UCL University College London Eprints
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.
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The novel MAPT mutation K298E: Mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons - Iovino, M; Calo, L; Spillantini, MG; Pfisterer, U; Parmar, M; Holton, JL; Lashley, T; Revesz, T; Swingler, RJ; Muqit, MMK; Treacy, R; Goedert, M
Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and...
The significance of α-synuclein, amyloid-β and tau pathologies in parkinson's disease progression and related dementia - Compta, Y; Kempster, P; Parkkinen, L; Selikhova, M; Lashley, T; Holton, JL; Lees, AJ; Revesz, T
Background: Dementia is one of the milestones of advanced Parkinson's disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. Objective: The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer's tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD. Methods: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. Results: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn,...
More than A to B: The role of free bus travel for the mobility and wellbeing of older citizens in London - Green, J; Jones, A; Roberts, H
This study contributes to the literature on mobility and wellbeing at older ages through an empirical exploration of the meanings of free bus travel for older citizens, addressing the meanings this holds for older people in urban settings, which have been under-researched. Taking London as a case study, where older citizens have free access to a relatively extensive public transport network through a Freedom Pass, we explore from a public health perspective the mechanisms that link this travel benefit to determinants of wellbeing. In addition to the ways in which the Freedom Pass enabled access to health-related goods and services,...
Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C - Petersen, JR; Stevenson, HL; Snyder, N; Kasturi, KS; Naniwadekar, A; Parkes, J; Cross, R; Rosenberg, WM; Xiao, S-Y
BACKGROUND:: The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. METHODS:: We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio...
Carer-led health interventions to monitor, promote and improve the health of adults with intellectual disabilities in the community: A systematic review - Hithersay, R; Strydom, A; Moulster, G; Buszewicz, M
Using carers to help assess, monitor, or promote health in people with intellectual disabilities (ID) may be one way of improving health outcomes in a population that experiences significant health inequalities. This paper provides a review of carer-led health interventions in various populations and healthcare settings, in order to investigate potential roles for carers in ID health care. We used rapid review methodology, using the Scopus database, citation tracking and input from ID healthcare professionals to identify relevant research. 24 studies were included in the final review. For people with ID, the only existing interventions found were carer-completed health diaries...
The influence of drug physical state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: A case study using olanzapine - Pina, MF; Sousa, JJ; Zhao, M; Craig, DQM; Pinto, JF
In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug-polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated...
Differences in cortical coding of heat evoked pain beyond the perceived intensity: An fMRI and EEG study - Haefeli, J; Freund, P; Kramer, JLK; Blum, J; Curt, A; Luechinger, R
Imaging studies have identified a wide network of brain areas activated by nociceptive stimuli and revealed differences in somatotopic representation of highly distinct stimulation sites (foot vs. hand) in the primary (S1) and secondary (S2) somatosensory cortices. Somatotopic organization between adjacent dermatomes and differences in cortical coding of similarly perceived nociceptive stimulation are less well studied. Here, cortical processing following contact heat nociceptive stimulation of cervical (C4, C6, and C8) and trunk (T10) dermatomes were recorded in 20 healthy subjects using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Stimulation of T10 compared with the C6 and C8 revealed significant...
Concordance between peri-areolar blue dye and peri-incisional radiotracer injections for sentinel node mapping in patients with a history of primary breast cancer excisonal biopsy - Mehrabibahar, M; Azizi, S; Jangjoo, A; Saremi, E; Dabbagh Kakhki, VR; Sadeghi, R; Chicken, DW; Keshtgar, M; Ramin, S
Background: We evaluated the concordance between peri-areolar blue dye and peri-incisional radiotracer injections for axillary sentinel node mapping of patients with the history of previous breast lesion excisional biopsy. Methods: 80 patients with the history of previous excisional biopsy of the breast lesions were included. All patients received two injections of 99mTc-antimony sulfide colloid in both ends of incision line in an intradermal fashion. 2 mL patient blue V dye was injection to all patients in the peri-areolar area of the index quadrant after induction of anesthesia. All blue or hot nodes were harvested as sentinel lymph nodes. Results: At...
Managing latent tuberculosis in UK renal transplant units: How does practice compare with published guidance? - Maynard-Smith, L; Lipman, M; Fernando, B; Harber, M; Hopkins, S
Renal transplantation significantly increases the risk of active tuberculosis (TB) in individuals with latent TB infection (LTBI). UK transplant recipients are often born in TB endemic areas. Using a self-completed questionnaire, we evaluated how the 23 UK renal transplant units' LTBI management compared with recently published national guidance. Three-quarters had a management protocol, but only one-third of these were in line with the guidance. Interferon-gamma release assays were rarely used to confirm LTBI. Almost half of the units prescribed LTBI treatment at the wrong dose or duration. We conclude that units should develop local protocols in line with evidence-based guidance....
Multifunctional hybrid nanocarrier: Magnetic CNTs ensheathed with mesoporous silica for drug delivery and imaging system - Singh, RK; Patel, KD; Kim, J-J; Kim, T-H; Kim, J-H; Shin, US; Lee, E-J; Kim, H-W; Knowles, JC
Here we communicate the development of a novel multifunctional hybrid nanomaterial, magnetic carbon nanotubes (CNTs) ensheathed with mesoporous silica, for the simultaneous applications of drug delivery and imaging. Magnetic nanoparticles (MNPs) were first decorated onto the multiwalled CNTs, which was then layered with mesoporous silica (mSiO) to facilitate the loading of bioactive molecules to a large quantity while exerting magnetic properties. The hybrid nanomaterial showed a high mesoporosity due to the surface-layered mSiO, and excellent magnetic properties, including magnetic resonance imaging in vitro and in vivo. The mesoporous and magnetic hybrid nanocarriers showed high loading capacity for therapeutic molecules including...
Significant hypotension following buccal midazolam administration - Kensche, M; Sander, JW; Sisodiya, SM
Buccal midazolam is a rescue medication to reduce the duration of or stop an epileptic seizure, and is used to prevent status epilepticus. It is available in various forms, including a buccal preparation with a strength of 10 mg/1 ml. Midazolam is a licensed medication, but the buccal formulation is currently used off-licence. The prescriber takes ultimate responsibility for its use in this way. Administered by a trained person, it is receiving widespread acceptance as an alternative and effective treatment to rectally-administered diazepam in the community. The commonest side effects of midazolam are drowsiness and somnolence, although respiratory depression and...
The impact of strabismus on quality of life in adults with and without diplopia: a systematic review. - McBain, HB; Au, CK; Hancox, J; Mackenzie, KA; Ezra, DG; Adams, GG; Newman, SP
Strabismus affects approximately 4% of the adult population and can cause substantial physical disturbance and changes to appearance. This article aims to examine the impact of strabismus in adults both with and without diplopia, focusing primarily on quality of life (QoL). We highlight the value of measuring QoL, assess the ways in which it can be measured, and the impact the disease, diplopia, and surgery have on the patient. QoL differs for strabismus patients based on their diplopia status. Patients with diplopia tend to have more concerns relating to functional QoL, whereas patients without diplopia have primarily psychosocial concerns. Two...