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This study investigated (a) differences between males and females for changes in serum, tear, and urine osmolality, hematocrit, and urine specific gravity following acute passive dehydration and (b) assessed the reliability of these biomarkers separately for each sex. Fifteen males (age: 26.3 ± 3.5 years, body mass: 76 ± 7 kg) and 15 females (age: 28.8 ± 6.4 years, body mass: 63 ± 7 kg) completed a sauna protocol twice (5–28 days apart), aiming for 4% body mass loss (BML). Urine, blood, and tear markers were collected pre- and postdehydration, and change scores were calculated. Male BML was significantly greater than that of females in Trial 1 (3.53% ± 0.55% vs. 2.53% ± 0.43%, p <.001) and Trial 2 (3.36% ± 0.66% vs. 2.53% ± 0.44%, p =.01). Despite significant differences in BML, change in hematocrit was the only change marker that displayed a significant difference in Trial 1 (males: 3% ± 1%, females: 2% ± 1%, p =.004) and Trial 2 (males: 3% ± 1%, females: 1% ± 1%, p =.008). Regression analysis showed a significant effect for sex (male) predicting change in hematocrit (β = 0.8, p =.032) and change in serum osmolality (β = −3.3, p =.005) when controlling for BML but not for urinary or tear measures. The intraclass correlation coefficients for females (ICC 2, 1) were highest for change in urine specific gravity (ICC =.62, p =.006) and lowest for change in tear osmolarity (ICC = −.14, p =.689), whereas for males, it was posthematocrit (ICC =.65, p =.003) and post tear osmolarity (ICC =.18, p =.256). Generally, biomarkers showed lower test–retest reliability in males compared with females but, overall, were classified as poor–moderate in both sexes. These findings suggest that the response and reliability of hydration biomarkers are sex specific and highlight the importance of accounting for BML differences. [ABSTRACT FROM AUTHOR]

Background: The prolificacy of sows (litter size at birth) has markedly increased, leading to higher post-natal mortality. Heat stress can exacerbate this issue. Arginine plays an important role in several physiological pathways; its effect on gestating sows can depend on the period of supplementation. This study evaluated the effects of arginine supplementation on the productive performance and physiological status of sows during different gestation periods and seasons, using a multi-omics approach. Methods: A total of 320 sows were divided into 4 groups over 2 seasons (warm/cold); a control group (CO) received a standard diet (including 16.5 g/d of arginine) and 3 other groups received the standard diet supplemented with 21.8 g/d of arginine (38.3 g/d of arginine) either during the first 35 d (Early35), the last 45 d (Late45) or throughout the entire gestation period (COM). The colostrum was analyzed for nutritional composition, immunoglobulins and metabolomic profile. Urine and feces were analyzed on d 35 and 106 for the metabolomic and microbial profiles. Piglet body weight and mortality were recorded at birth, d 6, d 26, and on d 14 post-weaning. Results: Interactions between arginine and season were never significant. The Early35 group had a lower percentage of stillborn (P < 0.001), mummified (P = 0.002) and low birthweight (LBW) piglets (P = 0.02) than the CO group. The Late45 group had a lower percentage of stillborn piglets (P = 0.029) and a higher percentage of high birthweight piglets (HBW; P < 0.001) than the CO group. The COM group had a higher percentage of LBW (P = 0.004) and crushed piglets (P < 0.001) than the CO group. Arginine supplementation modifies the metabolome characterization of colostrum, urine, and feces. Creatine and nitric oxide pathways, as well as metabolites related to microbial activity, were influenced in all matrices. A slight trend in the beta diversity index was observed in the microbiome profile on d 35 (P = 0.064). Conclusions: Arginine supplementation during early gestation reduced the percentage of stillborn and LBW piglets, while in the last third of pregnancy, it favored the percentage of HBW pigs and reduced the percentage of stillbirths, showing that arginine plays a significant role in the physiology of pregnant sows. [ABSTRACT FROM AUTHOR]

Background: Fluoride plays a vital role in preventing dental caries, with its addition to oral care products significantly promoting oral hygiene. A no-rinse brushing method aims to increase fluoride retention in the oral cavity, as rinsing with water decreases fluoride levels in saliva, which could affect remineralization. While the no-rinse brushing method holds promise for improving fluoride retention in the oral cavity, critical inquiries persist regarding its safety. This study investigated the kinetics of oral fluoride and potential risks to fully assess its effectiveness and implications for oral health. Methods: Ten healthy adults participated in a crossover study comparing the no-rinse with the rinse method. All subjects followed American Dental Association (ADA) brushing guidelines. Levels of fluoride in saliva (supernatant and sediment) and urine were measured over time, and plasma fluoride was measured one hour after brushing. Pharmacokinetic parameters were also calculated from the data. Results: Participants using the no-rinse method had higher fluoride levels in supernatant immediately and up to 30 min post-brushing compared to the rinse method. Fluoride levels in sediment were higher only immediately after brushing. The total fluoride concentration in saliva remained elevated for up to 5 min with the no-rinse method. Systemic fluoride absorption showed no significant difference between the two methods based on blood and urine analysis. Conclusion: This research indicates that the no-rinse method can enhance fluoride retention in the oral cavity for up to 30 min after a single brushing. In addition, our findings suggest that this method does not significantly influence systemic fluoride levels or toxicity. Registry: Thai Clinical Trials Registry, TCTR (http://thaiclinicaltrials.org). Clinical trial registration number: TCTR20231104001 (4/11/2023). [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion Tidal peritoneal dialysis (TPD) provides better fluid flow mechanics and is more comfortable for the patient, owing to fewer alarms and less pain during inflow and outflow. The long‐term characteristics of patients with TPD were not evident. In this randomized controlled follow‐up study, we aimed to explore the characteristics of patients with TPD, compared to IPD.A total of 85 patients were randomized to either IPD or 70% TPD between January 2019 and December 2020, and all patients were followed up on December 2021. The characteristics of patients between the two groups were analyzed using a t‐test or chi‐square as appropriate. The overall survival and technical survival were analyzed using Kaplan–Meier analysis.Forty‐two patients were assigned to IPD, and 43 patients were assigned to TPD. The basal characteristics of patients were not different between the two groups. In an average of 16 months of follow‐up, 19 patients died, and 25 patients dropped out of peritoneal dialysis. The two groups had no difference in overall survival and technical survival. TPD was associated with high urine volume (p = 0.001), lower blood urea nitrogen (p = 0.002), lower phosphorus (p = 0.004), and fewer cycler alarms (p < 0.001). The chance of patients reporting abdominal fullness was higher in patients with TPD (p = 0.001).In the randomized, controlled, follow‐up study, TPD may preserve residual renal function and is associated with lower urea nitrogen and phosphorus in chronic peritoneal dialysis patients. TPD is associated with fewer cycler alarms but may increase the chance of patients reporting abdominal distension. [ABSTRACT FROM AUTHOR]

The challenges of long-term graft survival and the side effects of current immunosuppressive therapies in kidney transplantation highlight the need for improved drugs with fewer adverse effects. Biomarkers play a crucial role in quickly detecting post-transplant complications, with new biomarkers showing promise for ongoing monitoring of disease and potentially reducing the need for unnecessary invasive biopsies. The chemokines such as C-X-C motif chemokine ligand 10 (CXCL10), are particularly promising protein biomarkers for acute renal rejection, with urine samples being a desirable source for biomarkers. The aim of this review is to analyze the literature on the potential role of urinary CXCL10 protein in predicting kidney graft injuries. The results of this study demonstrate that evaluating urinary CXCL10 levels is more successful in identifying post-transplant injuries compared to assessing the CXCL10/Cr ratio. [ABSTRACT FROM AUTHOR]

Proteins, saccharides, and low molecular organic compounds in the blood, urine, and saliva could potentially serve as biomarkers for diseases related to diet, lifestyle, and the use of illegal drugs. Lifestyle-related diseases (LSRDs) such as diabetes mellitus (DM), non-alcoholic steatohepatitis, cardiovascular disease, hypertension, kidney disease, and osteoporosis could develop into life-threatening conditions. Therefore, there is an urgent need to develop biomarkers for their early diagnosis. Advanced glycation end-products (AGEs) are associated with LSRDs and may induce/promote LSRDs. The presence of AGEs in body fluids could represent a biomarker of LSRDs. Urine samples could potentially be used for detecting AGEs, as urine collection is convenient and non-invasive. However, the detection and identification of AGE-modified proteins in the urine could be challenging, as their concentrations in the urine might be extremely low. To address this issue, we propose a new analytical approach. This strategy employs a method previously introduced by us, which combines slot blotting, our unique lysis buffer named Takata's lysis buffer, and a polyvinylidene difluoride membrane, in conjunction with electrospray ionization-mass spectrometry (ESI)/matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). This novel strategy could be used to detect AGE-modified proteins, AGE-modified peptides, and free-type AGEs in urine samples. [ABSTRACT FROM AUTHOR]

In this report, a polytetrahydrofuran-coated polyester fabric phase sorptive extraction (FPSE) for the determination of doxycycline in human urine was described. The sol-gel polytetrahydrofuran sorbent proved to be superior against other sol-gel coated cellulose and polyester membranes tested. The effect of the extraction parameters including membrane surface area, sample pH and volume, salt concentration, extraction time, stirring rate, etc., on the extraction efficiency of the analyte was studied using the "one-factor-at-a-time" (OFAT) and Box–Behnken design approaches. The analytical method proposed was validated in compliance with FDA guidelines for bioanalytical procedures. The method was linear in the determination range of 100–5000 ng/mL with the determination coefficient of 0.9953. The limit of detection (LOD) and the lower limit of quantification for doxycycline was 17 and 100 ng/mL, respectively. The relative recoveries for intra-day and inter-day studies ranged from 98.5–112.2% and 89.6–96.8%, respectively. The relative standard deviation was lower than 14.7% in all cases, exhibiting good precision. The sol-gel polytetrahydrofuran-modified FPSE membranes were reusable for at least 30 times. The greenness of the developed method was evaluated using Sample Preparation Metric of Sustainability (SPMS) and Blue Applicability Grade Index (BAGI) metric tools. Finally, the analytical scheme was successfully employed for the quantitation of urinary doxycycline collected at various time points following the administration of doxycycline-containing tablets. [ABSTRACT FROM AUTHOR]

Background Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages. Methods This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics. Results A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing. Conclusion Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources. [ABSTRACT FROM AUTHOR]

The aim of this literature review was to identify and provide a summary update on the validity and applicability of the most promising dietary biomarkers reflecting the intake of important foods in the Western diet for application in epidemiological studies. Many dietary biomarker candidates, reflecting intake of common foods and their specific constituents, have been discovered from intervention and observational studies in humans, but few have been validated. The literature search was targeted for biomarker candidates previously reported to reflect intakes of specific food groups or components that are of major importance in health and disease. Their validity was evaluated according to 8 predefined validation criteria and adapted to epidemiological studies; we summarized the findings and listed the most promising food intake biomarkers based on the evaluation. Biomarker candidates for alcohol, cereals, coffee, dairy, fats and oils, fruits, legumes, meat, seafood, sugar, tea, and vegetables were identified. Top candidates for all categories are specific to certain foods, have defined parent compounds, and their concentrations are unaffected by nonfood determinants. The correlations of candidate dietary biomarkers with habitual food intake were moderate to strong and their reproducibility over time ranged from low to high. For many biomarker candidates, critical information regarding dose response, correlation with habitual food intake, and reproducibility over time is yet unknown. The nutritional epidemiology field will benefit from the development of novel methods to combine single biomarkers to generate biomarker panels in combination with self-reported data. The most promising dietary biomarker candidates that reflect commonly consumed foods and food components for application in epidemiological studies were identified, and research required for their full validation was summarized. [ABSTRACT FROM AUTHOR]

Context Although the nutritional composition of organic food has been thoroughly researched, there is a dearth of published data relating to its impact on human health. Objective This systematic review aimed to examine the association between organic food intake and health effects, including changes in in vivo biomarkers, disease prevalence, and functional changes. Data Sources PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception through Nov 13, 2022. Data Extraction Both observational and interventional studies conducted in human populations were included, and association between level of organic food intake and each outcome was quantified as "no association," "inconsistent," "beneficial correlation/harmful correlation," or "insufficient". For outcomes with sufficient data reported by at least 3 studies, meta-analyses were conducted, using random-effects models to calculate standardized mean differences. Data Analysis Based on the included 23 observational and 27 interventional studies, the association between levels of organic food intake and (i) pesticide exposure biomarker was assessed as "beneficial correlation," (ii) toxic metals and carotenoids in the plasma was assessed as "no association," (iii) fatty acids in human milk was assessed as "insufficient," (iv) phenolics was assessed as "beneficial", and serum parameters and antioxidant status was assessed as "inconsistent". For diseases and functional changes, there was an overall "beneficial" association with organic food intake, and there were similar findings for obesity and body mass index. However, evidence for association of organic food intake with other single diseases was assessed as "insufficient" due to the limited number and extent of studies. Conclusion Organic food intake was found to have a beneficial impact in terms of reducing pesticide exposure, and the general effect on disease and functional changes (body mass index, male sperm quality) was appreciable. More long-term studies are required, especially for single diseases. Systematic Review Registration PROSPERO registration no. CRD42022350175. [ABSTRACT FROM AUTHOR]

