Urinary Concentrations Research Articles

Micronutrient deficiencies and their co-occurrence among pregnant women in Mbeya region, Tanzania

Micronutrient deficiencies, a global concern affecting vulnerable populations, including pregnant women, pose significant public health challenges. Specifically, micronutrient deficiencies in iron, vitamin A, iodine and folate have been of greatest public health concern among pregnant women. This study aimed to evaluate the co-occurrence of selected multiple micronutrient deficiencies among pregnant women attending Antenatal Care (ANC) in Mbeya, Tanzania. Employing a cross-sectional design, data were gathered from 420 pregnant women aged 15–49 years attending ANC in Mbeya Region. Semi-structured questionnaires captured socio-demographic data, and blood samples were collected for biomarkers assessment. The study used Stata 17.0 to analyze the data. Results revealed that six out of ten pregnant women exhibited at least one form of micronutrient deficiency, with 15.0% experiencing double deficiencies and 2.2% experiencing triple deficiencies. Iron Deficiency Anemia (IDA) was prevalent among 61.7% of anaemic pregnant women. Individual micronutrient deficiency rates were as follows: folate (21.7%), vitamin B12 (9.9%), iron (38.4%), vitamin A (9.8%), with a median Urinary Iodine Concentration (UIC) of 279.4μg/L. Pregnant women with anemia were more likely to have Multiple Micronutrient Deficiencies (MMD) compared to non-anemic counterparts (p-value <0.005). Additionally, those in the second trimester were at a higher risk of MMD than those in the first trimester (p-value <0.005). A higher wealth quantile appeared to protect against MMD (p-value <0.005). The study highlights the co-occurrence of MMD among pregnant women in Tanzania, indicates the necessity for an improved strategy to enhance multiple micronutrients intake through dietary diversity, MMS and fortified foods.

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

The diagnostic utility of urinary Transferrin excretion rate as predictor for micro albuminuria in patients with Type 2 Diabetes Mellitus among Karbala province

One of the factors responsible of end-stage renal disease and chronic kidney disease is diabetic nephropathy. Microalbuminuria itself is regarded as the initial indication of diabetic nephropathy, and it affects 20% to 40% of patients with diabetes mellitus. Because of the limited accuracy and precision of microalbuminuria, more susceptible markers may be developed to more accurately identify diabetic nephropathy early on. The purpose of this research was to ascertain whether urine transferrin could be used as a marker for diabetic nephropathy. In our research, 80 subjects with type 2 diabetes were divided into two categories: 10 healthy controls and group 1 (normoalbuminuric, with albumin excretion up to 30 mg/d) and group 2 (microalbuminuric, with albumin excretion between 30 and 300 mg/d). all subjects was over the age of 18, had diabetes for further than a year, and had a glomerular filtration rate greater than 60 mL/min/1.73 m2. The concentration of transferrin, serum creatinine, and glycosylated hemoglobin (HbA1c) in both spot urine and 24-hour urine samples were assessed using a super accurate sandwich enzyme - linked immunosorbent assay kit. subjects with microalbuminuria had substantially greater urinary transferrin levels than both normoalbuminuric and healthy control participants. We discovered a significantly positive correlation r = 0.584 (p < 0.001) when we compared these categories based on the urinary transferrin concentration. Urinary transferrin levels did not correlate with glycoregulation, and neither did transferrin levels and the length of diabetes. Urinary transferrin levels may be utilized as an important indicator of diabetic nephropathy, according to the findings of the research.

Antibiotic efficacy and resistance patterns of urinary tract infection-causing bacteria in dogs and resistome of multidrug-resistant Klebsiella pneumoniae via whole genome sequencing in South Korea

Bacterial urinary tract infections (UTIs) are prevalent in dogs and necessitate antibiotic intervention. However, the emergence of multidrug-resistant (MDR) bacteria poses significant challenges to antibiotic therapy. Although fosfomycin has been demonstrated to achieve and maintain high concentrations in urine, suggesting its potential for treating UTIs in dogs, its efficacy and the resistance profiles of urinary pathogens from canine UTIs remain elusive. Therefore, this study was conducted to investigate the antibiotic susceptibility of bacterial pathogens isolated from companion dogs with UTIs, with a particular focus on their susceptibility and resistance to fosfomycin. A total of 70 isolates from urine samples were analyzed, of which Escherichia coli (n = 18), Proteus mirabilis (n = 9), Klebsiella pneumoniae (n = 5), and Staphylococcus pseudintermedius (n = 5) were predominant. Resistance to erythromycin was most prevalent (94.59%), followed by clindamycin (91.89%) and ampicillin (78.37%), whereas the lowest resistance rate was observed for amikacin (5.40%). Resistance to fosfomycin was observed in 15 out of the 37 predominant isolates (40.54%), including all K. pneumoniae isolates (100%). All isolates, except 4 E. coli strains, were categorized as MDR (33 out of 37; 89.18%). The resistance rates for amoxicillin/clavulanic acid and trimethoprim-sulfamethoxazole, which are common first-line antibiotics for canine UTIs, were 48.64 and 56.75%, respectively. Whole-genome sequencing of K. pneumoniae isolates, which exhibited high resistance to fosfomycin, revealed multiple antibiotic resistance genes, with chromosomal fosA present in all isolates. Among the 27 dogs with recurrent infection included in this study, 2 were administered fosfomycin, resulting in clinical remission, as evidenced by negative urine culture tests. Overall, this study is the first to demonstrate the importance of assessing fosfomycin resistance profile for optimal treatment of canine UTIs, particularly in cases involving MDR strains.

Effect of contrasting water-soluble carbohydrate to crude protein ratio’s in perennial ryegrass on nitrogen metabolism in lambs

ABSTRACT The effect of high and low water-soluble carbohydrate (WSC) to crude protein (CP) ratios on nitrogen balance in lambs was evaluated. Ryegrasses containing either 35.4% WSC and 12% CP (High WSC) or 14.8% WSC and 23.8% CP (High N) were harvested, frozen and fed to lambs in metabolism crates. These contrasts in WSC and CP delivered diets with markedly different WSC:CP ratios (3.17:1 and 0.70:1). These ratios were higher than those reported in ryegrass previously. There was no difference in urinary nitrogen concentration (0.46 vs 0.48 g/l) but as the total urinary volume was higher on the High N diet (4.2 vs 1.5 l/d, P < 0.001), the end result was that more N was excreted in the urine on the high N diet (18.8 vs 7.3 g/d, P < 0.001). However, the proportion of nitrogen intake that was excreted in urine and faeces was higher on the High WSC diet so there was no evidence that a high WSC forage diet improved nitrogen utilisation.

Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy.

Mucopolysaccharidosis type VI (MPS VI) is due to a deficiency of the lysosomal enzyme arylsulfatase B (ARSB) that results in multi-organ accumulation of glycosaminoglycans (GAGs). Limitations of current treatments prompted the development of a liver-directed gene therapy clinical trial for MPS VI. We report the long-term follow-up of patients with MPS VI who discontinued enzyme replacement therapy (ERT) and received a single intravenous infusion of high-dose (6×1012 genome copies/kg) recombinant adeno-associated virus serotype 8 (AAV8) vector expressing ARSB under the control of a liver-specific promoter (ClinicalTrials.gov: NCT03173521). Primary outcomes were safety and urinary GAG excretion. Secondary outcomes were endurance and respiratory function. Median follow-up time was 45months (n= 4, three females and one male; age range: 5-10 years). No late-emergent safety events were observed. Patients showed sustained serum ARSB activity (38%-67% of mean healthy reference values), a modest increase in urinary GAG concentrations, and no relevant changes in endurance, cardiac, or pulmonary function. In one of the four patients, ERT was restarted because of elevated urinary GAGs without decreased serum ARSB activity up to about 2.5 years after gene transfer. Liver and spleen size remained within the reference ranges. A single intravenous administration of AAV8.TBG.hARSB was safe and resulted in sustained ARSB expression and a modest increase in urinary GAGs in most patients, thus supporting liver-directed gene therapy for MPS VI. This study was sponsored by the Telethon Foundation ETS, the European Union, the Isaac Foundation, and the Italian Ministry of University and Research.

