Effects of red blood cell transfusion on patients undergoing cardiac surgery in Queensland - a retrospective cohort study.

BACKGROUND: Packed red blood cell (pRBC) transfusion is a relatively safe and mainstay treatment commonly used in cardiac surgical patients. However, there is limited evidence on clinical effects of transfusing blood nearing end-of shelf life that has undergone biochemical changes during storage. OBJECTIVE: To investigate evidence of associations between morbidity/mortality and transfusion of blood near end of shelf-life (> 35 days) in cardiac surgical patients. METHODS: Data from the Queensland Health Admitted Patient Data Collection database 2007-2013 was retrospectively analysed. Coronary artery bypass graft and valvular repair patients were included. Multivariable logistic regression was used to examine the effect of pRBC age (< 35 days vs. ≥ 35 days) on in-hospital mortality and morbidity. As secondary analysis, outcomes associated with the number of pRBC units transfused (≤ 4 units vs. ≥ 5 units) were also assessed. RESULTS: A total of 4514 cardiac surgery patients received pRBC transfusion. Of these, 292 (6.5%) received pRBCs ≥ 35 days. No difference in in-hospital mortality or frequency of complications was observed. Transfusion of ≥ 5 units of pRBCs compared to the ≤ 4 units was associated with higher rates of in-hospital mortality (5.6% vs. 1.3%), acute renal failure (17.6% vs. 8%), infection (10% vs. 3.4%), and acute myocardial infarction (9.2% vs. 4.3%). Infection carried an odds ratio of 1.37 between groups (CI = 0.9-2.09; p = 0.14) and stroke/neurological complications, 1.59 (CI = 0.96-2.63; p = 0.07). CONCLUSION: In cardiac surgery patients, transfusion of pRBCs closer to end of shelf-life was not shown to be associated with significantly increased mortality or morbidity. Dose-dependent differences in adverse outcomes (particularly where units transfused were > 4) were supported.

Could oxygen gradient ektacytometry help to detect sickle cell trait carriers at risk for kidney disorders or exercise-related complications?

The study of Ellsworth et al. (Br J Haematol, 2024) demonstrated the usefulness of oxygen gradient ektacytometry technique to better identify the physiological parameters that could increase the risk of sickling of red blood cells (RBCs) from sickle cell trait (SCT) carriers. Oxygen gradient ektacytometry combined with pH and osmolality modulations could help in identifying SCT carriers at risk for kidney disorders or exercise-related complications. Other factors than the percentages of haemoglobin S are probably involved in the propensity of RBCs from SCT carriers to sickle during deoxygenation. Commentary on: Ellsworth et al. Hypertonicity and/or acidosis induce marked rheological changes under hypoxic conditions in sickle trait red blood cells. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19669.

Application of image recognition technology in pathological diagnosis of blood smears.

Traditional manual blood smear diagnosis methods are time-consuming and prone to errors, often relying heavily on the experience of clinical laboratory analysts for accuracy. As breakthroughs in key technologies such as neural networks and deep learning continue to drive digital transformation in the medical field, image recognition technology is increasingly being leveraged to enhance existing medical processes. In recent years, advancements in computer technology have led to improved efficiency in the identification of blood cells in blood smears through the use of image recognition technology. This paper provides a comprehensive summary of the methods and steps involved in utilizing image recognition algorithms for diagnosing diseases in blood smears, with a focus on malaria and leukemia. Furthermore, it offers a forward-looking research direction for the development of a comprehensive blood cell pathological detection system.

Role of Piezo1 in Terminal Density Reversal of Red Blood Cells.

Density reversal of senescent red blood cells has been known for a long time, yet the identity of the candidate ion transporter(s) causing the senescent cells to swell is still elusive. While performing fractionation of RBCs from healthy individuals in Percoll density gradient and characterization of the separated fractions, we identified a subpopulation of cells in low-density fraction (1.02% ± 0.47) showing signs of senescence such as loss of membrane surface area associated with a reduction in band 3 protein abundance, and Phosphatidylserine (PS) exposure to the outer membrane. In addition, we found that these cells are overloaded with Na+ and Ca2+. Using a combination of blockers and activators of ion pumps and channels, we revealed reduced activity of Plasma membrane Ca2+ ATPase and an increase in Ca2+ and Na+ leaks through ion channels in senescent-like cells. Our data revealed that Ca2+ overload in these cells is a result of reduced PMCA activity and facilitated Ca2+ uptake via a hyperactive Piezo1 channel. However, we could not exclude the contribution of other Ca2+-permeable ion channels in this scenario. In addition, we found, as a universal mechanism, that an increase in intracellular Ca2+ reduced the initially high selectivity of Piezo1 channel for Ca2+ and allowed higher Na+ uptake, Na+ accumulation, and swelling.

Acute Pain Transfusion Reaction: A Case Report.

Transfusion-related adverse events involving packed red blood cells (PRBCs) and fresh frozen plasma (FFP) are not unusual. Reactions can happen at any time during the transfusion, as well as hours or days later. An acute pain transfusion reaction (APTR) is defined as sudden, intense joint pain, usually in the back and trunk, that appears right after transfusion after all other potential causes of transfusion reactions have been eliminated. The present article discusses two similar cases. A 38-year-old female presented with complaints of right-sided headache and photophobia for four days, associated with nausea, vomiting, and vertigo. She was evaluated for a migraine headache. Due to anemia, a one-unit PRBC was requested. After pre-transfusion testing, a one-unit non-leuko-reduced, coombs cross-match compatible B-positive packed red blood cell (PRBC) was issued and transfused. During the transfusion, the patient complained of chest pain. The transfusion was stopped. Her vitals did not vary much from the baseline. No other symptoms were present at that time. A 69-year-old female presented with complaints of vomiting, abdominal pain, and black tarry stool for a one-month duration. On evaluation, she was diagnosed with adenocarcinoma of the stomach. Given the increased prothrombin time/international normalized ratio (PT/INR) of 1.8, four-units of fresh frozen plasma (FFP) was requested, which was issued after performing minor cross-match compatibility. After five minutes of transfusion, she complained of severe pain at the transfusion site with chills and rigors. The transfusion was stopped. There was no change in the vitals of the patient from baseline. A complete workup was done to rule out other transfusion reactions in both cases. Thus, these patients experienced what is known as an acute pain transfusion reaction. APTR is typically self-limited and requires treatment of symptoms with pain control, supplemental oxygen, and emotional support. In both cases, supportive treatments were enough to control the pain symptoms of the patients.

Systemic CRP (C-reactive protein) Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Observational Study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. METHODS: We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission CRP levels than those without these complications (P < 0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI and co-occurring CVS and DCI (P < 0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). CONCLUSIONS: Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

Optimizing O red blood cell concentrate usage in the emergency department in the era of patient blood management.

BACKGROUND: Emergency transfusion may require the availability of O-negative red blood cell concentrates without pre-transfusion testing. At the Cliniques Universitaires Saint-Luc, the emergency department was used to having access to two decentralized O-negative red blood cell concentrates. This study aims to analyze the consumption of O-negative red blood cell concentrates in emergency situations both before and after the implementation of a novel strategy aiming at optimizing stocks. This strategy provides a combined allocation of one unit of O-positive red blood cell concentrate and one unit of O-negative red blood cell concentrate decentralized in the emergency department and reserve the transfusion of the negative unit only to under 45-year-old women and under 20-year-old men. MATERIALS AND METHODS: A retrospective study was conducted of the transfusion and medical records of all patients who received immediate transfusions in the emergency department without pre-transfusion testing between 2008 and 2022. RESULTS: A total of 193 patients received O red blood cell concentrates without pre-transfusion testing in emergency situations between 2008 and 2022. During the first 24 h of hospitalization, 354 O-negative units were transfused. Mean ratios of number of O-negative bags between 2008 and 2020 was 1.98 unit/patient. After implementation of the new strategy, the ratio in 2021 was 1.46 unit/patient and drastically decreased in 2022 to 0.79 unit/patient. CONCLUSION: In situations of emergency, allocating O-negative units only for women younger than 45 years and men younger than 20 years could have saved 85% of O-negative red blood cell concentrates transfused (303/354) yet balancing the immunological risk. Limiting the number of delocalized units of O-negative red blood cell concentrates in the emergency department seems to lower O-negative consumption. With this strategy, the units spared could have been transfused to patients with greater needs (e.g., sickle cell patients or chronically transfused patients).

Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Significance: Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. Aim: We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). Approach: We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. Results: We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ϕ ) for nEGs fabricated using 100 µ M of BrCy112 is ∼ 41 -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their ϕ as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Conclusions: Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

Clearance of erythrocytes from the subarachnoid space through cribriform plate lymphatics in female mice.

BACKGROUND: Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways. METHODS: Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts. FINDINGS: RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis. INTERPRETATION: This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH. FUNDING: Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

51Cr Red Blood Cells in the Study of Hematologic Disease: A Historical Review.

The early years of nuclear medicine included the development and clinical use of several in vitro or nonimaging procedures. The use of radionuclides as replacements for nonradioactive dyes brought improved accuracies and less subjective measurements to indicator dilution studies of body compartments such as the gastrointestinal system, lungs, urinary system, and vascular space. A popular nuclear medicine procedure was the radionuclide dilution method for quantitation of whole-blood volume or red blood cell volume or mass using 51Cr-labeled red blood cells-an important diagnostic element in patients suspected of having polycythemia vera, congestive heart failure, hypertension, shock, syncope, and other abnormal blood volume disorders. The radionuclide dilution method led to improved evaluation of red blood cell survival, which is important for clinical treatment planning in anemia and confirmation of splenic sequestration of damaged red blood cells. Although it was discovered that 51Cr was a chemically stable radiolabel of red blood cells after binding to intracellular hemoglobin, few nuclear medicine departments offered the clinical study for referring physicians because it required laboratory expertise for technologists, patient coordination, and a time-consuming procedure. The introduction of improved methods that are less time-consuming and have clinically acceptable results, along with the discontinuation of the sodium chromate 51Cr injection radiopharmaceutical by manufacturers, has consigned 51Cr red blood cells for red blood cell volume, mass, or survival evaluation to the list of retired nuclear medicine studies.

Corrigendum: Drug transport by red blood cells.

[This corrects the article DOI: 10.3389/fphys.2023.1308632.].

[Factors associated with normal leukocyte count and C-reactive protein in adults with acute appendicitis: a retrospective cohort study]. / Faktory, svyazannye s normal'nym kolichestvom leikotsitov i urovnem S-reaktivnogo belka u vzroslykh bol'nykh s ostrym appenditsitom: retrospektivnoe kogortnoe issledovanie.

OBJECTIVE: To identify the factors associated with normal leukocyte count and C-reactive protein (CRP) in adults with acute appendicitis. MATERIAL AND METHODS: A retrospective cohort study included patients aged 18-60 years after surgeries for acute appendicitis. Convenience sampling was used to select medical records, and variables such as age, sex, weight, height, origin, self-medication, diabetes (DM2), high blood pressure (HBP), type of appendicitis, duration of illness, preoperative time, type of appendectomy, operative time, and hospital stay were analyzed. Patients were categorized into those with normal and abnormal inflammatory parameters. The SPSS version 28 software was used for analysis. RESULTS: We included 333 patients; 11.11% ones had normal inflammatory parameters. Both groups had mean age of approximately 33 years. Men comprised 56.76% and 57.43%in both groups, respectively. The abnormal group had shorter mean preoperative time, and catarrhal appendicitis was more common in the normal group. Multivariate analysis revealed that rural origin and self-medication were significantly associated with normal inflammatory parameters. CONCLUSION: The prevalence of normal inflammatory parameters in acute appendicitis patients was 11.11%. Rural origin, self-medication, shorter preoperative time, and catarrhal appendicitis were significantly associated with normal inflammatory parameters in this context.

An explainable AI-based blood cell classification using optimized convolutional neural network.

White blood cells (WBCs) are a vital component of the immune system. The efficient and precise classification of WBCs is crucial for medical professionals to diagnose diseases accurately. This study presents an enhanced convolutional neural network (CNN) for detecting blood cells with the help of various image pre-processing techniques. Various image pre-processing techniques, such as padding, thresholding, erosion, dilation, and masking, are utilized to minimize noise and improve feature enhancement. Additionally, performance is further enhanced by experimenting with various architectural structures and hyperparameters to optimize the proposed model. A comparative evaluation is conducted to compare the performance of the proposed model with three transfer learning models, including Inception V3, MobileNetV2, and DenseNet201.The results indicate that the proposed model outperforms existing models, achieving a testing accuracy of 99.12%, precision of 99%, and F1-score of 99%. In addition, We utilized SHAP (Shapley Additive explanations) and LIME (Local Interpretable Model-agnostic Explanations) techniques in our study to improve the interpretability of the proposed model, providing valuable insights into how the model makes decisions. Furthermore, the proposed model has been further explained using the Grad-CAM and Grad-CAM++ techniques, which is a class-discriminative localization approach, to improve trust and transparency. Grad-CAM++ performed slightly better than Grad-CAM in identifying the predicted area's location. Finally, the most efficient model has been integrated into an end-to-end (E2E) system, accessible through both web and Android platforms for medical professionals to classify blood cell.

