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Background Postoperative delirium has eluded attempts to define its complex aetiology and describe specific risk factors. The role of neuroinflammation as a risk factor, determined by measuring blood levels of preoperative ‘innate' inflammatory mediator levels, has been investigated. However, results have been conflicting. We conducted a systematic review and meta-analysis of the evidence on associations between preoperative blood levels of inflammatory mediators and postoperative delirium in the older person. Influence of type of surgery was also assessed. Methods Original, low risk of bias studies, published in peer-reviewed journals, which fulfilled the eligibility criteria were included. Seventeen articles fulfilled study criteria. Data extraction, synthesis, and risk of bias analysis were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and quality in prognostic studies guidelines. Meta-analyses used a random-effects model. Inflammatory mediators included C-reactive protein, interleukin-6, -8, and -10, tumour necrosis factor-α, insulin-like growth factor-1, cortisol, and neopterin. Surgical groups were cardiac, noncardiac, and hip fracture. Results Higher preoperative interleukin-6 was associated with postoperative delirium with a standardised mean difference (95% confidence interval) of 0.33 (0.11–0.56) and P=0.003. Higher neopterin was also associated with postoperative delirium. Conclusions The association of preoperative blood levels of inflammatory mediators with postoperative delirium may be influenced by the type of surgery and the specific mediator. The potential modulating effect of type of surgery, intrinsic brain vulnerability, and the complex interactions between inflammatory mediators and binding proteins will need to be considered in future studies. Clinical trial registration CRD42019159471 (PROSPERO).

Flavonoids are naturally-occurring polyphenolics that have been implicated in a wide range of biological activities. The major obstacles to flavonoid applications are the poor solubility in common solvents. Phosphorylation of flavonoids yields a new class of flavonoid derivatives which are very soluble in aqueous solutions and hence have the potential to be used in biological studies. We hereby report the sequential phosphorylation of Quercetin leading to the synthesis of Quercetin pentaphosphate (QPP), Apigenin triphosphate (ATRP), 5,4′-Quercetin Diphosphate (5,4′-QDP) and 4′-Quercetin monophosphate (4′-QP) with solubility of 848 mg/mL, 367 mg/mL, 315 μg/mL and 106 μg/mL respectively. The synthesis of 4′-QP, 5,4′-QDP, QPP and ATRP was successful with 85%, 60.5%, 56% and 99% yield respectively. These compounds have been characterized using 1H NMR, 13C NMR, 31P NMR.

Thinning of retinal layers, measured using optical coherence tomography (OCT), is associated with some neurodegenerative disorders such as established Alzheimer's disease and multiple sclerosis. The evidence for retinal layer thinning in both mild cognitive impairment (MCI), a precursor of dementia, and delirium, a potential pre-clinical stage of neurodegenerative disorder, is unclear. We performed a systematic review of the associations, in older people, between retinal layer thickness changes (measured using OCT) and delirium or MCI compared to controls (Protocol registration ID (Prospero) CRD42019122165). We did not identify any relevant studies on delirium. This report is therefore a review of retinal nerve layer changes in mild cognitive impairment. Databases were searched using predetermined keywords such as mild cognitive impairment, retinal nerve fibre layer and delirium. Where there were sufficient data, meta-analyses were performed. Twenty-six relevant studies were identified on retinal layer thickness in people with MCI compared to controls. There was significant heterogeneity in the studies for all retinal layers investigated (retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIP), foveal thickness and macular volume). Analysis of 17 studies of mean RNFL thickness in MCI (n = 622) compared to controls (n = 1154), irrespective of the type of OCT device, demonstrated a significant thinning in MCI (SMD: - 0·42 and 95 % confidence interval: - 0·68 to - 0·16). This difference was non-significant when studies using only spectral-domain devices were analysed. Subgroup analysis of studies using spectral-domain devices in amnestic MCI diagnosed using comparable criteria, showed statistically significant thinning of RNFL in amnestic MCI (p = 0·02). Meta-analysis of foveal thickness did not show a significant difference between MCI and controls. In conclusion, there is some evidence of an association between retinal nerve fibre layer thinning and MCI. We found no data on the association between RNFL and delirium.

