Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.

Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becomes deposited in collagenous tissues and subsequently undergoes polymerisation, principally in the cartilages of loaded joints, in a process known as ochronosis. This results in an early-onset, devastating osteoarthropathy for which there is currently no effective treatment. We recently described the natural history of ochronosis in a murine model of AKU, demonstrating that deposition of ochronotic pigment begins very early in life and accumulates with age. Using this model, we were able to show that lifetime treatment with nitisinone, a potential therapy for AKU, was able to completely prevent deposition of ochronotic pigment. However, although nitisinone has been shown to inhibit ochronotic deposition, whether it can also facilitate removal of existing pigment has not yet been examined. We describe here that midlife administration of nitisinone to AKU mice arrests further deposition of ochronotic pigment in the tibiofemoral joint, but does not result in the clearance of existing pigment. We also demonstrate the dose-dependent response of plasma HGA to nitisinone, highlighting its efficacy for personalised medicine, where dosage can be tailored to the individual AKU patient

Childhood exposure to external ionising radiation and solid cancer risk

The increasing use of ionising radiation for diagnostic purposes has raised concern about potential iatrogenic damage, especially in children. In this review, we discuss some aspects of radiation-induced cancer in relation to age at exposure and measures that should be taken for limiting exposure in this sensitive population

Hybridization and hybrid speciation under global change

An unintended consequence of global change is an increase in opportunities for hybridization among previously isolated lineages. Here we illustrate how global change can facilitate the breakdown of reproductive barriers and the formation of hybrids, drawing on the flora of the British Isles for insight. Although global change may ameliorate some of the barriers preventing hybrid establishment, for example by providing new ecological niches for hybrids, it will have limited effects on environment-independent post-zygotic barriers. For example, genic incompatibilities and differences in chromosome numbers and structure within hybrid genomes are unlikely to be affected by global change. We thus speculate that global change will have a larger effect on eroding pre-zygotic barriers (eco-geographical isolation and phenology) than post-zygotic barriers, shifting the relative importance of these two classes of reproductive barriers from what is usually seen in naturally produced hybrids where pre-zygotic barriers are the largest contributors to reproductive isolation. Although the long-term fate of neo-hybrids is still to be determined, the massive impact of global change on the dynamics and distribution of biodiversity generates an unprecedented opportunity to study large numbers of unpredicted, and often replicated, hybridization ‘experiments’, allowing us to peer into the birth and death of evolutionary lineages

Epidemic space

The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

(Working title) Are We Meeting Oral Health Needs of Care Home Populations?

Aim: To evaluate care home (N) staff knowledge of oral care in comparison to NHS Quality Improvement Scotland (NHS QIS) guidelines. To identify barriers to delivering oral care and determine if Oral Health Educator (OHE) training had an effect upon staff knowledge of oral care delivery. Setting: The study was undertaken within Greater Glasgow, 2005 to 2007. Subjects and Methods: From 33 care homes (N), 28 participated in data gathering comprising 109 staff. A ‘knowledge check-list’ based upon daily oral care protocol from NHS QIS Best Practice Statement (BPS) served as template for knowledge assessment. An OHE undertook small group discussions related to the BPS in a sub-group of original participants and a second round of data collected. Results: The majority of staff (n=86, 79%) agreed that residents required assistance with oral care and placed oral care (n=85, 78%) as a moderate to high priority. Only 57% of managers and 49% of nurses had received training in oral care. Most staff (79% of managers, 85% of nurses) were unaware of the NHS QIS BPS. Deficiencies in knowledge of key areas within the BPS were identified. Between pre- and post-OHE training, significant differences were identified in prioritisation of oral care (p =0.009), perceived competence (p =0.005) and confidence giving advice (p =0.004). Following OHE intervention, knowledge of BPS protocol increased by 45%. Conclusion: Knowledge of oral care provision by carers for home residents requires substantial improvement. An OHE training programme structured around the NHS QIS BPS demonstrated a measurable increase in levels of staff knowledge of oral care