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1.
Can. Med. Assoc. J ; 192(31): 875-891, 20200804.
Artigo em Inglês | BIGG | ID: biblio-1451334

RESUMO

Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.1 Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify obesity-related health risks at the population level. Obesity is operationally defined as a BMI exceeding 30 kg/m2 and is subclassified into class 1 (30­34.9), class 2 (35­39.9) and class 3 (≥ 40). At the population level, health complications from excess body fat increase as BMI increases.2 At the individual level, complications occur because of excess adiposity, location and distribution of adiposity and many other factors, including environmental, genetic, biologic and socioeconomic factors.


Assuntos
Humanos , Adulto , Determinantes Sociais da Saúde , Manejo da Obesidade , Obesidade/terapia , Índice de Massa Corporal , Terapia Nutricional , Estilo de Vida Saudável , Obesidade/complicações
2.
Edmonton; Obesity Canada; Aug. 4, 2020. 14 p. tab.
Não convencional em Inglês | BIGG | ID: biblio-1509780

RESUMO

Exploring obesity within the context of multiple co-occurring health, socioeconomic, environmental and cultural factors, and situating these within policy/jurisdictional structures specific to Indigenous populations (e.g., federal versus provincial health funding), can facilitate emerging opportunities for obesity management. These contexts highlight a tension that providers must navigate, between drivers of obesity embedded in social- and system-level inequities and protective factors that promote healing through relationships and culturally contextualized approaches to care. Healthcare professionals should consider the following contextual factors when providing obesity care for Indigenous peoples: Structural inequities (i.e., social and systemic in origin) are embedded in health, education, social services and other systems, and they maintain social disadvantage for a large segment of the Indigenous population. These inequities influence food security, for example, through lower wages perpetuated by inaccessible education and high food costs in urban and remote areas, or through limited access to activity-based resources at individual and community levels. Indigenous people have experienced systemic disadvantage throughout their lifespan and those of their family members, producing a cumulative effect on obesity. In Indigenous contexts, obesity is therefore deeply affected by responses to pervasive stressors, as individuals navigate social and systemic barriers to meeting their goals. Overwhelming stress from social (e.g., discrimination) and systemic exclusion (e.g., poor or absent primary healthcare) can disempower Indigenous people in maintaining healthy behaviours. Patients may appear to be resistant to healthcare recommendations, where together with healthcare providers they may come to feel fatalistic toward their capacity to address obesity. Healthcare professionals often interpret such patient incongruity with recommendations in a deficit lens, labeling it as patient non-compliance or non-adherence. This non-concordance, or seeming apathy, may actually be a sense of paralysis in the face of overwhelming stress. Exploration of the patient's social reality can open opportunities for contextualized approaches to obesity management. Reflection on assumptions about seeming apathy may contextualize patient motivations, where deep exploration of one's own perceptions, attitudes and behaviours toward Indigenous patients may uncover anti-Indigenous sentiment implicit in healthcare practices or systems. Validation of a patient's experiences of inequity can empower both patients and providers to identify steps to address social factors that influence health behaviours. Culture and relationships facilitate learning of complex knowledge. The interaction of obesity with co-occurring structural factors represents complex knowledge that is critical for patients to gain deep understanding of their health. Non-Indigenous healthcare providers may have ways of knowing and doing that are inconsistent with Indigenous patient perspectives on health knowledge and how it should be exchanged. Obesity management in this context requires a longitudinal, relationship-centred approach that engages and explores interactions with co-existing factors to build both knowledge and trust, in a manner aligned with Indigenous principles for communication. Connection: When patients connect with healthcare providers around their co-occurring health needs, there are complex linkages between wider structures and their health. The therapeutic relationship may be critically supportive when knowledge is delivered in a relevant way and makes sense to the patient. Trust-building: Healing of the therapeutic relationship is itself fundamental to engaging and supporting patients within contexts of multi-generational trauma to explore complex intersections in relation to health and health behaviour change. Differing worldviews: Western concepts of healthy behaviours related to obesity management, including preferences for body size, activity and food, may be dis­cordant with Indigenous perspectives. Patients may not identify with provider perspectives, and providers must not assume that patients share provider worldviews or principles around how to communicate health knowl­edge. Discordant perspectives may involve a distinct sense of locus of control, self-efficacy and modes for speaking about the pathways into and out of obesity. An Indigenous approach to knowledge exchange in­cludes contextualizing knowledge within the world of the patient and employing a narrative-based and indi­rect approach to sharing knowledge.


