Metal in biological samples from electronic cigarette users and those exposed to their second-hand aerosol: a narrative review.

Introduction: Electronic nicotine delivery systems (ENDS) are gradually becoming more popular, particularly, among today's youth. Despite being marketed as safe by the tobacco industry, the notable absence of regulation in their composition is evident. Both the generated fluids and aerosol exhibit a wide variety of substances that are not yet fully identified. In addition to additives, the aerosol contains metals, the presence of which can be attributed to the excessive heating of metallic filaments used in vaporizing the liquid. Objective: This review aimed to identify and describe studies that have assessed metal levels in biological samples obtained from electronic cigarette users and those exposed to their second-hand aerosol. This involved detailing the types and concentrations of metals identified and the biological samples in which the metals were detected. Methods: Two independent researchers conducted searches in the MEDLINE and EMBASE databases to identify studies that measured the metal levels in human non-invasive biological samples from electronic cigarette users and second-hand exposure. Data were presented as a narrative review. Results: In total, 18 articles were included in this review. Overall active and passive exposure to ENDS was related to higher levels of many metals, including lead and cadmium, in biological samples. ENDS users, in general, have lower metal concentrations in biological samples compared to the users of combustible cigarettes. Conclusion: The exposure to primary and second-hand e-cigarette aerosol is related to higher metal concentrations in the biological samples. The adverse effects of this exposure on long-term users are yet to be determined.

A Retrospective Cohort Study of Disparities in Urine Drug Testing During the Perinatal Period in an Urban, Academic Medical Center.

The purpose of this study was to evaluate disparities in urine drug testing (UDT) during perinatal care at a single academic medical center. This retrospective cohort study included patients who had a live birth and received prenatal care at our institution between 10/1/2015 and 9/30/2020. The primary outcomes were maternal UDT during pregnancy (UDTPN) and UDT only at delivery (UDTDEL). Secondary outcomes included the number of UDTs (UDTNUM) and the association between a positive UDT test result and race/ethnicity. Mixed model logistic regression and negative binomial regression with clustering based on prenatal care locations were used to control for confounders. Of 6,240 live births, 2,265 (36.3%) and 167 (2.7%) received UDTPN and UDTDEL, respectively. Black (OR 2.09, 95% CI 1.54-2.84) and individuals of Other races (OR 1.64, 95% CI 1.03-2.64) had greater odds of UDTPN compared to non-Hispanic White individuals. Black (beta = 1.12, p < 0.001) and Hispanic individuals (beta = 0.78, p < 0.001) also had a positive relationship with UDTNUM. Compared to individuals with non-Medicaid insurance, those insured by Medicaid had greater odds of UDTPN (OR 1.66, 95% CI 1.11-2.49) and had a positive relationship with UDTNUM (beta = 0.89, p < 0.001). No significant associations were found for UDTDEL and race/ethnicity. Despite receiving more UDT, Black individuals were not more likely to have a positive test result compared to non-Hispanic White individuals (OR 0.95, 95% CI 0.72-1.25). Our findings demonstrate persistent disparities in substance use testing during the perinatal period.

High-Risk Patients Undergoing Holmium Laser Enucleation of the Prostate Have Fewer Infections with a Longer Course of Preoperative Antibiotics.

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t-test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07-0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Urinary dipeptidase 1 and trefoil factor 1 are promising biomarkers for early diagnosis of colorectal cancer.

BACKGROUND: Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). METHODS: Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0-III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. RESULTS: Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825-0.956 for stage 0-III CRC and 0.792-0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. CONCLUSIONS: This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity.

Genotypic and Phenotypic Spectrum of maple syrup urine disease in Zhejiang of China.

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB, and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated. AIM: Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD. DESIGN: Retrospective population-based cohort. METHODS: We analyzed 20 MSUD patients from the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to May 2023. Patients' blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability, and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect. RESULTS: We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing. CONCLUSIONS: This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]). Setting & Participants: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies. Exposures: Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1. Outcome: Incident CKD or end-stage kidney disease. Analytical Approach: Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts. Results: 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31). Limitations: Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts. Conclusions: In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.

Robot-assisted staged bilateral reno-lymphatic disconnection for massive idiopathic chyluria: A case report.

Chyluria, an abnormal lymphatic disorder, results in excessive abdominal lymph drainage into the urinary system, causing protein loss, nutritional deficiencies, and immune issues. Mainly linked to parasitic infections in developed countries, non-parasitic causes like trauma or tumors are rare. Typically appearing in adults with bilateral involvement, management options include conservative or surgical approaches. We present the case of a 13-year-old with congenital chyluria, treated with robot-assisted staged reno-lymphatic disconnection after failed interventional radiology. Bilateral scleroangiography followed, leading to persistently milky urine for a month. Finally, urine clarity improved, correlating with better urinalysis, emphasizing the need for a comprehensive, multi-disciplinary approach.

Assessing Acute and Chronic Risks of Human Exposure to Arsenic: A Cross-Sectional Study in Ethiopia Employing Body Biomarkers.

Background: Arsenic, a widely recognized and highly toxic carcinogen, is regarded as one of the most hazardous metalloids globally. However, the precise assessment of acute and chronic human exposure to arsenic and its contributing factors remains unclear in Ethiopia. Objective: The primary goal of this study was to assess the levels of acute and chronic arsenic exposure, as well as the contributing factors, using urine and nail biomarkers. Methods: A community-based analytical cross-sectional study design was employed for this study. Agilent 7900 series inductively coupled plasma mass spectrometry was used to measure the concentrations of arsenic in urine and nail samples. We performed a multiple linear regression analysis to assess the relationships between multiple predictors and outcome variables. Results: The concentration of arsenic in the urine samples ranged from undetectable (<0.01) to 126.13, with a mean and median concentration of 16.02 and 13.5 µg/L, respectively. However, the mean and median concentration of arsenic in the nails was 1.01, ranging from undetectable (<0.01 µg/g) to 2.54 µg/g. Furthermore, Pearson's correlation coefficient analysis showed a significant positive correlation between arsenic concentrations in urine and nail samples (r = 0.432, P < .001). Also, a positive correlation was observed between urinary (r = 0.21, P = .007) and nail (r = 0.14, P = .044) arsenic concentrations and the arsenic concentration in groundwater. Groundwater sources and smoking cigarettes were significantly associated with acute arsenic exposure. In contrast, groundwater sources, cigarette smoking, and the frequency of showers were significantly associated with chronic arsenic exposure. Conclusions: The study's findings unveiled the widespread occurrence of both acute and chronic arsenic exposure in the study area. Consequently, it is crucial to prioritize the residents in the study area and take further measures to prevent both acute and chronic arsenic exposure.

Minimizing the time to evaluate pheromone-mediated reduction of aggressive behavior in Mozambique tilapia (Oreochromis mossambicus).

Some cichlid fishes release urine-containing chemical cues that lower aggression in their opponents. Bioassays to identify the aggression-modulating pheromone include assessing the effect of urine fractions on the behavior towards a mirror image or in interactions with another male. However, many of these methods can be time-consuming and require many fish. The objective of the present study was to assess the behavior of male Mozambique tilapia (Oreochromis mossambicus) towards male urine using two methods with the intent of simplifying the bioassays: aggression towards a mirror image (mirror assay) and real opponents in which the urogenital papilla was tied using surgical silk to prevent urination. The results confirm the aggression-reducing effect of dominant male urine in both experimental approaches. Ten minutes of biting or 15 min of tail-beating behaviors in the mirror assay, or 5 min of opercular expansion or 15 min of lateral display in interactions with real opponents were necessary to detect a statistically significant reduction in aggressive behavior towards dominant male urine. We also found that males with subordinate status had lower latency to initiate aggressive behaviors towards the mirror than dominants in the same condition, even though fish had been isolated for 1 week. However, no such differences in latency were found in the real opponent assay. We conclude that 5 min of opercular expansion behavior in real opponent fights or 10 min of biting behavior in the mirror assay are the shortest times necessary to test aggressive behavior in urine fractions in bioassay-guided identification of pheromones.

A case of disseminated strongyloidiasis diagnosed by worms in the urinary sediment.

Strongyloidiasis is a chronic infection caused by the intestinal nematode parasite Strongyloides stercoralis and is characterized by a diverse spectrum of nonspecific clinical manifestations. This report describe a case of disseminated strongyloidiasis with urination difficulty, generalized weakness, and chronic alcoholism diagnosed through the presence of worms in the urinary sediment. A 53-year-old man was hospitalized for severe abdominal distension and urinary difficulties that started 7-10 days prior. The patient also presented with generalized weakness that had persisted for 3 years, passed loose stools without diarrhea, and complained of dyspnea. In the emergency room, approximately 7 L of urine was collected, in which several free-living female adult and rhabditiform larvae of S. stercoralis, identified through their morphological characteristics and size measurements, were detected via microscopic examination. Rhabditiform larvae of S. stercoralis were also found in the patient's stool. During hospitalization, the patient received treatment for strongyloidiasis, chronic alcoholism, peripheral neurosis, neurogenic bladder, and megaloblastic anemia, and was subsequently discharged with improved generalized conditions. Overall, this report presents a rare case of disseminated strongyloidiasis in which worms were detected in the urinary sediment of a patient with urination difficulties and generalized weakness combined with chronic alcoholism, neurogenic bladder, and megaloblastic anemia.

Activation of TGR5 Increases Urine Concentration by Inducing AQP2 and AQP3 Expression in Renal Medullary Collecting Ducts.

Introduction: G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular signaling pathways after interacting with bile acids. TGR5 plays an important role in multiple physiological processes and is considered to be a potential target for the treatment of various metabolic diseases, including type 2 diabetes. Evidence has emerged that genetic deletion of TGR5 results in an increase in basal urine output, suggesting that it may play a critical role in renal water and salt reabsorption. The present study aims to elucidate the effect and mechanism of TGR5 activation on urine concentration. Methods: Mice were treated with TGR5 agonists (LCA and INT-777) for 3 days. The 24-h urine of mice was collected and analyzed for urine biochemical parameters. The mRNA expressions were detected by real-time PCR, and the protein expressions were detected by western blot. Immunohistochemistry and immunofluorescence were performed to examine the cellular location of proteins. The cultured primary medullary collecting duct cells were pretreated with H89 (a PKA inhibitor) for 1 h, followed by 12-h treatment of LCA and INT-777. Luciferase reporter assays were used to detect the effect of CREB on the gene transcription of AQPs. Gel electrophoretic mobility shift assays were used to analyze DNA-protein interactions. Results: Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation. In cultured primary medullary collecting duct cells, LCA and INT-777 dose-dependently upregulated AQP2 and AQP3 expression in a cAMP/PKA-dependent manner. Mechanistically, both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays. Conclusion: Collectively, our findings demonstrate that activation of TGR5 can promote urine concentration by upregulation of AQP2 and AQP3 expression in renal collecting ducts. TGR5 may represent an attractive target for the treatment of patients with urine concentration defect.

Dosimetry of human exposure to furan and 2-methylfuran by monitoring urinary biomarkers.

Furan and 2-methylfuran (2-MF) can form during food processing and accumulate in foods at various concentrations depending on processing technology and beverage/meal preparation methods applied prior to consumption. Here, we report a controlled dosimetry study with 20 volunteers (10 male, 10 female) to monitor dietary furan/2-MF exposure. The volunteers followed an eleven-day furan/2-MF-restricted diet in which they consumed freshly prepared coffee brew containing known amounts of furan and 2-MF on two separate occasions (250 mL and 500 mL on days 4 and 8, respectively). Urine was collected over the whole study period and analyzed for key metabolites derived from the primary oxidative furan metabolite cis-2-butene-1,4-dial (BDA) (i.e., Lys-BDA, AcLys-BDA and cyclic GSH-BDA) and the primary 2-MF metabolite acetylacrolein (AcA, 4-oxo-pent-2-enal) (i.e., Lys-AcA and AcLys-AcA). A previously established stable isotope dilution analysis (SIDA) method was utilized. Excretion kinetics revealed two peaks (at 0-2 and 24-36 h) for AcLys-BDA, Lys-BDA, AcLysAcA and LysAcA, whereas GSH-BDA showed a single peak. Notably, women on average excreted the metabolite GSH-BDA slightly faster than men, indicating gender differences. Overall, the study provided further insights into the spectrum of possible biomarkers of furan and 2-methyfuran metabolites occurring in the urine of volunteers after coffee consumption.

Urine Proteomic Signatures of Mild Hypothermia Treatment in Cerebral Ischemia-Reperfusion Injury in Rats.

Mild hypothermia (MH) is an effective measure to alleviate cerebral ischemia-reperfusion (I/R) injury. However, the underlying biological mechanisms remain unclear. This study set out to investigate dynamic changes in urinary proteome due to MH in rats with cerebral I/R injury and explore the neuroprotective mechanisms of MH. A Pulsinelli's four-vessel occlusion (4-VO) rat model was used to mimic global cerebral I/R injury. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to profile the urinary proteome of rats with/without MH (32 °C) treatment after I/R injury. Representative differentially expressed proteins (DEPs) associated with MH were validated by western blotting in hippocampus. A total of 597 urinary proteins were identified, among which 119 demonstrated significant changes associated with MH. Gene Ontology (GO) annotation of the DEPs revealed that MH significantly enriched in endopeptidase activity, inflammatory response, aging, response to oxidative stress and reactive oxygen species, blood coagulation, and cell adhesion. Notably, changes in 12 DEPs were significantly reversed by MH treatment. Among them, 8 differential urinary proteins were previously reported to be closely associated with brain disease, including NP, FZD1, B2M, EPCR, ATRN, MB, CA1and VPS4A. Two representative proteins (FZD1, B2M) were further validated by western blotting in the hippocampus and the results were shown to be consistent with urinary proteomic analysis. Overall, this study strengthens the idea that urinary proteome can sensitively reflect pathophysiological changes in the brain, and appears to be the first study to explore the neuroprotective effects of MH by urinary proteomic analysis. FZD1 and B2M may be involved in the most fundamental molecular biological mechanisms of MH neuroprotection.

Legionella pneumonia: A Case of Fever Prolonged for 10 Days.

Legionnaires' disease is a potentially severe type of pneumonia most often caused by the organism Legionella pneumophila. Exposure to this bacterial pathogen typically happens in the community but may also occur in the hospital setting. This report describes the case of a patient who presented due to 10 days of fever, shortness of breath, and diarrhea, with initial imaging demonstrating multifocal pneumonia. The patient was appropriately started on empiric antibiotics for community-acquired pneumonia and admitted to the medicine floor. The patient showed no meaningful improvement in his initial hospital course on empiric antibiotics with continued oxygen requirements. Meanwhile, urine Legionella antigen testing returned positive on hospital day four, and after tailoring antibiotics accordingly, the patient's clinical status improved significantly. This case report highlights the efficacy of broad testing in the initial admission and the need for constant re-evaluation in the context of a patient not improving with appropriate therapy.

Environmental and occupational exposure to bisphenol compounds in Finland.