Aim: To assess missed urinary tract infections (UTI) in febrile infants ≤2 months when adhering to recent guidelines suggesting not to send a urine culture with a negative dipstick. Methods: A retrospective cohort study of 308 infants ≤2 months with a positive urine culture admitted in 2013–2023, divided into subgroups without exposure to urine dipstick results: 'urosepsis' (UTI with bacteraemia), 'UTI' (positive urine culture, elevated inflammatory markers, no other cause of fever) and 'bacteriuria' (positive urine culture, not meeting the above‐mentioned criteria). After retrieving the dipstick results, the 'missed UTI' group (UTI+ negative dipstick) was described. Results: A negative dipstick was found in 2/20 (10%), 32/127 (25%) and 126/161 (78%) of infants with 'urosepsis', 'UTI' and 'bacteriuria', respectively. In the 'missed UTI' group (n = 34), there were more non‐Escherichia coli UTI (68% vs. 9% with positive dipstick, p < 0.001), and lower inflammatory markers (leukocytes 15.5 vs. 17.2 k/μL, p = 0.007, C‐reactive protein 21 vs. 58 mg/L, p < 0.001). Three infants had high‐grade vesicoureteral reflux (VUR) and renal scarring. Conclusions: There is a non‐negligible rate of infants ≤2 months with UTI and without pyuria, including those with urosepsis, VUR and renal scarring. We suggest obtaining a urine culture regardless of dipstick results. [ABSTRACT FROM AUTHOR]

Background Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx) are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance. Methods Blood plasma, urine, peripheral blood mononuclear cells, and erythrocytes from patients with and without SDHx PVs were investigated for central carbon metabolites. These were measured by liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance spectroscopy and included among others, succinate, fumarate, α-ketoglutarate, and lactate. Results Plasma succinate to fumarate ratios effectively distinguished tumor-bearing and asymptomatic patients with and without SDHx PV with promising diagnostic performance (areas under the receiver operating characteristic curve 0.86-0.95), although higher levels were noted in individuals with SDHB PV. Metabolites in urine and in peripheral blood mononuclear cell extracts were largely similar between groups. Erythrocytes showed strong metabolic alterations in patients with SDHx PV compared to controls, with 8 of 13 low-molecular organic acids being significantly different (P <.05). The lactate-α-ketoglutarate-ratio of erythrocytes identified individuals with SDHx PV equally well as plasma, with a sensitivity and specificity of 92% (AUC 0.97). Conclusion Blood biomarkers have been underutilized for identifying carriers of SDHx PV or to validate variants of unknown significance. Our findings advocate for further investigation into a combined approach involving plasma and erythrocytes for future diagnostic strategies. [ABSTRACT FROM AUTHOR]

This study introduces a miniaturised solid-phase extraction (µ-SPE) method coupled with ultra-high performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous quantification of 23 compounds, including psychoactive drugs, narcotics and their metabolites, in urine samples. The µ-SPE method, using standard laboratory equipment such as a centrifuge, was developed and validated, offering a practical and economical alternative to more traditional SPE methods. The key extraction parameters: elution solvent composition, sample and elution volumes, and sorbent mass were optimized to enhance performance. The method demonstrated high sensitivity, with detection limits between 0.06 and 0.41 ng cm−3 and quantification limits from 0.19 to 1.24 ng cm−3. The precision was confirmed with an intra-day precision ranging from 0.2% to 7.5% and an inter-day precision from 1.2% to 13.4%. Recovery rates ranged from 84.2% to 109.4%, with minimal matrix effects observed for most analytes (|ME|< 10%). The relative error remained below 5%, indicating good accuracy. The method was also evaluated in terms of greenness, practical, and analytical aspects using the WAC model. Based on the validation results, it was concluded that the developed method could be a good confirmatory method for results obtained by immunochemical tests and could also be used in both clinical analyses and forensic toxicology. [ABSTRACT FROM AUTHOR]

Purpose: Post-procedural urinary tract infections (ppUTIs) following voiding cystourethrography (VCUG) vary widely, with rates from 0 to 42%, though recent studies suggest rates typically below 5%. Verifying urine sterility before VCUG is traditionally done but questioned. This study assessed the 7-day ppUTI rate post-VCUG without prior urine sterility confirmation and identified associated risk factors. Methods: A retrospective review of VCUG cases in children under three years at a pediatric hospital over two years was conducted. Exclusions included neuropathic bladder, bladder exstrophy, pre-VCUG urine cultures, and lost-to-follow-up cases. Achieving a ppUTI rate below 5% would support safe VCUG practice without pre-urine culture. Results: Of 318 VCUGs performed on 300 children, 248 (78%) were males (8% circumcised) with a median age of 5 months. Retrograde VCUG was more common than suprapubic cystography (63% vs. 37%). Before the test, 33.6% received antibiotics, mostly prophylactically. Hydronephrosis was present in 66.4%, and 69% had a history of UTI. VCUG results were abnormal in 43% of cases: 85% had vesicoureteral reflux (VUR), 10% had posterior urethral valves (PUV), and 28% had other abnormalities. The 7-day ppUTI rate was 3.8%, with 67% of ppUTI cases having abnormal VCUG results versus 41% without ppUTI (p = 0.06). No significant risk factors for ppUTI were identified. Conclusions: Omitting systematic urine culture before VCUG was not associated with a high ppUTI rate, even in children with pre-existing urologic conditions or a history of UTI, indicating that VCUG can be safely performed without prior urine sterility confirmation. No risk factors for ppUTI were identified. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant K. pneumoniae infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections. [ABSTRACT FROM AUTHOR]

