Calculating expected effects of treatment effectivity and river flow rates on the contribution of WWTP effluent to the ARG load of a receiving river.

Concentrations of genetic markers for antibiotic resistance genes (ARGs) were measured in the effluents of three Norwegian wastewater treatment plants (WWTPs) and in a receiving river upstream and downstream of the discharge point of one WWTP. Calculations based on mass balances were carried out to evaluate the impact of river flow rates and treatment effectivity on the WWTP's contribution to the load of genetic markers in the river. At average river flow rates, the WWTP effluent contributes 5-15% to the genetic marker load of the respective river. However, at minimum river flow rates, the WWTP effluent contributes 22-55% to the loads of different genetic markers. Scenarios of an improved or worsened removal of genetic markers in the WWTP showed that a further 1-log removal using additional treatment would be sufficient to improve considerably the river water quality with respect to genetic markers. Then, at an average flow rate, the contribution of the WWTP effluent to the load of the river would be less than 2%. However, in the case of low treatment effectivity or malfunction of the WWTP, the marker load of the river would increase dramatically. Even at average flow rate, 75-92% of the marker load would then originate from the WWTP. The results demonstrate the importance of considering the flow rates and hydrologic characteristics of the recipient water body when deciding on priorities regarding the upgrade of WWTPs for further removal of ARGs.

Water quality aspects related to domestic drinking water storage tanks and consideration in current standards and guidelines throughout the world - a review.

In many parts of the world, drinking water storage takes place in near-house or in-house tanks. This can impact drinking water quality considerably. International and numerous national standards and guidelines addressing the construction, installation and operation of domestic drinking water storage tanks are reviewed on their consideration of water quality aspects and the minimisation of health risks associated with drinking water storage. Several national and international standards and guidelines are reviewed in terms of drinking water quality requirements. Factors that have an impact on water quality in relation to the use of domestic drinking water storage tanks are summarised comprehensively. The impact of the domestic storage of drinking water on water quality, the points and locations of use, their positioning, the materials they are made of, their design and operation, as well as aspects of how they are operated and maintained is outlined and discussed in detail. Finally, the incorporation of aspects regarding water quality in drinking water storage tanks in standards and guidelines is presented and assessed. To make the use of domestic drinking water storage tanks safer and more efficient, recommendations for modifications, improvements and extensions of respective standards are made.

Impact of Different Combinations of Water Treatment Processes on the Concentration of Disinfection Byproducts and Their Precursors in Swimming Pool Water.

To mitigate microbial activity in swimming pools and to ensure hygienic safety for bathers, pool systems have a recirculating water system ensuring continuous water treatment and disinfection by chlorination. A major drawback associated with the use of chlorine as disinfectant is its potential to react with precursor substances present in pool water to form harmful disinfection byproducts (DBPs). In this study, different combinations of conventional and advanced treatment processes were applied to lower the concentration of DBPs and their precursors in pool water by using a pilot-scale swimming pool model operated under reproducible and fully controlled conditions. The quality of the pool water was determined after stationary concentrations of dissolved organic carbon (DOC) were reached. The relative removal of DOC (Δc cin-1) across the considered treatment trains ranged between 0.1  ±  2.9% and 7.70  ±  4.5%, where conventional water treatment (coagulation and sand filtration combined with granular activated carbon (GAC) filtration) was revealed to be the most effective. Microbial processes in the deeper, chlorine-free regions of the GAC filter have been found to play an important role in the degradation of organic substances. Almost all treatment combinations were capable of removing trihalomethanes to some degree and trichloramine and dichloroacetonitrile almost completely. However, the results demonstrated that effective removal of DBPs across the treatment train does not necessarily result in low DBP concentrations in the basin of a pool. This raises the importance of the DBP formation potential of the organic precursors, which has been shown to depend strongly on the treatment concept applied. Irrespective of the filtration technique employed, treatment combinations employing UV irradiation as a second treatment step revealed higher concentrations of volatile DBPs in the pool compared to those employing GAC filtration as a second treatment step. In the particular case of trichloramine, results confirm that its removal across the treatment train is not a feasible mitigation strategy because it cannot compensate for the fast formation in the basin.

Removal of antibiotic resistant E. coli in two Norwegian wastewater treatment plants and by nano- and ultra-filtration processes.

The effectivity of different treatment stages at two large wastewater treatment plants (WWTPs) located in Oslo, Norway, to remove antibiotic resistant Escherichia coli from municipal wastewater was investigated. The WWTPs were effective in reducing the total cultivable E. coli. The E. coli in WWTP samples were mainly resistant to ampicillin (6-27%) and trimethoprim-sulfamethoxazole (5-24%), and, to a lesser extent, tetracycline (3-14%) and ciprofloxacin (0-7%). In the first WWTP, a clear decrease in the percentage of E. coli resistant to these antibiotics was found, with the main removal occurring during physical/chemical treatment. In the second WWTP, the percentage of cultivable resistant E. coli did not display a considerable change. During laboratory-scale membrane filtration of WWTP effluents using ultrafiltration (UF) and nanofiltration (NF) membranes, all E. coli, including those resistant to antibiotics, were removed completely. The results imply that UF and NF processes are potent measures to remove antibiotic resistant bacteria (ARB) during post-treatment of WWTP effluents, thus reducing the potential spread of antibiotic resistance in the receiving aquatic environment.

Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant human chorionic gonadotropin in healthy Japanese and Caucasian women and recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin in healthy Japanese women.

Purpose: Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r-hCG was investigated. Methods: An open-label, partly randomized, single-center, single-dose, group-comparison, Phase I PK-bridging study was done that compared a single 250 µg dose of r-hCG with a single 5000 IU dose of urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250 µg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants were weight-matched to the Japanese participants who were receiving r-hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞) and the maximum serum concentration (Cmax). Results: The mean serum hCG concentration-time profiles of r-hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r-hCG resulted in an 11% lower Cmax but a 19% higher AUC 0-∞ compared with u-hCG. No new safety signal was identified. Conclusion: This study cannot exclude a potential difference in the PK profile of r-hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r-hCG and u-hCG in the Japanese participants.

The practical influence of rapid mixing on coagulation in a full-scale water treatment plant.

This study focuses on the effect of rapid mixing on the coagulation efficiency in a full-scale drinking-water treatment plant and discusses the mechanisms involved in the floc-formation process. The results refer to three periods of operation of the waterworks when no mechanical mixing was provided in the tanks for coagulant dosing due to mechanical failure of the rapid mixers. Although a certain deterioration of the subsequent flocculation process was observed, as assessed using the data for suspended solids, turbidity, and chemical oxygen demand, the overall water treatment performance was not affected. This suggests an insignificant role for intense rapid mixing in sweep flocculation during full-scale water treatment and reveals the potential to reduce the required energy costs for mechanical mixers.

Safety, tolerability, and pharmacokinetics of the novel αv-integrin antibody EMD 525797 (DI17E6) in healthy subjects after ascending single intravenous doses.

PURPOSE: We evaluated the safety, tolerability, and pharmacokinetics (PK) of EMD 525797 (DI17E6), a humanized monoclonal antibody targeting αv-integrins, in healthy subjects. METHODS: In this first-in-human, double-blind, placebo-controlled, randomized Phase 1 study, healthy male volunteers were consecutively assigned to 6 ascending single-dose cohorts of 35, 100, 250, 500, 1000, or 1500 mg. Per dose cohort, EMD 525797 or placebo was administered over 1 h as an intravenous 250-mL infusion to 6 and 3 volunteers, respectively. Escalation to the next dose level was based on evaluation of safety, tolerability, and PK data. RESULTS: Fifty-five subjects (aged 18-45 years) were randomized. Twenty-seven of 37 (73 %) subjects receiving EMD 525797 reported a total of 61 adverse events (AEs), including 38 events (in 17 subjects) considered by the investigator to be treatment related. A total of 35 AEs were reported by 14 of 18 (78 %) placebo-treated subjects. The most commonly occurring AEs were gastrointestinal disorders, abnormal laboratory values, and increased or decreased biochemistry and/or hematology values, as well as headaches, which occurred at a slightly higher frequency in the EMD 525797 group compared with placebo. There were no serious AEs or deaths. EMD 525797 PK appeared to be dose dependent, especially at lower doses. CONCLUSION: Ascending single doses of EMD 525797 were shown to be safe and well tolerated. No safety concerns were identified. This study supports the ongoing investigation of EMD 525797.

Membrane Separation of Chicken Byproduct Hydrolysate for Up-Concentration of Bioactive Peptides.

Membrane processes, such as microfiltration, ultrafiltration, and nanofiltration, are increasingly used for various applications in both upstream and downstream processing. Membrane-based processes play a critical role in the field of separation/purification of biotechnological products, including protein production/purification. The possibility of using membranes to separate peptides from a chicken byproduct hydrolysate and the effect of the performed downstream processing on the DPP-IV dipeptidyl peptidase IV (DPP-IV) inhibitory activity of mechanical deboning chicken residue (MDCR) has been investigated. The chicken byproduct hydrolysate was prepared by enzymatic hydrolysis followed by microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) separation. Comparing all separation treatments, hydrolysates processed only by MF and UF show the best DPP-IV inhibition (59.5-60.0% at 1 mg/mL and 34.2-40.7% at 0.5 mg/mL). These samples show dose-responsive behavior. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. The nanofiltration process notably decrease the inhibitory activity, and these permeates show low DPP-IV inhibition (9.5-21.8% at 1 mg/mL and 3.6-12.1% at 0.5 mg/mL). The size-exclusion chromatography-organic carbon detection-organic nitrogen detection (LC-OCD-OND) analysis confirms that NF and RO would retain the bioactive peptides in the concentrate in comparison to MF and UF. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. Permeates after ultrafiltration show an IC50 value of 0.75 mg/mL, comparable to other potent DPP-IV inhibitors derived from various food sources, and significantly more potent compared to the microfiltration sample, which shows an IC50 value of 1.04 mg/mL. The average molecular weight of the permeates calculated from the SEC chromatograms was 883 g/mol for UF and 1437 g/mol for MF. Of the four membranes studied, the UF membrane shows the best separation properties with respect to maximizing the yield and up-concentration of the bioactive peptides. Overall, UF was demonstrated to be a feasible technology for the removal of the undesired high-molecular-weight substances and up-concentration of small-molecular-weight bioactive peptides from chicken byproduct hydrolysate. These peptides might exhibit biological activity and could offer several health benefits. There is a high potential for the use of bioactive peptides, and more research in this field can lead to promising results that have significant effects in the food and medical industries.

Removal and release of microplastics and other environmental pollutants during the start-up of bioretention filters treating stormwater.

Untreated stormwater is a major source of microplastics, organic pollutants, metals, and nutrients in urban water courses. The aim of this study was to improve the knowledge about the start-up periods of bioretention filters. A rain garden pilot facility with 13 bioretention filters was constructed and stormwater from a highway and adjacent impervious surfaces was used for irrigation for ∼12 weeks. Selected plants (Armeria maritima, Hippophae rhamnoides, Juncus effusus, and Festuca rubra) was planted in ten filters. Stormwater percolated through the filters containing waste-to-energy bottom ash, biochar, or Sphagnum peat, mixed with sandy loam. Influent and effluent samples were taken to evaluate removal of the above-mentioned pollutants. All filters efficiently removed microplastics >10 µm, organic pollutants, and most metals. Copper leached from all filters initially but was significantly reduced in the biochar filters at the end of the period, while the other filters showed a declining trend. All filters leached nutrients initially, but concentrations decreased over time, and the biochar filters had efficiently reduced nitrogen after a few weeks. To conclude, all the filters effectively removed pollutants during the start-up period. Before being recommended for full-scale applications, the functionality of the filters after a longer period of operation should be evaluated.

Bioequivalence Evaluation in Healthy Volunteers: New Generic Formulations of Sitagliptin and Sitagliptin-Metformin Fixed-Dose Combination Compared with the Originator Products.

INTRODUCTION: Three studies compared the bioequivalence (BE) of new generic tablet formulations of sitagliptin (100 mg; fasting) and the fixed-dose combination (FDC) of sitagliptin/metformin (50/850 mg, 50/1000 mg; both fed) in healthy volunteers with the same tablet strengths of the reference products Januvia and Janumet. METHODS: The study design was open-label, single-dose, randomized with two-way crossover periods. Blood sampling was performed for 72/48 h in the sitagliptin/FDC studies, respectively. Primary pharmacokinetic (PK) parameters for sitagliptin and metformin were area under the plasma concentration-time curve from time 0 to last timepoint of measurable concentration (AUC0-t) and maximum plasma concentration (Cmax). Test (T) and reference (R) formulations proved bioequivalent if 90% confidence interval (CI) of geometric least-squares mean ratio for AUC0-t and Cmax were within BE acceptance range of 80.00-125.00%. Safety evaluations included vital signs, clinical laboratory tests, and adverse events (AEs). RESULTS: Treated/evaluable volunteers for BE per study were: 30/28 (sitagliptin 100 mg), 26/25 (FDC 50/850 mg), and 26/24 (FDC 50/1000 mg). The 90% CI of the geometric means of T/R ratios for primary PK parameters were within predefined BE limits: CI for AUC0-t and Cmax were 95.83-100.37% and 91.85-109.56% (sitagliptin 100 mg); 100.84-103.69% and 93.44-105.10% (FDC 50/850 mg), and 101.26-105.20% and 98.71-112.89% (FDC 50/1000 mg); respective values for metformin were 94.23-101.89% and 91.66-99.38% (FDC 50/850 mg) and 98.45-104.89% and 96.79-105.62% (FDC 50/1000 mg). All AEs were nonserious, transient, and mostly mild. Safety evaluations did not reveal any relevant difference between T and R formulations. CONCLUSIONS: The new generic tablet formulations of sitagliptin 100 mg and the FDCs sitagliptin/metformin 50/850 mg and 50/1000 mg demonstrated bioequivalence to originator reference products. Therefore, the new products are expected to provide efficacy and tolerability similar to those of the reference products in the treatment of patients with type 2 diabetes (T2D). TRIAL REGISTRATION: EudraCT EU Clinical Trials Registry (2014-005437-31); ClinicalTrials.gov Registry (NCT05549570 and NCT05549583, both retrospectively registered on 20 September 2022).