Hematological Parameters Research Articles

Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment. Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed. Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed. Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.

Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study. Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters. Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels. Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).

Systemic immune-related spleen radiomics predict progression-free survival in patients with locally advanced cervical cancer underwent definitive chemoradiotherapy.

Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity. This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters. Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001). Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity.

Sex-Induced Changes in Microbial Eukaryotes and Prokaryotes in Gastrointestinal Tract of Simmental Cattle

This study investigates gender-based differences in the gut microbiota of Simmental cattle, focusing on bacterial, archaeal, and fungal communities. Fecal samples were collected and analyzed using high-throughput sequencing, with taxonomic classification performed through the SILVA and UNITE databases. Alpha and beta diversity metrics were assessed, revealing significant differences in the diversity and composition of archaeal communities between males and females. Notably, females exhibited higher alpha diversity in archaea, while beta diversity analyses indicated distinct clustering of bacterial and archaeal communities by gender. The study also identified correlations between specific microbial taxa and hematological parameters, with Treponema and Methanosphaera showing gender-specific associations that may influence cattle health and productivity. These findings highlight the importance of considering gender in microbiota-related research and suggest that gender-specific management strategies could optimize livestock performance. Future research should explore the role of sex hormones in shaping these microbial differences.

Clinical characteristics of monoclonal immunoglobulin-associated renal disease: a retrospective cohort study.

Clinical epidemiological data on monoclonal gammopathy of renal significance (MGRS) are lacking. In this retrospective observational study, MGRS was compared with B-cell or plasma cell malignancies (BCM/PCM) with renal involvement to clarify differences in their clinical features. Among the 1408 renal biopsies performed at our hospital, 25 MGRS and 18 BCM/PCM patients were identified. We investigated baseline characteristics and hematologic parameters of MGRS in reference to BCM/PCM using multivariable analysis. Cox proportional hazards analysis was performed for end-stage kidney disease (ESKD) and all-cause mortality. Comparing the MGRS with the BCM/PCM, meandifferences in creatinine level, estimated glomerular filtration rate, and clonal bone marrow plasma cell percentage were -2.76mg/dL, 27.72mL/min/1.73m2, and -18.86%, respectively (all P < 0.001). MGRS group had a predominance of glomerular lesions such as immunoglobulin-associated amyloidosis, cryoglobulinemic GN, and MIDD, and a lower risk of acute kidney injury/acute renal disease compared to BCM/PCM. During a median observation period of 23.7months, clone-directed therapy was performed in 32.0% of patients in the MGRS group, compared to 83.3% of patients in the BCM/PCM group. Compared with BCM/PCM, MGRS had a hazard ratio of 0.66 (95% confidence interval (CI) 0.23-1.92, P = 0.45) for ESKD and 0.33 (95% CI 0.11-1.03, P = 0.06) for death in multivariate logistic regression analysis. The clinical characteristics of MGRS and BCM/PCM with monoclonal immunoglobulin-associated renal disease are disparate. Understanding these differences is crucial for developing tailored clinical approaches and therapeutic strategies to improve patient outcome.

Toxicological evaluation of Carthamus lanatus L (Carthame laineux) hydro-alcoholic extract in Wistar rats: acute oral toxic effects

Background: Despite the well-known phytotherapeutic properties of Carthamus lanatus L in traditional medicine, there is little evidence on its toxicity profile in hematological and biochemical parameters. Objective: This study was intended to evaluate the acute toxicity effect of Carthamus lanatus L. Methods: The toxicological impact of a hydroalcholic extract of Carthamus lanatus (HAECL) at 200, 400, and 800 mg/kg body weight on hematological indices in rats was assessed gradually at 24 hours after 1, 10, and 14 days. Results: We observed no significant difference in the consumption of food, body weight, or relative organ weights. Hematological and biochemical parameters revealed the non-adverse effects of prolonged oral consumption of Carthamus lanatus except for a slight increase but no significant increase in ASAT and ALAT and a no significant decrease in the percentage of basophils. Conclusions: These data imply that the extract has a non-hematotoxic potential. Overall, the impact of carthamus lanatus extract in this study shows that it is unlikely to be hematotoxic and might be a promising candidate in the treatment of coronary heart disease if taken at the levels tested.

