Increasing Levels Of Exposure Research Articles

Bioconcentration and lethal effects of gas-condensate and crude oil on nearshore copepod assemblages

The progressive establishment of gas platforms and increasing petroleum accidents pose a threat to zooplankton communities and thus to pelagic ecosystems. This study is the first to compare the impacts of gas-condensate and crude oil on copepod assemblages. We conducted microcosm experiments simulating slick scenarios at five different concentrations of gas-condensate and crude oil to determine and compare their lethal effects and the bioconcentration of low molecular weight polycyclic aromatic hydrocarbons (LMW-PAHs) in eastern Mediterranean coastal copepod assemblages. We found that gas-condensate had a two-times higher toxic effect than crude oil, significantly reducing copepod survival with increased exposure levels. The LMW-PAHs bioconcentration factor was 1–2 orders of magnitude higher in copepods exposed to gas-condensate than in those exposed to crude oil. The median lethal concentration (LC50) was significantly lower in calanoids vs. cyclopoid copepods, suggesting that calanoids are more susceptible to gas-condensate and crude oil pollution, with potential trophic implications.

Crystal Plane Regulation Promotes the Oriented Conversion of Radicals in Heterogeneous Persulfate Catalyzed Oxidation Process.

In heterogeneous persulfate-catalyzed oxidation systems, the mechanism underlying the crystal plane effects of the catalyst on the selective conversion of reactive oxygen species (ROS) remains ambiguous. In this study, nano-Co3O4 catalysts with varying crystallinity and exposure levels of (111) crystal planes are prepared via a hydrothermal method. Compared to low crystalline catalysts, high crystallinity catalysts predominantly expose (111) planes containing higher concentrations of Co2+ and oxygen vacancies (Ov), resulting in an increase degradation efficiency of p-nitrobenzaldehyde (4-NBA) from 74.5% to 100%. Radical quenching experiments and EPR characterization reveal that the degradation of 4-NBA occurs through a radical pathway, and quantification of radicals demonstrates that increasing exposure levels of (111) planes effectively promote radical yield (CSO4•- increase from 18.2 to 172.8 µm and C•OH increase from 1 to 58.9 µm). Furthermore, XPS and DFT calculations indicate that high crystallinity catalyst possesses more Ov active sites on (111) planes. The presence of Ov not only facilitates the adsorption of PMS molecules but also enhances electron transfer from Co2+ to PMS, leading to directed formation and efficient transformation of radicals. This study presents a novel strategy for promoting efficient radical formation in persulfate-activated systems.

Exposure characteristics and health risk assessment of 97 typical chemical pollutants in human serum

Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 μL of a serum sample was mixed with 10 μL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 ℃. Each sample was then deproteinized by the addition of 200 μL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6∶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 μL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 μm) with temperature programming. The column temperature was maintained at 70 ℃ for 2 min, increased at a rate of 25 ℃/min to 150 ℃, increased at a rate of 3 ℃/min to 200 ℃, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 ℃/min to 300 ℃ and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), β-hexachlorocyclohexane (β-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of β-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and β-HCH. Increased exposure levels to p,p'-DDE and β-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.

Effect of Fluconazole on the Pharmacokinetics of Pyrotinib Maleate: A Single-Center, Open, Single-Dose, Self-Controlled Study in Healthy Chinese Participants

What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes pyrotinib, and its metabolism is influenced apparently by CYP3A4 strong inhibitor, but the effect of CYP3A4 moderate inhibitor is still unclear as a moderate inhibitor of CYP3A4 enzyme. This study evaluated the effect of fluconazole, a widespread antifungal medication, on the pharmacokinetics and safety tolerance of pyrotinib. Methods. This study was an open, single-dose, and self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All participants were administered fluconazole on days 6–18 and pyrotinib on days 1 and 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration–time curve from time 0 to the last measurable concentration (AUC0−t), area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) were calculated using WinNonlin software (version 8.1). Safety tolerance was assessed throughout the process. Results and Discussion. Compared with the single administration of pyrotinib, the exposure level was enhanced significantly after the coadministration of pyrotinib and fluconazole. The geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) of Cmax, AUC0−t, and AUC0−∞ were 2.16, 3.6, and 3.5, respectively. The parameter of t1/2 is 14.16 h and 24.03 h, and CL/F is 275.06 L/h and 78.42 L/h, for pyrotinib alone and with fluconazole. No serious adverse events were reported in this trial, and no participant withdrew from the trial because of adverse events. What Is New and Conclusion. The PK profile of pyrotinib, a CYP3A4 substrate, was significantly influenced by fluconazole, with increased exposure levels and prolonged t1/2. Dosage adjustment is suggested for the clinical application of pyrotinib when coadministered with fluconazole or other CYP3A4 inhibitors/inducers.

