Local Exposure Research Articles

Comparison of Three Antagonists of Hedgehog Pathway to Promote Skeletal Muscle Regeneration after High Dose Irradiation.

The current geopolitical context has brought the radiological nuclear risk to the forefront of concerns. High-dose localized radiation exposure leads to the development of a musculocutaneous radiation syndrome affecting the skin and subcutaneous muscles. Despite the implementation of a gold standard treatment based on an invasive surgical procedure coupled with autologous cell therapy, a muscular defect frequently persists. Targeting the modulation of the Hedgehog (Hh) signaling pathway appears to be a promising therapeutic approach. Activation of this pathway enhances cell survival and promotes proliferation after irradiation, while inhibition by Cyclopamine facilitates differentiation. In this study, we compared the effects of three antagonists of Hh, Cyclopamine (CA), Vismodegib (VDG) and Sonidegib (SDG) on differentiation. A stable cell line of murine myoblasts, C2C12, was exposed to X-ray radiation (5 Gy) and treated with CA, VDG or SDG. Analysis of proliferation, survival (apoptosis), morphology, myogenesis genes expression and proteins production were performed. According to the results, VDG does not have a significant impact on C2C12 cells. SDG increases the expression/production of differentiation markers to a similar extent as CA, while morphologically, SDG proves to be more effective than CA. To conclude, SDG can be used in the same way as CA but already has a marketing authorization with an indication against basal cell cancers, facilitating their use invivo. This proof of concept demonstrates that SDG represents a promising alternative to CA to promotes differentiation of murine myoblasts. Future studies on isolated and cultured satellite cells and invivo will test this proof of concept.

Mercury distribution, exposure and risk in Poyang Lake and vicinity, China

Mercury (Hg), especially methylmercury (MeHg), which is highly neurotoxic, is a global pollutant that can affect human health because of its accumulation in aquatic products. Poyang Lake, an inland lake in China, has been significantly affected by human activity, yet there is limited understanding of local mercury contamination and potential exposure pathways to humans. In this study, we explored the risks of mercury exposure by sampling sediments, plants, and aquatic organisms in the lake and surrounding areas and analyzing total Hg (THg) and MeHg levels. Sediment sampling was conducted at the main lake, rivers, rice paddies, and fishponds. Two dominant species of plants and 15 species of aquatic organisms were sampled and analyzed. We assessed the characteristics of mercury in sediments using the geo-accumulation index (Igeo), mercury exposure using the biomagnification factor (BMF) and biota sediment accumulation factor (BSAF), and risks using thresholds for adverse effects. The highest THg concentrations (137.04 ± 44.3 ng g−1 dw) were detected in the main lake sediments, whereas the highest MeHg concentrations (0.47 ± 0.6 ng g−1 dw) were detected in fishpond sediments. Mercury accumulation in the main lake sediments could be assessed as contaminated (Igeo > 0: 81.6%). Yellow catfish had the highest mercury concentration (THg 770.69 ± 199.7 ng g−1 dw; MeHg 741.93 ± 168.8 ng g−1 dw). Piscivores were adversely affected by carnivorous fish (50.8%), but all fish concentrations did not exceed the food safety standards recommend by China and the WHO. The mercury exposure results revealed significant Hg biomagnification and enrichment (BMF >1: 94.55%; BSAFmax = 1218). Long-term monitoring of aquatic organisms is warranted.

Abstract A030: Fusion between macrophages and cancer cells up-regulates signal regulatory protein pathway and contributes to malignant progression of pancreatic cancer after radiation

