Human Excretion Research Articles

Continuous flow microfluidic system with magnetic nanoparticles for the spectrophotometric quantification of urea in urine and plasma samples.

Urea, synthesized exclusively in the liver, is primarily transported through the bloodstream to the kidneys, where it is excreted in urine, accounting for 80-90% of nitrogen excretion in humans. Elevated blood urea levels, indicative of kidney dysfunction, make it a crucial biomarker for assessing renal function. Previous studies on urea detection using microdevices have largely focused on conductometric methods. In this study, we demonstrated the application of a continuous flow miniaturized system for rapid spectrophotometric urea quantification using polydimethylsiloxane (PDMS) microdevices. The microdevice featured two distinct zones: an enzymatic reaction zone, where urease-conjugated magnetic nanoparticles were immobilized, and a detection zone, where reagents were incorporated to produce a colored reaction product via a modified Berthelot reaction. Integrating magnetic nanoparticles as a solid support for the enzyme enabled the reuse of PDMS microdevices without compromising the analytical signal. Spectrophotometric detection was performed in an additional microdevice acting as a microflow cell coupled with optical fibers. A calibration curve was constructed using urea standards diluted in phosphate buffer solution (PBS), yielding a linear range of 0.12-3.00 mg dL-1. The method demonstrated detection and quantification limits of 0.04 mg dL-1 and 0.12 mg dL-1, respectively. Precision and accuracy assessments yielded a repeatability of 0.90% and intermediate precision of 4.52%, with recovery rates near 100%. The method was applied to plasma and urine samples, showing urea concentrations within normal physiological ranges and an analysis throughput of 36 measurements per hour.

Sewerage surveillance tracking characteristics of human antibiotic resistance genes in sewer system

Sewage surveillance is widely applied to track valid human excretion information and identify public health conditions during corona virus disease 2019 (COVID-19) pandemic. This approach can be applied to monitor the antibiotic resistance level in sewers and to assess the risk of spreading antibiotic resistance in municipal wastewater systems. However, there is still little information about human antibiotic resistance occurrence characteristics in sewer system. This study conducted a field trial for whole year to advance understanding on spatial and temporal occurrence of antibiotic resistance genes (ARGs) in gravity sewerage. The spatial distribution of ARGs along the drainage pipe line (from human settlements to wastewater treatement pant (WWTP)) was insignificant, which may be affected by irregular human emission alongside the pipeline. The correlation between ARGs and antibiotics in sewage was insignificant. The temporal distribution showed that the effect of temperature on ARGs abundance was evident, the ARGs abundance in sewage was generally higher during the cold season. Metagenomic analysis revealed that the detected ARGs were mainly distributed in Proteobacteria (47.51 %) and Antinobacteria (20.11 %). Potential hosts of ARGs in sewage were mainly identified as human gut microorganisms, including human pathogenic bacteria, such as Prevotella, Kocuria, and Propionibacterium, etc. This study provides a new insight into the sewerage surveillance tracking characteristics of human ARGs in sewer system, and suggesting that the sewage-carried ARGs surveillance is a promising method for assessment and management of antibiotic resistance level on population size.

The effect of itraconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics of the first-in-class ACKR3/CXCR7 antagonist, ACT-1004-1239.

Cytochrome P450 (CYP) 3A4 is an enzyme involved in the metabolism of many drugs that are currently on the market and is therefore a key player in drug-drug interactions (DDIs). ACT-1004-1239 is a potent and selective, first-in-class ACKR3/CXRC7 antagonist being developed as a treatment for demyelinating diseases including multiple sclerosis. Based on the human absorption, distribution, metabolism, and excretion (ADME) study results, ACT-1004-1239 is predominantly metabolized by CYP3A4. This study investigated the effect of the strong CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of single-dose ACT-1004-1239 in healthy male subjects. In the open-label, fixed-sequence DDI study, a total of 16 subjects were treated. Each subject received a single dose of 10 mg ACT-1004-1239 (Treatment A) in the first period followed by concomitant administration of multiple doses of 200 mg itraconazole and a single dose of 10 mg ACT-1004-1239 in the second period. We report a median of difference in tmax (90% confidence interval, CI) of 0.5 h (0.0, 1.0) comparing both treatments. The geometric mean ratio (GMR) (90% CI) of Cmax and AUC0-∞ was 2.16 (1.89, 2.47) and 2.77 (2.55, 3.00), respectively. The GMR (90% CI) of t1/2 was 1.46 (1.26, 1.70). Both treatments were well-tolerated with an identical incidence in subjects reporting treatment-emergent adverse events (TEAE). The most frequently reported TEAEs were headache and nausea. In conclusion, ACT-1004-1239 is classified as a moderately sensitive CYP3A4 substrate (i.e., increase of AUC ≥2- to <5-fold), and this should be considered in further clinical studies if CYP3A4 inhibitors are concomitantly administered.