Abstract LB064: Using a genomic only approach to a radiation-age association for supplementing differentiation amongst lung diseases and cancer using PMBCs

Abstract Purpose: Ionizing radiation may serve as a reference variable to estimating biological age since it mirrors cumulative DNA damage similar to aging processes. To do this, we aim to establish a rad-age association using genomics as its foundation and clinical applicability with lung disease as an overlapping health concern. Methods: Two datasets were combined and used to empirically find the age cutoff between young and old patients: GSE42488 (Data-A1) and GSE53351 (Data-A2). With age as both a categorical and continuous variable, two other datasets that include radiation exposure are used to test the interaction between radiation and age: GSE21240 (Data-B1) and GSE23515 (Data-B2). A radiation only data was also used in conjunction to evaluate trend analysis with increasing exposure levels: GSE20173 (Data-R1). The gene lists are oriented in preranked lists for both pathway and diseases functional analysis. Finally, these genes are used to evaluate another dataset via GSE42834 (Data-D1) on the clinical relevance in differentiating lung diseases given ethnicity and sex using both pairwise t-tests and linear models including pneumonic, tuberculosis, active and non-active sarcoidosis, lung cancer, and healthy controls. Results: Using 12 well-known genes associated with aging, a threshold of 29 years old was found to be the difference between young and old patients. The two interaction tests (rad and age as continuous plus rad and age as categorical) yielded 234 unique genes such that pathway analysis flagged IL-1 signaling and PRPP biosynthesis as significant with high cell proliferation diseases and carcinomas being a common trend. From the radiation only t-tests, we see a trend of continued upregulation in gene expression as radiation levels increase in 15 of the 17 common genes. When looking at pairwise comparison of disease, ethnicity, or sex, 10 genes were statistically significant, 3 of which had a combination of pairwise significance and fold-change, while LAPTM4B (probe identifier ILMN1680196) was the only gene with significant interaction (p-value=0.004) between lung disease, ethnicity, and sex and fold change greater than two. Conclusion: The results corroborate an initial association between radiation and age given inflammation and metabolic pathways and multiple genes emphasizing mitochondrial function, oxidation, and histone modification. Being able to tie rad-age genes to lung disease supplements a geroscience approach in future work. Citation Format: Nathan A. Ruprecht, Sonalika Singhal, Kalli Schaefer, Jappreet S. Gill, Benu Bansal, Sandeep K. Singhal. Using a genomic only approach to a radiation-age association for supplementing differentiation amongst lung diseases and cancer using PMBCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB064.

Hazardous Exposures of Prosthetic and Orthotic Workshop

Background Prosthetic and orthotic PampO professionals are exposed to noise and chemicals in amounts greater than statutorily allowed and this can have adverse effect on their health. This cross-sectional project work was based on a number of difficulties faced by PampO professionals and effects on their health along with the causes.Objectives 1. To analyse the effects of hazardous exposures due to continuous noise of machines and chemical used in PampO workshop. 2. To check the frequency of noise produced due to the use of machinery and to determine the level of noise emission from the machines. 3. To propose solution within the limits of the PampO workshop of Mobility India MI.Methods Fifty prosthetic and orthotic PampO professionals were included in the study. Data was collected through personal and telephonic interviews using a questionnaire survey. Sound levels of the individual machines and all the machines operated together were measured using a sound level meter.Results The exposure to noise level was found to be higher indicating an urgent need for attention of the management and supervisor. One of the problems observed was the lack of awareness among participants about noise pollution and safety procedures or devices to prevent these hazards in the work environment.Conclusion This study found increased exposure levels of sound and chemicals thus affecting the well-being of the participants.

