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1.
Malar J ; 19(1): 308, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854713

RESUMO

BACKGROUND: Malaria is a leading cause of morbidity and mortality among children under 5 years in Malawi, and especially among those from rural areas of central Malawi. The goal of this study was to examine the prevalence and determinants of malaria infection among children in rural areas of Dowa district in central Malawi. METHODS: A multistage, cross-sectional study design was used to systematically sample 523 child-mother dyads from postnatal clinics. A survey was administered to mothers and a rapid malaria infection diagnostic test was administered to children. The main outcome was positive malaria diagnostic tests in children. Logistic regressions were used to determine risk factors associated with malaria among children aged 2 to 59 months. RESULTS: The prevalence of malaria among children under 5 years was 35.4%. Results suggest that children of mothers who experienced recent intimate partner violence (IPV) were more likely to be diagnosed with malaria (AOR: 1.88, 95% CI 1.19-2.97; P = 0.007) than children of mothers who did not. Children of mothers who had no formal education were more likely to be diagnosed with malaria (AOR: 2.77, 95% CI 1.24-6.19; P = 0.013) than children of mothers who had received secondary education. Children aged 2 to 5 months and 6 to 11 months were less likely to be diagnosed with malaria (AOR: 0.21, 95% CI 0.10-0.46; P = 0.000 and AOR: 0.43; 95% CI 0.22-0.85; P = 0.016, respectively) than children aged 24 to 59 months. CONCLUSION: The prevalence of malaria infection among children in the study area was comparable to the national level. In addition to available malaria control programmes, further attention should be paid to children whose mothers have no formal education, children aged 24 to 59 months, and children of mothers that are exposed to IPV in the area.


Assuntos
Fazendeiros/estatística & dados numéricos , Malária/epidemiologia , Pré-Escolar , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Humanos , Lactente , Malaui/epidemiologia , Masculino , Mães , Prevalência , Fatores de Risco , Inquéritos e Questionários
2.
Health Promot Pract ; 21(5): 802-810, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-30724108

RESUMO

INTRODUCTION: This article reports on the micro-, meso-, and macro-level impacts of sharing digital stories created by Indigenous youth leaders about HIV prevention activism in Canada. METHOD: Eighteen participants created digital stories and hosted screenings in their own communities to foster dialogue. Data for this article are drawn from individual semistructured interviews with the youth leaders, audio-recordings of audience reflections, and research team member's field notes collected between 2012 and 2015 across Canada. Data were coded using NVivo. A content analysis approach guided analysis. RESULTS: The process of sharing their digital stories had a positive impact on the youth themselves and their communities. Stories also reached policymakers. They challenged conventional public health messaging by situating HIV in the context of Indigenous holistic conceptions of health. DISCUSSION: The impact(s) of sharing digital stories were felt most strongly by their creators but rippled out to create waves of change for many touched by them. More research is warranted to examine the ways that the products of participatory visual methodologies can be powerful tools in creating social change and reducing health disparities.


Assuntos
Infecções por HIV , Saúde Pública , Adolescente , Canadá , Infecções por HIV/prevenção & controle , Humanos
3.
Cult Health Sex ; 17(7): 906-19, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25702802

RESUMO

Focusing on gender, race and colonialism, this paper foregrounds the voices of Indigenous young people, their histories of oppression, their legacies of resistance and the continuing strengths rooted in Indigenous peoples, their cultures and their communities. Exploring the relationship between gender and colonialism, the paper speaks to the lived realities of young people from Indigenous communities across Canada. Over 85 young people participated in six different Indigenous community workshops to create artistic pieces that explored the connections between HIV, individual risk and structural inequalities. In the course of the research, Indigenous young people, and young Indigenous women in particular, talked about how gender intersects with race and colonisation to create experiences that are, at times, especially difficult for them. In this paper, young people discuss the ways in which colonialism has demeaned women's roles and degraded women's sexuality, and how continuing cultural erasure and assimilationist policies impact on their lives and on their bodies.


