The Building Partnerships Program: An Approach to Community-based Learning for Medical Students in Australia

The Building Partnerships Program at the University of Queensland, Australia seeks to address the dual challenge of preparing doctors who are responsive to the community while providing a meaningful context for social sciences learning. Through partnerships with a diverse range of community agencies, the program offers students opportunities to gain non-clinical perspectives on health and illness through structured learning activities including: family visits; community agency visits and attachments; and interview training. Students learn first-hand about psychosocial influences on health and how people manage health problems on a day-to-day basis. They also gain insights into the work of community agencies and how they as future doctors might work in partnership with them to enhance patient care. We outline the main components of the program, identify challenges and successes from student and community agency perspectives, and consider areas that invite further development.

Bioactivation of tamoxifen by recombinant human cytochrome P450 enzymes

Tamoxifen is a major drug used for adjuvant chemotherapy of breast cancer; however, its use has been associated with a small but significant increase in risk of endometrial cancer. In rats, tamoxifen is a hepatocarcinogen, and DNA adducts have been observed in both rat and human tissues. Tamoxifen has been shown previously to be metabolized to reactive products that have the potential to form protein and DNA adducts. Previous studies have suggested a role for P450 3A4 in protein adduct formation in human liver microsomes, via a catechol intermediate; however, no clear correlation was seen between P450 3A4 content of human liver microsomes and adduct formation. In the present study, we investigated the P450 forms responsible for covalent drug-protein adduct formation and the possibility that covalent adduct formation might occur via alternative pathways to catechol formation. Recombinant P450 3A4 catalyzed adduct formation, and this correlated with the level of uncoupling in the P450 incubation, consistent with a role of reactive oxygen species in potentiating adduct formation after enzymatic formation of the catechol metabolite. Whereas P450s 1AI, 2D6, and 3A5 generated catechol metabolite, no covalent adduct formation was observed with these forms. By contrast, P450 2136, 2C19, and rat liver microsomes catalyzed drug-protein adduct formation but not catechol formation. Drug protein adducts formed specifically with P450 3A4 in incubations using membranes isolated from bacteria expressing P450 3A4 and reductase, as well as in reconstitutions of purified 3A4, suggesting that the electrophilic species reacted preferentially with the P450 enzymes concerned.

Immunological response mounted by Aboriginal Australians living in the Northern Territory of Australia against Streptococcus pyogenes serum opacity factor

Streptococcus pyogenes (Group A streptococcus) interacts with host fibronectin via a number of distinct surface components. The streptococcal serum opacity factor (SOF) is a cell-surface protein of S. pyogenes which opalescence of human serum and mediates bacterial binding to fibronectin. In this study, hexahistidyl-tagged fusion proteins encompassing full-length SOF, and domains of SOF encompassing opacity factor activity and fibronectin-binding regions, were used in the characterization of the Aboriginal immune response to SOF. Anti-SOF serum IgG responses were found to be significantly higher (P

Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages

During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.

NEW Solutions: An Australian health promotion programme for people with mental illness

The prevalence of people who are overweight or obese is continuing to rise. This is a key risk indicator of preventable morbidity and mortality resulting from many diseases. The increase in the number of obese people is associated with dietary practices and a reduction in physical activity. There is a need to implement strategies for the reduction of obesity in at-risk groups. People with a mental illness are at high risk of many physical illnesses related to behavioural factors, which include poor diet and lack of exercise. Health promotion programmes need to be incorporated into mental-health services to improve the general health and wellbeing of people with a mental illness. An Australian psychiatric rehabilitation service developed and implemented a health promotion programme, NEW Solutions, which aimed to address issues related to weight gain, dietary practice and physical inactivity.

Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers

Human cytomegalovirus (HCMV) can establish both nonproductive (latent) and productive (lytic) infections. Many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the CD8(+)-T-cell response to HCMV is mainly based on the pp65 antigen. Very little is known about T-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermines the importance of these antigens in several aspects of HCMV disease pathogenesis. In the present study, an efficient and rapid strategy based on predictive bioinformatics and ex vivo functional T-cell assays was adopted to profile CD8(+)-T-cell responses to a large panel of HCMV antigens expressed during different phases of replication. These studies revealed that CD8(+)-T-cell responses to HCMV often contained multiple antigen-specific reactivities, which were not just constrained to the previously identified pp65 or IE-1 antigens. Unexpectedly, a number of viral proteins including structural, early/late antigens and HCMV-encoded immunomodulators (pp28, pp50, gH, gB, US2, US3, US6, and UL18) were also identified as potential targets for HCMV-specific CD8(+)-T-cell immunity. Based on this extensive analysis, numerous novel HCMV peptide epitopes and their HLA-restricting determinants recognized by these T cells have been defined. These observations contrast with previous findings that viral interference with the antigen-processing pathway during lytic infection would render immediate-early and early/late proteins less immunogenic. This work strongly suggests that successful HCMV-specific immune control in healthy virus carriers is dependent on a strong T-cell response towards a broad repertoire of antigens.