Abstract 4135443: A Phase 1, Single Ascending Dose Study to Evaluate ALN-TTRsc04, a Next-Generation RNA Interference Therapeutic, in Healthy Participants for Potential Treatment of Transthyretin Amyloidosis

Introduction: Transthyretin amyloidosis (ATTR) is a progressive, debilitating, fatal disease caused by deposition of misfolded toxic transthyretin (TTR) amyloid fibrils in multiple organs and tissues. Major ATTR manifestations include polyneuropathy and cardiomyopathy. Ongoing amyloid deposition drives rapid progression of ATTR, leading to morbidity and mortality. ALN-TTRsc04 is an investigational small interfering RNA that targets hepatic TTR mRNA to reduce circulating TTR protein levels. Hypothesis: ALN-TTRsc04 rapidly knocks down serum TTR and is well tolerated. Aims: Describe safety, pharmacokinetics, and pharmacodynamics of single ascending ALN-TTRsc04 doses. Methods: This ongoing, Phase 1, randomized, double-blind, placebo-controlled study (NCT05661916) enrolled healthy adults (18–65 yrs; 18.0–30 kg/m 2 ) sequentially included in 6 cohorts receiving subcutaneous single ascending doses of ALN-TTRsc04 (5, 25, 100, 300, 600, or 900 mg) or placebo (randomized 3:1). Urine and plasma concentrations were measured on Days 1–2 and 1–4, respectively; change from baseline (BL) in serum TTR and AEs will be assessed over 12 months. Results: Overall, 36 and 12 adults (of similar age/sex distribution) were randomized to 1 of the 6 ALN-TTRsc04 groups or placebo, respectively. ALN-TTRsc04 plasma concentrations declined below lower limit of quantification within 24–48 hrs; mean (SD) plasma half-life ranged from 4.5 (1.5) hrs (300 mg dose) to 7.6 (3.2) hrs (100 mg dose). ALN-TTRsc04 was minimally excreted by renal route (&lt;20%) after 24 hrs. Rapid and sustained knockdown in serum TTR occurred following all ALN-TTRsc04 doses ( Figure ). Mean (SD) serum TTR was 236.2 (47.4) µg/mL and 290.1 (73.3) µg/mL at BL and 22.2 (1.8) µg/mL and 289.0 (59.1) µg/mL at Day 15, for ALN-TTRsc04 300 mg and placebo, respectively. Mean percent knockdown at Day 15 was 90.3% vs 1.8%, respectively. Robust mean serum TTR knockdown of &gt;90% from BL was seen with ALN-TTRsc04 doses ≥300 mg at Day 29 and sustained until Day 90 (or Day 180 with 300 mg dose, 92.6% reduction). Majority of AEs across doses were mild; none were considered related to treatment. No injection-site reactions or safety signals, including liver-related signals, were identified. Conclusion: A single ALN-TTRsc04 dose led to a rapid and sustained knockdown in serum TTR; a reduction &gt;90% from BL was sustained until Day 180 with the 300 mg dose. All ALN-TTRsc04 doses have been well tolerated to date; data through 12 months will be assessed.

Effect of desmopressin on water and solute circadian rhythms in treatment-naïve children with monosymptomatic enuresis and nocturnal polyuria.

Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors. Solute handling and osmotic excretion have been studied in refractory patients. Nevertheless, data on the effect of desmopressin on these factors are sparse. We conducted a post hoc analysis of the SLEEP study. We analyzed the circadian rhythm of solute and water excretion before and after desmopressin in 30 children with monosymptomatic enuresis and nocturnal diuresis > 100% of expected bladder capacity by means of a 24-h urine concentration profile (four daytime and four nighttime urine portions at equivalent time intervals). Under desmopressin, nocturnal diuresis (rate) and Na/creatinine ratio were significantly lower compared to day values (p = 0.009, p = 0.021, respectively). Osmolality, Na/creatinine, and osmotic excretion showed a significant day vs. night variance only after desmopressin. Nighttime osmotic and sodium excretion were significantly lower (p = 0.004, p = 0.019, respectively) under treatment, indicating the impact of desmopressin on kidney sodium handling. During desmopressin treatment, nocturnal diuresis (rate) showed strong positive correlation with nighttime Na/creatinine (r = 0.436, p < 0.05) and very strongly with nighttime osmotic excretion (r = 0.875, p < 0.0001). However, no correlation was observed with osmolality under desmopressin treatment. The anti-enuretic and antidiuretic effects of desmopressin therapy are not only related to urinary concentration and nocturnal diuresis but also to the amelioration of circadian rhythms of sodium and solute handling.

Association between selenium biomarkers and insulin resistance in women with obesity: A case-control study.

Although literature demonstrates controversial results regarding the association between selenium and glucose metabolism, no studies have specifically targeted a population with obesity even though this group is vulnerable to insulin resistance. To evaluate the association between selenium biomarkers and insulin resistance in women with obesity. This case-control study recruited 84 women with obesity and 129 with healthy weight (control). Selenium intake was assessed by 3-day food record. Selenium concentration in plasma, erythrocyte, and urine was assessed by inductively coupled plasma optical emission spectrometry. Serum glucose, insulin, and glycated hemoglobin (HbA1c) were assessed in a fasting blood sample. Homeostasis Model Assessment of Beta Cell Function (HOMA-β) and Homeostasis Model Assessment of Insulin Resistance were calculated according to standard methods. Women with obesity had higher dietary selenium intake in comparison to the control group (p < 0.001). Further, the plasma and erythrocyte concentrations were lower in individuals with obesity (p < 0.001), while selenium in urine was higher (p < 0.001) than in controls. No significant differences in insulin resistance markers were observed between groups. Selenium intake was positively associated with HOMA-β in both groups. In women with obesity, selenium intake was also positively associated with insulin and HbA1c, while in the controls the clearance of selenium was negatively associated with insulin and HbA1c. There was a positive correlation between dietary selenium intake, fasting insulin, HbA1c, and HOMA-β (p < 0.05). Women with obesity present impaired selenium metabolism. Further, we observed an association between dietary selenium and markers of insulin resistance, which may reflect the possible negative action of selenium on insulin signaling.

Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration.

Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulation (MCS). With IH salbutamol, the maximum plasma concentration was 0.12 ± 0.06 ng/mL at 0.29 ± 0.17 h after administration. Typical values were, for clearance, 1.53 L/kg/h; distribution volume at steady state, 5.43 L/kg; terminal half-life, 6.06 h; IH bioavailability, 19.0%; and urine to plasma ratio, 2057. Statistically estimated 95th percentile detection times in the urine at levels below the international screening limit (0.5 ng/mL) proposed by the International Federation of Horseracing Authorities, as simulated in 5000 horses by MCS, were 44 h after 1.6 μg/kg q 24 and 54 h after 1.6 μg/kg q 4 h over a 3-day IH administration period.

Analysis of risk factors for autoimmune thyroid disease based on blood indicators and urinary iodine concentrations

ObjectiveThe aim of this study was to elucidate the relationships between thyroid hormones, lifestyle factors, biochemical markers, and autoimmune thyroid disease (AITD), thereby identifying the factors influencing the development of these diseases.MethodsThe study encompassed 517 patients with AITD and 549 patients with non-autoimmune thyroid disease. Demographic and clinical data were collected, and various laboratory indicators, including urinary iodine and thyroid hormones, were measured and compared between the groups. Lasso regression was employed to select the independent variables, while logistic regression analysis determined the factors associated with the development of AITD.ResultsThe prevalence of drinking alcohol history, median urinary iodine, and TSH concentrations proved significantly greater in the AITD group compared to the control group, while FT3 levels demonstrated lower values within the AITD group (p&amp;lt;0.05). Furthermore, there was a significant difference in the distribution of iodine nutrition status between the two groups (p&amp;lt;0.05). Both univariate and multivariate logistic regression analyses revealed significant associations among excessive iodine intake, drinking alcohol history, TSH, FT3, and the development of AITD.ConclusionsExcessive iodine intake and drinking alcohol history are implicated in an augmented risk of developing AITD. The prevention of AITD may necessitate the regular monitoring of TSH and FT3 concentrations.

