Urine Samples Research Articles

Cobalamin Deficiency in Children and Adolescents with Sickle Cell Disease

Background/Objective: Cobalamin (B12) deficiency is reported in 18% of adults with sickle cell disease (SCD) and only 10% without SCD; limited data are available on children. Diagnosing B12 deficiency is challenging given the lack of an established gold standard method of assessment and the unique renal features of SCD. B12 metabolism can be impacted by the clinical use of nitrous oxide gas (N2O), which is a standard therapy for SCD pain in some European countries. In response to emerging reports of neurologic sequalae in patients with SCD receiving N2O, we evaluated the prevalence of B12 deficiency in children with SCD pain. Methods: Secondary analysis of prospective blood and urine samples in children aged 3–21 hospitalized with SCD pain. B12 deficiency was defined as plasma methylmalonic acid (MMA) > 592 nmol/L or urine MMA/creatinine ≥ 2.2 mmol/mol. Results: Ninety-four children (13 ± 4 years, 54% female, 68% hemoglobin-SS, and 72% on hydroxyurea) were assessed. Further, 53% (50/94) had B12 deficiency diagnosed by either urine, plasma, or both; 27% (25/94) were deficient based on urine; 39% (37/94) were deficient by plasma; and 13% (12/94) were deficient by both plasma and urine. Plasma MMA and urine MMA/creatinine did not correlate with hemoglobin or mean corpuscular volume. Conclusions: B12 deficiency was common in children with SCD. The absence of a gold standard for diagnosing B12 deficiency compounded with the reliability issues of testing modalities make it impractical to determine whether this is an over- or under-estimation of the true prevalence. Future studies to better understand the dynamics of B12 metabolism during acute and steady states in SCD are warranted and could elucidate the influence of acute SCD pain on these biomarkers.

Urease-Driven Janus Nanomotors for Dynamic Enrichment and Multiplexed Detection of Bladder Cancer MicroRNAs in Urine.

Bladder cancer diagnosis typically involves approaches such as cystoscopy, biopsy, urine cytology, and medical imaging. However, these invasive procedures carry a risk of complications, and direct in vitro detection on clinical samples often results in low sensitivity. Therefore, this study proposed urease-driven magnetic nanomotors for the simultaneous detection of bladder cancer biomarkers miRNA-21 and miRNA-182 in urine samples, aiming for noninvasive diagnosis. The nanomotor was constructed from gold nanorods, mesoporous organo-silica, Fe3O4, and hairpin DNA (hDNA), functioning as a recognition probe for the target miRNAs. In the urea solution, urease catalyzed urea into ammonia and carbon dioxide, propelling the nanomotor for about 60 min, which enhanced the capacity of the probes to capture the target miRNAs. Subsequently, magnetic enrichment enabled highly sensitive dual-miRNA analysis, allowing quantification of miRNA-21 and miRNA-182 with detection limits of 29 and 362 fM, respectively. The nanoprobes also effectively detected miRNAs in spiked urine samples. This simultaneous detection of multiple miRNAs increased the reliability of cancer diagnosis, presenting a novel noninvasive strategy for bladder cancer detection through precise in vitro analysis of actual urine samples.

Comparison of Operational Jet Fuel and Noise Exposure for Flight Line Personnel at Japanese and United States Air Bases in Japan

