Search Results (351)

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease with a heterogeneous organ involvement, for which reliable biomarkers are still being studied. The implication of advanced glycation end products (AGEs), resulting from oxidative stress, and their interaction with the receptor for AGEs (RAGE) has been studied in pathologies with chronic proinflammatory status, offering potential relevance in SLE. This systematic review aimed to evaluate the utility of skin autofluorescence (SAF)—a non-invasive proxy for AGE accumulation—as a biomarker for disease severity, activity, and impact in SLE patients. Following PRISMA guidelines, six studies assessing SAF and/or circulating AGEs and soluble RAGE (sRAGE) in SLE were analyzed. Findings consistently showed higher AGE levels in SLE patients compared to healthy controls, with several correlations between SAF/AGEs and disease features such as SLEDAI scores, organ involvement, inflammatory markers, and damage indices. Decreased sRAGE levels were also observed, possibly due to consumption by AGEs. Some studies further reported predictive associations between specific AGEs or their ratios with sRAGE and particular clinical phenotypes. Although heterogeneity among studies limits definitive conclusions, the AGEs–sRAGE axis—and especially SAF—emerges as a promising candidate for future biomarker development in SLE. Further large-scale longitudinal studies are needed to confirm its clinical utility. Full article

Background: Iatrogenic nerve injuries (NIs) are an under-recognized complication of urological surgery. Though less common than vascular or organ damage, they may cause lasting sensory and motor deficits, significantly affecting patients’ quality of life. With increasing complexity in pelvic procedures, a consolidated understanding of nerve injuries is essential. Purpose: This review aims to synthesize current knowledge regarding peripheral and autonomic NIs in urological surgery, highlighting mechanisms of injury, associated procedures, preventative strategies, and treatment options. Scope: Focused on common urological interventions such as radical prostatectomy, cystectomy, pelvic lymphadenectomy, and reconstructive techniques, the review explores injuries from positional compression, traction, and intraoperative transection to their surgical management. Key Findings: The review categorizes nerve injuries into crush and transection types and details intraoperative signs and repair techniques. Skeletonization of nerves, avoidance of energy devices near neural structures, and prompt end-to-end anastomosis using 7-0 polypropylene are central to management. Adoption of novel sutureless nerve coaptation devices have also been described with promising outcomes. Early repair offers a better prognosis. New intraoperative technologies like NeuroSAFE during robotic-assisted procedures may enhance nerve preservation. Conclusion: Iatrogenic NIs, although rare, are clinically significant and often preventable. Prompt intraoperative recognition and repair are critical. Further research is warranted to develop standardized preventative protocols and enhance intraoperative nerve monitoring. A multidisciplinary approach, extended across surgical specialties, could improve outcomes and guide timely treatment of nerve injuries. Full article

Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article

Healthy peatlands provide valuable ecosystem services. Peat extraction damages peatlands, leading to carbon emissions. One of the main reasons for peat extraction is for use in horticulture. Replacing peat with recycled organic materials in horticulture is critical to preserve the valuable ecosystems provided by peatlands and to establish more circular supply chains that are reliant on recycling rather than extraction. Despite the strong policy commitment and budget allocation to restore peatlands, the demand for peat-based growing media remains high and drives most of the peat demand. In our research, we mapped the growing media supply chain, held semi-structured interviews with key stakeholders representing different interests, and surveyed amateur gardeners in the UK to understand the bottlenecks experienced by each profile in ending peat use and how to overcome them. We employed semi-structured key expert surveys to understand the supply chain dynamics and consumer demand, informed by these early interviews and the previous literature, we prepared and distributed an online consumer survey and interviewed supply-side stakeholders to understand their perspectives. The findings indicate that the barriers of availability, cost, and performance are shared between the supply-and-demand-side stakeholders. A portfolio of financial, educational and logistic interventions is required to simultaneously support the supply side to accelerate the transformation of production and supply patterns and to aid the demand side to adapt to growing with compost of recycled organic materials. The policies promoting recycled organic material use in horticulture must be coordinated within the UK and with other parts of Europe focusing on the elimination of the peat content in products rather than peat extraction to avoid extraction and the associated destruction of peat stocks elsewhere. Full article