Antibiotic exposure and risk of overweight/obesity in children: a biomonitoring-based study from eastern Jiangsu, China

ObjectiveTo describe antibiotic exposure in children and explore its association with overweight/obesity.MethodsIn June 2022, 328 kindergarten and primary school children were selected from Nantong city in Jiangsu Province. Questionnaires were distributed, and morning urine samples were obtained. Total urinary concentrations of 41 antibiotics were measured using ultra-performance liquid chromatography and tandem mass spectrometry. The rates of antibiotic exposure were expressed as percentages (%), specific percentiles (P95 and P99), and the maximum values were used to describe the concentration of antibiotics. The association between urinary antibiotic creatinine-adjusted and overweight/obesity was analyzed using logistic regression.ResultsA total of 328 children were initially recruited, of which 295 aged 3–8 years met the inclusion criteria and were finally included in the study. The biomonitoring results revealed that 35 antibiotics were detected, with a total detection frequency of 98.31%. Among the included children, 24.75% were classified as overweight/obesity. Multinomial logistic regression analyses revealed significant associations between overweight/obese and exposure to veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs). After adjusting for various overweight/obesity-relevant variables, higher exposure to sulfamethoxazole [OR = 2.35, 95% confidence interval (CI):1.17–4.70], norfloxacin (OR = 2.66, 95% CI: 1.01–7.08), and fluoroquinolones (OR = 1.97, 95% CI: 1.02–3.78) were significantly associated with overweight/obesity (p &amp;lt; 0.05). In addition, after stratification by sex and adjustment for confounding variables, sex-specific differences were observed in the association between antibiotic exposure and overweight/obesity. Notably, these associations were predominantly observed among boys.ConclusionChildren were extensively exposed to antibiotics. Exposure to certain types of veterinary antibiotics and preferred veterinary antibiotic exposure, mainly through food or drinking water, are associated with an increased risk of overweight/obesity in children.

Use of biomarkers of metals to improve prediction performance of cardiovascular disease mortality

BackgroundWhether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods.MethodsOur sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods.Results420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p < 0.005) with CVD mortality. Including these blood metals in a Cox model, initially containing only traditional risk factors, raised the C-index from 0.845 to 0.847. Additionally, the Net Reclassification Index showed that 23% of participants received a more accurate risk prediction. Further inclusion of urinary metals improved risk reclassification but not risk discrimination.ConclusionsIncorporating blood metals slightly improved CVD mortality risk discrimination, while blood and urinary metals enhanced risk reclassification, highlighting their potential utility in improving cardiovascular risk assessments.

β-Hydroxy β-Methyl Butyric Acid (HMB) and Its Potential Doping Relevance: A Pilot Study on Its Urinary Excretion Profile.

β-hydroxy β-methyl butyric acid (HMB), either as the free acid or in the form of its calcium salt, is a component of several dietary supplements marketed to enhance sports performance, due to its role in protein synthesis. In this pilot study, we investigated the urinary excretion profile of HMB, an endogenous metabolite of the essential amino acid leucine. The endogenous reference ranges of HMB, in human urine samples, were monitored by collecting samples from 20 volunteers. Data obtained were compared with those from controlled excretion studies, following the intake of a 3-g oral dose of HMB. Urine samples were analyzed through a targeted procedure employing a conventional GC-MS system operating in SIM mode. Our results show that the excreted urinary concentration of HMB significantly exceeds the range of endogenous concentrations for at least 24 h, making possible to detect its exogenous origin.

Machine learning model for age-related macular degeneration based on heavy metals: The National Health and Nutrition Examination Survey 2005 to 2008

Age-related macular degeneration (AMD) is the leading cause of blindness in older people in developed countries. It has been suggested that heavy metal exposure may be associated with the development of AMD, but most studies have focused on the effects of a single metal with traditional methods. In this study, we analyzed the relationship between 13 urinary heavy metal concentrations and AMD using NHANES data between 2005 and 2008. We constructed and compared 11 machine learning models to identify the best model for predicting AMD risk. We further interpreted the models by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis. 216 AMD patients out of 2380 participants. The random forest (RF) model performed optimally in predicting the risk of AMD, with an AUC value of 0.970. PFI analyses revealed that age and urinary cadmium (Cd) were the main factors influencing the risk of AMD. SHAP analyses further confirmed the significance of Cd concentration in predicting the risk of AMD, and we revealed a significant interaction with significant interaction of race. Our study firstly explored the relationship between heavy metal exposure levels and AMD based on machine learning techniques, found that urinary Cd concentration had the greatest impact on AMD, and revealed the superior predictive performance of machine learning methods. Furthermore, our study provided a new perspective for early screening and intervention of AMD.