Exposure to air pollution is associated with an increased risk of metabolic dysfunction-associated fatty liver disease

Accumulating animal studies have demonstrated the harmful contribution of ambient air pollution (AP) to metabolic dysfunction-associated fatty liver disease (MAFLD), but corresponding epidemiological evidence is limited. We examined the associations between long-term AP exposure and MAFLD prevalence in a Chinese population. We conducted a cross-sectional study of 90,086 participants recruited in China from 2018 to 2019. MAFLD was assessed based on radiologically diagnosed hepatic steatosis and the presence of overweight/obese status, diabetes mellitus, or metabolic dysregulation. Residence-specific levels of air pollutants, including particulate matter with aerodynamic diameters of ≤1 μm (PM1), ≤2.5 μm (PM2.5), and ≤10 μm (PM10), and nitrogen dioxide (NO2), were estimated by validated spatiotemporal models. We used logistic regression models to examine the AP-MAFLD associations and further evaluated potential effect modifications by demographics, lifestyle, central obesity, and diabetes status. Increased exposure levels to all 4 air pollutants were significantly associated with increased odds of MAFLD, with odds ratios (ORs) of 1.13 (95% CI 1.10-1.17), 1.29 (1.25-1.34), 1.11 (1.09-1.14), and 1.15 (1.12-1.17) for each 10 μg/m3 increase in PM1, PM2.5, PM10, and NO2, respectively. Further stratified analyses revealed that individuals who are male, alcohol drinkers, and current and previous smokers, those who consume a high-fat diet, and those with central obesity experience more significant adverse effects from AP exposure than other individuals. This study provides evidence that long-term exposure to ambient PM1, PM2.5, PM10, and NO2 may increase the odds of MAFLD in the real world. These effects may be exacerbated by unhealthy lifestyle habits and central obesity. We conducted an epidemiological study on the potential effect of ambient air pollution on the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in approximately 90 thousand adults in China. We found that long-term exposure to ambient air pollution may increase the odds of MAFLD, especially in individuals who are male, smokers, and alcohol drinkers, those who consume a high-fat diet, and those with central obesity.

Chlorinated polyfluoroalkyl ether sulfonic acids in fish, dust, drinking water and human serum: From external exposure to internal doses.

Exposure to per- and polyfluoroalkyl substances (PFASs) has raised significant public health concerns due to their persistence and toxicity in the human body. Here, we aimed to investigate the characteristics of exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) and legacy PFASs and the relative contribution from different external pathways to human exposure. Three Cl-PFESAs and fourteen legacy PFASs were detected in human serum, fish, indoor dust and drinking water collected from Shijiazhuang, China. Results showed that 6:2 Cl-PFESA was the third most predominant compound, with an average concentration of 2.70ng/mL in serum, which was lower than those of perfluorooctane sulfonate (PFOS) and perfluorooctane acid (PFOA) (14.79 and 4.91ng/mL). The estimated daily intake of 6:2 Cl-PFESA via dust ingestion (mean: 0.008ng/kg bw/day) was found to be highest among all detected PFASs, while the highest value via fish and drinking water was found for PFOS and PFOA (0.438-9.799 and 0.034-0.155ng/kg bw/day), respectively. The similar composition of PFASs between serum and fish suggests that fish consumption is a major contributor to human exposure to PFASs. However, the increasing ratios of EDIindoor dust/EDIfish for PFOS, PFOA and 6:2 Cl-PFESA indicated that the contribution of dust ingestion for PFASs, especially 6:2 Cl-PFESA, could not be ignored. The modeled serum concentrations of 6:2 Cl-PFESA higher than its observed levels hint at its gradually increasing exposure levels in the general population. Combined with the lower modeled levels of PFOS than the observed levels, the substituent with 6:2 Cl-PFESA for PFOS is obvious in China. Therefore, further studies on contributions from more detailed external sources and risk assessments of Cl-PFESAs are recommended, especially for some vulnerable subpopulations, considering their widespread exposure and similar environmental behaviors compared with those of their predecessors.