Assuntos
Atitude Frente a Saúde/etnologia , Colonialismo , Infecções por HIV/prevenção & controle , Promoção da Saúde/métodos , Indígenas Norte-Americanos/estatística & dados numéricos , Adulto , Canadá , Características Culturais , Feminino , Serviços de Saúde do Indígena/organização & administração , Humanos , Masculino , Adulto Jovem
4.
Nurs Educ Perspect ; 36(4): 259-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26328298

RESUMO

This article outlines processes followed during a two-day offsite retreat for nurse faculty planned for the purpose of curricular redesign and content mapping. Faculty identified and leveled content for all baccalaureate clinical courses and engaged in dialogue specific to promoting student connections between didactic and clinical outcomes. Faculty developed two core simulation scenarios for every clinical course and leveled learning outcomes for each. Faculty defined where within the curriculum key concepts were introduced and planned depth of knowledge, application, and synthesis from sophomore through senior levels. Evaluation revealed the process led faculty to a stronger overall understanding of the curriculum.


Assuntos
Currículo , Bacharelado em Enfermagem/organização & administração , Docentes de Enfermagem/organização & administração , Reforma dos Serviços de Saúde/organização & administração , Formação de Conceito , Humanos , Pesquisa em Educação em Enfermagem , Estados Unidos
5.
J Health Commun ; 18(12): 1465-76, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24015829

RESUMO

Young adults often lack access to confidential, long-lasting, and nonjudgmental interactions with sexual health professionals at brick-and-mortar clinics. To ensure that patients return for their STI test results, post-result counseling, and STI-related information, computer-mediated health intervention programming allows them to receive sexual health information through onsite computers, the Internet, and mobile phone calls and text messages. To determine whether young adults (age: M = 21 years) prefer to communicate with health professionals about the status of their sexual health through computer-mediated communication devices, 303 second-year university students (183 from an urban North American university and 120 from a periurban university in South Africa) completed a paper-based survey indicating how they prefer to communicate with doctors and nurses: talking face to face, mobile phone call, text message, Internet chat programs, Facebook, Twitter, or e-mail. Nearly all students, and female students in South Africa in particular, prefer to receive their STI test results, post-results counseling, and STI-related information by talking face to face with doctors and nurses rather than communicating through computers or mobile phones. Results are clarified in relation to gender, availability of various technologies, and prevalence of HIV in Canada and in South Africa.


Assuntos
Comunicação , Aconselhamento/métodos , Relações Enfermeiro-Paciente , Preferência do Paciente/estatística & dados numéricos , Relações Médico-Paciente , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/terapia , Adolescente , Adulto , Canadá , Telefone Celular , Correio Eletrônico , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Mídias Sociais , África do Sul , Envio de Mensagens de Texto , Adulto Jovem
6.
J Contin Educ Nurs ; 44(7): 313-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23713436

RESUMO

Staff development departments are challenged with addressing the entry of new graduates into the work force, updating the competencies of practicing nurses, and providing nurses with educational support to reduce turnover. Knowing how to develop simulations, integrate them into teaching, and effectively assess simulated performance is becoming a core role for educators in health care. For many educators, a knowledge and skill gap exists between the demand for simulation and competence in developing and using simulation. This article shares a cost-effective, three-step train-the-trainer model to prepare nurse educators to use simulation effectively. The three steps include champion identification, champion development, and champion integration. Strategies for addressing the challenges and lessons learned in implementing this model are outlined. The model is an effective and efficient approach for developing a core of champions in any topic area. These champions can then mentor and train others throughout the organization.


Assuntos
Educação em Enfermagem/métodos , Docentes de Enfermagem , Desenvolvimento de Pessoal/métodos , Humanos , Modelos Educacionais , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estados Unidos
7.
Hepatology ; 53(2): 618-27, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21274882