Associations of maternal urinary nitrophenol concentrations with adverse birth outcomes and neurodevelopment delay at 4 years of age: The Japan environment and children's study

Maternal urinary nitrophenol concentrations are reportedly associated with preterm birth and foetal/offspring development delay, but the evidence is still inconclusive. We investigated the association between maternal urinary concentrations of 4-nitrophenol (4NP) and 3-methyl-4-nitrophenol (3M4NP) and adverse birth outcomes, as well as offspring neurodevelopment delay, defined using the Ages and Stages Questionnaires at 4 years of age, stratified by offspring sex. A total of 3650 non-hypertensive mothers with singleton births were enrolled from the Japan Environment and Children's Study. High 4NP (≥0.41 μg/L) and 3M4NP (≥0.29 μg/L) were defined as ≥ lowest concentration minimum reporting level. Four groups were created using these dichotomized 4NP and 3M4NP concentrations: ‘both low’, ‘either high/low’, and ‘both high’. Multivariable logistic regression models were used to estimate the adjusted odds ratios (aOR) and population attributable fraction (PAF). For 4NP and 3M4NP, 68.4% and 19.0% of participants had ’high’ urinary concentrations, respectively. Compared to ‘both low’, the overall analysis showed no significant associations between ‘both high’ and any of the outcomes. However, the stratified analysis showed that the aOR (95% confidence interval [CI]) and PAF (95% CI) for ‘both high’ regarding preterm birth (<37 weeks' gestation) were 2.7 (1.3, 5.7) and 16.3% (2.5%, 28.1%), respectively, in male offspring. Among female offspring, the aOR and PAF for the ‘both high’ regarding small-for-gestational-age (SGA)—defined as weight-for-gestational age <10 percentile based on the Japanese neonatal anthropometric charts—were 1.7 (1.0, 2.8) and 10.6% (−0.2%, 20.2%), respectively. Urinary 4NP and 3M4NP concentrations showed no association with low birth weight (<2500 g) and neurodevelopment delay.In conclusion, offspring sex-specific associations of maternal urinary nitrophenols with preterm birth and SGA were observed. Even slight elevations in their levels may explain a certain proportion of preterm birth and SGA. The exposure source, expressed by urinary nitrophenols, should be identified.

Cross-sectional study on urinary metal concentrations in young adult residents of Emirate of Sharjah, United Arab Emirates.

Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits. A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation. Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels. This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE.

Copper Oxide Nanoparticles Impair Mouse Preimplantation Embryonic Development through Disruption of Mitophagy-Mediated Metabolism.

Copper oxide nanoparticles (CuONPs) have been widely applied, posing potential risks to human health. Although the toxicity of CuONPs on the liver and spleen has been reported, their effects on reproductive health remain unexplored. In this study, we investigate the effects of CuONPs on embryonic development and their potential mechanisms. Our results demonstrate that CuONPs exposure impairs mouse preimplantation embryonic development, particularly affecting the morula-to-blastocyst transition. Additionally, CuONPs were found to reduce the pluripotency of the inner cell mass (ICM) and mouse embryonic stem cells (mESCs). Mechanistically, CuONPs block autophagic flux and impair mitophagy, leading to the accumulation of damaged mitochondria. This mitochondrial dysfunction leads to reduced tricarboxylic acid (TCA) cycle activity and decreased α-ketoglutarate (α-KG) production. Insufficient α-KG induces the failure of DNA demethylation, reducing corresponding chromatin accessibility and consequently inhibiting ICM-specific genes expressions. Similar reduced development and inhibitions of pluripotency gene expression were observed in CuONPs-treated human blastocysts. Moreover, in women undergoing assisted reproductive technology (ART), a negative correlation was found between urinary Cu ion concentrations and clinical outcomes. Collectively, our study elucidates the mitophagy-mediated metabolic mechanisms of CuONPs embryotoxicity, improving our understanding of the potential reproductive toxicity associated with it.

