Non-exposed Subjects Research Articles

Metabolomic and Lipidomic Analysis of Manganese-Associated Parkinsonism: a Case-Control Study in Brescia, Italy.

Excessive Manganese (Mn) exposure is neurotoxic and can cause Mn-Induced Parkinsonism (MnIP), marked by cognitive and motor dysfunction. Although metabolomic and lipidomic research in Parkinsonism (PD) patients exists, it remains limited. This study hypothesizes distinct metabolomic and lipidomic profiles based on exposure status, disease diagnosis, and their interaction. We used a case-control design with a 2×2 factorial framework to investigate the metabolomic and lipidomic alterations associated with Mn exposure and their link to PD. The study population of 97 individuals was divided into four groups: non-exposed controls (n=23), exposed controls (n=25), non-exposed with PD (n=26) and exposed with PD (n=23). Cases, defined by at least two cardinal PD features (excluding vascular, iatrogenic, and traumatic origins), were recruited from movement disorder clinics in four hospitals in Brescia, Northern Italy. Controls, free from neurological or psychiatric conditions, were selected from the same hospitals. Exposed subjects resided in metallurgic regions (Val Camonica and Bagnolo Mella) for at least 8 continuous years, while non-exposed subjects lived in low-exposure areas around Lake Garda and Brescia city. We conducted untargeted analyses of metabolites and lipids in whole blood samples using ultra-high-performance liquid chromatography (UHPLC) and mass spectrometry (MS), followed by statistical analyses including Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and Two-Way Analysis of Covariance (ANCOVA). Metabolomic analysis revealed modulation of alanine, aspartate, and glutamate metabolism (Impact=0.05, p=0.001) associated with disease effect; butanoate metabolism (Impact=0.03, p=0.004) with the exposure effect; and vitamin B6 metabolism (Impact=0.08, p=0.03) with the interaction effect. Differential relative abundances in 3-sulfoxy-L-Tyrosine (β=1.12, FDR p<0.001), glycocholic acid (β=0.48, FDR p=0.03), and palmitelaidic acid (β=0.30, FDR p<0.001) were linked to disease, exposure, and interaction effects, respectively. In the lipidome, ferroptosis (Pathway Lipids=11, FDR p=0.03) associated with the disease effect and sphingolipid signaling (Pathway Lipids=9, FDR p=0.04) associated with the interaction effect were significantly altered. Lipid classes triacylglycerols, ceramides, and phosphatidylethanolamines showed differential relative abundances associated with disease, exposure, and interaction effects, respectively. These findings suggest that PD and Mn exposure induce unique metabolomic and lipidomic changes, potentially serving as biomarkers for MnIP and warranting further study.

NMR Untargeted and HPLC-MS/MS Targeted Metabolomic Approaches for Evaluating Styrene Exposure in the Urine of Shipyard Workers.

Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.

Obstructive sleep apnoea and nocturnal atrial fibrillation in patients with ischaemic heart disease.

Arrhythmias, especially atrial fibrillation (AF) and ventricular arrhythmias, are independent risk factors of mortality in patients with ischaemic heart disease (IHD). While there is a growing body of evidence that suggests an association between obstructive sleep apnoea (OSA) and cardiac arrhythmias, evidence on this relationship in patients with IHD has been scant and inconsistent. We hypothesised that in patients with IHD, severe OSA is associated with an increased risk of nocturnal arrhythmias. We studied 103 consecutive patients with IHD who underwent an overnight polysomnography. Exposed subjects were defined as patients who had an apnoea-hypopnoea index (AHI) ≥30/h (severe OSA), and nonexposed subjects were defined as patients who had an AHI <30/h (nonsevere OSA). All electrocardiograms (ECGs) were interpreted by the Somte ECG analysis software and confirmed by a physician blinded to the presence or absence of exposure. Arrhythmias were categorised as supraventricular and ventricular. Arrhythmia subtypes (ventricular, atrial and conduction delay) were analysed as dichotomous outcomes using multiple logistic regression models. Atrial fibrillation and AF/flutter (odds ratio 13.5, 95% confidence interval 1.66-109.83; P = 0.003) were found to be more common in the severe OSA group than in the nonsevere OSA group. This association remained significant after adjustment for potential confounders. There was no significant difference in the prevalence of ventricular and conduction delay arrhythmias between the two groups. In patients with IHD, there was a significant association between severe OSA and nocturnal AF/flutter. This underscores the need to evaluate for OSA in patients with IHD, as it may have important implications on clinical outcomes.

