Nilssonsehested1304

Mitochondrial abundance and thermogenic capacity are two imperative components that distinguish brown, beige and white adipose tissues. Most importantly, the lipid composition is vital for maintaining the quantity, quality and function of mitochondria. Therefore, we employed quantitative lipidomics to probe the mitochondrial lipidome of adipose tissues. The mitochondrial lipidome reveals β3-adrenergic stimulation and aging drastically altered the levels of phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio and acyl chain desaturation. Precisely, PC362 and PE384 levels correlate with the increased brown and beige fat activity in young mice. While aging increased lysoPC species in white adipose tissue (WAT) mitochondria, CL-316,243 administration reduced lysoPC species and increased lyso-PE181 and 182 content during WAT browning. Also, non-thermogenic mitochondria accumulate sphingomyelin (SM), phosphatidylserine (PS), phosphatidic acid (PA) and ether-linked PC (ePC). Similarly, enrichment of phosphatidylglycerol (PG) and cardiolipin (CL) levels are associated with thermogenic mitochondria. Also, our in vitro experiment supports that blocking the de novo sphingolipid synthesis pathway by myriocin, SPT1 inhibitor increased the thermogenic capacity and oxygen consumption rate in mature adipocytes. Overall, our study suggests mitochondria of brown, beige and white adipose tissues own a unique pattern of lipid molecular species and their levels are altered by aging and CL-316,243 administration.Bile acids are key components of bile required for human health. In humans and mice, conditions of reduced bile flow, cholestasis, induce bile acid detoxification by producing tetrahydroxylated bile acids (THBA), more hydrophilic and less cytotoxic than the usual bile acids, which are typically di- or tri-hydroxylated. Mice deficient in the Bile Salt Export Pump (Bsep, or Abcb11), the primary bile acid transporter in liver cells, produce high levels of THBA, and avoid the severe liver damage typically seen in humans with BSEP deficiencies. THBA can suppress bile acid-induced liver damage in Mdr2-deficient mice, caused by their lack of phospholipids in bile exposing their biliary tracts to unbound bile acids. Here we review THBA-related works in both animals and humans, and discuss their potential relevance and applications as a class of functional bile acids.Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO2/FiO2 ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO2/FiO2 ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.Lung transplantation is the only treatment for end-stage lung disease; however, donor organ shortage and intense immunosuppression limit its broad clinical impact. Bioengineering of lungs with patient-derived cells could overcome these problems. We created bioartificial lungs by seeding human-derived cells onto porcine lung matrices and performed orthotopic transplantation to assess feasibility and in vivo function. Porcine decellularized lung scaffolds were seeded with human airway epithelial cells and human umbilical vein endothelial cells. Following in vitro culture, the bioartificial lungs were orthotopically transplanted into porcine recipients with planned 1-day survival (n = 3). Lungs were assessed with histology and in vivo function. Orthotopic transplantation of cadaveric lungs was performed as control. Engraftment of endothelial and epithelial cells in the grafts were histologically demonstrated. Technically successful orthotopic anastomoses of the vasculatures and airway were achieved in all animals. Perfusion and ventilation of the lung grafts were confirmed intraoperatively. The gas exchange function was evident immediately after transplantation; PO2 gradient between pulmonary artery and vein were 178 ± 153 mm Hg in the bioartificial lung group and 183 ± 117 mm Hg in the control group. At time of evaluation 24 hours after reperfusion, the pulmonary arteries were found to be occluded with thrombus in all bioartificial lungs. Engineering and orthotopic transplantation of bioartificial lungs with human cells were technically feasible in a porcine model. Early gas exchange function was evident. Further progress in optimizing recellularization and maturation of the grafts will be necessary for sustained perfusability and function.Enlarged left atrium (LA) is a risk factor for ablation failure after atrial fibrillation (AF) surgery. It predisposes patients to thromboembolic events, even in successful ablation; therefore, concomitant resection of the LA wall during surgical ablation was introduced. This study examined the clinical impacts of LA reduction in patients undergoing concomitant ablation for AF. This study enrolled 1484 patients with enlarged LA (≥50 mm) who underwent surgical AF ablation during major cardiac surgery between January 2001 and August 2018. Among them, 876 (59%) patients underwent concomitant LA reduction (Reduction group), whereas in the remaining 608 (41%), the LA wall was unresected (Preservation group). The primary outcome of interest was overall stroke. The secondary outcomes were overall mortality, late recurrence of AF, early postoperative complications and postoperative echocardiographic parameters. Outcomes were compared after adjusting baseline characteristics with inverse probability of treatment weighting (IPTW) using propensity score. The median follow-up was 60.1 months. After IPTW adjustment, long-term mortality (P = 0.250) and AF-free rates (P = 0.196) did not significantly differ between groups. However, the Reduction group showed a decreased risk of stroke (hazard ratio 0.54; 95% confidence interval 0.32-0.90; P = 0.018). Early postoperative complications rate such as mortality or reoperation for bleeding, was not significantly different between the 2 groups. The Reduction group showed smaller LA diameter (50.6 ± 8.0 mm vs 53.6 ± 8.9 mm; P less then 0.001) on follow-up echocardiography. buy ITD-1 LA reduction effectively decreased LA size and appeared to decrease the stroke risk in patients with enlarged LA undergoing ablation for AF.Detailed knowledge of aortic anatomy is necessary before new prostheses can be developed. Our aim was to provide a thorough analysis of aortic arch anatomy in patients who are potential candidates for arch repair. Patients' charts were screened between 2001 and 2019 for all those with a dissection or aneurysm involving aortic arch. Aortic diameters, segmental lengths, aortic arch type, tortuosity, diameters and length of supraaortic vessels were analyzed via computed tomography angiography. We included 558 patients who underwent thoracic aortic treatment for type A, B, non-A non-B dissection, or aortic arch aneurysm. Incidence of all three arch types was similar in patients with type A dissection. In type B dissection and arch aneurysm patients, arch type III was most commonly observed (47% and 52%, respectively). The left vertebral artery offspring from aortic arch was observed in 6.6%. The mid-ascending aorta and aortic arch were not dilated in type B and non-A non-B dissection patients. The innominate, left common carotid and left subclavian arteries median diameters were 16 (14; 18), 8 (7; 9) and 11 (10; 12) mm, respectively. The median innominate artery length was 37 (30; 44) mm. The median left subclavian artery length was 40 (34; 46) mm. Arch types are distributed differently among patients with various arch pathologies. Patients with aortic dissection type B and non-A non-B have a non-dilated ascending aorta and aortic arch. Aortic arch tortuosity, innominate and left subclavian artery lengths do not differ among aortic pathologies.Venous thromboembolism (VTE), which comprises pulmonary embolus (PE) and deep vein thrombosis (DVT), is a significant cause of postoperative morbidity and mortality. This pilot randomized control trial (RCT) evaluated the feasibility of a full-scale RCT investigating extended thromboprophylaxis in patients undergoing oncological lung resections. Patients undergoing oncological lung resections in 2 tertiary centers received in-hospital, thromboprophylaxis and were randomized to receive post-discharge low-molecular-weight heparin (LMWH) or placebo injections once-daily for 30 days. At 30 days postoperatively, all patients underwent chest computed tomography with PE protocol and bilateral leg venous ultrasound. Primary outcomes included feasibility and safety; VTE incidence and 90-day survival were secondary outcomes. Between December 2015 and June 2018, 619 patients were screened, of whom 62.7% (165/263) of eligible patients consented to participate, and 133 (81%) were randomized. One-hundred and 3 patients, (77.