Urine Collection Research Articles

Effect of γ-tocopherol supplementation on premenstrual symptoms and natriuresis: a randomized, double-blind, placebo-controlled study

BackgroundThis randomized, double-blind, placebo-controlled study aimed to investigate the effects of γ-tocopherol (Toc) supplementation on premenstrual symptoms and natriuresis.MethodsWe enrolled 51 Japanese women with premenstrual symptoms, particularly those who showed increased symptoms induced by water retention during the luteal phase compared with the follicular phase. Premenstrual symptoms were recorded in the first cycle’s postmenstrual follicular phase; physical measurements and urine collection were conducted during the 48-h run-in period. The test supplement, which contained 180 mg of γ-Toc or placebo, was orally administered twice a day for 7 days during the luteal phase of the first and second cycles in a crossover manner. The same evaluation was conducted during the luteal phase, beginning in the morning of the sixth day of supplement administration.ResultsCompared with placebo intake, γ-Toc intake significantly reduced “fatigue” and “irritability/anger” symptoms. Furthermore, compared with placebo intake, γ-Toc intake significantly reduced the thigh circumference. Regarding the “swelling of the legs” and “heavy legs” symptoms and the thigh circumference, the biphasic trend of increasing and decreasing values in the daytime and morning, respectively, during the follicular phase was not observed at the luteal phase with placebo intake. Contrastingly, γ-Toc intake resulted in significantly lower values in the morning than placebo intake. The mean difference in 24-h urinary sodium excretion between γ-Toc and placebo intake was 10.6 mEq (95% confidence interval (CI): -0.1, 21.4, p = 0.05, power 55%). Plasma γ-Toc and its metabolite γ-carboxyethyl hydroxychroman (CEHC) levels were significantly higher with γ-Toc intake than with placebo intake. There were no significant between-supplement differences in serum electrolyte levels or cumulative urinary potassium excretion.Conclusionγ-Toc intake could effectively alleviate certain premenstrual syndrome symptoms, particularly those related to water retention during the luteal phase. Furthermore, the underlying mechanism may involve the diuretic effect of γ-CEHC, which is a γ-Toc metabolite.Trial registrationUMIN000047989; registration date: 10/06/2022, retrospectively registered.

Prior to versus after Metformin Treatment-Effects on Steroid Enzymatic Activities.

Background: We recently reported that metformin administration has substantial effects on steroid hormone concentrations. In this study, we specifically explored which enzymatic activities were affected before a first treatment versus after a time of metformin treatment. Material and Methods: Twelve male subjects (54.2 ± 9.1 years, 177.3 ± 4.1 cm, 80 ± 10.4 kg) and seven female subjects (57.2 ± 18.9 years, 162.7 ± 4.1 cm, 76.1 ± 10.4 kg) were recruited based on an indication of metformin. Prior to the first intake of metformin and after 24 h, urine collections were performed. Urine steroid analysis was completed using gas chromatography-mass spectrometry. Results: The average reduction in steroid hormone concentrations after the metformin treatment was substantial and relatively equally distributed in all metabolites and the sum of all metabolites with 35.4%. An exception was dehydroepiandrosterone, with a decrease of almost three hundred percent of average concentration. In addition, the sum of all cortisol metabolites and 18-OH cortisol (indicative of oxidative stress) were lower after the metformin treatment. Furthermore, significant inhibition of 3ß-HSD activity was detectable. Discussion: Effects prior to and after the metformin treatment on inhibiting 3ß-HSD activity were detected in line with findings from others. Furthermore, the pattern of a reduction, for example, in the sum of all glucocorticoids following the metformin treatment supported an effect on oxidative stress, which was further supported by the reduction in 18-OH cortisol. Nevertheless, we do not understand all steps in the complex pattern of the enzymes that affect steroid hormone metabolism and, consequently, further studies are necessary to improve our understanding.

