Occupational exposure to pesticides and neurobehavioral outcomes. Impact of different original and recalled exposure measures on the associations.

BACKGROUND: Several measures of occupational exposure to pesticides have been used to study associations between exposure to pesticides and neurobehavioral outcomes. This study assessed the impact of different exposure measures for glyphosate and mancozeb on the association with neurobehavioral outcomes based on original and recalled self-reported data with 246 smallholder farmers in Uganda. METHODS: The association between the 6 exposure measures and 6 selected neurobehavioral test scores was investigated using linear multivariable regression models. Exposure measures included original exposure measures for the previous year in 2017: (i) application status (yes/no), (ii) number of application days, (iii) average exposure-intensity scores (EIS) of an application and (iv) number of EIS-weighted application days. Two additional measures were collected in 2019: (v) recalled application status and (vi) recalled EIS for the respective periods in 2017. RESULTS: Recalled applicator status and EIS were between 1.2 and 1.4 times more frequent and higher for both pesticides than the original application status and EIS. Adverse associations between the different original measures of exposure to glyphosate and 4 neurobehavioral tests were observed. Glyphosate exposure based on recalled information and all mancozeb exposure measures were not associated with the neurobehavioral outcomes. CONCLUSIONS: The relation between the different original self-reported glyphosate exposure measures and neurobehavioral test scores appeared to be robust. When based on recalled exposure measures, associations observed with the original exposure measures were no longer present. Therefore, future epidemiological studies on self-reported exposure should critically evaluate the potential bias towards the null in observed exposure-response associations.

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.

Elevated 2-oxoglutarate antagonizes DNA damage responses in cholangiocarcinoma chemotherapy through regulating aspartate beta-hydroxylase.

Cholangiocarcinoma (CCA) is resistant to systemic chemotherapies that kill malignant cells mainly through DNA damage responses (DDRs). Recent studies suggest that the involvement of 2-oxoglutarate (2-OG) dependent dioxygenases in DDRs may be associated with chemoresistance in malignancy, but how 2-OG impacts DDRs in CCA chemotherapy remains elusive. We examined serum 2-OG levels in CCA patients before receiving chemotherapy. CCA patients are classified as progressive disease (PD), partial response (PR), and stable disease (SD) after receiving chemotherapy. CCA patients classified as PD showed significantly higher serum 2-OG levels than those defined as SD and PR. Treating CCA cells with 2-OG reduced DDRs. Overexpression of full-length aspartate beta-hydroxylase (ASPH) could mimic the effects of 2-OG on DDRs, suggesting the important role of ASPH in chemoresistance. Indeed, the knockdown of ASPH improved chemotherapy in CCA cells. Targeting ASPH with a specific small molecule inhibitor also enhanced the effects of chemotherapy. Mechanistically, ASPH modulates DDRs by affecting ATM and ATR, two of the major regulators finely controlling DDRs. More importantly, targeting ASPH improved the therapeutic potential of chemotherapy in two preclinical CCA models. Our data suggested the impacts of elevated 2-OG and ASPH on chemoresistance through antagonizing DDRs. Targeting ASPH may enhance DDRs, improving chemotherapy in CCA patients.

Potential contribution of vaccination uptake to occupational differences in risk of SARS-CoV-2: analysis of the ONS COVID-19 Infection Survey.

OBJECTIVES: To assess variation in vaccination uptake across occupational groups as a potential explanation for variation in risk of SARS-CoV-2 infection. DESIGN: We analysed data from the UK Office of National Statistics COVID-19 Infection Survey linked to vaccination data from the National Immunisation Management System in England from 1 December 2020 to 11 May 2022. We analysed vaccination uptake and SARS-CoV-2 infection risk by occupational group and assessed whether adjustment for vaccination reduced the variation in risk between occupational groups. RESULTS: Estimated rates of triple vaccination were high across all occupational groups (80% or above), but were lowest for food processing (80%), personal care (82%), hospitality (83%), manual occupations (84%) and retail (85%). High rates were observed for individuals working in health (95% for office based, 92% for those in patient-facing roles) and education (91%) and office-based workers not included in other categories (90%). The impact of adjusting for vaccination when estimating relative risks of infection was generally modest (ratio of hazard ratios across all occupational groups reduced from 1.37 to 1.32), but was consistent with the hypothesis that low vaccination rates contribute to elevated risk in some groups. CONCLUSIONS: Variation in vaccination coverage might account for a modest proportion of occupational differences in infection risk. Vaccination rates were uniformly very high in this cohort, which may suggest that the participants are not representative of the general population. Accordingly, these results should be considered tentative pending the accumulation of additional evidence.

Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

OBJECTIVE: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda. METHODS: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers. Also in the 84 farmers the measured pre-work and post-work biomarker concentrations were used (8). Multivariable logistic regression models were used to assess the association between the exposure measures and selected Medical Outcomes Study Sleep Scale (MOS-SS) indices (6-item, sleep inadequacy and snoring). RESULTS: We observed positive associations between (1) any pesticide application in the last 7 days with all three MOS-SS indices. Glyphosate application in the last 7 days (3) and mancozeb application in the last 12 months (3) were associated with the 6-item sleep problem index. The estimated average urinary glyphosate concentrations showed an exposure-response association with the 6-item sleep problem index and sleep inadequacy in the same direction as based on self-reported glyphosate application in the last 7 days. In the analysis with the subset of 84 farmers, both measured and modelled post-work urinary glyphosate concentration showed an association with snoring. CONCLUSIONS: Self-reported, estimated average biomarker concentrations and measured urinary biomarker exposure measures of glyphosate and mancozeb showed similar exposure-response associations with sleep outcomes.

Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities.

NGLY1 deficiency: a prospective natural history study.

N-glycanase 1 (NGLY1) deficiency is a debilitating, ultra-rare autosomal recessive disorder caused by loss of function of NGLY1, a cytosolic enzyme that deglycosylates other proteins. It is characterized by severe global developmental delay and/or intellectual disability, hyperkinetic movement disorder, transient elevation of transaminases, (hypo)alacrima and progressive, diffuse, length-dependent sensorimotor polyneuropathy. A prospective natural history study (NHS) was conducted to elucidate clinical features and disease course. Twenty-nine participants were enrolled (15 onsite, 14 remotely) and followed for up to 32 months, representing ~29% of the ~100 patients identified worldwide. Participants exhibited profound developmental delays, with almost all developmental quotients below 20 on the Mullen Scales of Early Learning, well below the normative score of 100. Increased difficulties with sitting and standing suggested decline in motor function over time. Most patients presented with (hypo)alacrima and reduced sweat response. Pediatric quality of life was poor except for emotional function. Language/communication and motor skill problems including hand use were reported by caregivers as the most bothersome symptoms. Levels of the substrate biomarker, GlcNAc-Asn (aspartylglucosamine; GNA), were consistently elevated in all participants over time, independent of age. Liver enzymes were elevated for some participants but improved especially in younger patients and did not reach levels indicating severe liver disease. Three participants died during the study period. Data from this NHS informs selection of endpoints and assessments for future clinical trials for NGLY1 deficiency interventions. Potential endpoints include GNA biomarker levels, neurocognitive assessments, autonomic and motor function (particularly hand use), (hypo)alacrima and quality of life.

Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in N -glycanase 1 deficient Drosophila.

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N -glycanase 1 (Pngl) leads to gut barrier defects, which cause starvation and increased JNK activity. These defects result in Foxo overactivation, which induces a hyperactive innate immune response and lipid catabolism, thereby contributing to lethality associated with loss of Pngl . Notably, germ-free rearing of Pngl mutants did not rescue lethality. In contrast, raising Pngl mutants on isocaloric, fat-rich diets improved animal survival in a dosage-dependent manner. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the immune and metabolic consequences of loss of Pngl are primarily mediated through non-infectious mechanisms.

Establishing relationships between particle-induced in vitro and in vivo inflammation endpoints to better extrapolate between in vitro markers and in vivo fibrosis.

BACKGROUND: Toxicity assessment for regulatory purposes is starting to move away from traditional in vivo methods and towards new approach methodologies (NAM) such as high-throughput in vitro models and computational tools. For materials with limited hazard information, utilising quantitative Adverse Outcome Pathways (AOPs) in a testing strategy involving NAM can produce information relevant for risk assessment. The aim of this work was to determine the feasibility of linking in vitro endpoints to in vivo events, and moreover to key events associated with the onset of a chosen adverse outcome to aid in the development of NAM testing strategies. To do this, we focussed on the adverse outcome pathway (AOP) relating to the onset of pulmonary fibrosis. RESULTS: We extracted in vivo and in vitro dose-response information for particles known to induce this pulmonary fibrosis (crystalline silica, specifically α-quartz). To test the in vivo-in vitro extrapolation (IVIVE) determined for crystalline silica, cerium dioxide nanoparticles (nano-CeO2) were used as a case study allowing us to evaluate our findings with a less studied substance. The IVIVE methodology outlined in this paper is formed of five steps, which can be more generally summarised into two categories (i) aligning the in vivo and in vitro dosimetry, (ii) comparing the dose-response curves and derivation of conversion factors. CONCLUSION: Our analysis shows promising results with regards to correlation of in vitro cytokine secretion to in vivo acute pulmonary inflammation assessed by polymorphonuclear leukocyte influx, most notable is the potential of using IL-6 and IL-1ß cytokine secretion from simple in vitro submerged models as a screening tool to assess the likelihood of lung inflammation at an early stage in product development, hence allowing a more targeted investigation using either a smaller, more targeted in vivo study or in the future a more complex in vitro protocol. This paper also highlights the strengths and limitations as well as the current difficulties in performing IVIVE assessment and suggestions for overcoming these issues.