Delineation of the exposure-response causality chain of chronic copper toxicity to the zebra mussel, Dreissena polymorpha, with a TK-TD model based on concepts of biotic ligand model and subcellular metal partitioning model

A toxicokinetic-toxicodynamic model was constructed to delineate the exposure–response causality. The model could be used: to predict metal accumulation considering the influence of water chemistry and biotic ligand characteristics; to simulate the dynamics of subcellular partitioning considering metabolism, detoxification, and elimination; and to predict chronic toxicity as represented by biomarker responses from the concentration of metals in the fraction of potentially toxic metal. The model was calibrated with data generated from an experiment in which the Zebra mussel Dreissena polymorpha was exposed to Cu at nominal concentrations of 25 and 50 μg/L and with varied Na+ concentrations in water up to 4.0 mmol/L for 24 days. Data used in the calibration included physicochemical conditions of the exposure environment, Cu concentrations in subcellular fractions, and oxidative stress-induced responses, i.e. glutathione-S-transferase activity and lipid peroxidation. The model explained the dynamics of subcellular Cu partitioning and the effect mechanism reasonably well. With a low affinity constant for Na + binding to Cu2+ uptake sites, Na + had limited influence on Cu2+ uptake at low Na+ concentrations in water. Copper was taken up into the metabolically available pool (MAP) at a largely higher rate than into the cellular debris. Similar Cu concentrations were found in these two fractions at low exposure levels, which could be attributed to sequestration pathways (metabolism, detoxification, and elimination) in the MAP. However, such sequestration was inefficient as shown by similar Cu concentrations in detoxified fractions with increasing exposure level accompanied by the increasing Cu concentration in the MAP.

Impact of aqueous exposure to silver nanoparticles on growth performance, redox status, non-specific immunity, and histopathological changes of Nile Tilapia, Oreochromis niloticus, challenged with Aeromonas hydrophila

Silver nanoparticles (AgNP) are one of the most synthesised nanomaterials due to their widespread applications, which in turn increases the potential of release and accumulation in nature. Moreover, they are known as antibacterial and recommended to be used in different commercial drugs. However, the evaluation of their effect on living organisms, especially fish, at low levels is still not completely understood. Therefore, the present study was conducted to investigate the effects of aqueous exposure of AgNPs on growth performance, oxidative status, non-specific immunity, and histopathological changes of epidermis, gills, liver, and intestine of Nile Tilapia, Oreochromis niloticus. The fish were exposed to four concentrations of AgNP (0, 10, 20, and 30 μg L-1) for 8 weeks. At the end of the experiment, fish were intraperitoneally injected with pathogenic bacteria Aeromonas hydrophila and fish mortalities were recorded up to 14 days post-challenge. The results revealed that growth performance and feed utilisation of fish exposed to the lower AgNPs concentration improved significantly compared to other treatments. The increasing AgNP exposure levels decreased different growth indicators in a dose-dependent manner. The highest catalase, superoxide dismutase, glutathione peroxidase, lysozyme, and respiratory burst activities were recorded with 10 μg AgNPs L−1 and the enzyme activities were retarded with increasing AgNP concentrations. The total bacteria count in the water decreased with increasing AgNP concentrations. Meanwhile, the relative percentage of survival improved with low AgNP concentration and decreased with increasing exposure levels. The histopathological investigation of different studied tissues (gills, skin, liver, and intestine) revealed an increase of histological lesions’ frequency and severity with increasing AgNP concentrations. It can be concluded that the exposure of Nile Tilapia to AgNP at levels exceeding 10 μg L−1 could interrupt growth performance, immunity, and antioxidant status and induced histopathological changes.

Association of Cigarette Smoking with Muscle Mass Reduction and Low Muscle Strength in Community-Dwelling Elderly Men

Recently, attention has been paid to the impact of cigarette smoking on skeletal muscles, as its underlying pathophysiological mechanism has been gradually elucidated. In this study, we aimed to examine whether cigarette smoking is associated with muscle mass reduction and low muscle strength in elderly men. The study participants comprised 417 community-dwelling elderly men (aged 73±6 years) without severe glucose intolerance, chronic kidney disease, or liver disease. Bioelectrical impedance analysis was performed to estimate appendicular skeletal muscle mass (ASM), which was normalized for height (ASM index, kg/m2). Handgrip strength (HGS) was measured using a Smedley grip dynamometer. Cumulative smoking exposure level during a lifetime was expressed in pack-years, which is a product of the average number of packs of cigarettes smoked per day and smoking duration in years. When the participants were stratified on the basis of cumulative smoking exposure (<10 pack-years, 10-39 pack-years, ≥40 pack-years), the ASM index and HGS progressively decreased with increasing exposure level (P for trend <0.01). In multiple regression analysis, heavy smoking (defined as ≥40 pack-years) was found to be a significant determinant of the ASM index and HGS, independent of potential confounding factors. Among former smokers, the subgroup that quit smoking for ≥20 years had a significantly higher ASM index and HGS than the subgroup that quit smoking for <10 years. The duration of smoking cessation was significantly associated with the ASM index and HGS, even after adjusting for cumulative smoking exposure. These findings suggest that cigarette smoking contributes to the loss of muscle mass and function in elderly men and that smoking cessation could reverse the impact of cigarette smoking on skeletal muscles.

