Use of Swedish smokeless tobacco during pregnancy: a systematic review of pregnancy and early life health risk

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background and Aims: Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy. Method: Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta-analysis and assessed confidence in effectestimates using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results: We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence. Conclusions: This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.publishedVersio

Organic chemicals from diesel exhaust particles affects intracellular calcium, inflammation and β-adrenoceptors in endothelial cells

Exposure to diesel exhaust particles (DEP) may contribute to endothelial dysfunction and cardiovascular disease. DEP, extractable organic material from DEP (DEP-EOM) and certain PAHs seem to trigger [Ca2+]i increase as well as inflammation via GPCRs like βARs and PAR-2. In the present study we explored the involvement of βARs and PAR-2 in effects of DEP-EOM on [Ca2+]i and expression of inflammation-associated genes in the endothelial cell-line HMEC-1. We exposed the human microvascular endothelial cell line HMEC-1 to DEP-EOM fractionated by sequential extraction with solvents of increasing polarity: n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol (Methanol-EOM) and water (Water-EOM). While Methanol-EOM and Water-EOM had no marked effects, n-Hex-EOM and DCM-EOM enhanced [Ca2+]i (2–3 times baseline) and expression of inflammation-associated genes (IL-1α, IL-1β, COX-2 and CXCL8; 2–15 times baseline) in HMEC-1. The expression of βARs (60–80% of baseline) and βAR-inhibitor carazolol suppressed the increase in [Ca2+]i induced by both n-Hex- and DCM-EOM. Carazolol as well as the Ca2+-channel inhibitor SKF-96365 reduced the DCM-EOM-induced pro-inflammatory gene-expression. Overexpression of βARs increased DCM-EOM-induced [Ca2+]i responses in HEK293 cells, while βAR-overexpression suppressed [Ca2+]i responses from n-Hex-EOM. Furthermore, the PAR-2-inhibitor ENMD-1068 attenuated [Ca2+]i responses to DCM-EOM, but not n-Hex-EOM in HMEC-1. The results suggest that βAR and PAR-2 are partially involved in effects of complex mixtures of chemicals extracted from DEP on calcium signalling and inflammation-associated genes in the HMEC-1 endothelial cell-line

Low-voltage electrical accidents, immediate reactions and acute health care associated with self-reported general health 4 years later

Background and aims Electricians frequently experience low-voltage electrical accidents. Some such accidents involve long-term negative health consequences. Early identification of victims at risk for long-term injury may improve acute medical treatment and long-term follow-up. This study aimed to determine acute exposure, health effects and treatment associated with general health ≥ 2 years after low-voltage electrical accidents. Methods In a cross-sectional study, 89 male electricians who had experienced an electrical accident between 1994 and 2001 participated in a 2003 follow-up health examination. They were identified from a registry of low-voltage electrical accidents and included in the study. Based on exposure descriptions in the original accident reports, they were stratified into the following three groups: a current arc accident group (N = 34, mean age 38.8 years [standard deviation, SD = 12.2, range = 21–59]) and two groups with the passage of current through the body, either fixed to the current source (“no-let-go” group; N = 35, mean age 34.0 years [SD = 10.5, range = 21–57]) or not (“let-go” group; N = 20, mean age = 38.7 years [SD = 10.3, range = 21–63]). They retrospectively described acute reactions and assessed their current general health at the health examination. Multivariate linear regression, ordinal logistic regression and Fisher’s exact test were used to compare acute reactions with health at follow-up in each exposure group. Results The multivariate analysis indicated that after accidents with the passage of current through the body, severe acute headache (β = − 0.56, p = 0.013), years since the accident (β = − 0.16, p = 0.017) and the accident being perceived as frightening (β = − 0.48, p = 0.040) were negatively associated with general health ≥ 2 years later (R2 = 0.25, p = 0.002). If the exposure included a no-let-go experience, then acute severe body numbness (β = − 0.53, p = 0.029) was also negatively associated with general health (R2 = 0.38, p = 0.002). Without such experience, only acute confusion (β = − 0.90, p = 0.029) was negatively associated with the health at follow-up (R2 = 0.24, p = 0.029). In univariate analyses, after the passage of current through the body, acute dizziness (p = 0.029), apathy (p = 0.028), confusion (p = 0.007) and irregular heartbeat (p ≤ 0.05) were associated with poor long-term general health. The no-let-go group, more often than the let-go group, reported panic (p = 0.001), fear of death (p = 0.029), confusion (p = 0.014), exhaustion (p = 0.009), bodily numbness (p = 0.013) and immediate unconsciousness (p = 0.019). Acute symptoms beyond the first day after a current arc accident were associated with poor long-term general health (p = 0.015). Discussion and conclusions The acute reactions negatively associated with general health ≥ 2 years after low-voltage electrical accidents should alert the clinician in the acute phase after an electrical accident to the risk of developing negative long-term health effects. Future studies should specify long-term health beyond the concept of general health

Low-voltage electrical accidents, immediate reactions and acute health care associated with self-reported general health 4 years later

