Serum Neurofilament Light concentrations are not associated with renal function in secondary progressive multiple sclerosis

BACKGROUND: Neurofilament Light (NFL) is a promising biomarker of neuroaxonal injury. Its utility may be improved by expression relative to age-matched controls and by adjusting for other covariates, such as body mass index. It has recently been suggested that renal function may modulate the rate of clearance of NFL from circulation, which if confirmed would make renal function an important additional covariate to take into account when interpreting NFL data in research or clinical settings. Here we explore the relationship between renal function and NFL in a cohort of patients with secondary progressive multiple sclerosis (SPMS). METHODS: We examined data from patients with SPMS who took part in the MS-STAT randomised controlled trial. We use multivariable linear regression to explore the relationship between serum NFL and renal function, and additionally to examine whether including renal function as a covariate improves the ability of NFL to predict the subsequent rate of whole brain atrophy. RESULTS: Data on renal function and serum NFL was available for 122 patients. Mean eGFR 88 ml/min/1.73 m^{2} (range 38.2–121.9). We found no evidence to support a relationship between renal function and serum NFL in this cohort. Furthermore, the inclusion of eGFR as a covariate in models assessing the relationship between NFL and the rate of whole brain atrophy had no significant effect upon the relationships observed. CONCLUSIONS: We find no evidence for a relationship between renal function and NFL in a cohort of patients with secondary progressive multiple sclerosis. We hypothesise that the previously observed relationships between NFL and renal function related to associations between renal function and subclinical neuropathology, rather than due to modulating clearance of NFL from the circulation, but further research would be required to confirm such mechanisms

Cerebral time domain near-infrared spectroscopy of people with multiple sclerosis: A feasibility study

We present a feasibility study on the use of a time domain NIRS instrument, named MAESTROS, to explore the cerebral optical parameters and physiology of people with multiple sclerosis

Cerebral time domain near-infrared spectroscopy of people with multiple sclerosis: A feasibility study

We present a feasibility study on the use of a time domain NIRS instrument, named MAESTROS, to explore the cerebral optical parameters and physiology of people with multiple sclerosis

Immune-mediated encephalitis with daclizumab: The final nail

We provide clinical commentary on this edition's case report of immune-mediated encephalitis related to daclizumab therapy

Purification and characterization of a novel alginate lyase from a marine streptomyces species isolated from seaweed

Alginate, a natural polysaccharide derived from brown seaweed, is finding multiple applications in biomedicine via its transformation through chemical, physical, and, increasingly, enzymatic processes. In this study a novel alginate lyase, AlyDS44, was purified and characterized from a marine actinobacterium, Streptomyces luridiscabiei, which was isolated from decomposing seaweed. The purified enzyme had a specific activity of 108.6 U/mg, with a molecular weight of 28.6 kDa, and was composed of 260 amino acid residues. AlyDS44 is a bifunctional alginate lyase, active on both polyguluronate and polymannuronate, though it preferentially degrades polyguluronate. The optimal pH of this enzyme is 8.5 and the optimal temperature is 45¿C. It is a salt-tolerant alginate lyase with an optimal activity at 0.6 M NaCl. Metal ions Mn2+, Co2+, and Fe2+ increased the alginate degrading activity, but it was inhibited in the presence of Zn2+ and Cu2+. The highly conserved regions of its amino acid sequences indicated that AlyDS44 belongs to the polysaccharide lyase family 7. The main breakdown products of the enzyme on alginate were disaccharides, trisaccharides, and tetrasaccharides, which demonstrated that this enzyme acted as an endo-type alginate lyase. AlyDS44 is a novel enzyme, with the potential for efficient production of alginate oligosaccharides with low degrees of polymerization.T.N.T.N. would like to acknowledge the financial support provided by Flinders Research Scholarships, Flinders University, for offering the opportunity to complete her PhD project

Innovating for improved healthcare: Sociotechnical and innovation systems perspectives and lessons from the NHS

Healthcare systems with limited resources face rising demand pressures. Healthcare decision-makers increasingly recognise the potential of innovation to help respond to this challenge and to support high-quality care. However, comprehensive and actionable evidence on how to realise this potential is lacking. We adopt sociotechnical systems and innovation systems theoretical perspectives to examine conditions that can support and sustain innovating healthcare systems. We use primary data focussing on England (with 670 contributions over time) and triangulate findings against globally-relevant literature. We discuss the complexity of factors influencing an innovating healthcare system’s ability to support the development and uptake of innovations and share practical learning about changes in policy, culture, and behaviour that could support system improvement. Three themes are examined in detail: skills, capabilities, and leadership; motivations and accountabilities; and collaboration and coordination. We also contribute to advancing applications of sociotechnical systems thinking to major societal transformation challenges