Identification and validation of ferroptosis related markers in erythrocyte differentiation of umbilical cord blood-derived CD34+ cell by bioinformatic analysis.

Ferroptosis has been observed to play an important role during erythrocyte differentiation (ED). However, the biological gene markers and ferroptosis mechanisms in ED remain unknown. We downloaded the datasets of ED in human umbilical cord blood-derived CD34+ cells from the Gene Expression Omnibus database. Using median differentiation time, the sample was categorized into long and short groups. The differentially expressed ferroptosis-related genes (DE-FRGs) were screened using differential expression analysis. The enrichment analyses and a protein-protein interaction (PPI) network were conducted. To predict the ED stage, a logistic regression model was constructed using the least absolute shrinkage and selection operator (LASSO). Overall, 22 DE-FRGs were identified. Ferroptosis-related pathways were enriched using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Gene Set Enrichment Analysis and Gene Set Variation Analysis revealed the primary involvement of DE-FRGs in JAK-STAT, MAPK, PI3K-AKT-mTORC1, WNT, and NOTCH signaling pathways. Ten-hub DE-FRGs were obtained using PPI analysis. Furthermore, we constructed mRNA-microRNA (miRNA) and mRNA-transcription factor networks. Immune cell infiltration levels differed significantly during ED. LASSO regression analysis established a signature using six DE-FRGs (ATF3, CDH2, CHAC1, DDR2, DPP4, and GDF15) related to the ED stage. Bioinformatic analyses identified ferroptosis-associated genes during ED, which were further validated. Overall, we identified ferroptosis-related genes to predict their correlations in ED. Exploring the underlying mechanisms of ferroptosis may help us better understand pathophysiological changes in ED and provide new evidence for clinical transformation.

Comparison of erythrocyte sedimentation rate measurement between Westergren method and automated method among patients attending Jigjiga University Sheik Hassen Yabare Referral Hospital, Jigjiga, Ethiopia.

Introduction: Erythrocyte sedimentation rate (ESR) is a widely used screening test in clinical practice as an indicator of inflammatory and degenerative malignant diseases. The Westergren method, renowned as the gold standard, is valued for its accuracy and cost-effectiveness but demands considerable time and blood volume. Emerging automated methods offer quicker and more convenient alternatives, aiming to replace manual techniques. Nonetheless, validating these automated methods against the reference Westergren method is essential to ensure reliability. Therefore, this study aimed to evaluate ESR measurement results obtained from both the reference Westergren method and the automated (SFRI ESR 3000) method. Methods: A Hospital-based comparative cross-sectional study was conducted at Jigjiga University Sheik Hassen Yabare Referral Hospital from July 15 to September 16, 2023. Following the acquisition of informed consent, blood samples were obtained from 158 participants, five milliliters of blood from each participant. These samples were then subjected to ESR estimation using both the Westergren (reference) method and the automated (SFRI ESR 3000) method. Subsequently, the collected data were analyzed using SPSS version 20 and MedCalc version 12.3.0.0 statistical Softwares. Statistical analyses such as Paired t-tests, Pearson correlation, linear regression, and the Bland and Altman plot were employed. A p-value of < 0.05 was considered statistically significant. Results: The paired sample t-test analysis revealed no significant difference between the use of the reference Westergren method and the automated method for ESR determination, with a mean difference (MD) of 0.7 ± 9.2 mm/h (P = 0.36). Additionally, a significant correlation was observed between the two methods, with a remarkable correlation coefficient (r = 0.94, p < 0.001). The Bland-Altman data analysis indicated no evidence of systematic bias and demonstrated good agreement of ESR values between the two methods, with a limit of agreement of -17.3 to +18.7. Moreover, within-run imprecision analysis for the automated method across a range of ESR values showed coefficient of variation of 27.08, 12.65, and 10.32% for low, medium, and high ESR levels, respectively. Conclusions: The SFRI ESR 300 automated method demonstrates the potential for interchangeable use with the Westergren method for determining ESR, given the strong correlation and good agreement. Additionally, the same reference range could be applied during interpretation.

Abnormal erythrocyte-related parameters in children with Pb, Cr, Cu and Zn exposure.