Concordance between urine and self-collected vaginal samples for high-risk HPV detection in cervical cancer screening

Background: A system comprising of screening for pre-cancerous lesions succeeded by therapeutic interventions can greatly reduce the incidence of cervical cancer. High risk HPV detection in urine has proven itself as a potential primary screening tool. However, only a few studies have showed it’s concordance with matched self-collected vaginal samples while screening for high risk HPV infection in the community. Objective of the study was to determine the concordance between first void urine sample and self-collected vaginal sample for high risk HPV detection using Cobas 4800. The sensitivity and positive predictive value of screening by urine HPV testing for CIN 2+ detection would also be done along with its acceptability and cost analysis in community screening. Methods: This study will include women between 30-60 years with intact cervix and no precancerous lesions. Self-sampling will be provided by participants in the form of urine and vaginal swab collection by the Collipee device and vaginal swab stick respectively. This will be followed by high risk HPV testing using Cobas 4800 technology. The participants will also be asked to fill up a questionnaire about the acceptability of urine sampling for cancer screening. Conclusions: Screening tools can perhaps be diversified in order to suit the needs of low and middle income countries. Research and development of cervical cancer screening tools could hence bring to light feasible alternatives that could further improve compliance of non-attenders. Trial registration: The trial is registered with clinical trials registry (CTRI/2023/01/049322).

Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors.

The advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%. We recently reported about urinary flow cytometry-based detection of urinary PD-L1-positive (PD-L1+) kidney cells correlating with tubular PD-L1-positivity that reflected susceptibility to develop ICI-related nephrotoxicity as an irAE attending ICI treatment. Therefore, we designed a study protocol to evaluate urinary detection of PD-L1+ kidney cells as a tool for non-invasive biomonitoring of renal complications in cancer patients treated with ICIs. A prospective, controlled, non-interventional, longitudinal, single-center observational study will be conducted at the Department of Nephrology and Rheumatology of the University Medical Center Göttingen, Germany. We intend to enroll approximately 200 patients treated with immunotherapy from the Departments of Urology, Dermatology, and Hematology and Medical Oncology of the University Medical Center Göttingen, Germany. First, we will assess clinical, laboratory, histopathological, and urinary parameters in addition to urinary cell collection. Then, we will perform a correlative analysis between urinary flow cytometry of different PD-L1+ cell of renal origin with the onset of ICI-related nephrotoxicity. Because of growing ICI-treatment applicability with an expectable incidence of renal complications, providing cost-efficient and easily performable diagnostic tools for treatment-attendant and non-invasive biomonitoring becomes vital to improve both renal and overall survival rates in cancer patients receiving immunotherapy. https://www.drks.de, DRKS-ID DRKS00030999.

Tobacco Smoke Is a Major Source of Aromatic Amine Exposure in U.S. Adults: 2013-2014 National Health and Nutrition Examination Survey (NHANES).

Cigarette smoking increases the risk of cancer, cardiovascular diseases, and premature death. Aromatic amines (AA) are found in cigarette smoke and are well-established human bladder carcinogens. We measured and compared total urinary levels of 1-aminonaphthalene (1AMN), 2-aminonaphthalene (2AMN), and 4-aminobiphenyl (4ABP) in adults who smoked cigarettes exclusively and in adult nonusers of tobacco products from a nationally representative sample of non-institutionalized U.S. population in the 2013-2014 National Health and Nutrition Examination Survey. Sample-weighted geometric mean concentrations of AAs in adults who smoked cigarettes exclusively compared with adult nonusers were 30 times higher for 1AMN and 4 to 6 times higher for 2AMN and 4ABP. We evaluated the association of tobacco-smoke exposure with urinary AAs using sample-weighted multiple linear regression models to control for age, sex, race/ethnicity, diet, and urinary creatinine. Secondhand smoke exposure status was categorized using serum cotinine (SCOT) among adult nonusers (SCOT ≤ 10 ng/mL). The exposure for adults who smoked cigarettes exclusively (SCOT > 10 ng/mL) was categorized on the basis of the average number of self-reported cigarettes smoked per day (CPD) in the five days prior to urine collection. The regression models show AAs concentration increased with increasing CPD (P < 0.001). Dietary-intake variables derived from the 24-hours recall questionnaire were not consistently significant predictors of urinary AAs. This is the first characterized total urinary AA concentrations of the U.S. adult non-institutionalized population. Our analyses show that smoking status is a major contributor to AA exposures. These data provide a crucial baseline for exposure to three AAs in U.S. non-institutionalized adults.