Background: This study compared the clinical sensitivity and the time-to-result of an individual testing (IT) and a cascaded pooled testing approach (CPT; a positive test result in a pooled sample triggers examination of smaller-sized pools or individual samples) for assessing the prevalence and the intensity of Schistosoma haematobium infection. We also compared the sensitivity of the CPT in detecting S. haematobium infection when deploying urine filtration microscopy (UFM) vs. urine reagent strips (URS), and testing 10 mL vs. 15 mL of urine. Methodology/Principal findings: Between October 2021 and April 2022, S. haematobium eggs were counted in urine samples collected from school-aged children living in the Afar and Gambella Regional States of Ethiopia. Urine samples were collected at baseline (n = 1,288), and one month after administration of praziquantel (n = 118). All urine samples were processed through both an IT and a CPT approach (pools of 5, 10, 20, and 40 individual samples), deploying UFM (10 mL) and URS (10 mL). In addition, 15 mL urine was processed through the CPT deploying UFM. At baseline, the prevalence of S. haematobium infection estimated when using UFM and deploying a CPT approach was significantly lower (17.3%) compared to an IT approach (31.5%). The clinical sensitivity of the CPT in detecting S. haematobium eggs was 51.7%. The sensitivity increased significantly as a function of increasing log transformed urine egg counts (UECs) of the individual samples (OR 2.71, 95%CI 1.63 ― 4.52). The sensitivity was comparable when the amount of urine examined was 10 mL (51.7%) vs. 15 ml (50.8%), and when UFM was used for testing vs. URS (51.5%). The mean log UECs estimated following the CPT approach was lower compared to the estimate by the IT (p <0.001). UECs of the individual samples estimated using the IT and CPT approaches were moderately correlated (r = 0.59 when 10 mL and 15 mL urine was examined after pooling). CPT reduced the time needed for processing urine samples and testing for S. haematobium infection by 29% with UFM and by 27.7% with URS. Conclusions/Significance: CPT based on UFM and URS techniques may help to rapidly identify areas with higher prevalence of S. haematobium infection (hotspots) in a population. However, the performance of this approach in estimating the prevalence of infection may be compromised, particularly in endemic areas with low intensity infection. Author summary: We examined the sensitivity and the time-to-result of a cascaded pooled testing approach for detecting and estimating the intensity of Schistosoma haematobium infection. Urine samples collected from school-aged children in the Afar and Gambella regions of Ethiopia were analyzed individually and in pools using both urine filtration microcopy (UFM) and urine reagent strips (URS). The cascaded pooled testing approach detected close to 52% of urine samples with S. haematobium eggs. The sensitivity increased as the egg count of the individual samples increased but was comparable when the amount of urine examined was 10 mL vs. 15 mL, and when the diagnostic test used was UFM vs. URS. Pooled testing reduced the time needed for processing urine samples and counting S. haematobium eggs by 29%. Pooled testing based on UFM may help rapidly identify areas with higher prevalence of S. haematobium infection in a population. [ABSTRACT FROM AUTHOR]

Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity. [ABSTRACT FROM AUTHOR]

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours postingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems. [ABSTRACT FROM AUTHOR]

Confirmatory identification of dyes in the physical pieces of evidence, such as hair and fabric, is critically important in forensics. This information can be used to demonstrate the link between a person of interest and a crime scene. High performance liquid chromatography is broadly used for dye analysis. However, this technique is destructive and laborious. This problem can be overcome by near-Infrared excitation Raman spectroscopy (NIeRS), non-invasive and non-destructive technique that can be used to determine chemical structure of highly fluorescent dyes. Analyzed fabric materials often possess body fluid stains, which may obscure the accuracy of NIeRS-based identification of dyes. In this study, we investigate the extent to which fabric contamination with body fluids can alter the accuracy of NIeRS. Our results showed that NIeRS coupled with partial-least squared discriminant analysis (PLS-DA) enabled on average 97.6% accurate identification of dyes on fabric contaminated with dry blood, urine and semen. We also found that NIeRS could be used to identify blood, urine and semen on such fabric with 99.4% accuracy. Furthermore, NIeRS could be used to differentiate between wet and dry blood, as well as reveal the presence of blood on washed fabric. These results indicate that NIeRS coupled with PLS-DA could be used as a robust and reliable analytical approach in forensic analysis of fabric. [ABSTRACT FROM AUTHOR]

The rapid and sensitive indicator of inflammation in the human body is C-Reactive Protein (CRP). Determination of CRP level is important in medical diagnostics because, depending on that factor, it may indicate, e.g., the occurrence of inflammation of various origins, oncological, cardiovascular, bacterial or viral events. In this study, we describe an interferometric sensor able to detect the CRP level for distinguishing between no-inflammation and inflammation states. The measurement head was made of a single mode optical fiber with a microsphere structure created at the tip. Its surface has been biofunctionalized for specific CRP bonding. Standardized CRP solutions were measured in the range of 1.9 µg/L to 333 mg/L and classified in the initial phase of the study. The real samples obtained from hospitalized patients with diagnosed Urinary Tract Infection or Urosepsis were then investigated. 27 machine learning classifiers were tested for labeling the phantom samples as normal or high CRP levels. With the use of the ExtraTreesClassifier we obtained an accuracy of 95% for the validation dataset. The results of real samples classification showed up to 100% accuracy for the validation dataset using XGB classifier. [ABSTRACT FROM AUTHOR]

Simple Summary: Heretofore, a series of research has targeted enhancing feed efficiency and identifying dependable feed efficiency biomarkers, yet less research has focused on improving RFI in Chuanzang black pigs. Therefore, our study facilitates a deeper understanding of the differences in serum and urine metabolites of Chuanzang black pigs with different residual feed intakes in seeking to identify differential metabolites with residual feed intake. Our study used a nontargeted metabolomics approach to analyze pig metabolite markers by differences in Chuanzang black pigs' serum and urine metabolites, providing new insights into the biological differences in residual feed intake selection in Chuanzang black pigs. We believe this paper would be of great interest to breeders of animals. This study was conducted to evaluate associations of blood variables and urine variables with different residual feed intakes (RFIs) in growing Chuanzang black (CB) pigs. A total of 228 growing CB boars from 99 days were used. The same basal diet was offered ad libitum and individual feed intake and body weight were measured over a period of 181 d. The CB pigs were categorized based on their residual feed intake values, with six individuals each from the high and low ends selected and divided into two groups: the low residual feed intake group (LS) and the high residual feed intake group (HS). Serum and urine samples were collected at the end of the experiment for determination of metabolomics profiling. Results showed that there were significantly different metabolites in serum and urine of different RFI groups (fold-change, FC > 2.0 or FC < 0.5, and p < 0.05), and 21 metabolites were identified in serum and 61 in urine. Cluster analysis showed that 20 metabolites were up-regulated and one metabolite was down-regulated in serum; 44 metabolites were up-regulated and 17 metabolites were down-regulated in urine. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differential metabolites of serum were enriched in linoleic acid metabolism, and the differential metabolites of urine were enriched in steroid hormone biosynthesis, taurine and hypotaurine metabolism, and primary bile acid biosynthesis. The correlations between serum metabolites and urine metabolites indicated a significant positive correlation between all fatty acyls in serum metabolites and L-glutamate in urine. However, no compelling genetic or blood biomarkers have been found to explain the differences in RFI, suggesting multiple approaches to effective feed use in pigs. This study provides new insights into the subsequent assessment of RFI by metabolomics profiling, as well as the development of novel feed additives for the factors that will facilitate future research directions in CB pigs. [ABSTRACT FROM AUTHOR]

Metasurfaces exhibit excellent optical performance to enhance the light–matter interaction of target molecules in biosensing based on its well‐optimized nanostructured unit cells. In the meantime, fluorescence (FL) biosensors with aggregation induced emissions (AIE) features also demonstrate outstanding performance in biomarker detection due to their fast response, high selectivity, and low background noise. Nevertheless, extremely low‐level analytes are difficult to detect in practical applications since complex urine samples include a number of uncontrolled variables such as impurities, autofluorescence, other urine components, etc. At present, improving optical signal sensitivity of human serum albumin (HSA) detection is always a big challenge to overcome such interference in human urine scenarios. In this work, first an AIE‐based FL biosensor TPE‐4TA is combined with an all‐dielectric metasurface platform to achieve quantitative detection of trace HSA in urine by utilizing biofunctionalization protocols on the silicon (Si) nanostructures. The results indicate significant FL enhancement in the metasurface platform that offers a promising pathway for improving biomarker detection in the future. [ABSTRACT FROM AUTHOR]