RESUMO

UNLABELLED: Acute liver failure (ALF) is a rare syndrome with a difficult clinical management and a high mortality rate. During ALF, several molecular pathways governing oxidative stress and apoptosis are activated to induce massive tissue injury and suppress cell proliferation. There are few anti-ALF drug candidates, among which is the C-type lectin Reg3α, or human hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which displayed promising properties for tissue regeneration and protection against cellular stress in transgenic mice. We report on substantial preclinical and clinical advances in the development of a recombinant (rc) full-length human HIP/PAP protein as an anti-ALF drug. The curative effects and mechanisms of action of rcHIP/PAP were investigated in murine Fas-induced ALF. Primary hepatocytes were cultured with cytotoxic doses of tumor necrosis factor α/actinomycin-D, transforming growth factor ß, agonistic Fas antibody or hydrogen peroxide, and various concentrations of rcHIP/PAP. Cell viability, proliferation index, apoptosis, and oxidation were monitored. We found that rcHIP/PAP significantly improved survival in Fas-intoxicated mice in a dose-dependent and time-dependent manner, with optimum effects when it was injected at advanced stages of ALF. Primary hepatocytes were efficiently protected against multiple cell death signals by rcHIP/PAP. This survival benefit was linked to a depletion of oxidized biomolecules in injured liver cells due to a strong reactive oxygen species scavenging activity of rcHIP/PAP. Clinically, an escalating dose phase 1 trial demonstrated a good tolerability and pharmacokinetic profile of rcHIP/PAP in healthy subjects. CONCLUSION: The rcHIP/PAP protein exhibited significant curative properties against ALF in mice. It is a free-radical scavenger that targets a broad spectrum of death effectors and favors liver regeneration. The good safety profile of rcHIP/PAP during a phase 1 trial encourages evaluation of its efficacy in patients with ALF.


Assuntos
Antígenos de Neoplasias/uso terapêutico , Biomarcadores Tumorais/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Radicais Livres/metabolismo , Lectinas Tipo C/uso terapêutico , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/tratamento farmacológico , Receptor fas/efeitos adversos , Adolescente , Adulto , Animais , Antígenos de Neoplasias/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/farmacocinética , Biomarcadores Tumorais/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Método Duplo-Cego , Sequestradores de Radicais Livres/farmacocinética , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Falência Hepática Aguda/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Associadas a Pancreatite , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Adulto Jovem
8.
JMIR Res Protoc ; 11(1): e33525, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023844

RESUMO

BACKGROUND: Digital stories-first-person, self-made, 2- to 3-minute videos-generate awareness, impart knowledge, and promote understanding on topics such as mental illness. Digital stories are a narrative-based art form often created by individuals without formal training in filmmaking to relate personal experiences. Somewhat like digital narratives, video testimonies created within the social marketing or fundraising campaigns of government agencies and private or public corporations aim to reduce the stigma of mental illness while supporting research and services. In video testimonies, personal stories are captured on camera by professional filmmakers. Sharing critical life events greatly benefits tellers and listeners alike, supporting catharsis, healing, connectiveness, and citizenship. OBJECTIVE: This study explores digital stories and video testimonies featuring mental illness and recovery in their ability to elicit empathy and compassion while reducing stigma among viewers. METHODS: Using mixed methods, phase 1 will involve a search of Canadian social marketing activities and fundraising campaigns concerning mental illness and recovery. Phase 2 will involve the organization of digital storytelling workshops in which participants will create digital stories about their own experiences of mental illness and recovery. In phase 3, a pilot randomized controlled trial will be undertaken to compare marketing and fundraising campaigns with digital stories for their impact on viewers, whereas phase 4 will focus on knowledge dissemination. RESULTS: Ethics approval for this study was received in March 2021. Data on the feasibility of the study design and the results of the controlled trial will be generated. This study will produce new knowledge on effective ways of promoting mental health awareness and decreasing stigma, with practical importance for future social marketing and fundraising campaigns. The anticipated time for completion within the 2-year study period includes 9 months for phase 1 (knowledge synthesis activities identifying social marketing and fundraising campaigns) and phase 2 (storytelling workshops), 11 months for phase 3 (feasibility assessment and data collection: randomized controlled trial), and 2 months for phase 4 (knowledge dissemination). CONCLUSIONS: The knowledge generated will have practical implications for the public and for future social marketing and fundraising campaigns promoted by government agencies as well as nonprofit and for-profit organizations by enhancing our understanding of how individuals and societies respond to stories of mental distress and what prompts citizens to help others. TRIAL REGISTRATION: ClinicalTrials.gov NCT04881084; https://clinicaltrials.gov/ct2/show/NCT04881084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33525.

