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Air pollution exposure is associated with adverse respiratory health outcomes. Evidence from occupational and community-based studies also suggests agricultural pesticides have negative health impacts on respiratory health. Although populations are exposed to multiple inhalation hazards simultaneously, multidomain mixtures (e.g. environmental and chemical pollutants of different classes) are rarely studied. We investigated the association of ambient air pollution-pesticide exposure mixtures with urinary leukotriene E4 (LTE4), a respiratory inflammation biomarker, for 75 participants in four Central California communities over two seasons. Exposures included three criteria air pollutants estimated via the Community Multiscale Air Quality model (fine particulate matter, ozone, and nitrogen dioxide) and urinary metabolites of organophosphate (OP) pesticides (total dialkyl phosphates (DAPs), total diethyl phosphates (DE), and total dimethyl phosphates (DM)). We implemented multiple linear regression models to examine associations in single pollutant models adjusted for age, sex, asthma status, occupational status, household member occupational status, temperature, and relative humidity, and evaluated whether associations changed seasonally. We then implemented Bayesian kernel machine regression (BKMR) to analyse these criteria air pollutants, DE, and DM as a mixture. Our multiple linear regression models indicated an interquartile range (IQR) increase in total DAPs was associated with an increase in urinary LTE4 in winter ( β : 0.04, 95% CI: [0.01, 0.07]). Similarly, an IQR increase in total DM was associated with an increase in urinary LTE4 in winter ( β :0.03, 95% CI: [0.004, 0.06]). Confidence intervals for all criteria air pollutant effect estimates included the null value. BKMR analysis revealed potential non-linear interactions between exposures in our air pollution-pesticide mixture, but all confidence intervals contained the null value. Our analysis demonstrated a positive association between OP pesticide metabolites and urinary LTE4 in a low asthma prevalence population and adds to the limited research on the joint effects of ambient air pollution and pesticides mixtures on respiratory health., (© 2024 The Author(s). Published by IOP Publishing Ltd.)

Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Challenges arise in researching health effects associated with chemical mixtures. Several methods have recently been proposed for estimating the association between health outcomes and exposure to chemical mixtures, but a formal simulation study comparing broad-ranging methods is lacking. We select five recently developed methods and evaluate their performance in estimating the exposure-response function, identifying active mixture components, and identifying interactions in a simulation study. Bayesian kernel machine regression (BKMR) and nonparametric Bayes shrinkage (NPB) were top-performing methods in our simulation study. BKMR and NPB outperformed other contemporary methods and traditional linear models in estimating the exposure-response function and identifying active mixture components. BKMR and NPB produced similar results in a data analysis of the effects of multipollutant exposure on lung function in children with asthma., Competing Interests: The authors have declared that no competing interests exist.

Background: Ambient environmental pollutants have been shown to adversely affect respiratory health in susceptible populations. However, the role of simultaneous exposure to multiple diverse environmental pollutants is poorly understood., Objective: We applied a multidomain, multipollutant approach to assess the association between pediatric lung function measures and selected ambient air pollutants and pesticides., Methods: Using data from the US EPA and California Pesticide Use Registry, we reconstructed three months prior exposure to ambient air pollutants ((ozone (O 3 ), nitrogen dioxide (NO 2 ), particulate matter with a median aerodynamic diameter < 2.5 μm (PM 2.5 ) and <10 μm (PM 10 )) and pesticides (organophosphates (OP), carbamates (C) and methyl bromide (MeBr)) for 153 children with mild intermittent or mild persistent asthma from the San Joaquin Valley of California, USA. We implemented Bayesian kernel machine regression (BKMR) to estimate the association between simultaneous exposures to air pollutants and pesticides and lung function measures (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75 ))., Results: In BKMR analysis, the overall effect of mixtures (pollutants and pesticides) was associated with reduced FEV 1 and FVC, particularly when all the environmental exposures were above their 60th percentile. For example, the effect of the overall mixture at the 70th percentile (compared to the median) was a -0.12SD (-50 mL, 95% CI: -180 mL, 90 mL) change in the FEV 1 and a -0.18SD (-90 mL, 95% CI: -240 mL, 60 mL) change in the FVC. However, 95% credible intervals around all of the joint effect estimates contained the null value., Conclusion: At this agricultural-urban interface, we observed results from multipollutant analyses, suggestive of adverse effects on some pediatric lung function measures following a cumulative increase in ambient air pollutants and agricultural pesticides. Given the uncertainty in effect estimates, this approach should be explored in larger studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives : We explored the short-term impact of pesticide exposure on asthma exacerbation among children with asthma in an agricultural community. Methods : We obtained repeated urine samples from a subset of 16 school-age children with asthma (n = 139 samples) as part of the Aggravating Factors of Asthma in a Rural Environment (AFARE) study cohort. Biomarkers of organophosphate (OP) pesticide exposure (dialkylphosphates (DAPs)), and asthma exacerbation (leukotriene E4 (uLTE4)) were assessed in urine samples. We used generalized estimating equations to examine the association of summed measures of creatinine-adjusted DAPs (total dimethyl alkylphosphate (EDM), total diethyl alkylphosphate (EDE), and total dialkylphosphate pesticides (EDAP)) and uLTE4 concentration, adjusting for multiple confounders, yielding beta-coefficients with 95% CIs. Results : A total of 139 observations were obtained from the 16 children over the study period, the total number of samples per subject ranged from 1 to 12 (median: 10.5). The geometric mean (GM) of creatinine-adjusted EDE, EDM, and EDAP in this population were 81.0, 71.8 and 168.0 nmol/g, respectively. Increase in uLTE4 levels was consistently associated with increased exposures to DAPs (interquartile range in μg/g): β EDE : 8.7 (95%CI: 2.8, 14.6); β EDM : 1.1 (0.5, 1.7); β EDAP : 4.1 (0.7, 7.5). Conclusion : This study suggests that short-term OP exposure is associated with a higher risk of asthma morbidity, as indicated by increased uLTE4 levels in this cohort of children with asthma in an agricultural community. Additional studies are required to confirm these adverse effects, and explore the mechanisms underlying this relationship.

