Glutathione <em>S</em>-transferase P1 (<em>GSTP1</em>) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

BACKGROUND: Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. METHODS: Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT–PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. RESULTS: Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC(50), respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. CONCLUSIONS: Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients

Restrictive pattern on spirometry: association with cardiovascular risk and level of physical activity in asymptomatic adults

Objective : To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL), as well as with cardiovascular disease (CVD) risk factors, in asymptomatic adults. Methods : A total of 374 participants (mean age, 41 ± 14 years) underwent spirometry, which included the determination of FVC and FEV1. A restrictive pattern on spirometry was defined as an FEV1/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer. Results : A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness), the following variables retained significance (OR; 95% CI) as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8), smoking (11.6; 1.56-87.5), physical inactivity (8.1; 1.43-46.4), larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71); and dyslipidemia (1.89; 1.12-1.98). Conclusions : A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies

HIV prevalence among female sex workers, drug users and men who have sex with men in Brazil: A Systematic Review and Meta-analysis

<p>Abstract</p> <p>Background</p> <p>The Brazilian response towards AIDS epidemic is well known, but the absence of a systematic review of vulnerable populations ─ men who have sex with men (MSM), female sex workers (FSW), and drug users (DU) remains a main gap in the available literature. Our goal was to conduct a systematic review and meta-analysis of studies assessing HIV prevalence among MSM, FSW and DU, calculating a combined pooled prevalence and summarizing factors associated the pooled prevalence for each group.</p> <p>Methods</p> <p>Nine electronic databases (MEDLINE via PubMed, EMBASE, Cochrane CENTRAL, AIDSLINE, AMED, CINAHL, TOXNET, SciELO, and ISI-Web of Science) were searched for peer-reviewed papers published in English, French, Spanish or Portuguese, from 1999 to 2009. To be included in the review, studies had to measure HIV prevalence and/or incidence as the primary outcome among at least one specific population under analysis.</p> <p>Results</p> <p>The studies targeting the three populations analyzed mostly young participants aged 30 years or less. Among FSW, eight studies were selected (3,625 participants), consistently identifying higher condom use with sexual clients than with occasional and stable partners. The combined HIV prevalence for FSW was 6.2 (95% CI: 4.4-8.3). Ten studies targeting MSM were identified (6,475 participants). Unprotected anal intercourse was commonly reported on those studies, but with great variability according to the nature of the relationship - stable vs. occasional sex partners - and sexual practice - receptive vs. insertive anal sex. Pooled HIV prevalence for MSM was 13.6 (95% CI: 8.2-20.2). Twenty nine studies targeting DU were identified (13,063 participants). Those studies consistently identified injection drug use and syringe/needle sharing as key predictors of HIV-infection, as well as engagement in sex work and male-to-male sex. The combined HIV prevalence across studies targeting DU was 23.1 (95% CI: 16.7-30.2).</p> <p>Conclusions</p> <p>FSW, MSM and DU from Brazil have a much risk of acquiring HIV infection compared to the general population, among which HIV prevalence has been relatively low (~0.6%). Those vulnerable populations should be targeted by focused prevention strategies that provide accurate information, counseling and testing, as well as concrete means to foster behavior change (e.g. access to condoms, drug abuse treatment, and clean syringes in the case of active injecting drug users), tailored to gender and culture-specific needs. Programs that provide these services need to be implemented on public health services throughout the country, in order to decrease the vulnerability of those populations to HIV infection.</p

The unsupported upper limb exercise test in people without disabilities: assessing the within-day test–retest reliability and the effects of age and gender

Purpose: To estimate the within-day test–retest reliability and standard error of measurement (SEM) of the unsupported upper limb exercise test (UULEX) in adults without disabilities and to determine the effects of age and gender on performance of the UULEX. Method: A cross-sectional study was conducted with 100 adults without disabilities (44 men, mean age 44.2 [SD 26] y; 56 women, mean age 38.1 [SD 24.1] y). Participants performed three UULEX tests to establish within-day reliability, measured using an intra-class correlation coefficient (ICC) model 2 (two-way random effects) with a single rater (ICC[2,1]) and SEM. The effects of age and gender were examined using two-factor mixed-design analysis of variance (ANOVA) and one-way repeated-measures ANOVA. For analysis purposes, four sub-groups were created: younger adults, older adults, men, and women. Results: Excellent within-day reliability and a small SEM were found in the four sub-groups (younger adults: ICC[2,1]=0.88; 95% CI: 0.82, 0.92; SEM∼40 s; older adults: ICC[2,1]=0.82; 95% CI: 0.72, 0.90; SEM∼50 s; men: ICC[2,1]=0.93; 95% CI: 0.88, 0.96; SEM∼30 s; women: ICC[2,1]=0.85; 95% CI: 0.78, 0.91; SEM∼45 s). Younger adults took, on average, 308.24 seconds longer than older adults to perform the test; older adults performed significantly better on the third test (p0.05). Conclusion: The within-day test–retest reliability and SEM values of the UULEX may be used to define the magnitude of the error obtained with repeated measures. One UULEX test seems to be adequate for younger adults to achieve reliable results, whereas three tests seem to be needed for older adults.Objectif : évaluer la fiabilité d'un test-retest en une même journée et l'erreur type de mesure (ETM) du test d'exercice des membres supérieurs sans appui (UULEX) chez des adultes sans incapacités et déterminer les effets de l'âge et du sexe sur leur exécution. Méthodologie : les chercheurs ont réalisé une étude transversale auprès de 100 adultes sans incapacités (44 hommes, d'un âge moyen de 44,2 ans [ÉT 26], et 56 femmes, d'un âge moyen de 38,1 ans [ÉT 24,1]). Les participants ont effectué trois UULEX pour établir la fiabilité du test-retest en une même journée, mesurés à l'aide du modèle 2 de coefficient de corrélation intraclasse (ICC, effets aléatoires bilatéraux) comportant un ICC(2,1) et une ETM à un seul évaluateur. Les chercheurs ont examiné les effets de l'âge et du sexe à l'aide d'une analyse de variance bifactorielle à mesures mixtes et d'une analyse de variance unifactorielle à mesures répétées. Pour les besoins de l'analyse, les chercheurs ont créé quatre sous-groupes: jeunes adultes, adultes plus âgés, hommes et femmes. Résultats : les quatre sous-groupes affichaient une excellente fiabilité en une même journée et une petite ETM (jeunes adultes: ICC[2,1]=0,88 [IC 95% : 0,82, 0,92] et ETM∼40 secondes; adultes plus âgés : ICC[2,1]=0,82 [IC 95 % : 0,72, 0,90] et ETM∼50 secondes; hommes: ICC[2,1]=0,93 [IC 95% : 0,88, 0,96] et ETM∼30 secondes; femmes: ICC[2,1]=0,85 [IC 95 % : 0,78, 0,91] et ETM∼45 secondes). En moyenne, les jeunes adultes ont effectué le test pendant 308,24 secondes de plus que les adultes plus âgés; ceux-ci ont obtenu un résultat nettement meilleur au troisième test (p0,05). Conclusion : il est possible d'utiliser la fiabilité de test-retest en une même journée et les valeurs d'ETM de l'UULEX pour définir l'importance de l'erreur obtenue lors de mesures répétées. Un UULEX semble suffire pour que les jeunes adultes obtiennent des résultats fiables, tandis que trois tests semblent nécessaires chez les adultes plus âgés