Average Concentration Research Articles

Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.

There is a significant medical need for improved long-acting local anesthetics to decrease postsurgical pain and reduce postoperative opioid use. While ropivacaine is considered a safer local anesthetic than bupivacaine, no long-acting ropivacaine formulation is currently marketed. Available formulations of bupivacaine show inconsistent pharmacokinetics (PK) among different surgical models, and inconsistency in PK may lead to a reluctance to use the medication owing to fear of local anesthetic systemic toxicity (LAST) or unreliable efficacy. CPL-01 is a novel extended-release formulation of ropivacaine. This analysis used existing published literature to compare the PK of CPL-01 and liposomal bupivacaine (LB) across five surgical models. Published results of LB PK were used to construct dose-normalized curves in total knee arthroscopy, hemorrhoidectomy, and bunionectomy after a 200 mg dose, which were compared with a 200 mg dose of CPL-01 in abdominoplasty, herniorrhaphy, and bunionectomy. The shape of the CPL-01 systemic concentration curves was consistent across multiple surgical models; however, in LB it was not. The median time to peak concentration (Tmax) of CPL-01 was 8-12 h and the median Tmax of LB varied from < 1 to 36 h. CPL-01 showed tighter ranges in average peak concentration (Cmax) compared with average concentration (Cavg) ratios (less "swing") throughout 72h, suggesting a more predictable and consistent release over time compared with the biphasic release in LB, with two distinct Tmax peaks. CPL-01 demonstrates a more predictable and consistent release of ropivacaine over time, in contrast to LB's erratic and biphasic release of bupivacaine. If approved, the predictability of CPL-01 PK may give physicians greater confidence in more consistent efficacy and less fear of inadvertent LAST.

510. Bacteriophages as Drug Delivery Vehicles for Polymyxin B

Abstract Background The goal of this project is to develop a safer, more effective formulation of polymyxin B for E. coli bacteremia. Polymyxins are a family of cyclic lipopeptides that display exceptional antibiotic activities toward gram-negative pathogens such as E. coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. The PMB label includes an FDA black box warning for serious nephrotoxicity and neurotoxicity. However, today, with the growing emergence of “superbugs” and a dry antibiotic discovery pipeline, PMB is increasingly used as a last-line therapy to treat systemic infections. Thus, although PMB is a potent antibacterial agent, its toxicity currently prevents its use as an earlier or more widespread treatment. Transmission electron microscopy (TEM; negative stain) images of anti-LPS phage bound to gram-negative organisms. Phages were labeled with gold nanoparticles (dark spheres) coated with antibodies against pVIII, allowing phages to be easily identified (red darts). Gold-labeled anti-LPS phage are shown (A) without bacteria; or incubated with (B) E. coli DH5α; (C) E. coli ATCC BAA 1161; (D) A. baumannii ATCC 19606. Phage width is increased by the labeling reagents. Scale bars = 500 nm. Methods We engineered M13 to bind the core antigen of lipopolysaccharide (LPS), enabling binding to a variety of top-priority pathogenic gram-negative bacterial species, including E. coli, P. aeruginosa, A. baumannii, Klebsiella pneumoniae, and Burkholderia cepacia. Since the anti-LPS phages are able to bind but do not infect (nonviable), they are not cytotoxic by themselves. However, delivery of PMB by the anti-LPS phage confers antibiotic activity. Thus, in our strategy, PMB molecules are conjugated to the anti-LPS phage capsid, and delivered specifically to gram-negative bacterial cells through the specificity and high affinity of the anti-LPS binding domain. We have shown that the PMB – anti-LPS phage conjugate (termed “PMB–Phage” hereafter) effectively lowers the minimal inhibitory concentration of PMB by multiple orders of magnitude in vitro compared to PMB sulfate. MIC and MBC of PMB and PMB-Phage, determined in vitro for several gram-negative organisms. The heat map corresponds to the MIC or MBC values. Equivalent PMB concentrations for PMB-Phage MIC and MBC were calculated from the measured phage concentration and the average amount of PMB loaded per virion. * = resistant. ND = not determined due to technical limitation on phage concentration. Results We have already demonstrated following results.A broad-spectrum anti-LPS phage was engineered and verified to bind to several gram-negative bacterial species including E. coli.Polymyxin B was conjugated to the anti-LPS phage, creating PMB-Phage, which was highly antibacterial in vitro.PMB-Phage is non-toxic to mammalian cells in vitro and non-toxic in mice.PMB-Phage is distributed to various organs within 1 hour and has an elimination half-life of approximately 1 day.PMB-Phage appears to be effective in treating E. coli bacteremia in a mouse model. PMB-Phage Biodistribution Figure 9: Time course biodistribution of PMB-Phage in various organs, over time in male mice with (red) or without (blue) 1×10^7cfu (non-lethal dose) of E. coli ATCC BAA 1161 injected (n=3). Signals are measured as a percentage of the injected dose (ID) per volume (per cc). Representative biodistribution images (j) of 1 animal. Conclusion PMB-Phage will greatly reduce the nephrotoxicity of PMB, enabling safe treatment for a broader patient population. Liver and kidney blood biomarkers at end point of 7-day toxicity studies. Animals in experimental groups were injected 100µL of test materials through IV tail vein injection daily for 7 consecutive days. Experimental group animals for each condition (N=3), receiving either PMB or PMB-Phage at different doses show no significant difference comparing to control groups of animals group receiving no treatment (N=5) and 1xPBS buffer (N=3), in light and dark grey columns respectively. The only exception being all animals receiving 72 mg/kg body weight PMB (N=3) did not survive a single dose and died on day 1 (indicated by red cross in figure). Disclosures All Authors: No reported disclosures