9.
JMIR Res Protoc ; 11(3): e36060, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35289762

RESUMO

BACKGROUND: Adolescents (10-19 years) are a big segment of the Nigerian population, and they face serious risks to their health and well-being. Maternal mortality is very high in Nigeria, and rates of pregnancy and maternal deaths are high among female adolescents. Rates of HIV infection are rising among adolescents, gender violence and sexual abuse are common, and knowledge about sexual and reproductive health risks is low. Adolescent sexual and reproductive health (ASRH) indicators are worse in the north of the country. OBJECTIVE: In Bauchi State, northern Nigeria, the project will document the nature and extent of ASRH outcomes and risks, discuss the findings and codesign solutions with local stakeholders, and measure the short-term impact of the discussions and proposed solutions. METHODS: The participatory research project is a sequential mixed-methods codesign of a pragmatic cluster randomized controlled trial. Focus groups of local stakeholders (female and male adolescents, parents, traditional and religious leaders, service providers, and planners) will identify local priority ASRH concerns. The same stakeholder groups will map their knowledge of factors causing these concerns using the fuzzy cognitive mapping (FCM) technique. Findings from the maps and a scoping review will inform the contextualization of survey instruments to collect information about ASRH from female and male adolescents and parents in households and from local service providers. The survey will take place in 60 Bauchi communities. Adolescents will cocreate materials to share the findings from the maps and survey. In 30 communities, randomly allocated, the project will engage adolescents and other stakeholders in households, communities, and services to discuss the evidence and to design and implement culturally acceptable actions to improve ASRH. A follow-up survey in communities with and without the intervention will measure the short-term impact of these discussions and actions. We will also evaluate the intervention process and use narrative techniques to assess its impact qualitatively. RESULTS: Focus groups to explore ASRH concerns of stakeholders began in October 2021. Baseline data collection in the household survey is expected to take place in mid-2022. The study was approved by the Bauchi State Health Research Ethics Committee, approval number NREC/03/11/19B/2021/03 (March 1, 2021), and by the Faculty of Medicine and Health Sciences Institutional Review Board McGill University (September 13, 2021). CONCLUSIONS: Evidence about factors related to ASRH outcomes in Nigeria and implementation and testing of a dialogic intervention to improve these outcomes will fill a gap in the literature. The project will document and test the effectiveness of a participatory approach to ASRH intervention research. TRIAL REGISTRATION: ISRCTN Registry ISRCTN18295275; https://www.isrctn.com/ISRCTN18295275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36060.

10.
Lab Invest ; 91(2): 273-82, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20856227

RESUMO

The role of hepatocyte apoptosis in the physiopathology of obstructive cholestasis is still controversial. Although some data have strongly suggested that hepatocellular cholestatic injury is due to Fas-mediated hepatocyte apoptosis, some others concluded that necrosis, rather than apoptosis, represents the main type of hepatocyte death in chronic cholestasis. Moreover, it has also been suggested that the reduced liver injury observed in the absence of Fas receptor after bile duct ligation was not due to lower hepatocyte apoptosis but to the indirect role of this receptor in non-hepatocytic cells such as cholangiocytes and inflammatory cells. The aim of this work was therefore to determine whether a protection against cell death limited to hepatocytes could be sufficient to reduce liver injury and delay cholestatic fibrosis. With this purpose, we performed bile duct ligation in transgenic mice overexpressing Bcl-2 in hepatocytes and in wild-type littermates. We found that, compared with necrosis, apoptosis was negligible in this model. Our results also showed that hepatocyte Bcl-2 expression protected hepatocytes against liver injury only in the early steps of the disease. This protection was correlated with reduced mitochondrial dysfunction and lipid peroxidation. However, in contrast to Fas receptor-deficient lpr mice, fibrosis progression was not hampered and liver inflammatory response was not reduced by Bcl-2 overexpression. These results therefore comfort the hypothesis that Fas-mediated apoptotic hepatocyte pathway is not a significant contributing factor to the clinical features observed in cholestasis. Moreover, in the absence of a blunted inflammatory response in transgenic mice, Bcl-2 protection against hepatocyte mitochondrial dysfunction and lipid peroxidation was not sufficient to block fibrosis progression.


Assuntos
Apoptose/fisiologia , Colestase Intra-Hepática/metabolismo , Hepatócitos/metabolismo , Necrose/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Ductos Biliares/cirurgia , Western Blotting , Caspases/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Técnicas Histológicas , Marcação In Situ das Extremidades Cortadas , Ligadura , Peroxidação de Lipídeos/fisiologia , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
J Hepatol ; 55(1): 86-95, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21145869

RESUMO

BACKGROUND & AIMS: ß-Catenin is an oncogene frequently mutated in hepatocellular carcinoma. In this study, we investigated target genes of ß-catenin signaling in hepatocyte proliferation. METHODS: We studied transgenic mice displaying either inactivation or activation of the ß-catenin pathway, focusing on analysis of liver proliferation due to aberrant ß-catenin activation, and on the regeneration process during which ß-catenin signaling is transiently activated. We localized in situ the various partners involved in proliferation or identified as targets of ß-catenin in these transgenic and regenerating livers. We also performed comparative transcriptome analyses, using microarrays. Finally, we extracted, from deep-sequencing data, both the DNA regulatory elements bound to the ß-catenin/Tcf nuclear complex and the expression levels of critical targets identified in microarrays. RESULTS: ß-Catenin activation during liver regeneration occurred during G1/S cell cycle progression and allowed zonal extension of the normal territory of active ß-catenin and panlobular proliferation. We found that ß-catenin controlled both cell-autonomous and non-cell-autonomous hepatocyte proliferation, through direct transcriptional and complex control of cyclin D1 gene expression and of the expression of a new target gene, Tgfα. CONCLUSIONS: We propose that ß-catenin controls panlobular hepatocyte proliferation partly by controlling, together with its Tcf4 nuclear partner, expression of the pro-proliferation cyclin D1 and Tgfα genes. This study constitutes a first step toward understanding the oncogenic properties of this prominent signaling pathway in the liver.


Assuntos
Genes bcl-1 , Hepatócitos/citologia , Hepatócitos/metabolismo , Fator de Crescimento Transformador alfa/genética , beta Catenina/metabolismo , Animais , Sequência de Bases , Ciclo Celular , Proliferação de Células , DNA/genética , Perfilação da Expressão Gênica , Fígado/anatomia & histologia , Fígado/metabolismo , Regeneração Hepática/genética , Regeneração Hepática/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Modelos Biológicos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais , beta Catenina/deficiência , beta Catenina/genética
12.
Gastroenterology ; 138(3): 1155-65.e1-2, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19919837

RESUMO

BACKGROUND & AIMS: p53 Mutations are very common in human hepatocellular carcinoma, and induction of hepatic p53 expression causes lysis of implanted hepatoblastoma cells in a chimeric mouse. Ataxia Telangiectasia Mutated (ATM) kinase senses DNA strand breaks and induces p53. Our aims were to establish whether ATM deficiency alters the carcinogenic response of hepatocytes to diethylnitrosamine (DEN). METHODS: Male ATM-deficient (ATM(-/-)), heterozygote (ATM(+/-)), and wild-type (WT) mice were injected with DEN at age 15 days, and animals were killed up to 12 months to assess p53, cell cycle, apoptosis, and liver tumor development. RESULTS: Whereas >80% of WT and ATM(+/-) mice developed hepatocellular carcinoma (HCC), at 9-12 months, ATM(-/-) mice remained refractory to DEN-induced HCC up to 15 months. At 6 and 9 months, and compared with WT mice, p53 and p19(ARF) expression were greatly enhanced in ATM(-/-) liver associated with up-regulation of ATR and Chk1; cleaved caspase-3 immunohistochemistry and caspase-3 activity were also significantly increased. Whereas livers of DEN-treated ATM(-/-) mice showed markers of senescence (beta-galactosidase, Cxcl-1), up-regulation of telomerase occurred concurrently. The possibility that such balanced senescence could result in immortalization was demonstrated in hepatocytes prepared at 9 months from DEN-treated ATM(-/-) liver. CONCLUSIONS: Hepatocarcinogenesis is abrogated in ATM-deficient mice in association with induction of ATR, Chk1, p53, and p19(ARF). Resultant cell cycle arrest and apoptosis of DNA-damaged cells are possible mechanisms that underlie this unique "refractoriness" to malignant transformation in DEN-initiated ATM(-/-) hepatocytes. The findings also show that prolonged up-regulation of p53 associated with some features of senescence does not inevitably cause organ failure.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Transformação Celular Neoplásica/metabolismo , Proteínas de Ligação a DNA/deficiência , Neoplasias Hepáticas/prevenção & controle , Proteínas Serina-Treonina Quinases/deficiência , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/deficiência , Animais , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Senescência Celular , Quinase 1 do Ponto de Checagem , Aberrações Cromossômicas , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas de Ligação a DNA/genética , Dietilnitrosamina , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Heterozigoto , Cariotipagem , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Telomerase/metabolismo , Fatores de Tempo , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Regulação para Cima
13.
Qual Health Res ; 21(8): 1127-35, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21508252

