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23 pages, 2179 KB  
Article
Semi-Quantitative ΔCt Thresholds for Bacteriuria and Pre-Analytic Drivers of PCR-Culture Discordance in Complicated UTI: An Analysis of NCT06996301
by Moustafa Kardjadj, Itoe P. Priestly, Roel Chavez, DeAndre Derrick and Thomas K. Huard
Diagnostics 2025, 15(23), 2959; https://doi.org/10.3390/diagnostics15232959 - 21 Nov 2025
Cited by 1 | Viewed by 508
Abstract
Background: Quantitative urine culture (CFU/mL) remains the reference standard for diagnosing urinary tract infections (UTIs) but is limited by delayed turnaround times and sensitivity to pre-analytic factors. Multiplex PCR panels offer rapid detection; however, standardized mappings between molecular signals and viable bacterial [...] Read more.
Background: Quantitative urine culture (CFU/mL) remains the reference standard for diagnosing urinary tract infections (UTIs) but is limited by delayed turnaround times and sensitivity to pre-analytic factors. Multiplex PCR panels offer rapid detection; however, standardized mappings between molecular signals and viable bacterial burdens are insufficiently defined. We used the multicenter NCT06996301 paired dataset to evaluate the analytical validity (AV), clinical validity (CV), and pre-analytic robustness of ΔCt (Ct_target − IC_Ct) as a semi-quantitative indicator of bacterial load. Methods: We analyzed 1027 paired PCR and quantitative urine culture specimens from six sites. The primary molecular predictor was ΔCt (Ct_target − IC_Ct). Species-level Spearman and Pearson correlations, species-specific linear mixed-effects calibration models (log10CFU ~ ΔCt + (1|site)), and ROC analyses were performed for the taxa meeting pre-specified sample thresholds. A pooled multilevel model assessed the collection method and time-to-processing (hours) effects (log10CFU ~ ΔCt × collection_method + ΔCt × time_to_processing_h + (1|site) + (1|run)). AV was assessed via reproducibility, internal control normalization, and site run variance. CV was assessed by ΔCt calibration and discrimination. Clinical utility (CU) was contextualized using outcomes from the parent randomized trial. Results: PCR positivity exceeded culture positivity across all sites (PCR ~82–88% vs. culture ~66–70%); this excess likely reflects a combination of molecular detection of non-viable DNA, detection of fastidious taxa less readily recovered by culture, and pre-analytic effects. For six common uropathogens (n = 90 pairs/species), ΔCt correlated strongly with log10CFU (Spearman ρ = −0.64 to −0.75; Pearson r = −0.75 to −0.83). Species-specific mixed models yielded slopes of −0.746 to −0.922 log10CFU per ΔCt unit (all p < 0.001), indicating that each 1 unit ΔCt change corresponds to a ~5.6–8.4-fold CFU difference. ROC AUCs for ΔCt discrimination were 0.78–0.84 (interpreted as good discrimination, i.e., ΔCt meaningfully improves the clinician’s probability estimate of a high CFU but does not perfectly classify every specimen). The collection method (catheter vs. clean-catch) did not materially modify the ΔCt→CFU relationship, whereas the processing delay was associated with reduced recovered CFU (~0.048 log10CFU lost per hour) and a significant ΔCt × time interaction, consistent with time-dependent viability loss driving the PCR+/culture discordance. Conclusions: ΔCt from the DOC Lab UTM 2.0 panel shows a reproducible, analytically valid semi-quantitative measure of urinary bacterial load. Laboratories can derive assay- and workflow-specific ΔCt cut points for semi-quantitative reporting, but thresholds must be validated prospectively and paired with operational controls for specimen handling. Full article
(This article belongs to the Special Issue Advances in the Laboratory Diagnosis)
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20 pages, 661 KB  
Article
Work as a Predictor of Ethylenethiourea (ETU) Exposure During Pregnancy Among Participants Enrolled in the SEMILLA Birth Cohort Study
by Alexis J. Handal, Fadya Orozco, Stephanie Montenegro, Nataly Cadena, Fabián Muñoz, Eileen Ramírez del Rio and Niko Kaciroti
Toxics 2025, 13(11), 988; https://doi.org/10.3390/toxics13110988 - 17 Nov 2025
Viewed by 556
Abstract
Background: Ethylenebisdithiocarbamates, widely used in floriculture, degrade into ethylenethiourea (ETU), a teratogen. The SEMILLA study investigates prenatal ETU exposure and infant health in Ecuador’s flower-growing region. This analysis examines whether prenatal ETU metabolite levels differ by work sector and whether maternal urinary ETU [...] Read more.