The Relationship Between Systemic Immune Inflammatory Level and Dry Eye in Patients with Sjögren’s Syndrome

Background and objectives: Sjögren Syndrome (SS) is a chronic, systemic, and progressive autoimmune disease in which inflammatory processes play a role. Dry eyes or mouth are present in approximately 95–98% of patients with pSS. This study aimed to evaluate the relationship between SII level and disease activity as well as dry eye involvement in patients with pSS. Materials and methods: A cross-sectional design was employed, and a total of 28 female patients who were aged 18–65 years and were diagnosed with pSS were involved. The Sjögren Syndrome Disease Activity Index (ESSDAI) was calculated in patients. The Schirmer test was applied to all patients. The relationship between SII level and disease activity as well as dry eye involvement in pSS patients was evaluated. Results: In our study, a strong positive correlation was found between the SII value and pSS disease activity, while a negative correlation was found between the Schirmer test, which shows dry eye findings, and eye drying time, and a positive correlation was found with the OSDI. Conclusions: this study reported a correlation between hematological parameters and the development of dry eye in pSS. NLR, PLR, and SII showed statistically significant changes in pSS patients.

Leukocyte formula of the Walser’s Viper (Vipera walser)

Vipera walser is a recently assessed species of North-Western Italian Alps, that has been regarded as an isolated population of V. berus until 2016, when it has been identified as a separate taxonomical unit according to molecular markers. Due to its restricted and fragmented range and the potential threat of climate change in mountain systems, it complies with the IUCN criteria to be classified as EN. In order to investigate, in part, the health status of this taxon, we have performed blood smears to describe whether a haematological parameter such as leukocytes is consistent with those of more widespread viperids of the Italian peninsula. Overall, we sampled 20 Walser’s Vipers across the species range and characterised leukocyte formula. We found that lymphocytes were the most common (~ 70% of total leukocytes). Eosinophils and heterophils were less abundant, while neutrophils and monocytes are the least represented. Our data is in accordance with that of other European viperids

Dietary Effect of Withania somnifera (Ashwagandha) Root Powder on Growth and Blood Parameters of Cyprinus carpio (Common Carp)

Aims: The present study evaluated the effect of different levels of Withania somnifera root powder in fish formulated diets on the growth performance of economically important freshwater fish species in Asia Cyprinus carpio and compare the hematological changes occurred in fishes fed with control feed and herbal formulated diet. Study Design: The experiment was planned with the size group of 30.0±1.0g. Fish of the respective size group of Cyprinus carpio were subjected to different herbal formulated diets at a concentration 0%, 0.5%, 1.0%, 1.5%, 2.0% of Withania somnifera root powder extract through their diet, while the control group received a standard diet without any supplementation. Duration of Study: The study was conducted over a period of 4 weeks. Methodology: During which growth parameters such as Average Daily Growth, Specific Growth Rate and Absolute Growth Rate were monitored at regular (10 days) intervals. The blood samples were collected at 4th week from each group to assess hematological parameters including Red Blood Cell count, White Blood Cell count, Hemoglobin, Total Cholesterol and Total serum protein levels. The overall results revealed that the inclusion of Withania somnifera extract in the diet of Cyprinus carpio significantly influenced both growth and blood parameters. Results: Fish exposed to Withania somnifera extract exhibited enhanced growth performance compared to the control group, with increased Average Daily Growth, Specific Growth Rate and Absolute Growth Rate. Moreover, hematological analysis revealed positive effects on the blood parameters of treated fish, including improvements in Red Blood Cell count, White Blood Cell count, Hemoglobin, Total Cholesterol and Total serum protein levels. Conclusion: The overall results revealed that the inclusion of Withania somnifera extract in the diet of Cyprinus carpio significantly influenced both growth and blood parameters.

Serum lactate dehydrogenase as a prognostic marker for treatment response in IDH wild-type glioblastoma patients undergoing stupp protocol.

