced participant motivation to engage in physical activity. Accuracy and usability concerns highlighted warrant consideration in the selection of this pedometer within a population with multiple sclerosis. Trial registration: Changing physical activity behaviour in people with MS: the iStep-MS trial; ISRCTN15343862; https://doi.org/10.1186/ISRCTN15343862Implications for rehabilitationUse of self-monitoring tools such as pedometers can enhance physical activity awareness.Objective, numeric step count feedback is an effective motivational tool for physical activity.Accuracy and usability concerns may limit the value of the Yamax SW-200 Digiwalker for people with MS.Identification of individualised, reliable, usable and acceptable tools is important to ensure engagement with self-monitoring.

6.
BMJ Open ; 10(3): e029831, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144172

RESUMO

OBJECTIVES: The purpose of this study was to explore the experiences of people with multiple sclerosis (MS) who participated in iStep-MS, a feasibility randomised controlled trial of a behaviour change intervention that aimed to increase physical activity and reduce sedentary behaviour. DESIGN: A qualitative approach was undertaken embedded in the feasibility randomised controlled trial. One-to-one semi-structured interviews were conducted and analysed using Framework analysis. SETTING: Participants were recruited from a single MS therapy centre in the southeast of England, UK. PARTICIPANTS: Sixty people with MS were randomly allocated in a 1:1 ratio to the intervention or usual care. Following a purposive sampling strategy, 15 participants from the intervention arm undertook 1:1 semi-structured interviews. INTERVENTIONS: The iStep-MS intervention consisted of four therapist-led sessions over 12 weeks, supported by a handbook and pedometer. RESULTS: Three themes were identified from the data. "I can do this": developing competence in physical activity highlights the enhanced physical activity confidence gained through goal setting and accomplishment. "I felt valued": the nurturing culture provides an overview of the supportive and non-judgemental environment created by the programme structure and therapeutic relationship. Finally, "What can I do?": empowered enactment describes the transition from the supported iStep-MS intervention to intrinsically motivated physical activity enactment. CONCLUSIONS: Overall, this study supports the acceptability of the iStep-MS intervention and identified key areas that supported participants to be physically active. TRIAL REGISTRATION NUMBER: ISRCTN15343862.


Assuntos
Empoderamento , Terapia por Exercício/psicologia , Exercício Físico/psicologia , Esclerose Múltipla/reabilitação , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autoeficácia , Adulto , Idoso , Inglaterra , Terapia por Exercício/métodos , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Pesquisa Qualitativa , Comportamento Sedentário
7.
Mult Scler ; 26(14): 1907-1918, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31668138

RESUMO

BACKGROUND: There is limited information regarding the safety, feasibility and acceptability of behaviour-change interventions to increase physical activity (PA) and reduce sedentary behaviour among people with multiple sclerosis (MS). Prior to evaluating efficacy, it is important to identify problems with feasibility and acceptability, which may undermine effectiveness. OBJECTIVE: To examine the safety, feasibility and acceptability of a behaviour-change intervention to increase PA and reduce sedentary behaviour among people with MS. METHODS: Sixty people received a 3-month intervention or usual care. Fatigue, pain and adverse events (AEs) were assessed. Feasibility and acceptability were explored through focus groups with physiotherapists and interviews with participants. Fidelity to intervention content, delivery skills, programme receipt and programme task were assessed. RESULTS: There was no difference in AE rate between groups (p = 0.965). Fatigue and pain were not higher in the intervention group at 3 or 9 months. Therapists reported the intervention was feasible to deliver and fidelity was acceptable. Twenty-nine participants (97%) attended at least 75% of sessions. Participants found the intervention acceptable but suggested some amendments were required to intervention components. CONCLUSIONS: The intervention was safe, feasible and acceptable. Although modifications are required to intervention components, the intervention warrants further evaluation in a future trial.


Assuntos
Esclerose Múltipla , Exercício Físico , Terapia por Exercício , Estudos de Viabilidade , Humanos , Esclerose Múltipla/terapia , Comportamento Sedentário
8.
BMC Med Educ ; 19(1): 117, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029114

RESUMO

BACKGROUND: Motivational Interviewing (MI) is an evidenced based talking therapy designed to affect client Health Behaviour Change. Previous research indicates that Allied Health Professionals (AHP) can effectively use the approach and training at pre-registration level has been piloted. However, student experiences of training is underexplored. AIM: To explore Physiotherapy and Occupational Therapy students' experiences of training in and implementation of Motivational Interviewing. METHODS: Four focus groups including 24 undergraduates (14 OT and 10 PT) were conducted at the completion of the training and a subsequent clinical placement. Transcribed texts were analysed thematically. Data were triangulated with student written post-it notes and open questions in a post training questionnaire. RESULTS: Two overarching themes were developed from the data. Learning different ways to interact and the challenge of transformation illuminates specific aspects of the training which enabled learning as well as areas of contention. Using the spirit of MI, but not every contact counts highlights the facilitators and challenges of implementation on placements. CONCLUSIONS: Motivational interviewing is a useful addition to training neophyte health students. Key skills were adopted and in some cases transferred into practice. The process of learning indicates areas of potential improvement to enhance relevance of practice scenarios. The transfer to practice is more complex illustrating a need to negotiate professional and institutional expectations which should be considered in training.


Assuntos
Educação Baseada em Competências , Entrevista Motivacional/normas , Terapia Ocupacional/educação , Especialidade de Fisioterapia/educação , Estudantes de Ciências da Saúde/psicologia , Adulto , Estudos de Avaliação como Assunto , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional/métodos , Especialidade de Fisioterapia/métodos
9.
Neurosci Lett ; 704: 126-132, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30862494

RESUMO

BACKGROUND: Recent investigations demonstrate that cardiorespiratory fitness may benefit brain health and plasticity with concurrent enhancements in cognitive performance; possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. While a number of studies have demonstrated an increase in BDNF concentration post exercise the relationship between BDNF, cardiorespiratory fitness and cognitive function requires further investigation. OBJECTIVE: The present cross-sectional study assessed the association between cardiorespiratory fitness (VO2max), cognitive performance and circulating BDNF concentration. METHODS: Thirty-nine healthy male volunteers (mean age 21.7 ± 0.5 years) participated. Cognitive performance was measured by reaction time on a standard detection task and accuracy in a n-back and Continuous Paired Associative Learning (CPAL) task. Cardiorespiratory fitness was assessed using a standardised graded exercise test. Plasma and serum BDNF concentrations were assayed by ELISA. RESULTS: A significant negative correlation between VO2max and reaction time was demonstrated (p < 0.05). However VO2max was not associated with circulating BDNF concentration, or performance in the n-back and CPAL tasks (p > 0.05). CONCLUSIONS: Enhanced psychomotor speed was associated with higher cardiorespiratory fitness. In contrast to previous research no significant association between cardiorespiratory fitness and BDNF concentration was observed.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Aptidão Cardiorrespiratória , Cognição , Humanos , Masculino , Adulto Jovem
10.
Patient Educ Couns ; 102(4): 694-700, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30482468

RESUMO

OBJECTIVE: To examine the effectiveness of a three-day training programme on knowledge, confidence and fidelity to Motivational Interviewing (MI) delivery in an undergraduate occupational therapy and physiotherapy cohort (n = 25). METHODS: Training outcomes were assessed pre-training, post-training and following a subsequent clinical placement. The Motivational Interviewing Knowledge and Attitudes Test (MIKAT) and an 8-item survey assessed knowledge, attitudes and confidence respectively. MI fidelity was evaluated by a simulated patient interview rated with the Motivational Interviewing Treatment Integrity scale (MITI). Analysis was by one-way repeated measures ANOVA. RESULTS: Self-report measurements indicated increased confidence but no effect on knowledge or attitude. MITI analysis showed superior performance in all four global criteria and an increased frequency of MI adherent behaviours post-training. Positive changes were maintained following clinical placement. MITI summary scores indicated an improvement in question to reflection ratio in line with beginner competency. CONCLUSION(S): Participation in a three-day MI training programme significantly improved student confidence and MI skilfulness. PRACTICE IMPLICATIONS: Where feasible, MI training should be embedded within the curriculum. Further research is needed elucidate the best practices to incorporate teaching this skill set within the curriculum in order to best prepare students to counsel clients in behaviour change in their applied settings.