Background: Ethylenebisdithiocarbamates, widely used in floriculture, degrade into ethylenethiourea (ETU), a teratogen. The SEMILLA study investigates prenatal ETU exposure and infant health in Ecuador’s flower-growing region. This analysis examines whether prenatal ETU metabolite levels differ by work sector and whether maternal urinary ETU increases with longer work hours. Methods: Participants (agricultural workers, non-agricultural workers, and non-workers) provided baseline urine samples, which were processed and stored for ETU analysis. Surveys captured ETU exposure predictors. Regression models assessed associations between work sector, weekly work hours, and urinary ETU levels (specific gravity-corrected), controlling for key covariates. Results: The sample includes 111 agricultural workers (92% floriculture), 149 non-agricultural workers, and 149 non-workers. At baseline, maternal age averaged 27 years (SD = 5.8) and gestational age 15 weeks (SD = 3.2). Urinary ETUSG levels were elevated across the sample (geometric mean: 3.38 µg/L). Agricultural workers had significantly higher ETUSG levels than others (5.61 vs. 3.07 and 2.57 µg/L; p < 0.001). Among agricultural workers, ETUSG levels increased with weekly hours (B = 0.288, p = 0.001). Conclusions: Agricultural work strongly predicts higher prenatal ETU exposure, with evidence of a dose–response relationship. Research on prenatal fungicide exposure and infant health among pregnant workers is limited. Findings highlight the need for targeted interventions to protect pregnant workers and infant health. Full article
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20 pages, 2357 KB  
Article
Betaine Supplementation Improves 60 km Cycling Time Trial Performance and One-Carbon Metabolism in Cyclists During Recovery
by David C. Nieman, Camila A. Sakaguchi, James C. Williams, Jackie Lawson and Kevin C. Lambirth
Nutrients 2025, 17(17), 2765; https://doi.org/10.3390/nu17172765 - 26 Aug 2025
Viewed by 3728
Abstract
Background/Objectives: This study examined the effects of 2 weeks of betaine versus placebo supplementation (3 g/d) on 60 km cycling performance, gut permeability, and shifts in plasma metabolites. Methods: Participants included 21 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind, crossover design [...] Read more.
Background/Objectives: This study examined the effects of 2 weeks of betaine versus placebo supplementation (3 g/d) on 60 km cycling performance, gut permeability, and shifts in plasma metabolites. Methods: Participants included 21 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 60 km cycling time trial. Six blood samples were collected before and after supplementation (overnight fasted state), and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Five-hour urine samples were collected pre-supplementation and post-60 km cycling after ingesting a sugar solution containing lactulose 5 g, 13C mannitol 100 mg, and 12C mannitol 1.9 g in 450 mL water. Other outcome measures included plasma intestinal fatty acid binding protein-1 (I-FABP), muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: The time to complete the 60 km cycling bout differed significantly between the betaine and placebo trials (mean ± SE, 112.8 ± 2.3, 114.2 ± 2.6 min, respectively, (−1.41 ± 0.7 min) (effect size = 0.475, p = 0.042). No trial differences were found for I-FABP (interaction effect, p = 0.076), L:13CM (p = 0.559), the neutrophil/lymphocyte ratio (p = 0.171), serum cortisol (p = 0.982), serum myoglobin (p = 0.942), or serum creatine kinase (p = 0.694). Untargeted metabolomics showed that 214 metabolites exhibited significant trial treatment effects and 130 significant trial x time interaction effects. Betaine versus placebo supplementation was linked to significant increases in plasma betaine, dimethylglycine (DMG), sarcosine, methionine, S-adenosylhomocysteine (SAH), alpha-ketoglutaramate, and 5′methylthioadensone (MTA), and decreases in plasma carnitine and numerous acylcarnitines. Conclusions: Betaine supplementation modestly improved 60 km cycling performance but had no effect on gut permeability. The metabolomics data supported a strong influence of 2-week intake of betaine on the one-carbon metabolism pathway during the 24 h recovery period. Full article
(This article belongs to the Section Sports Nutrition)
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16 pages, 1942 KB  
Article
Relationship of Melatonin Levels in Blood and Urine with Sleep Quality in Children Admitted to Pediatric Intensive Care Unit
by Miriam García-San Prudencio, Gema Manrique, Raquel Cieza, Cristina Corraliza, Patricia Arias, Elena Medina, Jesús López-Herce and Santiago Mencía
Children 2025, 12(8), 1074; https://doi.org/10.3390/children12081074 - 15 Aug 2025
Viewed by 1978
Abstract
Objectives: Melatonin regulates the sleep–wake cycle, which may be altered in children admitted to the pediatric intensive care unit (PICU). The aim is to analyze whether blood and urine melatonin levels are related to sleep quality in children admitted to the PICU. Methods: [...] Read more.
