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1.
Int J Epidemiol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670764

RESUMO

The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.

2.
Dis Markers ; 2019: 8628612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481984

RESUMO

Malignant pleural mesothelioma (MPM) is an incurable cancer of the pleura that can be difficult to diagnose. Biomarkers for an easier and/or earlier diagnosis are needed. Approximately 90% of MPM patients develop a pleural effusion (PE). PEs are ideal sources of biomarkers as the fluid would almost always require drainage for diagnostic and/or therapeutic reasons. However, differentiating MPM PE from PE caused by other diseases can be challenging. MicroRNAs are popular biomarkers given their stable expression in tissue and fluid. MicroRNAs have been analysed in PE cytology samples for the diagnosis of MPM but have not been measured in frozen/fresh PE. We hypothesise that microRNAs expressed in PE are biomarkers for MPM. TaqMan OpenArray was used to analyse over 700 microRNAs in PE cells and supernatants from 26 MPMs and 21 other PE-causing diseases. In PE cells, combining miR-143, miR-210, and miR-200c could differentiate MPM with an area under the curve (AUC) of 0.92. The three-microRNA signature could also discriminate MPM from a further 40 adenocarcinomas with an AUC of 0.9887. These results suggest that the expression of miR-143, miR-210, and miR-200c in PE cells might provide a signature for diagnosing MPM.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31433952

RESUMO

RATIONALE: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial. OBJECTIVES: To define the relationship between pleural plaques and lung cancer risk. METHODS: Subjects were from two cohorts: (1) crocidolite mine and mill workers, and Wittenoom township residents and (2) a mixed asbestos fiber, mixed occupation cohort. All subjects underwent annual review since 1990, chest x-ray (CXR) or low dose computed tomography (LDCT) scan and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios for lung cancer incidence by sex, tobacco smoking, asbestos exposure, and presence of asbestosis and pleural plaques. MEASUREMENTS AND MAIN RESULTS: For all 4240 subjects, mean age at follow up was 65.4 years, 3486 (82.0%) were male, 1315 (31.0%) had pleural plaques and 1353 (32.0%) had radiographic asbestosis. 3042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR 1.03, 95% CI 0.64-1.67, p=0.89; cohort 2: HR 0.75, 95% CI 0.45-1.25, p=0.28). CONCLUSIONS: The presence of pleural plaques on radiological imaging does not confer an additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.

4.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

5.
Ann Work Expo Health ; 63(7): 719-728, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31120100

RESUMO

OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates. METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates. RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively. CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.

7.
PLoS One ; 13(4): e0195313, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29652910

RESUMO

There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation. All elderly DC subsets demonstrated comparable up-regulation of co-stimulatory molecules (CD40, CD80 and/or CD86), intracellular pro-inflammatory cytokine levels (IFN-γ, tumour necrosis factor (TNF)-α, IL-6 and/or IL-12), and/or secreted cytokine levels (IFN-α, IFN-γ, TNF-α, and IL-12) to their younger counterparts. Furthermore, elderly-derived LPS/IFN-γ or CD40L-activated MoDCs induced similar or increased levels of CD8+ and CD4+ T cell proliferation, and similar T cell functional phenotypes, to their younger counterparts. However, elderly LPS/IFN-γ-activated MoDCs were unreliable in their ability to up-regulate chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and IL-6 secretion, implying an inability to dependably induce an inflammatory response. A key age-related difference was that, unlike young-derived MoDCs that completely lost their ability to process antigen, elderly-derived MoDCs maintained their antigen processing ability after LPS/IFN-γ maturation, measured using the DQ-ovalbumin assay; this response implies incomplete maturation that may enable elderly DCs to continuously present antigen. These differences may impact on the efficacy of anti-pathogen and anti-tumour immune responses in the elderly.


Assuntos
Envelhecimento/imunologia , Ligante de CD40/farmacologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD1/metabolismo , Antígeno B7-2/metabolismo , Antígenos CD40/metabolismo , Células Dendríticas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/metabolismo , Adulto Jovem
8.
Respirology ; 23(6): 576-582, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29365367

RESUMO

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.


