Search Results (6,402)

Laparoscopic lens fogging and contamination pose significant challenges, leading to a reduced surgical field of view. Intraoperative cleaning to address these issues extends the surgical duration and elevates the risk of surgical site infections. The authors propose that a hydrophilic diamond-like carbon (DLC) coating would effectively mitigate fogging and fouling, thereby eliminating the requirement for intraoperative cleaning, while the scratch-resistant nature of DLC would provide additional benefits. The present study investigates the efficacy of aluminum oxide (Al₂O₃) as a dopant in diamond-like carbon (DLC) films for antifogging applications. The authors hypothesized that adding oxygen to the DLC matrix would increase surface energy by increased hydrogen bonding, resulting in a highly hydrophilic coating. Varying dopant concentrations were tested to observe their effects on hydrophilicity, transparency, biocompatibility, and wear properties. The doped films displayed a notable improvement in transparency throughout the visible spectrum. Plasma-cleaned samples demonstrated a substantial reduction in contact angles, achieving values less than 8°. The biocompatibility of these films was analyzed with CellTiter-Glo assays; the films demonstrated statistically similar levels of cell viability when compared to the control media. The absence of adenosine triphosphate released by blood platelets in contact with the DLC coatings suggests in vivo hemocompatibility. These films, characterized by high transparency, biocompatibility, and biostability, could be valuable for biomedical applications necessitating transparent coatings. Full article

The Philippines has a high diversity of venomous snake species, but there is minimal information on their envenomation effects. This is evidenced by the small number of case reports, the poor reporting of envenomation cases, and the absence of specific antivenoms apart from one against the Philippine cobra (Naja philippinensis). This study sought to profile the action of selected Philippine pit viper venoms on blood coagulation and to investigate whether commercially available non-specific antivenoms can provide adequate protection against these venoms. Venom from the pit vipers Trimeresurus flavomaculatus and Trimeresurus mcgregori were subjected to coagulation assays, antivenom cross-neutralization tests, and thromboelastography. Venoms from both species were able to clot human plasma and isolated human fibrinogen. Consistent with pseudo-procoagulant/thrombin-like activity, the resulting fibrin clots were weak and transient, thereby contributing to net anticoagulation through the depletion of fibrinogen levels. Clotting factors fIXa and fXa were also inhibited by the venoms, further contributing to the net anticoagulant activity. Monovalent and polyvalent antivenoms from the Thai Red Cross Society were effective against both venoms, indicating cross-neutralization of venom toxins; the polyvalent antivenom was able to rescue fibrinogen clotting to a greater degree than the monovalent antivenom. Our findings highlight the coagulopathic effects of these pit viper venoms and suggest the utility of procuring the non-specific antivenoms for areas in the Philippines with a high risk for pit viper envenomation. Full article

Recent studies show that patients with Alzheimer’s disease (AD) harbor specific methylation marks in the brain that, if accessible, could be used as epigenetic biomarkers. Liquid biopsy enables the study of circulating cell-free DNA (cfDNA) fragments originated from dead cells, including neurons affected by neurodegenerative processes. Here, we isolated and epigenetically characterized plasma cfDNA from 35 patients with AD and 35 cognitively healthy controls by using the Infinium^® MethylationEPIC BeadChip array. Bioinformatics analysis was performed to identify differential methylation positions (DMPs) and regions (DMRs), including APOE ε4 genotype stratified analysis. Plasma pTau181 (Simoa) and cerebrospinal fluid (CSF) core biomarkers (Fujirebio) were also measured and correlated with differential methylation marks. Validation was performed with bisulfite pyrosequencing and bisulfite cloning sequencing. Epigenome-wide cfDNA analysis identified 102 DMPs associated with AD status. Most DMPs correlated with clinical cognitive and functional tests including 60% for Mini-Mental State Examination (MMSE) and 80% for Global Deterioration Scale (GDS), and with AD blood and CSF biomarkers. In silico functional analysis connected 30 DMPs to neurological processes, identifying key regulators such as SPTBN4 and APOE genes. Several DMRs were annotated to genes previously reported to harbor epigenetic brain changes in AD (HKR1, ZNF154, HOXA5, TRIM40, ATG16L2, ADAMST2) and were linked to APOE ε4 genotypes. Notably, a DMR in the HKR1 gene, previously shown to be hypermethylated in the AD hippocampus, was validated in cfDNA from an orthogonal perspective. These results support the feasibility of studying cfDNA to identify potential epigenetic biomarkers in AD. Thus, liquid biopsy could improve non-invasive AD diagnosis and aid personalized medicine by detecting epigenetic brain markers in blood. Full article

The aim of this investigation was to measure the natural nocturnal plasma melatonin concentration in gestating and fresh ewes. Studies in humans showed that maternal melatonin had a significant increase as pregnancy progressed and then decreased after birth. Two studies conducted in sheep so far, considering the entire gestation, have led to conflicting results. The breed of 16 pregnant ewes selected for the research was the Tsigai. Blood samples were taken into EDTA vacutainers predetermined times a night at different stages of their gestation. The RIA method was used to determine the melatonin concentrations. For estimation of its variations during gestation, population genetic statistics was applied. It was found that the average plasma melatonin concentration of 134 pg mL⁻¹ is characteristic for the investigated period, and that it rises between the autumnal equinox and the winter solstice. Secondly, it was revealed that the average melatonin concentration adjusted for midnight is 162.4 pg mL⁻¹, and its moderate variation is characteristic for the night. The investigation showed that there is no connection between the plasma melatonin concentration of the ewes and their gestational age in the Tsigai breed in Middle Europe. Our result is consistent with the results of single studies in sheep and donkey, in contrast to human observations. With regard to the nocturnal plasma melatonin, the concentration is reduced at the same level (30 pg mL⁻¹) in ewes and lambs during the early postpartum period without nightly fluctuation. The expelled placenta, the constant vigilance between the mother and her lamb, and the opposition between melatonin and prolactin may provide a plausible explanation for this. Full article

Background: Invasive fungal disease is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Posaconazole, a broad-spectrum triazole, is widely used as prophylaxis. Methods: We conducted a monocentric, retrospective study to present real-world data on posaconazole trough levels in paediatric alloHSCT patients. The main objective was to determine the required daily dose of posaconazole in paediatric patients. We analysed factors influencing posaconazole levels, and the association between posaconazole levels and breakthrough fungal infection. Results: Among 102 allogeneic HSCT recipients, we measured posaconazole plasma concentrations in 548 blood samples. The required daily doses to reach a target range of 0.7–2.0 mg/L were 15.22 (suspension), 7.52 (tablet), and 7.84 mg/kg (intravenous). Patients aged < 13 years needed higher doses to achieve the target range. The presence of enteral symptoms during prophylaxis was associated with lower plasma concentrations (p < 0.001), while co-administration of proton pump inhibitors did not (p = 0.09). Eight breakthrough infections occurred; low levels of posaconazole (<0.7 mg/L) were observed in five out of eight cases. The Cox regression model showed that higher mean plasma concentrations decreased the hazard of breakthrough infections. Conclusions: The tablet and intravenous formulations of posaconazole outperformed the suspension in terms of predictability. Our analyses on breakthrough infections and posaconazole plasma levels suggest an exposure–response relationship. Full article

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western world. Targeted therapies have made CLL manageable for many patients, but the ongoing threat of disease relapse or transformation beckons a deeper understanding of CLL pathogenesis, and thus, its durable eradication. This study identifies bile acids (BAs) as elevated in the peripheral blood of CLL patients and a murine model of CLL, in comparison to healthy controls. Elevated BA concentrations have been associated with intestinal malignancies and immunomodulation; however, their role in CLL is relatively unknown. Methods: Metabolomic analysis was performed on murine and human plasma. Flow cytometry analysis of CLL patient B-cells and healthy donor T-cells were utilized to evaluate the immunomodulatory impact of differentially abundant BAs. Results: Herein, BAs were found to be differentially abundant in CLL. Elevated BAs demonstrated minimal impact on CLL cell proliferation or CLL-associated T-cell function. Conclusions: Future studies are needed to determine the mechanistic influence of BAs on CLL pathogenesis. Full article

Although the pathogenesis of the neurodegenerative phenomena of Huntington’s disease (HD) is not well known, in the last 30 years, numerous data have been published that suggest a possible role of oxidative stress. The majority of studies regarding this issue were performed in different experimental models of this disease (neurotoxic models such as intraperitoneal injection of 3-nitropropionic acid or intrastriatal injection of quinolinic acid, transgenic animal models for HD, and cell cultures) and, less frequently, in samples of brain tissue, plasma/serum, blood cells, and other tissues from patients with a genetic–molecular diagnosis of presymptomatic and symptomatic HD compared to healthy controls. In this narrative review, we have summarized the data from the main studies in which oxidative stress parameters have been measured both in patients with HD and in experimental models of the same disease, as well as the few studies on gene variants involved in oxidative stress in patients with HD. Most studies addressing this issue in experimental models of HD have shown an increase in markers or oxidative stress, a decrease in antioxidant substances, or both. However, the results of studies on patients with HD have not been conclusive as few studies have been published on the matter. However, a meta-analysis of blood studies on HD patients (including a pool of serum and blood cell studies) has shown an increase in lipid peroxidation markers, OH8dG concentrations, and GPx activity and a decrease in GSH levels. Future prospective and multicenter studies with a long-term follow-up period involving a large number of HD patients and healthy controls are needed to address this topic. Full article

hiPSC-derived blood–brain barrier (BBB) models are valuable for pharmacological and physiological studies, yet their translational potential is limited due to insufficient cell phenotypes and the neglection of the complex environment of the BBB. This study evaluates the plasma compatibility with hiPSC-derived microvascular endothelial-like cells to enhance the translational potential of in vitro BBB models. Therefore, plasma samples (sodium/lithium heparin, citrate, EDTA) and serum from healthy donors were tested on hiPSC-derived microvascular endothelial-like cells at concentrations of 100%, 75%, and 50%. After 24 h, cell viability parameters were assessed. The impact of heparin-anticoagulated plasmas was further evaluated regarding barrier function and endothelial phenotype of differentiated endothelial-like cells. Finally, sodium-heparin plasma was tested in an isogenic triple-culture BBB model with continuous TEER measurements for 72 h. Only the application of heparin-anticoagulated plasmas did not significantly alter viability parameters compared to medium. Furthermore, heparin plasmas improved barrier function without increasing cell density and induced a von Willebrand factor signal. Finally, continuous TEER measurements of the triple-culture model confirmed the positive impact of sodium-heparin plasma on barrier function. Consequently, heparin-anticoagulated plasmas were proven to be compatible with hiPSC-derived microvascular endothelial-like cells. Thereby, the translational potential of BBB models can be substantially improved in the future. Full article

Background/Objectives: The complex pathophysiology of painful cervical radiculopathy is only partially understood. Neuroimmune activation in the dorsal root ganglion and spinal cord is assumed to underlie the genesis of radicular pain. Molecular positron emission tomography (PET) using the radiotracer [¹¹C]DPA713, which targets the 18-kDa translocator protein (TSPO), offers the ability to quantify neuroinflammation in humans in vivo. The primary objectives of this study were to (1) assess whether uptake of [¹¹C]DPA713, a metric of neuroinflammation, is higher in the neuroforamina and spinal cord of patients with painful cervical radiculopathy compared with that in pain-free participants and (2) assess whether [¹¹C]DPA713 uptake is associated with clinical parameters, such as pain intensity. Methods: Dynamic 60 min [¹¹C]DPA713 PET/CT scans were acquired, and regions of interest were defined for neuroforamina and spinal cord. Resulting time-activity curves were fitted to a single-tissue compartment model using an image-derived input function, corrected for plasma-to-whole blood ratios and parent fractions, to obtain the volume of distribution (V_T) as the primary outcome measure. Secondary neuroinflammation metrics included 1T2k V_T without metabolite correction (1T2k_WB) and Logan V_T. Results: The results indicated elevated levels of 1T2k V_T at the neuroforamina (p < 0.04) but not at the spinal cord (p = 0.16). Neuroforamina and spinal cord 1T2k V_T lack associations with clinical parameters. Secondary neuroinflammatory metrics show associations with clinical parameters such as the likelihood of neuropathic pain. Conclusions: These findings enhance our understanding of painful cervical radiculopathy’s pathophysiology, emphasizing the neuroforamina levels of neuroinflammation as a potential therapeutic target. Full article

This study investigated the effects of iron supplementation and inflammatory disease on cortisol, white blood cell (WBC) count, total protein (TP), lactate, interleukin 1 β (IL1β), interleukin 6 (IL6), substance P (SP), hepcidin, haptoglobin, and ferric-reducing ability of plasma (FRAP) in calves. Correlation analyses for the aforementioned parameters with serum iron and ferritin were performed in 40 neonatal calves over the first 10 days of life. Neither iron supplementation, disease status, nor sex had statistically significant effects on the areas under the curve of ferritin, WBC, TP, IL1β, IL6, SP, hepcidin, haptoglobin, or FRAP. However, cortisol concentrations were influenced by disease development. Cortisol concentrations were higher at birth (44.1 ± 1.95 ng/mL) than on day 2 (38.8 ± 1.87 ng/mL) (p = 0.0477), and healthy animals exhibited lower cortisol concentrations than diseased calves (p = 0.0028). Correlation analyses indicated weak positive correlations between ferritin and IL1β (p = 0.0015; ρ = 0.49) and IL6 (p = 0.0011; ρ = 0.50), respectively. The clinical significance of these findings and resulting therapeutic consequences, especially with respect to iron supplementation, should be further investigated in calves and adult cattle. Full article

Background: Long COVID is characterized by persistent symptoms following acute SARS-CoV-2 infection. This study aims to evaluate immune system markers, including antigen-specific antibodies, B cell subsets, and Th2-related cytokines, in individuals with long COVID and to investigate their potential impact on the development of this condition. Methods: We analyzed blood plasma from 63 individuals diagnosed with long COVID based on clinical presentation and 47 healthy individuals with COVID-19 history but no clinical symptoms. Antigen-specific IgG antibodies were measured using commercial ELISA kits. Lymphocyte subpopulations were assessed via flow cytometry and a gating strategy based on CD27 and CD38. Th2 cytokines (IL-4, IL-5, IL-13) were quantified using the xMAP multiplex assay. Results: We noted no significant differences in IgG levels between groups. Notably, individuals with long COVID demonstrated a higher percentage of naive mature B cells (CD27−CD38+), while transitional (CD27−CD38+++) and double-negative (DN, CD27−CD38-) cells were significantly reduced. Elevated levels of IL-5 and IL-13 were observed in long COVID patients. Classification analysis revealed that the percentage of transitional B cells (CD27−CD38+++) was a strong predictor of long COVID. Conclusions: Our findings highlight alterations in B cell dynamics among individuals with long COVID, which may contribute to autoimmune processes. Full article

Platelet-rich plasma (PRP) is an extract enriched with growth factors that facilitate skin regeneration and rejuvenation. Here, the functionalities of PRP derived from various animal sources have been investigated and compared, focusing on its potential therapeutic applications in skin regeneration. Total antioxidant capacity, wound closure, and melanin content in cultured keratinocytes were used to evaluate the efficacy of different animal PRP sources. The PRP derived from deer exhibited the highest performance and was selected for subsequent proteomic and metabolomic analyses. Our findings indicate that deer blood is an optimal source of animal-derived PRP, demonstrating significant properties in promoting wound healing, anti-inflammatory responses, and skin regeneration. This identified PRP from deer sources can be developed as a safe and effective product for skin rejuvenation and regeneration. Full article

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor associated with vascular disease, which is prevalent in human plasma. Two isoforms of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), DDAH 1 and 2, degrade ADMA. This study investigates the association of DDAH 1 (rs669173, rs7521189) and DDAH 2 gene polymorphisms (rs805305, rs3131383) with the risk of preeclampsia (PE) comorbidity with human immunodeficiency virus (HIV) infection in pregnant women of African ancestry. A total of 405 women were enrolled in this study: 204 were PE, 201 were normotensive pregnant, and 202 were HIV positive. DNA was extracted from whole blood, and SNPs (rs669173, rs7521189, rs805305, and rs3131383) were amplified to detect single-nucleotide polymorphisms (SNPs). After PCR amplification, allelic discrimination was examined. Comparisons were conducted utilizing the Chi-squared test. Our findings indicated that preeclamptic women displayed a greater prevalence of the three variants compared to those with both PE and HIV infection. There is an association between the rs669173 and rs7521189 SNPs of the DDAH 1 gene and rs3131383 of the DDAH 2 gene, which could play a role in reducing the bioavailability of nitric oxide (NO), which affects endothelial function, leading to the development of PE in pregnant women of African ancestry. In contrast, the rs805305 variant of the DDAH 2 gene was not significantly associated with PE development. Interestingly, none of the SNPs investigated correlated with HIV infection or could be attributed to the human allelic variant influence on HIV infection outcome. Full article

Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in reports on EAE across animal strains/studies, limiting the utility of these biomarkers for predicting disease activity. In this study, we investigated blood-based analyte profiles, including neural markers (NFL and GFAP) and cytokines (IL-6, IL-17, IL-12p70, IL-10, and TNF-α), in two clinically distinct EAE models: relapsing-remitting (RR)-EAE and chronic-EAE. Ultrasensitive single-molecule array technology (SIMOA, Quanterix) was used to profile the analytes in the blood plasma of mice at the acute, chronic, and progressive phases of disease. In both models, NFL was substantially increased during post-disease onset across all phases, with a pronounced increase observed in chronic-EAE. The leakage of GFAP into peripheral blood was also greater after disease onset in both EAE models, especially in the acute phase of chronic-EAE. Among all cytokines, only IL-10 had consistently lower levels in both EAE models throughout the course of disease. This study suggests NFL, GFAP, and IL-10 as potential translational predictors of disease activity in EAE, making them potential candidates as surrogate markers for the preclinical testing of therapeutic interventions in animal models of MS. Full article

Background and Objectives: Despite notable advances in diagnosing and managing laryngeal cancer, the disease continues to present challenges, particularly in the advanced stages. Circulating microRNAs (miRNAs) are increasingly recognized as accessible biomarkers for cancer detection and follow-up. This exploratory study centers on identifying and evaluating miRNAs that are specifically downregulated in laryngeal carcinoma patients, aiming to clarify their clinical relevance in distinguishing pre- and post-therapeutic states. Methods: A total of 30 patients with laryngeal cancer provided paired blood samples before and after undergoing surgical or non-surgical treatment. To reduce variability and resource demand, each set of 10 samples was pooled into three pre-treatment groups (P1, P2, and P3) and three corresponding post-treatment groups (C1, C2, and C3). Total RNA, including miRNAs, was isolated from both plasma and exosomes, followed by qPCR-based profiling (Qiagen platform). Downregulated miRNAs were singled out through statistical comparisons using Mann–Whitney U tests; receiver operating characteristic (ROC) analyses and logistic regression were further applied to assess diagnostic utility. Results: Seven miRNAs demonstrated significant downregulation in the pre-treatment samples (fold changes ranging from 0.20 to 0.64, p < 0.05). Notably, hsa-miR-107 and hsa-let-7a-5p both showed marked reductions of approximately fivefold (p < 0.01), suggesting a strong association with active tumor presence. In ROC analysis, hsa-miR-107 achieved an area under the curve (AUC) of 0.78 (95% CI: 0.62–0.90) with 72% sensitivity and 74% specificity in differentiating pre- from post-treatment states. A logistic regression model incorporating downregulated candidates produced odds ratios between 0.52 and 0.64 (p < 0.05), pointing to their potential additive value in clinical decision-making. Conclusions: These preliminary findings indicate that certain miRNAs, when suppressed in circulation, may be linked to the oncogenic milieu of laryngeal cancer. Confirming these observations in larger, multicenter investigations is critical, but this pilot work underscores the promise of downregulated miRNAs as biomarkers of disease activity and potential guides to therapy response. Full article