Elevated lactate dehydrogenase (LDH), a marker of tumor aggressiveness and metabolic alterations, may predict treatment response and overall survival across various tumors. This study investigates the correlation between serum LDH levels and clinical outcomes in glioblastoma patients treated with radiotherapy (RT) and temozolomide (TMZ). This retrospective study analysed patients with IDH wild-type glioblastoma (IDH-wt GB) treated at the Radiotherapy Department of Azienda Ospedaliero-Universitaria Senese from 2018 to 2023. Clinical data, including hematologic parameters (e.g., LDH), imaging (MRI), and MGMT promoter methylation status, were collected. All patients received RT and TMZ following the Stupp protocol. Serum LDH levels were measured one week before RT, and Radiological Response (RR) was assessed using RANO criteria. Overall survival (OS), progression-free survival (PFS), and RR were primary endpoints. Statistical analyses included Kaplan-Meier, Cox regression, and decision tree analysis for LDH cut-off determination. In a cohort of 147 IDH wild-type glioblastoma patients treated with the Stupp protocol, the median OS was 14 months and median PFS was 8 months. Elevated baseline LDH levels were associated with significantly poorer outcomes, showing a median OS of 9 months versus 20 months and a median PFS of 6 months versus 13 months for lower LDH levels (p < 0.001 and p = 0.0001, respectively). LDH levels also correlated with RR (p = 0,001), Multivariate analysis confirmed high LDH as an independent predictor of worse OS (HR = 2.31) and PFS (HR = 2.60), suggesting its utility as a prognostic biomarker. Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.

Abstract I008: Antisense Oligonucleotides as Therapeutics for Difficult-to-Drug Targets in Oncology

Abstract Many potential oncology targets are difficult to modulate by conventional classes of agents. Interfering with these targets at the level of RNA is a novel approach for difficult-to target proteins, as well as for non-coding RNAs, emerging targets that are part of the “dark matter’ of the genome. Antisense oligonucleotide (ASO) therapeutics are short sequences of 12- 30 DNA/RNA residues, designed to bind the cognate transcribed RNA. The ASO is chemically modified to increase stability, improve binding affinity, optimize pharmacokinetic properties and reduce immunostimulatory potential. The hybridization of ASO to cognate RNA results in cleavage of bound RNA by RNAse H1 and subsequent degradation. Several ASOs are marketed for treatment of rare diseases, but to date none have been approved for oncology indications. The long-noncoding RNA (lncRNA) MALAT1 is an example of an oncology target uniquely suited for an ASO therapeutic. This lncRNA is not translated and resides mostly in the nucleus, limiting access for most therapeutic approaches. MALAT1 is highly upregulated in various cancers, appears to play a role in epithelial to mesenchymal transition, and is associated with disease progression in patients. Inhibition of MALAT1 in preclinical breast cancer models, either genetic or pharmacologic using a murine ASO, leads to changes in tumor architecture and reduction in metastasis. FLM-7523 is a 16-mer ASO designed to bind to human MALAT1. It is a generation 2.5 design based on the constrained ethyl (cEt) modification to the 3 residues on the 3’ and 5’ ends of the ASO, and administered in a saline solution without any delivery vehicle. Preclinical studies have shown that FLM-7523 effectively inhibits MALAT1 expression in in vitro and in vivo models, and GLP toxicology studies have been completed to support a First-in-Human clinical trial. The signal transduction molecule STAT3 is another oncology target of interest that has, to date, been difficult to modulate. Danvatirsen is a 16-mer generation 2.5 ASO targeting human STAT3 mRNA and is currently in clinical trials. Preclinical in vivo studies in murine tumor models have demonstrated a reduction in STAT3 mRNA and protein following treatment with a STAT3 targeting ASO, along with tumor growth inhibition. Combination treatments with immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1, demonstrate improved tumor growth inhibition relative to monotherapy. In clinical trials, tumor uptake of danvatirsen is observed in post-treatment biopsies, with corresponding reduction in STAT3 protein. Danvatirsen is generally well tolerated with the most common adverse events being increased liver function tests and decreased myeloid hematologic parameters, both of which are easily monitored, manageable, and reversible. Clinical responses have been observed with the most robust being in combination with a PD-L1 inhibitor in recurrent/metastatic head and neck squamous cell carcinoma. In conclusion, ASOs are novel therapies that can inhibit oncology targets not tractable by traditional approaches. Citation Format: Andrew Denker. Antisense Oligonucleotides as Therapeutics for Difficult-to-Drug Targets in Oncology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr I008.

Glucocorticoids influence on rat hematological parameters and catalase activity

In this study, the impact of glucocorticoid, betamethasone dipropionate on enzyme activity in vitro and its effects on hematological parameters in vivo was investigated. The immobilized catalase, crucial for cell oxidative stress response via hydrogen peroxide reduction, exhibited a robust electrocatalytic response, maintaining its biological activity. The in vitro inhibition kinetics of catalase, as determined by electrocatalytic methods and expressed using Lineweaver-Burke diagrams, revealed an uncompetitive type of inhibition with altered Imax and Km in the presence of a range of betamethasone dipropionate concentrations. The in vivo experiments conducted on Rattus norvegicus demonstrated significant alterations in hematological parameters following betamethasone dipropionate administration. These changes included a decrease in erythrocyte count, an increase in hemoglobin, a reduction in mean corpuscular volume (MCV), and an elevation in mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Notably, the leukocyte counts substantially increased. The observed hematological shifts suggest an impact of betamethasone dipropionate on the hematopoietic system, reinforcing the need for cautious corticosteroid administration. The findings underline the necessity for judicious corticosteroid treatment, acknowledging both enzymatic and systemic repercussions.

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Dietary intervention of propolis and/or turmeric boosted growth, hematology, biochemical profile, and antioxidant-immune responses and their associated gene expression in Nile tilapia (Oreochromis niloticus) challenged with Edwardsiella tarda

AbstractImmunostimulant phytogenic feed additives are given great concern for improving fish health, growth, immune responses, and resistance to diseases. This research investigated the impact of dietary propolis (PRO), turmeric (TUR), and their combination on the growth, hematology, antioxidant-immune responses, and their regulating genes in Nile tilapia (Oreochromis niloticus) during Edwardsiella tarda challenge. For 8 weeks, a total number of 320 fish (20.70 ± 0.14 g) were allocated into four groups at random, each with eight replicates (10 fish each). The first group (1st) was given the basal diet (control) without any supplements. The 2nd, 3rd, and 4th groups were supplemented with 1% PRO, 1% TUR, and the mixture (1%PRO + 1%TUR), respectively. The experimental groups were challenged intraperitoneally with E. tarda at a dose of 0.1 mL (1 × 105 CFU) at the termination of the feeding trial, and the fish survival was estimated for an additional 7 days. The results demonstrated that fish-fed diets supplemented with PRO and/or TUR showed higher body weight, condition factor, specific growth rate, feed intake, and feed efficiency utilization than the control group (P &lt; 0.05). The hematological, protein profile, and antioxidant-immune (total antioxidant capacity, lysozymes, and IgM) parameters were substantially improved in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed fish. The lipid profile and malondialdehyde were substantially decreased in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed group. Notably, a down-turning of nuclear factor kappa B (NFκB) and tumor necrosis factor-alpha (TNF-α) expression with up-turning of nuclear factor erythroid 2-related factor 2 (Nrf2) and transforming growth factor-beta (TGF-β) expression was noticed in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed fish. Noteworthy, dietary PRO and/or TUR improved the fish survival during E. tarda challenge. The mixture of PRO and TUR can be added to Nile tilapia diets to enhance their growth, immune response, and resistance to E. tarda. These outcomes help in the sustainable development of the Nile tilapia culture industry. Graphical Abstract

Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?

As white-footed mice, Peromyscus leucopus, are considered the primary animal reservoir of Borreliella burgdorferi sensu stricto (Bb), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen, P. leucopus adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for Bb-infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for Peromyscus mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of P. leucopus mice to the borrelial infection, presenting no restriction to a long-term host-pathogen co-existence.

Assessment of Haematological Profiles in Apparently Healthy Male Kombai Dogs in Theni District, Tamil Nadu

The hematological profiles of apparently healthy male Kombai dogs in Theni district was studied in this research. Twelve male Kombai dogs had their cephalic veins venipunctured to obtain blood samples, which were then analysed. Red blood cell count, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular hemoglobin concentration, and haemoglobin content were among the haematological parameters measured. The study also included a total white blood cell count, which includes eosinophils, neutrophils, lymphocytes, monocytes, granulocytes, and platelets. This information may be helpful to veterinary clinicians and biomedical researchers.

Hematological changes in women with cervical cancer before and after cancer treatment: retrospective cohort study.

Hematological changes is one of the most common complications occurred in cancer patients. Therefore, the current study aimed to assess the hematological toxicity of cervical cancer patients before and after the initiation of treatment. The retrospective cohort study was conducted from 2015 to 2022 at the University of Gondar Comprehensive Specialized Hospital. The hematological profile and sociodemographic and clinical data of the cervical cancer patients were collected using data extraction sheets. The Epidata version 3.1 and SPSS version 25 were used for data entry and analysis, respectively. Descriptive statistics were employed to summarize the data. To compare the median differences in hematological parameters before and after treatment, the Wilcoxon rank test was used. In addition, to assess the presence of an independent association between hematological abnormalities and the independent variables, logistic regression models were used. A p value less than 0.05 was considered to indicate statistical significance for all tests. In current study, the median (Interquartile range) of hemoglobin levels, white blood cell counts, and platelet counts, before treatment were 13.2 (12.1, 15) g/dl, 7.5 (5.8, 11.8) *109/L, and 330 (252, 383) *109/L, respectively. However, after treatment the median (Interquartile range) value of hemoglobin levels, white blood cell counts, and platelet counts were significantly lowered. On the other hand, red cell distribution width was significantly greater after treatment. At baseline, the magnitude of leucocytosis, anemia, and thrombocytosis were 27.9%, 24.6%, and 18.7%, respectively. After the treatment, anemia increased to 44.3%, but leucocytosis and thrombocytosis were replaced by leucopenia 18.3% and thrombocytopenia 17.8%, respectively. Hematological abnormalities such as anemia, leucopenia and thrombocytopenia were high after chemo-radiotherapy, and surgery. As the stage of cancer advances, the risk of developing anemia, leucocytosis, and thrombocytosis increased in 7.6, 6.9 and 9 times, respectively. Furthermore, being HIV patients and rural resident increased the risk of developing anemia about twofold. In conclusion hematological abnormalities were observed before and after cervical cancer treatment, with significance increment after chemo-radiotherapy and surgery. As the stage of cancer advances, the risk of developing hematological abnormalities increases. Therefore, routine monitoring of hematological changes before and after treatment and screening for major risk factors are important for improved patients' management.

Haematological parameters and biochemical indices of African catfish (Clarias gariepinus) exposed to glyphosate-based herbicide (Force up®) for 96 hours

