Individual variability in cardiac biomarker release after 30 min of high-intensity rowing in elite and amateur athletes

This study had two objectives: (i) to examine individual variation in the pattern of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) release in response to high-intensity rowing exercise, and (ii) to establish whether individual heterogeneity in biomarker appearance was influenced by athletic status (elite vs. amateur). We examined cTnI and NT-proBNP in 18 elite and 14 amateur rowers before and 5 min, 1, 3, 6, 12, and 24 h after a 30-min maximal rowing test. Compared with pre-exercise levels, peak postexercise cTnI (pre: 0.014 ± 0.030 μg·L–1; peak post: 0.058 ± 0.091 μg·L–1; p = 0.000) and NT-proBNP (pre: 15 ± 11 ng·L–1; peak post: 31 ± 19 ng·L–1; p = 0.000) were elevated. Substantial individual heterogeneity in peak and time-course data was noted for cTnI. Peak cTnI exceeded the upper reference limit (URL) in 9 elite and 3 amateur rowers. No rower exceeded the URL for NT-proBNP. Elite rowers had higher baseline (0.019 ± 0.038 vs. 0.008 ± 0.015 μg·L–1; p = 0.003) and peak postexercise cTnI (0.080 ± 0.115 vs. 0.030 ± 0.029 μg·L–1; p = 0.022) than amateur rowers, but the change with exercise was similar between groups. There were no significant differences in baseline and peak postexercise NT-proBNP between groups. In summary, marked individuality in the cTnI response to a short but high-intensity rowing bout was observed. Athletic status did not seem to affect the change in cardiac biomarkers in response to high-intensity exercise

Current and projected heatwave-attributable occupational injuries, illnesses, and associated economic burden in Australia

Introduction: The costs of global warming are substantial. These include expenses from occupational illnesses and injuries (OIIs), which have been associated with increases during heatwaves. This study estimated retrospective and projected future heatwave-attributable OIIs and their costs in Australia. Materials and methods: Climate and workers’ compensation claims data were extracted from seven Australian capital cities representing OIIs from July 2005 to June 2018. Heatwaves were defined using the Excess Heat Factor. OIIs and associated costs were estimated separately per city and pooled to derive national estimates. Results were projected to 2030 (2016–2045) and 2050 (2036–2065). Results: The risk of OIIs and associated costs increased during heatwaves, with the risk increasing during severe and particularly extreme heatwaves. Of all OIIs, 0.13% (95% empirical confidence interval [eCI]: 0.11–0.16%) were heatwave-attributable, equivalent to 120 (95%eCI:70–181) OIIs annually. 0.25% of costs were heatwaveattributable (95%eCI: 0.18–0.34%), equal to $AU4.3 (95%eCI: 1.4–7.4) million annually. Estimates of heatwaveattributable OIIs by 2050, under Representative Concentration Pathway [RCP]4.5 and RCP8.5, were 0.17% (95% eCI: 0.10–0.27%) and 0.23% (95%eCI: 0.13–0.37%), respectively. National costs estimates for 2030 under RCP4.5 and RCP8.5 were 0.13% (95%eCI: 0.27-0.46%) and 0.04% (95%eCI: 0.66-0.60), respectively. These estimates for extreme heatwaves were 0.04% (95%eCI: 0.02–0.06%) and 0.04% (95%eCI: 0.01–0.07), respectively. Cost-AFs in 2050 were, under RCP4.5, 0.127% (95%eCI: 0.27-0.46) for all heatwaves and 0.04% (95%eCI: 0.01-0.09%) for extreme heatwaves. Attributable fractions were approximately similar to baseline when assuming theoretical climate adaptation. Discussion: Heatwaves represent notable and preventable portions of preventable OIIs and economic burden. OIIs are likely to increase in the future, and costs during extreme heatwaves in 2030. Workplace and public health policies aimed at heat adaptation can reduce heat-attributable morbidity and costs.Matthew A. Borg, Jianjun Xiang, Olga Anikeeva, Bertram Ostendorf, Blesson Varghese, Keith Dear, Dino Pisaniello, Alana Hansen, Kerstin Zander, Malcolm R. Sim, Peng B

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as