Unveiling Small-Sized Plastic Particles Hidden behind Large-Sized Ones in Human Excretion and Their Potential Sources.

Health risks of microplastic exposure have drawn growing global concerns due to the widespread distribution of microplastics in the environment. However, more evidence is needed to understand the exposure characteristics of microplastics owing to the limitation of current spectrum technologies, especially the missing information on small-sized particles. In the present study, laser direct infrared spectroscopy and thermal desorption-gas chromatography-mass spectrometry combined pyrolysis using a tubular furnace (TD-GC/MS) were employed to comprehensively detect the presence of plastic particles down to 0.22 μm in human excreted samples. The results showed that polyethylene (PE), polyvinyl chloride, PE terephthalate (PET), and polypropylene dominated large-sized (>20 μm) and small-sized plastic plastics (0.22-20 μm) in feces and urine. Moreover, fragments accounted for 60.71 and 60.37% in feces and urine, respectively, representing the most pervasive shape in excretion. Surprisingly, the concentration of small-sized particles was significantly higher than that of large-sized microplastics, accounting for 56.54 and 50.07% in feces (345.58 μg/g) and urine (6.49 μg/mL). Significant positive correlations were observed between the level of plastic particles in feces and the use of plastic containers and the consumption of aquatic products (Spearman correlation analysis, p < 0.01), suggesting the potential sources for plastic particles in humans. Furthermore, it is estimated that feces was the primary excretory pathway, consisting of 94.0% of total excreted microplastics daily. This study provides novel evidence regarding small-sized plastic particles, which are predominant fractions in human excretion, increasing the knowledge of the potential hazards of omnipresent microplastics to human exposure.

Human urinary excretion kinetics of the antimycotic climbazole: Biomonitoring of two new metabolites after oral and dermal dosage

Climbazole is an antimycotic compound used in cosmetic products as a preservative or as an active ingredient in anti-dandruff (AD) formulations. In this study we provide human toxicokinetic data on climbazole. Using our previously published analytical method, we investigated the urinary excretion of two climbazole metabolites, (OH)2-climbazole and cx-OH-climbazole, for 48 h after oral ingestion (n = 5, 49–77 µg/kg bw) and for 72 h after dermal application of either a climbazole-containing rinse-off AD shampoo or a leave-on hair tonic (n = 2×3). In total, 23.9 % (18.0–33.4 %) of the oral dose were excreted as the two abovementioned metabolites over 48 h. In one volunteer, who used an over-the-counter phytopharmaceutical, metabolite excretion was about three times lower and we found influences on diastereoselectivity of (OH)2-climbazole formation using a modified analytical method. After dermal application, urinary concentration maxima occurred considerably later than after oral intake. The two different dermal exposure scenarios also revealed a relevance of exposure duration and product formulation on the systemic availability of climbazole. Back-calculated oral-dose-equivalent intakes from the dermal exposures showed a maximum climbazole intake of 18.5 µg/kg bw/d after hair tonic use, or 6.6 µg/kg bw/d after AD shampoo application.