RESUMO

Encouraging youth voice, visibility, and active participation in adolescent-related research is strongly advocated in the literature. In this article, we describe how participatory approaches informed by arts-based methods (e.g., reflective writing, dramatization) were used with adolescents to enhance the research process in an exploratory study designed to develop and evaluate prevention resources for sexual risk-taking behaviors.Youth aged 15 to 17 years participated in iterative focus groups conducted over a 1-year period in school settings in Prince Edward Island, Canada. Descriptions of our experiences, strategies, and insights provide evidence for guiding practice to optimize adolescent participation in research.


Assuntos
Comportamento do Adolescente/psicologia , Pesquisa Participativa Baseada na Comunidade/métodos , Educação Sexual/métodos , Comportamento Sexual/psicologia , Adolescente , Feminino , Grupos Focais , Humanos , Masculino , Ilha do Príncipe Eduardo , Assunção de Riscos , Instituições Acadêmicas , Fatores Sexuais , Infecções Sexualmente Transmissíveis/prevenção & controle
14.
Am J Pathol ; 175(3): 947-57, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19700759

RESUMO

Liver regeneration after two-thirds partial hepatectomy (2/3 PH) results in synchronized proliferation of hepatocytes and rapid restoration of liver mass. Understanding the mechanisms that regulate this process has both biological and clinical importance. Using cDNA microarray analysis, we investigated whether gene activation after 2/3 PH is specifically related to liver growth and hepatocyte proliferation. We generated gene expression profiles at 4, 12, 20, and 30 hours after 2/3 PH and compared them with profiles obtained at the same time points after 1/3 PH, a procedure that causes minimal DNA replication. Surprisingly, a significant number of genes whose expression is altered after 2/3 PH are similarly up- or down-regulated after 1/3 PH, particularly at 4 hours. We identified a number of genes and transcription factors that are more highly expressed ("preferential expression") after 2/3 PH and show that a shift in transcriptional programs in the regenerating liver occurs between 4 and 12 hours after 2/3 PH, a time at which the decision to replicate appears to be made. These results show that the liver responds to PH with massive changes of gene expression, even in the absence of DNA replication. We suggest that the changes in gene expression during the first 4 to 6 hours after 2/3 PH may induce chromatin remodeling and facilitate the binding of new sets of transcription factors required for DNA replication.


Assuntos
Regulação da Expressão Gênica , Regeneração Hepática/genética , Fígado/fisiologia , Animais , Contagem de Células , Proliferação de Células , Montagem e Desmontagem da Cromatina , Replicação do DNA , Perfilação da Expressão Gênica , Hepatectomia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Tempo , Transcrição Gênica
15.
Am J Pathol ; 175(5): 1929-37, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19808650

