Molecular mechanisms of xeroderma pigmentosum (XP) proteins

Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA-XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase., which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins

Evaluation of the impact of a school gardening intervention on children's fruit and vegetable intake: a randomised controlled trial.

Background: Current academic literature suggests that school gardening programmes can provide an interactive environment with the potential to change children’s fruit and vegetable intake. This is the first cluster randomised controlled trial (RCT) designed to evaluate whether a school gardening programme can have an effect on children’s fruit and vegetable intake. Methods: The trial included children from 23 schools; these schools were randomised into two groups, one to receive the Royal Horticultural Society (RHS)-led intervention and the other to receive the less involved Teacher-led intervention. A 24-hour food diary (CADET) was used to collect baseline and follow-up dietary intake 18 months apart. Questionnaires were also administered to evaluate the intervention implementation. Results: A total of 641 children completed the trial with a mean age of 8.1 years (95% CI: 8.0, 8.4). The unadjusted results from multilevel regression analysis revealed that for combined daily fruit and vegetable intake the Teacher-led group had a higher daily mean change of 8 g (95% CI: −19, 36) compared to the RHS-led group -32 g (95% CI: −60, −3). However, after adjusting for possible confounders this difference was not significant (intervention effect: −40 g, 95% CI: −88, 1; p = 0.06). The adjusted analysis of process measures identified that if schools improved their gardening score by 3 levels (a measure of school gardening involvement - the scale has 6 levels from 0 ‘no garden’ to 5 ‘community involvement’), irrespective of group allocation, children had, on average, a daily increase of 81 g of fruit and vegetable intake (95% CI: 0, 163; p = 0.05) compared to schools that had no change in gardening score. Conclusions: This study is the first cluster randomised controlled trial designed to evaluate a school gardening intervention. The results have found very little evidence to support the claims that school gardening alone can improve children’s daily fruit and vegetable intake. However, when a gardening intervention is implemented at a high level within the school it may improve children’s daily fruit and vegetable intake by a portion. Improving children’s fruit and vegetable intake remains a challenging task

Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any 'gold standard'. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability

The value of intraoperative neurophysiological monitoring in tethered cord surgery

The value of intraoperative neurophysiological monitoring (IONM) with surgical detethering in dysraphic patients has been questioned. A retrospective analysis of our series of 65 patients is presented with special focus on technical set-up and outcome. All patients were diagnosed with a tethered cord (TC) due to spinal dysraphism. A high-risk group (HRG) was determined consisting of 40 patients with a lipomyelomeningocele and/or a split cord malformation sometimes in combination with a tight filum terminale. The surgical procedure was a detethering operation in all cases performed by a single surgeon during a 9-year period (1999-2008). A standard set-up of IONM was used in all patients consisting of motor-evoked potentials (MEP) evoked by transcranial electrical stimulation (TES) and electrical nerve root stimulation. In young patients, conditioning stimulation was applied in order to improve absent or weak MEPs. IONM responses could be obtained in all patients. Postoperative deterioration of symptoms was found in two patients of whom one patient belonged to the HRG. Mean maximal follow-up of all 65 patients was 4.6 years (median 4.1 years). Long-term deterioration of symptoms was found in 6 of 65 patients with a mean follow-up of 5 years (median 5.3 years). The use of IONM is feasible in all TC patients. The identification of functional nervous structures and continuous guarding of the integrity of sacral motor roots by IONM may contribute to the safety of surgical detethering

Pollen sterols are associated with phylogenetics and environment but not with pollinators

Phytosterols are primary plant metabolites that have fundamental structural and regulatory functions. They are also essential nutrients for phytophagous insects, including pollinators, that cannot synthesize sterols. Despite the well-described composition and diversity in vegetative plant tissues, few studies have examined phytosterol diversity in pollen. We quantified 25 pollen phytosterols in 122 plant species (105 genera, 51 families) to determine their composition and diversity across plant taxa. We searched literature and databases for plant phylogeny, environmental conditions, and pollinator guilds of the species to examine the relationships with pollen sterols. 24-methylenecholesterol, sitosterol and isofucosterol were the most common and abundant pollen sterols. We found phylogenetic clustering of twelve individual sterols, total sterol content and sterol diversity, and of sterol groupings that reflect their underlying biosynthesis pathway (24 carbon alkylation, ring B desaturation). Plants originating in tropical-like climates (higher mean annual temperature, lower temperature seasonality, higher precipitation in wettest quarter) were more likely to record higher pollen sterol content. However, pollen sterol composition and content showed no clear relationship with pollinator guilds. Our study is the first to show that pollen sterol diversity is phylogenetically clustered and that pollen sterol content may adapt to environmental conditions

Perceived needs and satisfaction with care in people with multiple sclerosis: A two-year prospective study

<p>Abstract</p> <p>Background</p> <p>Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration.</p> <p>Methods</p> <p>The sample consisted of 219 outpatients at a MS specialist clinic. Data on perceived needs and satisfaction with care were collected every six months using a questionnaire which included various dimensions of care. The data was analysed for the whole sample and on an individual level, as well as in subgroups with regard to sex and disease severity.</p> <p>Results</p> <p>There were no statistically significant variations in the proportion of PwMS with perceived needs concerning different health-related services during the study period. However, individual variations were found with regard to both perceived needs and satisfaction with care. Few PwMS perceived a continuous need for a specific service. However, the majority perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at least sometimes. Severe MS was associated with a greater perceived need for almost all the services studied and women experienced a need for psychosocial support/counselling to a greater extent than men. In relation to the different categories of health care staff, PwMS were most satisfied with nurses with regard to all dimensions of care. They were least satisfied with the availability of psychosocial support/counselling; and information about social insurance/vocational rehabilitation.</p> <p>Conclusion</p> <p>Despite the large proportion of individuals with mild disease severity in our sample, a considerable number of needs were identified of which many, on an individual level, varied over time. Key services demanded by PwMS were identified. Also the level of satisfaction with care varied and areas with a potential for improvement were identified such as the availability of rehabilitation services including an increase in the supply of psychosocial support and counselling.</p

Disability activism in the new media ecology: campaigning strategies in the digital era

This article examines the changing nature of disability activism through the influence of social media. As disabled people in the UK have been subjected to acute austerity, this has coincided with a new era of disability activism channelled through increased social media participation. Drawing on the analysis of one group's online activities and a qualitative content analysis of disability protest coverage in traditional news media during the 2012 Paralympic Games, this article positions this shift in the broader framework of ‘new media ecology’ (Hoskins and O’Loughlin, 2010). We explore how emerging structures of disability activism have begun to offer a more visible profile to challenge government policy and negative stereotypes of disabled people. This highlights the usefulness of campaigning strategies for generating favourable news coverage for disability protest

Has Motivational Interviewing fallen into its own Premature Focus Trap?

Since the initial conception of the behaviour change method Motivational Interviewing, there has been a shift evident in epistemological, methodological and practical applications, from an inductive, process and practitioner-focussed approach to that which is more deductive, research-outcome, and confirmatory-focussed. This paper highlights the conceptual and practical problems of adopting this approach, including the consequences of assessing the what (deductive outcome-focussed) at the expense of the how (inductively process-focussed). We encourage a return to an inductive, practitioner and client-focussed MI approach and propose the use of Computer Assisted Qualitative Data Analysis Systems such as NVivo in research initiatives to support this aim