Pharmaceutical emissions on the example of the Baltic Sea catchment: comparing measurements with multi-tier predictive models

Currently, there is uncertainty about emissions of pharmaceuticals into larger closed ecosystems that are at risk such as the Baltic Sea. There is an increasing need for selecting the right strategies on advanced wastewater treatment. This study analysed 35 pharmaceuticals and iodinated X-ray contrast media in effluents from 82 Wastewater Treatment Plants (WWTPs) across Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Poland and Sweden. Measured concentrations from Finland and Denmark were compared to predicted effluent concentrations using different levels of refinement. The concentrations predicted by the Total Residue Approach, as proposed by the European Medicines Agency, correlated with R2 of 0.18 and 0.031 to measured ones for Denmark and Finland, respectively and the predicted data were significantly higher than the measured ones. These correlations improved substantially to R2 of 0.72 and 0.74 after adjusting for estimated human excretion rates and further to R2 = 0.91 and 0.78 with the inclusion of removal rates in WWTPs. Temporal analysis of compound variations in a closely monitored WWTP showed minimal fluctuation over days and weeks for most compounds but revealed weekly shifts in iodinated X-ray contrast media due to emergency-only operations at X-ray clinics during weekends and an abrupt seasonal change for gabapentin. The findings underscore the limitations of current predictive models and findings (...) demonstrate how these methodologies can be refined by incorporating human pharmaceutical excretion/metabolization as well as removal in wastewater treatment plants to more accurately forecast pharmaceutical levels in aquatic environments.

Analysis of Junior High School Students’ Misconceptions About the Human Excretion Using a Four-Tier Diagnostic Test

This study aimed to measure middle school students’ conceptions and misconceptions related to human excretion using a four-tiered diagnostic test. Using a cross-sectional survey design, responses of 113 eighth-grade students, convenience sampled from two schools in Bandung were collected. A four-tiered instrument was developed specifically for the focus of this study and the data analyzed below consists of test results and interviews with teachers. The findings indicate that students’ conceptions of the human excretory system fall into several categories: scientific knowledge (SK) at 46.90%, false positive (FP) at 13.09%, false negative (FN) at 6.13%, misconception (M) at 20.45%, and lack of knowledge (LK) at 13.43%. The most common misconceptions relate to diseases and disorders (38%) and sweating and body thermoregulation (31%). These misconceptions may arise due to factors such as students’ lack of enthusiasm for learning and limited engagement during the learning process. Consequently, there is a need for improved teaching approaches to address misconceptions associated with human excretion and to foster a more comprehensive scientific understanding among students.

Effects of PFAS on human liver transporters: implications for health outcomes.

Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to gauge the risk that historically used, and newly produced, PFAS may cause to human health. Numerous studies report toxic effects of PFAS on the human liver as well as increased serum cholesterol levels in adults. A major concern with PFAS, also dubbed "forever chemicals," is that they accumulate in the liver and kidney and persist in serum. The mechanisms responsible for their disposition and excretion in humans are poorly understood. A better understanding of the interaction of PFAS with liver transporters, as it pertains to the disposition of PFAS and other xenobiotics, could provide mechanistic insight into human health effects and guide efforts toward risk assessment of compounds in development. This review summarizes the current state of the literature on the emerging relationships (eg, substrates, inhibitors, modulators of gene expression) between PFAS and specific hepatic transporters. The adaptive and toxicological responses of hepatocytes to PFAS that reveal linkages to pathologies and epidemiological findings are highlighted. The evidence suggests that our understanding of the molecular landscape of PFAS must improve to determine their impact on the expression and function of hepatocyte transporters that play a key role in PFAS or other xenobiotic disposition. From here, we can assess what role these changes may have in documented human health outcomes.

A regulatory framework for bottled water quality monitoring: A case of Emfuleni local municipality

