Yildizhelms9653

Alzheimer's disease (AD), the most prevalent form of dementia, affects globally more than 30 million people suffering from cognitive deficits and neuropsychiatric symptoms. Substantial evidence for the involvement of mitochondrial dysfunction in the development and/or progression of AD has been shown in addition to the pathological hallmarks amyloid beta (Aβ) and tau. Still, the selective vulnerability and associated selective mitochondrial dysfunction cannot even be resolved to date. We aimed at optically quantifying mitochondrial function on a single-cell level in primary hippocampal neuron models of AD, unraveling differential involvement of cell and mitochondrial populations in amyloid precursor protein (APP)-associated mitochondrial dysfunction. NADH lifetime imaging is a highly sensitive marker-free method with high spatial resolution. However, deciphering cellular bioenergetics of complex cells like primary neurons has still not succeeded yet. To achieve this, we combined highly sensitive NADH lifetime imaging with respiratory inhibitor treatment, allowing characterization of mitochondrial function down to even the subcellular level in primary neurons. Measuring NADH lifetime of the same neuron before and after respiratory treatment reveals the metabolic delta, which can be taken as a surrogate for cellular redox capacity. Correlating NADH lifetime delta with overexpression strength of Aβ-related proteins on the single-cell level, we could verify the important role of intracellular Aβ-mediated mitochondrial toxicity. Subcellularly, we could demonstrate a higher respiration in neuronal somata in general than dendrites, but a similar impairment of somatic and dendritic mitochondria in our AD models. This illustrates the power of NADH lifetime imaging in revealing mitochondrial function on a single and even subcellular level and its potential to shed light into bioenergetic alterations in neuropsychiatric diseases and beyond.Owing to its clinical significance, modulation of functionally relevant amino acids in protein-protein complexes has attracted a great deal of attention. To this end, many approaches have been proposed to predict the partner-selecting amino acid positions in evolutionarily close complexes. These approaches can be grouped into sequence-based machine learning and structure-based energy-driven methods. In this work, we assessed these methods' ability to map the specificity-determining positions of Axl, a receptor tyrosine kinase involved in cancer progression and immune system diseases. For sequence-based predictions, we used SDPpred, Multi-RELIEF, and Sequence Harmony. For structure-based predictions, we utilized HADDOCK refinement and molecular dynamics simulations. As a result, we observed that (i) sequence-based methods overpredict partner-selecting residues of Axl and that (ii) combining Multi-RELIEF with HADDOCK-based predictions provides the key Axl residues, covered by the extensive molecular dynamics simulations. Expanding on these results, we propose that a sequence-structure-based approach is necessary to determine specificity-determining positions of Axl, which can guide the development of therapeutic molecules to combat Axl misregulation.Background Little is known about video-assisted thoracoscopic surgery in the Nuss procedure (VATS-NUSS) and its postoperative outcomes in the resource-scarce conditions in clinical practice such as Vietnam. Available evidence in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to review our initial large single-center experience in the use of the VATS-NUSS for patients with pectus excavatum (PE) within 5 years. Methods Data from 365 consecutive PE patients between January 2015 and December 2019 who were surgically treated with VATS-NUSS were retrospectively analyzed. Results Of 365 patients, median age at operation was 15.61 ± 3.73 years (range = 5-27 years), most being child and adolescent. Three hundred nine patients (84.65%) were male. PE was commonly detected at puberty (n = 328, 89.9%). Postoperatively, early complications consisted of pneumothorax (n = 5, 1.37%), pleural bleeding/pleural fluid (n = 2, 0.55%), pleural hematoma (n = 1, 0.27operative complications. Current rare evidence enables to give a real picture in the application, modification, and development of VATS-NUSS in the countries having similar resource-scarce conditions.Background The use of living-donor kidney allografts with multiple vessels continues to rise in order to increase the donor pool. This requires surgeons to pursue vascular reconstructions more often, which has previously been associated with a higher risk of developing early post-transplant complications. We therefore wanted to investigate the prognostic role of using living-donor renal allografts with a single artery (SA) vs. multiple arteries (MA) at the time of transplant. Methods We retrospectively analyzed a cohort of 210 consecutive living-donor kidney transplants performed between January, 2008 and March, 2019, and compared the incidence of developing postoperative complications and other clinical outcomes between SA vs. MA recipients. Results No differences were observed between SA (N = 161) and MA (N = 49) kidneys in terms of the incidence of developing a postoperative (or surgical) complication, a urologic complication, hospital length of stay, delayed graft function, estimated glomerular filtration rate at 3 or 12 mo post-transplant, and graft survival. Conclusions The use of live-kidney allografts with MA requiring vascular reconstruction shows excellent clinical outcomes and does not increase the risk of developing postoperative complications or other adverse outcomes when compared with SA renal allografts.Introduction Primary hepatic leiomyoma (PHL) is a rare benign hepatic tumor with unclear pathogenesis. It more commonly occurs in immunosuppressed patients, while only 24 cases have been described among immunocompetent individuals. To date, only one successful preoperative diagnosis of PHL has been achieved. Case Presentation Here we report a case of PHL in a middle-aged woman with no history of immunosuppression. Preoperative diagnosis of PHL was established using ultrasound-guided fine needle trucut biopsy (FNTB). Nevertheless, due to the growing nature of tumor and patient's symptoms, we proceeded with surgical resection, which confirmed the diagnosis of PHL. At 6-month follow up, the patient is in good condition with no evidence of tumor recurrence. check details Conclusions PHL is an uncommon tumor that should be considered in the differential diagnosis of rare liver tumors. Image guided FNTB appears to be effective in achieving preoperative diagnosis of PHL. Surgical resection, however, remains both diagnostic and curative in the management of PHL.