An Ecological Study of COVID-19 Infection Rates within the UK Food and Drink Processing Industry.

OBJECTIVES: Food processing facilities represent critical infrastructure that have stayed open during much of the COVID-19 pandemic. Understanding the burden of COVID-19 in this sector is thus important to help reduce the potential for workplace infection in future outbreaks. METHODS: We undertook a workplace survey in the UK food and drink processing sector and collected information on workplace size, characteristics (e.g. temperature, ventilation), and experience with COVID-19 (e.g. numbers of positive cases). For each site, we calculated COVID-19 case rates per month per 1000 workers. We performed an ecological analysis using negative binomial regression to assess the association between COVID-19 rates and workplace and local risk factors. RESULTS: Respondents from 33 companies including 66 individual sites completed the survey. COVID-19 cases were reported from the start of the pandemic up to June 2021. Respondents represented a range of industry subgroups, including grain milling/storage (n = 16), manufacture of malt (n = 14), manufacture of prepared meals (n = 12), manufacture of beverages (n = 8), distilling (n = 5), manufacture of baked goods (n = 5), and other (n = 6), with a total of 15 563 workers across all sites. Average monthly case rates per 1000 workers ranged from 0.9 in distilling to 6.1 in grain milling/storage. Incidence rate ratios were partially attenuated after adjusting for several local and workplace factors, though risks for one subgroup (grain milling/storage) remained elevated. Certain local and workplace characteristics were related to higher infection rates, such as higher deprivation (5 km only), a lower proportion of remote workers, lower proportion of workers in close proximity, and higher numbers of workers overall. CONCLUSIONS: Our analysis suggests some heterogeneity in the rates of COVID-19 across sectors of the UK food and drink processing industry. Infection rates were associated with deprivation, the proportions of remote workers and workers in close proximity, and the number of workers.

Exploring the relationship between job characteristics and infection: Application of a COVID-19 job exposure matrix to SARS-CoV-2 infection data in the United Kingdom.

OBJECTIVE: This study aimed to assess whether workplace exposures as estimated via a COVID-19 job exposure matrix (JEM) are associated with SARS-CoV-2 in the UK. METHODS: Data on 244 470 participants were available from the Office for National Statistics Coronavirus Infection Survey (CIS) and 16 801 participants from the Virus Watch Cohort, restricted to workers aged 20-64 years. Analysis used logistic regression models with SARS-CoV-2 as the dependent variable for eight individual JEM domains (number of workers, nature of contacts, contact via surfaces, indoor or outdoor location, ability to social distance, use of face covering, job insecurity, and migrant workers) with adjustment for age, sex, ethnicity, index of multiple deprivation (IMD), region, household size, urban versus rural area, and health conditions. Analyses were repeated for three time periods (i) February 2020 (Virus Watch)/April 2020 (CIS) to May 2021), (ii) June 2021 to November 2021, and (iii) December 2021 to January 2022. RESULTS: Overall, higher risk classifications for the first six domains tended to be associated with an increased risk of infection, with little evidence of a relationship for domains relating to proportion of workers with job insecurity or migrant workers. By time there was a clear exposure-response relationship for these domains in the first period only. Results were largely consistent across the two UK cohorts. CONCLUSIONS: An exposure-response relationship exists in the early phase of the COVID-19 pandemic for number of contacts, nature of contacts, contacts via surfaces, indoor or outdoor location, ability to social distance and use of face coverings. These associations appear to have diminished over time.

AAV9-NGLY1 gene replacement therapy improves phenotypic and biomarker endpoints in a rat model of NGLY1 Deficiency.