Flight line personnel are constantly exposed to noise and jet fuel while working on flight lines. Studies suggest that jet fuel in combination with noise affects hearing loss more than noise exposure alone. This study examined the combined effects of jet fuel and noise exposure on the hearing of flight line personnel stationed at Japan Air Self-Defense Force Air Bases (Hamamatsu, Matsushima, Hyakuri, Yokota, and Iruma) and US Air Force Air Bases (Kadena and Misawa) in Japan. Samples were collected from all participants, 97 flightline-exposed and 71 control volunteers, to measure their individual noise levels with a personal sound level meter and volatile organic chemicals (VOCs) with a chemical sampling pump during a single shift. Blood samples were collected post shift. Urine samples (entire void) were collected prior to the shift (morning first void) and post shift. VOCs were measured in air, blood, and urine. An audiometric test battery, consisting of immittance measurements, audiograms, distortion product otoacoustic emissions, and the auditory brain response, was conducted after the shift to examine the hearing of participants. Total VOCs in personal air samples were in the ppb range for each group. Tinnitus and temporary hearing loss were reported in audiological histories but were also present in some controls. Noise levels on the flight line were greater than the action level for requiring hearing protection and exceeded exposure limits, but all exposed subjects reported wearing hearing protection. Audiometric tests identified significant differences and trends between flight line and control personnel, indicating the potential for hearing disorders. In spite of very low levels of VOC exposure and wearing hearing protection for noise, there is still the potential for hearing issues in flight line personnel.

Identification of Fatty Acid-Binding Protein 4 as a Potential Biomarker and Therapeutic Target for ANCA-Associated Glomerulonephritis

Introduction: Fatty acid-binding protein 4 (FABP4) is a novel adipokine that is critically involved in many inflammatory and immune diseases. However, the role of FABP4 in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) remains unclear. The current study aimed to investigate the role of FABP4 in patients with ANCA-GN. Methods: Plasma and urine samples from 37 patients with active ANCA-GN and kidney biopsy specimens from another group of 56 patients with ANCA-GN were collected. The plasma and urinary level of FABP4 were measured by enzyme-linked immunosorbent assay and the kidney FABP4 expression was determined by immunohistochemistry and immunofluorescence staining. Associations between FABP4 levels with clinical and pathologic parameters were analyzed. To further elucidate the role of FABP4 in ANCA-GN, a novel FABP4 inhibitor BMS309403 was employed in a recognized rat model of experimental autoimmune vasculitis (EAV). Results: Plasma and urinary levels of FABP4 in active ANCA-GN patients were significantly higher than those in normal controls (52.8 ± 23.6 ng/ml vs. 16.9 ± 8.8 ng/ml, P<0.01; median 126.6 [interquartile range (IQR) 28.4-311.2] ng/g Cr vs. median 0.0 [IQR 0.0-0.0] ng/g Cr, P<0.01, respectively). Immunohistochemical analysis revealed higher glomerular and tubular expression of FABP4 in the kidneys of ANCA-GN patients than those in normal controls (0.015 ± 0.012 vs. 0.004 ± 0.003, P<0.001; 0.053 ± 0.026 vs. 0.011 ± 0.010, P<0.001, respectively). Moreover, for ANCA-GN patients, urinary FABP4 levels were significantly higher in active ANCA than those in remission (184.3 ± 187.0 ng/g Cr vs. 9.4 ± 23.9 ng/g Cr, P<0.01). Correlation analysis showed that urinary levels of FABP4 correlated with serum creatinine (r=0.596, P<0.0001), urinary albumin/Cr (r=0.523, P=0.001), blood neutrophil ratio (r=0.386, P=0.018), PT (r=0.583, P=0.001), APTT (r=0.364, P=0.034), hemoglobin level (r=-0.398, P=0.015), eGFR (r=-0.680, P<0.0001), crescent proportion (r=0.661, P=0.032) and all-cause death of ANCA-GN patients (HR 2.93, 95%CI (1.05-8.19)). Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN. Conclusions: Urinary FABP4 levels might reflect the disease activity and renal involvement of ANCA-associated vasculitis, and FABP4 might act as a promising therapeutic target against ANCA-GN.