Assessment of buccal mucosa genotoxicity in insecticide-exposed urban fumigators in Cali, Colombia.

This study aimed to evaluate cytogenetic damage in the buccal mucosa of non-exposed subjects (N = 33) and insecticide-exposed fumigators (N = 31) in the urban area of Cali, Colombia. Through a questionnaire sociodemographic data, anthropometric measurements, state of health, and lifestyle were collected. Buccal micronucleus cytome (BMCyt) assay was using for evaluate cytogenetic damage. The study showed that all fumigators used adequate personal protective equipment (PPE) and had low alcohol consumption. The authors did not find significant differences in BMCyt biomarkers between the groups (p > 0.05). Multivariate analysis showed a 13% increase in micronucleus (MN) frequency for every year of increasing age (OR = 1.13, p = 0.029), and higher MN with the decrease in daily fruit consumption (OR = 4.71, p = 0.084), without statistical significance. The results between groups could be related to healthy habits and PPE use among the subjects. Int J Occup Med Environ Health. 2024;37(1):128-37.

Joint modeling approaches for censored predictors due to detection limits with applications to metabolites data.

Measures of substance concentration in urine, serum or other biological matrices often have an assay limit of detection. When concentration levels fall below the limit, exact measures cannot be obtained, and thus are left censored. The problem becomes more challenging when the censored data come from heterogeneous populations consisting of exposed and non-exposed subjects. If the censored data come from non-exposed subjects, their measures are always zero and hence censored, forming a latent class governed by a distinct censoring mechanism compared with the exposed subjects. The exposed group's censored measurements are always greater than zero, but less than the detection limit. It is very often that the exposed and non-exposed subjects may have different disease traits or different relationships with outcomes of interest, so we need to disentangle the two different populations for valid inference. In this article, we aim to fill the methodological gaps in the literature by developing a novel joint modeling approach to not only address the censoring issue in predictors, but also untangle different relationships of exposed and non-exposed subjects with the outcome. Simulation studies are performed to assess the numerical performance of our proposed approach when the sample size is small to moderate. The joint modeling approach is also applied to examine associations between plasma metabolites and blood pressure in Bogalusa Heart Study, and identify new metabolites that are highly associated with blood pressure.

Central sleep apnea and exposure to ambient hydrogen sulfide emissions from massive strandings of decomposing sargassum in the Caribbean

BackgroundSargassum invasion of Caribbean and American shorelines is a recurring environmental hazard. Potential health effects of long-term chronic exposure to sargassum gaseous emissions, notably hydrogen sulfide (H2S), are overlooked. H2S plays an important role in neurotransmission and is involved in generating and transmitting respiratory rhythm. Central sleep apnea (CSA) has been attributed to the depression of respiratory centers. ObjectiveEvaluate the effects of exposure to sargassum-H2S on CSA. MethodsThis study, set in the Caribbean, describes the clinical and polysomnographic characteristics of individuals living and/or working in areas impacted by sargassum strandings, in comparison with non-exposed subjects. Environmental exposure was estimated by the closest ground H2S sensor. Multivariate linear regression was applied to analyze CSA changes according to cumulative H2S exposure over time. Effects of air pollution and other sargassum toxic compounds (NH3) on CSA were also controlled. ResultsAmong the 685 study patients, 27 % were living and/or working in sargassum impacted areas. Compared with non-exposed patients, exposed ones had similar sleep apnea syndrome risk factors, but had increased levels of CSA events (expressed as absolute number or % of total sleep apnea). Multivariate regression retained only male gender and mean H2S concentration over a 6-month exposure period as independent predictors of an increase in CSA events. A minimal exposure length of 1 month generated a significant rise in CSA events, with the latter increasing proportionally with a cumulative increase in H2S concentration over time. ConclusionThis pioneer work highlights a potential effect of sargassum-H2S on the central nervous system, notably on the modulation of the activity of the brain's respiratory control center. These observations, jointly with previous studies from our group, constitute a body of evidence strongly supporting a deleterious effect of sargassum-H2S on the health of individuals chronically exposed to low to moderate concentration levels over time.