RESUMO

Accumulating evidence indicates that oxidative stress is involved in the physiopathology of liver fibrogenesis. However, amid the global context of hepatic oxidative stress, the specific role of hepatocyte mitochondrial dysfunction in the fibrogenic process is still unknown. The aim of this study was to determine whether a targeted protection of hepatocytes against mitochondrial dysfunction could modulate fibrosis progression. We induced liver fibrogenesis by chronic carbon tetrachloride treatment (3 or 6 weeks of biweekly injections) in transgenic mice expressing Bcl-2 in their hepatocytes or in normal control mice. Analyses of mitochondrial DNA, respiratory chain complexes, and lipid peroxidation showed that Bcl-2 transgenic animals were protected against mitochondrial dysfunction and oxidative stress resulting from carbon tetrachloride injury. Picrosirius red staining, alpha-smooth muscle actin immunohistochemistry, and real-time PCR for transforming growth factor-beta and collagen alpha-I revealed that Bcl-2 transgenic mice presented reduced fibrosis at early stages of fibrogenesis. However, at later stages increased nonmitochondrial/nonhepatocytic oxidative stress eventually overcame the capacity of Bcl-2 overexpression to prevent the fibrotic process. In conclusion, we demonstrate for the first time that specific protection against hepatocyte mitochondrial dysfunction plays a preventive role in early stages of fibrogenesis, delaying its onset. However, with the persistence of the aggression, this protection is no longer sufficient to impede fibrosis progression.


Assuntos
Hepatócitos/citologia , Hepatócitos/patologia , Mitocôndrias Hepáticas , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Tetracloreto de Carbono/toxicidade , Caspases/metabolismo , Progressão da Doença , Fibrose/metabolismo , Fibrose/patologia , Fibrose/fisiopatologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
16.
Am J Pathol ; 174(5): 1766-75, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19359521

RESUMO

Inflammation has been shown to induce the progression of fibrosis in response to liver injury. Among inflammatory cells, macrophages and lymphocytes play major roles in both the constitution and resolution of liver fibrosis. The chemokine receptor CCR2 is involved in the recruitment of monocytes to injury sites, and it is known to be induced during the progression of fibrosis in humans. However, its specific role during this process has not yet been unveiled. We first demonstrated that, compared with wild-type mice, CCR2 knockout animals presented a delay in liver injury after acute CCl(4) injection, accompanied by a reduction in infiltrating macrophage populations. We then induced fibrosis using repeated injections of CCl(4) and observed a significantly lower level of fibrotic scars at the peak of fibrosis in mutant animals compared with control mice. This diminished fibrosis was associated with a reduction in F4/80(+)CD11b(+) and CD11c(+) populations at the sites of injury. Subsequent analysis of the kinetics of the resolution of fibrosis showed that fibrosis rapidly regressed in wild-type, but not in CCR2(-/-) mice. The persistence of hepatic injury in mutant animals was correlated with sustained tissue inhibitor of metalloproteinase-1 mRNA expression levels and a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-13 expression levels. In conclusion, these findings underline the role of the CCR2 signaling pathway in both the constitution and resolution of liver fibrotic scars.


Assuntos
Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Receptores CCR2/fisiologia , Animais , Western Blotting , Antígeno CD11b/metabolismo , Antígeno CD11c/metabolismo , Tetracloreto de Carbono/toxicidade , Citometria de Fluxo , Técnicas Imunoenzimáticas , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
17.
Ann Clin Transl Neurol ; 7(5): 757-766, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32342672

RESUMO

OBJECTIVE: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities. METHODS: Registration is patient-initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor function and muscle strength, respiratory and cardiac function, medication, quality of life and pain. RESULTS: Of 663 registered participants, 305 were genetically confirmed LGMDR9 patients from 23 countries. A majority of LGMDR9 patients carried the common mutation c.826C > A on one or both alleles; 67.9% were homozygous and 28.5% were compound heterozygous for this mutation. The mean ages of symptom onset and disease diagnosis were higher in individuals homozygous for c.826C > A compared with individuals heterozygous for c.826C > A. This divergence was replicated in ages of loss of running ability, wheelchair-dependence and ventilation assistance; consistent with the milder phenotype associated with individuals homozygous for c.826C > A. In LGMDR9 patients, 75.1% were currently ambulant and 24.6%, nonambulant (unreported in 0.3%). Cardiac impairment was reported in 23.2% (30/129). INTERPRETATION: The Global FKRP Registry enables the collection of patient natural history data, which informs academics, healthcare professionals and industry. It represents a trial-ready cohort of individuals and is centrally placed to facilitate recruitment to clinical studies.