Objectives: Melatonin regulates the sleep–wake cycle, which may be altered in children admitted to the pediatric intensive care unit (PICU). The aim is to analyze whether blood and urine melatonin levels are related to sleep quality in children admitted to the PICU. Methods: A single-center, prospective observational study was conducted at the PICU in a tertiary referral center in Madrid, Spain. It included patients (1 month–16 years) admitted to the PICU. Results: A total of 40 children were included in the study (52.5% male), analyzing 2 days for each patient (80 total study days). The median age of the patients was 34.5 months. The median number of hours of sleep over the whole day was 9.9 h (IQR 8.4–12.6); nighttime was 7.5 h (IQR 6.5–9) and daytime was 2.5 h (IQR 1.4–5.7). Only 8.5% of patients slept the appropriate number of hours of nighttime sleep for their age. High serum melatonin levels in the morning were correlated with more nocturnal awakenings (r = 0.35, p = 0.01) and less continuous sleep time (r = −0.29, p = 0.03). Altered urine levels in the morning correlated with shorter 24 h total sleep time (r = −0.43, p = 0.01). Inadequate urine levels at 7 pm correlated with a shorter duration of continuous nocturnal sleep (r = −0.37, p = 0.03). Conclusions: Children admitted to the PICU often do not achieve the recommended hours of sleep for their age. A significant percentage of these children exhibit an altered melatonin secretion pattern, which is associated with shorter nighttime sleep duration and longer daytime sleep duration. Full article
(This article belongs to the Section Pediatric Emergency Medicine & Intensive Care Medicine)
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21 pages, 3409 KB  
Article
Mapping the AMR Infection Landscape in Bihar: Implications for Strengthening Policy and Clinical Practice
by Vinay Modgil, Sundeep Sahay, Neelam Taneja, Burhanuddin Qayyumi, Ravikant Singh, Arunima Mukherjee, Bibekananda Bhoi and Gitika Arora
Antibiotics 2025, 14(7), 684; https://doi.org/10.3390/antibiotics14070684 - 5 Jul 2025
Cited by 2 | Viewed by 2457
Abstract
Background: Antimicrobial resistance (AMR) poses a significant threat to public health, especially in low- and middle-income countries (LMICs), where surveillance infrastructure is underdeveloped. Bihar, India’s third most populous state and one of its least-resourced states, has remained largely absent from national AMR monitoring [...] Read more.
Background: Antimicrobial resistance (AMR) poses a significant threat to public health, especially in low- and middle-income countries (LMICs), where surveillance infrastructure is underdeveloped. Bihar, India’s third most populous state and one of its least-resourced states, has remained largely absent from national AMR monitoring initiatives. Methods: This study aimed to characterize the AMR infection landscape across five public tertiary care hospitals in Bihar over three years (2022–2024) and to assess the feasibility of integrating digital workflows for real-time microbiological reporting. Standardized antimicrobial susceptibility testing (AST) was performed on >48,000 urine, pus, and blood samples using CLSI guidelines. Facility-level data were digitized into an open-source AMR reporting system, enabling automated antibiogram generation. Results: The findings revealed substantial resistance: high resistance to beta-lactams, carbapenems, and fluoroquinolones across pathogens. For instance, E. coli sensitivity to nitrofurantoin varied from 86.5% at NMCH (Patna) to 44.7% at JLNMCH (Bhagalpur), while cephalosporin sensitivity in Klebsiella spp. dropped below 2% in several hospitals. MRSA prevalence exceeded 65% in two facilities, far above the national average of 47.8%. Digital integration led to a four-fold increase in culture testing in all facilities and improved data completeness and turnaround times. Spatial analysis and microbiology laboratory assessment revealed significant geographic disparities in diagnostic access, with facilities in remote districts facing delays of over four hours for basic testing. Conclusions: Our study is the first study from India to create such a broad, facility-associated AMR picture over time at a state level. Policy implications include the need for a state-level AMR surveillance dashboard, alignment of procurement with facility-specific resistance patterns, and routine stewardship audits. Clinically, this study demonstrates the utility of localized antibiograms for guiding empirical therapy in resource-limited settings. This study provides a scalable framework for embedding AMR surveillance into routine health system workflows in LMICs. Full article
(This article belongs to the Special Issue Antibiotic Stewardship Implementation Strategies)
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10 pages, 228 KB  
Article
Dipstick Proteinuria and Hematuria as Triggers for Manual Microscopic Review in Nephrology Patients
by Priscila Aparecida Correa Freitas, Yasmini Dandara Silva da Silva, José Antonio Tesser Poloni, Francisco José Veríssimo Veronese and Luiz Felipe Santos Gonçalves
J. Clin. Med. 2025, 14(13), 4522; https://doi.org/10.3390/jcm14134522 - 26 Jun 2025
Viewed by 1879
Abstract
Background/Objectives: Automation improves efficiency in laboratory workflow but may fail to detect clinically relevant abnormalities in patients with nephropathy. This study aimed to identify dipstick parameters associated with nephropathy-related sediment findings and to propose practical criteria to guide manual microscopy review based on [...] Read more.
Background/Objectives: Automation improves efficiency in laboratory workflow but may fail to detect clinically relevant abnormalities in patients with nephropathy. This study aimed to identify dipstick parameters associated with nephropathy-related sediment findings and to propose practical criteria to guide manual microscopy review based on these associations. Methods: Urine samples from in- and outpatients, primarily from the nephrology unit, were collected at a university hospital from July 2022 to September 2023. Samples were analyzed within two hours using LabUMat 2 and UriSed 3 analyzers. Manual microscopy was performed on all specimens by two experienced technicians. Sediments were classified as suggestive or not of nephropathy based on hematuria with dysmorphism, hyaline and pathological casts, lipiduria, or renal tubular epithelial cells. Results: Of 503 samples, 146 (29%) showed sediment findings indicative of nephropathy, which were significantly associated with dipstick positivity for protein and blood. Among nephropathy samples, 71.2% had protein ≥1+ or blood ≥2+. Using this combination as a criterion for manual sediment review yielded a sensitivity of 71.2%, a specificity of 73.9%, and a 3.84-fold increased relative risk of detecting nephropathy-related elements (p < 0.001). The criteria performed best among nephrology outpatients, with sensitivity of 79.5%, specificity of 63.9%, and relative risk of 3.91 (p < 0.001). Conclusions: Dipstick protein ≥1+ or blood ≥2+ helps identify patients who may benefit from manual sediment review, supporting diagnostic accuracy in nephropathy. Each institution should define its criteria based on patient profile, analytical methods, and workflow. Full article
23 pages, 5667 KB  
Article
Effects of Pork Protein Ingestion Prior to and Following Performing the Army Combat Fitness Test on Markers of Catabolism, Inflammation, and Recovery
by Drew E. Gonzalez, Kelly E. Hines, Ryan J. Sowinski, Landry Estes, Sarah E. Johnson, Jisun Chun, Hudson Lee, Sheyla Leon, Adriana Gil, Joungbo Ko, Jacob Broeckel, Nicholas D. Barringer, Christopher J. Rasmussen and Richard B. Kreider
Nutrients 2025, 17(12), 1995; https://doi.org/10.3390/nu17121995 - 13 Jun 2025
Viewed by 6638
Abstract
Tactical athletes and military personnel engaged in intense exercise need to consume enough quality protein in their diet to maintain protein balance and promote recovery. Plant-based protein sources contain fewer essential amino acids (EAAs), while pork loin contains a higher concentration of EAAs [...] Read more.
Tactical athletes and military personnel engaged in intense exercise need to consume enough quality protein in their diet to maintain protein balance and promote recovery. Plant-based protein sources contain fewer essential amino acids (EAAs), while pork loin contains a higher concentration of EAAs and creatine than most other animal protein sources. This study aimed to determine whether the ingestion of plant-based or pork-based military-style meals ready-to-eat (MREs) affects recovery from and subsequent Army Combat Fitness Test (ACFT) performance. Methods: Twenty-three (n = 23) University Corps of Cadets members participated in a randomized, double-blind, placebo-controlled, and crossover-designed study. Diets were prepared by a dietitian, food scientist, and chef to have similar taste, appearance, texture, and macronutrient content. The chef also labeled the meals for double-blind administration. Participants refrained from intense exercise for 48 h before reporting to the lab in a fasted condition with a 24 h urine sample. Participants donated a blood sample, completed questionnaires and cognitive function tests, and consumed a pre-exercise meal. After four hours, participants performed the ACFT according to military standards. Participants were fed three MREs daily while returning to the lab in a fasted condition at 0600 with 24 h urine samples after 24, 48, and 72 h of recovery. On day 3, participants repeated the ACFT four hours after consuming an MRE for breakfast. Participants resumed normal training and returned to the lab after 2–3 weeks to repeat the experiment while consuming the alternate diet. Data were analyzed using general linear model statistics with repeated measures and percent changes from baseline with 95% confidence intervals. Results: Results revealed that 3 days were sufficient for participants to replicate ACFT performance. However, those consuming the pork-based diet experienced less muscle soreness, urinary urea excretion, cortisol, inflammation, and depression scores while experiencing a higher testosterone/cortisol ratio and appetite satisfaction. There was also evidence of more favorable changes in red and white blood cells. Conversely, blood lipid profiles were more favorably changed when following a plant-based diet. Conclusions: These findings suggest that protein quality and the availability of creatine in the diet can affect recovery from intense military-style exercise. Minimally, plant-based MREs should include 6–10 g/d of EAA and 2–3 g/d of creatine monohydrate to offset dietary deficiencies, particularly in military personnel following a vegetarian diet. Registered clinical trial #ISRCTN47322504. Full article
(This article belongs to the Section Nutrition and Metabolism)
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15 pages, 1475 KB  
Article
AI-Driven Prediction of Renal Stone Recurrence Following ECIRS: A Machine Learning Approach to Postoperative Risk Stratification Incorporating 24-Hour Urine Data
by Takahiro Yanase, Rei Unno, Theodoros Tokas, Vineet Gauhar, Yuya Sasaki, Kengo Kawase, Ryosuke Chaya, Shuzo Hamamoto, Mihoko Maruyama, Takahiro Yasui and Kazumi Taguchi
J. Clin. Med. 2025, 14(12), 4037; https://doi.org/10.3390/jcm14124037 - 7 Jun 2025
Cited by 1 | Viewed by 2369
Abstract
Background/Objectives: Predicting kidney stone recurrence after active stone treatment remains challenging due to its multifactorial nature. Artificial intelligence, particularly machine learning, provides new methods for identifying hidden patterns in high-dimensional clinical data. We conducted a study applying machine learning to identify key [...] Read more.
Background/Objectives: Predicting kidney stone recurrence after active stone treatment remains challenging due to its multifactorial nature. Artificial intelligence, particularly machine learning, provides new methods for identifying hidden patterns in high-dimensional clinical data. We conducted a study applying machine learning to identify key predictors of recurrence following endoscopic combined intrarenal surgery (ECIRS) in patients with calcium stones. Methods: This retrospective cohort analysis included 72 patients with calcium stones who underwent ECIRS between June 2019 and May 2022 and achieved a complete stone-free status on postoperative CT. Patients were followed for two years, with recurrence assessed through protocolized imaging. We collected 235 variables, including clinical data, 24 h urine collections, stone composition, imaging features, and perioperative findings. Several machine learning models were developed, and SHapley Additive exPlanations (SHAP) analysis identified features associated with recurrence. Results: Within two years, 29 of 72 patients (40.3%) experienced recurrence. The TabNet model demonstrated the highest predictive accuracy (AUC = 0.89), outperforming traditional machine learning algorithms. SHAP analysis identified urinary oxalate ≥ 25.4 mg/day and hemoglobin (Hb) drop ≥ 0.3 g/dL at 3 months postoperatively as independent predictors, even within normal limits. A simplified TabNet-based model using three key features (oxalate, urine volume, and 3-month ΔHb) maintained a strong performance (AUC = 0.75), supporting its clinical utility. Conclusions: Machine learning enabled the accurate prediction of kidney stone recurrence after ECIRS. The inclusion of 24 h urine data significantly improved the performance. Even patients with “normal” oxalate levels showed increased risk, suggesting current clinical thresholds may require re-evaluation. Full article
(This article belongs to the Special Issue Clinical Advances in Artificial Intelligence in Urology)
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12 pages, 2281 KB  
Article
Short-Term Reactions to Oliguria in Critically Ill Patients: A Retrospective Cohort Study
by Dekel Stavi, Amir Gal Oz, Nimrod Adi, Asaph Nini, Yoel Angel, Andrey Nevo, Daniel Aviram, Itay Moshkovits, Yael Lichter, Ron Wald and Noam Goder
J. Clin. Med. 2025, 14(9), 3107; https://doi.org/10.3390/jcm14093107 - 30 Apr 2025
Cited by 1 | Viewed by 2041
Abstract
Background/Objective: Oliguria is common in critically ill patients and may indicate impaired kidney perfusion or acute injury, contributing to increased mortality. Effective management is essential to improve outcomes. To assess clinician reactions to oliguria and evaluate the effectiveness of fluid bolus and [...] Read more.
Background/Objective: Oliguria is common in critically ill patients and may indicate impaired kidney perfusion or acute injury, contributing to increased mortality. Effective management is essential to improve outcomes. To assess clinician reactions to oliguria and evaluate the effectiveness of fluid bolus and furosemide interventions. Methods: A retrospective cohort study was conducted using ICU data from a single center (2017–2023). Oliguria was defined as two consecutive hours of urine output < 20 mL/h following at least three hours > 20 mL/h. Clinicians’ reactions within four hours were categorized as no intervention, fluid bolus (>250 mL), or furosemide administration. Outcomes included urine output, fluid balance, and serum creatinine. Results: Among 4987 oliguria episodes, 4007 events in 1825 patients were analyzed: no reaction (2536), fluid bolus (923), and furosemide (548). Furosemide significantly increased urine output (53.9 to 75.3 mL/h, p < 0.001), while fluid bolus had no significant effect. Resolution of oliguria (mean urine output > 40 mL/h for 5 h post-intervention) was more frequent with furosemide (66.4%) than with fluid bolus (28.4%) or no reaction (27.6%) (p < 0.001). Treatment choices varied significantly among ICU attendings (p < 0.001). Conclusions: Furosemide was more effective than fluid bolus or no treatment in improving urine output and resolving oliguria. The observed variation in clinician practices underscores the need for standardized management protocols to enhance patient care. Full article
(This article belongs to the Special Issue Acute Kidney Events in Intensive Care Patients)
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18 pages, 2566 KB  
Article
Selective Influence of Hemp Fiber Ingestion on Post-Exercise Gut Permeability: A Metabolomics-Based Analysis
by David C. Nieman, Camila A. Sakaguchi, James C. Williams, Wimal Pathmasiri, Blake R. Rushing, Susan McRitchie and Susan J. Sumner
Nutrients 2025, 17(8), 1384; https://doi.org/10.3390/nu17081384 - 19 Apr 2025
Cited by 1 | Viewed by 1735
Abstract
Objectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive [...] Read more.
Objectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT), with potential gut health benefits. Methods: The study participants included 23 male and female cyclists. A three-arm randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and 2-week washout periods. Supplement bars provided 20, 5, or 0 g/d of hemp hull powder. Participants engaged in an intensive 2.25 h cycling bout at the end of each of the three supplementation periods. Five blood samples were collected before and after supplementation (overnight fasted state), and at 0 h-, 1.5 h-, and 3 h-post-exercise. Five-hour urine samples were collected pre-supplementation and post-2.25 h cycling after ingesting a sugar solution containing 5 g of lactulose, 100 mg of 13C mannitol, and 1.9 g of mannitol in 450 mL of water. An increase in the post-exercise lactulose/13C mannitol ratio (L:13CM) was used as the primary indicator of altered gut permeability. Other outcome measures included muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: No trial differences were found for L:13CM, cortisol, blood cell counts, and muscle damage biomarkers. Orthogonal partial least-squares discriminant analysis (OPLSDA) showed distinct trial differences when comparing high- and low-dose hemp fiber compared to placebo supplementation (R2Y = 0.987 and 0.995, respectively). Variable Importance in Projection (VIP) scores identified several relevant metabolites, including 3-hydroxy-4-methoxybenzoic acid (VIP = 1.9), serotonin (VIP = 1.5), 5-hydroxytryptophan (VIP = 1.4), and 4-methoxycinnamic acid (VIP = 1.4). Mummichog analysis showed significant effects of hemp fiber intake on multiple metabolic pathways, including alpha-linolenic acid, porphyrin, sphingolipid, arginine and proline, tryptophan, and primary bile acid metabolism. Conclusions: Hemp fiber intake during a 2-week supplementation period did not have a significant effect on post-exercise gut permeability in cyclists (2.25 h cycling bout) using urine sugar data. On the contrary, untargeted metabolomics showed that the combination of consuming nutrient-rich hemp fiber bars and exercising for 135 min increased levels of beneficial metabolites, including those derived from the gut in healthy cyclists. Full article
(This article belongs to the Special Issue Sports Nutrition: Current and Novel Insigh (2nd Edition))
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11 pages, 959 KB  
Article
Metabolic Differences in 24-Hour Urine Parameters Between Calcium Oxalate Monohydrate and Dihydrate Kidney Stones: A Clinical Study
by Nariman Gadzhiev, Vitaliy Gelig, Gennadii Rodionov, Vineet Gauhar and Guohua Zeng
Diagnostics 2025, 15(8), 994; https://doi.org/10.3390/diagnostics15080994 - 14 Apr 2025
Cited by 4 | Viewed by 3434
Abstract
Background: Different types of kidney stones are associated with distinct changes in urine chemistry. Methods: We assessed urinary parameters of 98 patients with calcium oxalate (CaOx) stones one month following endoscopic stone removal. The 24 h urine analysis encompassed the assessment of various [...] Read more.
Background: Different types of kidney stones are associated with distinct changes in urine chemistry. Methods: We assessed urinary parameters of 98 patients with calcium oxalate (CaOx) stones one month following endoscopic stone removal. The 24 h urine analysis encompassed the assessment of various parameters, including volume, sodium, chloride, sulfate, nitrate, fluoride, phosphate, calcium, potassium, magnesium, oxalate, uric acid, citrate, creatinine, and pH levels. Results: Hypocitraturia was the most prevalent urinary abnormality (61.2%, n = 63), followed by low urine volume (53%, n = 52) and hypercalciuria (50%, n = 49). We did not find any statistically significant differences between patients with whewellite (COM) (n = 69) and weddellite (COD) stones (n = 29) (p > 0.05). However, oxalate concentration was the only parameter with a statistically significant intergroup difference (p = 0.0297). Additionally, in univariate linear regression analysis, urinary phosphate levels ≥ 48.0 mmol/d showed a trend towards significance (OR 0.17, 95% CI 0.02–1.15, p = 0.0692), indicating that phosphaturia is associated with a significant increase in the odds ratio of COD stones. To further explore metabolic heterogeneity among stone formers, we conducted cluster analysis, which revealed three distinct metabolic subgroups. Cluster 1 was predominantly associated with COM stones (80.5%) and exhibited significantly higher urinary excretion of sodium, calcium, oxalate, phosphate, and uric acid compared to Cluster 2, which had a more balanced distribution of monohydrate and dihydrate stones. Conclusions: These findings suggest that a specific metabolic phenotype may be linked to COM stone formation, providing a framework for risk stratification and personalized prevention strategies in calcium oxalate stone formers. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Urologic Diseases)
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16 pages, 2051 KB  
Article
Oxidative Stress and Antioxidant Status in Pregnant Women with Gestational Diabetes Mellitus and Late-Onset Complication of Pre-Eclampsia
by Kamelia Petkova-Parlapanska, Denitsa Kostadinova-Slavova, Mariya Angelova, Rafaah Sadi J. Al-Dahwi, Ekaterina Georgieva, Petya Goycheva, Yanka Karamalakova and Galina Nikolova
Int. J. Mol. Sci. 2025, 26(8), 3605; https://doi.org/10.3390/ijms26083605 - 11 Apr 2025
Cited by 3 | Viewed by 1653
Abstract
Oxidative stress is a critical factor in the onset of gestational diabetes and its associated complication, pre-eclampsia. This study aimed to evaluate (1) reactive oxygen species, reactive nitrogen species, and superoxide radical levels as indicators of oxidative stress, (2) lipid and protein oxidation, [...] Read more.