Abstract Introduction: Fusion between tumor cells with leukocytes contributes to tumor heterogeneity, resulting in tumorigenesis, metastasis, and treatment resistance. Recent studies demonstrate that an inflammatory microenvironment enhances tumor-macrophage fusion. We hypothesize that tumor-macrophage fusion hybrids contribute to radiation induced pancreatic cancer progression. Materials and Methods: Tumor tissues of female patients receiving previous bone marrow transplantation (BMT) from male donors due to leukemia/lymphoma were collected for Y chromosome and immunofluorescence study. Murine subcutaneous tumor models of cre-loxP or dual fluorescence system were established to demonstrate fusion between Pan02, a murine pancreatic adenocarcinoma cell line, and stromal cells of ROSA (Gt(ROSA)26Sor tm4(ACTB-tdTomato,-EGFP)Luo/Jnarl) mice with or without local radiation exposure. KC (pdx-1-cre-KrasLSL-G12D) mice, were given whole body irradiation followed by BMT from ROSA mice to measure fusion between pancreatic cancer and hematopoietic cells. Liposomal chlodronate, a macrophage depleting agent, and immunofluorescence staining of fusion hybrids in ROSA mice tumors were used to demonstrate macrophage as a fusion partner. Fusion hybrid clones of murine/human pancreatic adenocarcinoma cells with macrophages were selected from co-culture and sorting followed by studies including ploidy, clonogenicity, migration and radio-sensitivity. Affymetrix microarray analysis was used to find differentially expressed genes of fusion hybrids. Results: Fusion phenomenon was demonstrated by showing colocalization of Y chromosomes with epithelial markers in cancer tissues from female patients receiving prior BMT from male donors. Fusion hybrids were found in pancreas tumors of KC mice after BMT from ROSA mice. Fusion hybrids within tumors increased by time, three folds within 6 weeks; and 2.5 folds after 20Gy radiation exposure. Liposomal clodronate reduced fusion hybrids and tumor growth. Immunofluorescence stain of tumor tissues demonstrated CD11b(+) macrophage to be the major fusion partner. Purified Fusion hybrids showed enhanced migration, proliferation, aneuploidy and radio-resistance. Model based gene analysis of microarray study disclosed signal regulatory protein (SIRP) signal pathway was significantly upregulated in fusion hybrids. Upregulated SIRP signal molecules, including DAP12, PyK2, were validated by immunoblots. Silencing DAP12 in myeloid cells from human peripheral blood showed decreased fusion rate with Panc-1 cells. DAP12mRNA depletion in Panc-1 fusion hybrids disclosed enhanced radio-sensitivity. Defactinib (VS6063), a PyK2 inhibitor, reduced fusion phenomenon and suppressed pancreatic tumor growth of mice after local radiation. Conclusions: Fusion between pancreatic cancer cells and macrophages contribute to radiation enhanced malignant progression of pancreatic cancer. SIRP signal pathway is a potential target to disrupt fusion phenomenon and ameliorate pancreatic cancer progression after radiation. Citation Format: Hui Ju Ch'ang, Yi-Chih Tsai, Ting Wei Li, Rui-Jun Liu, Tze-Sing Huang, Sse-Pei Wan, Su-Liang Chen, Shih-Sheng Jiang. Fusion between macrophages and cancer cells up-regulates signal regulatory protein pathway and contributes to malignant progression of pancreatic cancer after radiation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A030.

The Dunes Contribution to the Ecosystem Service of Coastal Protection on the Northern Coast of RS

Coastal dunes have a crucial role in offering the ecosystem service of natural coastal protection. This paper investigates the importance of dunes in providing the ecosystem service of natural coastal protection on the North Coast of the State of Rio Grande do Sul (RS) in southern Brazil. The Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST®) Coastal Vulnerability Model was used to quantify the relative susceptibility to coastal erosion and flooding within the study area. First, the model was run to assess the susceptibility to coastal hazards considering the presence of dunes. Then, the model was run again without the presence of dunes. By comparing the results of the two model simulations, it was possible to identify where dunes contribute to reducing coastal exposure, which indirectly reflects their role in providing the ecosystem service of natural coastal protection. There are two main dune fields in the study area, one in the northern coastal sector and one in the southern sector, respectively in the municipalities of Torres and Cidreira. The index of exposure values produced by the two model simulations were very similar for locations along the Torres coastline. In contrast, along the coast of Cidreira, results from the model simulation without dunes produced higher exposure values than the simulation with the presence of dunes, suggesting that the dunes have an important role in offering natural coastal protection. Dunes are a natural barrier against coastal erosion and flooding, but they are not the only factor influencing the ecosystem service of coastal protection. In Torres, for instance, the local topography and the wind patterns contribute to reducing local exposure. The greatest threat in this sector is the urban sprawl.