Sphingolipid metabolism is being increasingly recognized as a key pathway in regulating cancer cell survival and proliferation. However, very little is known about its role in multiple myeloma (MM). We investigated the potential of targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2 was overexpressed in MM cell lines and in primary human bone marrow (BM) CD1381 myeloma cells. Inhibition of SK2 by SK2- specific short hairpin RNA or ABC294640 (a SK2 specific inhibitor) effectively inhibited myeloma cell proliferation and induced caspase 3–mediated apoptosis. ABC294640 inhibited primary human CD1381 myeloma cells with the same efficacy as with MM cell lines. ABC294640 effectively induced apoptosis of myeloma cells, even in the presence of BM stromal cells. Furthermore, we found that ABC294640 downregulated the expression of pS6 and directed c-Myc and myeloid cell leukemia 1 (Mcl-1) for proteasome degradation. In addition, ABC294640 increased Noxa gene transcription and protein expression. ABC294640, per se, did not affect the expression of B-cell lymphoma 2 (Bcl-2), but acted synergistically with ABT-737 (a Bcl-2 inhibitor) in inducing myeloma cell death. ABC294640 suppressed myeloma tumor growth in vivo in mouse myeloma xenograft models. Our data demonstrated that SK2 provides a novel therapeutic target for the treatment of MM.This trial was registered at www.clinicaltrials.gov as #NCT01410981.

This paper describes a hypothetical case of a HIV positive pilot. It explores legal and ethical aspects of medical confidentiality and discusses who, inside and outside military and medical circles, can be told of his condition in the light of the particular circumstances. Disclosure without the patient's consent is a serious step that should not be undertaken without advice from Service medico-legal departments and medical protection organisations.

Recent changes in the law and in patients' expectations have necessitated alterations to the way doctors maintain the medical confidentiality of their patients. This paper investigates the ethical and legal aspects of medical confidentiality in general, examines their relation to the military context and analyses the guidance offered. Military personnel give up some individual rights on enlistment. The requirement for the medical officer to share patients' medical information, without consent if necessary, with the Commanding Officer is ethically and legally acceptable provided recruits are adequately warned of this restriction to human rights before joining. Although the paper concentrates on the guidance given in the RAF, the principles are common to the 3 Armed Forces' medical services.

Objective: To review the clinical findings in the first 1000 veterans seen in the Ministry of Defence's Gulf war medical assessment programme to examine whether there was a particular illness related to service in the Gulf., Design: Case series of 1000 veterans who presented to the programme between 11 October 1993 and 24 February 1997., Subjects: Gulf war veterans., Main Outcome Measures: Diagnosis of veterans' conditions according to ICD-10 (international classification of diseases, 10th revision). Cases referred for psychiatric assessment were reviewed for available diagnostic information from consultant psychiatrists., Results: 588 (59%) veterans had more than one diagnosed condition, 387 (39%) had at least one condition for which no firm somatic or psychological diagnosis could be given, and in 90 (9%) veterans no other main diagnosis was made. Conditions characterised by fatigue were found in 239 (24%) of patients. At least 190 (19%) patients had a psychiatric condition, which in over half was due to post-traumatic stress disorder. Musculoskeletal disorders and respiratory conditions were also found to be relatively common (in 182 (18%) and 155 (16%) patients respectively)., Conclusion: Many Gulf war veterans had a wide variety of symptoms. This initial review shows no evidence of a single illness, psychological or physical, to explain the pattern of symptoms seen in veterans in the assessment programme. As the veterans assessed by the programme were all self selected, the prevalence of illness in Gulf war veterans cannot be determined from this study. Furthermore, it is not known whether the veterans in this study were representative of sick veterans as a group.

Background: Various symptoms in military personnel in the Persian Gulf War 1990-91 have caused international speculation and concern. We investigated UK servicemen., Methods: We did a cross-sectional postal survey on a random sample of Gulf War veterans (Gulf War cohort, n=4248) and, stratified for age and rank, servicemen deployed to the Bosnia conflict (Bosnia cohort, n=4250) and those serving during the Gulf War but not deployed there (Era cohort, n=4246). We asked about deployment, exposures, symptoms, and illnesses. We analysed men only. Our outcome measures were physical health, functional capacity (SF-36), the general health questionnaire, the Centers for Disease Control and Prevention (CDC) multisymptom criteria for Gulf War illness, and post-traumatic stress reactions., Findings: There were 8195 (65.1%) valid responses. The Gulf War cohort reported symptoms and disorders significantly more frequently than those in the Bosnia and Era cohorts, which were similar. Perception of physical health and ability were significantly worse in the Gulf War cohort than in the other cohorts, even after adjustment for confounders. Gulf War veterans were more likely than the Bosnia cohort to have substantial fatigue (odds ratio 2.2 [95% CI 1.9-2.6]), symptoms of post-traumatic stress (2.6 [1.9-3.4]), and psychological distress (1.6 [1.4-1.8]), and were nearly twice as likely to reach the CDC case definition (2.5 [2.2-2.8]). In the Gulf War, Bosnia, and Era cohorts, respectively, 61.9%, 36.8%, and 36.4% met the CDC criteria, which fell to 25.3%, 11.8%, and 12.2% for severe symptoms. Potentially harmful exposures were reported most frequently by the Gulf War cohort. All exposures showed associations with all of the outcome measures in the three cohorts. Exposures specific to the Gulf were associated with all outcomes. Vaccination against biological warfare and multiple routine vaccinations were associated with the CDC multisymptom syndrome in the Gulf War cohort., Interpretation: Service in the Gulf War was associated with various health problems over and above those associated with deployment to an unfamiliar hostile environment. Since associations of ill health with adverse events and exposures were found in all cohorts, however, they may not be unique and causally implicated in Gulf-War-related illness. A specific mechanism may link vaccination against biological warfare agents and later ill health, but the risks of illness must be considered against the protection of servicemen.

An epidemiological study to document the endemicity and transmission characteristics of bancroftian filariasis was conducted in an irrigation project community in southern Ghana. In a 50% random sample of the population, the prevalence of microfilaraemia was 26.4% and the geometric mean microfilarial intensity among positives was 819 microfilariae/ml of blood. Hydrocoele was found in 13.8% of the males aged > or =18 years, and 1.4% of the residents examined, all females, had tymphoedema/elephantiasis. Detailed monitoring of the microfilarial intensity in 8 individuals over a 24-h period confirmed its nocturnal periodicity with a peak at approximately 0100 hours. The most important vector was Anopheles gambiae s.l., followed by An. funestus. The abundance of these mosquitoes and their relative importance as vectors varied considerably between the wet and the dry season. Opening of the irrigation canals late in the dry season resulted in a remarkable increase in the population of An. gambiae (8.3% of which carried infective filarial larvae) to levels comparable to those seen during the wet season, suggesting that the irrigation project is responsible for increased transmission of lymphatic filariasis in the community.

A retrospective study of 46 posterior fracture-dislocations of the hip showed that reduction of the dislocation within 24 hours was the most important initial treatment. Open reduction and fixation of the fracture could be delayed up to 4 weeks to allow associated injuries to be treated, and this technique was indicated to remove intra-articular bone fragments or for residual instability. Long-term disability resulted in every patient, regardless of the severity of the initial injury or the method of treatment. Half of the patients never returned to work. Of the 46 patients 43 were unrestrained occupants in vehicular accidents. Multiple injury occurred in 75% of the patients.

Colonies of three strains of Aëdes aegypti resistant to DDT were obtained from Trinidad, Haiti and Malaya and reared beside a normal colony. From their relative resistance to a series of compounds analogous to DDT, characteristic resistance "spectra" were obtained. The two colonies from the West Indies showed a similar type of resistance, rather different from the (smaller) resistance of the Malay strain. No resistance to methoxychlor or dieldrin was found.