Associations between lifestyle factors, physiological conditions, and epigenetic age acceleration in an Asian population

Epigenetic clocks use DNA methylation (DNAm) levels to predict an individual’s biological age. However, relationships between lifestyle/biomarkers and epigenetic age acceleration (EAA) in Asian populations remain unknown. We here explored associations between lifestyle factors, physiological conditions, and epigenetic markers, including HannumEAA, IEAA, PhenoEAA, GrimEAA, DunedinPACE, DNAm-based smoking pack-years (DNAmPACKYRS), and DNAm plasminogen activator inhibitor 1 level (DNAmPAI1). A total of 2474 Taiwan Biobank (TWB) individuals aged between 30 and 70 provided physical health examinations, lifestyle questionnaire surveys, and blood and urine samples. Partial correlation analysis (while adjusting for chronological age, smoking, and drinking status) demonstrated that 29 factors were significantly correlated with at least one epigenetic marker (Pearson’s correlation coefficient |r|> 0.15). Subsequently, by exploring the model with the smallest Akaike information criterion (AIC), we identified the best model for each epigenetic marker. As a DNAm-based marker demonstrated to predict healthspan and lifespan with greater accuracy, GrimEAA was also found to be better explained by lifestyle factors and physiological conditions. Totally 15 factors explained 44.7% variability in GrimEAA, including sex, body mass index (BMI), waist-hip ratio (WHR), smoking, hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-C), creatinine, uric acid, gamma-glutamyl transferase (GGT), hemoglobin, and five cell-type proportions. In summary, smoking, elevated HbA1c, BMI, WHR, GGT, and uric acid were associated with more than one kind of EAA. At the same time, higher HDL-C and hemoglobin were related to epigenetic age deceleration (EAD). These findings offer valuable insights into biological aging.

Rate of Urine Culture Contamination with Different Methods of Urine Specimen Collection.

Midstream urine (MSU) samples are commonly collected at the time of patient evaluation despite known high rates of contamination. The primary objective of this study was to evaluate the rate of mixed flora results in urine specimens obtained by MSU compared to straight catheterization urine (SCU). This was a quality improvement project evaluating urine culture results of women who provided either an MSU or SCU sample for analysis. Adult women seen within urogynecology clinics at a tertiary care center between April and August 2023 who had urine cultures performed for any indication were included. Mixed flora was defined as the presence of ≥ 2 non-uropathogens or 1 uropathogen in low quantity (at least 10 times fewer) compared to the concentration of nonsignificant organisms. Three hundred forty women provided a urine specimen during the study period. SCU collection was performed for 171 (50.3%) women while 169 (49.7%) provided an MSU sample. Overall, 18.8% of urine cultures were reported as mixed flora (33.1% in MSU and 4.7% in SCU, p < 0.001). Mixed flora was more common with MSU specimens (87.5%, p < 0.001) and associated with a higher BMI compared to positive or negative cultures (mixed flora 29.8kg/m2 ± 16.3, positive or negative cultures 27.8kg/m2 ± 7.0, p = 0.04). MSU samples had increased odds of urine contamination compared to SCU collection (7.40 aOR, 95% CI 3.01-18.24). The prevalence of mixed flora was reduced significantly when SCU samples were obtained. Clinicians should consider performing SCU collection when a urine specimen is required for patient evaluation.

Detection of Exchangeable Protons in NMR Metabolomic Analysis Using AI-Designed Water Irradiation Devoid Pulses.

1H NMR spectroscopy has enabled the quantitative profiling of metabolites in various biofluids, emerging as a possible diagnostic tool for metabolic disorders and other diseases. To boost the signal-to-noise ratio and detect proton resonances near the water signal, current 1H NMR experiments require solvent suppression schemes (e.g., presaturation, jump-and-return, WATERGATE, excitation sculpting, etc.). Unfortunately, these techniques affect the quantitative assessment of analytes containing exchangeable protons. To address this issue, we introduce two new one-dimensional (1D) 1H NMR techniques that eliminate the water signal, preserving the intensities of exchangeable protons. Using GENETICS-AI, a software that combines an evolutionary algorithm and artificial intelligence, we tailored new water irradiation devoid (WADE) pulses and optimized the 1D 1H NOESY sequence for metabolomic analysis. When applied to human urine samples, kidney tissue extract, and plasma, the WADE technique allowed for accurate measurement of typical metabolites and direct quantification of urea, which is usually challenging to measure using standard NMR experiments. We anticipate that these new NMR techniques will significantly improve the accuracy and reliability of metabolite quantitative assessment for a wide range of biological fluids.

Sodium Reduction Legislation and Urinary Sodium and Blood Pressure in South Africa.

Reductions in dietary salt are associated with blood pressure reductions; however, national governments that have passed laws to reduce sodium intake have not measured these laws' impact. To determine if South African regulations restricting sodium content in processed foods were associated with reductions in sodium consumption and blood pressure. The HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) study is a population-based cohort study among adults aged 40 years or older randomly selected from individuals living in rural Mpumalanga Province in South Africa. This study incorporated 3 waves of data (2014/2015, 2018/2019, and 2021/2022) from the HAALSI study to examine how 24-hour urine sodium (24HrNa) excretion changed among a population-based cohort following mandatory sodium regulations. Spot urine samples were collected across 3 waves, and data analysis was performed from 2023 to 2024. South African regulations introduced in 2013 that reduced levels for the maximum amount of sodium in milligrams per 100 mg of food product by 25% to 80% across 13 processed food categories by 2019. 24HrNa was estimated using the INTERSALT equation, and generalized estimating equations were used to assess changes in sodium excretion and blood pressure. Among 5059 adults 40 years or older, mean (SD) age was 62.43 years (13.01), and 2713 participants (53.6%) were female. Overall mean (SD) estimated 24HrNa excretion at baseline was 3.08 g (0.78). There was an overall reduction in mean 24HrNa excretion of 0.22 g (95% CI, -0.27 to -0.17; P < .001) between the first 2 waves and a mean reduction of 0.23 g (95% CI, -0.28 to -0.18; P < .001) between the first and third waves. The reductions were larger when analysis was restricted to those with samples in all 3 waves (-0.26 g for both waves 2 and 3 compared to wave 1). Every gram of sodium reduction was associated with a -1.30 mm Hg reduction (95% CI, 0.65-1.96; P = .00) in systolic blood pressure. The proportion of the study population that achieved ideal sodium consumption (<2 g per day) increased from 7% to 17%. In this cohort study, following South African regulations limiting sodium in 13 categories of processed foods, there was a significant reduction in 24HrNa excretion among this rural South African population, which was sustained with reductions in blood pressure consistent with levels of sodium excreted. These results support the potential health effects anticipated by effective implementation of population-based salt reformulation policies.

The Prevalence of Xylazine in Patient Urine Samples That Were Positive for Fentanyl in Western New York.

Xylazine, a veterinary sedative, is increasingly being discovered in the illegal drug supply across the United States and is associated with overdose fatalities. Not approved for human use, xylazine poses life-threatening risks, particularly when used in conjunction with opioids such as fentanyl. This study evaluates the prevalence of xylazine in urine samples that screened positive for fentanyl. The evaluation involved measuring the parent drug xylazine and its metabolites, xylazine glucuronide and hydroxy-xylazine, as well as finding their correlation with fentanyl and norfentanyl concentrations in patient samples. Samples were collected over a one-month period. Urine samples were analyzed for fentanyl, norfentanyl, and 3 xylazine-specific analytes (i.e., xylazine, xylazine glucuronide, and hydroxy-xylazine). Briefly, reverse-phase chromatographic separation was performed on a Bonshell Phenyl-Hexyl column utilizing a binary mobile phase gradient. The eluents were detected through positive electrospray ionization and multiple reaction monitoring analysis on a triple quadrupole mass spectrometer. Out of a total of 230 urine samples, 184 were confirmed positive for fentanyl. Xylazine was detected in 56 out of the 184 fentanyl-positive samples, accounting for 30% of the fentanyl-positive confirmatory test. Xylazine (or its metabolites) was not observed in fentanyl-negative samples. Furthermore, the parent xylazine drug was detected in all 56 samples, whereas the metabolite glucuronide and hydroxy forms were only detected in 28 and 6 samples, respectively. This study estimated a xylazine prevalence of 30% in fentanyl-positive urine samples within our local Western New York population. This study represents the first report within our clinical population.