Estimation of Natural Radioactivity Concentrations of 238u, 232th and 40k in Soil Samples from Belagavi District, Karnataka, India

The natural radioactivity concentrations of Uranium (238U), Thorium (232Th), and Potassium (40K) in soil samples from Belagavi District in Karnataka, India were measured to assess the radiological impact on the environment and public health. Soil samples were collected from two different locations within the district, and the radioactivity levels of U, Th, and K were determined using NaI (Tl) a High-Resolution Gamma Spectrometer. The average activity concentrations of Uranium, Thorium, and Potassium were found to be 26.84 ± 0.16 Bq/kg, 48.33 ± 0.09 Bq/kg, and 150.71 ± 1.61 Bq/kg, respectively, in Savadatti soil samples, and 22.87 ± 0.19 Bq/kg, 54.43 ± 0.11 Bq/kg, and 219.99 ± 1.77 Bq/kg, respectively, in Belavadi soil samples. These results were compared with global and regional reference values to evaluate the radiological risk. The calculated Radium Equivalent Activity (Ra eq), External Hazard Index (H ex), were used to assess the potential health risks associated with the radioactivity levels in the soil. The study revealed that the radiological indices in the soil samples were within the safe limits, although certain areas showed slightly elevated concentrations. This study contributes to the understanding of natural radioactivity in the selected region and emphasizes the need for continuous monitoring to safeguard environmental and public health. The findings are compared with global safety limits set by international organizations like UNSCEAR.

Seasonal trends and sources of dicarboxylic acids in fine aerosol over the Brahmaputra valley, North-East India.

The atmospheric dicarboxylic acids (DCAs) have a significant impact on the climate and indirectly affect human health, making them important organic substances. PM2.5 bound DCAs were analysed for Jorhat, India, 2019. In addition to the temporal variability, seasonal variation throughout the year and the impact of varying meteorological factors on DCAs concentration have also been studied. It has been noted that precipitation and ambient air temperature considerably impact DCA concentrations, which affect the type of source contribution of DCAs. The average concentration of all DCAs was 107.04 ± 97.54ng/m3, with a higher prevalence of high molecular weight DCAs than low molecular weight DCAs. Correlation analysis, water-soluble inorganic species, EC-OC ratio and diagnostic ratios of DCAs were employed to determine whether DCAs originate from direct emission and/or from photochemical oxidation of biogenic or anthropogenic precursors. DCAs concentration varied seasonally in decreasing order, with the maximum in the monsoon (144.24 ± 101.62ng/m3) followed by winter (138.36 ± 95.11ng/m3), post-monsoon (80.72 ± 37.27ng/m3), and summer (36.64 ± 34.52ng/m3). Air mass back trajectory and concentration-weighted trajectory (CWT) were used to show both short and long-range air mass transport with moderate to high DCAs contribution regions. Photochemical oxidation of diacids precursors predominates during the monsoon season, whereas in winter, direct anthropogenic emissions account for the majority of DCAs.

Responsiveness of glycyrrhetinic acid modified liposome toward secretory phospholipase A2 and its growth inhibitory in Colo205 cells

This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A2 (sPLA2) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A2 (sPLA2). In vitro experiment, the sPLA2 levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5–4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA2 and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA2 in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.