Long-term risk of pulmonary embolism and deep venous thrombosis after COVID-19: a population-based cohort study

Abstract Background Venous thromboembolism (VTE) (pulmonary embolism (PE) or deep venous thrombosis (DVT)) is common during acute COVID-19. Long-term excess risk has not yet been established. Objective To study long-term VTE risk after COVID-19. Methods Swedish citizens aged 18-84 years, hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5) non-exposed population-derived subjects without COVID-19. Outcomes were incident VTE, PE or DVT recorded at &amp;lt;60, 60−&amp;lt;180, and ≥180 days. Results Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age 60.6 years) and 894,121 were without hospitalization (mean age 41.4 years) with 2,380 (4.9%) and 718 (0.08%) cases of VTE &amp;lt;60 days, compared to 142 (0.06%) and 1,033 (0.02%) among non-exposed controls (244,242 and 4,468,411, respectively). Among patients hospitalized for COVID-19, adjusted hazard ratios (HRs) during 60−&amp;lt;180 days were 6.05 (95% confidence interval (CI) 4.80─7.62) for PE and 3.97 (CI 2.96─5.33) for DVT, compared to non-exposed with corresponding estimates among COVID-19 without hospitalization 1.17 (CI 1.01─1.35) and 0.99 (CI 0.86─1.15), based on 475 and 2,311 VTE events, respectively. Long-term (≥180 days) HRs in patients hospitalized for COVID-19 were 2.01 (CI 1.51─2.68) for PE and 1.46 (CI 1.05─2.01) for DVT while non-hospitalized had similar risk to non-exposed, based on 467 and 2,030 VTE events, respectively. Conclusions Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to the non-exposed.

High Physical Activity Volume Is Associated With an Increase in the Calibre of the Lower Limb Veins Without Impact on Functional Discomfort: the VARISPORT Study

The relationship between physical activity and lower limb veins is complex. If a sedentary lifestyle is considered to be negative on lower limb veins, specific information on physical activity varicose vein volume is sparse, especially the effect of high physical activity volume. The main objective of the VARISPORT study was to evaluate lower limb veins (clinically, morphologically, and haemodynamically) and chronic venous disease symptoms in subjects exposed to high physical activity volume compared with a group of non-exposed subjects. A cross sectional study compared a group of high exercise training volume volunteers (more than eight hours of uninterrupted vigorous intensity physical activity per week for more than six months: high physical activity volume group, HPAV group) with a volunteer control group matched for age, sex, and body mass index. Clinical examination was performed to determine the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of each subject and the Carpentier score was used to assess symptoms related to possible chronic venous disease. Duplex ultrasonography was used to assess vein diameters and reflux in the deep and superficial veins. One hundred and nineteen subjects were included in each group. The lower limb veins (deep and superficial) were significantly more dilated in the HPAV group. More reflux was found in the great saphenous veins and non-saphenous veins in the HPAV group. High physical activity volume was associated with a higher frequency of visible varicose veins (stage C2 of the CEAP classification), odds ratio 3.37 (95% confidence interval 1.66 - 7.25) without impact on functional discomfort (44 subjects with a Carpentier score ≥ 1 in each group). The VARISPORT study reported an increase in the calibre of the lower limb veins without impact on functional discomfort. Further studies are needed to determine whether these athletic veins are truly pathological varicose veins or simply an adaptation to high physical activity volumes.