N-glycanase 1 (NGLY1) Deficiency is a progressive, ultra-rare, autosomal recessive disorder with no approved therapy and five core clinical features: severe global developmental delay, hyperkinetic movement disorder, elevated liver transaminases, alacrima, and peripheral neuropathy. Here, we confirmed and characterized the Ngly1 -/- / rat as a relevant disease model. GS-100, a gene therapy candidate, is a recombinant, single-stranded adeno-associated virus (AAV) 9 vector designed to deliver a functional copy of the human NGLY1 gene. Using the Ngly1 -/- rat, we tested different administration routes for GS-100: intracerebroventricular (ICV), intravenous (IV), or the dual route (IV + ICV). ICV and IV + ICV administration resulted in widespread biodistribution of human NGLY1 DNA and corresponding mRNA and protein expression in CNS tissues. GS-100 delivered by ICV or IV + ICV significantly reduced levels of the substrate biomarker N-acetylglucosamine-asparagine (GlcNAc-Asn or GNA) in CSF and brain tissue compared with untreated Ngly1-/- rats. ICV and IV + ICV administration of GS-100 resulted in behavioral improvements in rotarod and rearing tests, whereas IV-only administration did not. IV + ICV did not provide additional benefit compared with ICV administration alone. These data provide evidence that GS-100 could be an effective therapy for NGLY1 Deficiency using the ICV route of administration.

Transmission and Control of SARS-CoV-2 in the Food Production Sector: A Rapid Narrative Review of the Literature.

This review aimed to provide an overview of the literature assessing the extent of COVID-19 transmission in the food processing sector along with the risk factors associated with COVID-19 infection/mortality rates in this setting, and the preventive measures used to reduce transmission. An electronic search was conducted using scientific databases, including Web of Science, OVID, PubMed and MedRxiv. The search strategy identified 26 papers that met the inclusion criteria. Six of these studies were based in the UK and the country with the most papers was the USA, with a total of nine papers. Findings showed some evidence of a high transmission level of SARS-CoV-2 within some areas of the food production sector. Risk factors associated with the spread included ethnicity, poor ventilation, lack of social distancing and lack of sick pay. The preventative measures included/recommended were social distancing, testing, adequate ventilation, cleaning regimes and access to PPE. Additional research focusing on the food production sector could show the potential variations in transmission and risk between each sub-sector. Future research focusing on the application of various preventative measures and their efficacy by sub-sector would be beneficial, while further qualitative research could help provide in-depth information regarding knowledge gaps.

Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting.

BACKGROUND: Worldwide 85% of cervical cancer (CC) related deaths occur in low- and middle-income countries. Sub-Saharan Africa is burdend by an overlapping high incidence of CC as well as HIV infection, a risk factor for HPV associated disease progression. Recent upscaling of CC screening activities increased the number of CC diagnoses in a previous unscreened population. The aim of the 2H study was to follow up on women with CC in the context of available health care services in Tanzania in relation to their HIV infection status. METHODS: This longitudinal observational cohort study included women with histological confirmed CC from Mbeya, Tanzania, between 2013-2019. All women were referred for CC staging and cancer-directed therapies (CDT), including surgery and/or radio-chemotherapy, or palliative care. Annual follow-up focused on successful linkage to CDT, interventions and survival. We assessed factors on compliance, used Kaplan-Meier-Survivor functions to evaluate survival time and poisson regression models to calculate incidence rate ratios on mortality (IRR) two years after diagnosis. RESULTS: Overall, 270 women with CC (123 HIV infected) were included. Staging information, available in 185 cases, showed 84.9% presented with advanced stage disease (FIGO ≥ IIB), no difference was seen in respect to HIV status. HIV-infected women were 12 years younger at the time of cancer diagnosis (median age 44.8 versus 56.4 years, p < 0.001). Median follow up period was 11.9 months (range 0.2-67.2). Survival information, available in 231 cases, demonstrated for women diagnosed in early-stage disease a median survival time of 38.3 months, in advanced-stage 16.0 months and late-stage disease 6.5 months after diagnosis. Of all women, 42% received CDT or palliative support. HIV co-infection and education were associated with higher health care compliance. CDT was significantly associated with lower 2-year mortality rates (IRR 0.62, p = 0.004). HIV coinfection did not impact mortality rates after diagnosis. CONCLUSION: High numbers of advanced and late staged CC were diagnosed, compliance to CDT was low. A beneficial impact of CDT on CC mortality could be demonstrated for local health care services. This study indicates challenges for successful linkage and supports an effective scale up of cancer care and treatment facilities.