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study

ObjectivePharmacokinetic variability drives tuberculosis (TB) treatment outcomes but measurement of serum drug concentrations for personalised dosing is inaccessible for children in TB-endemic settings. We compared rifampin urine excretion for prediction...

Short-Term Soy Bread Intervention Leads to a Dose-Response Increase in Urinary Isoflavone Metabolites and Satiety in Chronic Pancreatitis.

Patients with chronic pancreatitis (CP) are particularly vulnerable to nutrient malabsorption and undernutrition caused by the underlying pathology of their disease. Dietary intervention trials involving soy isoflavones in patients with CP are limited and isoflavone metabolites have not yet been reported. We hypothesized soy bread containing plant-based protein, dietary fiber, and isoflavones would be well-tolerated and restore gut functional capacity which would lead to isoflavone metabolites profiles like those of healthy populations. Participants (n = 9) received 1 week of soy bread in a dose-escalation design (1 to 3 slices/day) or a 4-week maximally tolerated dose (n = 1). Dietary adherence, satiety, and palatability were measured. Isoflavone metabolites from 24 h urine collections were quantified using high-performance liquid chromatography. A maximum dose of three slices (99 mg of isoflavones) of soy bread per day was achieved. Short-term exposure to soy bread showed a significant dose-response increase (p = 0.007) of total isoflavones and their metabolites in urine. With increasing slices of soy bread, dietary animal protein intake (p = 0.009) and perceived thirst (p < 0.001) significantly decreased with prolonged satiety (p < 0.001). In this study, adherence to short-term intervention with soy bread in CP patients was excellent. Soy isoflavones were reliably delivered. These findings provide the foundation for evaluating a well-characterized soy bread in supporting healthy nutrition and gut function in CP.

Diet Preference, Feed Efficiency and Expression of the Sodium-Dependent Glucose Transporter Isoform 1 and Sweet Taste Receptors in the Jejunum of Lambs Supplemented with Different Flavours.

This study investigated the effect of dietary flavour supplements on the preference, feed efficiency and expression of the sweet taste receptor family 1 members 2 and 3 (T1R2 + T1R3), and sodium-glucose linked transporter 1 (SGLT1) genes in the lambs' small intestines. Eight, five-month-old, Israeli crossbred Assaf lambs were offered 16 different non-nutritive commercial flavours in rolled barley and ground corn. Capsicum and sucram were the most preferred non-aroma flavours (p = 0.020), while milky (p < 0.001) was the most preferred powder-aroma flavour. For the metabolic and relative gene expression study, eight lambs were randomly assigned to either sucram, capsicum, a mix containing sucram and capsicum at 1:1 ratio or no flavour for control in a 4 × 2 cross-over design. The total collection of urine (females only), faeces and refusals was carried out, and T1R2, T1R3 and SGLT1 relative gene expression evaluated from the proximal jejunum biopsies. Flavour had no significant effect on the feed intake (p = 0.934), but capsicum increased the average daily weight gain per metabolic body weight (p = 0.049). The T1R3 gene was expressed highest in the mix treatment (1.7; p = 0.005). Collectively, our findings indicate that flavours can be used to motivate feed acceptance and improve the weight gain in lambs.

Estimated 24-Hour urinary sodium and potassium excretion in adults in the Northwest Region of Morocco, 2017

BackgroundExcessive sodium (Na) and insufficient potassium (K) intake contribute to a high risk of cardiovascular events. Morocco lacks data on actual Na and K intake in adults. We estimated mean Na and K intake in a Moroccan population of adults residing in the Northwest region using 24-h urinary excretion and examined their association with blood pressure (BP).MethodsA total of 371 adults from this region, who were recruited for the STEPs Survey Morocco 2017, completed demographic, anthropometric as well as BP data and provided a valid 24-h urine collection according to the standard World Health Organization (WHO) protocol. Multiple Linear Regression analysis was used to examine the association between 24-h urinary sodium (24-hUNa) and 24-h potassium excretion (24-hUK) with BP.ResultsMean Na excretion was 2794 mg/day and mean K excretion was 1898 mg/day. Overall, only 114 (30.7%) adults met the WHO recommendation for Na intake (< 2000 mg/d) and 31 (8.4%) met the adequate level for K intake (⩾3510 mg/d). There was no association between 24-hUNa and 24-hUK with BP (P > 0.05 for all).ConclusionNa intake was higher and K intake was lower than WHO recommendations in the study population. There was no association between estimated Na and K intake levels with BP in this population.

