Differential Blood Cell Counts Research Articles

Advanced Bio-sensing Technologies for Sickle Cell Disease Diagnosis.

Sickle cell diseases are widespread in regions encompassing the Mediterranean, Middle East, sub-Saharan Africa, and specific parts of Asia, primarily due to the abnormal production of hemoglobin S. This genetic blood disorder stems from a mutation in the beta-globin gene, a crucial component of hemoglobin and the heme-containing protein found in red blood cells. Point mutations in the hemoglobin gene can be inherited as a heterozygous or homozygous pattern. These mutations disrupt the normal configuration of the protein, impeding its physiological function and altering the cell's shape, giving it a sickle-like appearance. The resulting sickle cells can lead to organ damage, intense physical discomfort, and anemia; in severe cases, the condition can be fatal. Early detection and effective treatment methods have the potential to progressively reduce the associated mortality rate over time. To diagnose sickle cell disease and its carrier states with unparalleled specificity, a variety of approaches have been developed. The most common method includes differential blood cell counts and their assessment, high-performance liquid chromatography (HPLC) and hemoglobin electrophoresis. Furthermore, innovative sensing technologies are currently under development, encompassing user-friendly, cost-effective and portable point-of-care devices that are capable of timely diagnosis at the genetic and molecular levels of these disorders. The review delves into a range of established and innovative strategies utilized in the detection of sickle cell disease, also underscoring the essential role played by diverse bio-sensing techniques in propelling the advancement of early diagnosis of SCD.

No evidence linking sleep traits with white blood cell counts: Multivariable-adjusted and Mendelian randomization analyses.

Disturbances in habitual sleep have been associated with multiple age-associated diseases. However, the biological mechanisms underpinning these associations remain largely unclear. We assessed the possible involvement of the circulating immune system by determining the associations between sleep traits and white blood cell counts using multivariable-adjusted linear regression and Mendelian randomization. Cross-sectional multivariable-adjusted linear regression analyses were done using participants within the normal range of total white blood cell counts (>4.5 × 109 and <11.0 × 109/μL) from UK Biobank. For the sleep traits, we examined (short and long) sleep duration, chronotype, insomnia symptoms and daytime dozing. Two-sample Mendelian randomization analyses were done using instruments for sleep traits derived from European-ancestry participants from UK Biobank (over 410,000 participants) and using SNP-outcome data derived from European-ancestry participants from the Blood Cell Consortium (N = 563,946) to which no data from UK Biobank contributed. Using data from 357,656 participants (mean [standard deviation] age: 56.5 [8.1] years, and 44.4% men), we did not find evidence that disturbances in any of the studied sleep traits were associated with differences in blood cell counts (total, lymphocytes, neutrophiles, eosinophiles and basophiles). Also, we did not find associations between disturbances in any of the studied sleep traits and white blood cell counts using Mendelian Randomization. Based on the results from two different methodologies, disturbances in habitual sleep are unlikely to cause changes in blood cell counts and thereby differences in blood cell counts are unlikely to be underlying the observed sleep-disease associations.

Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support.

To discover potential micro(mi)RNA biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep-sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9-24] days since symptoms initiation) and 21 healthy noninfected individuals. A total of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2-infected patients showed significantly (fold change [FC] > 1.2 and adjusted p [padj] < 0.05) altered expression of 190 miRNAs. The top-10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin, and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found, when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow.

Manipulation of neonatal ruminal populations at birth results in sustained effects on microbial populations and measures of health and production in merino and suffolk lambs

The efficiency of the microbial-driven fermentation process in the rumen is closely related to the efficiency of the ruminant host. This experiment examined the effect of manipulating the neonatal microbiota on postnatal development, immune function and productivity (liveweight gain and wool growth parameters). The trial examined the differences between naturally inoculated lambs (maternal control, n = 21) and those given ruminal fluid, which had been collected from ruminally-cannulated ewes, fed either a roughage diet (roughage, n = 14), or a grain-based diet (high grain, n = 14). At lambing, newborn lambs were tagged and weighed. Inoculation lambs received 10 ml of rumen fluid per inoculation, daily, for a total of 7 inoculations. Live weight, body condition scores, wool growth (greasy and clean wool weights), wool length, mean fibre diameter, and differential blood cell counts, and IgG and IgA in both blood and saliva) were quantified from birth until week 18 (slaughter). Total feed intake was recorded from weaning. Ruminal fluid was collected by stomach tube from 12 lambs from each treatment group and their dams (n = 7–8 per treatment, with the lower number of ewes coming about through ewes that had twins) at time of weaning (week 10). The pH of the ruminal fluid, the density of ciliated protozoa in ruminal fluid, and the composition of the ruminal bacterial populations were analysed. At slaughter (week 18), ileal samples were taken from the same focal lambs as were used for microbial analysis. The artificial inoculations resulted in significant differences in ruminal bacterial genera to those of naturally inoculated lambs at time of weaning (some 3 months post-lambing). Significant differences were also apparent in ileal bacterial communities at slaughter, between lambs which had received the inoculum from roughage-fed ewes and naturally inoculated lambs. Both the efficiency (growth, condition, feed conversion efficiency, carcass weight) and indices of health (mortalities, red blood cell count, blood haemoglobin concentration, haematocrit, and eosinophil counts) of the inoculated animals, were affected negatively by the inoculations ( < 0.05). There was a significant interaction between inoculum source and breed in terms of effects on all parameters measured. The effects of the high grain inoculation were significantly affected by breed, with high grain merinos found to have reduced mean fibre diameter (P < 0.05) and increased wool growth relative to the maternal control (P = 0.035). This effect was not noted in the suffolks. In summary, we have demonstrated that long-term effects on ruminal and intestinal microbiota can be generated by intervention in the normal process of ruminal inoculation in neonatal lambs. Moreover, there appeared to be genetic differences in response to artificial inoculation. Whilst the effects of artificial inoculation in this trial were negative in terms of indices of health and production, further studies of maternal diet and its effects on the natural establishment of the neonatal microbiota are warranted given the persistence of the effects and the interaction with breed.

Baseline haematological parameters in three common Australian frog species.

Amphibians are experiencing declines globally, with emerging infectious diseases as one of the main causes. Haematological parameters present a useful method for determining the health status of animals and the effects of particular diseases, but the interpretation of differential cell counts relies on knowing the normal ranges for the species and factors that can affect these counts. However, there is very little data on either normal haematological parameters or guides for blood cell types for free-ranging frog species across the world. This study aims to 1) create a visual guide for three different Australian frog species: Litoria paraewingi, Limnodynastes dumerilii, and Crinia signifera, 2) determine the proportions of erythrocytes to leukocytes and 3) differential leukocytes within blood smears from these three species and 4) assess the association between parasites and differential counts. We collected blood samples from free-ranging frogs and analysed blood smears. We also looked for ectoparasites and tested for the fungal disease chytridiomycosis. Overall, we found that the differentials of erythrocytes to leukocytes were not affected by species, but the proportions of different leukocytes did vary across species. For example, while lymphocytes were the most common type of leukocyte across the three species, eosinophils were relatively common in Limnodynastes dumerilii but rarely present in the other two species. We noted chytridiomycosis infection as well as ectoparasites present in some individuals but found no effect of parasites on blood parameters. Our results add baseline haematological parameters for three Australian frog species and provide an example of how different frog species can vary in their differential blood cell counts. More information is needed on frog haematological data before these parameters can be used to determine the health status of wild or captive frogs.

Immune response in men patients infected with toxoplasmosis

The primary aim of this study was to determine the differential count of white blood cells and the serum levels of (CCR2 and testosterone) in patients with Toxoplasmosis and the healthy group. The study was conducted on 260 Males suspected of Toxoplasmosis ages ranging from 20-50 years old. All these cases were examined by measuring Toxo IgM and IgG serum levels, who attended AL-Hakeem hospital, and (30) healthy males as the control group, collected randomly from AL-Najaf province, these samples were collected from March 2023 to August 2023. Any patient was using the drug or undergoing disease removal from the current study. The present study revealed the numbers and percentage of infected patients fifty out of 260 (19.23%) male patients. The current study was conducted on the effect of WBCs (Monocyte, Lymphocyte and Neutrophil) in patients infected with Toxoplasmosis. The results showed that high concentrations of Monocyte and Neutrophil (9.560± 0.244 ×103 µL) (10.65± 0.13%) (72.48± 0.575%) respectively for the patient, and (6.660 ± 0.067 ×103 µL) (6.933 ± 0.064 %) (52.50 ± 0.252 %) respectively for compared to the control group. However, no significant changes were recorded for lymphocytes (34.33± 0.881%) in patients infected with Toxoplasmosis compared to the control group. The current study revealed that the concentration of (testosterone, CCR2) inpatients infected with Toxoplasmosis was a significant increase (P&lt;0.05) compared to the control group. The current study has concluded that infection with Toxoplasmosis may be a risk factor. A chronic T. gondii infection is associated with variations in levels of serum hormones for can result in inducted behavioural alterations and these variations may influence the immune system by (Testosterone, CCR2).

Development of a Multi-Organ Radiation Injury Model with Precise Dosimetry with Focus on GI-ARS.

The goal of this study was to establish a model of partial-body irradiation (PBI) sparing 2.5% of the bone marrow (BM2.5-PBI) that accurately recapitulates radiological/nuclear exposure scenarios. Here we have reported a model which produces gastrointestinal (GI) damage utilizing a clinical linear accelerator (LINAC) with precise dosimetry, which can be used to develop medical countermeasures (MCM) for GI acute radiation syndrome (ARS) under the FDA animal rule. The PBI model (1 hind leg spared) was developed in male and female C57BL/6 mice that received radiation doses ranging from 12-17 Gy with no supportive care. GI pathophysiology was assessed by crypt cell loss and correlated with peak lethality between days 4 and 10 after PBI. The radiation dose resulting in 50% mortality in 30 days (LD50/30) was determined by probit analysis. Differential blood cell counts in peripheral blood, colony forming units (CFU) in bone marrow, and sternal megakaryocytes were analyzed between days 1-30, to assess the extent of hematopoietic ARS (H-ARS) injury. Radiation-induced GI damage was also assessed by measuring: 1. bacterial load (16S rRNA) by RT-PCR on days 4 and 7 after PBI in liver, spleen and jejunum, 2. liposaccharide binding protein (LBP) levels in liver, and 3. fluorescein isothiocyanate (FITC)-dextran, E-selectin, sP-selectin, VEGF, FGF-2, MMP-9, citrulline, and serum amyloid A (SAA) levels in serum. The LD50/30 of male mice was 14.3 Gy (95% confidence interval 14.1-14.7 Gy) and of female mice was 14.5 Gy (95% confidence interval 14.3-14.7 Gy). Secondary endpoints included loss of viable crypts, higher bacterial loads in spleen and liver, higher LBP in liver, increased FITC-dextran and SAA levels, and decreased levels of citrulline and endothelial biomarkers in serum. The BM2.5-PBI model, developed for the first time with precise dosimetry, showed acute radiation-induced GI damage that is correlated with lethality, as well as a response to various markers of inflammation and vascular damage. Sex-specific differences were observed with respect to radiation dose response. Currently, no MCM is available as a mitigator for GI-ARS. This BM2.5-PBI mouse model can be regarded as the first high-throughput PBI model with precise dosimetry for developing MCMs for GI-ARS under the FDA animal rule.

The Effect of Probiotics in a Milk Replacer on Leukocyte Differential Counts, Phenotype, and Function in Neonatal Dairy Calves.

Probiotics have been investigated for many health benefits; however, few studies have been performed to determine the effects of oral probiotics on peripheral blood and respiratory immune cells in cattle. Our objectives were to determine changes in health and growth status, differential blood cell counts and function, and blood and lung cell function using flow cytometry and PCR in dairy calves fed a milk replacer with (PRO, N = 10) or without (CON, N = 10) the addition of probiotics to the milk replacer and dry rations from birth to weaning. Performance and clinical scores were not different between the treatment groups. Treatment-by-day interactions for peripheral blood leukocyte populations differed in cell number and percentages. A greater percentage of leukocytes expressed the cell surface markers CD3, CD4, CD8, CD11b, and CD205 on d 21 in CON animals. Lung lavages were performed on five animals from each treatment group on d 52. There were no differences between treatment groups for the expression of cytokines and Toll-Like Receptors as measured using Polymerase Chain Reaction, possibly due to the small sample size. Oral probiotics appear to affect peripheral blood immune cells and function. Their effect on overall calf health remains to be determined.

Are sex differences in blood cell count and hemoglobin moderated by the 2D:4D ratio? A cross-sectional study in a Ghanaian population.

There are sex differences in blood cell count and hemoglobin (HGB) in adulthood due to differences in the levels of circulating sex hormones. The second-to-fourth digit ratio (2D:4D) is the putative marker of prenatal hormone exposure. The 2D:4D or the right-left difference (Dr-l) are sexually dimorphic and are correlates of sex hormones in adulthood. The study sought to determine whether sex differences in adult blood cell count and HGB can be partly explained by the 2D:4D or Dr-l. The study was cross-sectional between June and December 2021 at the University for Development Studies. The study involved 207 healthy participants (females = 113)aged from 18 to 32 years. The right-hand (2D:4DR), and the left-hand (2D:4DL) digit ratio and their difference (Dr-l) were measured using Computer-assisted analysis. Blood cell count, HGB, testosterone, and estradiol were measured from venous blood samples using an automated HGB analyzer and ELIZA technique. The platelet count was inversely related to the 2D:4DR in the total sample with the 2D:4DR accounting for about 0.2% (adjR 2 = 0.002) of the variability in platelet count. However, there was a sex difference as indicated by the significant interaction between sex and the 2D:4DR on platelet count (p = 0.03). The relationship between platelet count and the 2D:4DR was negative in females but positive in males. Also, there was a positive relationship between HGB concentration and the Dr-l in the total study sample, where the Dr-l accounted for about 0.6% (adjR 2 = 0.006) of the variability in HGB concentration. Sex interacted significantly with the Dr-l on HGB concentration (p = 0.01) such that the relationship between HGB and the Dr-l was positive in females but negative in males. Prenatal hormone exposure, as indexed by the 2D:4D ratio, may partly account for the observed sex differences in platelet count and HGB levels in adulthood.

UR-Net: An Integrated ResUNet and Attention Based Image Enhancement and Classification Network for Stain-Free White Blood Cells.

The differential count of white blood cells (WBCs) can effectively provide disease information for patients. Existing stained microscopic WBC classification usually requires complex sample-preparation steps, and is easily affected by external conditions such as illumination. In contrast, the inconspicuous nuclei of stain-free WBCs also bring great challenges to WBC classification. As such, image enhancement, as one of the preprocessing methods of image classification, is essential in improving the image qualities of stain-free WBCs. However, traditional or existing convolutional neural network (CNN)-based image enhancement techniques are typically designed as standalone modules aimed at improving the perceptual quality of humans, without considering their impact on advanced computer vision tasks of classification. Therefore, this work proposes a novel model, UR-Net, which consists of an image enhancement network framed by ResUNet with an attention mechanism and a ResNet classification network. The enhancement model is integrated into the classification model for joint training to improve the classification performance for stain-free WBCs. The experimental results demonstrate that compared to the models without image enhancement and previous enhancement and classification models, our proposed model achieved a best classification performance of 83.34% on our stain-free WBC dataset.

Seroprevalence of &lt;i&gt;Toxoplasma gondii&lt;/i&gt; infection in pregnant women attending selected general hospitals in Yobe State, Nigeria

Toxoplasma gondii is an obligate intracellular parasite which affects warm blooded animals including humans and causes toxoplasmosis. It is an endemic zoonotic disease which can be transmitted by consuming undercooked meat or contaminated foods, its primary host is the domesticated cats. The parasite causes wide range of diseases which is unapparent and asymptomatic in immune- competent individuals but leads to serious health problems in immunosuppressed individuals and pregnant women. It is the main cause of congenital toxoplasmosis in pregnant women. This study was carried out to detect the presence of T. gondii in pregnant women attending selected general hospitals in Yobe State. A total of 360 samples were obtained from 3 senatorial district which are Gashua, Potiskum and Gaidam general hospitals with 120 samples each from each district. Gashua recorded the highest prevalence of 18.3% while Potiskum and Gaidem recorded 15.0% and 5.0% respectively with an overall prevalence of 12.77%. It showed a statistical significance at p≤ 0.05 using Toxoplasma elisa IgM capture kit. The mean differential and white blood cell count recorded from pregnant women in the study was relatively low as participants from Gaidam hospital recorded the lowest mean value at 2.50x 109 cells/L while participants from Gashua hospital recorded 4.00x 109 cells/L and pregnant women from Pokiskum hospital recorded 3.30x 109cell/L. In conclusion, this zoonotic infection obtained from domesticated cats can be identified to cause congenital toxoplasmosis which can be fatal to the foetus.

Evaluating the Developed Model of Experimental Rhinitis in Laboratory Rats: Pre-Clinical Experimental Randomized Study

Background. Among the damaging factors affecting the mucociliary system of the nasal cavity, surgical wound is of particular relevance in the practice of an otorhinolaryngologist. The clinical assessment of regeneration of the mucociliary system is associated with certain diffi culties, since the intravital morphological examination of the nasal mucosa in patients is traumatic. Therefore, the development of animal models of experimental rhinitis is considered to be highly relevant in order to study the dynamics of mucociliary pathomorphological changes and assess the epithelium regeneration.Objectives. To evaluate the developed model of experimental rhinitis in laboratory rats by studying clinical, morphological and biochemical changes in the infl ammatory process.Methods. The experimental rhinitis model was developed and tested on 60 mature male Wistar rats. All animals were randomized into two groups: experimental group #1 (n = 30) — rats in which experimental rhinitis modeling was performed and group #2 (n = 30) — control, intact animals. In the course of the experiment, the authors examined the content of CRP in blood, evaluated the differential blood cell count, and studied a morphology of the nasal septum mucosa in 2, 5, 10 days after the injury to assess the dynamics of the infl ammatory process in rats of both groups. Statistical analysis of the study results was carried out by means of Statistica 8.0 (StatSoft Inc., USA).Results. After injury, the rats from group #1 developed acute rhinitis, which was clinically manifested by the release of mucous or mucopurulent secretion from the nostrils, sneezing and scratching the nose. An increase in CRP, band and segmented neutrophils, and a decrease in lymphocytes were observed in blood of the rats from group #1 in comparison with the control group. Microscopic analysis of changes in the nasal septum mucosa showed that the acute phase of exudative infl ammation developed on the second day: vascular congestion, edema, neutrophilic infl ammatory infi ltration of the submucosal membrane were observed against the background of foci of epithelial necrosis. The proportion of lymphocytes and macrophages in the infl ammatory infi ltrate increased by the fi fth day, initial signs of restoration of epithelial tissue — the formation of an undifferentiated regenerating epithelium — appeared by the tenth day.Conclusion. The results of the study show that an adequate experimental model of acute rhinitis in laboratory animals have been obtained. An acute infl ammatory process is characterized by clinical manifestations and changes in blood parameters. Particular destructive and reparative-proliferative changes develop in the mucous membrane of the nasal septum of experimental animals as a result of a surgical wound.

Clinical, Hematological, Biochemical and Radiological Characteristics for Patients With Splenic Infarction: Case Series With Literature Review.

Splenic infarction is a frequently missed diagnosis in acute clinical conditions and is often under-diagnosed due to the lack of high-quality evidence on pathophysiology of splenic infarction. Due to the scarcity of such evidence, no consensus guidelines regarding the diagnostic approach and management of patients with splenic infarction exist. Most of published articles on splenic infarction are case reports and there was no systematic review on splenic infarction. We conducted a retrospective analysis of all radiologically confirmed cases of splenic infarction patients with any history of admission at National Center for Global Health and Medicine Kohnodai Hospital, from 2014 to 2020. Further, to understand the pathophysiology that causes splenic infarction, we searched the literatures on splenic infarction. We found 18 patients with splenic infarction. The average age was 78 years, and about half of patients had abdominal pain; however, the other half did not have abdominal pain. One-third of patients with splenic infarction died. Leukocytosis with neutrophilia, a decrease of lymphocytes, anemia, hypoalbuminemia, and liver dysfunction were observed. Fibrinogen was decreased and D-dimer was remarkably elevated. Lactate dehydrogenase (LDH) and C-reactive protein (CRP) were remarkably increased. Six patients (33.3%) had cancer, four patients (22.2%) had atrial fibrillation, and four patients (22.2%) had infection. We found 466 case reports on splenic infarction published from 1975 to 2021. Recently, the number of case reports on splenic infarction due to infection, especially, coronavirus disease 2019 (COVID-19), has been remarkably increasing. Furthermore, we found that leukocytosis, a decrease of lymphocytes, elongated activated partial thromboplastin time, decrease of fibrinogen, liver dysfunction, elevation of LDH and blood urea nitrogen can be the prognosis predicting factors for patients with splenic infarction. Our study elucidated clinical, hematological, biochemical and radiological characteristics for patients with splenic infarction. We newly found significant differences in blood cell counts, coagulation markers, transaminases, LDH and blood urea nitrogen between patients who died and those who survived, suggesting that these parameters can be the prognosis predicting factors for splenic infarction. Further, our systematic review on case reports about splenic infarction showed the etiology of splenic infarction and the trend of the causative diseases.

Internal relative potency factors based on immunotoxicity for the risk assessment of mixtures of per- and polyfluoroalkyl substances (PFAS) in human biomonitoring

Relative potency factors (RPFs) for per- and polyfluoroalkyl substances (PFAS) have previously been derived based on liver effects in rodents for the purpose of performing mixture risk assessment with primary input from biomonitoring studies. However, in 2020, EFSA established a tolerable weekly intake for four PFAS assuming equal toxic potency for immune suppressive effects in humans. In this study we explored the possibility of deriving RPFs for immune suppressive effects using available data in rodents and humans. Lymphoid organ weights, differential blood cell counts, and clinical chemistry from 28-day studies in male rats from the National Toxicology Program (NTP) were combined with modeled serum PFAS concentrations to derive internal RPFs by applying dose–response modelling. Identified functional studies used diverse protocols and were not suitable for derivation of RPFs but were used to support immunotoxicity of PFAS in a qualitative manner. Furthermore, a novel approach was used to estimate internal RPFs based on epidemiological data by dose–response curve fitting optimization, looking at serum antibody concentrations and key cell populations from the National Health and Nutrition Examination Survey (NHANES). Internal RPFs were successfully derived for PFAS based on rat thymus weight, spleen weight, and globulin concentration. The available dose–response information for blood cell counts did not show a significant trend. Immunotoxic potency in serum was determined in the order PFDA > PFNA > PFHxA > PFOS > PFBS > PFOA > PFHxS. The epidemiological data showed inverse associations for the sum of PFOA, PFNA, PFHxS, and PFOS with serum antibody concentrations to mumps and rubella, but the data did not allow for deduction of reliable internal RPF estimates. The internal RPFs for PFAS based on decreased rat lymphoid organ weights are similar to those previously established for increased rat liver weight, strengthening the confidence in the overall applicability of these RPFs.

225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617.

In the present study, SibuDAB, an albumin-binding PSMA ligand, was investigated in combination with actinium-225 and the data were compared with those of [225Ac]Ac-PSMA-617. In vitro, [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617 showed similar tumor cell uptake and PSMA-binding affinities as their 177Lu-labeled counterparts. The in vitro binding to serum albumin in mouse and human blood plasma, respectively, was 2.8-fold and 1.4-fold increased for [225Ac]Ac-SibuDAB as compared to [177Lu]Lu-SibuDAB. In vivo, this characteristic was reflected by the longer retention of [225Ac]Ac-SibuDAB in the blood than previously seen for [177Lu]Lu-SibuDAB. Similar to [225Ac]Ac-PSMA-617, [225Ac]Ac-SibuDAB was well tolerated at 30 kBq per mouse. Differences in blood cell counts were observed between treated mice and untreated controls, but no major variations were observed between values obtained for [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617. [225Ac]Ac-SibuDAB was considerably more effective to treat PSMA-positive tumor xenografts than [225Ac]Ac-PSMA-617. Only 5 kBq per mouse were sufficient to eradicate the tumors, whereas tumor regrowth was observed for mice treated with 5 kBq [225Ac]Ac-PSMA-617 and only one out of six mice survived until the end of the study. The enhanced therapeutic efficacy of [225Ac]Ac-SibuDAB as compared to that of [225Ac]Ac-PSMA-617 and reasonable safety data qualify this novel radioligand as a candidate for targeted α-therapy of prostate cancer.

Influence of lactation stages on haematological and biochemical parameters in blood of Lacaune dairy sheep

The research objective was to determine haematological and biochemical parameters in blood of 30 Lacaune dairy sheep during different stages of lactation (early: 60th, medium: 120th and late: 180th days). The sheep were on average 4 years old, in 3rd lactation. Haematological parameters were determined in whole blood (white blood cell (WBC), red blood cell (RBC), haemoglobin (HGB) concentration, haematocrit (HCT) value, mean corpuscular volume (MCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC) and platelet (PLT) count), and a blood smear was used for determination of differential blood cell count. Determined biochemical parameters in blood serum were: concentration of minerals (Ca, P-inorganic, Mg and Fe), concentration of total proteins (TP), albumin (ALB), globulins (GLOB), urea, glucose (GUK), cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGC), beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFA), enzyme activities (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), creatine kinase (CK), activity of glutathione peroxidase (GPx) and total superoxide dismutase (SOD). With progression of lactation stages, sheep blood tests proved significant increase in WBC, RBC, HGB, HCT, monocytes, Fe, urea, TP, ALB, CHOL, HDL, LDL, BHB, AST, GGT and ALT as well as a decrease in lymphocytes, Mg, GUK and SOD. Determined changes in haematological and biochemical blood parameters of Lacaune dairy sheep during different lactation stages proved good quality nutrition of sheep and indicate the need to include this dairy breed/genotype in prospective schemes for definition of referential values for these indicators in sheep.

Seasonal Variations of Haematological and Biochemical Parameters Associated with Potential Laminitis in Apparently Healthy Horses

Early detection of laminitis in horses is valuable as it provides information that can be used as a basis for advice to trainers of race and performance horses. The study was aimed to determine the seasonal variations in haematological and biochemical parameters of horses developing laminitis at Polo Club Port Harcourt, River State, Nigeria. A total of 18 horses were sampled during the dry season (February) and rainy season (July). The horses sampled were aged between 3 and 8 years. The hoof temperature, weight, packed cell volume (PCV), red blood cell (RBC) count, hemoglobin (Hb) concentration, total and differential leucocyte counts, glucose level and fibrinogen concentration were determined using standard methods. The mean hoof temperature of the horses was 36.1± 0.11oC and 35.6 ± 0.2 oC during the dry and rainy season respectively. The mean body weight of the horses was 323 ± 8.90 kg in dry season while that of rainy season was 330 ± 11.0 kg. Glucose concentration during the dry season (71.6 ± 1.5 dl/mg) was significantly lower (P ˂ 0.05) than that obtained during the rainy season (91.7 ± 1.9 dl/mg). Furthermore, the PCV, RBC count and Hb concentration were significantly higher (P ˂ 0.05) in the rainy season than the corresponding parameters in the dry season. Similarly, the total leucocyte, neutrophil and lymphocyte counts were significantly higher (P ˂ 0.05) during the rainy season than the dry season. It was concluded that variations on the parameters determined may aid to identify early warning signs of laminitis.

Comparative study of fasting blood glucose and haematological parameters of Wistar rat, Rattus norvegicus and the common African toad, Bufo regularis

Haematological parameters are good indicators of the physiological status of animals and useful in understanding the relationship of blood to the environment. This study was carried out to compare the fasting levels of blood glucose and haematological parameters (Red blood cell count, Packed cell volume, Haemoglobin concentration, White blood cell count, Platelet count, and differential White blood cell counts) in Wistar rats, Rattus norvegicus and the common African toad, Bufo regularis. Ten rats and ten toads were used in the study. The animals were divided into two groups. Group I consists of 10 rats while Group II consists of 10 toads. The animals were fasted overnight before blood samples were collected for the determination of blood glucose and blood parameters. The blood glucose was determined using modified glucose oxidase method while the blood parameters were determined using standard laboratory techniques. The results of the study showed that the fasting blood glucose level in rats was significantly higher than that of toad. The fasting levels of blood parameters, packed cell volume, red blood cell counts, haemoglobin concentration in the toad were significantly lower than those of rats while the white blood cell counts of the toads were significantly higher compared with the rats. There were no significant differences in neutrophil, monocyte, eosinophil and lymphocyte counts of rats when compared with those of the toad.

A prognostic model for overall survival in primary central nervous system lymphoma using post-steroid neutrophil-lymphocyte ratio.

e14049 Background: Ratios of differential blood counts (hematological indices, HI) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSL), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HI could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HI were calculated at three time-points: baseline (pre-steroid), pre-chemoimmunotherapy (post-steroid) and post-chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan-Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan-Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR≥4.0, HR 0.42, 95% CI: 0.21-0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR≥241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03) respectively only. Decision-tree model using age ≤70, post-steroid NLR &gt; 4.0, and pre-steroid (baseline) NLR &lt; 2.5 divided patients into three risk categories – low, medium, high – and achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusions: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed accurate and well-calibrated stratification into three risk groups.

Using High-Resolution Differential Cell Counts (HRDCCs) in Bovine Milk and Blood to Monitor the Immune Status over the Entire Lactation Period

Simple SummarySince leukocytes enter the mammary gland as part of the immune defense, they can be analyzed in raw milk samples and used for diagnostics. In our study, we differentiated and measured several subtypes of immune cells in blood and milk samples of eight dairy cows over their whole lactation to monitor their immune status. In addition to these so-called high-resolution differential cell counts (HRDCCs), we determined routine laboratory biomarkers. We found considerable differences between the documented cell count progressions in the blood and milk. Some cell populations remained mostly stable, while others showed a certain dynamic during the course of lactation. Moreover, two types of lymphocytes were also noticeable due to changes in the case of inflammation. These findings suggest that HRDCCs can be a promising tool for more efficient milk diagnostics, ensuring milk quality, and supporting cattle health and wellbeing.Differential cell counts in milk offer a deeper insight into the immunology of the mammary gland and might even provide information about the systemic health status of a dairy cow. Consequently, their potential as a diagnostic method to identify biomarkers has been a subject of research for quite some time. The objective of our study was to closely monitor the immune status of eight healthy dairy cows throughout their whole lactation. For this, high-resolution differential cell counts in milk and blood were determined by means of flow cytometry, which included 10 subpopulations of the 3 main populations of immune cells and their viability. Milk and blood samples were taken twice a week in the first 100 days after calving and once a week during the remaining lactation period: in total, 55 (52–57) blood and 55 (52–57) milk samples per animal. In addition, six well-established routine laboratory biomarkers, i.e., haptoglobin, calcium, and different metabolic parameters (non-esterified fatty acids, β-hydroxybutyric acid, bilirubin, and glutamate dehydrogenase), were analyzed in all blood samples. Furthermore, a standard differential blood cell count was performed on all blood samples. We found substantial differences between cell count progressions in the blood and milk. The distribution of cell populations in the blood remained mostly stable throughout the lactation, albeit at different individual levels. Several cell populations in the milk showed a noticeable dynamic over time, which caused a separation of different lactation stages in clustering analyses. Gamma delta T cells and CD4+ T cells in the milk stood out as they showed characteristic fluctuations during the course of lactation as well as minor changes in the case of inflammation. The determination of a differential cell count has the potential to be a sensitive diagnostic and prognostic tool in bovine milk. Further studies need to show to what extent the method is suitable for routine diagnostics and how to deal with animal-specific differences.