A candidate panel of eight urinary proteins shows potential of early diagnosis and risk assessment for diabetic kidney disease in type 1 diabetes.

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations.

Optimization of benzene exposure risk assessment: An integrated approach utilizing internal and external concentrations with a focus on biomarkers S-PMA & t, t-MA.

In the majority of occupational settings within China, the concentrations of benzene are observed to fall markedly below the demarcated detection thresholds. Employing traditional risk assessment models, the presence of exceptionally low airborne benzene exposure concentrations may infuse heightened degrees of uncertainty. Consequently, the necessity arises to investigate risk assessment methodologies more apt for the prevalent exposure environment among employees. In the present study, a pharmacokinetic model premised on urinary benzene metabolites (S-PMA and t, t-MA) was employed to ascertain a more precise daily airborne benzene exposure concentration per individual. This value was integrated into the linear multistage model as the 'internal exposure concentration'. In conjunction with the U.S National Environmental Protection Agency's (EPA) inhalation risk assessment model predicated on the external exposure concentration, the Singapore Ministry of Manpower's (MOM) model, and the linear multistage (LMS) model, the carcinogenic and non-carcinogenic effects of benzene were evaluated for 1781 benzene-exposed employees across 76 enterprises in Jiangsu Province. Findings suggest that in the linear multilevel model assessment, the cancer risk levels based on t, t-MA and S-PMA were higher in the printing and recording media reproduction industry, automobile manufacturing industry, general equipment manufacturing industry and the furniture manufacturing industry (median 2.842 × 10-4, 2.819 × 10-4, 2.809 × 10-4, and 2.678 × 10-4), which align more consistently with the actual benzene exposure circumstances of each industry's study participants, with overall risk levels calculated by the linear multistage model exceeding those of the EPA inhalation risk assessment model and the MOM model. This implies that the linear multistage model of internal exposure, based on the reciprocal of benzene biomarkers S-PMA and t, t-MA for airborne benzene exposure, presents enhanced sensitivity and suitability for the current occupational health risk assessment of workers. Without doubt, biomarker-based benzene exposure risk assessment emerges as the optimal choice.

Biomarker Assessment of Nicotine Exposure Among Adolescent E-Cigarette Users: 2018-2019.

BACKGROUND: Despite the increasing prevalence of vaping e-cigarettes among adolescents, there remains a lack of population-level assessments regarding the objective measurement of nicotine exposure. METHODS: This study analyzed a nationally representative sample of adolescents aged 13 to 17 years from Wave 5 of the Population Assessment of Tobacco and Health Study conducted between 2018 and 2019. Urinary nicotine metabolites, including cotinine and trans-3'-hydroxycotinine (3-HC), were assessed among exclusive nonnicotine e-cigarette users (n = 56), exclusive nicotine e-cigarette users (n = 200), and nonusers (n = 1059). We further examined nicotine exposure by past 30-day vaping frequency (ie, occasional [1-5 days], intermittent [6-19 days], and frequent [20+ days]) and flavor types among nicotine e-cigarette users. Multivariable linear regressions tested pairwise group effects, and biomarkers were normalized by the log transformation. RESULTS: Compared with nonusers, both nonnicotine and nicotine e-cigarette users exhibited higher levels of cotinine and 3-HC. Nicotine e-cigarette users had mean cotinine concentrations (61.3; 95% confidence interval, 23.8-158.0, ng/mg creatinine) approximately 146 times higher (P < .0001) than nonusers (0.4; 0.3-0.5), whereas nonnicotine users (4.9; 1.0-23.2) exhibited cotinine concentrations ∼12 times higher (P = .02). Among nicotine e-cigarette users, the levels of cotinine and 3-HC increased by vaping frequency, with cotinine increasing from 10.1 (2.5-40.1) among occasional users to 73.6 (31.8-170.6) among intermittent users and 949.1 (482.5-1866.9) among frequent users. Nicotine exposure was not significantly different by flavor type. CONCLUSIONS: E-cigarette use poses health-related risks resulting from nicotine exposure among adolescents. Comprehensive regulations of e-cigarette products and marketing, vaping prevention, cessation, and public policies are needed to prevent youth from developing nicotine addiction.

Risk assessment and predictors of the exposure to polycyclic aromatic hydrocarbons in Spanish adults by urinary human biomonitoring.