Escherichia coli (E. coli) contamination in foods and water resources represents a major threat for human health and the environment. This work exploits the strong affinity of mannose-containing oligosaccharides with the fimbrial lectin of E. coli to design novel biosensors. Modified carbohydrate ligands were synthesized by introducing phenyl residues and aliphatic chains to mannose via reductive amination in order to increase both the affinity and selectivity to E. coli compared to other pathogenic bacteria. The synthesized ligands include p-thiolphenyl aminomannose (PTAM), p-carboxyphenyl aminomannose (PCAM), 1-deoxy-1-aminomannopyranoside (DAMP), glucosamine and low molecular weight chitosan bonded to mercapto undecanoic acid. The structures of the ligands were confirmed using (1)H NMR and 1H, (13)C, COZY NMR, and ESI/MS. The ligands were immobilized onto gold electrodes and SPR surfaces using-mercaptoundecanoic acid with glycine as deactivating agent. Two detection mechanisms were tested: (i) metal-enhanced electrochemical detection (MED) and (ii) label-free surface plasmon resonance (SPR) detection. The introduction of phenyl residues and aliphatic side groups to the mannose-containing oligosaccharides produced extremely high affinity for E. coli with detection limit of 1 cfu/mL. The relative selectivity of these ligands for E. coli, Citrobacter freundii, Staphylococcus epidermidis were 100%, 2.6% and 8.6% respectively. The biosensors were validated using spinach leaves at 3.0 cfu/mL. The work provides a generic biosensor for other pathogenic bacteria by enabling multivalent binding, immediate recognition for pathogens as well as inhibition of bacterial growth.

Hepatitis B virus capsid protein comprises a 149 residue “assembly” domain that polymerizes into icosahedral particles, and a 34 residue RNA-binding “protamine” domain. Recently, the capsid structure has been studied to resolutions below 10 A by cryo-electron microscopy, revealing much of its α-helical substructure and that it appears to have a novel fold for a capsid protein; however, the resolution is still too low for chain-tracing by conventional criteria. Aiming to establish a fiducial marker to aid in the process of chain-tracing, we have used cryo-microscopy to pinpoint the binding site of a monoclonal antibody that recognizes the peptide from residues 78 to 83. This epitope resides on the outer rim of the 30 A long spikes that protrude from the capsid shell. These spikes are four-helix bundles formed by the pairing of helix-turn-helix motifs from two subunits; by means of a tilting experiment, we have determined that this bundle is right-handed. Variants of the same protein present two clinically important and non-crossreactive antigens: core antigen (HBcAg), which appears early in infection as assembled capsids; and the sentinel e-antigen (HBeAg), a non-particulate form. Knowledge of the binding site of our anti-HBcAg antibody bears on the molecular basis of the distinction between the two antigens, which appears to reflect conformational differences between the assembled and unassembled states of the capsid protein dimer, in addition to epitope masking in capsids.

Three independently isolated mutants of Escherichia coli which apparently lacked protein L19 on their ribosomes, as judged by two-dimensional gels, were analyzed by a range of immunological tests to determine if the protein was indeed lacking. In two of the three, all the tests indicated that protein L19 was absent from both ribosome and supernatant. In the third, a drastically altered form of protein L19 was present on the ribosome. Electron micrographs of ribosomes obtained from the mutants were indistinguishable from those of wild type strains. The location of ribosomal protein L19 on the surface of the large subunit was determined. It was situated at the base of the 50 S particle facing the small subunit, on the side where the rod like appendage originates.

Ribosomes from three previously described mutants of Escherichia coli lacking L11 ( AM68 , AM76 , and AM77 ) supported in vitro termination with release factor 1 very poorly, but with release factor 2 had a severalfold elevation in activity for this function compared with ribosomes from a control strain or from a mutant containing unmethylated L11. L11 exerts its effect on the binding of the factors into a functional ribosomal complex with the termination codon. Reconstitution of L11 back into the L11-lacking ribosomes restored them to the control phenotype. The NH2-terminal part of L11 (amino acids 1-64) seems critical in modulating release factor binding. This part of L11 has been localized with the use of fragment-specific antibodies on the three-dimensional model of the 50 S subunit in the region from where the L7/L12 stalk originates. IgG antibodies from an antiserum specific for this fragment but not a middle fragment of L11 (amino acids 65-102) strongly inhibited in vitro termination. The activities of the two factors were inhibited differentially by several anti-L11 preparations recognizing antigenic determinants in the NH2-terminal part of L11. In all but one case, release factor 1 was more sensitive. These studies indicate that there are significant differences in the binding domains for the two release factors which are affected by the NH2-terminal part of L11.