Search Results (167)

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a significant public health concern, yet rare sublineages remain poorly characterized. Here, we described a K30-ST198 hvKp sublineage identified in four isolates from two patients, including three sequential strains (K30B1, K30B2, K30B3) recovered over eight months from recurrent liver abscesses and one strain (K30-HUMV1) from a urinary tract infection. All isolates exhibited a yYpermucoviscous phenotype and resistance restricted to ampicillin and amoxicillin. Screening with the eazyplex hvKp assay detected ybt and rmpA in all strains, yielding a virulence score of 1. Biofilm production was strong in K30B1, K30B2, moderate in K30-HUMV1, but weak in K30B3. In the Galleria mellonella infection model, K30B1 showed higher virulence than the other isolates. Whole-genome sequencing identified the ICEKp1 carrying hypervirulence-associated genes (ybt, pagO, rmpAC, iroBCDN) together with additional virulence factors (fim, mrkD, uge, ureA, wabG, wcaJ, mliC), while antibiotic resistance genes were limited to fosA and bla_SHV-77. Protein structures and their functional domains were predicted using AlphaFold v3.0.1 and ColabFold v1.5.5, based on pLDDT scores, providing further insights into gene functionality. This work represents one of the first detailed characterizations of K30-ST198 hvKp, underscoring the need for integrated genomic, phenotypic, and structural approaches in hvKp surveillance. Full article

Background/Objectives: Monitoring of 24 h urine analysis is currently used to assess diet-related stone risk factors due in most cases to low hydration and high osmole intake accounting for urine supersaturation. The aim of our study is to test whether urine conductivity could be a relevant surrogate marker of urine osmolality and a useful tool for monitoring salt and protein diets in primary care centers. Methods: 113 patients with kidney stone history referred for a routine evaluation of fasting and 24 h urine samples were included. Biochemical analysis of urine was performed, including measured osmolality (mUosm) and conductivity. Results: Among our population, 45% of patients have a low diuresis (high-risk group of stone recurrence) below the target of 2 L/day, with lower daily mUOsm and conductivity outflow compared to the low-risk patient group > 2 L/day (718 versus 852 mosm/Day, p < 0.0001, and 13,730 versus 17,890 mS/cm/day, p < 0.0001, respectively). Conversely to urine sodium and urea concentration, daily sodium and protein intake estimated by natriuresis and urea excretion are significantly lower in the high-risk group (p = 0.01 and <0.0001, respectively). In 24 h urine samples, osmolality and conductivity were strongly associated with diuresis. Moreover, a strong association between urinary osmolality and urine conductivity enables an estimated osmolality (eUosm) according to the following equation: eUosm = −41.656 + 0.057 × conductivity (r² = 0.93; p < 0.001) with a 95% limit of agreement (LoA) ranging from −7.2% to +7.3%. An eUosm threshold value < 900 mOsm/day is independently associated with sodium and protein intake targets (odd ratio: 19.2 and 6.4-fold, respectively, p < 0.0001 and 0.01). Conclusions: 24 h urine measured conductivity appears to be a reliable, easy-to-use tool for the screening and monitoring of diet-related stone patients in primary care centers. Full article

Bone marrow-derived mononuclear cells (BMMCs) have shown beneficial effects on tissue repair, largely attributed to the paracrine action of bioactive mediators such as lysophosphatidic acid (LPA). This study aimed to evaluate the effects of BMMC treatment in a rat model of renal ischemia/reperfusion (I/R) injury, focusing on LPA-related molecular pathways. Male Wistar rats were divided into three groups: control; I/R, subjected to bilateral renal artery clamping for 30 min followed by 24 h of reperfusion; and I/R + BMMC, which received 1 × 10⁶ BMMCs per kidney directly into the renal capsule post-ischemia. During reperfusion, the rats were placed in metabolic cages for urine collection, renal function and protein expression. BMMC treatment did not reverse the I/R-induced increase in urine volume or decrease in glomerular filtration rate, serum potassium, or filtered sodium load. However, it prevented proteinuria, increased blood urea nitrogen, and enhanced urinary potassium excretion. Mechanistically, BMMC treatment prevented I/R-induced upregulation of LPAR1, downregulated LPAR2 and LPAR3, restored plasma LPA levels, and reduced renal autotaxin content. These results suggest that BMMCs modulate harmful LPA-related signaling and may contribute to renal protection through paracrine mechanisms in the setting of acute I/R injury. Full article

Background and Objectives: Urinary tract infections (UTIs) are a major cause of emergency department (ED) visits and hospital admissions among older adults. Although most seniors present hemodynamically stable, a sizeable fraction deteriorate during hospitalization, and no ED-specific tool exists to identify those at greatest risk. We sought to determine risk factors for in-hospital mortality in this population and to develop a predictive model. Materials and Methods: We analyzed the MIMIC-IV-ED database (2011–2019) and enrolled culture-confirmed UTI patients aged ≥ 65 years who were hemodynamically stable—defined as a systolic blood pressure ≥ 100 mm Hg without vasopressor support. Demographics, comorbidities, triage vital signs, and initial laboratory tests were extracted. Least Absolute Shrinkage and Selection Operator (LASSO) regression with 10-fold cross-validation was performed for variable selection. Discrimination was quantified with the C-statistic, calibration with the Hosmer–Lemeshow test, and clinical utility with decision curve analysis. Internal validation was assessed via 1000-sample bootstrap resampling. Results: Among 1571 eligible encounters (median age 79 years, 33% male), in-hospital mortality was 4.5%. LASSO selected eight variables; six remained significant in multivariable analysis: age, systolic blood pressure, oxygen saturation, white blood cell count, red cell distribution width, and blood urea nitrogen. The predictive nomogram demonstrated a C-statistic of 0.73 (95% CI 0.66–0.79) and outperformed traditional early warning scores. Conclusions: A six-variable nomogram may stratify mortality risk in hemodynamically stable older adults with UTI. Because the model was developed in a single U.S. tertiary-care ED, it remains hypothesis-generating until validated in external, multicenter cohorts to confirm generalizability. Full article

Introduction: Endothelial dysfunction is a common feature of end-stage kidney disease, requiring hemodialysis (HD) and antiphospholipid antibody (aPL) persistent positivity. Endothelial dysfunction can be assessed with noninvasive tests such as flow-mediated dilation (FMD). In the HD population, it is not known whether aPL persistent positivity is associated with a more severe endothelial dysfunction. Methods: We performed a cross-sectional study in our HD patients. The FMD of the brachial artery was measured in 17 aPL-positive patients who fulfilled the inclusion criteria and were matched to 17 controls according to age, gender, diabetes mellitus, smoking status and markers of dialysis adequacy (Kt/V). Results: FMD was significantly lower in the aPL group with a mean of 6.9% and 11.8% in the aPL-positive and the control groups, respectively (mean difference (IC 95%): −4.9 (−8.3; −1.6), p = 0.006). aPL was associated with a higher c-reactive protein level, and longer HD vintage. There was no statistical difference between groups in terms of pre-dialysis urea and urinary output, dialysis adequacy (Kt/V), and history of cardiovascular disease or treatments. Conclusions: aPL persistent positivity in HD patients was associated with worse endothelial dysfunction, reflected by FMD measurements. These findings have to be confirmed in larger studies. Full article

The aim of this study was to evaluate the effect of different water restrictions on the thermoregulation and blood hematological and metabolite parameters of crossbred Santa Inês ewes in a semi-arid climate. Thirty-two ewes were subjected to four water supply levels (100%, 80%, 60%, and 40%), in a completely randomized design with eight replications. The confinement period lasted 77 days, with 14 days allocated for adaptation. Respiratory rate, heart rate, and rectal temperature exhibited a quadratic response. There was an increase in red blood cells and urea. The enzyme alanine aminotransferase decreased linearly with water restriction. Urinary creatinine decreased along with water supply. Regarding urine color characteristics, all groups showed different colors, ranging from clear to cloudy. For the chemical characteristics of urine, a quadratic effect was observed for pH, with the highest value (8.75) at 60%. An increase was observed in total urine proteins and urobilinogen. Crossbred Santa Inês ewes in a semi-arid climate exhibit physiological adaptations to water supply reduction up to 40%. Following an 80% reduction in water supply, animals exhibit mild dehydration, characterized by increased serum urea levels and decreased alanine aminotransferase activity. Full article

