Erythrocytes Research Articles

Diagnosis and Treatment of Polycythemia Vera

ImportancePolycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons.ObservationsErythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia.Conclusions and RelevancePV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

Association between anaemia and aflatoxin B1 and fumonisin B1 exposure in HIV-infected and HIV-uninfected pregnant women from Harare, Zimbabwe.

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are poisons that contaminate poorly stored staple foods in resource-limited settings. Antenatal AFB1 and FB1 exposure may cause anaemia. We aimed to determine the associations of urinary aflatoxin M1 (AFM1) and FB1, biomarkers of AFB1 and FB1 exposure, respectively, with erythrocyte parameters and anaemia. A retrospective cross-sectional study was conducted in 68 HIV-infected and 61 HIV-uninfected pregnant women ≥ 20 weeks gestational age in Harare, Zimbabwe. AFM1 and FB1 were measured in urine via competitive ELISA, and levels were grouped into tertiles. The erythrocyte parameters assessed were haemoglobin (Hb), mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell (RBC), haematocrit (HCT), and red blood cell distribution width. Associations of urinary AFM1 and FB1 with erythrocyte parameters, and anaemia were assessed in a multiple regression controlled for potential confounders. The presence of FB1 in urine decreased Hb levels in all women (β= -0.98, 95% CI: -1.94, 0.02) and HIV-uninfected (β= -1.99, 95% CI: -3.71, -0.26). FB1 tertile 3 decreased Hb levels (β= -0.88, 95% CI: -1.74, 0.01) and HCT levels (β= -2.65, 95% CI: -5.26, 0.03) in HIV-infected. AFM1 tertile 2 decreased RBC levels in HIV-infected (β= -0.34, 95% CI: -0.71, -0.03). The presence of FB1 in urine increased anaemia risk in HIV-uninfected (OR: 10.68 95% CI: 1.02, 112.34). AFM1 tertile 2 increased macrocytic anaemia risk in HIV-infected (OR: 13.72, 95% CI: 0.92, 203.55). There is need to ensure food safety through monitoring and nutritional interventions to improve maternal-infant health outcomes.

Toxic effects of chlorpyrifos on biochemical composition, enzyme activity and gill surface ultrastructure of three species of small fishes from India.

The effects of chlorpyrifos, a frequently detected organophosphate in aquatic ecosystems, on biochemical (protein and glycogen) contents and oxidative enzyme activities (catalase and lipid peroxidation) in liver, muscle and gill tissues of three freshwater fish Trichogaster fasciata, Mystus vittatus and Heteropneustes fossilis were evaluated after 21-day exposure to 1 and 10% of 96h LC50 of this pesticide, which were 1.63 and 16.3µg L-1; 5.87 and 58.7µg L-1 and 2.12 and 21.2µg L-1, respectively. On comparing with control, significant reductions in protein concentration were found in liver, muscle and gill of the three fishes treated with both higher as well as lower concentrations of the pesticide except in gill of M. vittatus and liver of H. fossilis treated with the lower concentrations. Glycogen content reductions were significant in the liver and muscle of the fishes, as well as gill tissue of T. fasciata treated with the two pesticide concentrations. Significant elevations of catalase activity were found in liver of the three fishes treated with the higher concentrations, in muscle tissues of both T. fasciata and M. vittatus treated with both the concentrations and in gills of the three fishes except H. fossilis treated with the lower concentration of the pesticide. Significant elevations of lipid peroxidation level were also found in liver of all the three fish species treated with the higher concentrations, in the muscle tissue of M. vittatus as well as in the gill of T. fasciata and H. fossilis treated with both the concentrations of the pesticide. Chlorpyrifos exposed gill ultrastructure of T. fasciata, M. vittatus and H. fossilis revealed concentration-dependent effects of the pesticide on gill surface ultrastructure which include distortion of primary and secondary lamellae, deterioration of pavement cell and microridge structures, extrusion of red blood cells (RBCs), secretion of mucous layer on filament, sloughing of primary lamellae and clumping of secondary lamellae. The present study parameters could serve as useful biomarkers for evaluating the risk of pesticide toxicity to fish. These findings also point out the possible health risks to the consumers of these fish captured from contaminated water bodies.

MEGALOBLASTIC CRISIS IN SICKLE CELL DISEASE–A RARE PHENOMENA WITH AVAILABLE REVIEW OF LITERATURE

Sickle cell disease (SCD) is an inherited disease where some red blood cells are shaped like sickles or crescent moons. This condition affects the blood and various organs of the body. These sickle cells also become rigid and sticky, which can slow or block blood flow, resulting in episodes of sickness that produce pain and other crisis. There are different types of crisis. SCD with a megaloblastic crisis is rare. The frequency of the carrier state determines the prevalence of sickle cell anemia. Here we describe a 20 y old female patient with sickle cell disease who experienced a megaloblastic crisis.

A glutamine metabolic switch supports erythropoiesis.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.

Hemoglobin-to-red blood cell distribution width ratio is negatively associated with stroke: a cross-sectional study from NHANES.

Numerous studies have suggested that the hemoglobin-to-red blood cell distribution width ratio (HRR) is associated with the onset, progression, and prognosis of various diseases. However, to the best of our knowledge, no research has conducted statistical analyses to determine the association between HRR and stroke. This cross-sectional study was conducted among adults with complete data on hemoglobin-red cell distribution width ratio (HRR) and stroke from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). HRR was calculated by dividing hemoglobin (HGB) in grams per deciliter (g/dL) by the red blood cell distribution width (RDW). Weighted multivariable logistic regression and generalized additive models were employed to investigate the independent and nonlinear relationships between HRR and stroke. Threshold effects were assessed using two-piece linear regression models. Additionally, subgroup analyses and interaction tests were performed. A total of 36,215 participants were included, with 2.92% classified as stroke patients. The prevalence of stroke decreased across increasing tertiles of HRR (Q1: 5.07%; Q2: 2.63%; Q3: 1.69%; P < 0.0001). A negative association between HRR and stroke was observed in both unadjusted and adjusted models. In Model III, each one-unit increase in HRR was associated with a 58% reduction in the likelihood of stroke (Model III: OR = 0.42, 95% CI: 0.29-0.63). Subgroup analyses and interaction tests revealed that the association between HRR and stroke was BMI-dependent (P < 0.05), with the negative association only observed in participants with BMI < = 25 and BMI 25-30, but not in those with BMI > 30. Using a two-piece linear regression model, a threshold effect was identified at a BMI of 30 (K = 1.16). To the left of this breakpoint, there was a negative association between HRR and stroke (OR = 0.55, 95% CI: 0.27-0.97), whereas no such association was detected to the right of the breakpoint (OR = 6.49, 95% CI: 0.75-56.11). HRR is negatively associated with the likelihood of stroke, with a lower risk of stroke in individuals with higher HRR levels.

Ferroptosis regulates hemolysis in stored murine and human red blood cells.

Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.

Large-scale genome-wide association studies identified causal relationship between multiple blood biomarkers and risk of acute pancreatitis.

Observational studies have shown that there is a connection between blood biomarkers and the occurrence of acute pancreatitis (AP). Nevertheless, the causal relationships are still not clear. The purpose of this study was to evaluate causal association between biomarkers and AP. A bidirectional two-sample Mendelian randomization (MR) analysis was applied to investigate the causal association between blood biomarkers and AP. Summary statistics obtained from genome-wide association studies were utilized for this analysis. The primary statistical approach employed was the inverse variance weighted (IVW) method, complemented by sensitivity analyses aimed at assessing heterogeneity and pleiotropy. Furthermore, a multivariable MR (MVMR) analysis was performed to adjust for confounders. A total of 11 red blood cell (RBC) traits, 6 white blood cell traits, platelet count, and 30 blood biomarkers were analyzed in this study. Genetically predicted RBC count (IVW odds ratio [OR]=1.144, P=0.004), the high light scatter reticulocyte count (HLSR) (OR=1.127, P=0.022), blood glucose (BG) (OR=1.480, P=0.019), and leptin (OR=1.234, P=0.050) were suggestively associated with an increased risk of AP. Reverse MR analysis showed no causal effect of AP on RBC, HLSR, BG, and leptin (IVW P>0.05). Sensitivity analyses and MVMR analysis still supported the earlier causality. Our findings provide evidence of a suggestive association between RBC count, HLSR, BG, and leptin with an increased susceptibility to AP. These findings aid in our comprehension of the cause of AP and may be used as potential prognostic markers or predictors of severity with AP.

Synthesis and evaluation of vanillin Schiff bases as potential antimicrobial agents against ESBL-producing bacteria: towards novel interventions in antimicrobial stewardship.

The escalating challenge of antimicrobial resistance necessitates the development of novel antibacterial agents. In this study, a series of five vanillin Schiff bases (SB-1 to SB-5) were synthesized from vanillin and various aromatic amines. The chemical structures of these compounds were characterized using Thin Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FT-IR), proton nuclear magnetic resonance ( -NMR), carbon-13 NMR ( -NMR), and mass spectrometry techniques. Antibacterial efficacy was evaluated against strains of bacteria producing extended-spectrum beta-lactamases (ESBL), including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae using the disc diffusion method. Cytotoxic effects were assessed through haemocompatibility and brine shrimp lethality assays. The Schiff bases demonstrated notable antibacterial activities, with SB-1, SB-2, SB-4, and SB-5 exhibiting zones of inhibition up to 16.0, 16.5, 16.6, and 15.5 mm against ESBL E. coli, respectively. SB-3 showed a maximum inhibition zone of 15.0 mm against ESBL K. pneumoniae. In cytotoxicity assays, the compounds exhibited IC values against red blood cells (RBCs) greater than 200 μg/mL and ranging from 45.7 to 50.5 μg/mL for the brine shrimp assay. While demonstrating potent antibacterial properties, the toxicity towards human RBCs suggests that further toxicity evaluations and structural modifications are essential for developing safer therapeutic agents based on vanillin Schiff bases.

Antimicrobial Activity of Copolymer Structures from Bio-Based Monomers.

The urgent need for new antimicrobial compounds has led scientists to explore antimicrobial peptides (AMPs) and antimicrobial polymers as solutions for multidrug resistance. In this study, we synthesized copolymers with cationic and hydrophobic moieties by free-radical polymerization (FRP) using a chain transfer agent to control molecular weights. The potential of natural products as part of the hydrophobic moiety was evaluated, along with variations in their monomer content (13-25%) and the molecular weight (MW) of the copolymer (5000-20,000 g·mol-1). Hydrophobicity was evaluated using the theoretical Log Poct values and surface areas (SAs). Biological assays included antimicrobial activity against Escherichia coli and Staphylococcus aureus standard strains, hemolytic activity in red blood cells (RBC), and cytotoxicity tests against HEK293T cells. Keys findings indicate that copolymers with tropolone moieties, lower MWs, and an optimal balance between hydrophobic and cationic moieties show a promising basis for future generations of antimicrobials.