Oxidative stress is a critical factor in the onset of gestational diabetes and its associated complication, pre-eclampsia. This study aimed to evaluate (1) reactive oxygen species, reactive nitrogen species, and superoxide radical levels as indicators of oxidative stress, (2) lipid and protein oxidation, (3) antioxidant enzyme activity, and (4) cytokine production in pregnant women with gestational diabetes, as well as those with both gestational diabetes and pre-eclampsia, comparing these with biomarkers of gestational diabetes mellitus. The study categorized pregnant patients with gestational diabetes mellitus into two groups based on the presence of new-onset hypertension, measured twice every four hours, and a 24 h urine protein test showing 300 mg/day or ≥1+ proteinuria detected via a visual dipstick at ≥20 weeks of gestation. These groups were compared with normotensive pregnant patients. The findings revealed that patients with both gestational diabetes and pre-eclampsia exhibited significantly elevated levels of reactive oxygen species, cytokine production, and lipid and protein oxidation end products compared to normotensive pregnant women. Additionally, these patients showed reduced nitric oxide (•NO) levels, impaired NO synthase systems (eNOS and iNOS), and decreased antioxidant enzyme activities (p < 0.05). These results indicate that patients with gestational diabetes and pre-eclampsia are unable to counteract oxidative stress effectively. The study underscores the compromised oxidative status as a contributing factor to these complications. The findings provide insights into the pathogenesis of gestational diabetes and the subsequent pre-eclampsia, the role of oxidative stress, and the resulting complications. Measuring oxidative stress levels and inflammatory biomarkers could help in the early detection and prediction of gestational-diabetes-related complications in pregnant women. Full article
(This article belongs to the Special Issue Molecular Research on Diabetes—2nd Edition)
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16 pages, 1732 KB  
Article
The Impact of a Commercial Electrolyte Beverage on the Hydration Status of Active Men and Women
by Cary Boyd-Shiwarski, Evan Ray, Harikesh Subramanian, Nicole Zharichenko, Amy Monroe and Aman Mahajan
Nutrients 2025, 17(3), 585; https://doi.org/10.3390/nu17030585 - 5 Feb 2025
Viewed by 15255
Abstract
Background/Objectives: Hypo-hydration is a major health concern that affects performance and is associated with increasing morbidity and growing health care costs. There is an emerging interest in optimizing hydration and identifying how factors such as ingestion rate and beverage composition affect hydration. This [...] Read more.
Background/Objectives: Hypo-hydration is a major health concern that affects performance and is associated with increasing morbidity and growing health care costs. There is an emerging interest in optimizing hydration and identifying how factors such as ingestion rate and beverage composition affect hydration. This study examined three beverages with varying ingestion rates and measured markers of hydration. Methods: Thirty healthy, active participants between the ages of 18 and 45 years were given three different beverages on three separate days. The beverages were of identical volumes (1 L), but differed in the rate of ingestion, carbohydrate content and electrolyte content. Beverage 1 and water alone were both consumed at a metered rate of one liter over four hours, whereas Beverage 2 was used as a positive control and was consumed at a bolus rate of one liter in 30 min. Results: After six hours, Beverage 1 significantly improved markers of hydration compared to water alone or Beverage 2. Beverage 1 decreased cumulative urine output vs. water alone by 32% (absolute difference −0.33 L; CI ± −0.16 to −0.51) and vs. Beverage 2 by 26% (absolute difference −0.26 L; CI ± −0.13 to −0.38). Beverage 1 increased the beverage hydration index vs. water alone by 64% (absolute difference +0.64 L; CI ± 0.36 to 0.92) and vs. Beverage 2 by 48% (absolute difference +0.53 L; CI ± 0.30 to 0.76). Conclusions: Beverage 1 is superior to water alone at improving hydration when it is ingested at similar rates. Moreover, metered ingestion of Beverage 1 improved hydration compared to a bolus ingestion of Beverage 2, this could be due to the dissimilar ingestion rates and/or beverage composition. Full article
(This article belongs to the Section Sports Nutrition)
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19 pages, 2622 KB  
Article
Radiofrequency Electromagnetic and Pulsed Magnetic Fields Protected the Kidney Against Lipopolysaccharide-Induced Acute Systemic Inflammation, Oxidative Stress, and Apoptosis by Regulating the IL-6/HIF1α/eNOS and Bcl2/Bax/Cas-9 Pathways
by Çağrı Balci, Mustafa S. Özcan, Halil Aşci, Pınar Karabacak, Oya Kuruşçu, Rümeysa Taner, Özlem Özmen, Muhammet Y. Tepebaşi, İlter İlhan and Selçuk Çömlekçi
Medicina 2025, 61(2), 238; https://doi.org/10.3390/medicina61020238 - 29 Jan 2025
Cited by 3 | Viewed by 4102
Abstract
Background/Objectives: Sepsis-associated acute kidney injury caused by lipopolysaccharide (LPS) is related to hypoxia, amplification of the inflammatory response, oxidative stress, mitochondrial dysfunction, and apoptosis. This study aims to explore the protective effects of a radiofrequency electromagnetic field (RF-EMF) and a pulsed magnetic [...] Read more.
Background/Objectives: Sepsis-associated acute kidney injury caused by lipopolysaccharide (LPS) is related to hypoxia, amplification of the inflammatory response, oxidative stress, mitochondrial dysfunction, and apoptosis. This study aims to explore the protective effects of a radiofrequency electromagnetic field (RF-EMF) and a pulsed magnetic field (PMF) on acute kidney injury in rats. Materials and methods: Forty female Wistar albino rats were randomly divided into five groups (each containing eight rats): control, LPS, RF-EMF, PMF, and RF-EMF + PMF groups. Six hours after LPS application, blood and tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analysis. Results: Histopathological findings, caspase-3, inducible nitric oxide synthase and tumor necrosis factor-alpha immunoexpressions, total oxidant status and oxidative stress index levels, and interleukin-6, hypoxia-inducible factor alpha, Bcl-2-associated X protein, and caspase 9 gene expression in kidney tissue and blood urine nitrogen and creatinine levels in blood were increased, whereas endothelial nitric oxide synthase and B-cell lymphoma 2 gene expression were decreased in the LPS groups. Both RF-EMF and PMF reversed all these findings and recovered renal tissues. Conclusions: Noninvasive, nontoxic, low-cost PMF and RF-EMF, both single and combined, have been demonstrated to have renoprotective anti-inflammatory, antioxidant, and antiapoptotic effects. Full article
(This article belongs to the Section Urology & Nephrology)
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10 pages, 276 KB  
Article
Comparison of Renal Tubular Damage with Kidney Injury Molecule-1 in Open and Laparoscopic Colorectal Cancer Surgery
by Abdullah Gürhan Duyan, Celalettin Vatansev, Rahim Kocabaş, Melek Yalçın Koç and Muhammed Ali Akbulut
Medicina 2025, 61(1), 42; https://doi.org/10.3390/medicina61010042 - 30 Dec 2024
Cited by 1 | Viewed by 1306
Abstract
Background and Objectives: Colorectal cancer is the third most common type of cancer in men and women. With advancements in technology, minimally invasive treatment options have become increasingly prominent in colorectal cancer surgery. This study aimed to compare the increased intra-abdominal pressure in laparoscopic [...] Read more.
Background and Objectives: Colorectal cancer is the third most common type of cancer in men and women. With advancements in technology, minimally invasive treatment options have become increasingly prominent in colorectal cancer surgery. This study aimed to compare the increased intra-abdominal pressure in laparoscopic colon and rectal surgery with open procedures using kidney injury molecule-1 (KIM-1) secreted from renal tubules. Materials and Methods: We enrolled 46 patients diagnosed with colon cancer who underwent laparoscopic and open surgical procedures at our clinic. The patients were prospectively randomized into five groups: 10 laparoscopic right hemicolectomies (Group 1), 8 open right hemicolectomies (Group 2), 8 laparoscopic anterior resections (LARs) (Group 3), 11 open anterior resections (Group 4), and 9 laparoscopic low anterior resections (Group 5). Urine samples were collected from the patients preoperatively, postoperatively at the 4th hour, and postoperatively on the 14th day, and the urine KIM-1 levels and urine creatinine (Cr) values were measured. The urine KIM-1/Cr ratios were subsequently calculated. Results: The urinary KIM-1/Cr levels increased at the 4th postoperative hour after the open and laparoscopic procedures. On postoperative day 14, the urinary KIM-1/Cr levels were lower than those in the preoperative period in all groups, except the LAR group. Conclusions: Our study shown that the average pressure in laparoscopic colon and rectal surgery did not have a long-term impact on kidney injury in comparison to open colon and rectal surgery. Full article
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