Residual Shift of Vibrotactile Perception Thresholds Following Repeated Hand-Arm Vibration Exposure: Screening Parameter for Early Signs of Neurosensory Disorders

Background: The purpose of this study was to validate the applicability of a new screening parameter of VPTW defined as the difference between the ascending and descending thresholds of vibrotactile perception to evaluation of the increasing risk of the neurological components of hand-arm vibration syndrome (HAVS) for repeated exposure to hand-arm vibration (HAV). Methods: Thirty subjects—10 old exposed (G1), 10 old non-exposed (G2), and 10 young non-exposed subjects (G3)—were required to carry out three 3 min grip tasks with exposure to two intensities of HAV at 10 min intervals. Vibration perception measurements, each of which lasted 90 s, were performed at 5 min intervals at the right index finger. Results: VPTWs calculated from pairs of the vibrotactile ascending and descending thresholds at the fingertips were not significantly affected by repeated HAV exposure. Moreover, the VPTWs measured for non-exposed subjects were almost invariant regardless of the subjects’ age or the time elapsed after repeated exposure to HAV. Residual TTSs at 125 Hz gradually recovered in all subject groups under both HAV exposure conditions. The residual TTSs of non-exposed subject groups significantly increased as the number of iterations of HAV exposure increased. Conclusions: VPTWs measured after exposure to repeated HAV are invariant and independent of the individual neurosensory characteristics of the fingertips, which supports the hypothesis that VPTWs can be used as a screening parameter to detect potential patients only with neurosensory components observed as early signs of HAVS.

Blood cholinesterase activities and oxidative stress status among farmworkers using pesticides in Duhok, KRG, Iraq

Background: The use of pesticides by farmworkers poses considerable health risks. This study was undertaken to examine plasma and erythrocyte cholinesterase activities, plasma oxidative biomarkers malondialdehyde (MDA), and total antioxidant status (TAS) among farmworkers using different pesticide products in Duhok, northern of Iraq. Methods: This is a case-control study conducted between November 2021 to July 2022 on 92 male farmworkers who were exposed to pesticides in comparison with 44 non-exposed male subjects (control). The availability and uses of pesticides were obtained from 19 agrochemical shops and the farmworkers exposed to pesticides. Demographic data of pesticide-exposed farmworkers and their practice of pesticide applications were recorded. Plasma and erythrocyte cholinesterase activities and plasma MDA and TAS levels were determined in both groups. Results: The farmworkers had a significant 10.0% increase in plasma MDA level, with no significant changes in blood cholinesterase activities or the TAS level. Odds and risk ratios of reduced plasma cholinesterase activity (20.0%) suggested an association of health risks in pesticide-exposed farmworkers. Most of the pesticide products (278) in use were insecticides (47.0%), which comprised mainly 26.0% pyrethroids and 3.0-7.0% anticholinesterase insecticides, among others. The majority of the farmworkers (51%) were merely aware of the general target use of the pesticide, and 75% had an exposure history of &gt; 5 years. Pesticide application was mostly (50.0%) manual, and 54.0% used insufficient personal protection equipment; 32.0% ate and drank at work, 48.0% practiced disposal of empty pesticide containers by burning and/or burying them, whereas 25.0% dumped the containers indiscriminately, and 25% disposed them at garbage sites openly. Conclusion: The farmworkers, with only a marginal increase in oxidative stress biomarker MDA, did not suffer from significant reductions in blood cholinesterase activities, although odds and risk ratios of reduced plasma cholinesterase activity suggested a health risk. Implementation of a national program is needed to measure pre-exposure blood cholinesterase activities in farmworkers.

Health Hazards, Hematological and Biochemical Alterations in Dry-Cleaning Workers using Perchloroethylene.

