Amyloid Oligomers as Blood Biomarkers in the Diagnosis of Alzheimer’s Disease

Oligomeric forms of the peptide, β-amyloid, (Aβ) are known to be toxic to human and rodent neurones, and have been identified as possible causative agents in the loss of cognitive function in Alzheimer’s Disease (AD). An ELISA assay has been developed capable of detecting oligomeric forms of Aβ in biological fluids, but not detecting monomeric species. The ELISA has been validated with a number of synthetic variant sequences of Aβ and the effects of known inhibitors of Aβ oligomer formation. Significantly raised levels of oligomers were detected in sera samples from AD patients, compared to age-matched control sera

Binary Polyhydroxyalkanoate Systems for Soft Tissue Engineering

Progress in tissue engineering is dependent on the availability of suitable biomaterials. In an effort to overcome the brittleness of poly(3-hydroxybutyrate), P(3HB), a natural biodegradable polyester, and widen its biomedical applications, plasticising of P(3HB) with oligomeric substances of related structure has been studied. A biosynthesised medium-chain-length polyhydroxyalkanoate (mcl-PHA) copolymer, the plasticizer precursor, was obtained using vegetable waste frying oil as a sole carbon source. The mcl-PHA was transformed into an oligomeric derivative by acid hydrolysis. The plasticising effect of the oligomeric mcl-PHA on P(3HB) was studied via characterisation of thermal and mechanical properties of the blends in the course of ageing at ambient conditions. Addition of oligomeric mcl-PHA to P(3HB) resulted in softer and more flexible materials based entirely on PHAs. It was shown that the oligomeric mcl-PHA transformed highly crystalline P(3HB) into materials with a dominant amorphous phase when the content of oligomeric mcl-PHA exceeded 10wt%. In vitro biocompatibility studies of the new binary PHA materials showed high viability and proliferation of C2C12 myoblast cells. Thus, the proposed approach for P(3HB) plasticisation has the potential for the generation of more pliable biomaterials based on P(3HB) which can find application in unique soft tissue engineering applications where a balance between stiffness, tensile strength and ductility is required

Viral Filtration Using Carbon-Based Materials

Viral infections alone are a significant cause of morbidity and mortality worldwide and have a detrimental impact on global healthcare and socioeconomic development. The discovery of novel antiviral treatments has gained tremendous attention and support with the rising number of viral outbreaks. In this work, carbonaceous materials, including graphene nanoplatelets and graphene oxide nanosheets, were investigated for antiviral properties. The materials were characterised using scanning electron microscopy and transmission electron microscopy. Analysis showed the materials to be two-dimensional with lateral dimensions ranging between 1 - 4 µm for graphene oxide, 110 ± 0.11nm for graphene nanoplatelets. Antiviral properties were assessed against a DNA virus model microorganism at concentrations of 0.5, 1.0 and 2.0 wt/v%. Both carbonaceous nanomaterials exhibited potent antiviral properties and gave rise to a viral reduction of 100% across all concentrations tested. Graphene oxide nanosheets were then incorporated into polymeric fibres and their antiviral behaviour was examined after 3 and 24 hours. A viral reduction of ~39% was observed after 24 hours of exposure. The research presented here showcases, for the first time, the antiviral potential of several carbonaceous nanomaterials, also included in a carrier polymer. These outcomes can be translated and implemented in many fields and devices to prevent viral spread and infection

PDS ‘To Go’? ‘Portability’ of Rights through Real-time Monitoring: the Centralised Online Real-time Electronic PDS in Chhattisgarh, India

Information and communications technology (ICT)-based reforms are increasingly being used to improve the delivery of public services. These reforms have taken the form of crowd-sourcing information (election monitoring), using ICTs to increase efficiency (e.g. computerised land registry systems), and connecting users to providers (e.g. mobile phone-based health services). These different approaches attempt to improve delivery through either (a) improving the quality of information, (b) reducing corruption or (c) making access more convenient and simple. The main question which the research reported here addressed was: through what processes, and under what conditions, do real-time monitoring technology-based reforms strengthen accountability and affect the delivery of public services? This was done by examining the Centralised Online Real-time Electronic (CORE) Public Distribution System (PDS) reforms introduced by the State Government of Chhattisgarh, India.UK Department for International Developmen

Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

Deep Eutectic Solvents Based on Natural Ascorbic Acid Analogues and Choline Chloride

Deep eutectic solvents (DES) are one of the most promising green technologies to emerge in recent years given their combination of environmentally friendly credentials and useful functionalities. Considering the continued search for new DES -- especially those that exemplify the aforementioned characteristics, we report the preparation of DES based on natural analogues of L-ascorbic acid for the first time. The onset of eutectic melting occurred at temperatures far below the melting point of the individual components and resulted in the generation of glass forming fluids with glass transition temperatures, viscosities and flow behavior that are comparable to similar systems. This work expands the current array of DES that can be produced using naturally occurring components, which given their potential to be bio-derived, interesting physicochemical properties (e.g. propensity to supercool and vitrify) and apparent antibacterial nature, may provide utility within a range of applications

Measuring health-related quality of life in chronic headache:a comparative evaluation of the Chronic Headache Quality of Life Questionnaire and Headache Impact Test (HIT-6)

Objective: To compare the quality and acceptability of a new headache-specific patient-reported measure the Chronic Headache Quality of Life Questionnaire (CHQLQ), with the Headache Impact Test–6 item (HIT-6), in people meeting an epidemiological definition of chronic headaches.Methods: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (N=130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness.Results: Both measures were well completed with few missing items. The CHQLQ’s inclusion of emotional wellbeing items increased its relevance to participant’s experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2-weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12-weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1). Conclusions: While both measures are structurally valid, internally consistent, temporally stable and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache. <br/

Measuring health-related quality of life in chronic headache: A comparative evaluation of the Chronic Headache Quality of Life Questionnaire and Headache Impact Test (HIT-6).

OBJECTIVE: To compare the quality and acceptability of a new headache-specific patient-reported measure, the Chronic Headache Quality of Life Questionnaire (CHQLQ) with the six-item Headache Impact Test (HIT-6), in people meeting an epidemiological definition of chronic headaches. METHODS: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (n = 130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness. RESULTS: Both measures were well completed with few missing items. The CHQLQ's inclusion of emotional wellbeing items increased its relevance to participant's experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2 weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12 weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1). CONCLUSIONS: While both measures are structurally valid, internally consistent, temporally stable, and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache.Trial registration number: ISRCTN79708100. Registered 16th December 2015, http://www.isrctn.com/ISRCTN79708100

Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial

Introduction: Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention. // Methods: A global, double-blind, 6-month study of patients with episodic migraine was undertaken with 915 intent-to-treat patients randomized to monthly galcanezumab 120 mg (n = 231) or 240 mg (n = 223) or placebo (n = 461) subcutaneous injections. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Key secondary endpoints were ≥50%,  ≥ 75%, and 100% response rates; monthly migraine headache days with acute migraine medication use; Patient Global Impression of Severity rating; the Role Function-Restrictive score of the Migraine-Specific Quality of Life Questionnaire. // Results: Mean monthly migraine headache days were reduced by 4.3 and 4.2 days by galcanezumab 120 and 240 mg, respectively, and 2.3 days by placebo. The group differences (95% CIs) versus placebo were 2.0 (−2.6, −1.5) and 1.9 (−2.4, −1.4), respectively. Both doses were superior to placebo for all key secondary endpoints. Injection site pain was the most common treatment-emergent adverse event, reported at similar rates in all treatment groups. Both galcanezumab doses had significantly more injection site reactions and injection site pruritus, and the 240 mg group had significantly more injection site erythema versus placebo. // Conclusions: Galcanezumab 120 or 240 mg given once monthly was efficacious, safe, and well tolerated. // Study identification: EVOLVE-2; NCT02614196; https://clinicaltrials.gov/ct2/show/NCT02614196. // Trial Registration: NCT02614196