Revealing differential expression patterns of piRNA in FACS blood cells of SARS-CoV-2 infected patients.

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID-19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV-2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID-19, we observed 3 significantly elevated piRNAs - piR-33,123, piR-34,765, piR-43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR-49039 piR-31623, piR-37213, piR-44721, piR-44720) and 35 downregulated. It has been previously shown that piR-31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated.

Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by delayed neurodevelopment, accelerated aging, and increased risk of many co-occurring conditions. Hypoxemia and dysregulated hematopoiesis have been documented in DS, but the underlying mechanisms and clinical consequences remain ill defined. We report an integrative multi-omic analysis of ∼400 research participants showing that people with DS display transcriptomic signatures indicative of elevated heme metabolism and increased hypoxic signaling across the lifespan, along with chronic overproduction of erythropoietin, elevated biomarkers of tissue-specific hypoxia, and hallmarks of stress erythropoiesis. Elevated heme metabolism, transcriptional signatures of hypoxia, and stress erythropoiesis are conserved in a mouse model of DS and associated with overexpression of select triplicated genes. These alterations are independent of the hyperactive interferon signaling characteristic of DS. These results reveal lifelong dysregulation of key oxygen-related processes that could contribute to the developmental and clinical hallmarks of DS.

Enzymic Activity, Metabolites, and Hematological Responses in High-Risk Newly Received Calves for "Clinical Health" Reference Intervals.

Enzymic activity, metabolites, and hematological responses for reference intervals (RIs) establish ranges of physiological normality, which are useful for diagnosing diseases and physiological alterations. Within the same species, RIs vary according to age, gender, productive and physiological states, and environmental factors including health management and nutrition. RIs have been extensively studied in dairy calves during a critical stage of life (from birth up to first 90 days of age). A critical stage for feedlot calves is their arrival at the feedlot, but no reports determine RIs for different enzymic activity, metabolites, and hematological responses during their initial period at the feedlot. Consequently, a total of 461 high-risk crossbreed beef calves, received on three different dates, were examined upon arrival at the feedlot. Of these, 320 calves (148.3 ± 1.3 kg body weight) whose "clinical health" was evaluated were included in the study. Blood samples were taken upon arrival and on days 14, 28, 42, and 56 to determine the following parameters: enzymic activity, metabolites, electrolytes, white blood cells, platelets, and red blood cells. Enzymic activity, metabolites, and complete blood count were determined by automated analyzers. The freeware Reference Value Advisor Software was used to calculate the non-parametric values of RIs. This study is the first to establish RIs for different enzymic activity, metabolites, and hematological responses in high-risk newly received calves during their initial period at the feedlot. This information will be useful for veterinary clinical practice and research related to the health and welfare of high-risk newly received calves during their initial period at the feedlot.

Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy.

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

Improving Interpretability of Leucocyte Classification with Multimodal Network.

White blood cell classification plays a key role in the diagnosis of hematologic diseases. Models can perform classification either from images or based on morphological features. Image-based classification generally yields higher performance, but feature-based classification is more interpretable for clinicians. In this study, we employed a Multimodal neural network to classify white blood cells, utilizing a combination of images and morphological features. We compared this approach with image-only and feature-only training. While the highest performance was achieved with image-only training, the Multimodal model provided enhanced interpretability by the computation of SHAP values, and revealed crucial morphological features for biological characterization of the cells.

Understanding the physiological transmission mechanisms of photoplethysmography signals: a comprehensive review.

Objective. The widespread adoption of Photoplethysmography (PPG) as a non-invasive method for detecting blood volume variations and deriving vital physiological parameters reflecting health status has surged, primarily due to its accessibility, cost-effectiveness, and non-intrusive nature. This has led to extensive research around this technique in both daily life and clinical applications. Interestingly, despite the existence of contradictory explanations of the underlying mechanism of PPG signals across various applications, a systematic investigation into this crucial matter has not been conducted thus far. This gap in understanding hinders the full exploitation of PPG technology and undermines its accuracy and reliability in numerous applications.Approach. Building upon a comprehensive review of the fundamental principles and technological advancements in PPG, this paper initially attributes the origin of PPG signals to a combination of physical and physiological transmission processes. Furthermore, three distinct models outlining the concerned physiological transmission processes are synthesized, with each model undergoing critical examination based on theoretical underpinnings, empirical evidence, and constraints.Significance. The ultimate objective is to form a fundamental framework for a better understanding of physiological transmission processes in PPG signal generation and to facilitate the development of more reliable technologies for detecting physiological signals.