Comparison of Radiation Levels in the Soil and Rocks in the Areas Surrounding Old Phosphate Mine, Russaifa, Jordan

Abstract The activity concentrations of the terrestrial naturally occurring radionuclides 214Pb, 214Bi (from 238U series), and 228Ac (from 232Th series) and 40K were measured in soil and rock samples obtained from three sites of the Russaifa mine and its surrounding in the Russaifa region using an HPGe-detector of 20 % relative efficiency. While the soil activity (in Bq/kg) was found to be: 408.63 ± 26, 383.9 ± 4.7, and 383.0 ± 4.0 for 238U, 214Bi, and 214Pb, respectively. The rock activity was found to be 225.4 ± 19, 180.36 ± 3.9, and 179.47 ± 3.1 for 238U, 214Bi, and 214Pb, respectively. Our results reveal that the average activity concentrations in the mine (site 1) are higher than worldwide average values [6] for 238U, 214Pb, and 214Bi. In contrast, the results show that the average absorbed dose rates in the other sites 2 and site 3 are lower than the world average for all radionuclides measured in this study. Also, the average activity concentrations in soil samples 238U, 214Pb, and 214Bi are higher than the average activity concentrations in rock samples in all sites. Furthermore, the average absorbed dose rate (in nGy h-1) was found to be 265.3 for 238U, 233.3 for 214Bi, and 13.3 for 214Pb, respectively, and the average absorbed dose rates for both 228Ac and 40K were below the minimum detectable activity (MDA). Moreover, the average annual effective dose rates in soil and rock samples were estimated. While it is found to be 366.90 µSv for 238U, 306.84 µSv for 214Bi, and 37.58 µSv for lead in soil samples, for the rock samples it is found to be 163.75 µSv for 238U, 105.83 µSv for 214Bi, 13.05 µSv for lead. However, the average annual effective dose rates for 214Bi and 40K in soil and rock samples are below the minimum detectable activity (MDA). The results display that the average outdoor annual effective doses for both 238U and 214Bi are higher than the world average and the average outdoor annual effective dose equivalents for the other radionuclides are lower than the world average. They also show that the average outdoor annual effective doses in soil samples for 238U, 214Pb, and 214Bi are higher than the average outdoor annual effective doses in rock samples.

BneR: A collaborative workflow for air pollution exposure modeling and uncertainty characterization using the Bayesian Nonparametric Ensemble.

Air pollution is a major public health threat globally. Health studies, regulatory actions, and policy evaluations typically rely on air pollutant concentrations from single exposure models, assuming accurate estimations and ignoring related uncertainty. We developed a modeling framework, bneR, to apply the Bayesian Nonparametric Ensemble (BNE) prediction model that combines existing exposure models as inputs to provide air pollution estimates and their spatio-temporal uncertainty. The bneR modeling framework (1) harmonizes air pollutant datasets to use standardized inputs for the BNE algorithm; (2) applies the BNE algorithm to obtain the posterior predictive distribution of pollutant concentrations; and (3) generates visualizations. We applied bneR to estimate NO2 concentrations and characterize uncertainty levels at high spatio-temporal resolution (daily, 1 km2) over New York State (NYS) for 2015. We met with stakeholders and modelers to discuss bneR user-friendliness and interpretation of its estimates. Using bneR, we harmonized the spatial scale of four input NO2 models (using the finer resolution, 1 km2 for BNE estimations), applied BNE to obtain the NO2 daily posterior predictive distribution, and visualized the results. Over NYS, the daily average NO2 concentration was 6.0 (interquartile range, IQR: 4.6-6.8) pbb with daily average uncertainty (as SD) of 1.2 (IQR: 1.0-1.3) ppb. BNE performed well with cross-validated RMSE=2.84 ppb and R2=0.80. Meeting stakeholders and modelers allowed us to understand that efficient communication on how uncertainty is estimated and interpreted is a key feature for these communities to engage in using bneR and its data products.