A Bioassay Analysis of Uranium and Lead in Urine Samples from a High Natural Background Radiation Area in Indonesia

Heavy metal pollution is a major environmental concern due to the high toxicity of heavy metals in humans. High natural background radiation areas (HNBRAs) contain high concentrations of the radioactive element 238U, which decays into 206Pb, in their soil, crops, and water. Concentrations of the heavy metals lead (Pb) and uranium (U) are, thus, correlated with HNBRAs. Mamuju in Indonesia is a recently studied HNBRA where high concentrations of Pb and U in the soil have been reported. The present study analyzes Mamuju residents’ exposure to Pb and U. Two zones in the study area were selected for comprehensive assessment. North Botteng was chosen to represent the HNBRA, and Topoyo was selected as the control zone, with 22 urine samples collected from each zone. The samples were analyzed using a quadrupole inductively coupled plasma mass spectrometer (ICP-MS). The average concentrations of Pb measured in the urine samples were 1.31 mg L−1 and 0.77 mg L−1 in North Botteng and Topoyo, respectively. These values are higher than the urine Pb reference value of 5 µg L−1. The urine Pb concentrations in both studied zones were alarmingly high, which may have serious health effects on the population and should warrant action to reduce Pb exposure in this area. The committed effective dose from the ingestion of 238U in North Botteng was higher than in Topoyo, measuring 36.0 mSv and 8.9 mSv, respectively. The area most affected by the ingestion of 238U was the red bone marrow, followed by the bone surface.

Molecular Profiling of Antibiotic-resistant Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infections in Rivers State University Teaching Hospital

Background: Antibiotic-resistant Pseudomonas aeruginosa poses a significant challenge in urinary tract infections (UTIs), particularly in hospital settings. Aim: The aim of this study was to analyze the molecular profile of antibiotic-resistant P. aeruginosa strains isolated from patients with urinary tract infections at the Rivers State University Teaching Hospital, Port Harcourt. Methods: As part of a cross-sectional study, 199 patients were interviewed, and urine samples were collected from subjects with symptoms of a urinary tract infection. A semiquantitative urine culture method was used to detect significant bacteriuria. Suspected uropathogenic P. aeruginosa isolates were then identified using conventional and molecular techniques for identification and gene detection. The data generated from this study was presented as frequencies and percentages using Microsoft Excel 365. Results: Of the 199 urine samples analyzed, P. aeruginosa was isolated in 17 cases, corresponding to a prevalence rate of 8.5%. Among the antimicrobial classes tested, aminoglycosides showed different resistance rates: amikacin (23.5%) and gentamicin (35.3%). Fluoroquinolones, including ofloxacin and ciprofloxacin, had resistance rates of 52.9%. Cephalosporins showed high resistance, particularly cefuroxime sodium (88.2%) and cefpodoxime (100%). Amoxicillin + clavulanic acid showed a resistance rate of 94.1%, while resistance to cefotaxime was 47.1%. Imipenem remained effective without resistance being observed. Several antimicrobial resistance indices (MAR) indices revealed complex resistance patterns across isolates, with the highest MAR index at 0.92. Genotypic analysis identified CTX-M as the most prevalent resistance gene (77.8%), followed by TEM (44.4%) and SHV (33.3%). Notably, no isolates harbored NDM or VIM genes, indicating the absence of carbapenem resistance genes among the studied isolates. Conclusion: This study highlights the prevalence of antibiotic-resistant P. aeruginosa in UTIs at Rivers State University Teaching Hospital, the study also evaluated the antimicrobial susceptibility of Pseudomonas isolates, and key finding is the high resistance rates of the Pseudomonas isolates to multiple antibiotics, especially within the fluoroquinolone and cephalosporin classes, while maintaining susceptibility to Imipenem.

Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome.

Chronic kidney disease (CKD) seriously affects the well-being and shortens the life expectancy of children and adolescents, but its progression is challenging to predict. Therefore, there is an urgent need for biomarkers that can identify children at risk of faster CKD progression. Alport syndrome (AS) is the most common monogenetic glomerular kidney disease. Urinary Dickkopf-related protein 3 (DKK3) is associated with a decline in estimated glomerular filtration rate (eGFR) in adults and children with advanced CKD. However, its potential for early detection of CKD and its prognostic value in children with AS remain unknown. Urine samples from 49 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to evaluate whether DKK3 could identify children with AS to be at risk for faster CKD progression. DKK3 levels in patients with AS were higher than those of healthy individuals reported in the literature. DKK3 levels were more elevated in patients with later stages of AS. Furthermore, children who were not treated with renin angiotensin system inhibitors (RASi) had higher DKK3 levels than treated children. Children with above-average DKK3 levels were more likely to have increased albuminuria after 2years of follow-up than children with below-average DKK3 levels. Urinary DKK3 is significantly elevated in children at early stages of AS. There was a potential association between higher DKK3 levels, worsening albuminuria, and a decline in kidney function. These findings suggest that DKK3 may be a prognostic marker for predicting the risk of kidney damage in children with AS.

Pure Shift NMR with Solvent Suppression: A Robust and General Method for Determining Quantitative Metabolic Profiles in Biofluids.

Ultrahigh-resolution pure shift NMR has recently been shown as a promising approach for providing quantitative metabolic profiles that can be used to study the metabolic footprint left by cancer cells in their aqueous growth medium. In this approach, a library of reference 1H pure shift spectra with water suppression was implemented to determine metabolite concentrations from the NOESY-presat-PSYCHE-SAPPHIRE spectrum recorded on the extracellular medium. This achievement clearly called for a generalization of a quantification method relying on ultrahigh-resolution data to other biological samples of interest (urine, plasma, tissue extracts, etc.), which requires evaluating the robustness of the analytical workflow. We have first addressed the influence of sample preparation on the quality of metabolite quantification. The quantification performed on a model mixture of metabolites prepared under different conditions shows good linearity, trueness, and precision, which highlights the high reproducibility of the proposed analytical protocol regardless of the physicochemical conditions in the sample. Second, we have successfully implemented this quantification protocol to determine metabolite levels in real urine and plasma samples, thereby paving the way for the use of the library of pure shift reference spectra for accurate and quantitative metabolic profiling of a broad range of aqueous samples.

Evaluation of Immunoassay Performance for the Detection of Opioids in Urine.

Immunoassay drug screens provide rapid analysis of urine for the presence of therapeutics and drugs of abuse. Compared to definitive (confirmatory) methods, immunoassays are prone to false-positive and -negative results. Laboratories generally rely on manufacturers' claims regarding method sensitivity and specificity; few have the resources to independently verify performance. In this study, we review the performance of our opioid immunoassay drug screens in comparison to a definitive method. Results of 859 urine samples tested via opioid immunoassay screens for buprenorphine, fentanyl, methadone metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EDDP), opiates, and oxycodone were compared to definitive results obtained via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data examined here included multiple samples from individual patients. Our quantitative LC-MS/MS method includes 19 opioid compounds (parent drugs plus metabolites). Immunoassay sensitivity and specificity ranged from 96% to 100% and 84% to 99%, respectively. The sensitivity and specificity of these screens were similar to manufacturers' claims with some exceptions. The opiates immunoassay had poor performance when limiting the comparison to its target compound, morphine, but improved when including all compounds listed in the manufacturer's instructions for use (IFU). While demonstrating good sensitivity, the buprenorphine immunoassay demonstrated lower specificity than stated in the IFU. The opioid immunoassay screens in use at our facility compared favorably to a definitive LC-MS/MS method. The urine fentanyl screen had the lowest sensitivity (96%) and had a specificity of 97%. The urine buprenorphine assay was the least specific (84%) and had a sensitivity of 99%.

Prediction of Area Under the Curve from Urinary Vancomycin Concentrations Measured Using a Simple Method.