Perchloroethylene (PERC) is commonly used as a dry-cleaning solvent, it is attributed to many deleterious effects in the biological system. The study aimed to investigate the harmful effect associated with PERC exposure among dry-cleaning workers. The study was carried out on 58 adults in two groups. PERC-exposed group; include thirty-two male dry-cleaning workers using PERC as a dry-cleaning solvent and twenty-six healthy non-exposed subjects. History of PERC exposure, use of personal protection equipment (PPE), safety measurement of the exposed group was recorded. Blood sample was taken from each participant for measurement of hematological markers, liver and kidney function tests. The results showed that 28.1% of the workers were using PPE regularly while 71.9% of the workers were not. Most of the workers 31(96.9%) were disposed of their waste products in improper way. Non-significant differences were observed in hematological indices between PERC-exposed group and non-exposed group. Serum level of kidney and liver function markers of the dry-cleaning workers were higher with statistically significant difference compared with the non-exposed group. In conclusion, a non-significant alteration in hematological parameters, while significant changes in part of liver and kidney functions indices have been demonstrated. Clinical observation indicated a harmful effect in PERC-exposed group.&#x0D; Key words: Occupational, PERC, personal protective equipment, dry cleaner

The impact of sulfur mustard on quality of life and mental health in Kurdish survivors in Sweden, thirty years after exposure

BackgroundThe Iraqi state used chemical warfare agents (CWAs) like sulfur mustard (SM) in al-Anfal genocide in the present-day Kurdistan Region of Iraq. In addition to somatic injuries, exposure to CWAs causes biopsychosocial complications. We investigated the long-term impact of SM exposure on quality of life (QoL) and depression severity in Kurdish survivors resettled in Sweden.MethodsThis is a case-control study, where subjects exposed to SM (n = 18, mean age 51.3 years, 50% women) and sex- and age-matched nonexposed subjects (n = 30, mean age 48.7 years, 47% women) of Kurdish residents in Sweden. Data were collected through in-person interviews based on the RAND 36-item Short Form Health Survey to assess QoL and the Montgomery-Åsberg Depression Rating Scale-self assessment (MADRS-S) to investigate the presence and the gravity of depressive symptoms.ResultsThe SM-exposed group had a significantly lower QoL than the nonexposed group (p < 0.001). Also, the overall mean MADRS-S scores among the SM-exposed group, corresponding to moderate depression, were higher than the scores of the nonexposed (22 points (p) vs. 9 p, p < .001). Overall, the participants within the exposed group reported worse mental than physical well-being 36p and 32p, respectively. Within the SM-exposed group, there was no gendered-related difference neither in terms of depression severity nor for QoL, but the groups were small.ConclusionIndividuals exposed to SM had worse QoL and a higher level of depressive severity compared with nonexposed individuals three decades after exposure, indicating the importance of increased clinician knowledge, guidelines, and an approach to assess and respond to the exposed groups’ biopsychosocial needs. These findings indicate that those exposed to SM might need early identification of mental illnesses and more support to promote QoL.

STATUS OF THE CELLULAR IMMUNITY IN CLEAN-UP WORKERS OF THE CHORNOBYL ACCIDENT AND PATIENTS WITH CANCER OF THE MOUTH CAVITY, ORAL AND LARYNGEAL PART OF THE PHARYNX.