Modelling copper toxicokinetics in the zebra mussel, Dreissena polymorpha, under chronic exposures at various pH and sodium concentrations

The stenohaline zebra mussel, Dreissena polymorpha, is uniquely sensitive to the ionic composition of its aquatic environment. Waterborne copper (Cu) uptake and accumulation in zebra mussels were examined at various conditions in an environmentally relevant range in freshwater, i.e. Cu exposure levels (nominal concentrations of 25 and 50 μg/L), pH (5.8–8.3), and sodium (Na+) concentrations (up to 4.0 mM). Copper accumulation was simulated by a kinetic model covering two compartments, the gills and the remaining tissues. The Cu uptake rate constant decreased with decreasing pH from 8.3 down to 6.5, indicating interactions between H+ and Cu at uptake sites. The kinetic simulation showed dose-dependent effects of Na+ on Cu uptake. At 25 μg/L Cu, addition of Na+ at 0.5 mM significantly inhibited the Cu uptake rate, while no significant differences were found in the uptake rate upon further addition of Na+ up to a concentration of 4.0 mM. At 50 μg/L Cu, the Cu uptake rate was not influenced by Na+ addition. Calibration results exhibited dose-dependent elimination rates with more profound elimination with increasing exposure levels. With kinetic parameters calibrated at environmentally relevant conditions, in terms of pH and Na+ concentrations, the model performed well in predicting Cu accumulation based on independent data sets. Estimates of the Cu concentration in mussels were within a factor of 2 of the measurements. This demonstrates potential application of kinetic models that are calibrated in environmentally relevant freshwater conditions.

Associations between Childhood Toenail Manganese Concentrations and Neurodevelopment in Rural Appalachian Ohio

Background: Manganese (Mn) is necessary in trace quantities; however, at increased exposure levels the metal poses a risk to neurologic functions. While there is no universally accepted biomarker of Mn exposure, toenails are novel, noninvasive measures that represent cumulative exposure. The Communities Actively Researching Exposure Study (CARES) is an established pediatric cohort in eastern Ohio which includes children aged 7-9 living near industrial sources of excess Mn exposure. This study aims to understand the relationship between Mn exposure, quantified through toenails, and neurodevelopmental outcomes among CARES participants.Methods: Toenail samples collected from participating children were analyzed for Mn content. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV), the Behavioral Assessment System for Children-2 (BASC2), and the Behavior Rating Inventory of Executive Functions (BRIEF). We assessed linear relationships between toenail Mn concentrations and Intelligence Quotient (IQ) and behavioral scores. Quartiles of the distribution for toenail Mn were represented with categorical variables and multiple regression models were ran to assess nonlinearity. Critical confounders such as blood lead and serum cotinine were included.Results: Exposure and outcome data were available for 404 children. Our study suggests a nonlinear relationship among boys, with lower Working Memory IQ scores observed among those with low (β = -3.46; 95% CI -7.54, 0.62) and high (β = -5.07; 95% CI -9.86, -0.29) levels of toenail Mn. The effect of Mn on the global executive function and BRIEF composite scales was 4 to 6 times greater among girls compared to boys, respectively.Conclusions: Toenails appear to be a valuable biomarker for Mn exposure. Gender is a crucial factor with regards to the neurotoxicology of Mn. Future research is needed to further elucidate the toxicokinetics of Mn in toenails as well as the mechanisms behind the influence of gender on the relationship between Mn and neurodevelopment.

Time course and local distribution of skin exposure of hand andfingers from [68Ga]Ga-DOTA-NOC synthesis using aself-shieldedmodule.

The study examined the local dose distribution as well as the time course of skin exposure of hand and fingers from [68Ga]Ga-DOTA-NOC synthesis using a self-shielded synthesis module. A compact calibrated electronic dosimeter (ED) with a miniaturized probe was used for real-time measurements of skin dose equivalent Hp (0.07) (reference point: left and right index finger). A time resolved assessment of exposure during radiotracer production was performed. Additionally, thermoluminescence dosimeters (TLD) were used to determine local dose distribution for five different positions (e. g. fingertips). Cumulated Hp (0.07) estimated by ED was analysed and correlated with the measurements obtained by a TLD positioned close to the ED. The cumulative skin exposure from the production process measured by ED, was 74.7 ± 32.7 µSv/GBq and 40.1 ± 14.3 µSv/GBq for the right and left hand, respectively. The exposure recorded by the ED was in the average 19.4 % ± 40.0 % (median = 21.3 %) lower compared to the results from TLD. Highest exposure was recorded during synthesis (guided hand: 24.5 ± 12.2 µSv/GBq) and measuring of product yield including preparation of probes for quality control (guided hand: 36.1 ± 12.7 µSv/GBq). The highest local exposure was measured by a TLD close to the tip of the index finger of the guiding hand (range: 773-1257 µS/GBq). The chosen methodology using ED, proved to be a good concept for identifying procedure steps with an increased exposure level and to determine the time course of skin exposure and to identify procedure steps for further optimization of handling. Furthermore, miniaturized electronic dosimeters may be used for online surveillance of local exposure rates at hands and fingers.

The role of macro- and microelements in the pathogenesis of polycystic ovary

PCOS is a common disease that occurs in 3–15% of women of childbearing age, according to various authors. Despite numerous studies, there are still many conflicting views on the etiology of PCOS, as well as on the diagnostic criteria and treatment methods for this disease.Purpose of the study. Evaluation of macro- and microelements in blood serum of women with PCOS and study of their role in development of this disease.Materials and methods. The control group consisted of 38 healthy women. The study group included 52 women with PCOS. In both groups magnesium (Mg), copper (Cu), manganese (Mn), nickel (Ni), zinc (Zn), chromium (Cr), selenium (Se), and vanadium (V) were determined in blood serum. Samples were analyzed by inductively coupled plasma mass spectrometry. Statistical significance of the results was evaluated using the Kolmogorov-Smirnov, Mann-Whitney criteria, Student’s t-test.Results of the study. Increase in Mn, Ni, and Zn was found in women with PCOS an. Cu, Mg, Cr, Se, V value in both groups were the same. The medians of the Mn, Ni and Cr level exceed the permissible standards in both groups of women, which indicate an increased exposure these metals on the population. Mn and Ni were significantly higher in women with PCOS compared to the control group. The authors of the study suggested that an increased exposure level of Mn and Ni may be the cause or background factor for the PCOS.Conclusion. Higher levels of manganese, nickel and zinc in the blood serum in women with PCOS compared with the control group were found. An increased manganese and nickel exposure on the body can cause PCOS. Increase in zinc in women with PCOS is likely due to the body's adaptive response.

Occupational exposures and male breast cancer: A nested case-control study in the Nordic countries

BackgroundMale breast cancer (MBC) is a rare and understudied disease. There is limited evidence on association between environmental and occupational agents and MBC. Some similarities in risk factors may be shared with female breast cancer. We evaluated solvents, metals, exhaust gases and other agents in relation to MBC within the large Nordic Occupational Cancer Study (NOCCA). MethodsThe study included 1469 MBC cases and 7345 controls from Finland, Iceland and Sweden, matched for the date of birth, sex and country. Cases were identified through national cancer registries. Data on occupation and other demographic indicators were collected from census records and population registries. Overall, 24 occupational exposures were assessed. Exposure estimates were assigned by linking job titles to job-exposure matrices (NOCCA-JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. ResultsSignificantly decreased overall OR was observed for physical workload (OR = 0.78, 95% CI 0.67–0.91). Protective effect of physical workload was stronger by increasing exposure level with significant dose-response relationship (p-trend<0.01). Non-significantly increased ORs were observed for trichloroethylene, iron, lead, chromium, welding fumes and wood dust, and decreased ORs for asbestos, silica dust and perchloroethylene. However, these results were not consistent across all analyses. ConclusionsThe current study showed 20–25% protective effect for physical workload at work, while no strong evidence for other agents was observed.