Correlation between 24-hour Urinary Total Protein Excretion and Single Urinary Protein Creatinine ratio in the Diagnosis of Childhood Nephrotic Syndrome : Study in a Tertiary Level Hospital

Introduction:Protein excretion varies in the course of the day, for this reason 24-hours urinary total protein excretion has been considered as the classic reference method for protein determination in nephotic syndrome. As the collection of urine for 24 hours is tedious and errors may occur during the process, so the protein:creatinine ratio was developed as a diagnostic alterative for Nephrotic syndrome.The main aim of this study is to determine the correlation between 24-hour urinary total protein excretion and single urinary protein creatinine ratio in childhood Nephrotic syndrome. Methods: This cross-sectional study was conducted in the department of Paediatrics,Shaheed Suhrawardy Medical College &amp; Hospital from June 2018 to May 2019. After taking valid consent total 60 cases of Nephrotic syndrome were selected purposively according to inclusion and exclusion criteria. Here we tried to determine the correlation between 24-hour urinary total protein excretion and single urinary protein creatinine ratio in the diagnosis of childhood Nephrotic syndrome by measuring the spot urinary protein creatinine ratio and the 24 hours urinary total protein excretion of the patients. Results : Among total 60(N) children of Nephrotic syndrome 42 (70%) patients were male and 18 (30%) patients were female with M:F = 2.16:1.The mean age was 4.57 ± 2.01SD years. Most of the patients were presented with some associated diseases like urinary tract infection (30%), upper respiratory tract infection (28.3%), viral illness(8.3%), atopic dermatitis(3.3%) and nonspecific illnesses(30%). The main physical findings were only puffy face(100%), with ascites (86.6%) and swelling of genitalia (38.3%).The mean 24 hours urinary total protein excretion was 3114.45 ± 1627.89 mg/24 hours and spot urinary protein creatinine ratio was 5.57 ± 3.13 SD. There was a very significant correlation between 24 hour total urinary protein excretion and spot urinary protein creatinine ratio. The sensitivity of the study was 80.49 – 100% and specificity of 91.78 - 100% at £2000 mg /sqm body surface area/ day protein excretion. The p value was .002 with correlation coefficient was 0.39. Conclusion: The protein creatinine ratio of a random urine sample might be used as an alternative method for the diagnosis of Nephrotic syndrome in children in view of the obvious advantages in terms of cost, time and patient convenience. J Shaheed Suhrawardy Med Coll 2021; 13(2): 137-142

Impact of ergot alkaloid and steroidal implant on whole-body protein turnover and expression of mTOR pathway proteins in muscle of cattle.

Holstein steers (n = 32) were used to determine if the ergot analog, bromocriptine decreases muscle protein synthesis through inhibitory action on the mTOR pathway via a direct effect on signal proteins, and if these negative effects can be alleviated with anabolic agents. Steers were treated with intramuscular administration of bromocriptine (vehicle or 0.1 mg/kg BW) and a subdermal commercial steroidal implant containing trenbolone acetate (TBA) and estradiol 17β (with or without), in a 2×2 factorial design. During the 35 day experiment, intake was restricted to 1.5 times maintenance energy requirement. On days 27 through 32, steers were moved to metabolism stalls for urine collection, and whole-body protein turnover was determined using a single pulse dose of [15N] glycine into the jugular vein on day 28. On day 35, skeletal muscle samples were collected before (basal state) and 60 min after (stimulated state) an i.v. glucose challenge (0.25 g glucose/kg). Blood samples were collected at regular intervals before and after glucose infusion for determination of circulating concentrations of glucose and insulin. Bromocriptine reduced insulin and glucose clearance following the glucose challenge, indicating decreased insulin sensitivity and possible disruption of glucose uptake and metabolism in the skeletal muscle. Conversely, analysis of whole-body protein turnover demonstrated that bromocriptine does not appear to affect protein synthesis or urea excretion. Western immunoblot analysis of skeletal muscle showed that it did not affect abundance of S6K1 or 4E-BP1, so bromocriptine does not appear to inhibit activation of the mTOR pathway or protein synthesis. Estradiol/TBA implant decreased urea excretion and protein turnover but had no effect on protein synthesis, suggesting that steroidal implants promote protein accretion through unchanged rates of synthesis and decreased degradation, even in the presence of bromocriptine, resulting in improved daily gains. Implanted steers likely experienced increased IGF-1 signaling, but downstream activation of mTOR, S6K and 4E-BP1, and thus increased protein synthesis did not occur as expected. Overall, this data suggests that bromocriptine does not have a negative impact on muscle protein synthetic pathways independent of DMI.

The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol

BackgroundCreutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.MethodsThe study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an “in-depth” visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a “brief” visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one “in-depth” visit, similar to the baseline visit of healthy relatives.DiscussionThis continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.Trial registrationThe study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

The impact of urine collection method on canine urinary microbiota detection: a cross-sectional study

BackgroundThe urinary tract harbors unique microbial communities that play important roles in urogenital health and disease. Dogs naturally suffer from several of the same urological disorders as humans (e.g., urinary tract infections, neoplasia, urolithiasis) and represent a valuable translational model for studying the role of urinary microbiota in various disease states. Urine collection technique represents a critical component of urinary microbiota research study design. However, the impact of collection method on the characterization of the canine urinary microbiota remains unknown. Therefore, the objective of this study was to determine whether urine collection technique alters the microbial populations detected in canine urine samples. Urine was collected from asymptomatic dogs by both cystocentesis and midstream voiding. Microbial DNA was isolated from each sample and submitted for amplicon sequencing of the V4 region of the bacterial 16 S rRNA gene, followed by analyses to compare microbial diversity and composition between urine collection techniques.ResultsSamples collected via midstream voiding exhibited significantly higher sequence read counts (P = .036) and observed richness (P = .0024) than cystocentesis urine. Bray Curtis and Unweighted UniFrac measures of beta diversity showed distinct differences in microbial composition by collection method (P = .0050, R2 = 0.06 and P = .010, R2 = 0.07, respectively). Seven taxa were identified as differentially abundant between groups. Pasteurellaceae, Haemophilus, Friedmanniella, two variants of Streptococcus, and Fusobacterium were over-represented in voided urine, while a greater abundance of Burkholderia-Caballeronia-Paraburkholderia characterized cystocentesis samples. Analyses were performed at five thresholds for minimum sequence depth and using three data normalization strategies to validate results; patterns of alpha and beta diversity remained consistent regardless of minimum read count requirements or normalization method.ConclusionMicrobial composition differs in canine urine samples collected via cystocentesis as compared to those collected via midstream voiding. Future researchers should select a single urine collection method based on the biological question of interest when designing canine urinary microbiota studies. Additionally, the authors suggest caution when interpreting results across studies that did not utilize identical urine collection methods.

Neutrophil gelatinase-associated lipocalin as a predictor of pre-eclampsia: A systematic review and meta-analysis.

Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found an association between maternal blood and urine levels and the development of pre-eclampsia. To examine whether maternal blood and urine levels of NGAL are good predictors of pre-eclampsia. The authors searched MEDLINE databases via PubMed, Embase, Scopus, Scielo, Google Scholar, PROSPERO International Prospective Register of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The authors included case-control observational clinical studies comparing protein levels of NGAL in serum and urine in women with pre-eclampsia with uncomplicated pregnancies. Only studies where the collection of blood or urine was peformed before the occurrence of pre-eclampsia were selected. The primary outcome was the difference in NGAL levels in blood or urine between women with and without pre-eclampsia. Seven studies in total were included: five studies measuring NGAL in blood and two in urine. Regarding the serum studies, 315 patients were included as cases and 540 as controls. Higher NGAL in maternal blood during all three trimesters together was associated with pre-eclampsia; the standardized mean difference was 1.15 ng/mL (95% confidence interval, 0.92-1.39; P < 0.01). Regarding the urine studies, 39 patients were included as cases and 220 as controls. There was no statistically significant difference between patients with pre-eclampsia and controls regarding urine NGAL. NGAL in maternal blood is higher in patients who later develop pre-eclampsia compared with controls and could be used as a potential predicting test in the routine clinical setting.