Cell salvage in obstetrics-Background and practical implementation

Postpartum hemorrhage (PPH) remains aleading cause of maternal mortality worldwide, with an increasing incidence in western countries over the past decades. During this period the numbers of PPH-related allogeneic red blood cell (RBC) transfusions have also significantly increased. Given the increasing scarcity and risks of allogeneic RBC transfusions, which are also associated with adverse maternal outcomes, optimized blood management strategies are urgently needed in obstetrics. In recent years, patient blood management (PBM) has been increasingly integrated into medical care, resulting in asignificant improvement in patient outcomes. Cell salvage (CS) is one of the PBM blood-sparing techniques that enables the collection, processing and retransfusion of the patient's own blood during major bleeding events. Although recent evidence indicates that CS can significantly reduce the demand for allogeneic RBC transfusions and improve patient outcomes, the utilization in obstetrics in German hospitals remains low, with ausage rate of only 0.07% of births with peripartum hemorrhage. It must be assumed that concerns about patient-related complications, such as amniotic fluid embolism and maternal alloimmunization contribute to this hesitancy, alongside alack of familiarity with the technique. This article provides an overview of the current evidence on the use and safety of CS in obstetrics. To facilitate a practical implementation, fundamental considerations and organizational precautions were prepared based on the experiences of the University Hospitals in Würzburg and Frankfurt and presented in the form of graphics and checklists for the perioperative use of CS during cesarean sections.

Viscoelastic haemostatic assays to guide therapy in elective surgery: an updated systematic review and meta-analysis.

Patients undergoing major surgery frequently experience major uncontrolled bleeding. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of using viscoelastic haemostatic assays to manage peri-operative bleeding in elective surgery. We searched PubMed/MEDLINE and Embase databases for randomised controlled trials according to pre-determined criteria. The primary outcomes were blood product requirements; duration of stay in the operating theatre or ICU; and surgical reintervention rate. We included 20 randomised controlled trials. The overall risk of bias was low to moderate. Twelve studies used thromboelastography-based transfusion algorithms, while eight used thromboelastometry. Viscoelastic haemostatic assay-guided therapy was associated with a statistically significant reduction in transfusion of red blood cells (standardised mean difference (95%CI) 0.16 (-0.29 to 0.02)), platelets (standardised mean difference (95%CI) -0.33 (-0.56 to -0.10)) and fresh frozen plasma (standardised mean difference (95%CI) -0.64 (-1.01 to -0.28)). There was no evidence of an effect of viscoelastic haemostatic assay-guided therapy on surgical reintervention (relative risk (95%CI) 1.09 (0.70-1.69)). Viscoelastic haemostatic assay-guided therapy was associated with lower blood loss and shorter ICU duration of stay. There was no evidence of any effect on total duration of stay and all-cause mortality. Viscoelastic haemostatic assay-guided therapy may reduce peri-operative blood product transfusion requirements and blood loss during major elective surgery, with no discernible effect on patient-centred outcomes. The overall quality of evidence was modest.

Imetelstat: A new addition to the Therapeutic Landscape of Lower-Risk MDS.

Anemia is the most prevalent cytopenia in lower-risk myelodysplastic neoplasms (LR-MDS). There is a paucity of drugs for red blood cell transfusion dependence (RBC-TD) and erythropoiesis-stimulating agents (ESAs) are the mainstay of therapy in many centers. Imetelstat, an oligonucleotide telomerase inhibitor, was recently approved for RBC-TD LR-MDS adults who are ineligible or failed prior ESA therapy. While not yet approved worldwide, here, we spotlight the current data for imetelstat and where it may fit in the therapeutic landscape of LR-MDS.

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.

Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria.

Malaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential for improving drug bioavailability and potency while reducing adverse effects. This study aimed to develop lipid-core nanocapsules containing ART and LUM and evaluate their effects in an experimental cerebral malaria model (ECM). The polymeric interfacial deposition method was used to develop lipid-core nanocapsules (LNCs) containing ART and LUM (LNCARTLUM) and were characterized using micrometric and nanometric scales. Male C57BL/6 mice were infected with Plasmodium (P.) berghei ANKA (PbA, 1 × 105 PbA-parasitized red blood cells, intraperitoneally). On day 5 post-infection, PbA-infected mice were orally administered with ART + LUM, LNCARTLUM, blank nanocapsules (LNCBL), or ethanol as a control. Parasitemia, clinical scores, and survival rates were monitored throughout the experiment. Organ-to-body weight ratios, cytokine quantification, and intravital microscopy analyses were conducted on day 7 post-infection. LNCs were successfully developed and characterized. The treatment with LNCARTLUM in ECM resulted in complete clearance of parasitemia at 10 dpi, decreased clinical scores, and maintained 100% survival rates. Thereated mice exhibited splenomegaly and reduced TNF-α, IL-1β, and MCP1 levels in the brain. Furthermore, the LNCARTLUM treatment protected the brain microvasculature, reducing the number of cells in the rolling process and adherent to the microvasculature endothelium. Nanoformulations can potentially improve the efficacy of antimalarial drugs and be considered a promising approach to treat malaria.