to establish cellular immunity in clean-up workers of the Chornobyl accident compared to patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx according to the subpopulation organization of peripheral blood leukocytes. We examined 112 males, age (56,92 ± 6,17) years (M ± SD), including 26 male clean-up workers exposed at the radiation dose 10-500 mSv; 20 male clean-up workers exposed at the dose range 504-990mSv; 33 patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx and 33 non-exposed subjects of the control group. Immune cell subsets analysis was performed by the expression of differential and activation antigens of peripheral blood leukocytes using flow cytometry. In assessing each group's cellular immunity, there was a decrease in the number of CD19+ B-lymphocytes, CD3+ HLA-DR+ T- and CD3- HLA-DR+ B-lymphocytes, CD3- 16+ 56+ natural killer cells, combined with an increase in the number of CD8+ T-lymphocytes. An increase in the relative number of CD4+ CD8+ T-lymphocytes was determined in clean-up workers (D < 500 mSv) and cancer patients. An increase in the number of CD8+ T-lymphocytes and a decrease in the number of CD4+ T-lymphocytes were observed in clean-up workers (D > 500 mSv), as well as in cancer patients. In addition, a decrease of monocytes, CD3+ 16+ 56+ , and CD3+ TCRαβ+ T-lymphocytes was determined in patients with oncological pathology. The obtained results show the unidirectionality of changes in cellular immunity in the participants of the liquidation of the consequences of the accident at the Chornobyl nuclear power plant and patients with the investigated oncological pathology, which indicates the formation of persistent violations of antitumor protection in the participants of the liquidation of the consequences of the accident as the basis of oncogenesis. Determining changes in the number of lymphocytes, monocytes, granulocytes, CD4+ T-lymphocytes, CD4+ CD8+ immature T-lymphocytes, the immunoregulatory ratio CD4+ / CD8+, CD3+TCRαβ+ T-lymphocytes and CD3+ 16+ 56+ CTL can have an additional effect on the effectiveness antitumor protection and the probability of oncogenesis risk in immunocompromised individuals.

Vibrotactile Perception Thresholds following Short-Term Exposure to Hand–Arm Vibration: Application for Identifying Potential Workers at Risk of Neurosensory Disorders

Background: The aim of this study was to propose and validate a novel indicator that characterizes the potential effects of exposure to hand–arm vibration (HAV) and evaluates the increasing risk of neurosensory components of hand–arm vibration syndrome (HAVS). The author focused on a quantity calculated from ascending and descending thresholds and residual shifts in vibrotactile perception thresholds (VPTs) observed at the fingertips in the recovery process after exposure to HAV. Methods: Thirty subjects—10 old exposed (G1), 10 old non-exposed (G2), and 10 young non-exposed subjects (G3)—were required to perform a series of grip tasks with exposure to two intensities of HAV, which was followed by 90 s of vibration perception measurements at the tip of each subject’s right index finger. Vibrotactile perception was measured every 5 min for 30 min. Results: Mean differences between ascending and descending thresholds (VPTWs) for G2 and G3 remained nearly unchanged over time after exposure to HAV. In contrast, the mean VPTWs for G1 gradually increased over time after exposure to HAV. The mean VPTWs for G1 were always larger than those for G2 and G3. TTS recovery was observed at 125 Hz under both of the HAV exposure conditions in each group. TTSs of nearly zero were observed for the low-HAV condition in G3. TTS recovery after exposure to HAV was not observed at 31.5 Hz in any of the subject groups. Regardless of elapsed time, the mean TTSs for G2 and G3 were smaller than those for G1. Negative TTS values showing a lower TTS than the baseline were sometimes observed for the low-HAV condition in G3. Conclusions: VPTWs can be a screening parameter that detects potential patients with only neurosensory components observed as an early sign of HAVS.

