Determinants of blood and saliva lead concentrations in adult gardeners on urban agricultural sites

Soil Pb concentrations at urban agriculture sites (UAS) commonly exceed recommended safe levels. There is a lack of evidence regarding uptake of Pb by gardeners using such sites for food crops. Our study aimed to elucidate whether gardening in soil with raised Pb levels results in Pb body burdens of concern to health, and to assess confounding factors influencing Pb body burden. Our cross-sectional case study measured Pb in saliva and blood of UAS gardeners (n = 43), soil and produce samples from their UAS, and home tap water. Blood and saliva Pb concentrations were compared with those from non-UAS gardener controls (n = 29). A health risk threshold of 5 µg dL−1 blood Pb level (BLL) was selected in keeping with international guidance. Detailed surveys investigated individuals’ anthropometrics and potential Pb exposures from diet, and historic and everyday activities. Saliva was not found to be a suitable biomarker of adult Pb exposure in this context. Predictors of higher BLLs were being older, being male and eating more root vegetables and shrub fruit. Eating more green vegetables predicted a lower BLL, suggesting a protective effect against Pb uptake. UAS gardeners’ BLLs (geometric mean 1.53; range 0.6–4.1 µg dL−1) were not significantly higher (p = 0.39) than the control group (geometric mean 1.43; range 0.7–2.9 µg dL−1). All BLLs were below 5 µg dL−1 except one resulting from occupational exposure. Having paired the UAS gardeners with closely matched controls, we found Pb in UAS soils (with range 62–1300 mg kg−1from common urban sources) unlikely to pose an additional risk to adult health compared to their neighbours who did not access UAS. As such, other Pb sources may be the dominant factor controlling BLL

Candidate Gene Association Study in Type 2 Diabetes Indicates a Role for Genes Involved in β-Cell Function as Well as Insulin Action

Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenotypes in 2,134 Caucasians in a case-control study and an independent quantitative trait (QT) cohort in the United Kingdom. Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic β-cell function—ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4α), and INS (insulin)—significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. We examined 35 genes predicted to have their major influence on insulin action, and three (9%)—INSR, PIK3R1, and SOS1—showed significant associations with diabetes. These results confirm the genetic complexity of Type 2 diabetes and provide evidence that common variants in genes influencing pancreatic β-cell function may make a significant contribution to the inherited component of this disease. This study additionally demonstrates that the systematic examination of panels of biological candidate genes in large, well-characterised populations can be an effective complement to positional cloning approaches. The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to reliably identify the size of effect we now expect for complex diseases

Evaluation of two-year recall of self-reported pesticide exposure among Ugandan smallholder farmers

OBJECTIVES: To evaluate smallholder farmers' recall of pesticide use and exposure determinants over a two-year period in a low-income country context. METHODS: The Pesticide Use in Tropical Settings (PESTROP) study in Uganda consists of 302 smallholder farmers who were interviewed in 2017. In the same season in 2019, these farmers were re-questioned concerning pesticide use (e.g., use of active ingredients) and exposure information (e.g., crops, personal protective equipment [PPE], hygienic behaviours) they had previously provided. The extent of recall bias was assessed by comparing responses at follow-up in 2019 with practices and behaviours reported from the baseline interview in 2017. RESULTS: An 84% (n = 255) follow-up response rate was attained. We found instances of better recall (e.g., overall agreement >70% and Area Under the Curve (AUC) values > 0.7) for the use of some active ingredients, commonly used PPE items, and washing clothes after application, whereas only 13.3% could correctly recall their three major crops. We observed a trend where more individuals reported the use of active ingredients, while fewer reported the use of PPE items, two years later. In general, we found better agreement in the recall of years working with pesticides compared to hours per day or days per week in the field, with no apparent systematic over or under reporting by demographic characteristics. CONCLUSIONS: While some of these findings provide consistency with those from high-income countries, more research is needed on recall in poorly educated agriculture communities in low- and middle-income settings to confirm these results