Assuntos
Competência Clínica/normas , Comunicação , Avaliação Educacional/métodos , Conhecimentos, Atitudes e Prática em Saúde , Entrevista Motivacional/normas , Terapia Ocupacional/educação , Especialidade de Fisioterapia/educação , Estudantes de Ciências da Saúde/psicologia , Adulto , Educação Baseada em Competências/métodos , Currículo , Feminino , Humanos , Masculino , Entrevista Motivacional/métodos , Terapeutas Ocupacionais , Terapia Ocupacional/métodos , Simulação de Paciente , Fisioterapeutas , Especialidade de Fisioterapia/métodos , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos
11.
BMJ Open ; 7(11): e018875, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29146660

RESUMO

INTRODUCTION: Although physical activity may reduce disease burden, fatigue and disability, and improve quality of life among people with multiple sclerosis (MS), many people with MS are physically inactive and spend significant time in sedentary behaviour. Behaviour change interventions may assist people with MS to increase physical activity and reduce sedentary behaviour. However, few studies have investigated their effectiveness using objective measures of physical activity, particularly in the long term. Further, interventions that have proven effective in the short term may not be feasible in clinical practice because of the large amount of support provided. The iStep-MS trial aims to determine the safety, feasibility and acceptability of a behaviour change intervention to increase physical activity and reduce sedentary behaviour among people with MS. METHODS AND ANALYSIS: Sixty people with MS will be randomised (1:1 ratio) to receive a 12-week intervention or usual care only. The intervention consists of four physical activity consultations with a physiotherapist supported by a handbook and pedometer. Outcomes assessed at baseline, 12 weeks and 9 months are physical activity (ActiGraph wGT3X-BT accelerometer), sedentary behaviour (activPAL3µ), self-reported activity and sitting time, walking capability, fatigue, self-efficacy, participation, quality of life and health service use. The safety of the intervention will be determined by assessing change in pain and fatigue and the incidence of adverse events during the follow-up period. A parallel process evaluation will assess the feasibility and acceptability of the intervention through assessment of fidelity to the programme and semistructured interviews exploring participants' and therapists' experiences of the intervention. The feasibility of conducting an economic evaluation will be determined by collecting data on quality of life and resource use. ETHICS AND DISSEMINATION: Research ethics committee approval has been granted from Brunel University London. Results of the trial will be submitted for publication in journals and distributed to people with MS and physiotherapists. TRIAL REGISTRATION NUMBER: ISRCTN15343862 (doi 10.1186/ISRCTN15343862). Protocol version: 1.0; Pre-results.


Assuntos
Terapia por Exercício/métodos , Esclerose Múltipla/economia , Esclerose Múltipla/reabilitação , Qualidade de Vida/psicologia , Exercício Físico , Fadiga/fisiopatologia , Humanos , Londres , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Comportamento Sedentário , Autoeficácia
12.
PLoS One ; 11(4): e0154467, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27123858

RESUMO

Do different cultures hold different views of intentionality? In four studies, participants read scenarios in which the actor's distal intent (a focus on a broader goal) and proximal intent (a focus on the mechanics of the act) were manipulated. In Studies 1-2, when distal intent was more prominent in the actor's mind, North Americans rated the actor more responsible than did Chinese and South Asian participants. When proximal intent was more prominent, Chinese and South Asian participants, if anything, rated the actor more responsible. In Studies 3-4, when distal intent was more prominent, male Americans rated the actor more responsible than did female Americans. When proximal intent was more prominent, females rated the actor more responsible. The authors discuss these findings in relation to the literatures on moral reasoning and cultural psychology.


Assuntos
Características Culturais , Julgamento , Responsabilidade Social , Ásia Sudeste , Canadá/etnologia , China/etnologia , Feminino , Humanos , Intenção , Masculino , América do Norte , Caracteres Sexuais , Adulto Jovem
13.
Eur J Immunol ; 42(11): 2937-48, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22886924

RESUMO

The utility of plasmid DNA as an immunogen has been limited by its weak immunogenicity. In the present study, we evaluated the ability of a family of linear polyethylenimine (PEI) polymers, complexed to plasmid DNA, to augment DNA expression in vivo and to enhance antigen-specific adaptive immune responses. We showed that four of five structurally different PEIs that we evaluated increased in vivo DNA expression 20- to 400-fold, and enhanced DNA-induced epitope-specific CD8⁺ T-cell responses 10- to 25-fold in BALB/c and C57BL/6J mice respectively, when delivered intravenously. Functional studies of the PEI-DNA-induced CD8⁺ T-cell responses demonstrated that formulation of DNA with PEI was associated with increased numbers of cells secreting type I cytokines. In addition, PEI-DNA complexes improved antigen-specific T(H) 1-helper cell and humoral responses. Most importantly, the PEI-DNA complexes elicited memory cellular responses, capable of rapid expansion and accelerated clearance of a lethal dose of recombinant Listeria monocytogenes. Lastly, we identified physical properties of PEI-DNA complexes that are associated with enhanced DNA-elicited immunogenicity. These findings demonstrate that PEI polymers can play an important role in the development of DNA-based vaccines in the setting of infectious disease prevention and cancer therapy.