Performance evaluation of four cascade impactors for airborne ultrafine-particle (UFP) collection: the influence of particle type, concentration, mass, and chemical nature

Abstract. Ultrafine particles (UFPs) have aerodynamic diameters of 100 nm or less. As UFPs potentially impact human and environmental health, their chemical composition is of interest. However, their small mass presents challenges for sampling and chemical characterization methods. Therefore, we conducted a comprehensive characterization and comparison of four cascade impactors suitable for separating and collecting UFPs – namely, the 120R Micro-Orifice Uniform Deposit Impactor (120R MOUDI-II), ultraMOUDI, electrical low-pressure impactor (ELPI), and personal nanoparticle sampler (PENS) – under controlled laboratory conditions and in a field application. In the laboratory, we evaluated pressure drops, cutoff diameters, the steepness of the cutoff curve, losses, particle bounce, and transmitted particle mass. We observed that the performance of the impactors varied between 59 and 116 nm in cutoff diameter (electromobility diameter), depending on the impactor's design and the type of test aerosol mixture – salt particles (NaCl), simulated secondary organic aerosol (SimSOA), or soot. All impactors separated UFPs, with the best agreement in cutoff diameters for SimSOA, which showed maximum deviations of about 4 nm. The cutoff curve was steeper for soot compared to SimSOA and NaCl. Pressure drops were measured at 260 ± 1 hPa (PENS), 420 ± 2 hPa (ultraMOUDI), 600 ± 3 hPa (120R MOUDI-II), and 690 ± 3 hPa (ELPI). Losses were assessed as maximum transmissions in the ultrafine fraction at 30 nm, yielding 83 ± 8 % for the PENS, 77 ± 8 % for the ultraMOUDI, 75 ± 8 % for the 120R MOUDI-II, and 69 ± 7 % for the ELPI. We compared two additional impactor-specific factors crucial for mass-based analyses of organic marker compounds: the evaporation of semi-volatile compounds due to a high-pressure drop across the impactor and material addition from larger particles bouncing off upper stages. “Bounce-off” was influenced by the particle number concentration in the sampled air and could be partially mitigated by applying a coating to the upper impaction plates. In the field application, we deployed the four cascade impactors side by side under environmental conditions to sample urban air. We analyzed six markers representing typical UFP sources and various molecular properties using HPLC-MS/FLD (high-performance liquid chromatography with mass spectrometry and fluorescence detection). These markers comprised benzo[a]pyrene (BaP), benzo[b]fluoranthene (BbF), levoglucosan (Levo), pinic acid (PA), terpenylic acid (TA), and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD). The impactors showed the best agreement for BaP and BbF. BaP had an average mass concentration of 175 ± 25 pg m−3 across all impactors and sampling days. However, concentrations were about 29 % higher when sampled with the PENS and 30 % lower when sampled with the 120R MOUDI-II, indicating a maximum disagreement of nearly 60 %. The mass concentrations of the semi-volatile markers (PA, TA, and Levo) decreased on average from the PENS to the ultraMOUDI, then to the 120R MOUDI-II, and finally to the ELPI. We attributed this tendency to the following two effects. (1) Evaporation losses of these markers were likely driven by the pressure drop within the impactor, which increased from the PENS to the ELPI. (2) Despite the applied coating, bounce-off might have affected the smallest impactors (i.e., the PENS and ultraMOUDI) the most as they have fewer stages for retaining larger particles and fragments.

Investigation of the Earliest Ozone Pollution Events in Hangzhou Bay, China Based on Observations and ERA5 Reanalysis Data

Abstract: Ozone pollution in Hangzhou Bay, one of the seven petrochemical clusters in China, is severe. Early ozone pollution has been detected recently, such as the maximum daily 8 h average (MDA8) ozone concentration in Jiaxing achieving 171.0 μg/m3 on 7 March 2023. Satellites have observed tropospheric column concentrations of ozone precursors formaldehyde (HCHO) and nitrogen dioxide (NOx), and quantitative models are proposed to reveal the causes of the early onset of ozone pollution. VOC-limited and transitional regimes dominate most areas in Hangzhou Bay, and NOx-limited regimes dominate the region around Hangzhou Bay, such as northeastern Jiangsu Province. Results show that HCHO column concentrations are increasing in VOC-limited regions, and NOx column concentrations are increasing more rapidly than HCHO in NOx-limited regions. According to multivariate linear regression (MLR), early spring ozone pollution in Hangzhou Bay is mainly caused by meteorological drivers. Hangzhou Bay has formed an atmospheric meteorological environment with high temperature and low humidity. The richer solar radiation intensifies the photochemical reactions associated with tropospheric ozone formation, producing more tropospheric ozone. Based on the Shapley Additive Explanation (SHAP) algorithm, ozone pollution increases when solar radiation exceeds 12 million J/m2 and is accompanied by high temperatures. Overall, reducing VOC emissions helps to mitigate ozone growth in Shanghai and northern Hangzhou Bay, while reducing NOx emissions is more effective in northeastern Jiangsu Province.