Polycyclic aromatic hydrocarbons (PAHs) are produced primarily during incomplete combustion of organic matter and in various industrial processes. They are widespread environmental pollutants that are of significant interest due to their potential toxicity. Humans can be exposed to PAHs through ingestion, inhalation and dermal contact. In the present study, ten urinary PAH biomarkers were determined in first-morning urine samples (n = 504) from the adult population (aged 18-65 years) residing in the Valencian Region of Spain. These samples were analysed using liquid-liquid extraction followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). All PAH biomarkers were quantified in more than 65 % of the urine samples. Naphthalene biomarkers, 1-hydroxynaphthalene (1OHNAP) and 2-hydroxynaphthalene (2OHNAP), exhibited the highest levels with geometric means (GMs) of 0.7 and 11.9 µg L-1, respectively. The 95th percentile of all PAH biomarkers ranged from 0.22 to 64.8 µg L-1. Estimated daily intakes (EDIs) for the analysed PAH families in the studied population ranged from 17 (pyrene) to 18581 (naphthalene) ng·kg-bw-1·day-1 (GM). Significant associations were observed between the quantified urinary metabolites of PAHs and smoking status, home location, annual household incomes, BMI, and the consumption of grilled food in the last 24 h. Hazard quotients (HQs) of naphthalene and consequently, hazard indexes (HIs) were above 1, especially for smokers. Therefore, potential health risks associated with PAH exposure in the target population could not be discarded.

Arsenic, polycyclic aromatic hydrocarbons, and metal exposure and risk assessment of stroke.

Globally, stroke is one of the primary causes of morbidity and mortality. In the USA, stroke is a major cause of death and disability. Limited studies assessed the impact of polycyclic aromatic hydrocarbons, arsenic, and other metal exposure and their association with the risk of stroke. This study aimed to assess different arsenic species, including total arsenic; two types of organic arsenic, i.e., arsenobetaine and arsenocholine; four types of inorganic arsenic, i.e., arsenic acid, arsenous acid, dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA); six types of urinary polycyclic aromatic hydrocarbon (PAH) compounds, i.e., 1-hydroxynaphthalene, 1-hydroxyphenanthrene, 1-hydroxypyrene, 2-hydroxynaphthalene, 2-hydroxyfluorene, and 3-hydroxyfluorene; and fourteen types of metals from urine specimen, i.e., manganese, cadmium, lead, mercury, barium, cobalt, strontium, molybdenum, cesium, thallium, antimony, tin, tungsten, and uranium and their association with those who reported having been told they had had a stroke by a medical professional. The National Health and Nutrition Examination Survey (NHANES) data used in this study include three data cycles from 2011-2016. In this study, data from a total of 5537 males and females who are aged 20 years and older were analyzed using logistic modeling of the complex weighted survey design. R version 3.6.3 software was used to conduct the analyses. Four species of urinary PAHs, including the third quantiles of 1-hydroxynaphthalene [odds ratio (OR): 2.327, 95% confidence interval (CI): 0.961-5.632], 2-hydroxynaphthalene [OR: 2.449, 95% CI: 1.067-5.622], and 3-hydroxyfluorene [OR: 2.289, 95% CI: 1.077-4.861] and the second quantiles of 3-hydroxyfluorene [OR: 2.201, 95% CI: 1.115, 4.346] and 1-hydroxypyrene [OR: 2.066, 95% CI: 1.037, 4.114], showed a positive correlation with increased odds of stroke. Among metals, the third (3rd) [OR: 3.566, 95% CI: 1.370, 9.280] and fourth (4th) [OR: 2.844, 95% CI: 0.947, 8.543] quantiles of urinary manganese showed a positive correlation with increased odds of stroke.

Validation of the smartphone-based dietary assessment tool "Traqq" for assessing actual dietary intake by repeated 2-h recalls in adults: comparison with 24-h recalls and urinary biomarkers.

BACKGROUND: Conventional dietary assessment methods are affected by measurement errors. We developed a smartphone-based 2-h recall (2hR) methodology to reduce participant burden and memory-related bias. OBJECTIVE: Assessing the validity of the 2hR method against traditional 24-h recalls (24hRs) and objective biomarkers. METHODS: Dietary intake was assessed in 215 Dutch adults on 6 randomly selected nonconsecutive days (i.e., 3 2hR-days and 3 24hRs) during a 4-wk period. Sixty-three participants provided 4 24-h urine samples, to assess urinary nitrogen and potassium concentrations. RESULTS: Intake estimates of energy (2052±503 kcal vs. 1976±483 kcal) and nutrients (e.g., protein: 78±23 g vs. 71±19 g; fat: 84±30 g vs. 79±26 g; carbohydrates: 220±60 g vs. 216±60 g) were slightly higher with 2hR-days than with 24hRs. Comparing self-reported protein and potassium intake to urinary nitrogen and potassium concentrations indicated a slightly higher accuracy of 2hR-days than 24hRs (protein: -14% vs. -18%; potassium: -11% vs. -16%). Correlation coefficients between methods ranged from 0.41 to 0.75 for energy and macronutrients and from 0.41 to 0.62 for micronutrients. Generally, regularly consumed food groups showed small differences in intake (<10%) and good correlations (>0.60). Intake of energy, nutrients, and food groups showed similar reproducibility (intraclass correlation coefficient) for 2hR-days and 24hRs. CONCLUSIONS: Comparing 2hR-days with 24hRs showed a relatively similar group-level bias for energy, most nutrients, and food groups. Differences were mostly due to higher intake estimates by 2hR-days. Biomarker comparisons showed less underestimation by 2hR-days as compared with 24hRs, suggesting that 2hR-days are a valid approach to assess the intake of energy, nutrients, and food groups. This trial was registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) registry as ABR. No. NL69065.081.19.

Performance assessment of an equine metabolomics model for screening a range of anabolic agents.

INTRODUCTION: Despite their ban, Anabolic Androgenic Steroids (AAS) are considered as the most important threat for equine doping purposes. In the context of controlling such practices in horse racing, metabolomics has emerged as a promising alternative strategy to study the effect of a substance on metabolism and to discover new relevant biomarkers of effect. Based on the monitoring of 4 metabolomics derived candidate biomarkers in urine, a prediction model to screen for testosterone esters abuse was previously developed. The present work focuses on assessing the robustness of the associated method and define its scope of application. MATERIALS AND METHODS: Several hundred urine samples were selected from 14 different horses of ethically approved administration studies involving various doping agents' (AAS, SARMS, ß-agonists, SAID, NSAID) (328 urine samples). In addition, 553 urine samples from untreated horses of doping control population were included in the study. Samples were characterized with the previously described LC-HRMS/MS method, with the objective of assessing both its biological and analytical robustness. RESULTS: The study concluded that the measurement of the 4 biomarkers involved in the model was fit for purpose. Further, the classification model confirmed its effectiveness in screening for testosterone esters use; and it demonstrated its ability to screen for the misuse of other anabolic agents, allowing the development of a global screening tool dedicated to this class of substances. Finally, the results were compared to a direct screening method targeting anabolic agents demonstrating complementary performances of traditional and omics approaches in the screening of anabolic agents in horses.

Factors affecting urinary organophosphate pesticide metabolite levels among Californian agricultural community members.

Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP exposure.

Joint Microbiota Activity and Dietary Assessment through Urinary Biomarkers by LC-MS/MS.

Accurate dietary assessment in nutritional research is a huge challenge, but essential. Due to the subjective nature of self-reporting methods, the development of analytical methods for food intake and microbiota biomarkers determination is needed. This work presents an ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method for the quantification and semi quantification of 20 and 201 food intake biomarkers (BFIs), respectively, as well as 7 microbiota biomarkers applied to 208 urine samples from lactating mothers (M) (N = 59). Dietary intake was assessed through a 24 h dietary recall (R24h). BFI analysis identified three distinct clusters among samples: samples from clusters 1 and 3 presented higher concentrations of most biomarkers than those from cluster 2, with dairy products and milk biomarkers being more concentrated in cluster 1, and seeds, garlic and onion in cluster 3. Significant correlations were observed between three BFIs (fruits, meat, and fish) and R24h data (r > 0.2, p-values < 0.01, Spearman correlation). Microbiota activity biomarkers were simultaneously evaluated and the subgroup patterns detected were compared to clusters from dietary assessment. These results evidence the feasibility, usefulness, and complementary nature of the determination of BFIs, R24h, and microbiota activity biomarkers in observational nutrition cohort studies.