Assuntos
Adjuvantes Imunológicos/farmacologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Polietilenoimina/farmacologia , Vacinas de DNA/imunologia , Imunidade Adaptativa/imunologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Feminino , Listeria monocytogenes/imunologia , Listeriose/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Plasmídeos/química , Plasmídeos/genética , Plasmídeos/imunologia , Polietilenoimina/química , Organismos Livres de Patógenos Específicos , Estatísticas não Paramétricas , Vacinas de DNA/administração & dosagem , Vacinas de DNA/química
14.
Pers Soc Psychol Bull ; 38(8): 985-96, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22825208

RESUMO

The authors propose that individuals transitioning to a novel environment will prefer upward comparisons, particularly those made with individuals who have experienced a similar transition. Such comparisons help to reduce uncertainty and demonstrate that future success is possible. Study 1 found that individuals facing transitions to unfamiliar situations seek upward comparisons as a result of their uncertainty. Study 2 demonstrated that individuals who perceive themselves to be making a significant life transition are especially motivated by upward comparisons. Study 3 provided evidence that upward comparisons are especially inspiring to individuals making a transition to a novel cultural environment. Study 4 provided experimental evidence that individuals in a novel cultural environment are particularly inspired by upward comparisons with other newcomers. These studies suggest that upward comparisons with individuals who have experienced a similar transition enhance individuals' sense of control over future outcomes and play a key role during adjustment to novel environments.


Assuntos
Acontecimentos que Mudam a Vida , Satisfação Pessoal , Autoimagem , Ajustamento Social , Logro , Adaptação Psicológica , Adulto , Canadá , Comparação Transcultural , Emigrantes e Imigrantes/psicologia , Feminino , Humanos , Masculino , Motivação , Estudantes/psicologia , Inquéritos e Questionários , Universidades , Adulto Jovem
15.
J Drug Deliv ; 2011: 204058, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21490747

RESUMO

We mechanistically explored the effect of increased hydrophobicity of the polycation on the efficacy and specificity of gene delivery in mice. N-Alkylated linear PEIs with varying alkyl chain lengths and extent of substitution were synthesized and characterized by biophysical methods. Their in vivo transfection efficiency, specificity, and biodistribution were investigated. N-Ethylation improves the in vivo efficacy of gene expression in the mouse lung 26-fold relative to the parent polycation and more than quadruples the ratio of expression in the lung to that in all other organs. N-Propyl-PEI was the best performer in the liver and heart (581- and 3.5-fold enhancements, resp.) while N-octyl-PEI improved expression in the kidneys over the parent polymer 221-fold. As these enhancements in gene expression occur without changing the plasmid biodistribution, alkylation does not alter the cellular uptake but rather enhances transfection subsequent to cellular uptake.

16.
Nanomedicine ; 7(4): 505-13, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21272669

RESUMO

UNLABELLED: This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNPs) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNPs with nitrogen-to-phosphorus ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNPs applied to corneal tissues collected after 12 hours, 72 hours, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNPs over time. Transmission electron microscopy detected GNPs in the keratocytes and the extracellular matrix of the rabbit corneas. Additionally, slit-lamp biomicroscopy in live animals even 7 days after topical PEI2-GNP application to the cornea detected no inflammation, redness, or edema in rabbit eyes in vivo, with only moderate cell death and immune reactions. These results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo. FROM THE CLINICAL EDITOR: This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles in the human cornea in vitro and rabbit cornea in vivo. The results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo.


Assuntos
Córnea/metabolismo , Ouro/química , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/química , Polietilenoimina/química , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Córnea/citologia , Ceratócitos da Córnea/citologia , Ceratócitos da Córnea/efeitos dos fármacos , Feminino , Técnicas de Transferência de Genes , Humanos , Técnicas In Vitro , Nanotecnologia/métodos , Coelhos
17.
Am J Physiol Lung Cell Mol Physiol ; 299(5): L652-63, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20729389