Anaemia during pregnancy: could riboflavin deficiency be implicated?

Anaemia affects more than 36% of all pregnancies globally and is associated with significant maternal and neonatal morbidity and mortality. Iron deficiency is widely recognised as the most common nutritional cause of anaemia but other nutrient deficiencies are also implicated, including the B vitamin riboflavin, albeit its role is largely under-investigated and thus typically overlooked. Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), is required for numerous oxidation-reduction reactions, antioxidant function, and in the metabolism of other B vitamins and iron. While clinical deficiency of riboflavin is largely confined to low-income countries, sub-clinical (functional) deficiency is much more widespread, including in high-income countries, and is particularly common among women of reproductive age and during pregnancy. Limited observational evidence from high-income populations suggests that suboptimal riboflavin status contributes to an increased risk of anaemia. Furthermore, randomised controlled trials in pregnant women from low- and middle-income countries have demonstrated beneficial effects of riboflavin on haematological status and anaemia. Various mechanisms have been proposed to explain the contribution of riboflavin deficiency to anaemia, with the strongest evidence pointing to an adverse effect on iron metabolism, given that riboflavin co-factors are required for the release of iron from storage ferritin in the production of red blood cells. Overall, this review investigates riboflavin intakes and status during pregnancy in different populations and evaluates the available evidence for the under-recognised role of riboflavin in the maintenance of haemoglobin concentrations together with its potential to protect against the development of anaemia during pregnancy.

The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy.

Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferative disease previously, little is known about their exact role in PDR. In this study, we address molecular and cellular alterations in the vitreous of PDR patients as a means towards assessing the potential contribution of hyalocytes to disease pathogenesis. A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of hyalocytes isolated from the vitreous of PDR and control patients, multiplex immunoassay and ELISA analyses of vitreous samples from PDR and control patients, as well as isolation and immunohistochemical staining of cultured porcine hyalocytes. Transcriptional analysis revealed an enhanced inflammatory response of hyalocytes contributing to the cytokine pool within the vitreous of PDR patients by expressing interleukin-6, among others. Further, increased angiopoietin-2 expression indicated that hyalocytes from PDR patients undergo a proangiogenic shift and may thus mediate the formation of retinal neovascularizations, the hallmark of PDR. Finally, RNA-Sequencing revealed an upregulation of factors known from hemoglobin catabolism in hyalocytes from PDR patients. By immunohistochemistry, cultured porcine hyalocytes exposed to red blood cells were shown to engulf and phagocytose these, which reveals hyalocytes' potential to dispose of erythrocytes. Thus, our data suggest a potential role for vitreous macrophages in erythrophagocytosis and, thereby, clearance of vitreous hemorrhage, a severe complication of PDR. Our results strongly indicate a critical role for vitreous hyalocytes in key pathophysiological processes of proliferative diabetic retinopathy: inflammation, angiomodulation and erythrophagocytosis. Immunomodulation of hyalocytes may thus prove an essential novel therapeutic approach in diabetic vitreoretinal disease.

Red cell specifications for blood group matching in patients with haemoglobinopathies: An updated systematic review and clinical practice guideline from the International Collaboration for Transfusion Medicine Guidelines.

