Fatty foci within the heart and the accompanying changes in the coronary arteries diagnosed in electrocardiogram-gated multislice computed tomography of the heart

Background: The purpose of our study was to analyse the relationship between fatty foci within the heart and the accompanying changes in the coronary arteries supplying the relevant heart chambers in a large group of patients referred to multi-slice computed tomography with electrocardiogram-gating examinations (ECG-MSCT) for various clinical reasons. Materials and methods: The ECG-MSCT examinations of 1,830 consecutive patients were analysed. The examinations were performed using 8-row (1,015 patients) and 64-row (815 patients) MSCT, in pre- and postcontrast scanning. In the group of patients with fatty foci within the heart the concomitant changes in the coronary arteries were assessed. It was analysed: the type of changes in the arteries; the relationship between the locations of the fatty deposits and the occurrence and type of changes in the coronary arteries. Results: In 200 (10.9%) subjects fatty foci within the heart (112 men; 88 women; mean age 57.8) were detected. The distribution of the fat was as follows: right ventricle (RV) — 32.5%, left ventricle (LV) — 22.0%, biventricular — 45.5%. One hundred and seventy-two patients had concomitant changes in the coronary arteries. In patients with normal coronary arteries, significantly more often fatty deposits were localised within RV. Fat was primarily located subendocardially in the LV in patients with atherosclerosis in the left anterior descending artery (p < 0.001), in the right coronary artery (RCA) (p = 0.003), and in the left circumflex artery (LCX) (p < 0.001). Subpericardial locations of fatty deposits in RV significantly correlated with RCA bridging (p < 0.02); the subpericardial location of fat in LV significantly correlated with LCX bridging (p = 0.001). Conclusions: Fatty replacement of the myocardium is common, occurring in up to 10% of diagnosed patients and the majority of this group had concomitant changes in the coronary arteries. However, in the group of patients without changes in the coronary arteries, the fatty deposits locate themselves significantly more frequently within the RV

4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells

Chronic and acute myeloid leukemia evade immune system surveillance and induce immunosuppression by expanding proleukemic Foxp31 regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse, and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers of effector proleukemic Tregs. Using mouse model of leukemia-like disease, we found that Rab27adependent secretion of leukemic EVs promoted leukemia engraftment, which was associated with higher abundance of activated, immunosuppressive Tregs. Leukemic EVs attenuated mTOR-S6 and activated STAT5 signaling, as well as evoked significant transcriptomic changes in Tregs. We further identified specific effector signature of Tregs promoted by leukemic EVs. Leukemic EVs-driven Tregs were characterized by elevated expression of effector/tumor Treg markers CD39, CCR8, CD30, TNFR2, CCR4, TIGIT, and IL21R and included 2 distinct effector Treg (eTreg) subsets: CD301CCR8hiTNFR2hi eTreg1 and CD391TIGIThi eTreg2. Finally, we showed that costimulatory ligand 4-1BBL/CD137L, shuttled by leukemic EVs, promoted suppressive activity and effector phenotype of Tregs by regulating expression of receptors such as CD30 and TNFR2. Collectively, our work highlights the role of leukemic extracellular vesicles in stimulation of immunosuppressive Tregs and leukemia growth. We postulate that targeting of Rab27a-dependent secretion of leukemic EVs may be a viable therapeutic approach in myeloid neoplasms

Influence of self-made saliva substitutes on tribological characteristics of human enamel

This paper describes the results of tests on the influence of human saliva and its substitutes on tribological characteristics of friction pairs. Each pair consists of enamel and one of the following materials: ceramics, the Meridian B2 dental composite, the GK dental amalgam, and Ti-6Al-4V titanium alloy. The saliva substitutes used were prepared using pyrophosphates, xanthan gum, and mucins dissolved in a saline buffer. The results of the tribological tests show that the values of the parameters under investigation (coefficient of friction and linear wear) were different from each other. Some similarity was observed between the evaluated level of wear characteristics after the friction process in the environment of human saliva and that in the environment of one of the mucins tested. Microscopic observations of the surfaces of the enamel samples after friction revealed varied forms of tribological wear