Prevalência e fatores associados à respiração oral em escolares participantes do projeto Santo Amaro-Recife,2005

OBJETIVO: Determinar prevalência de crianças portadoras de respiração oral inscritas no Projeto Santo Amaro/ ESEF/ UPE e verificar as principais alterações faciais e comportamentais associadas. FORMA DE ESTUDO: Estudo transversal. MATERIAL E MÉTODO: Amostra de 150 crianças de 8 a 10 anos. Dados coletados mediante aplicação de questionário e exames clínicos. Para o diagnóstico da respiração foram feitos dois testes. Teste 1, observado no espelho, vapor decorrente da respiração, e teste 2, a permanência de água na boca com os lábios em contato pelo tempo de 3 minutos. RESULTADOS: Prevalência de respiração oral foi de 53,3%. Não se comprovou diferença significante entre gênero, faixa etária, tipo de respiração. As alterações faciais da respiração oral foram: selamento labial inadequado (58,8% x 5,7%), olhos caídos (40,0% x 1,4%), palato ogival (38,8% x 2,9%), mordida aberta anterior (60,0% x 30,0%), lábios hipotônicos (23,8% x 0,0%) e olheiras (97,5% x 77,1%). CONCLUSÃO: Prevalência de respiração oral elevada sem diferença estatística entre os gêneros, faixa etária e tipo de respiração oral. Não houve associação entre características comportamentais e o tipo de respiração. Houve diferença significante entre as características físicas e o padrão de respiração.

Correlação da qualidade de vida e voz com atividade profissional

As disfonias podem comprometer a qualidade da comunicação e, por conseqüência, a relação social do indivíduo e assim afetar sua qualidade de vida. Existe hoje necessidade de protocolos objetivos para avaliação da qualidade vocal que mensurem suas implicações na qualidade de vida do paciente. OBJETIVOS: Relacionar qualidade de vida e voz com o grau de disfonia e o uso profissional da voz em um grupo de pacientes disfônicos. MATERIAL E MÉTODO: Realizou-se estudo clínico prospectivo aplicando-se protocolo internacional para avaliar a qualidade de vida e voz em um grupo de pacientes disfônicos. Realizou-se tratamento estatístico dos resultados considerando-se não-distinção entre profissionais da voz e não-profissionais da voz e, em seguida, considerando-se esta distinção profissional. RESULTADOS: A disfonia afetou a qualidade de vida em todos os indivíduos. Não houve diferença estatística entre os grupos, profissionais da voz e não-profissionais da voz, quanto ao grau de disfonia. Houve correlação entre qualidade de vida e grau de disfonia, no entanto, considerando-se os grupos separadamente, esta correlação foi significativa apenas no grupo de sujeitos não-profissionais da voz. CONCLUSÃO: A disfonia afetou a qualidade de vida em todos os sujeitos independente do uso profissional da voz.

A pesquisa científica emgerência de operações no Brasil

As grandes mudanças no cenário competitivo nas últimas décadas do século passado deram novo alento ao ensino e à pesquisa em Gerência de Operações nos principais centros mundiais de ensino de Administração de Empresas. Este artigo busca acompanhar a evolução da pesquisa científica em Gerência de Operações no país, traçando-se, dessa forma, a trajetória das preocupações, dos métodos e da relevância teórica e prática dessa pesquisa no Brasil. A análise inicia-se com o histórico de publicações nos Anais do Enanpad. Seguem as análises das publicações nos periódicos de âmbito nacional mais expressivos na área de Administração: RAE, RAUSP e RAC. A abordagem da literatura completa-se com uma apreciação das publicações de pesquisadores brasileiros em periódicos estrangeiros especializados na área de operações. O artigo é concluído com uma avaliação crítica do estado da pesquisa científica em Gerência de Operações no país.

IMERSÃO SOCIAL NA CADEIA DE SUPRIMENTOS E SEU EFEITO PARADOXAL NO DESEMPENHO OPERACIONAL

Este artigo buscou analisar os efeitos da imersão relacional e da imersão estrutural no desempenho operacional das firmas, medido em termos de ganhos de produtividade e de qualidade. O objeto de estudo foi a indústria moveleira, com base em seus laços com clientes e fornecedores. Especificamente, analisamos como a imersão relacional - confiança e solidariedade - reforça a imersão estrutural, que foi avaliada a partir do grau de concentração de fornecedores e clientes das firmas. Foi possível identificar que a imersão relacional teve efeitos positivos nos indicadores de desempenho operacional, porém de maneira distinta: ela afeta a qualidade nas relações com clientes e a produtividade nos laços com fornecedores. Identificamos ainda, dois efeitos paradoxais. No primeiro, níveis baixos de imersão relacional com fornecedores geram efeitos negativos da imersão estrutural na produtividade, mas, em níveis mais altos, esses efeitos são positivos. No segundo, a contradição reside no efeito positivo da combinação dos dois tipos de imersão na produtividade, mas negativo na qualidade.