Assuntos
Humanos , Isolamento Social , Estresse Psicológico , Saúde de Populações Indígenas , Povos Indígenas , Obesidade/prevenção & controle
3.
Can Fam Physician ; 65(1): 25-33, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30674510

RESUMO

OBJECTIVE: To present a clinical framework for addressing critical social elements for Indigenous patients with type 2 diabetes. SOURCES OF INFORMATION: The Educating for Equity (E4E) Care Framework was developed through a rigorous analysis of qualitative research that included the perspectives of Indigenous patients (n = 32), physicians (n = 28), and Indigenous health curriculum developers (n = 5) across Canada. A national advisory group of Indigenous health experts, educators, leaders, physicians, and community members provided feedback on integrating analysis from primary research into recommendations for physicians. Systematic literature reviews were conducted and a nominal group technique process helped forge research team consensus around the framework's themes and recommendations. MAIN MESSAGE: For Indigenous patients with type 2 diabetes, social factors arising from the legacy of colonization are often barriers to improved diabetes outcomes, while culture is often not recognized as a facilitator in diabetes management. Structural competency in balance with cultural safety should be central to the clinical process when negotiating diabetes management with Indigenous patients. The E4E Care Framework presented in this article provides recommendations to navigate this terrain. CONCLUSION: A focus on social and cultural elements is fundamental to effective diabetes care among Indigenous patients. The E4E Care Framework is a resource that can help clinicians improve Indigenous patients' capacity for change in a way that acknowledges the social factors that affect the increasing diabetes rates, while using a cultural lens to facilitate improved outcomes.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Educação/normas , Serviços de Saúde do Indígena/organização & administração , Educação de Pacientes como Assunto/normas , Canadá , Competência Cultural , Diabetes Mellitus Tipo 2/etnologia , Educação/métodos , Feminino , Humanos , Indígenas Norte-Americanos/psicologia , Pessoa de Meia-Idade
4.
Can Fam Physician ; 65(1): e19-e29, 2019 01.
Artigo em Francês | MEDLINE | ID: mdl-30674525

RESUMO

OBJECTIF: Présenter un cadre clinique afin de prendre en considération les éléments sociaux critiques pour les patients autochtones atteints de diabète de type 2. SOURCES DE L'INFORMATION: Le Cadre de soins fondé sur l'éducation pour l'équité (Educating for Equity [E4E] Care Framework) a été produit à la suite de l'analyse rigoureuse d'une recherche qualitative portant sur les points de vue de patients autochtones (n = 32), de médecins (n = 28) et d'élaborateurs de cursus en santé autochtone (n = 5) dans toutes les régions du Canada. Un groupe consultatif national formé d'experts en santé autochtone, d'enseignants, de dirigeants, de médecins et de membres de la collectivité a exprimé des commentaires sur une analyse intégrant la recherche primaire dans les recommandations à l'intention des médecins. Des revues systématiques de la documentation ont été effectuées, et la technique du groupe nominal a servi à en arriver à un consensus de l'équipe de recherche sur les thèmes et les recommandations du cadre. MESSAGE PRINCIPAL: Pour les patients autochtones atteints du diabète de type 2, les facteurs sociaux découlant des séquelles de la colonisation sont souvent des obstacles à l'amélioration des issues du diabète, et la culture n'est souvent pas reconnue comme une facilitatrice dans la gestion du diabète. Il est essentiel que le processus clinique unisse la compétence structurelle en juste équilibre avec la sécurité culturelle dans la négociation de la gestion du diabète avec des patients autochtones. Le Cadre de soins fondé sur l'éducation pour l'équité présenté dans cet article propose des recommandations pour naviguer dans ces eaux. CONCLUSION: Il est fondamental de mettre l'accent sur les éléments sociaux et culturels pour offrir des soins du diabète efficaces aux patients autochtones. Le Cadre de soins fondé sur l'éducation pour l'équité est une ressource qui peut aider les cliniciens à améliorer la capacité des patients autochtones à apporter des changements d'une façon qui reconnaît les facteurs sociaux qui influencent les taux croissants de diabète, tout en ayant une perspective culturelle pour favoriser de meilleurs résultats.

5.
Acad Med ; 94(4): 512-519, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30277958

RESUMO

The determinants of health inequities between Indigenous and non-Indigenous populations include factors amenable to medical education's influence-for example, the competence of the medical workforce to provide effective and equitable care to Indigenous populations. Medical education institutions have an important role to play in eliminating these inequities. However, there is evidence that medical education is not adequately fulfilling this role and, in fact, may be complicit in perpetuating inequities.This article seeks to examine the factors underpinning medical education's role in Indigenous health inequity, to inform interventions to address these factors. The authors developed a consensus statement that synthesizes evidence from research, evaluation, and the collective experience of an international research collaboration including experts in Indigenous medical education. The statement describes foundational processes that limit Indigenous health development in medical education and articulates key principles that can be applied at multiple levels to advance Indigenous health equity.The authors recognize colonization, racism, and privilege as fundamental determinants of Indigenous health that are also deeply embedded in Western medical education. To contribute effectively to Indigenous health development, medical education institutions must engage in decolonization processes and address racism and privilege at curricular and institutional levels. Indigenous health curricula must be formalized and comprehensive, and must be consistently reinforced in all educational environments. Institutions' responsibilities extend to advocacy for health system and broader societal reform to reduce and eliminate health inequities. These activities must be adequately resourced and underpinned by investment in infrastructure and Indigenous leadership.


Assuntos
Consenso , Serviços de Saúde do Indígena/normas , Disparidades em Assistência à Saúde/tendências , Serviços de Saúde do Indígena/provisão & distribuição , Serviços de Saúde do Indígena/tendências , Humanos , Racismo/prevenção & controle , Racismo/psicologia
6.
J Contin Educ Health Prof ; 38(1): 49-59, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29432332

RESUMO

INTRODUCTION: Health education about Indigenous populations in Canada (First Nations, Inuit, and Métis people) is one approach to enable health services to mitigate health disparities faced by Indigenous peoples related to a history of colonization and ongoing social inequities. This evaluation of a continuing medical education workshop, to enhance family physicians' clinical approach by including social and cultural dimensions within diabetes management, was conducted to determine whether participation in the workshop improved self-reported knowledge, skills, and confidence in working with Indigenous patients with type 2 diabetes. METHODS: The workshop, developed from rigorous national research with Indigenous patients, diabetes care physicians, and Indigenous health medical educators, was attended by 32 family physicians serving Indigenous populations on three sites in Northern Ontario. A same-day evaluation survey assessed participants' satisfaction with workshop content and delivery. Preworkshop and postworkshop surveys consisting of 5-point Likert and open-ended questions were administered 1 week before and 3 month after the workshop. Descriptive statistics and t test were performed to analyze Likert scale questions; thematic analysis was used to elicit and cluster themes from open-ended responses. RESULTS: Participants reported high satisfaction with all aspects of the workshop. Reporting improved understanding of socioeconomic (P = .002), psychosocial, and cultural factors (P = .001), participants also described adapting their clinical approach to more actively incorporating social and cultural factors and focusing on patient-centered care. DISCUSSION: The workshop was effective in shifting physician's self-reported knowledge, attitudes, and skills resulting in clinical approach modifications within social, psychosocial, and cultural domains for their Indigenous patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Educação/normas , Educação de Pacientes como Assunto/métodos , Grupos Populacionais/psicologia , Condições Sociais , Adulto , Competência Cultural/psicologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Educação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Educação de Pacientes como Assunto/normas , Grupos Populacionais/etnologia , Psicometria/instrumentação , Psicometria/métodos , Inquéritos e Questionários
7.
Can J Diabetes ; 42(3): 281-288, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28821421

RESUMO

OBJECTIVES: The perspectives of physicians caring for Indigenous patients with diabetes offer important insights into the provision of health-care services. The purpose of this study was to describe Canadian physicians' perspectives on diabetes care of Indigenous patients, a preliminary step in developing a continuing medical education intervention described elsewhere. METHODS: Through in-depth semistructured interviews, Canadian family physicians and specialists with sizeable proportions of Indigenous clientele shared their experiences of working with Indigenous patients who have type 2 diabetes. Recruitment involved a purposive and convenience sampling strategy, identifying participants through existing research and the professional relationships of team members in the provinces of British Columbia, Alberta and Ontario. Participants addressed their understanding of factors contributing to the disease, approaches to care and recommendations for medical education. The research team framed a thematic analysis through a collaborative, decolonizing lens. RESULTS: The participants (n=28) included 3 Indigenous physicians, 21 non-Indigenous physicians and 4 non-Indigenous diabetes specialists. They practised in urban, reserve and rural adjacent-to-reserve contexts in 5 Canadian provinces. The physicians constructed a socially framed understanding of the complex contexts influencing Indigenous patients with diabetes in tension with structural barriers to providing diabetes care. As a result, physicians adapted care focusing on social factors and conditions that take into account the multigenerational impacts of colonization and the current social contexts of Indigenous peoples in Canada. CONCLUSIONS: Adaptations in diabetes care by physicians grounded in the historical, social and cultural contexts of their Indigenous patients offer opportunities for improving care quality, but policy and health system supports and structural competency are needed.


Assuntos
Diabetes Mellitus Tipo 2 , Serviços de Saúde do Indígena , Médicos/estatística & dados numéricos , Qualidade da Assistência à Saúde , Canadá/epidemiologia , Assistência à Saúde Culturalmente Competente , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Indígenas Norte-Americanos/etnologia , Entrevistas como Assunto
8.
CMAJ ; 189(3): E106-E112, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28246155

RESUMO

BACKGROUND: Indigenous social determinants of health, including the ongoing impacts of colonization, contribute to increased rates of chronic disease and a health equity gap for Indigenous people. We sought to examine the health care experiences of Indigenous people with type 2 diabetes to understand how such determinants are embodied and enacted during clinical encounters. METHODS: Sequential focus groups and interviews were conducted in 5 Indigenous communities. Focus groups occurred over 5 sessions at 4 sites; 3 participants were interviewed at a 5th site. Participants self-identified as Indigenous, were more than 18 years of age, lived with type 2 diabetes, had received care from the same physician for the previous 12 months and spoke English. We used a phenomenological thematic analysis framework to categorize diabetes experiences. RESULTS: Patient experiences clustered into 4 themes: the colonial legacy of health care; the perpetuation of inequalities; structural barriers to care; and the role of the health care relationship in mitigating harm. There was consistency across the diverse sites concerning the root causes of mistrust of health care systems. INTERPRETATION: Patients' interactions and engagement with diabetes care were influenced by personal and collective historical experiences with health care providers and contemporary exposures to culturally unsafe health care. These experiences led to nondisclosure during health care interactions. Our findings show that health care relationships are central to addressing the ongoing colonial dynamics in Indigenous health care and have a role in mitigating past harms.


Assuntos
Diabetes Mellitus Tipo 2/economia , Acessibilidade aos Serviços de Saúde/economia , Serviços de Saúde do Indígena/economia , Disparidades em Assistência à Saúde/economia , Indígenas Norte-Americanos/estatística & dados numéricos , Atenção Primária à Saúde/economia , Adulto , Idoso , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Grupos Focais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde do Indígena/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-28096162

RESUMO

Artemisinin-based combination therapies are a key pillar in global malaria control and are recommended as a first-line Plasmodium falciparum treatment. They rely upon a rapid 4-log-unit reduction in parasitemia by artemisinin compounds with a short half-life and the killing of remaining parasites by a partner compound with a longer half-life. Current treatment guidelines stipulate giving three 24-h-interval doses or six 12-h-interval doses over a 3-day period. Due to the short half-life of artesunate and artemether, almost all of the resulting cytocidal activity is confined within a single 48-h asexual P. falciparum cycle. Here, we utilized a luciferase reporter, Plasmodium berghei ANKA, in a cytocidal model in which treatment was initiated at high parasitemia, allowing us to monitor a greater than 3-log-unit reduction in parasite density, as well as 30-day survival. In this study, we demonstrated that increasing the artesunate duration from spanning one asexual cycle to spanning three asexual cycles while keeping the total dose constant results in enhanced cytocidal activity. Single daily artesunate doses at 50 mg/kg of body weight over 7 days were the minimum necessary for curative monotherapy. In combination with a single sub-human-equivalent dose of the partner drug amodiaquine or piperaquine, the three-asexual-cycle artesunate duration was able to cure 75% and 100% of mice, respectively, whereas 0% and 33% cures were achieved with the single-asexual-cycle artesunate duration. In summary, cytocidal activity of the artemisinin compounds, such as artesunate, can be improved solely by altering the dosing duration.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Amodiaquina/uso terapêutico , Animais , Artemeter , Artesunato , Modelos Animais de Doenças , Feminino , Malária/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Quinolinas/uso terapêutico
10.
AIDS ; 31(5): 623-633, 2017 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-28005686

