Bergeragger9843

BACKGROUND CONTENT The risks and benefits of recombinant human bone morphogenetic protein-2 (BMP) in posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) have been widely reported. However, the BMP dose associated with such reports varied widely. Additionally, data on the location of BMP placement on complications and fusion is lacking. PURPOSE To determine the minimally effective dose (MED) of BMP which results in optimal fusion rates while minimizing complications; to determine the effects of the location of BMP placement has on fusion rates and complications. STUDY DESIGN Systematic review and meta-analysis. STUDY SAMPLE Adult patients undergoing PLIF/TLIF for degenerative indications. OUTCOME MEASURES Rates of radiculitis, fusion, osteolysis, heterotopic bone formation and new cancer diagnosis. METHODS PubMed, Embase, and Cochrane Database were used to identify studies published between 1/1/2011-8/1/2019 reporting BMP usage in adult patients who underwent PLIF/TLIF defusion and complication rates between different BMP doses. Thirteen studies included data on the location of BMP placement with 1,823 patients. At each BMP location, the fusion rate was not significantly different across the dose ranges (1.28-12 mg/level). We found the fusion rate to be marginally higher in the interspace + PLG group compared to the other groups. When BMP was placed in the interbody cage there was a mild increase in the rate of osteolysis compared to other placement locations. CONCLUSION Fusion and complication rates did not differ significantly between different doses of BMP with the lowest MED for fusion as low as 1.28 mg/level. The location of BMP placement does not significantly affect fusion or complication rates. BACKGROUND A bacterial cause of disc degeneration has evoked several controversies and, if true, would lead to a major shift in treatment paradigm.  Earlier studies analyzing the relationship of bacterial disc infection within a degenerative cohort featured prolonged cultures susceptible to contamination. The DISC trial aims to investigate this theory further by examining infection rates using a non-degenerative control cohort in comparison to a degenerative internal control cohort and a sham cohort (sampling only sterile paraspinal tissue).  To our knowledge, the current study is the largest evaluating the growth of organisms (or possible contamination rate) in paraspinal tissue if prolonged cultures are performed. Protocols on methodology have been previously published. PURPOSE (1) To investigate the infection rates across cohorts (degenerative vs non-degenerative control; paraspinal/disc controls vs combined sampling cohorts) using stringent standardized aseptic surgical technique and laboratory processing-degenerative and degenerative disc populations. These findings are suggestive of a contamination theory and against a common infective etiology in the setting of discogenic back and neck pain. We believe the rationale for antibiotic therapy in the management of discogenic back pain warrants further evidence to establish efficacy. BACKGROUND Intracerebral hemorrhage is a devastating vascular event. Clinical factors prognostic of recurrence facilitating individualized post-bleeding patient management are sparsely described. We aimed to describe incidence of recurrence of intracerebral hemorrhage and explore the prognostic value of 25 clinical characteristics in patients with and without atrial fibrillation. METHODS Cohort study of patients with incident intracerebral hemorrhage diagnosed from 2003 to 2016 identified using nationwide Danish administrative registries. Results reported as cumulative incidence of intracerebral recurrence accounting for competing risk of death. Univariate and multivariate prognostic factors for recurrence estimated using Cox regression (hazard ratios [HRs], 95% confidence intervals [CI]). RESULTS We identified 9255 patients with incident intracerebral hemorrhage (median age 73 years, 46.6% females, 16% with atrial fibrillation). Five-year risks of recurrence of intracerebral hemorrhage were approximately 10% in the study population, although slightly higher for patients without atrial fibrillation. Prognostic factors for recurrence were broadly similar for patients with and without atrial fibrillation. Age in categories 80 years (HR 1.19, 95% CI 0.91-1.55), nursing home residency (HR 1.48, 95% CI 1.02-2.13), and Scandinavian Stroke Scale score ('mild' versus 'moderate' (HR 1.40, 95% CI 1.13-1.72) and 'severe' (HR 1.96, 95% CI 1.61-2.39)) were the strongest prognostic factors. CONCLUSION Risk of recurrence of intracerebral hemorrhage after five years was approximately 10%. Clinical characteristics associated with recurrence were few and broadly similar for patients with and without atrial fibrillation, with age and measure of incident bleeding severity, as reflected by Scandinavian Stroke Scale score, being the most important. OBJECTIVES The aim was to review the clinical impact of lymph node ratio (LNR) of groin metastatic nodal disease in women with vulvar squamous cell carcinoma Material and methods Cohort study of women with vulvar squamous cell carcinoma managed between January 2005 and December 2015 in five institutions in France with prospectively maintained databases (French multicenter tertiary care centers). PIK75 POPULATION 636 women managed for VSCC of whom 508 (79.9%) underwent surgical groin nodal staging. MAIN OUTCOME MEASURES Comparison of overall and recurrence free survival between women according to LNR Results 176 women (34.6%) had at least one positive lymph node (LN). There was a significant differences for the 5-year Overall Survival and Recurrence Free survival rates between women with LNR>0.2 and women with LNR less then 0.2. CONCLUSION LNR seems to be a significant prognostic factor in women with vulvar squamous cell carcinoma. The drug efflux pump P-glycoprotein (P-gp) displays a complex transport mechanism involving multiple drug binding sites and two centres for nucleotide hydrolysis. Elucidating the molecular mechanism of transport remains elusive and the availability of P-gp structures in distinct natural and ligand trapped conformations will accelerate our understanding. The present investigation sought to provide biochemical data to validate specific features of these structures; with particular focus on the transmembrane domain that provides the transport conduit. Hence our focus was on transmembrane helices six and twelve (TM6/TM12), which are believed to participate in drug binding, as they line the central transport conduit and provide a direct link to the catalytic centres. A series of P-gp mutants were generated with a single cysteine in both TM6 and TM12 to facilitate measurement of inter-helical distances using cross-linking and DEER strategies. Experimental results were compared to published structures per se and those refined by MD simulations. This analysis revealed that the refined inward-facing murine structure (4M1M) of P-gp provides a good representation of the proximity, topography and relative motions of TM6 and TM12 in reconstituted human P-gp. To obtain the desired technological properties (pasting, texture, and rheology) of naturally aged rice (AR), the aging process of freshly harvested rice was accelerated by controlled microwave treatment at 540 W for 1-3 min. Similar to AR, the rice microwave treated for 2 min showed increased pasting viscosities (peak, trough, breakdown, final, and setback) and pasting temperature, enhanced gel hardness and strength, and reduced gel adhesiveness. The mechanism by which microwaves accelerated rice aging was illustrated. Microwave treatment promoted the formation of protein disulfide bonds and the release of free phenolic acids, which enhanced protein gel network and cell wall strength. This phenomenon inhibited the swelling of starch granules and consequently modified the technological properties of rice. The crystalline structure and fatty acid content of rice flour was uninvolved in the mechanism, but the microwave-induced micromechanical change (intercellular cleavage to intracellular cleavage) of rice endosperm may be involved. Medium-chain fatty acids (C6-C10) have attracted much attention recently for their unique properties compared to their long-chain counterparts, including low melting points and relatively higher carbon conversion yield. Thioesterase enzymes, which can catalyze the hydrolysis of acyl-ACP (acyl carrier protein) to release free fatty acids (FAs), are known to regulate both overall FA yields and acyl chain length distributions in bacterial and yeast fermentation cultures. These enzymes typically prefer longer chain substrates. Herein, seeking to increase bacterial production of MCFAs, we conducted structure-guided mutational screening of multiple residues in the substrate-binding pocket of the E. coli thioesterase enzyme 'TesA. Confirming our hypothesis that enhancing substrate selectivity for medium-chain acyl substrates would promote overall MCFA production, we found that mutation of residues lining the bottom of the pocket with more hydrophobic residues strongly promoted the C8 substrate selectivity of 'TesA. Specifically, two rounds of saturation mutagenesis led to the identification of the 'TesARD-2 variant that exhibited a 133-fold increase in selectivity for the C8-ACP substrate as compared to C16-ACP substrate. Moreover, the recombinant expression of this variant in an E. coli strain with a blocked β-oxidation pathway led to a 1,030% increase in the in vivo octanoic acid (C8) production titer. When this strain was fermented in a 5-L fed-batch bioreactor, it produced 2.7 g/L of free C8 (45%, molar fraction) and 7.9 g/L of total free FAs, which is the highest-to-date free C8 titer to date reported using the E. coli type II fatty acid synthetic pathway. Thus, reshaping the substrate binding pocket of a bacterial thioesterase enzyme by manipulating the hydrophobicity of multiple residues altered the substrate selectivity and therefore fatty acid product distributions in cells. Our study demonstrates the relevance of this strategy for increasing titers of industrially attractive MCFAs as fermentation products. Producing some small hydrophobic molecules in microbes is challenging. Often these molecules cannot cross membranes, and thus their production may be limited by lack of storage space in the producing organism. This study reports a new technology for in vivo storage of valuable hydrophobic products in/on biopolymer bodies in Escherichia coli. A biodegradable and biocompatible polyester - poly (3-hydroxybutyrate) (PHB) - was selected as the intracellular storage vessel to encapsulate lycopene, which is a chromogenic model compound. The hydrophobic interaction between lycopene and PHB was verified by using in vitro binding test and sucrose density gradient centrifugation. Further in vivo characterization was performed by using Confocal Laser Scanning Microscopy (CLSM). The images validated the in vivo co-localization between PHB granules and lycopene. The images also showed that lycopene aggregated in bacteria that did not produce PHB, which may challenge the commonly accepted hypothesis that most lycopene molecules are stored in cell membranes of recombinant host.