188Re-SSS Lipiodol Radioembolization in HCC Patients: Results of a Phase 1 Trial (Lip-Re-01 Study)

Despite the wide development of 90Y-loaded microspheres, 188Re-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to 188Re-SSS lipiodol, a new and more stable compound. Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade ≥3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST). Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 ± 0.4 GBq for activity Level 1 (n = 6), 3.6 ± 0.3 GBq for Level 2 (n = 6), and 5.0 ± 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 ± 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 ± 3.2% and 0.7 ± 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others). The high in vivo stability of 188Re-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.

Assessment of Energy and Nutrient Intake and the Intestinal Microbiome (ErNst Study): Protocol and Methods of a Cross-sectional Human Observational Study

On the national level, nutritional monitoring requires the assessment of reliable representative dietary intake data. To achieve this, standardized tools need to be developed, validated, and kept up-to-date with recent developments in food products and the nutritional behavior of the population. Recently, the human intestinal microbiome has been identified as an essential mediator between nutrition and host health. Despite growing interest in this connection, only a few associations between the microbiome, nutrition, and health have been clearly established. Available studies paint an inconsistent picture, partly due to a lack of standardization. First, we aim to verify if food consumption, as well as energy and nutrient intake of the German population, can be recorded validly by means of the dietary recall software GloboDiet, which will be applied in the German National Nutrition Monitoring. Second, we aim to obtain high-quality data using standard methods on the microbiome, combined with dietary intake data and additional fecal sample material, and to also assess the functional activity of the microbiome by measuring microbial metabolites. Healthy female and male participants aged between 18 and 79 years were recruited. Anthropometric measurements included body height and weight, BMI, and bioelectrical impedance analysis. For validation of the GloboDiet software, current food consumption was assessed with a 24-hour recall. Nitrogen and potassium concentrations were measured from 24-hour urine collections to enable comparison with the intake of protein and potassium estimated by the GloboDiet software. Physical activity was measured over at least 24 hours using a wearable accelerometer to validate the estimated energy intake. Stool samples were collected in duplicate for a single time point and used for DNA isolation and subsequent amplification and sequencing of the 16S rRNA gene to determine microbiome composition. For the identification of associations between nutrition and the microbiome, the habitual diet was determined using a food frequency questionnaire covering 30 days. In total, 117 participants met the inclusion criteria. The study population was equally distributed between the sexes and 3 age groups (18-39, 40-59, and 60-79 years). Stool samples accompanying habitual diet data (30-day food frequency questionnaire) are available for 106 participants. Current diet data and 24-hour urine samples for the validation of GloboDiet are available for 109 participants, of which 82 cases also include physical activity data. We completed the recruitment and sample collection of the ErNst study with a high degree of standardization. Samples and data will be used to validate the GloboDiet software for the German National Nutrition Monitoring and to compare microbiome composition and nutritional patterns. German Register of Clinical Studies DRKS00015216; https://drks.de/search/de/trial/DRKS00015216. DERR1-10.2196/42529.