Background: Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers. Methods: Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively. Conclusions: This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management. [ABSTRACT FROM AUTHOR]

Unlocking the potential of sustainable agriculture relies on innovative approaches such as recycling crop waste and exploiting wastewater. Herewith, human urine derivatives were integrated into the fertigation of soilless-grown lettuce. The effects were remarkable: not only did they impact primary metabolites such as amino acids, proteins, and sugars, but they also influenced secondary metabolites such as polyphenols and anthocyanins, along with antioxidant enzyme activity. K-struvite, a urine precipitate with CaO and NaOH, elicited responses comparable to those of the control NPK and correlated with high biometric values. Interestingly, urine precipitate-CaO and electrodialysis (ED) concentrate stimulated accumulation of leaf polyphenols and anthocyanins, while urine precipitate-CaO induced high ABTS antioxidant capacity, highlighting their potential to enhance antioxidant activity and nutritive quality. Moreover, hydrolyzed urine and aurin induced a significant boost of essential amino acid content, underlining their role in increasing the nutritive value of lettuce. However, they also correlated with higher levels of MDA, a marker of lipid peroxidation, and reduced APX activity, indicating the need for further optimization. These findings underscore the promising role of human urine as an organic component in soilless lettuce fertilization, paving the way for more sustainable and resource-efficient agricultural practices. [ABSTRACT FROM AUTHOR]

Cells exposed to stressors of various origin activate protective mechanisms that include the expression of heat shock proteins (Hsps)/molecular chaperones belonging to several families. Well-characterized inducible Hsp70 is present in all human cell-types and biological fluids, including blood, urine, and saliva. The presence of anti-Hsp70 autoantibodies in the serum of healthy individuals has already been confirmed, and their elevated titers positively correlated with the severity of several pathological conditions, including coeliac disease and dermatitis herpetiformis - a cutaneous manifestation of coeliac disease. Here, using an indirect enzyme-linked immunosorbent assay, we demonstrate, for the first time, that anti-Hsp70 autoantibodies are present in the saliva and urine of healthy individuals. Although the occurrence of anti-Hsp70 autoantibodies in the biological fluids of healthy individuals is intriguing, their physiological role is currently unknown. It is believed that antibodies reacting with self-molecules present in the serum of healthy individuals are part of natural autoantibody pool with multiple regulatory functions. On the other hand, some autoantibodies (e.g., typical of autoimmune bullous skin diseases or systemic lupus erythematosus) may be present before the onset of the disease and serve as specific predictive biomarkers. Therefore, we would like to initiate a discussion or future research direction on the use of anti-Hsp70 autoantibodies as a potential "biomarker" in the diagnosis or prediction of autoimmune diseases. Our findings can be considered in biomedical research to develop noninvasive, inexpensive and easy-to-use tests. Nevertheless, large-scale comparative studies should be initiated, involving the collection and analysis of biological samples such as saliva or urine from patients suffering from autoimmune diseases or other inflammatory or neoplastic diseases, to determine whether the levels of anti-Hsp70 autoantibodies are indeed elevated and whether they correlate with the clinical picture of any disease or established biomarkers. [ABSTRACT FROM AUTHOR]

Background: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. Methods: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. Results: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6–500, 0.4–500, and 0.7–10,000 µg·L− 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L− 1) and (0.60, 0.40, and 0.70 µg·L− 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3–4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L− 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. Conclusion: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments. [ABSTRACT FROM AUTHOR]

We present the development and validation of an impedance-based urine osmometer for accurate and portable measurement of urine osmolality. The urine osmolality of a urine sample can be estimated by determining the concentrations of the conductive solutes and urea, which make up approximately 94% of the urine composition. Our method utilizes impedance measurements to determine the conductive solutes and urea after hydrolysis with urease enzyme. We built an impedance model using sodium chloride (NaCl) and urea at various known concentrations. In this work, we validated the accuracy of the impedance-based urine osmometer by developing a proof-of-concept first prototype and an integrated urine dipstick second prototype, where both prototypes exhibit an average accuracy of 95.5 ± 2.4% and 89.9 ± 9.1%, respectively in comparison to a clinical freezing point osmometer in the hospital laboratory. While the integrated dipstick design exhibited a slightly lower accuracy than the first prototype, it eliminated the need for pre-mixing or manual pipetting. Impedance calibration curves for conductive and non-conductive solutes consistently yielded results for NaCl but underscored challenges in achieving uniform urease enzyme coating on the dipstick. We also investigated the impact of storing urine at room temperature for 24 hours, demonstrating negligible differences in osmolality values. Overall, our impedance-based urine osmometer presents a promising tool for point-of-care urine osmolality measurements, addressing the demand for a portable, accurate, and user-friendly device with potential applications in clinical and home settings. [ABSTRACT FROM AUTHOR]

Nowadays, kidney dysfunction is a common health issue due to the modernized lifestyle. Even though medications are commercially available to treat kidney diseases, early diagnosis is crucial and challenging. Clinically, measuring urine creatinine and pH has gained significant interest as a way to diagnose kidney diseases early. In the present work, we attempted to develop a low-cost, robust, accurate and naked-eye colorimetric method to determine both creatinine levels and pH variations in artificial urine samples using a simple 3D-printed hybrid microfluidic device. Creatinine was detected by the incorporation of the traditional Jaffe test onto the hybrid paper–PMMA microfluidic device and pH (4–8) was measured by a simple anthocyanin test. Notably, the tests were established without employing any sophisticated or costly instrument clusters. The developed 3D-printed microfluidic probe showed a limit of detection (LOD) of 0.04 mM for creatinine over a concentration range of 1–10 mM, with a regression coefficient (R2) of 0.995 in laboratory conditions. Interestingly, the experimental data obtained with artificial urine exhibited a wide linear range from 0.1 mM to 5 mM under different pH values ranging from 4 to 8 in the presence of matrices commonly found in urine samples other than proteins, indicating the potential use of this method in pre-clinical analysis. Since the wide linear range of urine creatinine in artificial urine samples falls well below the clinically relevant concentrations in humans (0.07–0.27 mM), the developed lab-on-chip device is further suitable for clinical evaluation with proper ethical clearance. This 3D-printed hybrid microfluidic colorimetry-based creatinine detection and pH indicator platform can be beneficial in the healthcare sector due to the on-site testing capability, cost-effectiveness, ease of use, robustness, and instrument-free approach. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3 months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD. [ABSTRACT FROM AUTHOR]