Assuntos
Distrofia Muscular do Cíngulo dos Membros/genética , Pentosiltransferases/genética , Sistema de Registros , Síndrome de Walker-Warburg/genética , Adolescente , Adulto , Idade de Início , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Fenótipo , Síndrome de Walker-Warburg/fisiopatologia , Adulto Jovem
18.
Nat Biotechnol ; 20(12): 1234-9, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12434157

RESUMO

Studying the effects of the loss of a specific cell type is a powerful approach in biology. Here we present a method based on the controlled activation of the apoptotic machinery. We expressed a modified caspase-3-containing chemical inducer of dimerization (CID)-binding sites in the livers of transgenic mice. In the absence of CID, no liver injury was detectable, underlining the absence of leakage in our system. In contrast, injection of the CID produced activation of the chimeric caspase-3, which led to a dose-dependent pure hepatocyte ablation with subsequent regeneration. This method is effective in both growing and nongrowing cells, and is therefore applicable to a wide range of cells and tissues. Moreover, because apoptosis has been described in numerous pathological circumstances, this system is useful for generating mouse models of human disorders as well as for studying the recovery or regeneration of tissues after cell loss.


Assuntos
Apoptose/fisiologia , Caspases/metabolismo , Regulação da Expressão Gênica/fisiologia , Hepatócitos/fisiologia , Tacrolimo/análogos & derivados , Tacrolimo/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Caspases/genética , Linhagem Celular , Dimerização , Relação Dose-Resposta a Droga , Ativação Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Substâncias Macromoleculares , Camundongos , Camundongos Transgênicos , Monitorização Intraoperatória , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Valores de Referência
19.
Can J Public Health ; 98(3): 179-82, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17626380

RESUMO

BACKGROUND: In Canada, Aboriginal people are overrepresented in the HIV epidemic and infected at a younger age than non-Aboriginal people. This paper discusses some of the ways Aboriginal youth in Toronto understand HIV/AIDS risk and the relevance of their comments for HIV prevention education. This research is part of a larger study conducted with Ontario youth through the Gendering Adolescent AIDS Prevention (GAAP) project. METHODS: We conducted 11 GAAP focus groups with Ontario youth. This paper focuses primarily on the four groups of Aboriginal youth. A modified grounded theory approach guided analyses. Data were coded using Nud*ist qualitative data management software. FINDINGS: Aboriginal youth were more aware of HIV/AIDS and the structural inequities that contribute to risk than their non-Aboriginal counterparts. In addition, they were the only group to talk about colonialism in the context of HIV in their community. Aboriginal youth were, however, more likely to hold a fatalistic view of their future and to blame their own community for high infection rates. INTERPRETATION: We argue for incorporating structural factors of risk, including the legacy of colonialism, in HIV prevention programs for all youth. This may help to eradicate the stigma and self-blame that negatively impact on Aboriginal youth while allowing other youth populations to distance themselves from the disease.


Assuntos
Atitude Frente a Saúde/etnologia , Infecções por HIV/etnologia , Comportamentos Relacionados com a Saúde/etnologia , Indígenas Norte-Americanos/psicologia , Adolescente , Adulto , Fatores Etários , Colonialismo , Feminino , Grupos Focais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Ontário/epidemiologia , Projetos Piloto , Medição de Risco , Fatores de Risco , Fatores Socioeconômicos
20.
Glob Public Health ; 11(5-6): 521-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27105078

RESUMO

This Introduction serves to map out a range of participatory visual approaches, as well as critical issues related to the use of participatory visual methodologies in global health. In so doing, it offers both an overview of these innovative practices in global health and a consideration of some of the key questions that researchers might ask themselves in design and implementation.


Assuntos
Recursos Audiovisuais , Pesquisa Participativa Baseada na Comunidade , Saúde Global , Política de Saúde/tendências , Promoção da Saúde/métodos , Pesquisa sobre Serviços de Saúde/métodos , Telecomunicações , Arte , Drama , Humanos , Mapas como Assunto , Mudança Social , Gravação em Vídeo
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