Temporal Changes in Lead and Cadmium Levels in Amanita muscaria Samples Collected in Poland

In recent years, an increasing popularity of consuming Amanita muscaria has been observed in Poland, aimed at reducing various medical symptoms. However, there is a lack of data regarding the impact of variations in the content of toxic elements, such as cadmium (Cd) and lead (Pb), in Amanita muscaria collected during late summer and mid-fall. The aim of this study was to determine the concentrations of Pb and Cd in Amanita muscaria samples collected at different times of the year, compare the concentrations of these elements in samples with and without cap skin, and compare the obtained values to permissible limits in dietary supplements. A total of 44 Amanita muscaria samples were collected during three different harvesting periods (August, September, and October 2023) from Puszcza Biała, located approximately 80 km from Warsaw. The mushrooms were subjected to mineralization using concentrated nitric acid and hydrogen peroxide, followed by the determination of Pb and Cd concentrations using an atomic absorption spectrometer. Significant statistical differences were found in the Pb concentrations of samples collected in three different seasons (η2 = 0.67, p &lt; 0.001), with the concentration increasing progressively, reaching its highest value in October. Similarly, the Cd concentration also increased in the later collections, although the effect of time was weaker (η2 = 0.13, p = 0.03). No significant differences were observed in Pb and Cd concentrations between samples with and without cap skin. The average Cd concentrations in mushrooms were significantly higher than the permissible levels in dietary supplements; they were four times higher in August (p &lt; 0.001), six times higher in September (p &lt; 0.001), and nine times higher in October (p &lt; 0.001). The Pb concentration in the October samples was close to the permissible limit but did not exceed it in a statistically significant manner (p = 0.85). Due to the high Cd concentrations and potentially hazardous levels of Pb, the consumption of Amanita muscaria carries a significant risk of toxicity, which may lead to serious health hazards, particularly in the context of prolonged exposure.

Acute effect of endurance exercise on human milk insulin concentrations: a randomised cross-over study

IntroductionInsulin is present in human milk and its concentration correlates with maternal circulating levels. Studies on the association between human milk insulin concentrations and infant weight or growth show conflicting results, but some studies indicate that higher insulin concentrations in the milk can promote infant weight gain. Circulating levels of insulin decrease acutely after exercise, but no prior study has investigated the acute effect of exercise on human milk insulin concentrations. Our aim was to determine the acute effects of two endurance exercise protocols on human milk insulin concentration in exclusively breastfeeding individuals.MethodsIn a randomised cross-over trial, 20 exclusively breastfeeding participants who were 6–12 weeks postpartum completed three conditions on separate days: (1) moderate-intensity continuous training (MICT), (2) high-intensity interval training (HIIT), and (3) no activity (REST). Milk was collected before exercise/rest (at 07:00 h), immediately after exercise/rest (11:00 h), 1 h after exercise/rest (12:00 h), and 4 h after exercise/rest (15:00 h). We determined insulin concentrations in the milk using enzyme-linked immunosorbent assay and compared insulin concentrations after MICT and HIIT with REST using a linear mixed model with time-points and the interaction between time and condition as fixed factors.ResultsWe detected insulin in all 240 samples, with an average concentration of 12.3 (SD 8.8) μIU/mL (range 3.2–57.2 μIU/mL). There was no statistically significant effect of exercise on insulin concentration, but a tendency of reduced concentrations 4 h after HIIT (p = 0.093). There was an overall effect of time at 11:00 h and 15:00 h. In the fasted sample obtained at 07:00 h, the concentration was 9.9 (SD 7.2) μIU/mL, whereas the concentration was 12.7 (SD 9.0) μIU/mL at 11:00 h (p = 0.009), and 15.0 (SD 11.7) μIU/mL at 15:00 h (p &amp;lt; 0.001).ConclusionOne session of endurance exercise, either at moderate- or high intensity, had no statistically significant effect on human milk insulin concentration. Future research should determine the effect of regular exercise on insulin in human milk and potential impact for infant health outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT05042414.

Heavy Metals Assessment in Selected Leafy Vegetables from Selangor, Malaysia

Leafy vegetables may contain heavy metals that possess negative impacts on human health. However, no structured monitoring has been available so far in terms of the heavy metal content of vegetables sold in markets across the country. Thus, the present study aimed to investigate heavy metals concentration [aluminium (Al), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe) and lead (Pb)] in selected leafy vegetables (Brassica oleracea subsp. capitata L., Brassica juncea Czern., Spinacia oleracea L., and Brassica rapa var. chinensis) from Selangor wholesale wet markets using inductively coupled plasma–optical emission spectrometry. Potential health risks linked to their consumption were assessed by estimating daily intake of toxic metals (EDI) and calculating both cancer and non-cancer risks, including hazard index and target hazard quotient (THQ). Results showed that the average concentrations of Al and Fe in vegetable samples were within the permissible limits, with the greatest amount of Al found in spinach (41.37 mg/kg). The mean levels of Fe in cabbage, mustard, spinach, and pak choi were 6.30 ± 5.78, 4.12 ± 1.84, 13.59 ± 4.73, and 4.14 ± 0.31 mg/kg, respectively. However, Cd, Cr, Cu, and Pb were undetected in all samples. THQ values derived from the EDI of heavy metals were discovered to be less than one, suggesting a low likelihood of adverse health effects. In conclusion, although leafy vegetables present negligible health risks, consumers should vary their vegetable intake to prevent long-term health effects.

Ultrasound-triggered release of vancomycin from a novel spinal device: Antibiotic release and efficacy in vivo.

Post-surgical spinal infection occurs in up to 20% of patients, despite aggressive peri-operative antibiotic treatments. To improve prophylaxis, we have designed and evaluated an ultrasound-activated prophylactic antibiotic release system to combat post-surgical bacterial survival. Polylactic acid (PLA) clips (1 cm3) were 3D-printed with an interior reservoir (0.8 cm3) for carrying drug payload, specifically vancomycin (VAN). Under IACUC approval, clips were surgically implanted into the spines of sheep (n = 9) and swine (n = 2) by removing the spinous process at several levels of the lumbar spine. In the sheep, clips were insonated and the interstitial wound fluid was collected to quantify the ultrasound-triggered VAN release. Uninsonated control sheep exhibited an average VAN concentration of 6.32 ± 5.99 µg/mL after 72 h, while ultrasound-triggered clips released significantly higher VAN concentrations at 72 h (22.98 ± 11.22 µg/mL, p = 0.033). In the swine, device efficacy against Staphylococcus aureus was evaluated. Insonated sites saw significant reduction in colony forming units (CFU) to 4.3 ± 3.2 CFU in the activated clips, compared to uninsonated controls where bacterial colonization was higher (2898 ± 1214 CFU, p = 0.017). Overall, these results demonstrate the ability to non-invasively release VAN from an implanted reservoir in vivo, and that this VAN release is effective in mitigating invading microbes in the wound site.

Association between exposure to particulate matter and heart rate variability in vulnerable and susceptible individuals

Particulate matter (PM) exposure can reduce heart rate variability (HRV), a cardiovascular health marker. This study examines PM1.0 (aerodynamic diameters <1 μm), PM2.5 (≥1 μm and <2.5 μm), and PM10 (≥2.5 μm and <10 μm) effects on HRV in patients with environmental diseases as chronic disease groups and vulnerable populations as control groups. PM levels were measured indoors and outdoors for five days in 97 participants, with 24-h HRV monitoring via wearable devices. PM exposure was assessed by categorizing daily cumulative PM concentrations into higher and lower exposure days, while daily average PM concentrations were used for analysis. Results showed significant negative associations between exposure to single and mixtures of different PM metrics and HRV across all groups, particularly in chronic airway disease and higher air pollution exposed groups. These findings highlight that even lower PM levels may reduce HRV, suggesting a need for stricter standards to protect sensitive individuals.

PM2.5 and NOX concentrations decrease as a result of a railway electrification.

This work examines the impact of the electrification of the Holon-Bat Yam passenger train line (central Israel) on air pollutant concentrations using data collected from air quality monitoring stations that operated at the train stations across the electrified train line. We present statistically significant reduction in the annual average NO2, NO and NOX concentrations (29-45%, 79-85% and 65-75%, respectively), attributed to the electrification of the passenger train line. The drop in the NO and NOX concentrations was much stronger than in the NO2 concentrations, since NO is the main nitrogen species emitted by diesel locomotives. PM2.5 concentrations also significantly decreased, but only in two (out of the three) train stations situated along the electrified line. Following various analyses, we conclude that electrification of train lines reduces train locomotive emissions and improves the air quality at the stations, as expected, thus protecting the passengers and reducing their exposure to air pollutants. Although this study presents a specific case, the findings are expected to be applicable, at least quantitatively, to other locations, as railway electrification removes emissions associated with fossil-fuel-powered locomotives. This work supports railway electrification policy, which has the potential to substantially lower air pollution levels and diminish the passengers' exposure to harmful air pollutants.