Luminescencja jonów chromu w naturalnych krzemianach

This work presented here results of electron absorption and luminescence investigations of 14 natural silicates, which have contained chromium Cr3 + ion. The contents of it was from 0,02% and less (kunzite) to 11,2% (uvarovite). Many of minerals had also manganese, vanadium and iron admixture. Luminescence measurement as well as decay time were taken at room temperature and 77 K—4 K. The luminescence dependence on ligand crystal-field was analysed. Examples of strong and weak ligand crystal fields were demonstrated. Kammererite, pyrope, Cr-grossular, tsavorite, tanzanite, spodumene, emerald, Cr-idocrase, kotchubeite and two crystal sites in kyanite were include to the first group. Weak crystal-field was found for uwarowite, one crystal site in kyanite, fuchsite diopsyde and Cr-amphibole. The dependence of the 2E level splitting on ligand crystal field symmetry was mentioned. The smallest splitting (65 cm"1) was found for trigonal crystal field C3j in grossulars and emerald. For comparison in Cr-doped corundum the R-lines splitting is 29 cm"1. For tetragonal C4v crystal field in idocrase the splitting is 132 cm1 and the biggest are for triclinic and monoclinic symmetry in tanzanite and kyanite up to 335 cm *. The influence of the first and next-neighbour coordination on crystal field parameters was discussed for fuchsite and kotchubeite, diopside and spodumene and grossular and idocrase. The influence of other transition elements on chromium luminescence was found, too. In kyanite the chromium ions were presented in different crystal sites and among them the energy transfer was very probable. Vanadium ions were presented in tsavorite and tanzanite and the energy from chromium ions was passed on to them. It was the cause of unexpected short decay time. Because of manganese ions in spodumene the several different chromium sites were created and their decay time were short, either. For pyrope and Cr-amphibole the chromium luminescence were completely quenched for reason of iron high content. For two chromium chlorites-kammererite and kotchubeite — the clusters and Cr-Cr pairs were found. It was because of low luminescence intensity and short decay time of them. The influence of other transition ions presented in studied crystals and the high chromium content on luminescence properties was detected only qualitatively. Author had not enough examples of each kind of minerals with different contents of doped ions to discusse this problem quantitatively. The electronic and vibronic energy levels — strong and weak — were discussed. In this work for the first time the luminescence of Cr3 + ions in Cr-grossular, tsavorite, uvarovite, tanzanite, idocrase, diopside, fuchsite, kotchubeite and kammererite were presented and discussed. For the first time for chromium ions in minerals the energies of excited levels and crystal-field parameters were calculated for Cr-grossular, kyanite, tanzanite and idocrase

Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom

Background: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g., as estimated by biomonitoring) would be valuable. Methods: Urine samples were collected from pesticide applicators in Malaysia, Uganda, and the UK during mixing/application days (and also during non-application days in Uganda). Samples were collected pre- and post-activity on the same day and analysed for biomarkers of active ingredients (AIs), including synthetic pyrethroids (via the metabolite 3-phenoxybenzoic acid [3-PBA]) and glyphosate, as well as creatinine. We performed multilevel Tobit regression models for each study to assess the relationship between exposure modifying factors (e.g., mixing/application of AI, duration of activity, personal protective equipment [PPE]) and urinary biomarkers of exposure. Results: From the Malaysia, Uganda, and UK studies, 81, 84, and 106 study participants provided 162, 384 and 212 urine samples, respectively. Pyrethroid use on the sampling day was most common in Malaysia (n = 38; 47%), and glyphosate use was most prevalent in the UK (n = 93; 88%). Median pre- and post-activity 3-PBA concentrations were similar, with higher median concentrations post-compared to pre-activity for glyphosate samples in the UK (1.7 to 0.5 μg/L) and Uganda (7.6 to 0.8 μg/L) (glyphosate was not used in the Malaysia study). There was evidence from individual studies that higher urinary biomarker concentrations were associated with mixing/application of the AI on the day of urine sampling, longer duration of mixing/application, lower PPE protection, and less education/literacy, but no factor was consistently associated with exposure across biomarkers in the three studies. Conclusions: Our results suggest a need for AI-specific interpretation of exposure modifying factors as the relevance of exposure routes, levels of detection, and farming systems/practices may be very context and AI-specific

The Association Between the Peroxisome Proliferator-Activated Receptor-γ2 (PPARG2) Pro12Ala Gene Variant and Type 2 Diabetes Mellitus: A HuGE Review and Meta-Analysis

The peroxisome proliferator-activated receptor-γ gene (PPARG) has been implicated in the etiology of type 2 diabetes mellitus and has been investigated in numerous epidemiologic studies. In this Human Genome Epidemiology review, the authors assessed this relation in an updated meta-analysis of 60 association studies. Electronic literature searches were conducted on September 14, 2009. Population-based cohort, case-control, cross-sectional, or genome-wide association studies reporting associations between the PPARG Pro12Ala gene variant (rs1801282) and type 2 diabetes were included. An updated literature-based meta-analysis involving 32,849 type 2 diabetes cases and 47,456 controls in relation to the PPARG Pro12Ala variant was conducted. The combined overall odds ratio, calculated by per-allele genetic model random-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, was 0.86 (95% confidence interval: 0.81, 0.90). The analysis indicated a moderate level of heterogeneity attributable to genuine variation in gene effect size (I2 = 37%). This may reflect the variation observed between ethnic populations and/or differences in body mass index. Work on PPARG Pro12Ala should now focus on the observed heterogeneity in the magnitude of the association between populations. Further investigations into gene-gene and gene-environment interactions may prove enlightening

Consumers’ experiences of back pain in rural Western Australia: Access to information and services, and self-management behaviours.

Background: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. Methods: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals’ access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. Results: Five key themes were identified that affected individuals’ experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP.Conclusions: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse