Void Urine Research Articles

Significant increase in prostaglandin E-major urinary metabolite with physical exercise suggesting muscle inflammation

Introduction: Prostaglandin E-major urinary metabolite (PGE-MUM) may be a good biomarker of inflammation and useful in monitoring diseases, without the necessity of invasive sampling. To see whether inflammation in muscles occurs during physical exercise, the influence of physical exercise on urinary PGE-MUM levels was analyzed in high school boys belonging to a soccer club. Materials and methods: Void urine samples were obtained before and after physical exercises 1 (mild exercise) and 2 (repeated mild exercise). To avoid the influence of a change in urinary volume, PGE-MUM values (ng/mL) were corrected by the concentration of urinary creatinine (mg/dL) and expressed as PGE-MUM·Cr (µg/g creatinine). Urinary total protein·Cr (µg/g creatinine) and L-type fatty acid-binding protein·Cr (µg/g creatinine) (L-FABP·Cr) were compared with PGE-MUM·Cr. Results: The PGE-MUM·Cr level increased significantly immediately after playing soccer (regular ‘mild’ exercise) in exercise study 1 or running (repeated mild exercise) in exercise study 2, but declined the next morning. PGE-MUM (ng/mL) levels in both exercises strongly correlated (Spearman correlation coefficient, ρ = 0.728; 0.480, respectively) with urinary creatinine (mg/dL) thought to be derived from muscle exercise. Conclusion: The early increase in the PGE-MUM·Cr level just after physical exercise may reflect muscle damage and inflammation caused by the exercise.

Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis.

To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach. First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects (n = 21) and processed for analysis using a standardized liquid chromatography-tandem mass spectrometry approach. Biomarkers with significantly altered levels were correlated with clinical measures of myositis disease activity and damage. A subset of candidate biomarkers was validated using commercially available ELISA kits. In total, 2348 proteins were detected in the samples, with 275 proteins quantified across all samples. Among the differentially altered proteins, cathepsin D and galectin-3 binding protein were significantly increased in the urine of JDM patients (adjusted P < 0.05), supporting previous findings in myositis patients. These two candidate biomarkers were confirmed with ELISAs. Cathepsin D positively correlated with Myositis Damage Index (r = 0.57, P < 0.05) and negatively correlated with the Childhood Myositis Assessment Scale (r = -0.54, P < 0.05). We also identified novel JDM candidate biomarkers involved with key features of myositis, including extracellular matrix remodelling proteins. This study confirmed the presence of several proteins in the urine of JDM patients that were previously found to be elevated in the blood of myositis patients and identified novel candidate biomarkers that require validation. These results support the use of urine as a source for biomarker development in JDM.

PS-C30-1: URINARY ANGIOTENSINOGEN-MELATONIN RATIO IN GESTATIONAL DIABETES AND PREECLAMPSIA

Objective: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. Design and Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.MethodsIn 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.ResultsAmong the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).ConclusionsOur study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

Trial in Progress: 2019-1001 A Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma (LAPC or BRPC)

<h3>Purpose/Objective(s)</h3> Patients with pancreatic ductal adenocarcinoma (PDAC), who are not eligible for surgery after induction chemotherapy often receive radiation. Although radiation therapy (RT) improves local disease control, the placement of the pancreas proves to be difficult when safely delivering therapeutic doses. NBTXR3 is a novel, potentially first-in-class radio enhancer, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by RT. Pre-clinical testing suggests up to a 9-fold enhancement of the RT dose delivered within tumor cells. In this phase 1 trial-in-progress, the primary objective is to determine the recommended phase II dose (RP2D) of NBTXR3 for LAPC and BRPC patients undergoing RT. The secondary objectives are to evaluate the safety, feasibility, and anti-tumor response of NBTXR3 intratumoral injection on PDAC patients as well as time-to-event outcomes of subjects. <h3>Materials/Methods</h3> For the dose-finding part 1 of the study, patients with LAPC and no metastatic disease after at least 2-6 months of chemotherapy will be eligible. For part 2, the expansion at RP2D, patients with BRPC or LAPC and no metastatic disease after chemotherapy will be eligible. The statistical design of the trial uses a Bayesian optimal interval (BOIN) design. A maximum of 24 patients will be enrolled. For baseline and follow-up, imaging and blood biomarkers will be collected. Patients enrolled will receive NBTXR3, once, through intratumoral injection via endoscopic ultrasound (Day 1). Pre-treatment biopsy will be collected. Post NBTXR3 injection, blood samples will be collected at 4 time points (0,5,30, and 120 minutes). Two urine voids will be collected post injection for hafnium quantification as well. At least three days later, patients will undergo imaging for RT dosimetry and planning where NBTXR3 can be visualized. Patients will then receive 45 Gy in 15 fractions with IMRT, with regional nodal basins receiving 37.5 Gy. Follow-up period will begin 4 weeks after end of treatment and continue every 3 months for a year. Patients will be evaluated for surgery 4-12 weeks post RT. At 11-13 weeks after end of RT, if the patient is not eligible for surgery, an endoscopic ultrasound procedure will be performed. In both events, a post-treatment biopsy will be obtained. The imaging collected of pancreatic target lesion will be used to determine tumor response as per RECIST v1.1 criteria. <h3>Results</h3> Trial is open and accruing, with 8 patients enrolled so far. <h3>Conclusion</h3> We expect to determine the RP2D, safety, and preliminary efficacy of NBTXR3 in pancreatic cancer with this study with blood, tissue, and imaging correlates in 2022.

PREVALENCE OF PHARYNGEAL AND RECTAL CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE INFECTIONS AMONG MSM IN SOFIA, BULGARIA

Abstract: Sexually transmitted infections (STIs) caused by Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health problem. Although they mainly affect the urogenital tract, N. gonorrhoeae and C. trachomatis can also be found in the pharynx and rectum. As data on extragenital chlamydia and gonorrhea in Bulgaria are still scarce, this study aimed to (1) determine the prevalence of pharyngeal and rectal infections with C. trachomatis and N. gonorrhoeae among men who have sex with men (MSMs) from Sofia and (2) to identify risk factors related to these infections to support screening recommendations based on scientific evidence. One hundred and fifteen MSM aged 16-50 were tested by systematic sampling during a visit to a sexual health center for voluntary and confidential HIV testing in Sofia. A questionnaire was used to collect demographics and risk factors, and clinical material from three anatomical sites: pharynx, rectum, and urogenital tract (first void urine or urethral swab) was examined to detect C. trachomatis and N. gonorrhoeae infections. The prevalence of C. trachomatis was 8.7% in the rectal samples tested, and the prevalence of N. gonorrhoeae was 0.9% and 5.2% in the pharyngeal and rectal samples, respectively. Local symptoms were reported in only 16.6% of rectal gonococcal infections and in 20% of C. trachomatis rectal infections. Patients reporting multiple partners had a significantly higher risk of being positive (OR = 3.8, 95% CI 1.03-14). The risk of HIV-positive MSM and those having unsafe sex was also higher (OR = 1.9 95% CI 0.19-20 and OR = 4.6 95% CI 0.98-21, respectively), but the findings were not statistically significant. Overall, more than 80% of extragenital infections would remain undetected and therefore transmissible if only symptomatic cases were investigated. These results suggest that in Bulgaria HIV-positive MSM and those having multiple sexual partners and unprotected sex would benefit from screening for extragenital STIs. Larger sample surveys could provide a better characterization of risk factors to guide screening choices.

Prevent postoperative urinary retention in day surgery adult patients: evidence-based quality improvement project.

Postoperative urinary retention (POUR) is a complication that often leads to adverse outcomes and prolonged hospital stay if treatment is delayed. The aim of this project was to improve the competence of nurses in the provision of preoperative POUR education and ensure all patients received preoperative POUR education, and hence reduce the incidence of POUR. The evidence-based quality improvement project utilized JBI's Practical Application of Clinical Evidence System and Getting Research into Practice module, adopting two POUR best practice recommendations and two audit criteria. The first criterion was for nurses to conduct preoperative education on POUR and the second criterion was to initiate early ambulation of postoperative patients. The project was implemented in three phases from June 2019 to August 2020 in short-stayer and day surgery wards. Criteria 1 and 2 revealed low compliance of 0 and 30%, respectively, during preimplementation audit. There were significant improvements in the first and second cycles of postimplementation audit for both criteria 1 and 2. Our results indicated that most of the patients who were ambulated early were able to void urine. However, there were a few incidents of urinary retention reported despite early ambulation. Following the audit of the third cycle of postimplementation, the compliance for both criteria were found to be satisfactory (criteria 1: 87%, criteria 2: 82%). The implementation of the evidence-based quality improvement project reduced the incidence of POUR. A standardized management would enable nurses to provide consistency in care and effective management and hence prevent the occurrence of POUR.

Urinary biomonitoring of glyphosate exposure among male farmers and non-farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study

BACKGROUND AND AIM: Glyphosate is the most widely applied herbicide worldwide. Despite potential health effects of glyphosate, biomonitoring data of glyphosate exposure in agriculture and other settings are limited. We measured urinary glyphosate concentrations and assessed their determinants among male farmers and non-farmers from Iowa and North Carolina in the BEEA study. METHODS: Based on questionnaire-assessed pesticide exposure histories, we selected four groups of BEEA participants: recently exposed farmers with occupational glyphosate use in the last 7 days (n=98), farmers with high cumulative lifetime days of glyphosate use (&amp;#x3e;80th percentile) but no use in the last 7 days (n=70), farmers with minimal lifetime glyphosate use (n=100), and non-farmers with no occupational pesticide exposure (n=100). We quantified glyphosate in first-morning void urine samples using ion chromatography isotope-dilution tandem mass spectrometry. We estimated geometric mean urinary glyphosate concentrations across groups and evaluated associations with potential determinants using linear regression. RESULTS: Glyphosate was detected in urine of most recently (91%), high-lifetime (93%), and low-lifetime (88%) exposed farmers, as well as non-farmers (81%); geometric mean concentrations were 0.86, 0.58, 0.44, and 0.37 µg/L, respectively. Compared to non-farmers, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P&amp;#x3c;0.0001), particularly those who used glyphosate within 1 day of urine collection [age- and creatinine-adjusted geometric mean ratio (GMR)=6.4, 95% confidence interval (CI)=4.3-9.3] and those not wearing gloves during glyphosate application (GMR=2.6, 95% CI=2.0-3.4). CONCLUSIONS: Preliminary results suggest that a high proportion of both farming and non-farming populations may be exposed to glyphosate. Substantial exposure contrast between those with and without recent occupational glyphosate use was detectable in urine. Given the short elimination half-life of glyphosate, the exposure differences between groups may be even greater than those reflected by measured urine concentrations. Continued biomonitoring of glyphosate in various settings is warranted. KEYWORDS: Glyphosate, exposure assessment, pesticide biomonitoring

The dark side of current analytic methods for Bence Jones Proteinuria.

Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of pre-analytical, analytical, and post-analytical phases. The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis performed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for increased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP. The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.

Aberrant gene expression of superoxide dismutases in Chlamydia trachomatis-infected recurrent spontaneous aborters

Study aimed to characterize the expression of antioxidant genes SOD1 and SOD2 in Chlamydia trachomatis-induced recurrent spontaneous aborters and further determine their role by in silico analysis. First void urine was collected from 130 non-pregnant women with history of recurrent spontaneous abortion (RSA) (Group I) and 130 non-pregnant women (Group II; control) attending Obstetrics and Gynecology Department, SJH, New Delhi, India. C. trachomatis detection was performed by conventional PCR in urine. Gene expression of SOD1 and SOD2 was performed by quantitative real-time PCR. Further, its interacting partners were studied by in silico analysis. 22 patients were positive for C. trachomatis in Group I. Significant upregulation was observed for SOD2 gene in C. trachomatis-infected RSA patients while SOD1 was found to be downregulated. Increased concentration of oxidative stress biomarkers 8-hydroxyguanosine and 8-isoprostane was found in C. trachomatis-infected RSA patients. Protein–protein interaction (PPI) of SOD proteins and its interacting partners viz.; CCS, GPX1, GPX2, GPX3, GPX4, GPX5, GPX7, GPX8, CAT, PRDX1, TXN, SIRT3, FOXO3, and AKT1 were found to be involved in MAPK, p53 and foxo signaling pathways. Molecular pathways involved in association with SODs indicate reactive oxygen species (ROS) detoxification, apoptotic pathways and cell cycle regulation. Overall data revealed alleviated levels of SOD2 gene and decreased expression of SOD1 gene in response to C. trachomatis-infection leading to production of oxidative stress and RSA.

Exposure to organophosphorus compounds of Japanese children and the indoor air quality in their residences

Several organophosphorus compounds such as organophosphate pesticides (OPPs) and trialkylphosphates (TAPs) are suspected to inhibit cholinesterase activities, to affect endocrine systems or to possibly be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially in children, we measured the household exposure to OPPs and TAPs by Japanese children via all exposure pathways and the contribution of indoor air quality. First-morning void urine was collected from subjects aged 6 to 15 years (n = 132), and airborne organophosphorus compounds were sampled in the subject's bedroom for 24 h. Airborne levels of nine OPPs and three TAPs and their urinary metabolites were determined.No significant correlations were detected for any compounds between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The estimated daily intakes were as follows (median, μg/kg b.w./d): chlorpyrifos, 0.042; diazinon, 0.067; tri-n-butylphosphate, 0.094. The 95th percentiles of the intakes for fenthion, fenitrothion and the above three compounds did not exceed their reference limit values, although one subject had a daily intake of tri-n-butylphosphate that was about twice its reference limit value. The concentration levels of the urinary metabolite of tri-n-butylphosphate in our subjects tended to be higher than those for children in many other countries. The fractions of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways was only 2.3 % (median) for tri-n-butylphosphate.Inhalation did not seem to contribute very much as an absorption pathway of the organophosphorus compounds in these Japanese children while they were at home. The exposure amounts of OPPs were not suggested to be high enough to adversely affect the health of these children at present on the basis of their daily intakes compared to their reference limit values.

Evaluation of Alcohol Markers in Urine and Oral Fluid after Regular and Hard Kombucha Consumption.

Although kombucha is a popular fermented beverage, the presence of alcohol markers has not been well studied despite being potential indicators of unintentional impairment. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were measured in oral fluid and urine collected after consumption of regular or hard kombucha. Participants drank within 20 min and provided all urine voids for 12 h, the first urine voids on days 2 and 3 and oral fluid specimens at fixed time points for 48 h. Screening employed liquid chromatography-tandem mass spectrometry (LC-MS-MS; EtS, 25 ng/mL cutoff [oral]; 100 ng/mL cutoff [urine]; EtG, 500 ng/mL cutoff [urine] and immunoassay (IA; EtG, 500 ng/mL cutoff [urine]). After consuming regular kombucha (n = 12 participants), EtS was not detected in oral fluid but both markers were detected by LC-MS-MS in urine specimens within the first five voids from 83% of participants with median (range) concentrations of 240 (100-3,700) ng/mL for EtS and 830 (530-2,200) ng/mL for EtG. Neither marker was positive by IA nor LC-MS-MS after day 1. After consuming hard kombucha (n = 7 participants), 2 (2.8%) of the 70 collected oral fluid specimens tested positive for EtS 3 h after consumption; however, 21 (30%) had EtS levels above the limit of detection (LOD, 10 ng/mL) after 0.5-8 h. Both markers were detected in urine specimens from all participants with median (range) concentrations of 3,381 (559-70,250) ng/mL for EtS and 763 (104-12,864) ng/mL For EtG. Urine specimens were negative for EtG and EtS by the end of the 48-hour study.

Long-term stability of several endocrine disruptors in the first morning urine samples and their associations with lifestyle characteristics

Parabens, triclosan (TCS), bisphenols, benzophenones, and phthalates are typical endocrine disruptors (EDs) with short half-lives in the human body. The concentration levels of those EDs in a spot urine sample are frequently used in exposure assessment studies, and the reproducibility of urinary levels of these nonpersistent EDs should be considered. In the present study, we consecutively collected 45-day first morning void (FMV) urine samples, as well as daily questionnaires, in six recruited participants and measured the urinary concentrations of six parabens, TCS, nine bisphenols, five benzophenones, and ten phthalate metabolites by using high-performance liquid chromatography-tandem mass spectrometry. MeP, EtP, PrP, TCS, BPA, BPS, BPF, and most phthalate metabolites were frequently detected (over 62 % of samples). The intraclass correlation coefficients (ICCs) for ED concentrations in FMV urine samples ranged from fair to excellent for MeP (0.683), EtP (0.702), BPA (0.505), BPS (0.908), BPF (0.887), BP-3 (0.712), mMP (0.661), mEP (0.523), mBP (0.500), miBP (0.724), mBzP (0.961) and all metabolites of DEHP (0.867–0.957), whereas they were low for PrP (0.321) and TCS (0.306). After creatinine adjustment, the values of ICCs for most target EDs were increased with mild to significant improvement. The stability of ED concentrations was affected by daily diet (MeP, TCS, BPA, mMP, miBP, mBP and mBzP), food containers (PrP and mECPP), use of personal care products (HMWP metabolites), pharmaceuticals (EtP) and recorded activities (BPS, mEHP, mBzP, mEHHP and mEOHP), as confirmed by a general linear mixed model. Furthermore, extending the FMV sampling period improved the probability of acceptable reproducibility (ICCs > 0.40) of MeP, EtP, BP-3 and mEP concentrations. For BPS, BPF and HMWP metabolite concentrations showed high probabilities (>80 %) of acceptable reproducibility in the last three days, and the increasing sample size slowly improved the ability to discriminate the subjects. The results were exactly the opposite for BPA concentrations.

KORUNMASIZ CİNSEL İLİŞKİ SONUCU ÜRETRİT TANISI ALAN SÜNNETLİ HASTALARDA ASEMPTOMATİK HIV, HEPATİT B, HEPATİT C VE SİFİLİZ GÖRÜLME SIKLIĞI

Aim: In this study, it was aimed to determine the frequency of asymptomatic Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C, and syphilis in circumcised patients diagnosed with urethritis transmitted by sexual intercourse because of unprotected sexual contact. Material and Methods: We retrospectively investigated the serological results of HIV, Hepatitis B, Hepatitis C, and Syphilis diseases in 364 male patients diagnosed with urethritis, all of them were circumcised during childhood. The study included patients who applied to the urology outpatient clinic of secondary state hospital between January 2017 and December 2019 with symptoms or signs of urethritis. In the examination, only urethral discharge could be seen without symptoms. After the patients were examined, first void urine samples were taken. Also at the first examination, peripheral blood samples were tested for HIV, Hepatitis B, Hepatitis C, and syphilis antibodies. Results: As a result of retrospective screening of the serological results of 364 male patients diagnosed with urethritis, Hepatitis B positivity was 1.09% with 4 cases, Hepatitis C positivity was found as 0.27% in 1 case and the Syphilis positivity rate was 1.92% with 7 cases in 364 patients. None of the patients had HIV positivity. Conclusions: The fact that there was not any encounter of HIV-positive patients in patients diagnosed with urethritis because of unprotected sexual contact led to the thought that circumcision had a protective contribution in these patients with urethritis, who were all circumcised. Also, screening tests, especially syphilis, should be performed on all patients diagnosed with STI infection.

Associations of First Void Urine Samples with Bacterial Vaginosis

Objective: The aim of this study was to investigate whether BV can be diagnosed from first-void urine (FVU). Study Design: Cross-sectional/case control study Place and Duration: Conducted at Hameed Latif Hospital Lahore, during from Sep, 2021 to Feb, 2022. Methods: There were 100 women had ages 20-65 years was presented in this study. Once informed written consent was obtained, participants' detailed demographic information was recorded. First void urine was collected from all women. According to Nugent's criteria, BV was indeed diagnosed. All of the qPCRs performed on the FVU and vaginal swabs for the selected vaginal bacteria (Atopobium vaginae, Prevotella spp., Gardnerella vaginalis, bacterial vaginosis-associated bacterium 2, Eggerthella-like bacterium, "Leptotrichia amnionii," Megasphaera type 1) had an area under the receiver operating characteristic (ROC) curve of &gt;85%, All data was examined using SPSS 24.0. Results: In current study, mean age of the women was 28.11±15.68 years and had mean BMI 24.9±7.49 kg/m2. Majority of the females were nulliparous 67 (67%). Most of the females had no genital hair remove among 60 (60%). Among 100 females, 49 (49%) females had bacterial vaginosis, 40 (40%) had normal vaginal flora and 11 (11%) had intermediate flora. Nugent scoring was used to determine the sensitivity and specificity of seven assays for BV-associated bacteria in urine (A. vaginae, Prevotella spp., G. vaginalis, BVAB 2, Eggerthella-like bacterium, L. amnionii, and Megasphaera type 1). By qualitative detection, the assays were 80%-100% sensitive but only 8%-80% specific (presence or absence). The area under the curve (AUC) was &gt; or = 91% for all seven bacterial species, indicating high diagnostic accuracy. Conclusion: Our research of ROC curves led us to the conclusion that FVU can be used to accurately diagnose BV. Combining qPCR findings for two bacteria, like Megasphaera type 1 and Prevotella spp., can improve sensitivity or specificity, respectively. Keywords: First Void Urine, BV, PCR, Nugnet scoring. 7-Assays

First confirmed Lymphogranuloma venereum (LGV) cases among MSM in Bulgaria, 2020–2021

Although the spread of Lymphogranuloma venereum (LGV) among European men who have sex with men (MSM) has been endemic since 2003, to the author’s knowledge no LGV cases have been confirmed in Bulgaria up to date and treatment in suspected LGV patients has been presumptive due to lack of diagnostic capacity. The objective of the study was to genotype C. trachomatis-positive samples from attendees of a sexual health center in Sofia from 2020-2021 in order to be able to detect LGV circulation among MSM in Bulgaria. During the study period, a total of 246 MSM were tested with commercially available nucleic acid amplification tests (NAATs) to detect C. trachomatis in first void urine (FVU), pharyngeal and rectal swabs. Thirty-one consecutive clinical samples found positive for C. trachomatis during diagnostic testing were retrospectively analyzed for the presence of C. trachomatis serovars L1-L3. LGV genovars-specific C. trachomatis DNA was detected by pmpH PCR from the same specimen. LGV genovars were confirmed with partial ompA gene sequencing. Altogether 31 C. trachomatis-positive samples (22 FVU, 1 pharyngeal and 8 rectal swabs) were successfully typed by pmpH PCR. Twenty-nine samples contained non-LGV and two samples LGV C. trachomatis types. All the LGV types were found in rectal samples. Detected L types were confirmed to be serovar L2 with ompA sequencing. The data show that LGV circulate also among Bulgarian MSM, which underscores the importance of expanding LGV testing capacity in order to better inform patient management. Enhanced surveillance and genotyping programs could help measure and monitor LGV prevalence in Bulgaria.

Sucrose and Fructose in Spot Urine as a Biomarker of Total Sugars Intake – Findings From a Controlled Feeding Study