Occupational differences in SARS-CoV-2 infection: analysis of the UK ONS COVID-19 infection survey.

BACKGROUND: Concern remains about how occupational SARS-CoV-2 risk has evolved during the COVID-19 pandemic. We aimed to ascertain occupations with the greatest risk of SARS-CoV-2 infection and explore how relative differences varied over the pandemic. METHODS: Analysis of cohort data from the UK Office of National Statistics COVID-19 Infection Survey from April 2020 to November 2021. This survey is designed to be representative of the UK population and uses regular PCR testing. Cox and multilevel logistic regression were used to compare SARS-CoV-2 infection between occupational/sector groups, overall and by four time periods with interactions, adjusted for age, sex, ethnicity, deprivation, region, household size, urban/rural neighbourhood and current health conditions. RESULTS: Based on 3 910 311 observations (visits) from 312 304 working age adults, elevated risks of infection can be seen overall for social care (HR 1.14; 95% CI 1.04 to 1.24), education (HR 1.31; 95% CI 1.23 to 1.39), bus and coach drivers (1.43; 95% CI 1.03 to 1.97) and police and protective services (HR 1.45; 95% CI 1.29 to 1.62) when compared with non-essential workers. By time period, relative differences were more pronounced early in the pandemic. For healthcare elevated odds in the early waves switched to a reduction in the later stages. Education saw raises after the initial lockdown and this has persisted. Adjustment for covariates made very little difference to effect estimates. CONCLUSIONS: Elevated risks among healthcare workers have diminished over time but education workers have had persistently higher risks. Long-term mitigation measures in certain workplaces may be warranted.

Longitudinal changes in proportionate mortality due to COVID-19 by occupation in England and Wales.

OBJECTIVE: This study aimed to understand whether the proportionate mortality of COVID-19 for various occupational groups has varied over the pandemic. METHODS: We used the Office for National Statistics (ONS) mortality data for England and Wales. The deaths (20-64 years) were classified as either COVID-19-related using ICD-10 codes (U07.1, U07.2), or from other causes. Occupational data recorded at the time of death was coded using the SOC10 coding system into 13 groups. Three time periods (TP) were used: (i) January 2020 to September 2020; (ii) October 2020-May 2021; and (iii) June 2021-October 2021. We analyzed the data with logistic regression and compared odds of death by COVID-19 to other causes, adjusting for age, sex, deprivation, region, urban/rural and population density. RESULTS: Healthcare professionals and associates had a higher proportionate odds of COVID-19 death in TP1 compared to non-essential workers but were not observed to have increased odds thereafter. Medical support staff had increased odds of death from COVID-19 during both TP1 and TP2, but this had reduced by TP3. This latter pattern was also seen for social care, food retail and distribution, and bus and coach drivers. Taxi and cab drivers were the only group that had higher odds of death from COVID-19 compared to other causes throughout the whole period under study [TP1: odds ratio (OR) 2.42, 95% confidence interval (CI) 1.99-2.93; TP2: OR 3.15, 95% CI 2.63-3.78; TP3: OR 1.7, 95% CI 1.26-2.29]. CONCLUSION: Differences in the odds of death from COVID-19 between occupational groups has declined over the course of the pandemic, although some occupations have remained relatively high throughout.

The relationship between greenspace and personal exposure to PM2.5 during walking trips in Delhi, India.

The presence of urban greenspace may lead to reduced personal exposure to air pollution via several mechanisms, for example, increased dispersion of airborne particulates; however, there is a lack of real-time evidence across different urban contexts. Study participants were 79 adolescents with asthma who lived in Delhi, India and were recruited to the Delhi Air Pollution and Health Effects (DAPHNE) study. Participants were monitored continuously for exposure to PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 µm) for 48 h. We isolated normal day-to-day walking journeys (n = 199) from the personal monitoring dataset and assessed the relationship between greenspace and personal PM2.5 using different spatial scales of the mean Normalised Difference Vegetation Index (NDVI), mean tree cover (TC), and proportion of surrounding green land use (GLU) and parks or forests (PF). The journeys had a mean duration of 12.7 (range 5, 53) min and mean PM2.5 personal exposure of 133.9 (standard deviation = 114.8) µg/m3. The within-trip analysis showed weak inverse associations between greenspace markers and PM2.5 concentrations only in the spring/summer/monsoon season, with statistically significant associations for TC at the 25 and 50 m buffers in adjusted models. Between-trip analysis also indicated inverse associations for NDVI and TC, but suggested positive associations for GLU and PF in the spring/summer/monsoon season; no overall patterns of association were evident in the autumn/winter season. Associations between greenspace and personal PM2.5 during walking trips in Delhi varied across metrics, spatial scales, and season, but were most consistent for TC. These mixed findings may partly relate to journeys being dominated by walking along roads and small effects on PM2.5 of small pockets of greenspace. Larger areas of greenspace may, however, give rise to observable spatial effects on PM2.5, which vary by season.

Exposure to urban greenspace and pathways to respiratory health: An exploratory systematic review.

BACKGROUND/OBJECTIVE: Urban greenspace may have a beneficial or adverse effect on respiratory health. Our objective was to perform an exploratory systematic review to synthesise the evidence and identify the potential causal pathways relating urban greenspace and respiratory health. METHODS: We followed PRISMA guidelines on systematic reviews and searched five databases for eligible studies during 2000-2021. We incorporated a broad range of urban greenspace and respiratory health search terms, including both observational and experimental studies. Screening, data extraction, and risk of bias, assessed using the Navigation Guide criteria, were performed independently by two authors. We performed a narrative synthesis and discuss suggested pathways to respiratory health. RESULTS: We identified 108 eligible papers (n = 104 observational, n = 4 experimental). The most common greenspace indicators were the overall greenery or vegetation (also known as greenness), green land use/land cover of physical area classes (e.g., parks, forests), and tree canopy cover. A wide range of respiratory health indicators were studied, with asthma prevalence being the most common. Two thirds (n = 195) of the associations in these studies were positive (i.e., beneficial) with health, with 31% (n = 91) statistically significant; only 9% (n = 25) of reported associations were negative (i.e., adverse) with health and statistically significant. The most consistent positive evidence was apparent for respiratory mortality. There were n = 35 (32%) 'probably low' and n = 73 (68%) 'probably high' overall ratings of bias. Hypothesised causal pathways for health benefits included lower air pollution, more physically active populations, and exposure to microbial diversity; suggested mechanisms with poorer health included exposure to pollen and other aeroallergens. CONCLUSION: Many studies showed positive association between urban greenspace and respiratory health, especially lower respiratory mortality; this is suggestive, but not conclusive, of causal effects. Results underscore the importance of contextual factors, greenspace metric employed, and the potential bias of subtle selection factors, which should be explored further.

Recall of exposure in UK farmers and pesticide applicators: trends with follow-up time.

BACKGROUND: Occupational epidemiological studies on pesticide use commonly rely on self-reported questionnaire or interview data to assess exposure. Insight into recall accuracy is important, as misclassification of exposures due to imperfect recall can bias risk estimates. METHODS: We assessed the ability of workers in three UK cohorts (Prospective Investigation of Pesticide Applicators' Health [PIPAH], Pesticide Users' Health Study [PUHS], and Study of Health in Agricultural Work [SHAW]) to remember their working history related to pesticide exposure over time periods ranging from 3 to 14 years prior. During 2019-2020, cohort participants were re-surveyed using a similar questionnaire to that used previously. We compared recall of responses at follow-up to those reported at baseline related to crops/areas of work, use of personal protective equipment (PPE) items, hygiene habits, frequency of pesticide use, and application method. To assess the extent of recall, we used sensitivity, specificity, the percentage of overall agreement, and area under the curve (AUC) values. We also examined the presence of over or underestimation of recalled years, and days and hours per year, of working with pesticides using geometric mean ratios (GMR) and regression analysis to investigate any trends based on demographic characteristics. RESULTS: There were 643 individuals who completed both the baseline and follow-up surveys in the three cohorts with response rates ranging from 17 to 46%. There was a strong correlation (rho = 0.77) between the baseline and recalled years working with pesticides, though higher values were reported at follow-up (GMR = 1.18 [95% confidence interval: 1.07-1.30]) with no consistent differences by demographic characteristics. There was stronger agreement in the recalled days compared to hours per year in two of the cohorts. Recall for a number of exposure determinants across short and longer periods entailed overall agreement of >70%, though with some differences: for example, sensitivity for long-term recall of crops was poor (<43% in PUHS), whereas short-term recall of hygiene practices was good (AUC range = 0.65-1.00 in PIPAH). CONCLUSION: Results indicate that recall ability may deteriorate over a longer period. Although low-response rates may require these findings to be interpreted with caution, recall for a number of exposure determinants appeared reliable, such as crops and hygiene practices within 3 years, as well as days per year working with pesticides.

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.