BackgroundThe quality of drinking water has recently become of utmost concern to consumers worldwide, especially in areas where Water Service Authorities (WSAs) failed to provide safe water. To combat this challenge, government entities regulate water to ensure that safe water is provided. The Emfuleni Local Municipality (ELM) has experienced cases of water contamination by human excretion, whereby communities were affected. As a result, there was a sharp increase in bottled water (BW) use, which however gave rise to unregulated and counterfeit versions of popular brands. This situation poses threats to public health. AimThis study sought to determine the regulation of drinking water and to assess whether environmental health practitioners (EHPs) monitor the quality of water sources (BW and tap water) in ELM as outlined by the National Environmental Health Norms and Standards (NEHNS). SettingsThe study was conducted in the Emfuleni Local Municipality in South Africa. MethodsA quantitative cross-sectional study design was employed in this research. Fifteen online questionnaires using a Google Forms survey were distributed amongst all EHPs servicing ELM. Secondary data that included the Integrated Development Plan (IDP) and Service Delivery Budget Implentation Plan (SDBIP) for the 2017–2020 financial years were also evaluated, specifically for water quality monitoring (tap and bottled water). The dataset was analysed using the Statistical Package for the Social Sciences (SPSS) version 29. ResultsDue to complexity in the legislation and NEHNS in relation to Municipal Health Services (MHS), bottled water was not sampled at all. A number of EHPs were also not conversant with the regulations governing BW. Moreover, NEHNS consider bottled water as food, which does not fall under the MHS. ConclusionThere should be clarity in the legislation to ensure that bottled water monitoring is intensified to protect public health within the WSAs. ContributionThe findings of this study could assist policy-makers to make informed decisions on water quality monitoring, as well as clarify legislative issues on bottled water.

Target and Nontarget Screening to Support Capacity Scaling for Substance Use Assessment through a Statewide Wastewater Surveillance Network in New York.

Wastewater-based epidemiology (WBE) has been widely implemented around the world as a complementary tool to conventional surveillance techniques to inform and improve public health responses. Currently, wastewater surveillance programs in the U.S. are evaluating integrated approaches to address public health challenges across multiple domains, including substance abuse. In this work, we demonstrated the potential of online solid-phase extraction coupled with liquid chromatography-high-resolution mass spectrometry to support targeted quantification and nontargeted analysis of psychoactive and lifestyle substances as a step toward understanding the operational feasibility of a statewide wastewater surveillance program for substance use assessment in New York. Target screening confirmed 39 substances in influent samples collected from 10 wastewater treatment plants with varying sewershed characteristics and is anticipated to meet the throughput demands as the statewide program scales up to full capacity. Nontarget screening prioritized additional compounds for identification at three confidence levels, including psychoactive substances, such as opioid analgesics, phenethylamines, and cathinone derivatives. Consumption rates of 12 target substances detected in over 80% of wastewater samples were similar to those reported by previous U.S.-based WBE studies despite the uncertainty associated with back-calculations. For selected substances, the relative bias in consumption estimates was sensitive to variations in monitoring frequency, and factors beyond human excretion (e.g., as indicated by the parent-to-metabolite ratios) might also contribute to their prevalence at the sewershed scale. Overall, our study marks the initial phase of refining analytical workflows and data interpretation in preparation for the incorporation of substance use assessment into the statewide wastewater surveillance program in New York.

A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy

Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [68Ga]Ga for diagnostic applications or [177Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probeʼs targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [177Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.

Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment.

Dasatinib (DAS), a potent anticancer drug, has been subjected to formulation enhancements due to challenges such as significant first-pass metabolism, poor absorption, and limited oral bioavailability. To improve its release profile, DAS was embedded in a matrix of the hydrophilic polymer polyvinylpyrrolidone (PVP). Drug amorphization was induced in a planetary ball mill by solvent-free co-grinding, facilitating mechanochemical activation. This process resulted in the formation of amorphous solid dispersions (ASDs). The ASD capsules exhibited a notable enhancement in the release rate of DAS compared to capsules containing the initial drug. Given that anticancer drugs often undergo limited metabolism in the body with unchanged excretion, the ecotoxicological effect of the native form of DAS was investigated as well, considering its potential accumulation in the environment. The highest ecotoxicological effect was observed on the bacteria Vibrio fischeri, while other test organisms (bacteria Pseudomonas putida, microalgae Chlorella sp., and duckweed Lemna minor) exhibited negligible effects. The enhanced drug release not only contributes to improved oral absorption but also has the potential to reduce the proportion of DAS that enters the environment through human excretion. This comprehensive approach highlights the significance of integrating advances in drug development while considering its environmental implications.