Background and Aims: Caffeine is a xanthine alkaloid found naturally in plants. Caffeine has cardiotonic and stimulant effects in humans and animals. For this reason, caffeine is on the monitoring list for human sports and is listed as a feed contaminant in horse racing. The aim of this study was to develop a rapid, practical, and specific method for the determination of caffeine in horse urine. Methods: In the new method, the pH of the sample was adjusted by the addition of phosphate buffer, and after solid phase extraction, it was dissolved in methanol before being analysed by gas chromatography mass spectrometry without derivatization. The method was validated according to the European Commission’s 2002/657/EC criteria. Results: The effects of different cartridge brands, pH, and elution solution were determined. Intraday and interday CV% values are 2.8 and 5.2 for the International Residue Limit (IRL), respectively. Five levels (blank, 0.5xIRL, IRL, 1.5xIRL, and 2xIRL) were used in constructing the curve, and the R2 value was greater than 0.99. The analysis run was 11.8 min. The decision limit (CCα) was determined to be 56.7 ng/mL due to IRL. The detection limit of the method was calculated to be 3.3 ng/mL. The method was determined to be robust according to changes in extraction pH, phosphate buffer concentration, centrifugation time, hexane volume in the wash step, different grades of methanol, inlet temperature, and operator. Conclusion: The applicability of the method was demonstrated by analysing positive and negative horse urine samples. Validation parameters showed the method to be selective, specific, and easy to apply. [ABSTRACT FROM AUTHOR]

Objective To establish an automated headspace -gas chromatography method for the determination of 1,1,2,2 - tetrachloroethene in human urine. Methods A urine sample of 5.00 mL was placed in a 20 mL headspace vial, and 2.0 g of anhydrous sodium sulfite was added before sealing the vial. The vial was placed in an automated headspace sampler and heated at 80 ℃ for 50.00 min to equilibrate. Under these heating conditions, 1,1,2,2 -tetrachloroethene in human urine was completely reacted with anhydrous sodium sulfite to form trichloroethylene. The trichloroethylene vapor above the headspace vial was separated by a DB-624 capillary column and detected with a flame ionization detector. Quantification was achieved by plotting a standard curve with the peak area of trichloroethylene and the mass concentration of 1,1,2,2- tetrachloroethane. Results The results showed good linear ranges of 1,1,2,2 -tetrachloroethene in urine between 0.008 3 and 32.000 mg/L, and the correlation coefficient was higher than 0.999 4. For this method, the limit of detection was 2.5 μg/L, and the lower limit of quantification was 8.3 μg/L; the intra-batch precision was 4.79% to 5.28%, and the interbatch precision was 4.61% to 6.44% ; the average recovery rate was 87.53% to 101.17% . Conclusions The automated headspace gas chromatography method for determining 1,1,2,2-tetrachloroethene in human urine was characterized by high sensitivity, good linearity, minimal interference, high precision, and simple sample preparation. It is suitable for measuring the concentration of 1,1,2,2-tetrachloroethene in human urine. [ABSTRACT FROM AUTHOR]

This research introduces a novel electrochemical sensor designed for the detection of chloroquine. The sensor was developed via a simple method to synthesize TiO2 nanoparticles on reduced graphene oxide. The modified electrodes created in this manner exhibited high electrocatalytic activity and distinct chemical reactivity. Various techniques were utilized to perform morphological characterization of the nanocomposites. These techniques revealed alterations revealed changes in functional groups and the attachment of titanium to the reduced graphene oxide present on the electrode surface, thereby elucidating the reasons for the enhanced electrochemical performance. The sensor had a broad measurement range for chloroquine, capable of detecting concentrations as low as 10−8 M. It is applicable for diverse sample analyses, including water, pharmaceuticals, human urine, and serum, with satisfaction ranging between 97 and 99%. The development strategy. An electrochemical sensor was developed using titanium oxide nanoparticles attached to reduced graphene oxide TiO2-NPs @RGO/GCE for real-time detection of chloroquine in real contaminated samples such as human urine, human serum, and tap water with low detection limit. [ABSTRACT FROM AUTHOR]

Urine-derived stem cells (USCs) are a promising source of adult stem cells for cell therapy, drug testing for renal toxicity, and biomarker discovery in kidney disease. USCs can be non-invasively isolated from the donor's own urine, making them a good candidate for precision medicine. Preclinical studies have shown that USCs and exosomes can be used to repair damaged tissues (particularly urinary tract tissues and organs, including the kidneys), to test the toxicity of new drugs, and to identify biomarkers for kidney disease. Further research is needed to fully understand the potential of USCs and to develop safe and effective ways to explore their full potential in precision medicine. Urine-derived stem cells (USCs) are a promising source of stem cells for cell therapy, renal toxicity drug testing, and renal disease biomarker discovery. Patients' own USCs can be used for precision medicine. In this review we first describe the isolation and characterization of USCs. We then discuss preclinical studies investigating the use of USCs in cell therapy, exploring the utility of USCs and USC-derived induced pluripotent stem cells (u-iPSCs) in drug toxicity testing, and investigating the use of USCs as biomarkers for renal disease diagnosis. Finally, we discuss the challenges of using USCs in these applications and provide insights into future research directions. USCs are a promising tool for advancing renal therapy, drug testing, and biomarker discovery. Further research is needed to explore their potential. [ABSTRACT FROM AUTHOR]

Background: Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is a biomarker for the early diagnosis of Alzheimer's disease (AD). It remains unclear whether hepatorenal function affects the urinary AD7c-NTP level. Objective: To evaluate the effects of hepatorenal function on urinary AD7c-NTP level. Methods: We enrolled 453 participants aged 60–100 years. An automated chemistry analyzer was used to determine the indicators of serum hepatorenal function. Enzyme-linked immunosorbent assay was used to measure the urinary AD7c-NTP level. Results: Spearman's correlation analysis showed a negative correlation between urinary AD7c-NTP levels and indicators of hepatorenal function, including albumin (r = –0.181, p < 0.001), albumin/globulin ratio (r = –0.224, p < 0.001), cholinesterase (r = –0.094, p = 0.046), total carbon dioxide (r = –0.102, p = 0.030), and glomerular filtration rate (r = –0.260, p < 0.001), as well as a positive correlation with globulin (r = 0.141, p = 0.003), aspartate transaminase (r = 0.186, p < 0.001), blood urine nitrogen (r = 0.210, p < 0.001), creatinine (r = 0.202, p < 0.001), uric acid (r = 0.229, p < 0.001), and cystatin C (r = 0.265, p < 0.001). The least absolute shrinkage and selection operator (LASSO) regression analysis and multiple linear regression model analyses showed that the statistically significant hepatorenal indicators for predicting AD7c-NTP were A/G (p = 0.007), AST (p = 0.002), BUN (p = 0.019), and UA (p = 0.003). Conclusions: The effects of hepatorenal indicators should be considered when using urinary AD7c-NTP levels in clinical settings. [ABSTRACT FROM AUTHOR]