Assuntos
Asma/epidemiologia , Bronquite/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Idoso , Asma/fisiopatologia , Índice de Massa Corporal , Bronquite/fisiopatologia , Estudos Transversais , Suplementos Nutricionais , Exercício , Feminino , Volume Expiratório Forçado , Envelhecimento Saudável , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Sons Respiratórios/fisiopatologia , Estações do Ano , Fumar/epidemiologia , Espirometria , Inquéritos e Questionários , Capacidade Vital , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue , Austrália Ocidental/epidemiologia
10.
J Allergy Clin Immunol ; 141(3): 991-1001, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29030101

RESUMO

BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. OBJECTIVE: We sought to investigate genetic susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. RESULTS: An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30. CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

11.
Occup Environ Med ; 75(1): 29-36, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28756413

RESUMO

OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom. METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers. RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL). CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers. IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.


Assuntos
Asbesto Crocidolita/efeitos adversos , Asbestos/efeitos adversos , Asbestose/mortalidade , Emigrantes e Imigrantes , Grupos Étnicos , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Exposição Ocupacional/efeitos adversos , Adulto , Asbestose/etiologia , Estudos de Coortes , Emprego , Feminino , Humanos , Itália , Neoplasias Pulmonares/etiologia , Masculino , Indústria Manufatureira , Mesotelioma/etiologia , Mineração , Exposição Ocupacional/análise , Modelos de Riscos Proporcionais , Migrantes , Austrália Ocidental , Adulto Jovem
12.
BMC Cancer ; 17(1): 386, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558669

RESUMO

BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin. METHODS: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype. RESULTS: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00). CONCLUSIONS: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.


Assuntos
Biomarcadores Tumorais/sangue , Calbindina 2/sangue , Neoplasias Pulmonares/sangue , Mesotelioma/sangue , Neoplasias Pleurais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestos/toxicidade , Austrália , Calbindina 2/genética , Alemanha , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/induzido quimicamente , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia
13.
Thorax ; 72(5): 400-408, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28174340

RESUMO

BACKGROUND: Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. OBJECTIVES: We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. METHODS: We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS: The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10-16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts. CONCLUSIONS: Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.


Assuntos
Variação Genética , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Respiração/genética , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Medição de Risco , Fatores de Risco , Espirometria , Fatores de Tempo , Austrália Ocidental
14.
PLoS One ; 11(10): e0163891, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27755543

RESUMO

BACKGROUND: Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM) in a representative population. METHODS: From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24%) were interviewed, examined [blood pressure (BP), anthropometry], tested for fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C). Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl) = 100-125 or HbA1C(%) = 5.7-6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2. RESULTS: Among participants, 28.62% [95% Confidence Interval (95%CI) = 23.19-34.06)] were overweight [body mass index(BMI) = (25-29.99)kg/meter2], 7.81% (4.58-11.03) were obese(BMI≥30kg/meter2), 20.82% (15.93-25.70) were current smokers, 12.64% (8.64-16.64) were current alcohol-drinkers and 46.32% of responders (39.16-53.47) had family history of diabetes. 17.84% (13.24-22.45) had stage-I [140≤average systolic BP (AvSBP in mm of mercury)<160 or 90≤average diastolic BP (AvDBP)<100] and 12.64% (8.64-16.64) had stage-II (AvSBP≥160 or AvDBP≥160) hypertension. Based on FPG and HbA1c, 10.41% (6.74-14.08) were diabetic and 27.88% (22.49-33.27) were pre-diabetic. Overall prevalence of diabetes was 15.61% (11.25-19.98). Among pre-diagnosed cases, 46.43% (26.74-66.12) had uncontrolled AGM. With one year increase in age [Odds Ratio(OR) = 1.05(1.03-1.07)], retired subjects [OR = 9.14(1.72-48.66)], overweight[OR = 2.78(1.37-5.64)], ex-drinkers [OR = 4.66(1.35-16.12)] and hypertensives [ORStage I = 3.75(1.42-9.94); ORStage II = 4.69(1.67-13.17)] had higher odds of diabetes. Relatively older subjects [OR = 1.06(1.02-1.10)], unemployed [OR = 19.68(18.64-20.78)], business-owners [OR = 25.53(24.91-16.18)], retired [OR = 46.53(45.38-47.72)], ex-smokers [OR = 4.75(1.09-20.78)], ex-drinkers [OR = 22.43(4.62-108.81)] and hypertensives [ORStage II = 13.17(1.29-134.03)] were more likely to have uncontrolled AGM. CONCLUSIONS: Burden of uncontrolled AGM was high among participants. Efforts to curb the diabetes epidemic in urban India should include interventions targeting appropriate diabetic control among relatively older persons, unemployed, business-owners, retired, ex-smokers, ex-drinkers and hypertensives.