Non-carcinogenic and cumulative risk assessment of exposure of kitchen workers in restaurants and local residents in the vicinity of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are often formed when organic substances do not burn completely. This study evaluates the non-carcinogenic and cumulative risks associated with PAHs levels by testing blood and urine samples in kitchen workers and residents near restaurants in Shiraz, Iran. Metabolites of PAH in the urine samples as well as clinical parameters in the blood samples were measured. The non-carcinogenic and cumulative risk assessments from exposure of the study groups to PAH metabolites were also evaluated. The highest average concentrations of PAH metabolites were related to kitchen workers (2126.7 ng/g creatinine (ng/g cr)). The metabolites of 1-Hydroxypyrene (1-OHP) and 9-Phenanthrene (9-OHPhe) had the highest and lowest mean concentrations, respectively. A direct correlation was observed between the levels of PAH metabolites with malondialdehyde (MDA) and total antioxidation capacity (TAC) levels (p < 0.05). Hazard Index (HIi) was obtained less than one (HIi < 1), indicating low-risk negative health impacts on the target groups. Nevertheless, conducting more studies to determine the health status of these people is quite evident.

Quantification and stability assessment of urinary phenolic and acidic biomarkers of non-persistent chemicals using the SPE-GC/MS/MS method.

Nowadays, people are exposed to numerous man-made chemicals, many of which are ubiquitously present in our daily lives, and some of which can be hazardous to human health. Human biomonitoring plays an important role in exposure assessment, but complex exposure evaluation requires suitable tools. Therefore, routine analytical methods are needed to determine several biomarkers simultaneously. The aim of this study was to develop an analytical method for quantification and stability testing of 26 phenolic and acidic biomarkers of selected environmental pollutants (e.g., bisphenols, parabens, pesticide metabolites) in human urine. For this purpose, a solid-phase extraction coupled with gas chromatography and tandem mass spectrometry (SPE-GC/MS/MS) method was developed and validated. After enzymatic hydrolysis, urine samples were extracted using Bond Elut Plexa sorbent, and prior to GC, the analytes were derivatized with N-trimethylsilyl-N-methyl trifluoroacetamide (MSTFA). Matrix-matched calibration curves were linear in the range of 0.1-1000 ng mL-1 with R > 0.985. Satisfactory accuracy (78-118%), precision (< 17%), and limits of quantification (0.1-0.5 ng mL-1) were obtained for 22 biomarkers. The stability of the biomarkers in urine was assayed under different temperature and time conditions that included freezing and thawing cycles. All tested biomarkers were stable at room temperature for 24 h, at 4 °C for 7 days, and at -20 °C for 18 months. The total concentration of 1-naphthol decreased by 25% after the first freeze-thaw cycle. The method was successfully used for the quantification of target biomarkers in 38 urine samples.

Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises.

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up ( P = 0.006, Hedge g : 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Associations between residential volatile organic compound exposures and liver injury markers: The role of biological sex and race.

While occupational exposures to volatile organic compounds (VOCs) have been linked to steatohepatitis and liver cancer in industrial workers, recent findings have also positively correlated low-dose, residential VOC exposures with liver injury markers. VOC sources are numerous; factors including biological make up (sex), socio-cultural constructs (gender, race) and lifestyle (smoking) can influence both VOC exposure levels and disease outcomes. Therefore, the current study's objective is to investigate how sex and race influence associations between residential VOC exposures and liver injury markers particularly in smokers vs. nonsmokers. Subjects (n = 663) were recruited from residential neighborhoods; informed consent was obtained. Exposure biomarkers included 16 urinary VOC metabolites. Serological disease biomarkers included liver enzymes, direct bilirubin, and hepatocyte death markers (cytokeratin K18). Pearson correlations and generalized linear models were conducted. Models were adjusted for common liver-related confounders and interaction terms. The study population constituted approximately 60% females (n = 401) and 40% males (n = 262), and a higher percent of males were smokers and/or frequent drinkers. Both sexes had a higher percent of White (75% females, 82% males) vs. Black individuals. Positive associations were identified for metabolites of acrolein, acrylamide, acrylonitrile, butadiene, crotonaldehyde, and styrene with alkaline phosphatase (ALP), a biomarker for cholestatic injury; and for the benzene metabolite with bilirubin; only in females. These associations were retained in female smokers. Similar associations were also observed between these metabolites and ALP only in White individuals (n = 514). In Black individuals (n = 114), the styrene metabolite was positively associated with aspartate transaminase. Interaction models indicated that positive associations for acrylamide/crotonaldehyde metabolites with ALP in females were dose-dependent. Most VOC associations with K18 markers were negative in this residential population. Overall, the findings demonstrated that biological sex, race, and smoking status influence VOC effects on liver injury and underscored the role of biological-social-lifestyle factor(s) interactions when addressing air pollution-related health disparities.

Associations between urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.

Assessment of inflammatory cytokines in exhaled breath condensate and exposure to mixtures of organic pollutants in brick workers.

Brick production causes a lot of pollution in the form of dust, fumes, and toxic substances. Therefore, brick workers are highly exposed to pollutants and present a high risk of developing respiratory diseases. The objective of this research was to determine the exposure to polycyclic aromatic hydrocarbons (PAHs) and toluene in urine and evaluate the effects on health using markers of oxidative stress in exhaled breath condensate (EBC) as well as the exposure to pollutants in suspended particles of the studied area. Exposure to PAHs and toluene was evaluated using hydroxylated markers (OH) of PAHs and hippuric acid in urine, respectively. Cytokines like TNF-α, INF-y, IL-2, IL-4, IL-6, IL-8, IL-10 y GMCSF in EBC were also evaluated. PM2.5 particles were measured during an 8-h work shift. The results in brick workers presented a total OH-PAHs concentration of 97.3 µg/L and hippuric acid concentration of 0.2 g/L. The environmental concentrations of suspended particles were found within a range of 41.67-3541.6 µg/m3. The median of cytokines oscillated between 11.8 pg/mL to 1041 pg/mL. In conclusion, these results are similar to those of occupations in which there is high exposure to pollutants and populations with lung diseases. For that reason, the brick production sector requires prevention and control strategies against the pollutants emitted.

Assessment of early kidney injury caused by asymptomatic bacteriuria in children with type 1 diabetes.

INTRODUCTION: Infection is one of the most frequent causes of morbidity and mortality in diabetic patients. Some microorganisms become more virulent in a high glucose concentration. Diabetics are more likely to have asymptomatic and symptomatic bacteriuria. NGAL is secreted in high concentrations into the blood and urine within two hours of AKI. OBJECTIVES: The aim of the study is early detection of UTI in type1diabetic children through screening of their urine samples, and measurement of NGAL urinary levels in cases with asymptomatic bacteriuria for early detection of AKI to prevent serious complications. PATIENTS AND METHODS: One thousand twenty-two known diabetic children on regular follow up in endocrine outpatient clinic at Minia Children University hospital were screened for UTI. From them only 52 diabetic children were diagnosed as asymptomatic bacteriuria (group I), 52 diabetic children with normal urine analysis (group II) and 52 apparently healthy children, age and sex matched, served as controls (group III). CBC, Renal function test, HbA1c, hs- CRP, Albumin/creatinine ratio, urine examination, urine culture, GFR and urinary NGAL were done to all children. RESULTS: Thirty-seven females (71.2%) had asymptomatic bacteriuria, Hs CRP and urinary NGAL were significantly higher, while GFR was significantly lower in diabetic children with bacteriuria than the other two groups. For diabetic children with bacteriuria, (AUC) for NGAL was 1 with optimal cutoff value of > 44.1 (Sensitivity 100% and Specificity 100%) while AUC for hsCRP was 0.887 with optimal cutoff value of > 1 (Sensitivity 82.69% and Specificity 90.38%). CONCLUSION: Routine urine analysis should be done for all diabetic children even if they are asymptomatic. NGAL and hsCRP are non-invasive methods that could detect early renal injury in these patients thus, early, and proper management of UTI should be started to prevent renal injury.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Comprehensive Urinomic Identification of Protein Alternatives to Creatinine Normalization for Diagnostic Assessment of Lupus Nephritis.