Risk from future climate change to Pakistan's protected area network: A composite analysis for hotspot identification

As climate change becomes a primary driver of global ecosystem deterioration and biodiversity loss, protected areas (PAs) are posed to play a crucial conservation role. At a global scale, 17 % of land is currently covered by PAs; a figure expected to reach 30 % by 2030 under the UN post-2020 global biodiversity framework. However, focusing only on the percent coverage of PAs without assessing their efficacy may not accomplish the intended conservation goals. Here, we present the first assessment of the risk from climate change to existing PAs and non-protected lands across Pakistan by combining data on the local exposure and vulnerability of 409 species of birds, mammals, reptiles and amphibians to multidimensional changes in climate by mid (2040–2060) and late (2061–2080) century under two climate emission scenarios (RCP4.5 and RCP8.5). We find that between 7 % (2050 RCP4.5) and 19 % (2080 RCP8.5) of the current network of PAs, mostly located in the eastern and southeastern parts of the country, are projected to be under future extreme risk (i.e., highly exposed areas containing highly vulnerable communities). Importantly, hotspots of risk within these PAs are projected to significantly expand over time and with increasing severity of the scenario. In contrast, PAs in the northern part of the country are projected to remain under moderate to low risk. Results are subject to variability across the country reflecting interesting differences in climate change exposure and species vulnerability between protected and non-protected lands. Importantly, significantly lower level of risks from future climate change are projected for PAs than non-protected lands across emission scenarios and periods suggesting potential candidate areas for the future expansion of the country's PA network. Our analysis provides novel insights that can help inform conservation decisions and management at a time when the country is investing in ambitious efforts to expand its network of protected areas.

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects

Breast cancer prevention only requires local exposure of the breast to active drug. However, oral preventive agents entail systemic exposure, causing adverse effects that limit acceptance by high-risk women. Drug-delivery through the breast skin is an attractive option, but requires demonstration of dermal safety and drug distribution throughout the breast. We formulated the tamoxifen metabolite (E/Z)-endoxifen for transdermal delivery and tested it in a placebo-controlled, double-blinded Phase I trial with dose escalation from 10 to 20 mg daily. The primary endpoint was dermal toxicity. Thirty-two women planning mastectomy were randomized (2:1) to endoxifen-gel or placebo-gel applied to both breasts for 3–5 weeks. Both doses of endoxifen-gel incurred no dermal or systemic toxicity compared to placebo. All endoxifen-treated breasts contained the drug at each of five sampling locations; the median per-person tissue concentration in the treated participants was 0.6 ng/g (IQR 0.4–1.6), significantly higher (p < 0.001) than the median plasma concentration (0.2 ng/mL, IQR 0.2–0.2). The median ratio of the more potent (Z)-isomer to (E)-isomer at each breast location was 1.50 (IQR 0.96–2.54, p < 0.05). No discernible effects of breast size or adiposity on tissue concentrations were observed. At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) and significant downregulation of gene signatures known to promote cancer invasion (FN1, SERPINH1, PLOD2, PDGFA, ITGAV) (p = 0.03). Transdermal endoxifen is an important potential breast cancer prevention agent but formulations with better dermal penetration are needed.

Effects of different fabrics on the Hoffmann reflex during local heat exposure.

[Purpose] The effects of multifunctional garments on neuromuscular performance have gained significant research attention in the health sciences. However, the spinal responses to different fabrics have not yet been considered. In the present study, we examined the effects of typical fabrics (cotton and polyester) on the Hoffmann reflex during local heat exposure. [Participants and Methods] Sixteen healthy males aged 20-40 years participated in this study. A heating device comprising a thermal mat, fabric, and a data logger was fabricated. The fabric was affixed to the skin as the contact surface. The temperature of the right posterior lower leg was increased to 39°C followed by 10 min for adaptation at 39-40°C. The H- and M-waves were recorded at each point, including those without heating. An identical trial was conducted seven days later using the alternative fabric. [Results] M-wave amplitude and latency were significantly decreased during heat exposure without fabric. The H-wave latency was prolonged by sustained thermal heat during the session with polyester. Interestingly, the H-wave amplitudes normalized by the maximal M-wave amplitudes decreased with prolonged heat exposure during the session with cotton. However, this index remains unchanged during the sessions using polyester. [Conclusion] During prolonged localized thermal exposure, cotton reduced spinal excitability, whereas polyester preserved spinal excitability.