ObjectivesTo investigate the utility of sucrose and fructose measured in spot urine (uSF) as a measure of 24-h urinary sucrose and fructose (24uSF) and a biomarker of total sugars (TS) intake.MethodsA hundred participants, 18–70 years of age, recruited from the Phoenix Metropolitan Area completed a 15-d controlled feeding study, which simulated their usual dietary behavior. Participants collected eight nonconsecutive 24-h urines; for two of the urine collections, each spot urine void was collected in a separate container. In the analysis, we considered four voids out of all voids collected for the day [AM void – 1st void after a meal or between 8:30 am to 12:30 pm; PM void - 1st void after a meal and between 12:31 pm to 5:30 pm; EVE void - 1st void after a meal and between 5:31 pm to 12:00 am; and Next-day (ND) void - 1st next day morning void and between 4:00 am to 12:00 pm]. We investigated the performance of uSF measured in one void, and uSF combined from two and three voids as a measure of 1) 24uSF and 2) TS intake.ResultsAmong the four selected voids, averaged over two collection days, uSF measured in the EVE void correlated best with 24uSF [partial r (adjusted for urinary creatinine) = 0.69]. For uSF biomarker combined from two voids, PM/EVE void produced the strongest correlation with 24uSF (r = 0.75). The correlation only marginally improved, when adding a 3rd void (PM/EVE/ND: r = 0.78). Based on these findings, we developed prediction equations for log(24uSF) based on log(uSF) measured in EVE, PM/EVE or PM/EVE/ND voids, adjusted for gender, log(age), BMI and log(creatinine). The R2 from the linear mixed model relating predicted 24uSF based on EVE, PM/EVE or PM/EVE/ND voids with observed TS, age and gender was 0.30, 0.46 and 0.48, respectively. Biomarker-estimated TS intake based on log(24uSF) predicted from PM/EVE voids had moderate model-based estimates of correlation with ‘usual’ TS intake (for uSF measured in PM/EVE voids from 1 day, r = 0.34; from 2 days, r = 0.45; and from 4 days, r = 0.52).ConclusionsOur findings suggest that uSF measured in PM/EVE voids performs well as a measure of 24uSF, and may be used to generate biomarker-based TS intake estimate when collecting of 24-urine is not feasible. Collecting PM and EVE voids over at least 2 nonconsecutive days rather than one day will produce less biased results.Funding SourcesNIH - National Cancer Institute.

FC052: Atrasentan for the Treatment of IGA Nephropathy: Interim Results from the Affinity Study

Abstract BACKGROUND AND AIMS IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the developed world. Up to 40% of patients with IgAN are at risk of progressing to end-stage kidney disease (ESKD), with proteinuria being a strong predictor of disease progression. Treatments that reduce proteinuria in IgAN are accompanied by eGFR preservation and improved kidney outcomes.[1] Endothelin A (ETA) receptor activation is a key driver of proteinuria, inflammation and fibrosis in patients with glomerular diseases.[2] Therefore, ETA receptor blockade has potential to be of therapeutic benefit for patients with proteinuric glomerular diseases, including IgAN. Atrasentan, a potent and selective ETA receptor antagonist that has demonstrated clinically significant reductions in proteinuria and risk of ESKD in a study of over 5300 patients with diabetic kidney disease (DKD), represents a potential therapy to reduce proteinuria and preserve kidney function in patients with IgAN and other glomerular diseases.[3] AFFINITY is a global, phase 2, open-label basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular diseases due to IgAN, Alport syndrome, focal segmental glomerulosclerosis and DKD. Here we present interim results from the first 17 patients enrolled in the IgAN cohort of the AFFINITY study, through week 12 of treatment. METHOD Approximately 20 patients will be enrolled in the IgAN cohort. They must have biopsy proven IgAN, be receiving a maximally tolerated and stable dose of renin angiotensin system inhibitor and have a urine protein creatinine ratio [UPCR] between 0.5 and &amp;lt;1.0 g/g from a first morning void urine sample. Patients are treated orally with 0.75 mg atrasentan daily. The primary endpoint is the change in 24-h UPCR from baseline to Week 12. Key exploratory endpoints include changes in eGFR from baseline to Week 56. RESULTS A total of 17 patients have enrolled in the IgAN cohort as of 4 January 2022. A total of 12 and 8 patients have completed visits through Week 6 and Week 12, respectively. The median age is 47 years and 41% are women. The geometric mean (GM) baseline proteinuria is 1.2 g/day, and median eGFR is 41 mL/min/1.73 m2 (Table 1). The 8 patients on treatment through Week 12 had a GM % reduction from baseline in 24-h UPCR of 43.6% [95% confidence interval (95% CI) 29.0–55.2] (Figure 1). Pharmacokinetic data are currently available for nine patients and showed a mean trough plasma atrasentan concentration in the targeted therapeutic range. Adverse events (AE) were observed in nne patients (53%), all mild or moderate in severity, most of which have resolved. One patient experienced an unrelated serious adverse event of traffic accident without long-term injuries. All patients remain on treatment with study drug except for one patient who discontinued drug due to an unrelated AE at week 13. CONCLUSION Treatment of patients with IgAN with atrasentan in addition to standard of care provided a &amp;gt;43% GM reduction in proteinuria after 12 weeks and was well tolerated, strongly supporting a key role of the endothelin pathway in the pathogenesis of IgAN. The ongoing phase 3 ALIGN study for patients with IgAN and proteinuria ≥1g/day will provide further assessment of the proteinuria lowering effects of atrasentan in this high-risk patient population.