Red blood cell (RBC) antigen matching beyond ABO and RhD is commonly recommended for patients with sickle cell disease (SCD) and thalassaemia. We present an updated systematic literature review to inform evidence-based guidelines on RBC matching. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool was used to develop recommendations. Six new observational studies (4 prospective, 2 retrospective) were identified. The six studies reported on 583 patients in total, including cross-over designs, with sample sizes from 10 to 343. Studies were heterogeneous, utilising varying degrees of RBC matching and different definitions for 'extended' matching. All reported on alloimmunisation. One study reported on molecular matching. The reported prevalence of alloimmunisation using limited matching was 0%-50% and with extended matching was 0%-24%. Eighty-two patients were alloimmunised before study entry. The risk of bias across studies was moderate to critical. The guideline panel recommends that ABO, RhDCcEe, and K-compatible RBCs are selected for individuals with SCD and thalassaemia, even in the absence of alloantibodies, and that RBCs which are antigen-negative to already existing clinically significant antibodies are chosen. There is a need for comparative research to define the benefit, impact, cost-effectiveness, and feasibility of extended RBC matching strategies to prevent alloimmunisation.

Long-term effects of continuous low dose-rate gamma-ray irradiation on mouse hematopoietic cells.

The present work investigates the long-term effects of continuous low dose-rate (20mGy/day to total doses of 1-8Gy) gamma-ray exposure on the hematopoietic cells of specific pathogen-free C3H/HeN mice. Peripheral white blood cell (WBC) counts decreased on days 206, 471, and 486, with no significant changes in red blood cell (RBC) and platelet (PLT) counts. The number of colony forming units (CFU-S and CFU-GM) in the bone marrow and spleen from irradiated mice decreased with increasing total dose on day-12 and day-7. The decrease in bone marrow CFU-S persisted throughout the 400-day irradiation period and did not show any recovery up to 210days postirradiation. These findings suggest that the effects of low-dose-rate (LDR) radiation on the hematopoietic system remain long after the 400-day irradiation was completed. Further investigation showed no significant difference in life spans of non-irradiated W/Wv (c-kit-deficient) mice inoculated with hematopoietic stem cells from irradiated (20mGy/day for 400days) or nonirradiated wild-type mice. These results suggest that the effects of continuous low-dose-rate irradiation are more pronounced in hematopoietic stromal cells than in HSCs themselves.

Evaluation of anemia Haemoprotozoan diseases in goats by using FAMACHA scoring in Barishal district, Bangladesh

Anemia in goats is a prevalent and significant health issue, characterized by pale mucous membranes, tachycardia, weakness, activity intolerance, reduced body weight, and stunted growth. It is often caused by hemoprotozoan diseases, parasitism (both internal and external), and nutritional deficiencies. For small ruminant farmers, anemia poses severe economic challenges by reducing productivity, including slower growth rates and lower milk yields, and increasing mortality if left untreated. This study was conducted in Barishal Sadar Upazila, Barishal district, over a 3 month period from November 2021, to January 2022 Out of 216 goats examined, 37 cases (17.12%) were diagnosed with anemia. The data revealed that Black Bengal goats had the highest prevalence of anemia (62.16%), followed by Jamunapari (29.73%) and crossbreeds (8.11%). Female goats (62.17%) were more affected than males (37.83%). Anemia was most prevalent in goats aged 13-18 months (59.46%), compared to 7-12 months (24.33%) and 0-6 months (16.21%). The FAMACHA scoring system was used to assess anemia severity, offering an affordable, practical, and accessible tool for evaluating conjunctival color on a scale from 1 (no anemia) to 5 (severe anemia). In this study, I standardized the FAMACHA chart for goats in the Barishal district. The results showed that as FAMACHA scores increased, red blood cell (RBC) counts, hemoglobin (Hb) levels, and packed cell volume (PCV) decreased, while white blood cell (WBC) counts increased, indicating more severe anemia. Elevated WBC counts also suggested possible underlying infections. This study underscores the FAMACHA chart’s effectiveness in diagnosing anemia and highlights its potential as a valuable tool for anemia management in tropical and subtropical regions.