Association between urinary cotinine level and hypertensive disorders of pregnancy in women with uterine myoma: findings from the Japan Environment and Children's Study.

The effect of smoking on hypertensive disorders of pregnancy is a public concern. Recent evidence suggests that the risk of hypertensive disorders of pregnancy is influenced by the presence of uterine fibroids. We explored the association between maternal smoking exposure and the risk of hypertensive disorders of pregnancy in relation to the presence of uterine fibroids using data from Japan's largest birth cohort study. This study focused on first-time mothers, and the study population comprised 2752 and 35,294 first-time mothers with and without uterine fibroids, respectively. Hypertensive disorders of pregnancy was categorized as early-onset (before 34 weeks) and late-onset (after 34 weeks). Maternal smoking exposure was assessed by measuring the urinary cotinine concentration during the mid-trimester. Participants were classified into four quartiles based on their urinary cotinine levels as follows: Q1 (low concentration) to Q4 (high concentration). Multivariate analysis adjusted for potential confounders revealed that in women without uterine fibroids, the Q3 urinary cotinine level was associated with a modified risk of early-onset hypertensive disorders of pregnancy (adjusted odds ratio: 0.63, 95% confidence interval: 0.44-0.89). Conversely, for women with uterine fibroids, Q4 urinary cotinine level was associated with an increased risk of hypertensive disorders of pregnancy (adjusted odds ratio: 1.68, 95% confidence interval: 1.05-2.72). In conclusion, this study indicated that the impact of maternal smoking exposure varied based on the presence of uterine fibroids, underscoring the importance of personalized preconception care.

Эффективность алгоритма назначения диуретической терапии под контролем натрийуреза у пациентов с острой декомпенсацией сердечной недостаточности в отделении реанимации и интенсивной терапии: проспективное интервенционное контролируемое исследование

INTRODUCTION: The European Society of Cardiology suggests using early and repeated assessment of sodium content in urine in patients admitted with heart failure to evaluate diuretic therapy. OBJECTIVES: Evaluation of the effectiveness of the algorithm for diuretic therapy under the control of natriuresis in patients with acute decompensation of chronic heart failure (ADCHF) in the intensive care unit (ICU). MATERIALS AND METHODS: A prospective study included 150 patients hospitalized in the ICU with ADCHF. All patients underwent standard physical, laboratory and instrumental examinations. The starting dose of furosemide was 20 mg i/v. After 2 hours, a quantitative assessment of sodium in urine was performed. If the natriuresis was ≥ 70 mmol/l, furosemide was continued at the same dose every 12 hours. If the natriuresis was &lt; 70 mmol/L, the dose of furosemide was doubled. Natriuresis was monitored every 12 hours. RESULTS: In the natriuresis-controlled group the duration of patients' stay in the ICU was significantly shorter (3 vs. 5 days, p = 0.01), achieving euvolemia was significantly more frequent (42 % vs. 12 %, p &lt; 0.05), the daily diuresis in patients was significantly higher on more daily (120 mg vs. 80 mg, p &lt; 0.05) and the total dose of furosemide (420 mg vs. 240 mg, p &lt; 0.05). There was a pronounced decrease in congestion in the group of patients with natriuresis control with less pulmonary (number of B-lines 9.6 ± 1.2 versus 23.4 ± 2.5) and venous congestion (GRADE 0–56 %, 1–20 %, 2–24 %, 3–0 % against 0–20 %, 1–35 %, 2–18 %, 3–27 %) on the 3rd day of hospitalization. CONCLUSION: The inclusion of an algorithm for diuretic therapy under the control of natriuresis in patients with ADCHF in the ICU is effective and contributes to a more pronounced and rapid reduction of congestion, as well as a 1.5-fold reduction of time in the ICU.