Diurnal Variation in Biomarkers of Exposure to Endocrine-Disrupting Chemicals and Their Association with Oxidative Damage in Norwegian Adults: The EuroMix Study.

Much evidence on the adverse health effects of endocrine-disrupting chemicals (EDCs) has accumulated during recent decades. EDCs are commonly found in various foods and personal care products (PCP). Data documenting a diurnally varying EDC metabolism in humans is scarce. This study examined (i) the time-of-day effect on the diurnal magnitude and variance of urinary biomarkers of exposure to EDCs, and (ii) the association between EDC exposures and oxidative damage in a Norwegian adult subpopulation. This was a cross-sectional panel study using biobanked samples from the EuroMix project. During a typical weekday, participants were asked to collect all day’s urine voids and record dietary and PCP habitual uses in a diary. Collected time stamps of urine voids were classified into three distinct periods in the day (morning 6 a.m.–12 p.m., mid-day 12 p.m.–6 p.m., evening 6 p.m.–6 a.m.). Questionnaires regarding demographic characteristics, personal care product usage, and dietary habits were completed. Urinary levels of EDCs (phthalates, parabens, and bisphenols) were measured using mass spectrometry and adjusted for urinary volume using specific gravity. Urinary 4-hydroxynonenal (4HNE), a lipid peroxidation marker, was measured using an immunoassay kit. Linear mixed-effect models identified EDCs under the influence of a diurnal variation effect that was adjusted for dietary habits and PCP use and examined associations between EDC and 4HNE. p-values were FDR-adjusted. Most phthalates appeared to be diurnally varying with higher urinary levels towards the evening (q < 0.001) than those measured during mid-day; this strong diurnal variation effect was not present for parabens and bisphenols. Significant (q < 0.001) positive associations were observed between all phthalates, parabens, and bisphenols (except bisphenol S) and 4HNE. This study’s findings highlighted the diurnal variation of excretion for certain EDC, but not for others, in real-life conditions. The degree of EDC chronotoxicity in distinct diurnal windows of the day warrants further investigation with longitudinal human studies.

Variability in urinary concentrations of primary aromatic amines

Despite their known carcinogenic potential, primary aromatic amines (AAs) continue to be used in various consumer products. Human exposure to AAs is a subject of current concern. Although urinary measurements are used in the assessment of exposure, little is known about within- and between-individual temporal variability in urinary concentrations of AAs. In this study, we determined the concentrations of 30 AAs, nicotine and cotinine in 213 first morning void (FMV) urine samples collected longitudinally for over a five-week period from 15 participants residing in the Albany area of New York State, USA. Eight AAs, namely, aniline, 2-naphthylamine (2-NA), p-cresidine (p-CD), p-toluidine (p-TD), o/m-toluidine (o/m-TD), 4-chloroaniline (4-CA), 4,4′-methylenedi-o-toluidine (4,4’-MDA), and 2,6-dimethylaniline (2,6-DMA) were found in urine at a detection frequency (DF) in the range of 68–100%. Aniline and 2,6-DMA were the predominant compounds found at median concentrations of 6.0 and 3.81 ng/mL, respectively. Intraclass correlation coefficients (ICCs) of all urinary AA concentrations, except for 4-CA, showed moderate to poor predictability (ICC values ranged 0.248–0.697). Gender and ethnicity-related variations in ∑8AA concentrations were significant. Spearman's correlations among AA concentrations suggested that the sources of exposure were not related to tobacco smoke. No significant correlations existed between AAs concentrations and oxidative stress biomarkers (OSBs). The estimated daily intakes of AAs calculated based on urinary concentrations were several orders of magnitude below the tolerable daily intakes.