Phenomenological Model of Radiation Hardness of LEDs Based on AlGaInP Heterostructures with Multiple Quantum Wells

Neutron degradation of LEDs based upon AlGaInP heterostructures (λ=630 nm and λ=590 nm) with multiple quantum wells are presented in the article. For the initial red LED (λ=630 nm) we can clearly distinguish three characteristic regions. In the small current region a low electron injection mode into the active region of the LEDs is observed. Further, as the operating current goes up, there are average and high electron injection in the active LEDs area regions. However, for the LEDY, the difference in the average and high electron injection regions is more pronounced and low electron injection region is absent. The boundary between the average and high electron injection regions can be characterized by the boundary current, which goes up with increasing exposure level. Three regions of electron injection in the active area of LEDs: low, average and high electron injection are illustrated for both types of LEDs under fast neutron irradiation. Based on the established relationships describing the emission power changing, a phenomenological model of the radiation hardness of LEDs based on AlGaInP heterostructures with MQW was shown. The LEDs radiation hardness is determined by the boundary current value, emission power in the low electron injection into the active LEDs area, the initial defective structure.

Co-crystals as a new approach to multimodal analgesia and the treatment of pain.

Pain is highly prevalent, but frequently untreated or under-treated, and health care professionals are faced with a range of treatment challenges. Multimodal therapy is recommended and can be achieved using open combinations (ie, concomitant administration) of individual agents, fixed-dose combinations (FDCs), or multimodal agents (ie, single agents with multiple mechanisms of action). Co-crystallization of active pharmaceutical ingredients (APIs) offers another approach, with the potential to provide drugs with unique properties and advantages for therapeutic applications compared to combinations. API–API co-crystals are single-entity forms that offer a unique possibility of improving the physicochemical properties of both constituent APIs, as well as permitting their synchronous release. Consequently, this may positively impact on their pharmacokinetic (PK) properties and profiles, providing a potential advantage over FDCs and translating into improved clinical efficacy and safety profiles. We report here a revision of the literature concerning API–API co-crystals for the treatment of pain. It becomes apparent that identifying APIs with complementary mechanisms of action that can be adequately co-crystallized in an appropriate molecular ratio applicable for therapeutic use is challenging. In addition, API–API co-crystals normally result in a mere increased exposure of an API without defined clinical benefits (since, to maintain the benefit-risk, the dose needs to be proportionally reduced to adjust for the increased exposure). An exception to this is the co-crystal of tramadol-celecoxib (CTC), that represents a unique concept in co-crystal technology. In CTC neither of its three active components that have complementary mechanisms of action (ie, the two enantiomers of tramadol and celecoxib) show increased exposure levels versus commercially available single-entity reference products, but rather show a change in their PK profile with potential clinical advantages. CTC is in Phase III clinical development for the treatment of pain.

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC)

ObjectivesPreviously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent....

Differences in the bioaccumulation of selenium by two earthworm species (Pheretima guillemi and Eisenia fetida)

Information on the bioaccumulation of selenium (Se) in soil invertebrates (e.g. earthworms) is rather scarce. In the present study, bioaccumulation of Se in two eco-physiologically different earthworms, namely anecic Pheretima guillemi and epigeic Eisenia fetida, was determined after 28 days exposure to a successive doses of Se-spiked soil, specifically 0.5, 5, 50, and 200 μg Se g−1 soil. The results showed that Se concentration in earthworms elevated with increasing exposure levels, and maximums were up to 54.6 and 83.0 μg g−1 dry weight in Pheretima guillemi and Eisenia fetida, respectively, after 4 weeks exposure to 200 μg Se g−1 soil. Exposure to Se caused significant inhibition on earthworm growth, with the fresh weight loss ranging from 8.9% to 80.5%. Bioaccumulation factors (BAFs), empirically-derived and non-steady state, ranged from 0.12 to 4.17 and generally declined at higher exposure levels. Moreover, BAFs of Pheretima guillemi were higher than those of Eisenia fetida in low-dose Se-spiked soils, but the opposite was true in high-dose soils, indicating there is a species-specific response to exposure of Se between different earthworms. Further research is thus needed to reveal the accumulation pattern of Se in a wider range of earthworm species other than Eisenia fetida, which allows a better risk assessment of excessive Se to soil invertebrates and higher order organisms.