The aim of the study was to assess non-occupational and occupational exposure to bisphenol compounds in Finland. The participants were 151 non-occupationally exposed volunteers and 15 potentially exposed employees of a sewage-pipe relining company and a floor-coating company. The following chemicals were measured in the urine samples: bisphenol A (BPA), bisphenol F (BPF), bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and the metabolites of the latter two [bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H2O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE·2H2O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE·HCl·H2O), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl), and bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE·2HCl) and bisphenol F bis(2,3-dihydroxypropyl) ether (BFDGE·2H2O), and bisphenol F bis(3-chloro-2-hydroxypropyl) ether (BFDGE·2HCl)]. BADGE and BFDGE were also measured in breathing zone air samples and hand-wipe samples of the sewage-pipe relining and floor-coating workers. Non-occupational exposure to BPA has decreased in Finland. The BPF level of the non-occupationally exposed was higher than the respective levels reported in the recent literature. BPA and BPF concentrations in the workers' urine samples were in the same range as those in the corresponding concentrations of the non-occupationally exposed population. Higher concentrations of BADGE and BFDGE metabolites were found in some of the workers' urine samples. Elevated urine concentrations were also observed in the samples collected the next morning. Some of the urinary BADGE and BFDGE metabolite results correlated with the hand-wipe results. The results show that occupational exposure to BADGE and BFDGE may occur in sewage-pipe relining and floor-coating work. They also indicate that dermal contamination plays a role in total exposure. Although the measured urinary levels indicate that the absorption of these bisphenol compounds are unlikely to pose a systemic health risk, the risk of dermal sensitization remains.

Urinary D-amino acid profiles in cats with chronic kidney disease.

Chronic kidney disease (CKD) is highly prevalent in domestic cats. This study aimed to compare urinary D-amino acid levels between control and CKD-afflicted cats as a novel noninvasive method for assessing CKD.Cats were divided into control and CKD stage II groups in accordance with the International Renal Interest Society guidelines. The urinary DL-amino acid levels of the cats were analyzed using chiral tandem liquid chromatography-tandem mass spectrometry, and their medical records were investigated. The CKD group had considerably lower urinary D-amino acid concentrations and enantiomeric ratios than the control group. The total urinary D-amino acid contents significantly correlated with blood parameters (creatinine and urea nitrogen). These findings may contribute towards the detection of CKD stage II in domestic cats.

Spot urine sodium-to-creatinine ratio surpasses sodium in identifying poor diuretic response in acute heart failure.

AIMS: We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment. METHODS: In this single-centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post-administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline-recommended markers, including spot urine sodium (UNa+) and its cut-off, and introduced the UNa+/UCr (urine creatinine concentration) ratio adjusting UNa+ for urine dilution. RESULTS: Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493-14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output <600 ml during the first 6 h). The mean 6 h cumulative diuresis in patients with poor and good diuretic response was 406 ± 142 and 2114 ± 1164 ml, respectively, P < 0.005. After an initial evaluation of several potential biomarkers, only UNa+, UCr and UNa+/UCr were selected as candidates with the highest predictive value. The cut-off for UNa+ adjusted for urine dilution: UNa+/UCr ratio <0.167 mmol/mg × 10-1 was determined by ROC analysis with the highest area under the curve (95% confidence interval): 0.956 (0.915-0.997), P < 0.001. When compared with the guideline-recommended cut-off (UNa+ <50 mmol/L as a reference, specificity-0.97; sensitivity-0.83), the odds ratio (OR) for UNa+/UCreat to identify a poor diuretic response was 2.5 times greater, regardless of kidney function (OR for estimated glomerular filtration rate in the logistic regression model was 0.978 [0.945-1.013, P = 0.222]). CONCLUSIONS: The UNa+/UCr ratio in a spot urine sample 2 h after intravenous diuretic administration is a simple, highly predictive marker for the identification of AHF patients with poor diuretic response, surpassing guidelines-recommended markers like UNa+.

Quantification of 11 metabolites in rat urine after exposure to organophosphates.

BACKGROUND: The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC-MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs). RESULTS: The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate. CONCLUSIONS: The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1-3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication.

Kidney Cancer and Potential Use of Urinary Extracellular Vesicles.

Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50-200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs' cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs' cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention.