British Valued Life Activities Scale [British VLAs]

Background The Valued Life Activities Scale (VLAs) measures difficulty in daily activities and social participation. With various versions involving a different number of items, we have linguistically and culturally adopted the full VLAs (33-items) and psychometrically tested it in adults with rheumatic and musculoskeletal diseases in the United Kingdom. Methods Participants with Rheumatoid Arthritis, Ankylosing Spondylitis, Chronic Pain/ Fibromyalgia, Chronic Hand/ Upper Limb Conditions, Osteoarthritis, Systemic Lupus, Systemic Sclerosis and Primary Sjogren’s Syndrome were recruited from out-patient clinics in National Health Service Hospitals, General Practice and patient organisations in the UK. Phase1 involved linguistic and cultural adaptation: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews. In Phase2 participants completed postal questionnaires to assess internal construct validity using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. Results Responders (n = 1544) had mean age of 59 years (SD13.3) and 77.2% women. A CFA failed to support a total score from the 33-items (Chi Square 3552:df 464: p < 0.0001). Mokken scaling indicated a strong non-parametric association between items. Fit to the Rasch model indicated that the VLAs was characterised by multidimensionality and item misfit, which may have been influenced by clusters of residual item correlations. An item banking approach resolved a 25-item calibrated set whose application could accommodate the ‘does not apply to me’ response option. Conclusions The UK version of the VLAs failed to satisfy classical and modern psychometric standards for complete item sets. However, as the scale is not usually applied in complete format, an item bank approach calibrated 25 items with fit to the Rasch model. Suitable Computer Adaptive Testing (CAT) software could implement the item set, giving patients the choice of whether an item applies to them, or not

Molecular evidence of Ureaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome

BACKGROUND: Ureaplasma urealyticum and U. parvum have been associated with respiratory diseases in premature newborns, but their role in the pathogenesis of the respiratory distress syndrome (RDS) is unclear. The aim of this study was to detect, using molecular techniques, the role of Mycoplasma spp. and Ureaplasma spp. in respiratory secretion and blood specimens of preterm newborns with or without RDS and to evaluate the prevalence of perinatal U. urealyticum or U. parvum infection. The influence of chemotherapy on the clinical course was also evaluated. METHODS: Tracheal aspirate or nasopharingeal fluid samples from 50 preterm babies with (24) or without RDS (26) were analysed for detection of U. urealyticum and U. parvum by culture identification assay and PCR. Sequencing analysis of amplicons allowed us to verify the specificity of methods. Clarithromycin (10 mg kg(-1 )twice a day) was administered in ureaplasma-positive patients who presented clinical signs of RDS. RESULTS: 15/24 neonates with RDS (p < 0.001) and 4/26 without RDS were found PCR-positive for U. urealyticum or U. parvum. Culture identification assay was positive in 5/50 newborns, three of which with RDS. Sequencing analyses confirmed the specificity of these methods. Association of patent ductus arteriosus with ureaplasma colonization was more statistically significant (p = 0.0004) in patients with RDS than in those without RDS. CONCLUSION: Colonization of the lower respiratory tract by Ureaplasma spp. and particularly by U. parvum in preterm newborns was related to RDS. The routine use of molecular methods could be useful to screen candidate babies for etiologic therapy

Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases

Background: The secondary structure and complexity of mRNA influences its accessibility to regulatory molecules (proteins, micro-RNAs), its stability and its level of expression. The mobile elements of the RNA sequence, the wobble bases, are expected to regulate the formation of structures encompassing coding sequences. Results: The sequence/folding energy (FE) relationship was studied by statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found that the FE (dG) associated with coding sequences is significant and negative (407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able to form structures. However, the FE has only a small free component, less than 10% of the total. The contribution of the 1st and 3rd codon bases to the FE is larger than the contribution of the 2nd (central) bases. It is possible to achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous codons. The sequence/FE relationship can be described with a simple algorithm, and the total FE can be predicted solely from the sequence composition of the nucleic acid. The contributions of different synonymous codons to the FE are additive and one codon cannot replace another. The accumulated contributions of synonymous codons of an amino acid to the total folding energy of an mRNA is strongly correlated to the relative amount of that amino acid in the translated protein. Conclusion: Synonymous codons are not interchangable with regard to their role in determining the mRNA FE and the relative amounts of amino acids in the translated protein, even if they are indistinguishable in respect of amino acid coding.Comment: 14 pages including 6 figures and 1 tabl

Captive reptile mortality rates in the home and implications for the wildlife trade

The trade in wildlife and keeping of exotic pets is subject to varying levels of national and international regulation and is a topic often attracting controversy. Reptiles are popular exotic pets and comprise a substantial component of the live animal trade. High mortality of traded animals raises welfare concerns, and also has implications for conservation if collection from the wild is required to meet demand. Mortality of reptiles can occur at any stage of the trade chain from collector to consumer. However, there is limited information on mortality rates of reptiles across trade chains, particularly amongst final consumers in the home. We investigated mortality rates of reptiles amongst consumers using a specialised technique for asking sensitive questions, additive Randomised Response Technique (aRRT), as well as direct questioning (DQ). Overall, 3.6% of snakes, chelonians and lizards died within one year of acquisition. Boas and pythons had the lowest reported mortality rates of 1.9% and chameleons had the highest at 28.2%. More than 97% of snakes, 87% of lizards and 69% of chelonians acquired by respondents over five years were reported to be captive bred and results suggest that mortality rates may be lowest for captive bred individuals. Estimates of mortality from aRRT and DQ did not differ significantly which is in line with our findings that respondents did not find questions about reptile mortality to be sensitive. This research suggests that captive reptile mortality in the home is rather low, and identifies those taxa where further effort could be made to reduce mortality rate

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Sensory Transduction Channel Subunits, tax-4 and tax-2, Modify Presynaptic Molecular Architecture in C. elegans

During development, neural activity is important for forming proper connections in neural networks. The effect of activity on the gross morphology and synaptic strength of neurons has been well documented, but little is known about how activity affects different molecular components during development. Here, we examine the localization of four fluorescently-tagged presynaptic proteins, RAB-3, SNG-1/synaptogyrin, SYD-2/Liprin-α, and SAD-1/SAD kinase, in the C. elegans thermosensory neuron AFD. We show that tax-4 and tax-2, two genes that encode the cyclic nucleotide-gated channel necessary for sensory transduction in AFD, disrupt the localization of all four proteins. In wild-type animals, the synaptic vesicle (SV) markers RAB-3 and SNG-1 and the active zone markers SYD-2 and SAD-1 localize in a stereotyped, punctate pattern in the AFD axon. In tax-4 and tax-2 mutants, SV and SYD-2 puncta are more numerous and less intense. Interestingly, SAD-1 puncta are also less intense but do not increase in number. The change in puncta number can be rescued cell-autonomously in AFD. These results suggest that sensory transduction genes tax-4 and tax-2 are necessary for the proper assembly of presynapses

Expression of Kruppel-Like Factor KLF4 in Mouse Hair Follicle Stem Cells Contributes to Cutaneous Wound Healing

Kruppel-like factor KLF4 is a transcription factor critical for the establishment of the barrier function of the skin. Its function in stem cell biology has been recently recognized. Previous studies have revealed that hair follicle stem cells contribute to cutaneous wound healing. However, expression of KLF4 in hair follicle stem cells and the importance of such expression in cutaneous wound healing have not been investigated.Quantitative real time polymerase chain reaction (RT-PCR) analysis showed higher KLF4 expression in hair follicle stem cell-enriched mouse skin keratinocytes than that in control keratinocytes. We generated KLF4 promoter-driven enhanced green fluorescence protein (KLF4/EGFP) transgenic mice and tamoxifen-inducible KLF4 knockout mice by crossing KLF4 promoter-driven Cre recombinase fused with tamoxifen-inducible estrogen receptor (KLF4/CreER™) transgenic mice with KLF4(flox) mice. KLF4/EGFP cells purified from dorsal skin keratinocytes of KLF4/EGFP transgenic mice were co-localized with 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells by flow cytometric analysis and immunohistochemistry. Lineage tracing was performed in the context of cutaneous wound healing, using KLF4/CreER™ and Rosa26RLacZ double transgenic mice, to examine the involvement of KLF4 in wound healing. We found that KLF4 expressing cells were likely derived from bulge stem cells. In addition, KLF4 expressing multipotent cells migrated to the wound and contributed to the wound healing. After knocking out KLF4 by tamoxifen induction of KLF4/CreER™ and KLF4(flox) double transgenic mice, we found that the population of bulge stem cell-enriched population was decreased, which was accompanied by significantly delayed cutaneous wound healing. Consistently, KLF4 knockdown by KLF4-specific small hairpin RNA in human A431 epidermoid carcinoma cells decreased the stem cell population and was accompanied by compromised cell migration.KLF4 expression in mouse hair bulge stem cells plays an important role in cutaneous wound healing. These findings may enable future development of KLF4-based therapeutic strategies aimed at accelerating cutaneous wound closure

Immigrant women’s experiences of maternity-care services in Canada: a systematic review using a narrative synthesis

Background: Canada’s diverse society and its statutory commitment to multiculturalism means that a synthesis of knowledge related to the healthcare experiences of immigrants is essential to realise the health potential for future Canadians. Although concerns about the maternity experiences of immigrants in Canada are relatively new, recent national guidelines explicitly call for the tailoring of services to user needs. We therefore assessed the experiences of immigrant women accessing maternity-care services in Canada. In particular, we investigated the experiences of immigrant women in Canada in accessing and navigating maternity and related healthcare services from conception to 6 months postpartum in Canada. Our focus was on (a) the accessibility and acceptability of maternity-care services for immigrant women and (b) the effects of the perceptions and experiences of these women on their birth and postnatal outcomes. Methods: We conducted a systematic review using a systematic search and narrative synthesis of peer-reviewed and non-peer-reviewed reports of empirical research, with the aim of providing stakeholders with perspectives on maternity-care services as experienced by immigrant women. We partnered with key stakeholders (‘integrated knowledge users’) to ensure the relevancy of topics and to tailor recommendations for effective translation into future policy, practice and programming. Two search phases and a three-stage selection process for published and grey literature were conducted prior to appraisal of literature quality and narrative synthesis of the findings. Results: Our knowledge synthesis of maternity care among immigrants to Canada provided a coherent evidence base for (a) eliciting a better understanding of the factors that generate disparities in accessibility, acceptability and outcomes during maternity care; and (b) improving culturally based competency in maternity care. Our synthesis also identified pertinent issues in multiple sectors that should be addressed to configure maternity services and programs appropriately. Conclusions: Although immigrant women in Canada are generally given the opportunity to obtain necessary services, they face many barriers in accessing and utilising these services. These barriers include lack of information about or awareness of the services, insufficient supports to access these services and discordant expectations between the women and their service providers. Systematic review registration: PROSPERO registration number: CRD42012002185