As the population of adults with congenital heart disease (ACHD) continues to grow, a significant and often underrecognized complication is the development of cardiorenal syndrome (CRS)—a complex, bidirectional interaction between cardiac and renal dysfunction. While CRS has been extensively studied in acquired heart failure, its manifestations and implications in ACHD remain insufficiently understood. Emerging data suggest that renal dysfunction is highly prevalent in ACHD, with significant associations to adverse outcomes regardless of cardiac lesion type or functional status. This review explores CRS within three key physiologic categories in ACHD: patients with a systemic right ventricle, those with a subpulmonary right ventricle, and those with Fontan circulation. Each subgroup presents unique hemodynamic challenges that affect renal perfusion, filtration pressure, and systemic congestion, contributing to both acute and chronic renal impairment. The utility of renal biomarkers such as albuminuria, cystatin C, and estimated glomerular filtration rate (eGFR) is emphasized, alongside the importance of early detection and multidisciplinary management. Heart failure therapy tailored to congenital anatomy, neurohormonal modulation, and careful volume control remain the cornerstones of treatment, while transplantation strategies must consider the potential for irreversible end-organ damage. Given the profound implications of CRS on quality of life and survival, a comprehensive understanding of its pathophysiology and management in ACHD is critical to optimizing long-term outcomes in this increasingly complex patient population. Full article

Background/Objectives: Activation of the immune system and subclinical inflammation participate in the pathogenesis of primary hypertension (PH) and the formation of hypertension-mediated organ damage. Our study aimed to investigate the relationship between subclinical inflammation and left ventricular hypertrophy (LVH) in pediatric patients with PH. Methods: In 34 untreated children with PH (15.1 ± 2.1 years, 28 boys, 6 girls), we investigated markers of subclinical inflammation (high-sensitivity CRP, interleukin 18, and complete blood count-derived indices), parameters of the left ventricle from 2D-echocardiography, office and ambulatory blood pressure, and selected clinical and biochemical parameters. Results: LVH was revealed in 12 (35.3%) patients, and abnormal relative wall thickness (RWT) was found in 6 (17.6%) children. Left ventricular inner dimension at end diastole (LVEDd) Z-score correlated negatively with neutrophils (r = −0.583, p = 0.001), neutrophil-to-lymphocyte ratio (NLR) (r = −0.562, p = 0.002), and positively with monocyte-to-neutrophil ratio (MNR) (r = 0.605, p = 0.001) and left ventricular mass (LVM) for lean body mass Z-score, while LVMI [g/m²] correlated positively with MNR (r = 0.495, p = 0.005 and r = 0.433, p = 0.011). RWT correlated positively with neutrophil count (r = 0.356, p = 0.039 and r = 0.347 p = 0.044) and with monocyte count (r = 0.378, p = 0.027 and r = 0.365, p = 0.034). Patients with LVH had significantly lower NLR (1.430 ± 0.409 vs. 1.797 ± 0.521, p = 0.043) and higher MNR ratios (0.171 ± 0.031 vs. 0.144 ± 0.037, p = 0.042). The receiver operating characteristic analysis demonstrated good diagnostic profiles for mean platelet volume (MPV), NLR, and MNR as predictors of LVH. In multivariate analysis, MNR was the only significant predictor of LVH (OR: 1.329, 95CI: 1.007–1.756). Conclusions: Monocyte-to-neutrophil ratio may be an easily accessible marker of left ventricular hypertrophy in children with primary hypertension. Full article