On radar and radio exposure and cancer in the military setting

IntroductionIn 2018, we reported a case series of 47 patients diagnosed with cancer following several years of exposure to high-intensity whole-body radiofrequency radiation (RFR) using the parameter of percentage frequency (PF). Consistent high and statistically significant PFs of hematolymphoid (HL) cancers were found in this group and in four previous reports on RFR-exposed groups in Belgium, Poland and Israel together with increased all-cancers rates. In this paper we report a new series of 46 young cancer patients who were exposed during military service to such radiation. Materials and methodsThe new group of patients comprises Israeli soldiers previously exposed to occupational RFR. The patients were self-selected to enroll in the research in cooperation with an NGO assisting patients with administrative counseling and legal and social services. The new group of patients was studied with respect to distribution (proportion) of cancer types using the method of PF. When possible, cancer risk ratios (RR) were estimated too. The results are compared to those of other occupational groups in three countries. ResultsMedian age at diagnosis was 23 years; duration of exposure was between 1 and 3 years and the latencies were short, median 4.6 years. The PF of HL cancers was 41.3%, 95% CI (27%–57%), versus 22.7% expected in non-exposed subjects matched for age and gender profiles, p = 0.003; 19 out of the 46 patients had HL cancers. The PF of Hodgkin lymphoma cancers was 21.7%, 95%CI (11%–36%), versus 11.6% expected, p = 0.033. For a subgroup of 6 patients, the number of soldiers in the units was known, and we were able estimate approximately the overall cancer risk ratio (RR) after 8 years as being 8.0 with 95% CI (2.9, 17), p < 0.002, with only 0.75 cases expected from the Cancer Registry data. In this subgroup, there were 3 HL cancer cases and 3 non-HL cases. Sarcoma PF was higher than expected, 7 out of the 46 patients were diagnosed with sarcoma, PF = 15.2%, 95%CI (6.3%–28.9%), p = 0.04 versus the expected PF of 7%. ConclusionThe HL PF was high and consistent with previous reports. Epidemiological studies on excess risk for HL and other cancers, brain tumors in cellphone users, and experimental studies on RFR and carcinogenicity strongly point to a cause-effect relationship. It is mandatory to reduce the RFR exposure of all personnel to that of the typical community levels, including the peak level of radar pulses. Radiation protection, safety instructions, cancer risk warnings and quantitative data on individual exposure together with regular medical monitoring must be instituted for all personnel exposed to such risks. The findings from our study add to the growing body of evidence underscoring the gross inadequacy of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) thermal standards. Based on our findings and on the previous accumulated research, we endorse the recommendations to reclassify RFR exposure as a human carcinogen, International Agency for Research on Cancer (IARC) group 1.

Plasma microRNA expression and immunoregulatory cytokines in an Indian population occupationally exposed to cadmium.

Following its accumulation in the body, cadmium (Cd) exposure is associated with devastating effects on multiple organ system of the human body. The immune system is one of the sensitive targets for Cd-inducedtoxicity. Recently, studies have demonstrated a significant role of Cd in inducing epigenetic alterations. With this background, the present study was planned to study the changes in candidate microRNA(miRNA) expression associated with immune regulation in occupationally Cd-exposedworkers. One hundred individuals involved in welding and metal handicraft manufacturing, while 80 apparently healthy subjects without any prior history of occupational exposure were recruited for the study. Blood Cd level was determined by atomic absorption spectrometry. Serum cytokine levels were measured using anenzyme-linked immunosorbent assay and serum miRNA expression of candidate miRNAs (miR-146a, miR-210, and miR-222) were determined by real-time polymerase chain reaction.The median Cd level (2.40 μg/L) in the occupationally exposed workers was significantly higher than the nonexposed subjects (0.90 μg/L). Among the cytokines, interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α)were significantly higher whileIL-2 and IL-10 were significantly lower in the exposed. The expression level of miR-146a and miR-222 were significantly different between the groups with the former showing downregulation and later showing upregulation. Correlation analysis revealed a positive and negative association of miR-222 and miR-146a with blood cadmium level, IL-17 as well as TNF-α, respectively. Furthermore, the in-silico analysis revealed a significant role of the studied miRNAs in various cellular and genetic pathways. The findings of the present study demonstrate significant involvement of Cd-inducedalteration in miRNAs in varied immune regulatory changes in exposed individuals.