Introduction: The current gold standard used for urine biomarker normalization, creatinine, poses a challenge to translate to the point of care because antibodies to creatinine are difficult to develop and currently available ligands to creatinine are sub-optimal for this purpose. Hence, protein alternatives to creatinine are clearly needed. To address this need, lupus nephritis was selected as a model disease where urine protein assessment is required for diagnosis. Methods: A comprehensive proteomic screen of 1129 proteins in healthy and lupus nephritis urine was executed to identify protein alternatives to creatinine for the normalization of urine biomarkers. Urinary proteins that correlated well with creatinine but did not vary with disease were further validated by ELISA in an independent cohort of lupus nephritis subjects. Results: The comprehensive proteomic screen identified 14 urine proteins that correlated significantly with urine creatinine but did not differ significantly between SLE and controls. Of the top five proteins selected for ELISA validation, urine HVEM and RELT once again showed significant correlation with urine creatinine in independent cohorts. Normalizing a lupus nephritis biomarker candidate ALCAM using urinary HVEM demonstrated comparable diagnostic ability to creatinine normalization when distinguishing active lupus nephritis from inactive SLE patients. Conclusions: The discovery of urine HVEM as a protein alternative to creatinine for biomarker normalization has applications in the engineering of antibody-based point of care diagnostics for monitoring lupus nephritis progression.

Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to acute and chronic health effects through the suggested pathways of oxidative stress and inflammation. However, evidence is still limited. We aimed to investigate jointly the relationship of PAHs, oxidative stress, and inflammation. METHODS: We measured 13 biomarkers of PAH exposure (n = 6: hydroxylated polycyclic aromatic hydrocarbons, [OH-PAHs]), oxidative stress (n = 6: malondialdehyde (MDA); 8-hydroxy-2'-deoxyguanosine (8-OHdG); and 4 representatives of the compound class of F2α-isoprostanes) in urine, and inflammation (n = 1: high-sensitivity C-reactive protein, [hs-CRP]) in serum from 400 participants at the second follow-up (2013/2014) of the German KORA survey S4. Multiple linear regression models were applied to investigate the interplay between biomarkers. RESULTS: Concentrations of biomarkers varied according to sex, age, smoking status, season, and a history of obesity, diabetes, or chronic kidney disease. All OH-PAHs were significantly and positively associated with oxidative stress biomarkers. An interquartile range (IQR) increase in sum OH-PAHs was associated with a 13.3% (95% CI: 9.9%, 16.9%) increase in MDA, a 6.5% (95% CI: 3.5%, 9.6%) increase in 8-OHdG, and an 8.4% (95% CI: 6.6%, 11.3%) increase in sum F2α-isoprostanes. Associations were more pronounced between OH-PAHs and F2α-isoprostanes but also between OH-PAHs and 8-OHdG for participants with potential underlying systemic inflammation (hs-CRP ≥ 3 mg/L). We observed no association between OH-PAHs and hs-CRP levels. While 8-OHdG was significantly positively associated with hs-CRP (13.7% [95% CI: 2.2%, 26.5%] per IQR increase in 8-OHdG), F2α-isoprostanes and MDA indicated only a positive or null association, respectively. CONCLUSION: The results of this cross-sectional study suggest, at a population level, that exposure to PAHs is associated with oxidative stress even in a low exposure setting. Oxidative stress markers, but not PAHs, were associated with inflammation. Individual risk factors were important contributors to these processes and should be considered in future studies. Further longitudinal studies are necessary to investigate the causal chain of the associations.

Exposure assessment of urinary deoxynivalenol in pregnant women in Wuhan, China.

Deoxynivalenol (DON) is a ubiquitous trichothecene mycotoxin in food. DON and its modified forms can cross the placental barrier and influence the foetus' health. Limited information is available on exposure of dietary DON intake of pregnant women in China recently. We estimated the exposure of dietary DON intake of pregnant women in a large sample size (n = 2534) from China. The total DON (tDON) and free DON (fDON) biomarkers in urine were detected by liquid chromatography-tandem mass spectrometry. The mean concentration of tDON was 34.8 ng/mg creatinine, and the fDON was 15.9 ng/mg creatinine. The estimated exposure of dietary DON intake was 0.96-1.91 µg/kg bw/day, and the difference in exposure of DON between the first and second trimesters was statistically insignificant. Approximately 26%-60% of individuals exceeded the provisional maximum tolerable daily intake (PMTDI). The age, pre-pregnancy BMI, and the sampling seasons may be the risk factor for the occurrence of exceeding PMTDI. This survey is the first exposure biomarker for DON in a large sample size from pregnant women in China. We found that the dietary DON exposure in pregnant women was relatively high and particular concern should be paid to the DON exposure during pregnancy.