Search Results (713)

Per- and polyfluoroalkyl substances (PFASs) have gained significant attention due to their widespread distribution in the environment and potential adverse health effects. While ingestion, especially through contaminated drinking water, is considered the primary route of human exposure, recent research suggests that other pathways, such as inhalation and dermal absorption, also play a significant role. This review provides a concise overview of the toxicological impacts of both legacy and emerging PFASs, such as GenX and perfluorobutane sulfonic acid (PFBS), with a particular focus on their effects on the liver, kidneys, and immune and nervous systems, based on findings from recent in vivo, in vitro, and epidemiological studies. Despite the transition to PFAS alternatives, much of the existing toxicity data focus on a few legacy compounds, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which have been linked to adverse immune outcomes, particularly in children. However, evidence for carcinogenic risk remains limited to populations with extremely high exposure levels, and data on neurodevelopmental effects remain underexplored. While epidemiological and experimental animal studies supported these findings, significant knowledge gaps persist, especially regarding emerging PFASs. Therefore, this review examines the visceral, neural, and immunotoxicity data for emerging PFASs and mixtures from recent studies. Given the known risks from well-studied PFASs, a precautionary principle should be adopted to mitigate human health risks posed by this large and diverse group of chemicals. Full article

Background and objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small- to medium-sized vessels and is characterized by the production of ANCAs. The ANCA-negative term is used if the patient otherwise fulfills the definition for AAV but has negative results on serologic testing for ANCAs. The objective of this study was to compare ANCA-positive and -negative vasculitis patients and to evaluate the main differences possibly related to the presence of ANCAs. Material and methods. A cross-sectional study of 73 patients treated at the tertiary Rheumatology Centre of University Hospital from the 1 January, 2001, to the 31August, 2023, with diagnoses of AAV was carried out. Clinical characteristics and laboratory data were collected at the onset or at the first year of the disease. Results. Forty-eight (65.8%) patients were ANCA-positive, while twenty-five (34.3%) were ANCA-negative. Distribution by gender was similar in both groups, with a female–male ratio of 2:1. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were elevated for all AAV patients, but values were higher in the ANCA-positive patients’ group. The median hemoglobin was 106 g/L in the seropositive group and 127 g/L in the seronegative group. A higher prevalence of kidney involvement (60.4%) with elevated serum creatinine level (93.5 µmol/L) was observed in the ANCA-positive group compared with 24% and 70 µmol/l in the ANCA-negative group (p < 0.05). Neurological involvement was more frequently found in the ANCA-positive patient group, too: 29.2% compared to 20%. Among patients with ANCA-negative vasculitis, 88% had pulmonary; 92% ear, nose, throat (ENT); 48% joint; and 28% skin presentation. In comparison, involvement of these organs was less common in the ANCA-positive patients’ group, at 79.2%, 60.4%, 31.3%, and 25 %, respectively. Conclusions. ANCA-positive patients appear to be in a more difficult clinical situation in terms of organ involvement and laboratory changes. Full article

Dietary protein is an essential macronutrient derived from both plant and animal sources required for muscle building, immune function, and wound healing. However, in the United States, protein consumption worsens as individuals age, with 30% of men and 50% of women over 71 consuming inadequate dietary protein due to a variety of factors, including changes in gut function, loss of appetite, tooth loss, financial concerns, and social isolation. The aim of this review is to underscore the need for increased protein requirements in aging populations, highlight potential barriers, synthesize these protein requirements, and also recommend strategies to meet these increased protein needs. Achieving adequate protein status, especially when facing chronic or acute health concerns, is essential to promote muscle and bone strength (because aging is associated with significant decreases in postprandial muscle protein synthesis), to support immune health (due to immunosenescence), and to maintain a good quality of life. For older adults, the literature suggests that a dietary protein intake of at least 1.0–1.2 g/kg/day is required in healthy, aging populations, and intakes of 1.2–1.5 g/kg/day are necessary for those with chronic or acute conditions. These protein intake recommendations can increase to 2.0 g/kg/day in more severe cases of illness, malnutrition, and chronic conditions. The reviewed literature also suggests that evenly balanced protein distributions of 25–30 g of dietary protein (0.4 g/kg) per meal from animal and plant protein sources alike are sufficient to maximize muscle protein synthesis (MPS) rates in older populations. Additionally, pre-sleep protein feeds of 40 g/night may be another strategy to improve daily MPS and amino acid utilization. Full article

Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article

We performed a diagnostic disease investigation on a wild smallmouth bass (Micropterus dolomieu) with skin ulcers that was collected from Lake Oahe, South Dakota, following reports from anglers of multiple fish with similar lesions. Gross and histologic lesions of ulcerative dermatitis, myositis, and lymphocytolysis within the spleen and kidneys were consistent with largemouth bass virus (LMBV) infection. LMBV was detected by conventional PCR in samples of a skin ulcer, and the complete genome sequence of the LMBV (99,184 bp) was determined from a virus isolate obtained from a homogenized skin sample. A maximum likelihood (ML) phylogenetic analysis based on the major capsid protein (MCP) gene alignment supported the LMBV isolate (LMBV-SD-2023) as a member of the species Ranavirus micropterus1, branching within the subclade of LMBV isolates recovered from North American largemouth (Micropterus salmoides) and smallmouth bass. This is the first detection of LMBV in wild smallmouth bass from South Dakota. The ultrastructure of the LMBV isolate exhibited the expected icosahedral shape of virions budding from cellular membranes. Viral nucleic acid in infected cells was visualized via in situ hybridization (ISH) within dermal granulomas, localized predominantly at the margin of epithelioid macrophages and central necrosis. Further sampling is needed to determine the geographic distribution, affected populations, and evolutionary relationship between isolates of LMBV. Full article

Background/Objectives: Glomerulonephritis (GNs) is a heterogeneous group of inflammatory kidney diseases. Novel genetic methods have revealed some disease-causing and susceptibility genes underlying primary and secondary GNs. We aimed to investigate the presence of the single nucleotide polymorphisms (SNPs) rs12917707, found in the UMOD gene, and rs17319721, found in the SHROOM3 gene, as well as different polymorphisms in immune system genes in a group of children with GN. Method: The study included 71 children with GN (40 with primary and 31 with secondary GN) and 119 healthy children (HC). SNPs of the UMOD (rs12917707), SHROOM3 (rs17319721), IL10 (rs1800871 and rs3024505), IL6 (rs1800795), IL12B (rs3212227), IL23R (rs11209026 and rs1800896), and TNF (rs361525 and rs1800629) genes were genotyped. Results: The median age of the patients was 8 years at the onset of GN and 14 years at sampling. Allele A for rs1800629 in the TNF gene was more common in patients with GN in comparison to HCs (p = 0.009), followed by the difference in genotype distributions (p = 0.021), where AA and GA genotypes were more prevalent in patients. We found a statistically significant difference in haplotype distributions between patients and HCs for TNF, with GN patients having the GGAG haplotype more frequently and HCs having GGGG (p < 0.05). No correlation between the investigated SNPs and patient clinical characteristics (disease onset, primary or secondary GN, severity of disease, occurrence of remission, and presence of hypertension) was observed. Conclusions: An association between the TNF gene and different types of GN was noticed in children with GN. This may help us to understand the pathogenesis of these disorders and develop new treatments to cover the unmet needs of children with GN. Full article