IntroductionGeometric aquaculture growth has resulted in exponentially increasing use of agrochemicals as either parasiticides or herbicides in the aquaculture environment. This study determines some of the toxicological (haematological and biochemical) effects of glyphosate-based herbicides on non-target aquatic animals using Clarias gariepinus as the animal model.MethodSeventy-five apparently healthy adult C. gariepinus (300 g) were sourced from a local farmer and acclimatised for 2 weeks; of these, sixty subjects were divided into four treatment groups (fifteen fish per group and five replicates per unit) by simple randomisation and labelled as T0 (control), T1 (first treatment), T2 (second treatment), and T3 (third treatment). The treatments were replicated thrice. Four concentrations of Force up® [0 mL, 0.15 mL (0.003 mL/L or 5.1 mg/L), 0.225 mL (0.0045 mL/L or 7.65 mg/L), and 0.3 mL (0.006 mL/L or 10.2 mg/L) were added to a 50-L tank of water for T0, T1, T2, and T3, respectively. Approximately 5 mL of blood was collected from the fish in each treatment group 96 h post-exposure for measurement of the blood parameters and biochemical indices using standard analytical methods as well as calculation of the mean values.ResultThe mean values of the packed cell volume, haemoglobin concentration, red blood cell count, and white blood cell count compared to the control group showed an initial increase at T1 but decreased as the glyphosate concentrations increased at T2 (0.0045 mL/L) and T3 (0.006 mL/L). The platelet mean values decreased at T1, increased at T2, and decreased at T3, while the mean values of the corpuscular volume, corpuscular haemoglobin, and corpuscular haemoglobin concentration increased with glyphosate concentration, with the mean corpuscular haemoglobin concentration decreasing at T2. Only the platelet value was statistically significant at a p-value of &amp;lt;0.05 using ANOVA and post hoc Tukey test. The biochemical indices showed decreases in the mean values of aspartate transaminase, blood urea nitrogen, creatinine, and triglycerides at T1, increases at T2, and decreases at T3, while the total protein (g/dL), cholesterol, alanine transaminase, and alkaline phosphatase values showed increases at T1 and decreases at T2 and T3. All these values were not statistically significant based on ANOVA and had p-values &amp;gt;0.05.DiscussionBased on the results of this study, it is deduced that glyphosate-based herbicide (Force up®) has genotoxic, hepatotoxic, and nephrotoxic effects on C. gariepinus even at sublethal doses, with more adverse effects at increasing concentrations.

IEPA, a novel radiation countermeasure, alleviates acute radiation syndrome in rodents

Repurposing therapeutic agents with existing clinical data is a common strategy for developing radiation countermeasures. IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling. Here, we evaluated IEPA’s radiomitigative efficacy in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) using total-body irradiation (TBI) models in C57BL/6J mice and WAG/RijCmcr rats, applying various posology schemes and introducing syringe feeding of the IEPA formulation in the pudding. Additionally, we assessed IEPA in the delayed effects of acute radiation exposure (DEARE) model after partial-body irradiation (PBI) in WAG/RijCmcr rats. Endpoints included survival, body weight, hematology, and pulmonary parameters, depending on the model. Results from mouse and rat TBI models demonstrated survival improvements with repeated IEPA dosing at 10 mg/kg, with the largest benefits observed in the bi-daily (BID) treatment over the 30-day ARS phase in female rats. Survival across PBI-DEARE subsyndromes was comparable between IEPA and vehicle groups, though IEPA improved pulmonary parameters in female rats during the lung-DEARE phase. Sex-related differences in response to irradiation and IEPA were noted, with females showing a survival advantage. IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA’s radiomitigative efficacy.

The Effect of Direct Anticoagulant Therapy on Haematological Parameters in Atrial Fibrillation: Clinical Significance of Subclinical Haemoglobin Decrease

Background and Objectives: Direct oral anticoagulants (DOACs) have become the cornerstone of stroke prevention in the management of atrial fibrillation (AF). While their efficacy in preventing catastrophic outcomes is well documented, the exploration of their effects on haematological parameters, particularly in clinically stable AF patients, remains markedly underrepresented in existing research. The aim of our investigation was to delineate the variations in key haematological parameters, with a special focus on haemoglobin (Hb), in a cohort of clinically stable patients afflicted with AF and receiving diverse oral anticoagulant treatments. Materials and Methods: In this retrospective study, 742 patients with AF were evaluated. Following exclusion criteria, 530 patients were included and categorised based on the change in their Hb levels (ΔHb &lt; 2 [n = 473] vs. ΔHb ≥ 2 [n = 57]) after one year of initial prescription of DOACs. Results: Patients in the ΔHb ≥ 2 g/dL group demonstrated significantly higher baseline haemoglobin levels during the pre-DOAC period (13.5 [12.3–14.6] vs. 14.6 [13.1–15.7]; p = 0.002). Baseline haemoglobin was identified as a predictive factor for a decrease in Hb ≥ 2 g/dL, with higher initial values being associated with more pronounced reductions (OR, 95% CI: 1.424 [1.178–1.723]; p &lt; 0.005). This pattern was observed consistently across various types and dosages of DOACs. Conclusions: This study underscores the importance of vigilant clinical monitoring for anaemia in patients undergoing DOAC therapy, even when their clinical course appears to be stable.