Long-term exposure to fine particulate matter components with obesity in children and adolescents in China: The age-sex disparities and key effect modifiers.

Long-term fine particulate matter (PM2.5) exposure was associated with childhood obesity. However, the key PM2.5 components and whether PM2.5 effect may vary by obesity type, growth stage, sex, and individual/family characteristics have yet been examined. In this study, we investigated 213,907 Chinese children and adolescents aged 3-18 years in 2017-2019. Three-year average concentrations of PM2.5 and five major components were assigned to each participant's address. Multivariable mixed-effects model and weighted quantile sum regression were used to estimate the effect sizes of each component. Stratified analyses were performed by age and sex groups, with the interactive effects of a series of individual/family features evaluated. The odds ratio of childhood obesity was 1.28 (95 %CI: 1.15-1.43) for per interquartile range increase in PM2.5, with organic matter identified as the key contributor. General central obesity and mixed obesity were more sensitive to PM2.5 exposure than peripheral obesity. As children aged, the effect size of PM2.5 attenuated for general central obesity, remained unchanged for mixed obesity and increased for peripheral obesity. Females, children with obese parents, and those with lower levels of physical activity were more vulnerable than others. Other adverse effect modifiers for certain children included family with one child, low family income, and less sleep duration. Our findings emphasize that the influence of exposure to PM2.5 and its components on risk of obesity in children and adolescents should be considered comprehensively in developing adequate obesity prevention strategies.

Twenty years of studying the origins and fate of atmospheric mercury over the Mediterranean Sea.

This study provides a review of 13 oceanographic campaigns between 2000 and 2017 to measure Hg in the Mediterranean, highlighting major findings from measurement and modelling activities during the Med-Oceanor program. The initial campaigns showed that high concentrations of RGM could be found far from industrial source regions and the observed daily variation in concentration, with peaks at midday and lower concentrations during darkness gave the first indications that photochemically mediated oxidation reactions were producing RGM in the MBL. Later atmospheric chemistry modelling studies showed the feasibility of Hg oxidation by bromine containing oxidants, which are released as a result of the acidification of sea salt aerosols in the Marine Boundary Layer (MBL). Spatial and seasonal variations of DGM were observed at different depths in the water column, with average DGM concentrations higher in the West and East Mediterranean deep and intermediate waters, than in overlaying Atlantic waters. DGM in water profiles typically increased with depth, together with nutrients and decreasing oxygen, indicating a possible bacterial and/or geogenic origin. Using measured DGM and meteorological variable values Hg fluxes can be calculated. When these are included in regional and global models they suggest that the net Hg evasion from the Mediterranean is around 30Mgyr-1. Repetition of these campaigns should be an extremely high priority, both to continue to monitor changes in atmospheric and aquatic Hg species concentrations, but also to perform RGM detection methodology intercomparisons so that the historical data is adequately contextualised and may be used to evaluate temporal trends.

Assessment of radioactivity in soil samples from Wolaita Sodo town, Ethiopia: implications for environmental and public health.

This study assesses the activity concentrations of the radionuclides 238U, 232Th, and 40K in soil samples collected from Wolaita Sodo town, located in the Southern Nations, Nationalities, and Peoples' (SNNP) Region, Ethiopia. A gamma-ray spectrometer equipped with a NaI(Tl) detector was used for the measurements. The concentrations of 238U, 232Th, and 40K varied from 3.25±1.5 to 13.84±2.2Bq.kg-1, 0.4±0.9 to 85.12±3.4Bq.kg-1, and 34.43±2.7 to 748.07±5.9Bq.kg-1, respectively. The average activity concentrations were 7.83±1.9Bq.kg-1, 40.74±2.7Bq.kg-1, and 161.63±3.9Bq.kg-1 for 238U, 232Th, and 40K, respectively. The average radium equivalent activity was 192.25Bq.kg-1, well below the recommended safety limit of 370Bq.kg-1. The average gamma dose rate, and annual effective dose rate were 35.68 nGy.h-1, and 0.18mSv.y-1, respectively. The internal and external indexes are below the recommended limit set by UNSCEAR and ICRP. However, the estimated excess lifetime cancer risk and indoor radon concentrations are slightly higher. Despite this, the overall radiological impact on the environment and public health in the study area remains negligible. This study provides valuable baseline data for radiation protection and informs urban and environmental policy in the region.