Umbilical cord mesenchymal stem cells (UCMSCs)-derived small extracellular vehicles (sEVs) are reported to offer therapeutic effects in regenerative medicine, but they lack safety and biodistribution profiles to support smooth translation at the clinical stage and regulatory requirements. Our study aimed to determine the safety and biodistribution profile in a healthy animal model before application in the metabolic syndrome model. Method: Healthy male Sprague Dawley (SD) rats were given an intravenous (IV) injection of normal saline (control group) or pooled fetal UCMSCs-derived sEVs (treated group) every three weeks for 90 days. Morbidity and mortality observation (daily), physical measurements (weekly), selected serum biochemistry (every three weeks), and hematology (every three weeks) were performed for 90 days. Acute toxicity (on day 14) and sub-chronic toxicity (on day 90) were assessed for gross necropsy, relative organ weight, and histopathological assessment of lungs, liver, spleen, kidney, and lymph nodes. Separately, a biodistribution study was conducted with the sEVs preparations labeled with PKH26 fluorescent dye, given intravenously to the rats. The organs were harvested 24 h post-injection. There were no drastic changes in either group’s morbidity or mortality, physical, hematological, and biochemistry evaluation. The histopathological assessment concluded moderate (focal) inflammation in the treated group’s kidneys and signs of recovery from the inflammation and vascular congestion in the liver. A biodistribution study revealed a higher accumulation of sEVs in the spleen. Multiple IV injections of the pooled fetal UCMSCs-derived sEVs in healthy male SD rats were deemed safe. The sEVs were abundantly distributed in the spleen 24 h post-injection. Full article

In this paper, we present the development of a new semi-distributed interferometer (SDI) biosensor with a Zn, Cu, and Co metal oxide nanopowder coating for the detection of a kidney disease biomarker as a model system. The combination of nanopowder coating with the SDI platform opens up unique opportunities for improving measurement reproducibility while maintaining high sensitivity. The fabrication of sensors is simple, which involves one splice and subsequent cutting at the end of an optical fiber. To ensure specific detection of the biomarker, a monoclonal antibody was immobilized on the surface of the probe. The biosensor has demonstrated an impressive ability to detect biomarkers in a wide range of concentrations, from 1 aM to 100 nM. The theoretical limit of detection was 126 fM, and the attomolar detection level was experimentally achieved. The sensors have achieved a maximum sensitivity of 190 dB/RIU and operate with improved stability and reduced dispersion. Quantitative analysis revealed that the sensor’s response gradually increases with increasing concentration. The signal varies from 0.05 dB at 1 aM to 0.81 dB at 100 nM, and the linear correlation coefficient was R² = 0.96. The sensor showed excellent specificity and reproducibility, maintaining detection accuracy at about 10⁻⁴ RIU. This opens up new horizons for reliable and highly sensitive biomarker detection, which can be useful for early disease diagnosis and monitoring using a cost-effective and reproducible sensor system. Full article

Background: Hemodialysis patients, due to impaired kidney function and compromised immune responses, face increased risks from SARS-CoV-2. Anti-nucleocapsid IgG (anti-IgG N) antibodies are a commonly used marker to assess prior infection in the general population; however, their efficacy for hemodialysis patients remains unclear. Methods: A retrospective study of 361 hemodialysis patients evaluated anti-IgG N antibodies for detecting prior SARS-CoV-2 infection. Antibody levels were measured using a chemiluminescence immunoassay (CLIA) over the four time points. Boxplots illustrated antibody distribution across sampling stages and infection status. Logistic regression and receiver operating characteristic (ROC) curve analysis determined diagnostic accuracy, sensitivity, specificity, and optimal cutoff values. Results: Among the 361 hemodialysis patients, 36 (10.0%) had SARS-CoV-2 infection. Sex distribution showed a trend toward significance (p = 0.05). Boxplot analysis showed that anti-IgG N levels remained low in non-infected patients but increased in infected patients, peaking at the third sampling. Anti-IgG N demonstrated high diagnostic accuracy (AUC: 0.973–0.865) but declined over time (p = 0.00525). The optimal cutoff at C1 was 0.01 AU/mL (sensitivity 1.00, specificity 0.94). Adjusted models had lower predictive value. Conclusions: Anti-IgG N antibodies showed high diagnostic accuracy for detecting prior SARS-CoV-2 infection in hemodialysis patients, though performance declined over time. These findings highlight the need for tailored diagnostic strategies in this vulnerable population. Full article

Repetitive DNA represents over 50% of the human genome and is an abundant component of circulating cell-free DNA (cfDNA). We previously showed that cfDNA levels and integrity can predict survival in elderly patients with cardiovascular disease. Here, we aimed to clarify whether a low-pass next-generation sequencing (NGS) approach can characterize the repeat content of cfDNA. Considering the bimodal distribution of cfDNA fragment lengths, we examined the occurrence of repetitive DNA subfamilies separately in dinucleosomal (>250 bp) and mononucleosomal (≤250 bp) cfDNA sequences from 24 patients admitted for heart failure. An increase in the relative abundance of Alu repetitive elements was observed in the longer fraction, while alpha satellites were enriched in the mononucleosomal fraction. The relative abundance of Alu, ALR, and L1HS DNA in the dinucleosomal fraction correlated with different prognostic biomarkers, and Alu DNA was negatively associated with the presence of chronic kidney disease comorbidity. These results, together with the observed inverse correlation between Alu DNA abundance and cfDNA integrity, suggest that the composition of plasma cfDNA could be determined by multiple mechanisms in different physio-pathological conditions. In conclusion, low-pass NGS is an inexpensive method to analyze the cfDNA repeat landscape and identify new cardiovascular disease biomarkers. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with limited therapeutic options. This study investigated the expression of HEAT repeat-containing protein 1 (HEATR1) and solute carrier family 27 member 2 (SLC27A2) in ccRCC and their potential as prognostic markers and therapeutic targets. Methods: Analysis of a public proteomic dataset (CPTAC) and immunohistochemistry (IHC) validation in an independent cohort of 52 ccRCC patients was performed. HEATR1 and SLC27A2 expression were correlated with survival outcomes. Reactome pathway analysis was conducted to explore the functional roles of HEATR1 and SLC27A2. Results: The analysis showed that HEATR1 is upregulated and associated with poor prognosis, while SLC27A2 is downregulated and similarly linked to shorter progression-free survival. High HEATR1 expression and low SLC27A2 expression correlated with shorter progression-free survival (PFS) and overall survival (OS) in patients with high-grade ccRCC. Reactome analysis indicated HEATR1’s involvement in RNA metabolism and SLC27A2’s role in lipid metabolism, particularly peroxisomal lipid metabolism and fatty acyl-CoA biosynthesis. HEATR1 exhibited a dual localization in both the cytoplasm and nucleus, while SLC27A2 was primarily observed at the cell membrane and the nucleus. This different subcellular distribution suggests multifaceted roles for both proteins in ccRCC pathogenesis. Conclusions: HEATR1 and SLC27A2 are potential prognostic markers in ccRCC. Further research is needed to validate these findings in larger, more diverse cohorts and elucidate their roles in ccRCC progression. Full article

Background: Understanding the absorption and distribution of herbicides in plants and animal tissues is essential for assessing their potential risks to human health. Method: In this study, we employed imprint desorption electrospray ionization mass spectrometry imaging (IDESI-MSI) to visualize in both vegetable and animal tissues the absorption of Roundup which is a widely used herbicide. Results: Using IDESI-MSI with a pixel size of 150 µm, we detected the herbicide alongside several endogenous metabolites on oil-absorbing films applied to carrot sections. Time-course experiments revealed progressive herbicide penetration into carrot tissue, with penetration depth increasing linearly over time at a rate of approximately 0.25 mm/h. In contrast, green pepper samples showed minimal herbicide infiltration, likely owing to their hydrophobic cuticle barrier. Additionally, mice fed with herbicide-treated carrots exhibited detectable levels of herbicide in liver and kidney tissues. Conclusions: These findings highlight the utility of IDESI-MSI as a powerful analytical platform for the rapid evaluation of chemical migration and absorption in food and biological systems, with important implications for food safety and toxicological research. Full article

Chronic kidney disease (CKD) is associated with the systemic accumulation of uremic toxins (UTs) due to impaired renal elimination. Among these, indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are particularly challenging because of their high protein binding and limited removal by dialysis. In addition to renal excretion, the transport of IS and PCS, and their microbiota-derived precursors, indole and p-cresol, across key physiological barriers—the intestinal barrier, blood–brain barrier, and renal proximal tubule—critically influences their distribution and elimination. This review provides an overview of transporter-mediated mechanisms involved in the disposition of IS, PCS, and their microbial precursors, indole and p-cresol. It also examines how these UTs may interact with commonly prescribed drugs in CKD, particularly those that share transporter pathways as substrates or inhibitors. These drug–toxin interactions may influence the pharmacokinetics and toxicity of IS and PCS, but remain poorly characterized and largely overlooked in clinical settings. A better understanding of these processes may guide future efforts to optimize pharmacotherapy and support more informed management of CKD patients, particularly in the context of polypharmacy. Full article

Introduction/Objectives: Although desmopressin is commonly used to reduce bleeding hazards in patients undergoing kidney biopsies, its effectiveness varies among individuals. This study aims to assess the impact of desmopressin on bleeding risk and hemodynamic stability in patients undergoing kidney biopsies while also identifying potential risk factors influencing these outcomes. Methods: A retrospective study was conducted at King Abdulaziz Medical City to evaluate adult patients who underwent either native or transplant kidney biopsies. The collected data included demographics, comorbidities, demographics, desmopressin usage, vital signs, lab results, and bleeding events. Bleeding was defined as a composite outcome encompassing both minor and major bleeding. Results: Data from 210 patients who received desmopressin during kidney biopsies were analyzed alongside 200 control patients. The distribution of gender and age was comparable between the two groups. However, the types of biopsies differed significantly, with a greater number of native kidney biopsies in the desmopressin group. Desmopressin was associated with a reduced incidence of major bleeding and shorter hospital stays. Longitudinal analyses revealed significant time-dependent changes in mean arterial pressure, hemoglobin, and hematocrit, although no treatment effect was observed. Logistic regression showed no significant impact of desmopressin on composite bleeding, hypotension, or hyponatremia, though comorbidities and transplant biopsies were associated with a reduced risk of hyponatremia. Conclusions: Desmopressin was associated with fewer episodes of major bleeding and shorter hospital stays but had no direct effect on hemodynamic parameters. Nevertheless, further research is necessary to explore its long-term clinical impact. Full article

Fc gamma receptors (FcγRs) control humoral and cellular immune responses and maintain the immune system balance. Functional polymorphisms of FcγRs, whose prevalence was dependent on ethnic origin, were found to be associated with systemic lupus erythematosus (SLE) or kidney injuries in several ethnic groups. We aimed at investigating the association between the functional single-nucleotide polymorphisms (SNPs) of FcγRIIa-H131R (rs1801274), FcγRIIb-I232T (rs1050501), FcγRIIIa-V158F (rs396991) and FcγRIIIb variants (NA1 and NA2) and lupus erythematosus systemic in an indigenous African Caribbean population. We compared the frequencies of the functional SNPs of FCGR2A (FcγRIIa-H131R, rs1801274), FCGR2B (FcγRIIb-I232T, rs1050501), FCGR3A (FcγRIIIa-V158F, rs396991) and FCGR3B variants (FcγRIIIb NA1 and NA2) between lupus and healthy controls in an indigenous African Caribbean population. We highlighted an association between the FCGR3B-NA1/NA1 and FCGR3A-158F alleles and systemic lupus erythematosus, in addition to an association between FCGR2A-131R and lupus nephritis. Furthermore, an increase in the 131R-158V haplotype in lupus nephritis (30.4%) vs. lupus non-nephritis (15.8%) was noticed. Surprisingly, in spite of the high frequency of the FCGR2B-232T allele in our population, our study did not highlight any association of this allele either with SLE or lupus nephritis (a severe and frequent form of SLE). CD72-Hap1, which has been shown to confer resistance to SLE against T232 allele, was not enhanced in the control group. Our results emphasize an association between FCGR2A-131R and lupus nephritis with a distinctive FCGR polymorphism distribution in an indigenous African Caribbean population, confirming the important variation in the FCGR locus depending on ethnic origin. Full article