Therapeutic drug monitoring (TDM) is recommended during vancomycin (VCM) administration to adjust the dosage such that the area under the curve (AUC) remains between 400 and 600µg·h/mL (minimum inhibitory concentration = 1µg/mL). However, measuring the AUC requires frequent blood sampling, which increases the burden of added time and cost for testing on both patients and healthcare personnel. Therefore, we aimed to address these issues by developing a simple and rapid method for measuring urinary VCM levels using solid-phase extraction and fluorescence spectrometry. The developed method had a quantification range of 100-2,000µg/mL, with an accuracy of 100.0%-108.5% for concentrations of 200, 1,000, and 2,000µg/mL. The intra- and inter-day relative standard deviations were below 3.39% and 4.48%, respectively. Furthermore, to predict the AUC from urinary VCM concentrations, we calculated the slope of the urinary concentrations at 7-12h post-VCM administration in six patients. The slope for one patient differed significantly from that for the others, and the AUC was obtained using practical AUC-guided TDM for vancomycin (PAT) ver. 3.0c for the patient whose value deviated from the recommended range. A negative correlation was observed between the slope and AUC, with a correlation coefficient of 0.65, suggesting the potential for predicting AUC from urinary concentration trends. The use of urine samples, which can be easily obtained, for VCM dose adjustment is expected to contribute to providing more appropriate drug therapy to patients and reduce the burden on healthcare professionals.

Study on the Mechanism of the Leaves of Dimocarpus longan Lour. in the Management of Type 2 Diabetes based on Metabolomics.

Diabetes mellitus (DM) is a chronic metabolic disease. The leaves of Dimocarpus longan Lour. (LYY), a well-known traditional Chinese medicine (TCM) with Guangxi national characteristics often used in simple recipes to treat DM has attracted increasing attention. In this study, we investigated the therapeutic effects of LYY in diabetic rats from a metabolomic perspective. The type 2 diabetes (T2DM) rat model was induced by a high-sugar and high-fat diet (HSFD) combined with 40 mg/kg streptozotocin (STZ). After oral administration of LYY (10.7 g/kg) for 28 d, their weight, fasted blood glucose (FBG), blood lipid levels, and inflammatory factors were assessed. The feces, urine, and serum samples of the rats were collected, and proton nuclear magnetic resonance (1H-NMR) technology was used to explore the changes in the sample's metabolism spectrum and analyze the relevant targeted metabolic pathways. Compared with the diabetes group, LYY rats significantly delayed the reduction of body weight and decreased the FBG level (P <0.01); the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C), IL-6, and TNF-α in serum significantly reduced (P < 0.05, 0.01), and the level of high-density lipoprotein-cholesterol (HDL-C) significantly increased (P < 0.01). 2 candidate biomarkers were identified from feces samples, and 4 associated metabolic pathways were discovered. 13 potential biomarkers were screened from urine samples, leading to the identification of 16 related metabolic pathways. Similarly, 5 potential biomarkers were screened from serum samples, and 11 related metabolic pathways were found. LYY can regulate the metabolic disorder caused by T2DM by regulating amino acid metabolism, amino acid synthesis, and tricarboxylic acid cycle, which provides a specific reference for the clinical treatment of T2DM.

Bioavailability, Metabolism, and Excretion of [14C]-Tazemetostat in Patients With B-Cell Lymphomas or Advanced Solid Tumors.

This open-label, multicenter study (NCT03010982) evaluated the absolute bioavailability, characterized the disposition and metabolism, and investigated the metabolic profile of tazemetostat, a US Food and Drug Administration-approved inhibitor of enhancer of zeste homolog 2, following intravenous and oral [14C]-labeled and unlabeled tazemetostat in patients with B-cell lymphomas or advanced solid tumors. Patients received oral tazemetostat 800mg twice daily for 14 days. On Day 15, patients received tazemetostat 800-mg tablets in a fasted state followed by an intravenous microdose of 12µg [14C]-tazemetostat. On Day16, patients received a [14C]-tazemetostat 800-mg solution with a meal, then continued tazemetostat 800mg twice daily. Blood, plasma, urine, and fecal samples were collected for pharmacokinetic analyses, and recovery and excretion of the radioactivity of [14C]-labeled/unlabeled tazemetostat and its metabolites. The median absolute bioavailability was 31.8% (range, 20.2%-49.8%). Notable plasma components were EPZ-6930, unchanged tazemetostat, EPZ006931, and EPZ034163, accounting for 31.8%, 22.4%, 11.0%, and 3.5% of total drug-related exposure, respectively. Recovery of radiolabeled material ranged from 93.2% to 94.7%, with most excreted doses recovered within 48 hours in urine and by 96 hours in feces. Fecal elimination represented the principal route of elimination with a mean of 78.9% of the administered radioactive dose and renal excretion accounted for 15.4%.

