Immunohistochemical Comparison of Ontogenic Development of Bone Marrow Hematopoiesis in Two Different Ossification Systems

It is well known that the body skeleton is formed by two different types of ossification systems, endochondoral and intramembranous ossification. Bone marrow is the main site of active hematopoiesis after the formation of the bone marrow cavities. However, it is unclear whether the hematopoiesis in the bone marrow of two types of ossification is regulated by the same system or not. In this study, we focused on the ontogenic development of bone marrow hematopoiesis in two different ossification systems using mouse humeral bones and palatal process of maxillary bones. Immunohistochemical and RT-PCR analyses were performed to examine the development of hematopoiesis and the expression of cytokines related to hematopoiesis in the forming bone marrow (16-days gestation stage to 1-day postnatal stage). Immunohistochemical studies showed the sequential difference of hematopoiesis between two different ossification systems. In humeral bone marrow, granulopoiesis appeared first at E16, followed by erythropoiesis from E17. On the contrary, erythropoiesis preceded one day in the maxillary bone marrow at E18, one day before the detection of granulopoiesis. G-SCF and GM-CSF were expressed at every examined stage in both types of bones while M-CSF was not expressed in the humeral bone marrow at E16. Erythropoietin was detetcted in the endothelial cells and its expression was coincident with the onset of erythopoiesis. These results suggest the time kinetic and sequential differences of hematopoiesis in two different ossification systems, which might relate to the differences of hematopoietic microenvironment

Molecular Cloning, Expression Analyses, and Physiological Roles of Cathelicidins in the Bursa of Fabricius of the Japanese Quail, <i>Coturnix japonica</i>

Antimicrobial peptides (AMPs) act directly on pathogens and maintain the anti-inflammatory effects and activation of immunocompetent cells. Therefore, the activation of the immune system in poultry via the elevation of endogenous AMPs has been attempted. In this study, we focused on the host defense mechanisms in the bursa of Fabricius (BF) of Japanese quail, cloned the cDNA of cathelicidin (CATH)-1 to -3, and analyzed their expression sites. In situ hybridization experiments revealed the mRNA expression of the CATHs in the interfollicular epithelium surrounding the lumen of the quail BF, which suggests that each CATH may exert its antimicrobial action directly in the BF. The intravenous injection of bacterial lipoteichoic acid and lipopolysaccharide endotoxins into the quail promoted the mRNA expression of CATH-1 and CATH-3 in the BF. The addition of CATH-1 or CATH-2 at the time of the antigen injection into mice resulted in antiserum with high antibody titers. Ad libitum administration of butyrate, a short-chain fatty acid, in the drinking water induced an increase in CATH-2 mRNA expression in the BF under certain conditions. These results may improve the defense mechanisms of quail by stimulating CATH expression in the BF through their diet

Development of postoperative delirium prediction models in patients undergoing cardiovascular surgery using machine learning algorithms

Abstract Associations between delirium and postoperative adverse events in cardiovascular surgery have been reported and the preoperative identification of high-risk patients of delirium is needed to implement focused interventions. We aimed to develop and validate machine learning models to predict post-cardiovascular surgery delirium. Patients aged ≥ 40 years who underwent cardiovascular surgery at a single hospital were prospectively enrolled. Preoperative and intraoperative factors were assessed. Each patient was evaluated for postoperative delirium 7 days after surgery. We developed machine learning models using the Bernoulli naive Bayes, Support vector machine, Random forest, Extra-trees, and XGBoost algorithms. Stratified fivefold cross-validation was performed for each developed model. Of the 87 patients, 24 (27.6%) developed postoperative delirium. Age, use of psychotropic drugs, cognitive function (Mini-Cog < 4), index of activities of daily living (Barthel Index < 100), history of stroke or cerebral hemorrhage, and eGFR (estimated glomerular filtration rate) < 60 were selected to develop delirium prediction models. The Extra-trees model had the best area under the receiver operating characteristic curve (0.76 [standard deviation 0.11]; sensitivity: 0.63; specificity: 0.78). XGBoost showed the highest sensitivity (AUROC, 0.75 [0.07]; sensitivity: 0.67; specificity: 0.79). Machine learning algorithms could predict post-cardiovascular delirium using preoperative data. Trial registration: UMIN-CTR (ID; UMIN000049390)

Tachykinins via Tachykinin NK(2) receptor activation mediate ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs

1. Acute exposure to ozone is known to cause airway hyperresponsiveness, which, at least in part, seems to result from an increase in the permeability of the airway mucosa. Recently, we demonstrated that depletion of sensory neuropeptides inhibits the ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs. The aim of this study was to determine whether tachykinins mediate ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs. 2. Anaesthetized guinea-pigs were exposed to either 3 p.p.m. ozone or filtered air for 30 min. Immediately after exposure, a tracheal segment was isolated in vivo and administered with horseradish peroxidase (HRP). The permeability was assessed by monitoring the appearance of HRP in the blood. 3. A low dose of NKA increased the permeability of the tracheal mucosa, whereas a low dose of SP was without effect. Low and high doses of the selective NK(3) receptor agonist, senktide, were also without effect. The effect of a low dose of NKA was abolished by the NK(2) receptor antagonist, SR-48,968. A high dose of SP increased the permeability in a manner reversible by the NK(1) receptor antagonist, CP-96,345. 4. Pretreatment with SR-48,968 completely inhibited the ozone-induced increase in the permeability, whereas CP-96,345 had no effect. 5. It is thus concluded that endogenous tachykinins mediate the ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs mainly via NK(2) receptor activation