Heart rate variability in association with frequent use of household sprays and scented products in SAPALDIA

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown.Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction.Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, 1, 1-3, or 4-7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products.Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4-7 days/week was associated with 11% [95% confidence interval (CI): -20%, -2%] and 29% (95% CI: -46%, -8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p > 0.05 for interactions).Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptibl

Machine learning-based lifetime breast cancer risk reclassification compared with the BOADICEA model: impact on screening recommendations

BACKGROUND: The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screening practices. METHODS: We used three different ML algorithms and the BOADICEA model to estimate lifetime breast cancer risk in a sample of 112,587 individuals from 2481 families from the Oncogenetic Unit, Geneva University Hospitals. Performance of algorithms was evaluated using the area under the receiver operating characteristic (AU-ROC) curve. Risk reclassification was compared for 36,146 breast cancer-free women of ages 20-80. The impact on recommendations for mammography surveillance was based on the Swiss Surveillance Protocol. RESULTS: The predictive accuracy of ML-based algorithms (0.843 </= AU-ROC </= 0.889) was superior to BOADICEA (AU-ROC = 0.639) and reclassified 35.3% of women in different risk categories. The largest reclassification (20.8%) was observed in women characterised as 'near population' risk by BOADICEA. Reclassification had the largest impact on screening practices of women younger than 50. CONCLUSION: ML-based reclassification of lifetime breast cancer risk occurred in approximately one in three women. Reclassification is important for younger women because it impacts clinical decision- making for the initiation of screening

Regional differences and trends in breast cancer surgical procedures and their relation to socioeconomic disparities and screening patterns

Background Important regional disparities in patterns of care in breast cancer have recently been described. In Switzerland, nationwide data on hospitalisations have been collected since 1998. They have not been used up to now to explore space–time patterns and trends of breast cancer healthcare-related procedures for control and health planning purposes. We aimed to assess geographical and temporal variation of mastectomy rates. Methods Bayesian negative-binomial spatio-temporal models have been applied. Covariates included patient characteristics as provided in the hospital data, data on mammography screening programme duration, and surgeon and gynaecologist density. Results We analyzed more than 70,000 patients. Mastectomy rates declined from 43% to 30% in Switzerland between 2000 and 2012 for patients aged 50–69 and from 61% to 43% for those 70+, and remained stable for those under 50. Important geographical differences in rates were present. Rates were significantly influenced by age [relative rate ratio (RR) 50–69: 0.92, RR 70+: 1.25], differences in co-morbidity (RR one co-morbidity: 1.17, RR more than one: 1.35), higher surgeon or gynaecologist density (RR surgeons: 1.01, RR gynaecologists: 1.06). Regions in the French-speaking part (RR: 0.72) and/or with mammography screening programmes showed significantly lower rates (RR: 0.87). No difference was found for patients in different socio-economic groups or with different insurance types. Conclusion This research unveiled important differences in mastectomy rates in Switzerland. The results play an essential role in the identification of regions where special attention is required, and indications for extensive surgery in breast cancer should be revisited

Metabolic syndrome in rural Peruvian adults living at high altitudes using different cookstoves

This study determined the prevalence of metabolic syndrome (MetS) in open fire stoves and improved cookstoves users (ICS) in the rural Peruvian Andes. Participants answered a socioeconomic questionnaire, one 24-hour food recall and underwent a physical examination. We analysed data from 385 participants, 190 (112 women and 78 men) were ICS users and 195 (123 women and 72 men) were open fire stove users. The prevalence of MetS was 21.3, 26.4% in women and 13.3% in men. We found no statistically significant association between the type of cookstove and MetS. Body mass index and altitude were important determinants of MetS. Research on cardiometabolic diseases and open fire stove use contributes to understanding the effect of household air pollution on health in high altitude populations

Common circuit defect of excitatory-inhibitory balance in mouse models of autism

One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement (Hensch Nat Rev Neurosci 6:877–888, 1), are disrupted across heterogeneous ASD mouse models. We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development and potential prevention by treatment of autism

The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore

Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint function, can promote cell proliferation or induce growth arrest and apoptosis depending on the cellular context. We hypothesized that the direction of the association between the (CCND1) G870A-polymorphism and breast cancer risk may be modified by dietary and genetic factors influencing the oxidant-antioxidant balance, such as a dietary pattern with a high intake of n-6 fatty acids and a low intake of n-3 fatty acids, or a genetic profile that is deficient in glutathione S-transferases. We tested our hypothesis in a case-control study nested into the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. Genomic DNA collected from 258 incident cases of breast cancer and 670 female cohort controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5′-nuclease assay. Unconditional logistic regression models were used to assess the effects with adjustment for potential confounders. All statistical tests were two-sided. The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR = 0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The association was restricted to women with a high (above median value) intake level of n-6 fatty acids (OR = 0.51, 95% CI 0.30-0.87), a low (below median value) intake level of the antagonistic marine n-3 fatty acids (OR = 0.54, 95% CI 0.32-0.93) or a total lack of the antioxidative GSTM1 (OR = 0.44, 95% CI 0.25-0.80) or GSTT1 genes (OR = 0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with advanced disease. The AA genotype did not affect breast cancer risk. The results of this study are compatible with the hypothesis that the oxidant-antioxidant balance in cells is an important determinant of the direction of the cyclin D1 effect, leading either to cell proliferation or cell deat

The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study

Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63 000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (≥2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.10-3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR = 0.56; 0.36-0.86) (P for interaction = 0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effec

Predictors of state-of-the-art management of early breast cancer in Switzerland

Background: The aim of this study was to investigate predictors of state-of-the-art management of early breast cancer in Switzerland. Patients and methods: The study included 3499 women aged 25-79 years diagnosed with invasive breast cancer stages I-IIIA in 2003-2005. Patients were identified through population-based cancer registries and treated in all kinds of settings. Concordance with national and international recommendations was assessed for 10 items covering surgery, radiotherapy, systemic adjuvant therapy and histopathology reporting. We used multivariate logistic regression to identify independent predictors of high (10 points) and low (≤7 points) concordance. Results: In one-third of the patients, management met guidelines in all items, whereas in about one-fifth, three or more items did not comply. Treatment by a surgeon with caseload in the upper tercile and team involved in clinical research were independent predictors of a high score, whereas treatment by a surgeon with a caseload in the lower tercile was associated with a low score. Socioeconomic characteristics such as income and education were not independent predictors, but patient's place of residence and age independently predicted management according to recommendations. Conclusion: Specialization and involvement in clinical research seem to be key elements for enhancing the quality of early breast cancer management at population leve