Association Between Microalbuminuria and Left Ventricular Hypertrophy in Hypertensive Patients: A Marker of Target Organ Damage

Microalbuminuria, an indicator of endothelial dysfunction and organ damage, is often linked to left ventricular hypertrophy (LVH) in individuals with hypertension. Identifying microalbuminuria early can offer critical insights into assessing cardiovascular risks. This research aimed to explore the relationship between microalbuminuria and LVH in hypertensive patients and to evaluate the clinical relevance of microalbuminuria as an indicator of organ damage. This cross-sectional study involved 150 hypertensive patients, divided into two groups: 75 with LVH (Group 1) and 75 without LVH (Group 2). LVH was diagnosed using echocardiography, specifically the left ventricular mass index (LVMI). Microalbuminuria was measured via the albumin-to-creatinine ratio (ACR) in a single urine sample, with a cutoff of 30–300 µg/mg. Data on blood pressure, hypertension duration, and body mass index (BMI) were collected. Statistical analyses included t-tests and chi-square tests. Microalbuminuria was significantly more common in Group 1 than in Group 2 (60% vs. 20%; p &lt; 0.001). The average ACR was also higher in Group 1 (65.4 ± 20.7 µg/mg vs. 22.5 ± 10.2 µg/mg; p &lt; 0.001). Patients with LVH had a longer history of hypertension, higher BMI, and increased blood pressure compared to those without LVH (p &lt; 0.05). Microalbuminuria is closely associated with LVH in hypertensive patients and can serve as a non-invasive marker for organ damage. Regular screening for microalbuminuria in hypertensive patients can enhance risk assessment and inform targeted treatments.

Study of urine samples received for culture, and sensitivity patterns of the urinary pathogens at a tertiary care hospital in Sri Lanka

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Dietary quality and adherence to dietary recommendations in Chinese patients with chronic kidney disease

ObjectivesThere is a lack of data regarding the quality of the diet and the adherence to dietary guidelines of patients with non-dialysis-dependent CKD (NDD-CKD) in China.Design and methodsSingle-center cross-sectional study of 261 patients with CKD stages 3–5, who responded to 3-day dietary records and undertook 24-h urine samples along with clinical, laboratory, and anthropometric assessments. We compared their food intake with Chinese recommendations for CKD patients, assessed dietary quality through the Chinese Healthy Eating Index (CHEI), and calculated the contribution to energy intake by processed foods according to the NOVA classification.ResultsAverage energy intake was 30 ± 9 Kcal/kg/d, and 65% consumed less energy than recommended. The average protein intake was 1.2 ± 0.5 g/Kg/d, and 81% consumed more than recommended. 71% of patients consumed excess sodium and 80% consumed too little fiber. These proportions worsened across more severe CKD stages (all P trend value &amp;lt;0.05). The diet was considered of moderate quality (CHEI score 59.5 ± 11.0), and patients with CKD stages 4–5 scored progressively worse (P trend = 0.008). Total grains and tubers supplied 50 and 30% of the total energy and protein intake, respectively. Processed and ultra-processed foods contributed to 23.3% of dietary energy and 11.7% of food weight.ConclusionA large proportion of NDD-CKD at our center showed low adherence to diet recommendations. Although consumption of processed foods was low, diet quality worsened with more severe CKD, with low intake of whole grains, dairy, and soybean.