RESUMO

OBJECTIVE: HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in vitro; however, the contribution of these factors in vivo in HIV-1-associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND. DESIGN: A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study including HIV-1-seronegative (N = 36) and HIV-1-seropositive individuals without neurocognitive symptoms (N = 16) or with mild neurocognitive disorder (MND) (N = 8) or HIV-associated dementia (HAD) (N = 16). METHODS: A systematic evaluation of global transcriptome of peripheral blood mononuclear cells (PBMCs) obtained from HIV-1-seronegative individuals and from HIV-1-positive men without neurocognitive symptoms, or MND or HAD was performed. RESULTS: MND and HAD were associated with specific changes in mRNA transcripts and microRNAs in PBMCs. Comparison of upstream regulators and TimePath analyses identified specific cellular factors associated with MND and HAD, whereas HIV-1 viral proteins played a greater role in HAD. In addition, expression of specific microRNAs - miR-let-7a, miR-124, miR-15a and others - were found to correlate with mRNA gene expression and may have a potential protective role in asymptomatic HIV-1-seropositive individuals by regulating cellular signal transduction pathways downstream of chemokines and cytokines. CONCLUSION: These results identify signature transcriptome changes in PBMCs associated with stages of HAND and shed light on the potential contribution of host cellular factors and viral proteins in HAND development.


Assuntos
Complexo AIDS Demência/fisiopatologia , Perfilação da Expressão Gênica , Infecções por HIV/complicações , HIV-1/patogenicidade , Interações Hospedeiro-Patógeno , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/virologia , Células Cultivadas , Estudos Transversais , Redes Reguladoras de Genes , Humanos , Masculino , Biologia de Sistemas/métodos
11.
J Gen Virol ; 95(Pt 3): 700-711, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24300552

RESUMO

Following infection with Human immunodeficiency virus 1 (HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and viral factors have been implicated in the observed differences in disease status. Here, we focus on understanding the contribution of HIV-1 viral protein R (Vpr) by evaluating the disease-associated Vpr polymorphism and its biological functions from HIV-1 positive rapid progressor (RP) and long-term nonprogressor (LTNP) subjects. Results presented here show distinct variation in phenotypes of Vpr alleles from LTNP and RP subjects. Most notably, the polymorphism of Vpr at R36W and L68M associated with RP shows higher levels of oligomerization, and increased virus replication, whereas R77Q exhibits poor replication kinetics. Interestingly, we did not observe correlation with cell cycle arrest function. Together these results indicate that polymorphisms in Vpr in part may contribute to altered virus replication kinetics leading to the observed differences in disease progression in LTNP and RP groups.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Polimorfismo Genético , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo , Progressão da Doença , Pontos de Checagem da Fase G2 do Ciclo Celular , Infecções por HIV/patologia , Infecções por HIV/fisiopatologia , HIV-1/classificação , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Filogenia , Replicação Viral
12.
Malar J ; 11: 180, 2012 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-22646748

RESUMO

BACKGROUND: Human malaria infections caused by the parasite Plasmodium falciparum often contain more than one genetically distinct parasite. Despite this fact, nearly all studies of multiple strain P. falciparum infections have been limited to determining relative densities of each parasite within an infection. In light of this, new methods are needed that can quantify the absolute number of parasites within a single infection. METHODS: A quantitative PCR (qPCR) method was developed to track the dynamic interaction of P. falciparum infections containing genetically distinct parasite clones in cultured red blood cells. Allele-specific primers were used to generate a standard curve and to quantify the absolute concentration of parasite DNA within multi-clonal infections. Effects on dynamic growth relationships between parasites under drug pressure were examined by treating mixed cultures of drug sensitive and drug resistant parasites with the anti-malarial drug chloroquine at different dosing schedules. RESULTS: An absolute quantification method was developed to monitor the dynamics of P. falciparum cultures in vitro. This method allowed for the observation of competitive suppression, the reduction of parasites numbers due to the presence of another parasite, and competitive release, the improved performance of a parasite after the removal of a competitor. These studies demonstrated that the presence of two parasites led to the reduction in density of at least one parasite. The introduction of drug to a mixed culture containing both a drug resistant and drug sensitive parasites resulted in an increased proportion of the drug resistant parasite. Moreover, following drug treatment, the resistant parasite experienced competitive release by exhibiting a fitness benefit greater than simply surviving drug treatment, due to the removal of competitive suppression by the sensitive parasite. CONCLUSIONS: The newly developed assay allowed for the examination of the dynamics of two distinct clones in vitro; both competitive suppression and release were observed. A deeper understanding of the dynamic growth responses of multiple strain P. falciparum infections, with and without drug pressure, can improve the understanding of the role of parasite interactions in the spread of drug resistant parasites, perhaps suggesting different treatment strategies.


Assuntos
Eritrócitos/parasitologia , Plasmodium falciparum/classificação , Plasmodium falciparum/isolamento & purificação , Antimaláricos/farmacologia , DNA de Protozoário/genética , Genótipo , Humanos , Interações Microbianas , Carga Parasitária , Plasmodium falciparum/genética
13.
Virol J ; 7: 119, 2010 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-20529298

RESUMO

HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC) method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection.


Assuntos
HIV-1/metabolismo , Vírion/metabolismo , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/química , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo , Sequência de Aminoácidos , Linhagem Celular , HIV-1/química , HIV-1/genética , Humanos , Conformação Molecular , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Alinhamento de Sequência , Vírion/química , Vírion/genética , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética
14.
Am J Orthod Dentofacial Orthop ; 128(4): 418-23, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16214621

RESUMO

INTRODUCTION: Precise 3-dimensional (3D) localization of impacted canines is central to their clinical management. Recently introduced dental 3D volumetric imaging systems make precise localization possible. The purpose of this study was to describe the spatial relationship of impacted canines by using images obtained with the NewTom QR-DVT 9000 (QR Srl, Verona, Italy). METHODS: Unilaterally and bilaterally impacted canines (n = 27) from 19 consecutive patients (15 female, 4 male) were evaluated on images taken with the NewTom QR-DVT 9000. The spatial relationships of the impacted canines relative to adjacent structures and incisor resorption were assessed with 3D visualization software. RESULTS: Most (92.6%) of the 27 impactions were palatal. Incisor resorption adjacent to the impacted canine was present in 66.7% of the lateral incisors and 11.1% of the central incisors. Follicle size did not play a major role in influencing impacted canine position. The alveolus was narrower at the impacted canine side compared with the erupted canine side; however, the width of the alveolus on the impacted canine side is independent of the deciduous canines. A correlation was found between the proximity of the impacted canine to the incisors and their resorption. There was no common location where eruption was arrested, and great variation in the inclination of the impacted canine was found. CONCLUSIONS: 3D volumetric imaging of impacted canines can show the following: presence or absence of the canine, size of the follicle, inclination of the long axis of the tooth, relative buccal and palatal positions, amount of the bone covering the tooth, 3D proximity and resorption of roots of adjacent teeth, condition of adjacent teeth, local anatomic considerations, and overall stage of dental development. In short, 3D imaging is clearly advantageous in the management of impacted canines.


Assuntos
Dente Canino/diagnóstico por imagem , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Erupção Ectópica de Dente/diagnóstico por imagem , Dente Impactado/diagnóstico por imagem , Adolescente , Adulto , Criança , Dente Canino/patologia , Saco Dentário/diagnóstico por imagem , Saco Dentário/patologia , Feminino , Humanos , Imageamento Tridimensional/instrumentação , Incisivo/diagnóstico por imagem , Incisivo/fisiopatologia , Masculino , Maxila , Radiografia Dentária , Reabsorção da Raiz/diagnóstico por imagem , Reabsorção da Raiz/etiologia , Erupção Ectópica de Dente/complicações , Alvéolo Dental/diagnóstico por imagem , Alvéolo Dental/patologia , Dente Impactado/complicações
15.
J Dent Child (Chic) ; 71(1): 77-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15272663

RESUMO

This is the case of a healthy 6-year old female with a clinically absent right mandibular second primary molar with no history of that tooth ever being present. Radiographic examination revealed a well-circumscribed pericoronal radiolucency surrounding the mandibular right primary second molar. The mandibular right second premolar was displaced mesially. Treatment consisted of enucleation of the lesion with removal of both the unerupted primary second molar and second premolar. The histopathology of the excised lesion revealed a hyperplastic dental follicle with a focal proliferation of odontogenic epithelium and duct-like structures, probably representing an incipient adenomatoid odontogenic tumor.


Assuntos
Dente Molar/patologia , Dente Decíduo/patologia , Dente não Erupcionado/patologia , Dente Pré-Molar/patologia , Dente Pré-Molar/cirurgia , Criança , Saco Dentário/patologia , Saco Dentário/cirurgia , Feminino , Humanos , Neoplasias Mandibulares/patologia , Dente Molar/cirurgia , Tumores Odontogênicos/patologia , Extração Dentária , Dente Decíduo/cirurgia , Dente não Erupcionado/cirurgia
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