P0639 Population pharmacokinetics of subcutaneous vedolizumab in Crohn’s disease and Ulcerative Colitis

Abstract Background Vedolizumab is a monoclonal antibody used for the treatment of inflammatory bowel disease (IBD). The pharmacokinetics (PK) of intravenously (IV) administered vedolizumab have been described previously.1 We aimed to develop a population PK model for subcutaneous (SC) vedolizumab and to evaluate whether current dose regimens are appropriate for SC dosing. Methods Data for model development were prospectively collected in a cohort of 61 patients with IBD receiving IV vedolizumab (300mg at week 0-2-6, thereafter every 4-11 weeks) who switched to SC treatment (108 mg every 2 weeks, Q2W). The PRIOR subroutine in NONMEM2 was used to develop a two-compartment population PK model for IV and SC vedolizumab including linear and non-linear clearance. The model was validated with goodness of fit plots, a visual predictive check and bootstrapping (n = 1000). Final model estimates were used to perform simulations in a virtual population (n = 10 000) with a white blood cell count of 7 x 109/L, randomly sampled serum albumin (mean = 44 g/L, SD = 3.0) and bodyweight (mean 77 kg, SD = 14), based on the distribution of the original dataset. Trough concentrations for an IV regimen of 300 mg vedolizumab once in 8 weeks were compared with SC regimens of 108 mg once in 2, 3, 4 and 5 weeks. For SC vedolizumab, we defined a target serum concentration of 26 mg/L, based on previously reported exposure-efficacy data.3 Results A patient with a bodyweight of 70 kg, serum albumin of 40 g/L and a white blood cell count of 7 x 109/L had a bioavailability of 66.8%, an absorption rate constant of 0.0938/day and a linear clearance of 0.157 L/day. The inter-individual variability for linear clearance was 22.9%. Most important predictors for linear clearance were serum albumin with a negative, and bodyweight and white blood cell count with a positive correlation. In the virtual population, 2.3-fold higher average trough concentrations were estimated for the SC-Q2W regimen (32 mg/L) compared to the IV-Q8W regimen (14 mg/L). Trough concentrations of at least 26 mg/L were achieved in 76% of virtual patients receiving SC vedolizumab every 2 weeks. Virtual patients with a serum vedolizumab concentration higher than 42 mg/L with Q2W dosing could de-escalate to Q3W, while still achieving a trough concentration of 26 mg/L (18% of virtual patients). Conclusion The development and evaluation of a population PK model for IV and SC vedolizumab was successful. This model could be used in the considerations of an extended SC dose regimen. Our results highlight the importance of defining clear targets for SC vedolizumab in clinical practice.

International pellet watch; origins and monitoring of oil markers in surface sediments and plastic resin pellets in southern Caspian Sea, Iran.

Oil pollution in marine environments, particularly along the southern coasts of the Caspian Sea, has become a serious issue due to anthropogenic activities such as shipping, tourism, fishing, and urban development. This study aimed to assess the concentration and origin of PAHs, n-alkanes, hopanes, and steranes in sediment samples (coastal area and coastal line) and resin pellets collected from 30 stations along the southern shores of the Caspian Sea (Golestan, Mazandaran, and Gilan provinces). The results showed that PAHs concentrationranged from 530.4 to 9201ng/g-dw in coastal area sediments, 753 to 10,528ng/g-dw in coastal line sediments, and 5920.7 to 16,548ng/g-pellet in resin pellets. The average total concentration of alkanes ranged from 251 to 7059μg/g-dw in coastal area sediments, 273 to 8401.6μg/g-dw in coastal line sediments, and 1967 to 22,258μg/g-pellet in resin pellets. The total terpene concentration in coastal area sediments was 60.5 to 537.5ng/g-dw, in coastal line sediments 120.6 to 811.3ng/g-dw, and in resin pellets 227 to 2886.5ng/g-pellet. Additionally, the highest concentrationwere observed in port-related areas (Bandar Anzali, Amirabad, and Astara), while the lowest concentrationwere found in recreational areas. Resin pellets generally exhibited higher concentrationof all investigated compounds compared to sediments. The classification of PAH pollution intensity based on global criteria indicated moderate to very high contamination in sediments and high to very high contamination in resin pellets. The determination of pollution levels based on the concentration of n-alkanes in southern Caspian Sea sediments revealed very high and considerable pollution. The categorization of hopane compounds' pollution intensity in resin pellets, according to International Pellet Watch classification, indicated a lack of pollution in all samples. The primary source of all compounds was identified as petrogenic.