Background: Rapid loss of residual kidney function (RKF) is associated with unfavorable outcomes. We conducted an RCT to compare the effects on RKF preservation of incremental HD between once-weekly HD (1-WHD) and twice-weekly HD (2-WHD). Methods: ESKD patients with an eGFR of 5–10 mL/min/1.73 m² and urine output of ≥800 mL/day were randomly assigned to receive either once-weekly HD (1-WHD) or twice-weekly HD (2-WHD) for 12 months. Patients in the 1-WHD group were prescribed once-weekly HD combined with low-protein diet (0.6 g/kg/day) supplemented with keto-analogues (KAs) 0.12 g/kg/day. In the 2-WHD group, patients received twice-weekly HD with a regular-protein diet. Primary outcomes were changes in RKF by renal clearance and urine volume. Nutritional status, muscle parameters, and quality of life (QoL) were also assessed. Results: A total of 30 incident HD patients were randomized. Baseline RKF, urine volume, and demographic were not different between groups. After 3 months, urine volume was significantly higher in the 1-WHD group than in the 2-WHD group (1921 ± 767 mL/day vs. 1305 ± 599 mL/day, p = 0.02), and these significant findings persisted throughout the entire study period. For RKF, 1-WHD also had a lesser decline in urinary urea (CUrea) and creatinine clearance (CCr) than 2-WHD, with statistically significant differences observed from months 6–12. By month 6, the 1-WHD group exhibited significantly higher CUrea and CCr compared to the 2-WHD group, with CUrea at 3.2 ± 2.3 vs. 1.7 ± 1.0 mL/min (p = 0.03) and CCr at 5.9 ± 3.6 vs. 3.8 ± 1.4 mL/min (p = 0.04), respectively. Serum albumin levels, skeletal muscle mass, anemia status, metabolic parameters, protein-bound uremic toxins, and QoL scores were comparable between the two groups. Conclusions: Incremental HD, starting with once-weekly HD combined with protein restriction supplemented with KAs, appears to better preserve RKF among incident HD patients compared to twice-weekly HD with a regular-protein diet. This HD regimen was also associated with safety in metabolic and nutritional profiles. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

Heartworm disease, caused by Dirofilaria immitis, often leads to pulmonary hypertension (PH), a serious cardiovascular complication in infected dogs. PH may impair renal function through hemodynamic and inflammatory mechanisms, even when traditional biomarkers such as serum creatinine and blood urea nitrogen (BUN) remain within normal ranges. This study aimed to assess urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in dogs naturally infected with D. immitis, with and without PH, to evaluate its potential as an early biomarker of renal dysfunction. Forty-two infected dogs were included and divided into two groups based on the presence (n = 14) or absence (n = 28) of PH, diagnosed via echocardiography. uNGAL concentrations were significantly higher in dogs with PH (mean 66.49 ± 6.67 ng/mL) compared to those without PH (mean 49.01 ± 14.48 ng/mL; p < 0.0001), despite normal creatinine and BUN values. No significant associations were found between uNGAL and sex, age, breed, or clinical signs. These findings suggest that uNGAL may serve as a sensitive biomarker of early renal impairment in dogs with heartworm disease and PH, even in the absence of overt azotemia, supporting its use in clinical evaluation and the monitoring of disease progression. Full article

Background: Chronic non-communicable diseases (NCDs) are a major global health challenge, with unhealthy diets contributing significantly to their burden. Metabolomics data offer new possibilities for identifying nutritional biomarkers, as demonstrated in short-term intervention studies. This study investigated associations between habitual dietary intake and urinary metabolites, a not well-studied area. Methods: Data were available from 496 participants of the population-based MEIA study. Linear and median regression models examined associations between habitual dietary intake and metabolites, adjusted for possible confounders. K-means clustering identified urinary metabolite clusters, and multinomial regression models were applied to analyze associations between food intake and metabolite clusters. Results: Using linear regression models, previously reported associations could be replicated, including citrus intake with proline betaine, protein intake with urea, and fiber intake with hippurate. Novel findings include positive associations of poultry intake with taurine, indoxyl sulfate, 1-methylnicotinamide, and trimethylamine-N-oxide. Milk substitutes were positively associated with urinary uracil, pseudouridine, 4-hydroxyhippurate, and 3-hydroxyhippurate, and inversely associated with quinic acid. Dietary fiber intake showed a positive association with 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and a negative association with indoxyl sulfate. We identified sucrose and taurine as key metabolites differentiating metabolite clusters. Multinomial regression analysis confirmed significantly different dietary associations across clusters, particularly for fruits, processed meat, poultry, and alcoholic beverages. Conclusions: This study highlights established and novel food–metabolite associations, demonstrating the potential of urinary metabolomics for use as nutritional biomarkers in individuals from the general population. Full article

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

Background: Pediatric neurogenic bladder (NB), often resulting from myelomeningocele, impairs bladder function due to disrupted neural control and is worsened by urinary retention, recurrent urinary tract infections, the absence of voluntary voiding, and additional sequelae of myelomeningocele, such as motor impairments, delayed colonic transit, and nutritional deficiencies. Oxidative stress arises from an imbalance between oxidant production and the body’s antioxidant defenses and is recognized as both a contributor to and a consequence of various pathological conditions. This study aims to assess the total antioxidant status (TAS) in NB patients, evaluate its impact on urinary antioxidants, and correlate the findings with the urodynamic parameters in NB patients compared to those in non-NB controls. Methods: This study included 29 patients with NB, who were compared with 57 non-NB individuals. The comparative analyses encompassed serum and urinary total antioxidant status normalized to creatinine (uTAS/creatinine) and renal function markers (creatinine, urea, uric acid, and the glomerular filtration rate [GFR]), as well as urodynamic findings. TAS was determined using the colorimetric ABTS method. Results: The patients with NB demonstrated a significantly lower serum TAS and elevated urinary TAS and uTAS/creatinine ratios in comparison to these values in the control group (p < 0.001). Furthermore, a positive correlation was observed between uTAS/creatinine and detrusor pressure at the maximum cystometric capacity, while a negative correlation was found between uTAS/creatinine and bladder wall compliance (r = 0.5, r = −0.68 respectively). Conclusions: The observed decrease in serum TAS and the increase in urinary TAS in NB may not only serve as evidence of an imbalance in antioxidant homeostasis but also suggest a potential contributory role to the deterioration of urodynamic function. Full article

Objectives: This study investigated the effects and mechanisms of electrolyzed alkaline water (EAW), a type of drinking water, on hyperuricemia (HUA) in mice. Methods: A hyperuricemia model was established by intraperitoneal injection of potassium oxonate and free access to a high-purine diet. EAW was provided ad libitum for 21 days. Results: The results showed that EAW had little impact on the levels of blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, or xanthine oxidase in mice (p > 0.05). Interestingly, EAW ingestion induced significant reductions in uric acid and creatinine levels (p < 0.05), along with increased urinary uric acid excretion (p < 0.05) and less renal pathological changes in mice. Additionally, EAW upregulated GLUT9 gene expression (p > 0.05) and downregulated URAT1 protein expression. Conclusions: In conclusion, this study demonstrates that EAW promotes uric acid excretion by downregulating URAT1 and GLUT9 protein expression, resulting in a significant reduction in uric acid levels. Full article

Background and Objectives: Immunosuppressed patients are at higher risk of delayed diagnosis and atypical presentations in the emergency department (ED), requiring prompt management. This study compares febrile (≥37.5 °C) and afebrile (<37.5 °C) immunosuppressed patients admitted to the ED regarding clinical and laboratory parameters, including blood and urine tests, vital signs, final diagnoses, outcomes, and mortality. Materials and Methods: Eighty immunosuppressed patients aged 18–82 were prospectively evaluated from May 2019 to May 2020. Data on blood and urine tests, final diagnoses, outcomes, and mortality were recorded using a standardized form. Results: Among the 80 patients, 44 (55%) were female and 36 (45%) were male, with a mean age of 58.5 ± 14.72 years. The febrile patients showed higher admission levels of lactate dehydrogenase (LDH), interleukin-6 (IL-6), procalcitonin (PCT), and longer hospital stays than the afebrile patients. Mortality correlated with low albumin, oxygen saturation, platelet count, and total protein levels and elevated PCT and lipase levels. ICU admissions were linked to low albumin, total protein, and systolic blood pressure levels and elevated LDH, blood urea nitrogen, neutrophil count, and PCT levels. The fever status (febrile versus afebrile) had no significant relationship with the immunosuppression type, complaints, diagnoses, outcomes, or mortality. Final diagnoses varied by immunosuppression type: cholangitis in liver transplant recipients, respiratory infections in cancer patients, and urinary tract infections in kidney transplant recipients. Conclusions: Immunosuppressed patients can present with severe conditions, even without fever. Based on our findings, our study emphasizes that measuring PCT in immunosuppressed patients presenting to the emergency department with various complaints but without fever may help reduce the risk of delayed diagnosis. Full article

This study evaluated the effects of supplementing rumen-protected methionine, threonine, isoleucine, and leucine to low-protein diets on lactating dairy cow performance. Sixty Holstein cows were assigned to one of four dietary treatments in a 9-week randomized complete block design: positive control (16% crude protein diet; 16% CP), negative control (12% CP), 12% CP plus the four essential amino acids (12% CP + EAA), and 14% CP supplemented with the four EAA (14% CP + EAA). The milk protein yield was significantly decreased in the 12% CP group compared to the 16% CP group but was restored to comparable levels with EAA supplementation of both the 12% and 14% CP diets. Dietary nitrogen intake and urinary nitrogen excretion both increased with higher dietary CP levels. Nitrogen utilization efficiency in milk was significantly improved by EAA supplementation, with the highest efficiency observed in the 12% CP + EAA treatment (39.0% vs. 33.3% in the 16% CP diet). Plasma urea levels increased with elevated dietary CP and EAA supplementation. Moreover, EAA supplementation significantly elevated venous methionine levels and showed a tendency to increase venous leucine levels. Additionally, compared to the negative control, EAA supplementation increased concentrations of glucagon and prolactin (p < 0.05). EAA supplementation of low-protein diets, particularly the 14% CP diet, improved the dietary protein efficiency of lactating cows without a concomitant decrease in milk protein yield. Full article