Background and aims Electricians frequently experience low-voltage electrical accidents. Some such accidents involve long-term negative health consequences. Early identification of victims at risk for long-term injury may improve acute medical treatment and long-term follow-up. This study aimed to determine acute exposure, health effects and treatment associated with general health ≥ 2 years after low-voltage electrical accidents. Methods In a cross-sectional study, 89 male electricians who had experienced an electrical accident between 1994 and 2001 participated in a 2003 follow-up health examination. They were identified from a registry of low-voltage electrical accidents and included in the study. Based on exposure descriptions in the original accident reports, they were stratified into the following three groups: a current arc accident group (N = 34, mean age 38.8 years [standard deviation, SD = 12.2, range = 21–59]) and two groups with the passage of current through the body, either fixed to the current source (“no-let-go” group; N = 35, mean age 34.0 years [SD = 10.5, range = 21–57]) or not (“let-go” group; N = 20, mean age = 38.7 years [SD = 10.3, range = 21–63]). They retrospectively described acute reactions and assessed their current general health at the health examination. Multivariate linear regression, ordinal logistic regression and Fisher’s exact test were used to compare acute reactions with health at follow-up in each exposure group. Results The multivariate analysis indicated that after accidents with the passage of current through the body, severe acute headache (β = − 0.56, p = 0.013), years since the accident (β = − 0.16, p = 0.017) and the accident being perceived as frightening (β = − 0.48, p = 0.040) were negatively associated with general health ≥ 2 years later (R2 = 0.25, p = 0.002). If the exposure included a no-let-go experience, then acute severe body numbness (β = − 0.53, p = 0.029) was also negatively associated with general health (R2 = 0.38, p = 0.002). Without such experience, only acute confusion (β = − 0.90, p = 0.029) was negatively associated with the health at follow-up (R2 = 0.24, p = 0.029). In univariate analyses, after the passage of current through the body, acute dizziness (p = 0.029), apathy (p = 0.028), confusion (p = 0.007) and irregular heartbeat (p ≤ 0.05) were associated with poor long-term general health. The no-let-go group, more often than the let-go group, reported panic (p = 0.001), fear of death (p = 0.029), confusion (p = 0.014), exhaustion (p = 0.009), bodily numbness (p = 0.013) and immediate unconsciousness (p = 0.019). Acute symptoms beyond the first day after a current arc accident were associated with poor long-term general health (p = 0.015). Discussion and conclusions The acute reactions negatively associated with general health ≥ 2 years after low-voltage electrical accidents should alert the clinician in the acute phase after an electrical accident to the risk of developing negative long-term health effects. Future studies should specify long-term health beyond the concept of general health

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Background Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Background Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages

A human relevant mixture of persistent organic pollutants induces reactive oxygen species formation in isolated human leucocytes: Involvement of the β2-adrenergic receptor

Exposure to chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) persistent organic pollutants (POPs) is associated with immunotoxicity and other adverse effects in humans and animals. Previous studies on POPs have mainly focused on single chemicals, while studies on complex mixtures are limited. Using DCF and luminol assays we examined effects on ROS generation in isolated human neutrophils, monocytes and lymphocytes, after in vitro exposure to a total mixture and sub-mixtures of 29 persistent compounds (Cl, Br, and PFAA). The mixtures were based on compounds prominent in blood, breast milk, and/or food. All mixture combinations induced ROS production in one or several of the cell models, and in some cases even at concentrations corresponding to human blood levels (compound range 1 pM – 16 nM). Whilst some interactions were detected (assessed using a mixed linear model), halogenated subgroups mainly acted additively. Mechanistic studies in neutrophils at 500× human levels (0.5 nM – 8 µM) indicated similar mechanisms of action for the Cl, PFAA, the combined PFAA + Cl and total (PFAA + Br + Cl) mixtures, and ROS responses appeared to involve β2-adrenergic receptor (β2AR) and Ca2+ signalling, as well as activation of NADPH oxidases. In line with this, the total mixture also increased cyclic AMP at levels comparable with the non-selective βAR agonist, isoproterenol. Although the detailed mechanisms involved in these responses remain to be elucidated, our data show that POP mixtures at concentrations found in human blood, may trigger stress responses in circulating immune cells. Mixtures of POPs, further seemed to interfere with adrenergic pathways, indicating a novel role of βARs in POP-induced effects

A human relevant mixture of persistent organic pollutants induces reactive oxygen species formation in isolated human leucocytes: Involvement of the β2-adrenergic receptor

Exposure to chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) persistent organic pollutants (POPs) is associated with immunotoxicity and other adverse effects in humans and animals. Previous studies on POPs have mainly focused on single chemicals, while studies on complex mixtures are limited. Using DCF and luminol assays we examined effects on ROS generation in isolated human neutrophils, monocytes and lymphocytes, after in vitro exposure to a total mixture and sub-mixtures of 29 persistent compounds (Cl, Br, and PFAA). The mixtures were based on compounds prominent in blood, breast milk, and/or food. All mixture combinations induced ROS production in one or several of the cell models, and in some cases even at concentrations corresponding to human blood levels (compound range 1 pM – 16 nM). Whilst some interactions were detected (assessed using a mixed linear model), halogenated subgroups mainly acted additively. Mechanistic studies in neutrophils at 500× human levels (0.5 nM – 8 µM) indicated similar mechanisms of action for the Cl, PFAA, the combined PFAA + Cl and total (PFAA + Br + Cl) mixtures, and ROS responses appeared to involve β2-adrenergic receptor (β2AR) and Ca2+ signalling, as well as activation of NADPH oxidases. In line with this, the total mixture also increased cyclic AMP at levels comparable with the non-selective βAR agonist, isoproterenol. Although the detailed mechanisms involved in these responses remain to be elucidated, our data show that POP mixtures at concentrations found in human blood, may trigger stress responses in circulating immune cells. Mixtures of POPs, further seemed to interfere with adrenergic pathways, indicating a novel role of βARs in POP-induced effects