Overdose deaths before and during the COVID-19 pandemic in a US county.

Globally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed. This retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery. There was an immediate 49% increase (95% CI 23-82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4-55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties. Service and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.

Validation of the dew point chilled mirror method for the measurement of water activity on solid pharmaceutical products, testing the effect of different temperatures, sample preparations, and environment exposure times

Abstract Objective The objective of this investigation is to validate the dew point chilled mirror method for quantifying water activity in tablets and capsules, evaluating the effects of different temperatures, sample preparations, and local environmental exposure times. Key findings The validation of an acute and precise water activity measurement method has become an important goal in the pharmaceutical industry, because it may help to predict the microbiological bioburden on solid products, since most xerophilic and osmophilic microorganisms are unable to grow at water activity levels below 0.60, to safely reduce the frequency of routine microbiological analysis using conventional methods. For all the solid samples tested, a suitability of method was carried out, considering the sample preparation, environmental exposure times, and different measuring temperatures. Following USP guidelines, essential parameters such as precision (SD &amp;lt; 0.5), accuracy (% recovery in the 95%–105% range), linearity (R2 &amp;gt; 0.99), ruggedness (ANOVA, P &amp;lt; .05), robustness, operative range (aw 0.17–1), limits of detection (aw = 0.17), and limit of quantification (aw = 0.25) were met by the dew point methodology. Conclusion The dew point chilled mirror method was proven to yield accurate, precise, and robust data, making it an outstanding methodology to be implemented in the pharmaceutical industry for measuring the water activity status in tablets and capsules as a direct assessment of the microbial burden.

Particulates Matter: The Influence of Cumulative Local Air Pollution Exposure on Sixth-Grade Academic Achievement in California

Particulates Matter: The Influence of Cumulative Local Air Pollution Exposure on Sixth-Grade Academic Achievement in California

Modeling of local and systemic exposure to metals and metalloids after inhalation exposure: Recommended update to the USEPA metals framework.

The USEPA issued the "Framework for Metal Risk Assessment" in 2007, recognizing that human and environmental exposure to metals and metalloids (MMEs) poses challenges risk assessment. Inhalation of aerosols containing MMEs is a primary pathway for exposure in the occupational setting, for consumer exposure, and to general population exposure associated with point-source emissions or ambient sources. The impacts of inhalation can be at the point of deposition (local exposure) or may manifest after uptake into the body (systemic exposure). Both local and systemic exposure can vary with factors that determine the regional deposition of MME-containing aerosols. Aerosol characteristics such as particle size combine with species-specific characteristics of airway morphology and lung function to modulate the deposition and clearance of MME particulates. In contrast to oral exposure, often monitored by measuring MME levels in blood or urine, inhalation exposure can produce local pulmonary impacts in the absence of significant systemic distribution. Exposure assessment for nutritionally essential MMEs can be further complicated by homeostatic controls that regulate systemic MME levels. Predictions of local exposure can be facilitated by computer models that estimate regional patterns of aerosol deposition, permitting calculation of exposure intensity in different regions of the respiratory tract. The utility of deposition modeling has been demonstrated in assessments of nutritionally essential MMEs regulated by homeostatic controls and in the comparison of results from inhalation studies in experimental animals. This facilitates extrapolation from animal data to humans and comparisons of exposures possessing mechanistic linkages to pulmonary toxicity and carcinogenesis. Pulmonary deposition models have significantly advanced and have been applied by USEPA in evaluations of particulate matter. However, regional deposition modeling has yet to be incorporated into the general guidance offered by the agency for evaluating inhalation exposure. Integr Environ Assess Manag 2024;20:952-964. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Local exposure misclassification in national models: relationships with urban infrastructure and demographics