Chemical composition and antifungal activity of Teucrium Leucocladum Boiss. essential oils growing in Egypt using two different techniques

BackgroundTeucrium Leucocladum Boiss. (TL) (family Lamiaceae), indigenous to Sinai, Egypt, and Mediterranean region, is considered a rich source of essential oils (EOs). This study aimed to extract the aerial parts essential oils utilizing hydro-distillation (HD) and microwave-assisted extraction (MAE), and analyze the volatile constituents by Gas Chromatography–Mass Spectrometry (GC/MS). The antifungal and cytotoxic potentials against Candida albicans (C. albicans) and non-small cell lung adenocarcinoma A549, triple-negative breast cancer MDA-MB-231 cell lines, respectively, were likewise estimated. Subsequently, the three main compounds were docked into the crystal structure of Candida albicansN-myristoyltransferase (NMT) with myristoyl-COA and peptidic inhibitor (PDB 1IYK), and predictions of human absorption, distribution, metabolism, and excretion (ADME) were performed to assess the drug-likeness of the compounds.ResultsThe chemical profile consisted of monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, and oxygenated sesquiterpenes. The MAE oil sample (TLM) yield was found to be double that of the HD oil sample (TLH). TLM afforded an inhibitory diameter (13 mm) comparable to the ketoconazole (20 mm), TLM 100 mg/mL showed the strongest antifungal potential against C. albicans. The cytotoxic assay revealed moderate activity against A549 and MDA-MB-231. In silico studies using molecular docking were processed on the major components in which nerolidol had the best-fitting energy to inhibit C. albicans (− 7.21 kcal/mol), while ADME results established a promising first step for the potential drug bioavailability.ConclusionIn this research, essential oil acquired from the aerial parts proved to contain monoterpenes and sesquiterpenes, which are classes of compounds known for their versatile usage in medicine. In vivo studies on Teucrium Leucocladum Boiss. active metabolites against clinical strains of fungi need to be further studied, as do the effects of combining the active compounds with antifungal agents to combat antimicrobial resistance.

A comparative study on heavy metal (cadmium) tolerance and biosorption capacity of locally isolated lactic acid bacteria

Heavy metals (HM) have less biological role but show extreme toxicity in living systems. Lactic acid bacteria (LAB) are beneficial microorganisms, some of which have the ability to chelate HM and may be used to treat heavy metals poisoning. The aim of the current study was to select and identify Cd-removing probiotic LAB strains, for future pharmaceutical application. Seventeen LAB strains, from human excretions and animal fecal matter, were initially verified for their probiotic properties. The strains which could survive in the presence of Cd (≥100 ppm) were selected. The metal removal efficiency of isolates was compared, through atomic absorption spectrophotometry (AAS), by measuring the reduction in Cd contents of CdCl2 5 mg/L (3.05 ppm of Cd) supplemented broth following 24 h culturing of the strains. The Cd reduction of 38–75% was recorded in culture broth. The Cd removal ability significantly varied (p < 0.05) with microbial surface charge, incubation period, temperature and pH of media. Levilactobacillus brevis MW362790 and Pediococcus pentosaceus MT323062, identified through 16S rRNA gene sequencing, were recognized as strong Cd chelators. These strains may have application in pharmaceutical or agriculture (farm animals) for protection against cadmium toxicity. Further studies are suggested on in vivo metal detoxification potential.

A critical and comprehensive review of the current status of 17β-estradiol hormone remediation through adsorption technology.

Even at low concentrations, steroid hormones pose a significant threat to ecosystem health and are classified as micropollutants. Among these, 17β-estradiol (molecular formula: C18H24O2; pKa = 10.46; Log Kow = 4.01; solubility in water = 3.90mgL-1 at 27°C; molecular weight: 272.4gmol-1) is extensively studied as an endocrine disruptor due to its release through natural pathways and widespread use in conventional medicine. 17β-estradiol (E2) is emitted by various sources, such as animal and human excretions, hospital and veterinary clinic effluents, and treatment plants. In aquatic biota, it can cause issues ranging from the feminization of males to inhibiting plant growth. This review aims to identify technologies for remediating E2 in water, revealing that materials like graphene oxides, nanocomposites, and carbonaceous materials are commonly used for adsorption. The pH of the medium, especially in acidic to neutral conditions, affects efficiency, and ambient temperature (298K) supports the process. The Langmuir and Freundlich models aptly describe isothermal studies, with interactions being of a low-energy, physical nature. Adsorption faces limitations when other ions coexist in the solution. Hybrid treatments exhibit high removal efficiency. To mitigate global E2 pollution, establishing national and international standards with detailed guidelines for advanced treatment systems is crucial. Despite significant advancements in optimizing technologies by the scientific community, there remains a considerable gap in their societal application, primarily due to economic and sustainable factors. Therefore, further studies are necessary, including conducting batch experiments with these adsorbents for large-scale treatment along with economic analyses of the production process.