Assuntos
Comportamento/fisiologia , Diabetes Mellitus Tipo 2/epidemiologia , Glucose/metabolismo , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Demografia , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipertensão/epidemiologia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Fatores de Risco , População Urbana
15.
Med J Aust ; 204(11): 406, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27318396

RESUMO

OBJECTIVES: To estimate the proportion of ever-smokers who are eligible for lung cancer screening in an Australian cohort, and to evaluate the effect of spirometry in defining chronic obstructive pulmonary disease (COPD) when assessing screening eligibility. DESIGN: Cross-sectional study of 3586 individuals aged 50-68 years who live in the Busselton Shire of Western Australia. OUTCOMES: Proportion of ever-smokers eligible for lung cancer screening based on United States Preventive Services Task Force (USPSTF) criteria, and PLCOm2012 lung cancer risk > 1.5%. The effect of using self-reported COPD, symptoms consistent with COPD, or spirometry to define COPD for screening eligibility according to the PLCOm2012 criteria. RESULTS: Of ever-smokers aged 55-68 years, 254 (20.1%) would be eligible for screening according to USPSTF criteria; fewer would be eligible according to PLCOm2012 criteria (225, 17.9%; P = 0.004). This is equivalent to 8.9-10.0% of the total population aged 55-68 years, which suggests about 450 000 individuals in Australia may be eligible for lung cancer screening. The proportions of eligible participants were not significantly different whether spirometry results or symptoms consistent with COPD were used to determine PLCOm2012 risk. CONCLUSIONS: The proportion of ever-smokers in this population who were eligible for lung cancer screening was 17.9-20.1%. Using symptoms to define COPD is an appropriate surrogate measure for spirometry when determining the presence of COPD in this population. There are significant challenges for policy makers on how to identify and recruit these eligible individuals from the wider population.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Definição da Elegibilidade/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco , Fumar/epidemiologia , Espirometria
16.
Oncoimmunology ; 5(2): e1082028, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27057464

RESUMO

Mesothelioma is an almost invariably fatal tumor with chemotherapy extending survival by a few months. One immunotherapeutic strategy is to target dendritic cells (DCs), key antigen-presenting cells involved in antigen presentation, to induce antigen-specific T cell responses. However, DC-targeting will only be effective if DCs are fit-for-purpose, and the functional status of DCs in mesothelioma patients was not clear. We found that mesothelioma patients have significantly decreased numbers of circulating myeloid (m)DC1 cells, mDC2 cells and plasmacytoid (p)DCs relative to healthy age and gender-matched controls. Blood monocytes from patients could not differentiate into immature monocyte-derived DCs (MoDCs), indicated by a significantly reduced ability to process antigen and reduced expression of costimulatory (CD40, CD80 and CD86) and MHC (HLA-DR) molecules, relative to controls. Activation of mesothelioma-derived MoDCs with LPS+/-IFNγ generated partially mature MoDCs, evident by limited upregulation of the maturation marker, CD83, and the costimulatory markers. Attempts to rescue mesothelioma-derived DC function using CD40Ligand(L) also failed, indicated by maintenance of antigen-processing capacity and limited upregulation of CD40, CD83, CD86 and HLA-DR. These data suggest that mesothelioma patients have significant numerical and functional DC defects and that their reduced capacity to process antigen and reduced expression of costimulatory molecules could induce anergized/tolerized T cells. Nonetheless, survival analyses revealed that individuals with mesothelioma and higher than median levels of mDC1s and/or whose MoDCs matured in response to LPS, IFNγ or CD40L lived longer, implying their selection for DC-targeting therapy could be promising especially if combined with another treatment modality.

20.
Ann Occup Hyg ; 59(6): 737-48, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25841001

RESUMO

INTRODUCTION: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. OBJECTIVE: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. METHODS: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. RESULTS: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. CONCLUSION: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation.


Assuntos
Poluentes Ocupacionais do Ar/análise , Asbestos/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Ocupações , Poluentes Ocupacionais do Ar/efeitos adversos , Asbestos/efeitos adversos , Asbestose , Austrália , Humanos , Mesotelioma , Doenças Profissionais
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