Blomjeppesen8257

OBJECTIVES The aim of this study was to study the impact of a decision-making protocol for shunt type in the Norwood procedure for hypoplastic left heart syndrome. Our cohort extends from 2004 to 2016. In era 1 (pre-2008), there was no policy for the choice of Norwood shunt. In era 2 (post-2008), a standard protocol was implemented. The right ventricle (RV)-to-pulmonary artery conduit was utilized for low-birth weight patients ( less then 2.5 kg). The right modified Blalock-Taussig Shunt (RBTS) was constructed for normal birth weight patients. METHODS The records of 133 consecutive operative patients with hypoplastic left heart syndrome anatomy between 2004 and 2016 were retrospectively reviewed. Survival risk factors were analysed using the Cox proportional hazards risk model. RESULTS The Norwood procedure was performed at a mean age of 2.9 ± 1.9 days. Bidirectional cavopulmonary shunt was performed at a median age of 99 days (interquartile range 91-107). In era 1, 38.6% (22/57) of patients received the RBTS and 61.4% (35/57) of patients received the RV-to-pulmonary artery conduit. In era 2, 86.8% (66/76) of patients received the RBTS and 13.2% (10/76) of patients received the RV-to-pulmonary artery conduit. The actuarial survival to Fontan was 72.2% (96/133). Era 1 patients were more likely to die within the 1st year (hazard ratio = 2.310, P = 0.025). CONCLUSIONS The shunt protocol may improve outcomes in high-risk patients, and we have demonstrated the reliability of the RBTS in low-risk patients. The short- and mid-term outcomes of our Norwood population justify the continued efforts to improve surgical and perioperative management. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.BACKGROUND The stability of orthodontic treatment is thought to be significantly affected by the compression and retraction of gingival tissues, but the underlying molecular mechanism is not fully elucidated. The objectives of our study were to explore the effects of mechanical force on the ECM-integrin-cytoskeleton linkage response in human gingival fibroblasts (HGFs) cultured on 3-dimension (3D) lactide-co-glycolide (PLGA) biological scaffold and to further study the mechanotransduction pathways that could be involved. MATERIAL AND METHODS A compressive force of 25 g/m² was applied to the HGFs-PLGA 3D co-cultured model. Rhodamine-phalloidin staining was used to evaluate the filamentous actin (F-actin) cytoskeleton. The expression level of type I collagen (COL-1) and the activation of the integrin alpha₅ß₁/focal adhesion kinase (FAK) signaling pathway were determined by using real-time PCR and Western blotting analysis. The impacts of the applied force on the expression levels of FAK, phosphorylated focal adhesion kinase (p-FAK), and COL-1 were also measured in cells treated with integrin alpha₅ß₁ inhibitor (Ac-PHSCN-NH 2, ATN-161). RESULTS Mechanical force increased the expression of integrin alpha₅ß₁, FAK (p-FAK), and COL-1 in HGFs, and induced the formation of stress fibers. Blocking integrin alpha₅ß₁ reduced the expression of FAK (p-FAK), while the expression of COL-1 was not fully inhibited. CONCLUSIONS The integrin alpha₅ß₁/FAK signaling pathway and actin cytoskeleton appear to be involved in the mechanotransduction of HGFs. There could be other mechanisms involved in the promotion effect of mechanical force on collagen synthesis in addition to the integrin alpha₅ß₁ pathway.New technologies of induced pluripotent stem cells (iPSCs) and genome editing have emerged, allowing for the development of autologous transfusion therapies. We previously demonstrated definitive β-globin production from human embryonic stem cell (hESC)-derived erythroid cell generation via hemangioblast-like ES-sacs. In this study, we demonstrated normal β-globin protein production from biallelic corrected sickle cell disease (SCD) iPSCs. We optimized our ES/iPS-sac method for feeder cell-free hESC maintenance followed by serum-free ES-sac generation, which is preferred for electroporation-based genome editing. Surprisingly, the optimized protocol improved yields of ES-sacs (25.9-fold), hematopoietic-like spherical cells (14.8-fold), and erythroid cells (5.8-fold), compared with our standard ES-sac generation. We performed viral vector-free gene correction in SCD iPSCs, resulting in one clone with monoallelic and one clone with biallelic correction, and using this serum-free iPS-sac culture, corrected iPSC-generated erythroid cells with normal β-globin, confirmed at DNA and protein levels. Our serum-free ES/iPS-sac protocol with gene correction will be useful to develop regenerative transfusion therapies for SCD. © 2020 The Authors. This article is a U.S. Government work and is in the public domain in the USA.Identification of the novel HLA-A*31177 allele that differs from HLA-A*31010204 in exon 5. Selleck SBI-115 © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.OBJECTIVE Previous studies have revealed decreased mitochondrial respiration in adipocytes of obese mice. This study aimed to identify the molecular underpinnings of altered mitochondrial metabolism in adipocytes. METHODS Untargeted proteomics of mitochondria isolated from adipocytes and metabolite profiling of adipose tissues were conducted in diet-induced obese (DIO) and lean mice. Subcutaneous and intra-abdominal adipose tissues were studied to depict depot-specific alterations. RESULTS In subcutaneous adipocytes of DIO mice, changes in proteins related to mitochondrial structure and function were observed. Mitochondrial proteins of the inner and outer membrane were strongly reduced, whereas proteins of key matrix metabolic pathways were increased in the obese versus lean state, as further substantiated by metabolite profiling. A pronounced decrease in the oxidative phosphorylation (OXPHOS) enzymatic equipment and cristae density of the inner membrane was identified. In intra-abdominal adipocytes, similar systematic downregulation of the OXPHOS machinery in obesity occurred, but there was no regulation of outer membrane or matrix proteins. CONCLUSIONS Protein components of the OXPHOS machinery are systematically downregulated in adipose tissues of DIO mice compared with lean mice. Loss of the mitochondrial OXPHOS capacity in adipocytes may aggravate the development of metabolic disease. © 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).