BackgroundNational-scale linear regression-based modeling may mischaracterize localized patterns, including hyperlocal peaks and neighborhood- to regional-scale gradients. For studies focused on within-city differences, this mischaracterization poses a risk of exposure misclassification, affecting epidemiological and environmental justice conclusions.ObjectiveCharacterize the difference between intraurban pollution patterns predicted by national-scale land use regression modeling and observation-based estimates within a localized domain and examine the relationship between that difference and urban infrastructure and demographics.MethodsWe compare highly resolved (0.01 km2) observations of NO2 mixing ratio and ultrafine particle (UFP) count obtained via mobile monitoring with national model predictions in thirteen neighborhoods in the San Francisco Bay Area. Grid cell-level divergence between modeled and observed concentrations is termed “localized difference.” We use a flexible machine learning modeling technique, Bayesian Additive Regression Trees, to investigate potentially nonlinear relationships between discrepancy between localized difference and known local emission sources as well as census block group racial/ethnic composition.ResultsWe find that observed local pollution extremes are not represented by land use regression predictions and that observed UFP count significantly exceeds regression predictions. Machine learning models show significant nonlinear relationships among localized differences between predictions and observations and the density of several types of pollution-related infrastructure (roadways, commercial and industrial operations). In addition, localized difference was greater in areas with higher population density and a lower share of white non-Hispanic residents, indicating that exposure misclassification by national models differs among subpopulations.ImpactComparing national-scale pollution predictions with hyperlocal observations in the San Francisco Bay Area, we find greater discrepancies near major roadways and food service locations and systematic underestimation of concentrations in neighborhoods with a lower share of non-Hispanic white residents. These findings carry implications for using national-scale models in intraurban epidemiological and environmental justice applications and establish the potential utility of supplementing large-scale estimates with publicly available urban infrastructure and pollution source information.

Lecture: "First Aid to the Population in Case of Thermal Burns during Accidents, Catastrophes, Natural Disasters and Terrorist Attacks" of the Subject "Life Safety" for Humanitarian and Technical Universities

To prepare the population to provide first aid for thermal burns in emergency situations, algorithms for modern didactics of the educational topic “Thermal burns” are proposed. The following educational issues are highlighted: 1) Local exposure to high temperature. Burns. Kinds. Classification according to the depth of the lesion; 2) Rules for determining the area of burns; 3) Signs of thermal burns; 4) The concept of burn disease; 5) First (pre-hospital emergency) aid to burnt people; 6). Domestic burns from boiling water; 7) Features of burns in children; 8) Treatment of burns; 9) Prevention of thermal burns.

Business model innovation and international performance of emerging market international businesses

This article is set to examine the effects of foreign market conditions – i.e. foreign market customer demandingness and foreign market stakeholder engagement – on business model innovation of emerging market international businesses (EMIBs) during the COVID-19 pandemic. First, it examines the impact of foreign market customer demandingness and foreign market stakeholder engagement on business model innovation of EMIBs. Second, it tests the moderating roles of international marketing agility and entrepreneurial bricolage on these relationships and third, it looks into the (direct and indirect) impact of business model innovation on EMIBs' international performance. We use the COVID-19 pandemic as a context and the dynamic capabilities view to formulate and test our hypotheses using longitudinal survey data between March and December 2020, on 211 Vietnamese manufacturing businesses engaged in cross-border activities. The results provide robust empirical support for all our hypotheses. Our findings suggest that foreign customer demandingness and foreign market stakeholder engagement can determine the adoption of new business models by EMIBs'. We also provide evidence on the mediating role of EMIBs' business model innovation in the relationship between foreign market conditions and international performance during the COVID-19 pandemic. Additionally, while international marketing agility can moderate positively the relationship between local market exposure and business model innovation by international businesses, entrepreneurial bricolage was found to moderate negatively this relationship. Our findings have important theoretical and practical implications for both international businesses and EMIBs.

Microarray molecular mapping of horses with severe asthma.

Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). This intentional cross-sectional study investigated the sensitization profiles of SA-affected and healthy horses via serological antigen microarray profiling. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non-affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. PLS-DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions.