RESUMO

Increased levels of atrial natriuretic peptide (ANP) in the models of sepsis, pulmonary edema, and acute respiratory distress syndrome (ARDS) suggest its potential role in the modulation of acute lung injury. We have recently described ANP-protective effects against thrombin-induced barrier dysfunction in pulmonary endothelial cells (EC). The current study examined involvement of the Rac effector p21-activated kinase (PAK1) in ANP-protective effects in the model of lung vascular permeability induced by bacterial wall LPS. C57BL/6J mice or ANP knockout mice (Nppa(-/-)) were treated with LPS (0.63 mg/kg intratracheal) with or without ANP (2 µg/kg iv). Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, Evans blue extravasation, and lung histology. Endothelial barrier properties were assessed by morphological analysis and measurements of transendothelial electrical resistance. ANP treatment stimulated Rac-dependent PAK1 phosphorylation, attenuated endothelial permeability caused by LPS, TNF-α, and IL-6, decreased LPS-induced cell and protein accumulation in bronchoalveolar lavage fluid, and suppressed Evans blue extravasation in the murine model of acute lung injury. More severe LPS-induced lung injury and vascular leak were observed in ANP knockout mice. In rescue experiments, ANP injection significantly reduced lung injury in Nppa(-/-) mice caused by LPS. Molecular inhibition of PAK1 suppressed the protective effects of ANP treatment against LPS-induced lung injury and endothelial barrier dysfunction. This study shows that the protective effects of ANP against LPS-induced vascular leak are mediated at least in part by PAK1-dependent signaling leading to EC barrier enhancement. Our data suggest a direct role for ANP in endothelial barrier regulation via modulation of small GTPase signaling.


Assuntos
Fator Natriurético Atrial/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pulmão/irrigação sanguínea , Quinases Ativadas por p21/metabolismo , Animais , Fator Natriurético Atrial/genética , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Fator de Necrose Tumoral alfa/metabolismo
18.
Biotechnol Prog ; 26(6): 1772-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20572294

RESUMO

The ability of radio frequency radiation (RFR) to exert irreversible nonthermal (i.e., not caused by accompanying heat) effects on biologics has been widely debated due to a relative paucity of comprehensive critical details in published reports dealing with this issue. In this study, we used rigorous control over experimental conditions to determine whether continuous RFR nonthermally affects commercially important enzymes and live bacterial and human cells using three most commonly used frequencies in current RF identification technology, namely 2.45 GHz, 915 MHz, and 13.56 MHz. Diverse biological samples were exposed to RFR under deliberately harsh conditions to increase the likelihood of observing such effects should they exist. Enzymatic activities of horseradish peroxidase and ß-galactosidase in aqueous solution exhibited no statistically discernable consequences of even very intense RFR. Likewise, with putative thermal effects excluded, the viabilities of bacteria (both gram-positive and gram-negative) and of human cells were not detectably compromised by such an RFR exposure.


Assuntos
Peroxidase do Rábano Silvestre/metabolismo , Viabilidade Microbiana/efeitos da radiação , Ondas de Rádio , beta-Galactosidase/metabolismo , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Ativação Enzimática , Escherichia coli/citologia , Escherichia coli/efeitos da radiação , Peroxidase do Rábano Silvestre/química , Humanos , Staphylococcus aureus/citologia , Staphylococcus aureus/efeitos da radiação , beta-Galactosidase/química
19.
Biochem Mol Biol Educ ; 38(4): 247-52, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21567836

RESUMO

Here, we present a six-session laboratory exercise designed to introduce students to standard biochemical techniques in the context of investigating a high impact research topic, acquired resistance to the cancer drug Gleevec. Students express a Gleevec-resistant mutant of the Abelson tyrosine kinase domain, the active domain of an oncogenic protein implicated in chronic myelogenous leukemia, and investigate the kinase activity of wild type and mutant enzyme in the presence of two cancer drugs. Techniques covered include protein expression, purification, and gel analysis, kinase activity assays, and protein structure viewing. The exercises provide students with a hands-on understanding of the impact of biochemistry on human health, and demonstrate their potential as the next generation of investigators.

20.
Pers Soc Psychol Bull ; 35(12): 1687-701, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19726810

RESUMO

The authors propose that two central ingredients in lay models of intentionality are (a) "distal intent" (the actor's mind is focused on a broader goal) and (b) "proximal intent" (the actor's mind is focused narrowly on the act itself). Study 1 established that participants rate an actor with both forms of intent more responsible than an actor with only one form of intent or neither form of intent. In Study 2, when the actor had only distal intent, participants with a high-level construal rated the actor more responsible than did those with a low-level construal. In Study 3, when the actor had only distal intent, participants primed with psychodynamic concepts rated the actor more responsible than did those primed with cognitive-control concepts. However, when the actor had only proximal intent, the effect reversed. The authors discuss the implications of these findings for the literatures on moral reasoning and law.


Assuntos
Intenção , Julgamento , Responsabilidade Social , Adolescente , Anedotas como Assunto , Feminino , Humanos , Masculino , Adulto Jovem
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