Background Retinal vein occlusion (RVO) is the second most common retinal vascular disorder that affected 16.4 million people worldwide in 2008. The last decade has seen new epidemiological data on RVO, enabling us to provide a contemporary estimation of RVO epidemiology. Methods We searched PubMed, Medline, Embase, GLOBAL HEALTH, World Health Organization Global Health Library, China National Knowledge Infrastructure for studies that reported prevalence or incidence of RVO in the general population. The age- and sex-specific prevalence of RVO was estimated by a multilevel mixed-effects logistic regression, the incidence of RVO and potential risk factors for RVO were respectively pooled by a random-effects meta-analysis. Results The prevalence of any RVO, branch RVO (BRVO) and central RVO (CRVO) all increased with advanced age, but didn’t differ significantly between sexes. In 2015, the global prevalence of any RVO, BRVO and CRVO in people aged 30-89 years was 0.77% (95% confidence interval CI = 0.55-1.08), 0.64% (95% CI = 0.47-0.87) and 0.13% (95% CI = 0.08-0.21), equivalent to an overall of 28.06 million, 23.38 million and 4.67 million affected people. For any RVO, the pooled five-year cumulative incidence was 0.86% (95% CI = 0.70-1.07) and the pooled ten-year cumulative incidence was 1.63% (95% CI = 1.38-1.92). Hypertension was the strongest risk factor for any RVO, with a meta- odds ratio (OR) of 2.82 (95% CI = 2.12-3.75). Conclusions This study provides an updated summary of RVO epidemiology in the general population. More epidemiological studies worldwide are still needed to better understand the global disease burden of RVO.
Background and objective: This study investigated whether circulating tumour cells (CTC) are detectable in patients with non-small cell lung cancer (NSCLC) and whether CTC count could provide prognostic information or serve as an indicator of patient response to chemotherapy. Methods: We enrolled 46 patients with newly diagnosed or recurrent NSCLC. CTC were measured at baseline in all patients and in 23 patients, CTC were also measured before every chemotherapy cycle. The relationship between CTC count and tumour size was analysed. Results: CTC were present in 40 patients (87%); among them, 29 (63%) had a CTC count of ≥3 cells/ 3.2 mL, 17 (37%) had a CTC count of ≥5 cells/3.2 mL and 7 (15.2%) had a CTC count of ≥8 cells/3.2 mL. The median progression-free survival (PFS) and overall survival (OS) were 7.3 months and 16 months, respectively. A CTC count of more than eight prior to chemotherapy was a strong predictor of reduced PFS (P = 0.018) and OS (P = 0.026). A multivariate analysis indicated that baseline CTC count was an independent negative prognostic factor for survival. However, no correlation was observed between CTC count and tumour size after two chemotherapy cycles, its relationship with chemotherapy response still needs to be defined. Conclusion: Baseline CTC count is an independent negative prognostic factor for NSCLC; The relationship of CTC and survival after chemotherapy still needs to be defined.
The Escherichia coli repressor of biotin biosynthesis (BirA) is a unique transcriptional repressor which catalyzes synthesis of its own corepressor and catalyzes attachment of a cofactor to an essential metabolic enzyme. BirA both catalyzes synthesis of biotinyl-5'-AMP from the substrates ATP and biotin and transfer of the biotin moiety from the adenylate to a lysine residue of a subunit of the acetyl-CoA carboxylase. BirA-bio-5'-AMP, moreover, binds sequence specifically to the biotin operator to repress transcription of the biotin biosynthetic genes. Using a combination of kinetic measurements of binding of the two ligands, biotin and bio-5'-AMP, to BirA as well as proteolytic digestion experiments, we have found evidence for at least three discrete conformational states of BirA. Results of stopped-flow fluorescence measurements of association of both ligands with BirA indicate that the process involves initial formation of a collision complex followed by a slow conformational change. The kinetics of the conformational change are distinct for the two ligands and are the basis for the difference in the thermodynamic stabilities of the two protein-ligand complexes. Different rates of proteolytic digestion of apoBirA and complexes of BirA with the two ligands were also observed. Results of the combined approaches indicate that apoBirA, and the BirA-bio-5'-AMP and BirA-biotin complexes are conformationally distinct.
The Escherichia coli repressor of biotin biosynthesis is both a biotin ligase and the repressor of transcriptional initiation at the biotin biosynthetic operon. The small molecule, biotinyl-5'-adenylate (bio-5'-AMP), is the intermediate in the biotin ligation reaction and the positive allosteric effector for sequence-specific DNA binding by BirA. Synthesis of the adenylate from the substrates biotin and ATP is catalyzed by BirA. Although BirA and other biotin holoenzyme synthetases have been the subject of biochemical studies, no direct measurements of the bio-5'-AMP synthesis reaction have been reported. No information relating to the mechanism and kinetic parameters governing adenylate synthesis is available. In addition to this lack of kinetic information, the thermodynamic stability of the BirA-bio-5'-AMP complex is not known. Since the BirA-adenylate complex plays a pivotal role in the biotin regulatory system, both the kinetic and thermodynamic information are essential to a quantitative understanding of the system. We have developed a method for measuring the time course of bio-5'-AMP synthesis. The results of these measurements indicate that the time course is characterized by an initial burst followed by a slow linear phase. The burst corresponds to the rapid synthesis of 1 mol of product per mole of enzyme, and the rate of the slow linear phase is limited by the release of product from the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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