Exposure to environmental pollutants: A mini-review on the application of wastewater-based epidemiology approach.

Wastewater-based epidemiology (WBE) is considered an innovative and promising tool for estimating community exposure to a wide range of chemical and biological compounds by analyzing wastewater. Despite scholars' interest in WBE studies, there are uncertainties and limitations associated with this approach. This current review focuses on the feasibility of the WBE approach in assessing environmental pollutants, including pesticides, heavy metals, phthalates, bisphenols, and personal care products (PCPs). Limitations and challenges of WBE studies are initially discussed, and then future perspectives, gaps, and recommendations are presented in this review. One of the key limitations of this approach is the selection and identification of appropriate biomarkers in studies. Selecting biomarkers considering the basic requirements of a human exposure biomarker is the most important criterion for validating this new approach. Assessing the stability of biomarkers in wastewater is crucial for reliable comparisons of substance consumption in the population. However, directly analyzing wastewater does not provide a clear picture of biomarker stability. This uncertainty affects the reliability of temporal and spatial comparisons. Various uncertainties also arise from different steps involved in WBE. These uncertainties include sewage sampling, exogenous sources, analytical measurements, back-calculation, and estimation of the population under investigation. Further research is necessary to ensure that measured pollutant levels accurately reflect human excretion. Utilizing data from WBE can support healthcare policy in assessing exposure to environmental pollutants in the general population. Moreover, WBE seems to be a valuable tool for biomarkers that indicate healthy conditions, lifestyle, disease identification, and exposure to pollutants. Although this approach has the potential to serve as a biomonitoring tool in large communities, it is necessary to monitor more metabolites from wastewater to enhance future studies.

Human Metabolism and Excretion of Kawakawa (Piper excelsum) Leaf Chemicals.

Piper excelsum (kawakawa) has a history of therapeutic use by Māori in Aotearoa New Zealand. It is currently widely consumed as a beverage and included as an ingredient in "functional" food product. Leaves contain compounds that are also found in a wide range of other spices, foods, and medicinal plants. This study investigates the human metabolism and excretion of kawakawa leaf chemicals. Six healthy male volunteers in one study (Bioavailability of Kawakawa Tea metabolites in human volunteers [BOKA-T]) and 30 volunteers (15 male and 15 female) in a second study (Impact of acute Kawakawa Tea ingestion on postprandial glucose metabolism in healthy human volunteers [TOAST]) consume a hot water infusion of dried kawakawa leaves (kawakawa tea [KT]). Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analyses of urine samples from BOKA-T identified 26 urinary metabolites that are significantly associated with KT consumption, confirmed by the analysis of samples from the independent TOAST study. Seven of the 26 metabolites are also detected in plasma. Thirteen of the 26 urinary compounds are provisionally identified as metabolites of specific compounds in KT, eight metabolites are identified as being derived from specific compounds in KT but without resolution of chemical structure, and five are of unknown origin. Several kawakawa compounds that are also widely found in other plants are bioavailable and are modified by phase 1 and 2 metabolism.

Addressing the ADME Challenges of Compound Loss in a PDMS-Based Gut-on-Chip Microphysiological System.