Background and Objectives: PAX2 serves as a critical transcription factor integral to the process of embryogenesis. Variations in the PAX2 gene could result in the aberrant development of numerous organs. Despite the identification of numerous mutations within the PAX2 gene, the correlation between specific genotypes has yet to be fully clarified. The objective of this study was to examine the clinical phenotypes and genotypes associated with PAX2 mutation-induced disorders in pediatric patients of Chinese descent. The aim of our study was to forecast the pathogenic potential of these genetic mutations and to ascertain possible correlations between genotypic variations and the clinical manifestations of disorders linked to PAX2 mutations. Materials and Methods: We recruited 14 pediatric subjects with PAX2 mutations, meticulously examining the clinical characteristics and genetic alterations present in these individuals. Computational techniques were utilized to evaluate the pathogenicity, stability, and biophysical characteristics. A range of computational tools were employed for this assessment, including PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf, and SNP effect. Results: The age at onset ranged from prenatal to 12 years. Five patients progressed to end-stage renal disease. Proteinuria and bilateral renal hypoplasia were observed in 92% of cases. Ocular and auditory abnormalities were also noted. We identified eleven different PAX2 mutations, including five novel variants not previously reported in the literature. We predicted that all mutations, with the exception of p.F27-L33 del and N188S, exhibited high pathogenicity scores. In particular, R117P and R140W are strongly associated with disease pathogenicity and are likely to cause more significant damage than other gene mutants. Conclusions: This study expands the mutational and phenotypic spectrum of PAX2-related disorders in the pediatric population. The identification of five novel variants enhances our understanding of the genetic basis of these conditions. Despite recurrent mutations, marked phenotypic heterogeneity persists, underscoring the need for further research. Full article

Background/Objectives: Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis, often presenting first with sinonasal symptoms diagnosed as vasculitis chronic rhinosinusitis (CRS). Patients with limited (L) GPA do not have renal involvement and often have more local sinonasal disease. Few studies have examined systemic progression in LGPA patients presenting with local sinonasal disease. Our objective was to compare GPA disease progression and activity in LGPA patients with and without CRS. Methods: Using the US Collaborative Network of the TriNetX platform, we conducted a retrospective study of adults with LGPA and CRS versus those without CRS. Outcomes were measured 1 month-5 years after patients met inclusion criteria. Primary outcomes were acute sinusitis, end-organ damage, and major GPA disease activity. Secondary outcomes were end-organ damage and major disease activity for each organ system and mortality. Results: There were n = 1097 in the LGPA with CRS cohort and n = 3331 in the LGPA without CRS cohort, with n = 1023 in each cohort after 1:1 propensity matching on age, gender, ethnicity, and race. We found a significantly greater risk of acute sinusitis (risk ratio: 4.80, 95% confidence interval: [2.89,7.99]), end-organ damage (2.99 [2.41, 3.70]), and major disease activity (2.41 [1.73, 3.35]) comparing patients with CRS to those without. LGPA patients with CRS had no significant difference in mortality compared to those without CRS (0.94, [0.64,1.38]). Conclusions: Patients with LGPA and CRS have greater risk of developing disease progression and increased organ system disease activity compared to LGPA without CRS. Full article

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs. Full article

Puerto Rico has faced significant damage from natural disasters and the COVID-19 pandemic, disrupting clinical services and scientific research logistics. In response, the RCMI-CCRHD Program at the UPR-MSC organized a retreat with the objective of understanding the challenges faced by its research network during the pandemic and strategies to overcome them. The retreat featured presentations on COVID-19 supplemental projects and included a discussion group. Twenty attendees identified the challenges they encountered and the strategies developed through an open-ended question and a satisfaction survey, implementing a mixed-method approach. We performed a content analysis on the open-ended survey questions and used descriptive statistics for the satisfaction survey. Key challenges included remote work implementation, recruitment difficulties, and mental health concerns. Attendees shared actions taken to address these issues, such as modifying protocols for remote planning and using digital platforms for improving communication. They also recognized opportunities that arose from remote work, which allowed them to focus on publishing and adapting mental health support tools. The retreat received positive feedback, with 93.8% of attendees giving a five-star rating. By reflecting on these experiences, investigators can refine strategies and implement effective solutions. Recommendations include flexible IRB protocols, improved digital tools, community involvement, and robust emergency preparedness plans. Full article

Objective: Various insulin resistance (IR) indices have been developed to assess cardiovascular (CVS) risk. We compared the association between ten IR indices and cardiac, renal, and vascular end-organ measures in a predominantly young (age 45.0 ± 18.3 years) South African Black population. Methods: We assessed the relationships between ten IR indices (homeostatic model assessment for IR [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], metabolic score for IR [METS-IR], triglyceride–glucose index [TyG], TyG–body mass index [TyG-BMI], TyG–waist circumference [TyG-WC], TyG–waist-to-height ratio [TyG-WHtR], triglyceride to high-density cholesterol concentration [TyG-HDL], lipid accumulation product [LAP], visceral adiposity index [VAI]) and end-organ measures in 779 community participants of African ancestry. Results: HOMA-IR and QUICKI were the only IR indices consistently associated with end-organ measures (left ventricular [LV] mass index, p ≤ 0.005; LV relative wall thickness, p < 0.0001; early-to-late mitral velocity, p ≤ 0.01; E/e’, p ≤ 0.002; e’, p < 0.0001; pulse wave velocity, p = 0.036 (HOMA-IR only); glomerular filtration rate [GFR], p < 0.0001), independent of confounders. Furthermore, HOMA-IR was consistently higher, and QUICKI lower, in those with compared to those without end-organ damage (LV hypertrophy [p ≤ 0.03], concentric LV [p < 0.03], and reduced GFR [p ≤ 0.008]), independent of confounders. Importantly, the associations between HOMA-IR or QUICKI and end-organ measures were independent of additional CVS risk factors, including adiposity measures, and were replicated in the participants without diabetes mellitus (n = 669) and in the participants without high blood pressure (n = 505). Conclusions: In a predominantly young community of African ancestry, of ten recommended IR indices, only HOMA-IR and QUICKI were consistently associated with end-organ damage independent of CVS risk factors. Full article

Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: Eleven patients (n = 11) with a diagnosis of idiopathic HES were included in the study [M/F: 6/5, median age: 54 (95% CI: 38.2 to 68.5), smokers/never smokers: 5/6]. Asthma was present in the majority of them (n = 8, 72.7%); four patients (n = 4, 36.4%) presented with eosinophilic pleural effusions, two patients (n = 2, 18.2%) with cardiac arrhythmias, and one with bilateral eyelid angioedema. Eight patients (72.7%) were treated with mepolizumab (300 mg/month) and three (27.3%) with benralizumab (30 mg/4 weeks). The median values of eosinophils at baseline and 12 months after initiation of biologic agent were 3000 (95% CI: 2172 to 11,365) K/μL and 50 (95% CI: 3 to 190) K/μL, respectively, p = 0.0002. All patients with concomitant asthma (n = 8) experienced elimination of asthma flares, asthma control (ACQ < 0.75), functional improvement (mean ΔFEV1: 857 ± 594 mL), and an 82% reduction in oral corticosteroids, p = 0.0001. Materials and Methods: Patients with highly characterized idiopathic HES treated with anti-eosinophilic agents between 1 October 2019 and 1 October 2023 were retrospectively included in the study. The aim of this study was to present clinical, laboratory, and functional features and outcomes in patients with thoroughly investigated idiopathic HES treated with biologic agents targeting eosinophils. Conclusions: Biologic agents in patients with idiopathic HES—following thorough diagnostic investigation—are both safe and effective, sparing the toxicity of immunosuppressive agents. Real-life data from larger registries are greatly anticipated. Full article

Background/Objectives: It is known that chronic alcohol consumption causes alterations to various organs of the body, mainly the liver, but there are no reports of the damage that weekend alcohol consumption can cause to the liver. The liver is the main organ responsible for metabolizing ethanol and therefore experiences the most significant adverse effects of this xenobiotic’s toxicity. In this study, we evaluated the effect of weekend alcohol consumption on the activity of hepatic antioxidant enzymes. Methods: Wistar rats weighing 170–200 g were divided into the following groups: (1) control group and (2) weekend alcohol consumption group, 2 days per week for 12 weeks at two different concentrations: (1) group of males and females consuming a 40% alcohol solution and (2) group of males and females consuming a 5% alcohol solution. At the end of the experiment, liver samples were obtained. The activity of the enzymes catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase, as well as the levels of total antioxidant capacity and thiobarbituric acid reactive substances, were determined. Results: surprisingly, the results showed an increase in the activity of antioxidant enzymes, as well as a decrease in thiobarbituric acid reactive substances. Conclusions: weekend alcohol consumption for a period of 3 months led to an elevation in antioxidant enzyme activity, but it was not sufficient to prevent the damage caused to the liver by weekend alcohol consumption. Full article

Cadmium (Cd) is a toxic, non-essential metal that primarily enters animal bodies through the digestive and respiratory systems, leading to damage to multiple organs and tissues. Cd can accumulate in cartilage and induce damage to chondrocytes. Procyanidins (PAs), also known as concentrated tannic acid or oligomeric proanthocyanidins (OPCs), exhibit diverse biological and pharmacological activities. However, the mechanism of OPCs alleviates Cd-induced damage to chondrocytes in chickens remains to be further explored in vitro. Chondrocytes were isolated from both ends of the tibia of 17-day-old SPF chicken embryos, and then subsequently treated with various concentrations of Cd (0, 1, 2.5, 5, and 10 μmol/L) or OPCs (0, 5, 10, 20, and 40 μmol/L) to investigate the mechanism underlying extracellular matrix (ECM) degradation and damage. Cd reduced cell viability, glycosaminoglycan (GAG) secretion, and ECM degradation in chondrocytes by decreasing the expression of type II collagen alpha 1 (COL2A1) and aggrecan (ACAN) while increasing the release of cartilage oligomeric matrix protein (COMP), along with elevated levels of matrix-degrading enzymes, such as matrix metalloproteinases 1 (MMP1), MMP10, and MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5. Cd induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and the expression of matrix-degrading enzymes, impairing ECM synthesis, an effect that could be alleviated by ERK1/2 inhibitor U0126. Chondrocytes were treated with 5 μmol/L Cd and 10 μmol/L OPCs, and it was found that OPCs inhibited the activation of the ERK1/2 signaling pathway and the expression of matrix-degrading enzymes, while promoting ECM synthesis and alleviating Cd-induced ECM damage in chickens. This study provides a theoretical basis for clinical research on OPCs with respect to the prevention and treatment of Cd-induced chondrogenic diseases in poultry. Full article

Considerable losses are inflicted by plant-parasitic nematodes (PPNs) due to their obligate parasitism; serious damage occurs in many susceptible crops, and the parasites have a broad distribution worldwide. As most PPNs have a subterranean nature, the complexity of soils in the plant rhizosphere and the structures and functions of the soil food webs necessitate a grasp of the relevant biotic/abiotic factors in order to ensure their effective control. Such factors frequently lead to the inconsistent performance and untapped activity of applied bionematicides, hindering efforts to develop reliable ones. Research efforts that take these factors into account to back the usage of these bionematicides by combining the disease-suppressive activities of two or more agricultural inputs are highlighted herein. These combinations should be designed to boost useful colonization in the rhizosphere, persistent expression of desirable traits under a wide range of soil settings, and/or antagonism to a larger number of plant pests/pathogens relative to individual applications. Relevant ecological/biological bases with specific settings for effective PPN management are exemplified. Determining the relative sensitivity or incompatibility of some biologicals entails studying their combinations and reactions. Such studies, as suggested herein, should be conducted on a case-by-case basis to avoid unsatisfactory outputs. These studies will enable us to accurately define certain outputs, namely, the synergistic, additive, neutral, and antagonistic interactions among the inputs. In optimizing the efficiencies of these inputs, researchers should consider their multi-functionality and metabolic complementarity. Despite previous research, the market currently lacks these types of safe and effective products. Hence, further explorations of novel integrated pest management plans that boost synergy and coverage to control multiple pathogens/pests on a single crop are required. Also, setting economic incentives and utilizing a standardized regulation that examines the authentic risks of biopesticides are still called for in order to ease cost-effective formulation, registration, farmer awareness, and usage worldwide. On the other hand, tank mixing that ensures legality and avoids physical and chemical agro-input-based incompatibilities can also provide superior merits. The end in view is the unraveling of the complexities of interactions engaged with in applying multiple inputs to develop soundly formulated, safe, and effective pesticides. Sophisticated techniques should be incorporated to overcome such complexities/limitations. These techniques would engage microencapsulation, nanopesticides, volatile organic compounds as signals for soil inhabitants, bioinformatics, and RNA-Seq in pesticide development. Full article