The effects of radiofrequency electromagnetic fields exposure on tinnitus, migraine and non-specific symptoms in the general and working population: A systematic review and meta-analysis on human observational studies

BackgroundApplications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). ObjectivesThe objective is to systematically review the effects of longer-term or repeated local and whole human body radiofrequency electromagnetic field (RF-EMF) exposure on the occurrence of symptoms. Primary hypotheses were tinnitus, migraine and headaches in relation to RF-EMF exposure of the brain, sleep disturbances and composite symptom scores in relation to whole-body RF-EMF exposure. MethodsEligibility criteria: We included case-control and prospective cohort studies in the general population or workers estimating local or whole-body RF-EMF exposure for at least one week.Information sources: We conducted a systematic literature search in various databases including Web of Science and Medline.Risk of bias: We used the Risk of Bias (RoB) tool developed by OHAT adapted to the topic of this review.Synthesis of results: We synthesized studies using random effects meta-analysis. ResultsIncluded studies: We included 13 papers from eight distinct cohort and one case-control studies with a total of 486,558 participants conducted exclusively in Europe. Tinnitus is addressed in three papers, migraine in one, headaches in six, sleep disturbances in five, and composite symptom scores in five papers. Only one study addressed occupational exposure.Synthesis of results: For all five priority hypotheses, available research suggests that RF-EMF exposure below guideline values does not cause symptoms, but the evidence is very uncertain. The very low certainty evidence is due the low number of studies, possible risk of bias in some studies, inconsistencies, indirectness, and imprecision. In terms of non-priority hypotheses numerous exposure-outcome combinations were addressed in the 13 eligible papers without indication for an association related to a specific symptom or exposure source. DiscussionLimitations of evidence: This review topic includes various challenges related to confounding control and exposure assessment. Many of these aspects are inherently present and not easy to be solved in future research. Since near-field exposure from wireless communication devices is related to lifestyle, a particular challenge is to differentiate between potential biophysical effects and other potential effects from extensive use of wireless communication devices that may compete with healthy behaviour such as sleeping or physical activity. Future research needs novel and innovative methods to differentiate between these two hypothetical mechanisms.Interpretation: This is currently the best available evidence to underpin safety of RF-EMF. There is no indication that RF-EMF below guideline values causes symptoms. However, inherent limitations of the research results in substantial uncertainty. OtherFunding: This review was partially funded by the WHO radioprotection programme.Registration: The protocol for this review has been registered in Prospero (reg no CRD42021239432) and published in Environment International (Röösli et al., 2021)

Dentoalveolar anomalies and modern views on the mechanisms of local stress-modeling effect of orthodontic appliances on the periodontal tissues (a literature review)

The aim of the study was to highlight the results of modern scientific developments in tracing the mechanisms of local stress-modeling effect of orthodontic appliances on the oral cavity and periodontal tissues during the active period of orthodontic treatment. Materials and methods. The research methodology was implemented in the collection and analysis of scientific results on the stress-modeling effect of orthodontic appliances in patients with dentoalveolar anomalies obtained from the processed sources – published full-text articles of original and fundamental research by national and foreign authors based on the evidential databases MEDLINE / PubMed, PMC, Scopus, Web of Science, Cochrane, Google Scholar, ResearchGate and other scientific and practical resources. Results. The main components of the stress-modeling effect of fixed orthodontic appliances on the oral cavity, and particularly on the periodontal tissues, were analyzed. The proportion of various complications is quite high and ranges from 32.7 % to 50.0 % of all cases. The development of oxidative stress during orthodontic treatment is potentiated by microcirculatory disorders and hypoxia of the periodontal tissues. The peculiarities of the periodontal cellular complex reaction, which has the ability to bear stress generated in the actin cytoskeleton by direct mechanical stimulation, to extracellular matrix proteins, affecting the three-dimensional organization of the extracellular matrix and its remodeling, have been traced. The role of lipid peroxidation, antioxidant system and enzymatic reaction of oral and crevicular fluids was also defined. Conclusions. The development of oxidative stress during orthodontic treatment can be caused by local and systemic exposure to metals, corrosion processes in particular; by inflammation of periodontal tissues due to poor oral hygiene and activation of periodontal pathogenic microflora; by aseptic inflammation in the periodontal ligament due to the use of mechanical force. Certain enzymes of the oral fluid, in particular lactate dehydrogenase, can act as a sensitive marker of changes in the periodontal ligament metabolism during orthodontic teeth movement. The localization and nature of free radical pathology are largely caused by the nature of an exogenous inducer of lipid peroxidation and the genotypic characteristics of antioxidant system. It is this ratio that determines the initiation and further chain branching of free radical reactions. Without normalization of all pathogenetic links, successful treatment of inflammatory and dystrophic-inflammatory diseases of the periodontal tissues, in particular in orthodontic patients, is impossible.

