Lundchristian0467

tRNA synthetases are responsible for decoding the molecular information, from codons to amino acids. Seryl-tRNA synthetase (SerRS), besides the five isoacceptors of tRNASer, recognizes tRNA[Ser]Sec for the incorporation of selenocysteine (Sec, U) into selenoproteins. The selenocysteine synthesis pathway is known and is dependent on several protein-protein and protein-RNA interactions. Those interactions are not fully described, in particular, involving tRNA[Ser]Sec and SerRS. Here we describe the molecular interactions between the Escherichia coli Seryl-tRNA synthetase (EcSerRS) and tRNA[Ser]Sec in order to determine their specificity, selectivity and binding order, leading to tRNA aminoacylation. The dissociation constant of EcSerRS and tRNA[Ser]Sec was determined as (126 ± 20) nM. We also demonstrate that EcSerRS binds initially to tRNA[Ser]Sec in the presence of ATP for further recognition by E. coli selenocysteine synthetase (EcSelA) for Ser to Sec conversion. The proposed studies clarify the mechanism of tRNA[Ser]Sec incorporation in Bacteria as well as of other domains of life. OBJECT Tumors of the cervical spine often encase one or both vertebral arteries (VA), presenting the treating surgeon with the dilemma of whether to sacrifice or skeletonize the artery. Here we propose an algorithm for VA management in surgeries for cervical neoplasms METHODS Retrospective review of 67 patients undergoing resection of cervical spine tumors with VA involvement. Patients were categorized by tumor origin (primary vs. metastatic) and degree of circumferential VA involvement 1) abutment only; 2) 180° of circumferential VA involvement should be considered as indications for intraoperative sacrifice of the vertebral artery pending preoperative angiographic evaluation for contraindications. BACKGROUND The use of targeted therapies and immune checkpoint inhibitors has drastically changed the management of patients with melanoma and brain metastases. Specifically, combination therapy with ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, has become a preferred systemic therapy option for patients with melanoma and asymptomatic brain metastases. However, the efficacy and toxicity profile of these agents in combination with brain-directed radiation therapy is not well-described. CASE DESCRIPTION In this case series, we highlight a series of patients with melanoma demonstrating severe radiation necrosis immediately refractory to surgical resection following brain-directed stereotactic radiation therapy with concurrent ipilimumab and nivolumab. Three patients described in this series each received stereotactic radiation therapy to a dose of 30 Gy in 5 fractions to a melanoma brain metastasis. These areas developed radiographic evidence of necrosis, which was managed surgically and progressed immediately and rapidly after resection. Re-resection, bevacizumab, steroids, and/or discontinuation of nivolumab was used to mitigate further necrosis with varying efficacy. CONCLUSION Patients with metastatic melanoma receiving brain-directed radiation therapy with concurrent ipilimumab and nivolumab are at risk for developing severe, surgically refractory radiation necrosis and should be closely followed clinically and with imaging. The exact mechanism for such severe necrosis is unknown, and future studies are needed to better understand this pathophysiology and identify optimal treatment strategies. OBJECTIVE The influence of graft type (non-autologous versus autologous) on surgical outcomes in endoscopic anterior skull base (EASB) reconstruction is not well-understood. This review systematically evaluated rates of post-operative complications of EASB repairs that utilized autologous or non-autologous grafts. METHODS Original studies reporting EASB reconstruction outcomes were extracted from PubMed, Ovid, and Cochrane Library from database inception to 2019. Risk ratios (RRs), risk differences (RDs), chi-square tests, and multivariate logistic regression were used to evaluate outcome measures post-operative CSF leaks, meningitis, and other major complications (OMCs). SM-102 in vitro RESULTS A total of 2275 patients from 29 studies were analyzed. Rates of post-operative CSF leaks, meningitis, and OMCs were 4.0%, 1.6%, and 2.3%, respectively, using autologous grafts and 5.0%, 0.3%, and 1.0%, respectively, using non-autologous grafts. Multivariate analysis of 118 patients demonstrated no significant differences in age, CSF flow rate, single or multilayer reconstruction, and presence of intra-operative CSF leak or lumbar drain. Meta-analyses of six studies yielded a RR of 0.64 (95% CI0.19-2.14; p=0.47) for post-operative CSF leakage and RDs of -0.01 (95% CI-0.06-0.05; p=0.80) and -0.02 (95% CI-0.09-0.05; p=0.51) for post-operative meningitis and OMCs, respectively. There were no significant differences in post-operative CSF leakage (p=0.95) and OMCs (p=0.41) between graft types among cases with intra-operative CSF leaks. However, meningitis rates were lower (p=0.04) in the non-autologous group. CONCLUSIONS EASB reconstructions utilizing autologous and non-autologous grafts are associated with similar rates of post-operative CSF leakage and OMCs. In cases with intra-operative CSF leakage, non-autologous grafts were associated with reduced post-operative meningitis. INTRODUCTION The prognosis for patients with glioblastoma depends particularly on the degree of tumour resection. Patients with tumour remnants in post-surgical MRI ( less then 72 hours) may benefit from early re-operation. We present our results concerning the impact on overall survival (OS) and progression-free survival (PFS) of re-operation in patients who have already undergone surgery for glioblastoma. MATERIAL AND METHODS This study included all patients who had undergone surgery for glioblastoma with control MRI, who received adjuvant therapy as per the STUPP protocol, with a minimum follow-up of 24 months. We recorded the number of complete resections, partial resections and early re-operations. We determined the impact on OS and PFS of the early re-operations and the functional status. We considered complete resection when the volume of the residual tumour was 0 cc. RESULTS 112 patients were diagnosed with glioblastoma between March 2014 and March 2017. The study included 58 patients who fulfilled all the inclusion criteria.