Microphysiological systems (MPSs) are promising in vitro technologies for physiologically relevant predictions of the human absorption, distribution, metabolism, and excretion (ADME) properties of drug candidates. However, polydimethylsiloxane (PDMS), a common material used in MPSs, can both adsorb and absorb small molecules, thereby compromising experimental results. This study aimed to evaluate the feasibility of using the PDMS-based Emulate gut-on-chip to determine the first-pass intestinal drug clearance. In cell-free PDMS organ-chips, we assessed the loss of 17 drugs, among which testosterone was selected as a model compound for further study based on its substantial ad- and absorptions to organ chips and its extensive first-pass intestinal metabolism with well-characterized metabolites. A gut-on-chip model consisting of epithelial Caco-2 cells and primary human umbilical vein endothelial cells (HUVECs) was established. The barrier integrity of the model was tested with reference compounds and inhibition of drug efflux. Concentration-time profiles of testosterone were measured in cell-free organ chips and in gut-on-chip models. A method to deduce the metabolic clearance was provided. Our results demonstrate that metabolic clearance can be determined with PDMS-based MPSs despite substantial compound loss to the chip. Overall, this study offers a practical protocol to experimentally assess ADME properties in PDMS-based MPSs.

THE EFFECT OF PROJECT BASED LEARNING MODEL WITH STEM APPROACH TO STUDENTS’ CRITICAL THINGKING SKILL ON HUMAN EXCRETION SYSTEM

This study was aimed to determine the effect of Project Based Learning Model with STEM approach to students' critical thinking skills on Human Excretion System material in class 8th grade at SMP Negeri 37 Medan. This research used quantitative methods with the type of research quasi experiment with pretest-posttest control group design. The sample of this study consisted of two classes randomly selected by simple random sampling technique, namely in class VIII-D and VIII-F. The first sample is an experimental class that was taught using the PjBL-STEM learning model, and the second sample is a control class that was taught using conventional learning methods. The research instrument that was used included critical thinking skills test instrument using essay questions totaling 5 questions. Analysis of research data used the Independent Sample T-Test test using SPSS version 26.0. The pretest data results of students' critical thinking skills in class VIII-D and class VIII-F are 33.71 and 29.35. After obtained the results of the initial ability of students by looking at the pretest results in both classes, class VIII-D was selected as the experimental class and class VII-F as the control class. The posttest data in the experimental class and control class are 80.00 and 52.58. Based on the hypothesis test, the calculated t value is 12.761 &gt; t table 1.671, and the significance value is 0.000 &lt; 𝛼, with 𝛼 = 0.05, so H0 is rejected and Ha was accepted, which meant that there was an effect of the PJBL-STEM model on the critical thinking skills of students on the material of the excretory system. The influence of the PJBL-STEM model on students' critical thinking skills was categorized as strong with a cohen's d value of 3.242. It can be concluded that the PJBL-STEM model have an effect on students' critical thinking skills with a strong effect category.

Fate of nitrogen in French human excreta: Current waste and agronomic opportunities for the future

Nitrogen (N) is essential for plant growth and protein synthesis but global reactive N losses, mainly from food systems, induce strong environmental impacts. N losses after human excretion are often overlooked because, in Western societies, they partly occur as inert N2, following denitrification in wastewater treatment plants (WWTP), and losses in waters are often small compared to diffuse agricultural emissions. Yet N from human excretions could be used for crop fertilization, potentially with very high recycling rates via source separation. In this study we use unique operational data from the ∼20,000 French WWTPs to produce a N mass-balance of excretions in the French sanitation system. Even though 75 % of WWTPs' sludge is spread on crops, only 10 % of the excreted N is recycled and 50 % of N is lost to the atmosphere, mainly through WWTP nitrification-denitrification. The remaining 40 % ends up in water or in diffuse losses in the ground, of which about half is lost outside of the WWTPs' discharge system, through sewers storm water and individual autonomous systems. While WWTPs removal efficiency increased in the 2000s, it has been followed by a decade of stagnation, reaching 70 % at the national level. This national average hides regional discrepancies, from 60 to 85 % in the 6 French water agencies basins. These differences closely correlate with the classification as “N sensitive areas” and is mainly due to large WWTPs which handle most of the N load. Recycling all N in excretions could supply 10 % of domestic protein consumption in the current French food system, and up to 30 % if it is prioritized towards crop production for human consumption. Redesigning the food system (decrease of nutrient losses, more plant-based diets) could further increase this contribution.