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Except for epidermis and liver, little is known about endogenous expression of 1-O-acylceramides (1-OACs) in mammalian tissue. Therefore, we screened several organs (brain, lung, liver, spleen, lymph nodes, heart, kidney, thymus, small intestine, and colon) from mice for the presence of 1-OACs by LC-MS2. In most organs, low levels of about 0.25-1.3 pmol 1-OACs/mg wet weight were recorded. Higher levels were detected in liver, small and large intestines, with about 4-13 pmol 1-OACs/mg wet weight. 1-OACs were esterified mainly with palmitic, stearic, or oleic acids. Esterification with saturated very long-chain fatty acids, as in epidermis, was not observed. Western-type diet induced 3-fold increased 1-OAC levels in mice livers while ceramides were unaltered. In a mouse model of Farber disease with a decrease of acid ceramidase activity, we observed a strong, up to 50-fold increase of 1-OACs in lung, thymus, and spleen. In contrast, 1-OAC levels were reduced 0.54-fold in liver. selleck inhibitor Only in lung 1-OAC levels correlated to changes in ceramide levels - indicating tissue-specific mechanisms of regulation. Glucosylceramide synthase deficiency in liver did not cause changes in 1-OAC or ceramide levels, whereas increased ceramide levels in glucosylceramide synthase-deficient small intestine caused an increase in 1-OAC levels. Deficiency of Dgat1 in mice resulted in a reduction of 1-OACs to 30% in colon, but not in small intestine and liver, going along with constant free ceramides levels. From these data, we conclude that Dgat1 as well as lysosomal lipid metabolism contribute in vivo to homeostatic 1-OAC levels in an organ-specific manner.The aim of this study was to characterize the echocardiographic phenotype of patients with Covid-19 pneumonia and its relation to biomarkers. Seventy-four patients (59±13 years, 78% male) admitted with Covid-19 were included after referral for transthoracic echocardiography (TTE) as part of routine care. A level 1 British Society of Echocardiography TTE assessed chamber size and function, valvular disease and likelihood of pulmonary hypertension. The chief abnormalities were right ventricular (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and CRP levels. In contrast, left ventricular (LV) function was hyper-dynamic or normal in most (89%) patients.Background Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary prevention implantable cardioverter defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of the study was to assess the incidence of ICD therapies at 30, 60 and 180 days after implantation. Methods and results DREAM-ICD is a retrospective cohort study that was conducted at 2 Canadian university centers enrolling patients with new implantation of a primary prevention ICD. Device programming was standardized according to current guidelines. A total of 803 patients were enrolled. The cumulative rate of appropriate ICD therapies at 30, 60 and 180 days was 0.12%, 0.50% and 0.75% respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, less than 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation. Conclusions The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary prevention ICD recipients.Background We aimed to assess long-term outcomes in S-ICD recipients with structural heart disease, especially focusing on shock incidence, predictors and associated prognoses. Methods In this multicenter registry-based study, we retrospectively included all patients who underwent S-ICD implantation in 3 tertiary centers. The prognostic impact of S-ICD shock was assessed with a composite outcome that included all-cause death and hospitalization for heart failure. Results A total of 351 patients with underlying cardiomyopathy were included. In multivariable Fine and Gray regression models, secondary prevention, LVEF, conditional shock threshold, and QRS duration appeared to be independent predictors of appropriate S-ICD shock occurrence. In the multivariate Cox regression model adjusted for age, baseline LVEF, underlying cardiomyopathy subtype, NYHA class and appropriate shocks were significantly associated with increased composite prognostic outcome risk (HR 2.61, 95% CI 1.21 to 5.65, p=0.014), whereas inappropriate shocks were not(HR 1.35, 95% CI 0.75 to 4.48, p=0.18) . The analysis of each component of the composite prognostic outcome highlighted that the occurrence of appropriate shocks was associated with an increased risk of hospitalization for heart failure (HR 3.10, 95% CI 1.26 to 7.58, p=0.013) and a trend for mortality (HR 2.19, 95% CI 0.78 to 6.16, p=0.14). Conclusions Appropriate S-ICD shocks were associated with a 3-fold increase in acute heart failure admission, whereas inappropriate shocks were not. Conditional shock threshold programming is an independent predictor of S-ICD shock, and its prognostic impact should be further investigated in patients with structural heart disease.d-Amino acids are physiologically important components of peptidoglycan in the bacterial cell wall, maintaining cell structure and aiding adaptation to environmental changes through peptidoglycan remodelling. Therefore, the biosynthesis of d-amino acids is essential for bacteria to adapt to different environmental conditions. The peptidoglycan of the extremely thermophilic bacterium Thermus thermophilus contains d-alanine (d-Ala) and d-glutamate (d-Glu), but its d-amino acid metabolism remains poorly understood. Here, we investigated the enzyme activity and function of the product of the TTHA1643 gene, which is annotated to be a Glu racemase in the T. thermophilus HB8 genome. Among 21 amino acids tested, TTHA1643 showed highly specific activity toward Glu as the substrate. The catalytic efficiency (kcat/Km) of TTHA1643 toward d- and l-Glu was comparable; however, the kcat value was 18-fold higher for l-Glu than for d-Glu. Temperature and pH profiles showed that the racemase activity of TTHA1643 is high under physiological conditions for T.
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