The link between exposure to a particular heavy metal or metalloid and the development of anemia is well established. However, the association between combined exposure to multiple heavy metal(loid)s and anemia in children is still lacking in evidence. In this study, a total of 266 children aged 3 to 7 were recruited from Guiyu, China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure blood heavy metal(loid) concentrations. Blood cell count, hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), and red blood cell distribution width (RDW) were measured by an automated hematology analyzer. Erythrocyte-related parameters were negatively correlated with the Cu and Cu/Zn ratios and positively correlated with Cr, Ni, Zn, and Se by Spearman correlation analysis. Only blood Cu level was negatively correlated with HGB [ß = -2.74, (95% Cl: -4.49, -0.995)], MCH [ß = -0.505, (95% Cl: -0.785, -0.226)], MCV [ß = -1.024, (95% Cl: -1.767, -0.281)], and MCHC [ß = -2.137, (95% Cl: -3.54, -0.734)] by multiple linear regression analysis. The Bayesian Kernel Machine Regression (BKMR) model analysis indicated a negative correlation between the combined exposure to Cu, Zn, Pb, and Cr and MCH and MCV. The single-factor analysis showed a considerable statistical difference only with Cu on MCV, MCH, and HGB. Furthermore, the interaction analysis highlighted the interdependent effects of Cu and Zn, Pb and Zn, and Cr and Zn on MCH and MCV levels. Additionally, the oxidation and/or antioxidation reactions may play a significant role in the development of metal(loid)-induced anemia risk. It is crucial to investigate the effects of co-exposure to multiple heavy metal(loid) elements on anemia, especially the interrelationships and mechanisms among them.

Correlations of erythrocytic oligomer α-synuclein levels with age, sex and clinical variables in patients with Parkinson's disease.

Introduction: Oligomeric alpha-synuclein in red blood cells (RBC-o-α-Syn) has been shown to be increased in patients with Parkinson's disease (PD). However, factors that affect RBC-o-α-Syn levels remain to be elucidated. The aim of this study is to analyze the correlations between RBC-o-α-Syn levels and the age, sex and different clinical variables of patients with PD. Methods: 167 patients with PD and 119 healthy controls (HC) were enrolled in this study. The patients with PD were diagnosed based on the MDS clinical diagnostic criteria for PD. All participants were evaluated for their clinical characteristics. Western blot analysis was used to examine the molecular sizes of RBC-o-α-Syn. A newly established chemiluminescent immunoassay was used to measure RBC-o-α-Syn levels. Results: Higher RBC-o-α-Syn levels were detected in PD patients than in HC subjects. The receiver operating characteristic (ROC) curve indicated that a cut off value of 55.29 ng/mg discriminated well between PD patients and HC subjects, with a sensitivity of 67.66% (95% CI: 60.24-74.29%), a specificity of 88.24% (95% CI: 81.22-92.86%), and an area under the curve (AUC) of 0.857. The levels of RBC-o-α-Syn were higher in female than male patients (p = 0.033). For different subtypes, the levels of RBC-o-α-Syn were higher in the MIX subtype than the tremor-dominant (TD) PD. In addition, the levels of RBC-o-α-Syn were higher in patients with than without cognitive impairment (p = 0.016), and negatively correlated with Mini-Mental State Examination (MMSE) scores (r = -0.156, p = 0.044). Conclusion: Our study demonstrates that RBC-o-α-Syn levels in patients with PD are higher than those in HC subjects and affected by the sex and the severity of cognitive impairment.

Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment.

Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.

Investigation of Antioxidant Mechanisms of Novel Peptides Derived from Asian Swamp Eel Hydrolysate in Chemical Systems and AAPH-Induced Human Erythrocytes.

Sixteen novel antioxidant peptides from Asian swamp eel (ASE) were identified in previous studies. However, their chemical and cellular antioxidant mechanisms remain unclear. Molecular docking of these peptides with ABTS and DPPH radicals revealed the critical role of hydrogen bonding and Pi-Pi stacking hydrophobic interactions between hydrophobic amino acid residues and free radicals. Residues, such as tryptophan, proline, leucine, and valine, played significant roles in these interactions. All these peptides exhibited notable erythrocyte morphoprotective effects in a model of AAPH-induced oxidative damage of human erythrocytes. Erythrocyte hemolysis was reduced primarily through the modulation of both non-enzymatic (GSH/GSSG) and enzymatic antioxidant systems (SOD, CAT, and GSH-Px) by these peptides. A decrease in levels of MDA, LDH release, and hemoglobin oxidation was observed. Among the peptides, VLYPW demonstrated superior chemical and cellular antioxidant activities, which may be attributed to its higher levels of tyrosine and tryptophan, as well as to its increased hydrophobic amino acid content.

Erythrocyte Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

BACKGROUND: This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). METHODS: A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). RESULTS: Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. CONCLUSIONS: This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals.

A Contemporary Review of Blood Transfusion in Critically Ill Patients.

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

Erythrocyte-Mimicking Nanovesicle Targeting Porphyromonas gingivalis for Periodontitis.

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.

ABO Blood System: Biosynthesis of Agglutinogenic Alkaline and Non-Agglutinogenic Acid Glycotopes of A and B Antigens at Different pHs of the Culture Medium.

The biosynthesis of agglutinogenic and adsorbing groups A and B glycotopes of the erythrocyte's membrane is mediated by the activity of specific glycosyltransferases. This study aimed to assess the nature of the biosynthesis of A and B antigenic glycotopes, depending on the pH of the medium during the cultivation of erythrocytes, and the antigenic (transferase) characteristics of the donor serum of the other group. Monoclonal antibodies (Mabs) were obtained from IGBRL under Program IV of the International Workshop on Monoclonal Antibodies and Red Blood Cell Antigens. Biosynthesis was performed using erythrocytes, fresh serum, medium 199, and an antibiotic solution. The agglutinogenic characteristics of 11 out of 33 samples changed by the end of the cultivation period due to the acquisition of additional agglutinogen corresponding to the donor serum. None of the samples lost their inherent agglutinogen due to its absence in the donor serum. Four of six samples of O(I) erythrocytes acquired the ability to be agglutinated by anti-A reagents, especially by the polyclonal anti-A, and the manifestation of agglutination depended on the reaction time. Two of the three samples with initial A(II) agglutinogenic specificity added to the donor serum with Bc'+ characteristic of the erythrocytes acquired this characteristic. However, none of the five A(II)Ac'+ samples cultured in the serum of Ac'-O(I)Ac'-Bc'+ and O(I)Ac'-Bc'- donors lost their inherent earlier Ac'+ characteristic. The investigation of the inhibitory ability of alkaline and acidic glycoconjugates isolated from membranes revealed that alkaline Alp-00 and Alp-1 glycotopes isolated from glycolipids had the highest inhibitory activity, and the degree of inhibition of polyclonal anti-A antibodies was even higher than that of monovalent BRIC-131. This study showed the possibility of the biosynthesis of specific non-agglutinogenic A and B glycotopes under the influence of a different group's serum as a source of the corresponding transferase.

Unveiling the diverse bioactivity of cobalt oxide nanoparticles produced through carboxymethyl cellulose extraction.

This study explores an eco-friendly method for synthesizing Cobalt oxide nanoparticles (Co3O4NPs) using extracted carboxymethyl cellulose (CMC) as a reducing and stabilizing agent. The Co3O4NPs, characterized via various analyses, demonstrated a crystalline structure with sizes ranging from 10.9 to 28.2 nm. Microscopic imaging confirmed a uniform spherical morphology with an average diameter of 27.2 nm. The biological activities of Co3O4NPs were investigated extensively, highlighting their superior antibacterial efficacy compared to amoxicillin-clavulanic acid. These nanoparticles exhibited potent antioxidant properties and demonstrated safety for potential applications based on erythrocyte viability results. Additionally, Co3O4NPs displayed significant potency against Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and showed promising α-amylase enzyme inhibitory activity, highlighting their multifunctional therapeutic potential as antioxidant, antibacterial, anticancer, and alpha-amylase inhibition assay.

Hypoxia-sonic hedgehog axis as a driver of primitive hematopoiesis development and evolution in cavefish.

The teleost Astyanax mexicanus consists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and exhibit a subset of phenotypic traits controlled by increased Sonic hedgehog (Shh) signaling along the embryonic midline. The enhancement of primitive hematopoietic domains, which are formed bilaterally in the anterior and posterior lateral plate mesoderm, are responsible for the development of more larval erythrocytes in cavefish relative to surface fish. In this study, we determine the role of hypoxia and Shh signaling in the development and evolution of primitive hematopoiesis in cavefish. We show that hypoxia treatment during embryogenesis increases primitive hematopoiesis and erythrocyte development in surface fish. We also demonstrate that upregulation of Shh midline signaling by the Smoothened agonist SAG increases primitive hematopoiesis and erythrocyte development in surface fish, whereas Shh downregulation via treatment with the Smoothened inhibitor cyclopamine decreases these traits in cavefish. Together these results suggest that hematopoietic enhancement is regulated by hypoxia and Shh signaling. Lastly, we demonstrate that hypoxia enhances expression of Shh signaling along the midline of surface fish embryos. We conclude that hypoxia-mediated Shh plasticity may be a driving force for the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish.

Predictive value of flexible proctosigmoidoscopy and laboratory findings for complete clinical responses after neoadjuvant chemoradiotherapy in patients with locally advanced primary rectal cancer: a retrospective cohort study.

PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.

Isolated Acromioclavicular Joint Septic Arthritis: A Case Report and Review of Literature.

A 60-year-old diabetic patient presented with acute pain and swelling localized to the left acromioclavicular joint. Laboratory and radiological investigations revealed the presence of pus in the left acromioclavicular joint along with bony erosion of the lateral end of the left clavicle. She was treated with open arthrotomy, debridement, and appropriate antibiotics for the causative methicillin-resistant Staphylococcus aureus (MRSA) infection. Prompt diagnosis and timely intervention can reduce the morbidity and mortality due to septic arthritis. We conducted a review of the literature on patients treated for isolated septic arthritis of the acromioclavicular joint.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Examining the impact of polyfluoroalkyl substance exposure on erythrocyte profiles and its related nutrients: Insights from a prospective study on young Taiwanese.

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects.

Developmental and heritable genetic defects induced in mice by municipal landfill leachate.

Environmental pollution by solid waste leachate is a serious environmental and public health concern. Leachate contamination and pollution of environmental matrices have been reported, but no report of embryotoxic and developmental defects, and heritable transfer of leachate-induced toxicity in mice. We investigated the ability of Aba-Eku landfill leachate to induce embryonic malformations, developmental toxicity, and germline and somatic DNA damage in the F1 of exposed pregnant mice. Pregnant mice (n = 100) were randomly distributed into 5 experimental groups of 20 animals/group and exposed to 0.2 mL of 5-75% concentrations of the leachate (v/v; Aba-Eku landfill leachate: distilled water) by daily gavage from gestational day (GD) zero to postnatal day (PND) 21. A similar treatment was given to pregnant female mice administered with distilled water (negative control). At GD 18, ten dams from the treatment and control groups were sacrificed by cervical dislocation after which the embryos were collected from the uterus for analyses of fetal morphometric and skeletal metamers respectively. We then monitored the developmental conditions of F1 mice from the remaining ten dams until they were weaned at PND 21 and sacrificed at PND 56 and PND 98 for bone marrow micronucleus and spermiogram analyses respectively. We also analyzed the leachate for inorganic and organic pollutants and calculated the Leachate Pollution Index (LPI). The leachate reduced maternal and fetal birth weight and increased fetal mortality and postnatal appearance of physiological markers in the F1 mice. There was a significant increase (p < 0.05) in the frequency of fetal skeletal malformations, micronucleated polychromatic erythrocytes, and apparent decline of epididymal sperm parameters. The concentrations of the inorganic and organic pollutants, and the LPI exceeded standard limits. Exposure of pregnant female mice to Aba-Eku landfill leachate caused embryonic defects and heritable DNA damage in subsequent generations.

Effect of apical foraminal enlargement on postoperative pain and inflammatory markers in asymtomatic single-rooted mandibular teeth with apical periodontitis - An in vivo randomized controlled trial.

Aim of the Study: This study aims to assess the effect of apical foraminal enlargement on inflammatory markers and pain in patients with asymptomatic single-rooted mandibular teeth with apical periodontitis. Materials and Methods: The study included 60 patients based on inclusion and exclusion criteria. Before beginning root canal treatment (RCT), a blood sample was obtained from the antecubital fossa to evaluate the inflammatory markers, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Access opening was done and initial irrigation was done. Working length (WL) was determined with an electronic apex locator and verified with a radiograph. In the control group, the determined WL was maintained, while in the experimental group, the WL was set till the apical foramen. Biomechanical preparation was done in both groups till F2 or F3 based on the initial apical file, followed by final irrigation and obturation based on the master apical file size. Patients were given a Visual Analog Scale to record pain sensations at 24, 48, and 72 h postoperative. After 72 h, patients were recalled for follow-up appointments, and blood was taken from the antecubital fossa again to evaluate inflammatory markers. Statistical Analysis: The resultant findings for the reduction in inflammatory markers before and after RCT with or without foraminal enlargement were statistically analyzed using the Student's t-test. The pain was statistically examined with one-way "analysis of variance" and Tukey's post hoc test for inter-group comparison of pain. The level of significance was set at P < 0.05. The statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 23 for Windows (SPSS Inc., Chicago, IL, USA). As pain in the control groups is zero before and after RCT, statistical analysis is not required as the overall pain score is zero. Results: The P values of the CRP and ESR of the control group were 0.02 and 0.03, respectively, which indicates it is significant whereas the P values of the ESR and CRP of the experimental group were 0.0002 and 0.0008 which indicates it is highly significant. Results indicate that the experimental group is more effective compared to the control group in reducing inflammatory markers. Pain in the control group after RCT was zero at the end of 24, 48, and 72 h. In the experimental group, where RCT was done with apical foraminal enlargement, mild pain was present at the end of 24 h which gradually decreased at the end of 48 h and no pain was reported at the end of 72 h. Conclusion: Reduction in inflammatory markers was more effective in RCT with apical enlargement than without apical enlargement. RCT with apical enlargement caused mild pain in the patients immediately after treatment which gradually decreased over time.

Non-specific markers of inflammation in bare-nosed wombats (Vombatus ursinus) with sarcoptic mange.

Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei, negatively impacts the health, welfare, and local abundance of bare-nosed wombats (Vombatus ursinus) in Australia. Improved understanding of the host immune response to disease and its contribution to pathophysiology could be used to inform management actions for this species in and ex situ. To evaluate the immune response of bare-nosed wombats to sarcoptic mange, we validated three assays (haptoglobin, agarose gel electrophoresis, and micro-erythrocyte sedimentation rate) measuring non-specific markers of inflammation using serum samples from free-living wombats from Tasmania (n = 33). We then analysed correlations between the assay results for each non-specific marker of inflammation and wombat's sarcoptic mange scores, and performed histopathological examinations to investigate association of the acute phase response with systemic amyloidosis. We present evidence that haptoglobin and erythrocyte sedimentation rate increased, and albumin decreased, in association with sarcoptic mange scores. This research demonstrates links between the acute phase response and sarcoptic mange severity in bare-nosed wombats, highlighting the utility of non-specific markers of inflammation for aiding assessment of the systemic effects of mange. Showing the value of agarose gel electrophoresis, we also identified specific acute phase proteins warranting future evaluation and found evidence of an immunoglobulin response in mange-affected wombats, revealed by increasing γ-globulins in association with apparent disease severity. Meanwhile, owing to its relatively low resource requirements and rapidity, the erythrocyte sedimentation rate assay may be useful as a point-of-care test to support therapeutic decisions in the field. Our methods and findings are likely to be applicable to a range of other clinical and population health scenarios in captive and free-living wombats, and species impacted by sarcoptic mange globally.

Assessing the Correlation of Periodontal Inflamed Surface Area (PISA) With Systemic Inflammatory Markers.

Background Periodontitis has a vital role in eliciting a cross-reactivity or systemic inflammatory response, making periodontal inflamed surface area (PISA) a primary contributor to the inflammatory burden posed by periodontitis. PISA helps in the quantification of the amount of inflamed periodontal tissue. However, the existing literature data concerning PISA as an indicator of inflammatory burden are scarce, with limited research on the relationship between systemic inflammatory markers and PISA. Aim The present clinic-hematological cross-sectional study aimed to correlate PISA with systemic inflammatory markers. The study also aimed to assess serum concentrations of inflammatory markers such as erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), and peripheral blood markers such as neutrophils and monocytes and to correlate these markers with PISA. Methods The study assessed 62 subjects, who were divided into two groups of 31 subjects, each following bleeding on probing (BOP) criteria. Group I consisted of subjects with generalized chronic gingivitis, and Group II included subjects with generalized chronic periodontitis. In two groups, BOP, probing pocket depth, clinical attachment level, and gingival recession were assessed along with PISA by a custom-made R function derived from a pre-existing, freely available MS Excel spreadsheet (Microsoft Corporation, Redmond, Washington). The results of the assessment were then compared. Results A statistically highly significant positive correlation was seen in PISA and CRP with a correlation coefficient of 0.4875 and p-value of 0.000059. A similar statistically significant positive correlation was seen in ESR and PISA with a correlation coefficient of 0.4089 and p-value of 0.000968. A statistically non-significant correlation was seen in neutrophils and PISA with p=0.576018. However, a moderate and positive statistically significant association was seen in monocyte and PISA with a correlation coefficient of 0.3258 and p-value of 0.009956. Conclusions The present study concludes that most of the common systemic inflammatory markers have a positive correlation with PISA. However, more studies are required to establish this correlation.