The Loser’s Long Curse: How Exposure to Class Conflict Shapes Election Outcomes

Understanding the political consequences of civil war exposure is a challenging task, given the myriad of overlapping and at times divergent mechanisms involved. This article provides evidence of the persistent political legacy stemming from exposure to a violent class conflict. We revisit the Finnish Civil War of 1918 and first trace out the impact of local conflict exposure on electoral outcomes over a quarter-century period between the World Wars. To do so, we combine a difference-in-differences approach with historical data on the geographical distribution of civil war casualties and election outcomes. We document that the local electoral performance of left-wing parties that were associated with the insurgents was persistently and negatively affected by civil war casualties on both sides of the conflict. We also discuss potential mechanisms behind this finding and further show that the civil war had an enduring impact on the Finnish political landscape over a hundred years.

Environmental exposure and sensitization patterns in a Swiss alpine pediatric cohort

BackgroundThe level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment. MethodsClinical and demographic data were collected with a questionnaire. Allergen content was assessed in residential settled dust samples, lifetime exposure to pollen and air pollution was calculated using data from national pollen and air pollution monitoring stations, and the allergic sensitization profile was determined with component resolved diagnostics (ISAC®). Univariate and multivariate regression models were used to estimate the relation between exposure and sensitization. ResultsIn a cohort of children born and raised in an alpine environment, sensitization to aeroallergens is quite common (38%), especially to grass (33%) and cat (16%). House dust mite allergen was detected in up to 38% of residential dust samples, but sensitization to HDM was low (2.5%). Pollutant levels were low, but an increasing trend was observed in the amount of ozone and PM10. Living close to a busy road was associated with increased odds OR (95% CI) for being sensitized to any allergen 2.7 (1.0–7.2), to outdoor allergens 2.8 (1.1–7.1) and being sensitized plus reporting symptoms of rhinoconjunctivitis 4.4 (1.3–14.8) and asthma 5.5 (1.4–21). Indoor living conditions, including the presence of visible mold, increased the odds of being sensitized to indoor allergens (1.9 (1.1–3.2) and being sensitized plus reporting symptoms of rhinoconjunctivitis 1.9 (1.0–3.6) and asthma 2.1 (1.0–4.1). ConclusionIn a healthy alpine environment, pollution might still be an important factor contributing to allergic sensitization.

Characterization of short-, medium-, and long-chain chlorinated paraffins in Tibetan butter and implications for local human exposure

Since short-chain chlorinated paraffins (SCCPs) were severely restricted under the Stockholm Convention in 2017, a shift to the production of other chlorinated paraffin (CP) groups has occurred, particularly medium-chain (MCCPs) and long-chain CPs (LCCPs), although data on the latter are sparser in the literature. This study described the occurrence of three types of CPs in butter samples from six livestock milk sources across 15 sites in Tibet. The median levels of SCCPs, MCCPs, and LCCPs were 132, 456, and 13.2 ng/g lipid, respectively. The detection rate of 97.6% suggests that LCCPs can be transmitted to humans. Thus, all CPs, regardless of their chain length and degree of chlorination, should be treated with caution. The differences in concentration were mainly caused by dynamic wet deposition and thermodynamic cold-trapping effects across the different districts. The homolog pattern of CPs varied widely across livestock species, which was attributed to the diverse impacts of the physicochemical properties of the homologs, especially the heterogeneity in the uptake and transfer of CPs across different organisms. Under three different criteria, the health risks associated with the daily intake of SCCPs should not be neglected, especially considering other intake exposure pathways and the degradation of longer-carbon-chain monomers.