Combat sports athletes often undergo rapid body mass loss (BML), which presents health risks. Hydration testing has been proposed as a possible solution to reduce or eliminate rapid BML. However, combat sports athletes may exhibit distinct physiological characteristics due to repeated exposure to BML. Thus, traditional and emerging hydration biomarkers should be investigated to determine their potential suitability for field use in this cohort. This study examined whether BML can explain changes in serum and urine osmolality (SosmΔ, UosmΔ), tear osmolarity (TosmΔ), hematocrit (HctΔ), and urine‐specific gravity (USGΔ) after mild–moderate passive dehydration. Biomarker reliability was also assessed across two trials. Fifteen male and female combat sports athletes (age: 26.3 ± 5.3 years, body mass: 67.7 ± 9.9 kg) underwent a sauna protocol twice (5–28 days apart) aiming for 4% BML. The average BML in Trials 1 and 2 was 3.0 ± 0.7%. Regression analysis revealed that BML explained HctΔ (R2 = 0.22, p = 0.009) but not SosmΔ (R2 = 0.11, p = 0.079) or other biomarkers. Intraclass correlation coefficients (ICCs) were significant for all biomarkers except TosmΔ (ICC = 0.06, p = 0.37) and post‐Tosm (ICC = 0.04, p = 0.42); post‐Hct performed best (ICC = 0.82, p < 0.001). Contingency tables with post‐Sosm (295 mOsm/kg) and post‐USG (1.020) cutoffs revealed an 80% true negative rate (TNR) and a 62% true positive rate (TPR). Increasing the Sosm cutoff to 301 mOsm/kg decreased the TNR to 52% but increased the TPR to 83%. Although blood parameters were most sensitive to BML, they could only explain 11%–22% of biomarker variation. The typical USG cutoff misclassified 42% of athletes postdehydration, and reliability was generally poor‐moderate. Alternative strategies should be pursued to manage rapid BML in combat sports. [ABSTRACT FROM AUTHOR]

Gefapixant (MK‐7264, RO4926219, AF‐219) is a first‐in‐class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single‐ and multiple‐dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single‐dose administration of 10‐450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter‐subject variability and a dose‐proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose‐proportional at doses ranging from 7.5 to 50 mg and less than dose‐proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post‐dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half‐life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single‐dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice‐daily dosing regimen. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether antibiotics impact delirium outcomes in older adults with pyuria or bacteriuria in the absence of systemic signs of infection or genitourinary symptoms. Methods: We registered our systematic review protocol with PROSPERO (CRD42023418091). We searched the Medline and Embase databases from inception until April 2023 for studies investigating the impact of antimicrobial treatment on the duration and severity of delirium in older adults (≥60 years) with pyuria (white blood cells detected on urinalysis or dipstick) or bacteriuria (bacteria growing on urine culture) and without systemic signs of infection (temperature > 37.9C [>100.2F] or 1.5C [2.4F] increase above baseline temperature, and/or hemodynamic instability) or genitourinary symptoms (acute dysuria or new/worsening urinary symptoms). Two reviewers independently screened search results, abstracted data, and appraised the risk of bias. Full‐text randomized controlled trials (RCTs) and observational study designs were included without restriction on study language, duration, or year of publication. Results: We screened 984 citations and included 4 studies comprising 652 older adults (mean age was 84.6 years and 63.5% were women). The four studies were published between 1996 and 2022, and included one RCT, two prospective observational cohort studies, and one retrospective chart review. None of the four studies demonstrated a significant effect of antibiotics on delirium outcomes, with two studies reported a worsening of outcomes among adults who received antibiotics. The three observational studies included had a moderate or serious overall risk of bias, while the one RCT had a high overall risk of bias. Conclusions: Our systematic review found no evidence that treatment with antibiotics is associated with improved delirium outcomes in older adults with pyuria or bacteriuria and without systemic signs of infection or genitourinary symptoms. Overall, the evidence was limited, largely observational, and had substantial risk of bias. [ABSTRACT FROM AUTHOR]

In recent years, blood anti-Müllerian hormone (AMH) levels have been investigated in female animals to diagnose many conditions, such as the presence of ovarian tissue, follicle reserve, and granulosa cell tumors. Since blood collection is an invasive method, diagnosis with a non-invasive method is important in terms of practicality and animal welfare. This study aimed to investigate the presence of AMH in cat urine and determine whether a correlation exists between blood and urine AMH levels. In addition, it was aimed at revealing whether there was a change in blood and urine AMH levels according to ovarian follicle distribution. Twenty-seven healthy, fertile female cats in the follicular phase were included. Following blood and urine sample collection, a routine ovariohysterectomy was performed. Histological analysis of the removed ovarian tissue was used to determine ovarian follicle types. While both AMH and estrogen levels were determined in blood samples, only AMH levels were investigated in urine samples. Blood AMH levels averaged 10.61 ± 0.75 ng/mL (range: 5–16 ng/mL), while urine AMH levels averaged 5.67 ± 0.91 ng/mL (range: 0.2–13 ng/mL). While urinary AMH level was <1 ng/mL in 7 cats, urinary AMH was >1 ng/mL in all remaining cats. While the study demonstrated AMH excretion in urine, no correlation was found between blood and urine AMH values. However, a significant positive correlation was observed between blood AMH levels and serum estrogen levels (P < 0.001). These findings suggest that urinary AMH may be a product of proteolytic degradation, potentially leading to inaccurate estimations of ovarian activity based solely on urine AMH levels. • In cats, AMH is excreted in the urine. • There is no correlation between blood and urine AMH levels in cats. • Urinary AMH levels in intact cats may be < 1 ng/mL. [ABSTRACT FROM AUTHOR]

Introduction: Amid the global health crisis, HIV/TB co-infection presents significant challenges, amplifying the burden on patients and healthcare systems alike. Metabolomics offers an innovative window into the metabolic disruptions caused by co-infection, potentially improving diagnosis and treatment monitoring. Aim: This study uses untargeted metabolomics to investigate the urinary metabolic signature of HIV/TB co-infection, enhancing understanding of the metabolic interplay between these infections. Methods: Urine samples from South African adults, categorised into four groups — healthy controls, TB-positive, HIV-positive, and HIV/TB co-infected — were analysed using GCxGC-TOFMS. Metabolites showing significant differences among groups were identified through Kruskal-Wallis and Wilcoxon rank sum tests. Results: Various metabolites (n = 23) were modulated across the spectrum of health and disease states represented in the cohorts. The metabolomic profiles reflect a pronounced disruption in biochemical pathways involved in energy production, amino acid metabolism, gut microbiome, and the immune response, suggesting a bidirectional exacerbation between HIV and TB. While both diseases independently perturb the host's metabolism, their co-infection leads to a unique metabolic phenotype, indicative of an intricate interplay rather than a simple additive effect. Conclusion: Metabolic profiling revealed a unique metabolic landscape shaped by HIV/TB co-infection. The findings highlight the potential of urinary differential metabolites for co-infection, offering a non-invasive tool for enhancing diagnostic precision and tailoring therapeutic interventions. Future research should focus on expanding sample sizes and integrating longitudinal analyses to build upon these foundational insights, paving the way for metabolomic applications in combating these concurrent pandemics. [ABSTRACT FROM AUTHOR]

Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3′-hydroxycotinine, and (2′S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans-3′-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1′S,2′S)-nicotine 1′-oxide in the samples of individuals from various groups. [ABSTRACT FROM AUTHOR]

• Follow-up of non-muscle-invasive bladder cancer (NMIBC) is based on cystoscopy • The relevance of urine markers in the surveillance of NMIBC is obscure. • This study intends to identify scenarios for the use of urine markers high-risk NMIBC. • The simulation suggests that marker-supported follow-up in high-risk NMIBC is safe. • Marker-supported follow-up will significantly reduce the number of cystoscopies. A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. Information on the course of disease of patients with high-risk NMIBC and performance data of a point-of-care test (UBC rapid™), an MCM-5 directed ELISA (ADXBLADDER™), and 2 additional novel assays targeting alterations of mRNA expression and DNA methylation (Xpert bladder cancer monitor™, Epicheck™) were retrieved from high-quality trials and/or meta-analyses. In addition, the sensitivity of white light cystoscopy (WLC) and the impact of a urine marker result on the performance of WLC were estimated based on fluorescence cystoscopy data and information from the CeFub trial. This information was applied to different scenarios in patient follow-up and sensitivity, estimated number of cystoscopies, and the numbers needed to diagnose were calculated. The sensitivity of guideline-based regular follow-up (SOC) at 1 year was calculated at 96%. For different marker-supported strategies sensitivities ranging from 77% to 97.9% were estimated. Calculations suggest that several strategies are effective for the SOC. While for the SOC 24.6 WLCs were required to diagnose 1 tumor recurrence (NND), this NND dropped below 5 in some marker-supported strategies. Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are highly toxic mycotoxins present in food and feed, posing serious health risks to humans and animals. This study aimed to validate an efficient and cost-effective analytical method for quantifying AFB1 and OTA in rat urine using immunoaffinity column extraction and liquid chromatography with fluorescence detection (IAC-LC-FD). Additionally, the study evaluated the effect of incorporating fermented whey and pumpkin into the feed on the urinary excretion of these mycotoxins. The limits of detection and quantification were determined to be 0.1 µg/kg and 0.3 µg/kg, respectively, for both mycotoxins in feed, and 0.2 ng/mL and 0.6 ng/mL, respectively, in urine. The method demonstrated robust recovery rates ranging from 74% to 119% for both AFB1 and OTA in both matrices. In feed samples, the levels of AFB1 and OTA ranged from 4.3 to 5.2 µg/g and from 5.4 to 8.8 µg/g, respectively. This validated method was successfully applied to analyze 116 urine samples from rats collected during the fourth week of an in vivo trial. The results indicated that the addition of fermented whey and pumpkin to the feed influenced mycotoxin excretion in urine, with variations observed based on the sex of the rats, type of mycotoxin, and exposure dosage. [ABSTRACT FROM AUTHOR]

Psychological disorders and dramatic social problems are serious concerns regarding the abuse of amphetamine and its stimulant derivatives worldwide. Consumers of such drugs experience great euphoria along with serious health problems. Determination and quantification of amphetamine-type stimulants are indispensable skills for clinical and forensic laboratories. Analysis of low drug doses in bio-matrices necessitates applications of simple and also effective preparation steps. The preparation procedures not only eliminate adverse matrix effects, but also provide reasonable clean-up and pre-concentration benefits. The current review presents different methods used for sample preparation of amphetamines from urine as the most frequently used biological matrix. The advantages and limitations of various sample preparation methods were discussed focusing on the miniaturized methods. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results. Study Design Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018–March 2019) and after (phase 2, October 2019–September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS. The turnaround time for LC-MS was 1 week in phase 1 and 24 hours in phase 2. For mothers with positive LC-MS confirmation, the infant's meconium was sent for drug screening. Positive results were determined to be true or false positive based on urinary LC-MS results. The primary outcome was the rate of opioid-positive mothers who were unanticipated. The secondary outcome was the difference in rate of neonates who were observed for NOWS, before and after implementation of RC with LC-MS. Results In phase 2, a total of 2,395 deliveries occurred of which 2,122 (88.6%) had available UDS results. Fifty-two (2.5%) women had a positive UDS for at least one drug with LC-MS confirmation. Of those, 25 were true positive and 27 were false positive. Twenty-one (84%) true positive mothers were taking opioids and 8 (37%) of them were unanticipated positives. Among mothers with positive UDS for opioids, the neonatal observation rate for development of NOWS was 100% (22/22) and 48% (21/44) before and after implementation of LC-MS RC, respectively. Conclusion Universal UDS and LC-MS RC in L&D may improve detection of unanticipated positive mothers whose infants are at risk of NOWS. RC of positive results allows intervention only for confirmed cases. Key Points Universal UDS can detect more infants at risk of NOWS. Rapid confirmation of positive UDS reduces burden. Only confirmed infants should be observed in the neonatal intensive care unit. Child Protective Services should only be notified of confirmed opioid-positive results. [ABSTRACT FROM AUTHOR]

Rationale: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. Objectives: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. Methods: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. Results: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. Conclusions: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD. [ABSTRACT FROM AUTHOR]

Little is known about using noninvasive samples for diagnosing Crimean-Congo hemorrhagic fever (CCHF). We investigated detection of CCHF virus in serum, saliva, and urine samples. Our results indicate that serum is the best sample type for CCHF diagnosis; saliva can be used for noninvasive sampling. [ABSTRACT FROM AUTHOR]

We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016-2020 at 10 US sites and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) during 2019-2020 at 6 US sites. Among 159 CRE cases in children (median age 5 years), CRE was isolated from urine for 131 (82.4%) and blood from 20 (12.6%). Annual CRE incidence rate (cases/100,000 population) was 0.47-0.87. Among 207 ESBLE cases in children (median age 6 years), ESBL-E was isolated from urine of 196 (94.7%) and blood of 8 (3.9%). Annual ESBL-E incidence rate was 26.5 in 2019 and 19.63 in 2020. CRE and ESBL-E rates were >2-fold higher among infants than other age groups. Most CRE and ESBL-E cases were healthcare-associated community-onset (68 [43.0%] for CRE vs. 40 [23.7%] for ESBL-E) or community- associated (43 [27.2%] for CRE vs. 109 [64.5%] for ESBL-E). Programs to detect, prevent, and treat multidrugresistant infections must include pediatric populations (particularly the youngest) and outpatient settings. [ABSTRACT FROM AUTHOR]