Effects of accelerometry-derived physical activity energy expenditure on urinary C-peptide levels in a wild primate (Papio ursinus)

Animals have finite energy reserves for growth, survival, and reproduction and must maintain a stable energy balance. Measuring energy balance in the wild, however, is beset with methodological challenges. Quantification of urinary C-peptide (uCP), a proxy for insulin secretion, has enabled researchers to non-invasively estimate energy balance, and positive relationships between uCP levels and energy intake have been documented in numerous non-human primates. Comparatively few studies show that, consistent with insulin physiology, energy expenditure also alters levels of uCP. The timescale and extent of this relationship, however, remains unclear given the reliance on crude measures of activity and inferred energy expenditure. Here, for the first time, we test for effects of accelerometer-derived Vectorial Dynamic Body Acceleration (VeDBA) - a continuous measure of physical activity energy expenditure - on urinary C-peptide (uCP) levels in n = 12 wild chacma baboons (Papio ursinus). Applying a model selection approach, we show that VeDBA summed over short timescales (30 min to 1 h) prior to urine collection was negatively associated with uCP levels. Using the acceleration-based time individuals spent ‘non-stationary’ (i.e. locomoting) prior to urine collection as a predictor - instead of summed VeDBA - revealed similar but less clear results. Overall, the negative relationship between VeDBA and uCP levels highlights the importance of quantifying physical activity energy expenditure when using uCP measures to estimate energy balance and has potential implications for the field of energetics accelerometry.

Creatinine Clearance in Acute Brain Injury: A Comparison of Methods.

Currently, the measurement of glomerular filtration rate is very complex and costly, so its daily evaluation is performed using endogenous markers, of which creatinine is the most frequently used. It allows the estimation of glomerular filtration rate by means of its clearance or by formulas based on its serum and urine concentration. Augmented renal clearance (ARC) is frequent among critically ill patients and is defined as creatinine clearance (CrCl) > 130ml/min/1.73 m2. The aim of this study was to compare measured CrCl (MCC) and estimated CrCl obtained with the Cockcroft-Gault formula (CG), the Modification of Diet in Renal Disease Study equation (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) in patients with severe traumatic brain injury and nontraumatic subarachnoid hemorrhage. The second aim was to assess the incidence of ARC in this population of neurocritical patients. This was a prospective, observational, single center study from a cohort of 74 patients admitted to the neurocritical intensive care unit due to traumatic brain injury or subarachnoid hemorrhage. Serum creatinine (at 7 a.m.) and a 6-h urine collection were analyzed, and CrCl was measured and estimated by using CG, MDRD, and CKD-EPI. The intraclass correlation coefficient (ICC) was evaluated for each pair, and Bland-Altman plots were used to assess clinical significance. Among 74 patients, the median age was 53 (interquartile range [IQR] 36-65), and the median Glasgow Coma Scale score at admission was 6. The median MCC at admission was 176 (IQR 135-214). The medians of CG, MDRD and CKD-EPI were, respectively, 129ml/min/1.73 m2(IQR 95-176), 158 (IQR 115-202), and 116 (97-132). An ICC was applied to evaluate the correlation between MCC and estimated methods and showed a weak correlation between MCC and estimated CrCl obtained with the three different methods. The strongest ICC statistical correlation was found between MCC and MDRD, and the weakest correlation was found between MCC and CKD-EPI. Bland-Altman plots showed that differences between each pair were not clinically acceptable. ARC was present in 78% of measurements, using MCC. A weak correlation was observed between MCC and calculated CrCl. CG, MDRD, and CKD-EPI overestimated MCC when MCC ≤ 130ml/min/1.73 m2 and underestimated it when MCC > 130ml/min/1.73 m2. In this population, there was a weak statistical correlation between measured and estimated methods. In patients with ARC, formulas underestimated MCC. MCC should probably be the preferred methodology for renal function assessment in the clinical setting to better adjust drug dosage and guarantee drug effectiveness.

Abstract 3296: A urine-based DNA methylation marker test to detect upper tract urothelial carcinoma: a prospective pilot study

Abstract Objectives: Upper tract urothelial carcinoma (UTUC) is an uncommon, yet lethal tumor of the urinary tract. Diagnosis and preoperative risk stratification of these patients present distinct challenges given the limitations of current available diagnostic tools, including endoscopic biopsy and imaging. Herein, we explore the feasibility and clinical performance of a urine-based epigenetic assay in the diagnosis of patients with UTUC. Methods: Under an institutional review board-approved protocol, voided urine samples were prospectively collected using the Bladder CARE Urine Collection Kit (Pangea Laboratory LLC, CA, USA) from primary UTUC patients before any genitourinary manipulation between November 2019 and March 2022. All patients were confirmed to have UTUC in the final specimen. A 1:1 age/sex-matched group of cancer-free healthy donors (control group) was also included in the study. “Healthy” status was based on self-reporting and defined as no history of any type of tumor. Urine samples were analyzed with Bladder CARE, a urine-based test that measures the methylation level of 3 urothelial cancer-specific biomarkers (TRNA-Cys, SIM2, and NKX1-1) and two internal control loci using methylation-sensitive restriction enzymes coupled with qPCR. Results were reported as Bladder CARE Index (BCI) score and categorized as “positive” (BCI &amp;gt; 5), “high risk” (2.5 &amp;lt; BCI ≤ 5) or “negative” (BCI ≤ 2.5). Association between BCI score and category, and clinical and pathological findings was assessed. Results: A total of 50 patients (40 males and 10 females) with a median age of 72 (64-79) years were included in the final analysis. Six patients received neoadjuvant chemotherapy. Surgical procedures included RNU (n=40), ureterectomy (n=7), and URS (n=3). All patients who underwent URS were confirmed to have UTUC through biopsy. Among UTUC patients, Bladder CARE test resulted positive in 47, high-risk in 1, and negative in 2 patients. Comparing Bladder CARE test results with tumor pathologic features demonstrated a statistically significant correlation between BCI values and tumor size (p = 0.009). UTUC patients had significantly higher BCI values compared to the controls (mean BCI 189.3 vs. 1.6, respectively; p &amp;lt; 0.0001). ROC curve showed an AUC of 0.9662 (95% CI = 0.9296-1). Sensitivity, specificity, PPV, and NPV of Bladder CARE to detect UTUC were 96%, 88%, 88.9%, and 95.7%, respectively. In comparison, the sensitivity of urine cytology in our cohort was 37%. Conclusions: In this prospective pilot study, the proposed urine-based epigenetic test (Bladder CARE) showed high sensitivity and negative predictive value in the diagnosis of patients with UTUC. In addition, the sensitivity of this test was exceedingly higher than the standard urine cytology. A larger sample size study to validate the accuracy of this test is the next step. Citation Format: Paolo Piatti, Alireza Ghoreifi, Sanam Seyedian, Yap Ching Chew, Benjamin Jara, Lucy Sanossian, Jeffrey Bhasin, Michael Basin, Taikun Yamada, Gerhard Fuchs, Sumeet Bhanvadia, Rene Sotelo, Andrew Hung, Monish Aron, Mihir Desai, Inderbir Gill, Siamak Daneshmand, Gangning Liang, Hooman Djaladat. A urine-based DNA methylation marker test to detect upper tract urothelial carcinoma: a prospective pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3296.

The association between hydration status and body composition in healthy children and adolescents.

Children 10-20years old in the US are currently obese, showing suboptimal hydration as 60% fail to meet the US Dietary Reference Intakes for water. Studies have shown a significant inverse association between hydration status and body composition in children, although most failed to use the Dual-X-Ray Absorptiometry Scan (DEXA), the gold standard for body composition. Limited studies used an objective marker to measure hydration, such as urine specific gravity (USG) from a 24-h urine collection. Therefore, this study aimed toexamine the association between hydration status (measured from USG in a 24-h urine sample and assessed from three 24-h dietary recalls) and body fat % and lean mass (assessed from a DEXA scan) in children (10-13 years, n=34) and adolescents (18-20 years, n=34). Body composition was measured using DEXA, total water intake (mL/d) was assessed from three 24-h dietary recalls and analyzed using the Nutrition Data System for Research (NDSR). Hydration status was objectively measured using USG via 24-h urine collection. Overall body fat % was 31.7±7.31, total water intake was 1746±762.0mL/d, and USG score was 1.020±0.011 uG. Linear regressions showed significance between totalwater intake and lean mass (B=12.2, p<0.05). Logistic regressions showed no significant association between body composition and USG and total water intake. Findings showed total water intake was significantly associated with lean mass. Future research should be conducted to explore other objective markers of hydration and with a larger sample.