Biomarkers of lead in occupationally exposed persons in Gurara and Suleja areas, Niger State, Nigeria

Human exposure to lead could pose serious health challenges, especially among occupationally-exposed workers. Though several toxicological studies have been carried out on toxic lead exposure in humans regarding their levels, reactions and disease conditions; dearth data exists in terms of correlation of lead levels with their exposure markers and subsequent manifested disease conditions. This study therefore aims to investigate the association between lead exposure and specific biomarkers used in monitoring lead levels in some occupationally exposed individuals and comparing the values with non-exposed individuals. A total of 116 subjects (72 occupationally exposed and 44 non-exposed subjects) within the age range of 17– 50 years were studied in a cross-sectional study conducted between August 2021 and November 2021 in Gurara and Suleja areas, in Niger state, Nigeria. Blood lead levels, hepato-renal indices and hematological parameters were analyzed using atomic absorption spectrophotometer (AAS) and abacus 380 analyzer, respectively. The mean blood levels of lead were 26.8±5.4 μg/dL in occupationally-exposed subjects, while in non-exposed subject’s 3.7±2.1 μg/dL. The results showed that occupational exposure increases the blood level of lead, implicating hematological variables and elevating specific hepato-renal indices which consequently increase the health risk of occupationally exposed individuals. Therefore, taking note of other body burdens, the synergistic adoption of these indicative biomarker tests could be used to give an implicative assessment on lead exposure and toxicity.

Nationwide study of sudden cardiac death in young persons diagnosed with chronic kidney disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Novo Nordisk Foundation, Copenhagen, Denmark. Background Chronic kidney disease (CKD) is associated with increased risk of cardiovascular morbidity and mortality. The increased cardiovascular mortality is partly explained by an increased risk of sudden cardiac death (SCD) among patients with CKD. Purpose The purpose of this study was to compare short- and long-term risk of SCD in individuals with and without CKD aged 18-49 years. Methods &amp; Results Using the Danish nationwide health registries, all persons aged 18-49 years diagnosed with non-failure stage CKD or kidney failure from 1st of July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were included 50:1. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified by thoroughly examining the Danish Registries, the Danish death certificates, autopsy reports and discharge summaries. In total, 9,476 incident cases of non-failure stage CKD and 1,283 incident cases of kidney failure were included. For patients with non-failure stage CKD and kidney failure, the absolute risk of all-cause mortality 10-year after diagnosis was 8.7% and 23.6%, respectively. Among patients with non-failure stage CKD, the absolute risk of SCD 1, 5 and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex matched subjects the corresponding relative risk was 20 (95%-CI 8.4-48.8), 7.1 (95%-CI 4.2-12.0), and 6.1 (95%-CI 3.8-9.7), respectively. Among patients with kidney failure, the absolute 1, 5, and 10 year risk of SCD was 0.17%, 0.56% and 2.07%, respectively. The corresponding relative risk was 12.5 (95%-CI 1.4-111.6), 7.9 (95%-CI 2.3-27.0) and 10.1 (95%-CI 4.5-22.6), respectively. Conclusions Persons with non-failure stage CKD and kidney failure had increased risk of SCD compared with the background population with a 20- and 13-fold increased risk one year after diagnosis, respectively. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

Biochemical and hematological effects of lead exposure in Iranian battery workers

Objectives. The purpose of this study was to evaluate the hematotoxic, hepatotoxic and nephrotoxic responses following lead exposure among battery workers. Methods. Seventy-eight battery workers exposed to lead and 78 non-exposed subjects were studied. Fasting blood samples were collected to assess kidney and liver function and hematological parameters. To determine the breathing zone and blood lead levels (BLLs), the samples were analyzed in accordance with NIOSH methods 7082 and 8003, respectively. Results. The battery workers had significantly higher breathing zone lead and BLLs than the non-exposed group. In battery workers, most hematological parameters, including red blood cells, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, have significantly decreased. In contrast, the white blood cell count has shown a significant increase as compared to the controls. The mean levels of alanine aminotransferase and aspartate aminotransferase as biomarkers of liver damage and the creatinine serum levels as a result of renal failure were significantly higher in the exposed group than in the non-exposed group. Conclusions. These observations indicate that occupational exposure to lead exceeding its current threshold limit value and biological exposure index is associated with hematological symptoms and liver and kidney dysfunction.

Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy.

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects.