Emotional stress as a trigger of falls leading to hip or pelvic fracture. Results from the ToFa study – a case-crossover study among elderly people in Stockholm, Sweden

<p>Abstract</p> <p>Background</p> <p>Sudden emotions may interfere with mechanisms for keeping balance among the elderly. The aim of this study is to analyse if emotional stress and specifically feelings of anger, sadness, worries, anxiety or stress, can trigger falls leading to hip or pelvic fracture among autonomous older people.</p> <p>Methods</p> <p>The study applied the case-crossover design and was based on data gathered by face to face interviews carried out in Stockholm between November 2004 and January 2006 at the emergency wards of two hospitals. Cases (n = 137) were defined as persons aged 65 and older admitted for at least one night due to a fall-related hip or pelvic fracture (ICD10: S72 or S32) and meeting a series of selection criteria. Results are presented as relative risks with 95% confidence intervals.</p> <p>Results</p> <p>There was an increased risk for fall and subsequent hip or pelvic fracture for up to one hour after emotional stress. For anger there was an increased relative risk of 12.2 (95% CI 2.7–54.7), for sadness of 5.7 (95% CI 1.1–28.7), and for stress 20.6 (95% CI 4.5–93.5) compared to periods with no such feelings.</p> <p>Conclusion</p> <p>Emotional stress seems to have the potential to trigger falls and subsequent hip or pelvic fracture among autonomous older people. Further studies are needed to clarify how robust the findings are – as the number of exposed cases is small – and the mechanisms behind them – presumably balance and vision impairment in stress situation.</p

Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden.

BACKGROUND: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport. OBJECTIVES: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined. METHODS: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants. RESULTS: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60. DISCUSSION: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure

Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study

BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk

Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet

Introduction: Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development. Methods: The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes. Results: GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers. Conclusions: Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes

Socio-demographic, lifestyle and health characteristics among snus users and dual tobacco users in Stockholm County, Sweden

<p>Abstract</p> <p>Background</p> <p>Socio-demographic and lifestyle characteristics of snus users have not been systematically described. Such knowledge is pivotal for tobacco control efforts and for the assessment of health effects of snus use.</p> <p>Methods</p> <p>A cross-sectional study was conducted, based on the Stockholm Public Health Survey, including a population-based sample of 34,707 men and women aged 18-84 years. We examined how socio-demographic, lifestyle and health-related characteristics were associated with the prevalence of current daily snus use, smoking and dual tobacco use. Logistic regression was used to calculate odds ratios of prevalence (ORs) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>Low educational level (OR = 1.60, CI = 1.41-1.81 and OR = 1.49, CI = 1.17-1.89, for men and women respectively), as well as occupational class and low income were associated with snus use. Some unfavourable lifestyle characteristics, including risky alcohol consumption (males: OR = 1.81, CI = 1.63-2.02; females: OR = 1.79, CI = 1.45-2.20), binge drinking and low consumption of fruit and vegetables were also associated with snus use. In contrast, physical inactivity and overweight/obesity were not, nor was perceived health. The prevalence of smoking followed steeper gradients for social as well as lifestyle characteristics. Overweight and obese men were however less often smokers. Perceived poor general health and psychological distress were highly related to smoking. Social disadvantage, as well as unhealthy lifestyle and self-reported poor health were strongly associated with dual use. There were limited differences between men and women.</p> <p>Conclusions</p> <p>The social, lifestyle and health profiles of exclusive snus users in Stockholm County are less favourable than those of non-users of tobacco, but more advantageous than those of exclusive smokers. This knowledge should guide tobacco control measures as well as the interpretation of health risks linked to snus use.</p

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology