Refining the indications for scapula tip in mandibular reconstruction

Mandibular reconstruction in osteoradionecrosis or salvage surgery can often be complicated by the lack of suitable recipient vessels in the ipsilateral neck and the associated requirement for significant extraoral skin reconstruction. The scapula tip with its long vascular pedicle and option of a chimeric soft tissue component offers a versatile reconstructive solution in such cases. This article reports four consecutive cases of mandibular reconstruction with poor ipsilateral vascular options and additional soft tissue requirements in which the scapula tip was justified and preferred. The blood supply to the lateral scapula through the circumflex scapular system is well established in the literature and this would be the preferred reconstruction in class I mandibular defects associated with a significant soft tissue requirement. The scapula tip would suit cases where the ipsilateral recipient vessels are compromised, and so justify the potential for mandibular reconstruction with inferior bone stock

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC, all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors

Heat Shock Protein 70 family members interact with Crimean-Congo hemorrhagic fever virus and Hazara virus nucleocapsid proteins and perform a functional role in the nairovirus replication cycle

The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast HAZV is non-pathogenic to humans, and thus represents an excellent model to study aspects of CCHFV biology under more accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N, and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells using small molecule inhibitors significantly reduced HAZV titres, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease

Turbulent thermal diffusion in a multi-fan turbulence generator with the imposed mean temperature gradient

We studied experimentally the effect of turbulent thermal diffusion in a multi-fan turbulence generator which produces a nearly homogeneous and isotropic flow with a small mean velocity. Using Particle Image Velocimetry and Image Processing techniques we showed that in a turbulent flow with an imposed mean vertical temperature gradient (stably stratified flow) particles accumulate in the regions with the mean temperature minimum. These experiments detected the effect of turbulent thermal diffusion in a multi-fan turbulence generator for relatively high Reynolds numbers. The experimental results are in compliance with the results of the previous experimental studies of turbulent thermal diffusion in oscillating grids turbulence (Buchholz et al. 2004; Eidelman et al. 2004). We demonstrated that turbulent thermal diffusion is an universal phenomenon. It occurs independently of the method of turbulence generation, and the qualitative behavior of particle spatial distribution in these very different turbulent flows is similar. Competition between turbulent fluxes caused by turbulent thermal diffusion and turbulent diffusion determines the formation of particle inhomogeneities.Comment: 9 pages, 9 figure, REVTEX4, Experiments in Fluids, in pres

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD

A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts.

Recognition of antigen by T cells requires the formation of a specialized junction between the T cell and the antigen-presenting cell. This junction is generated by the recruitment and the exclusion of specific proteins from the contact area. The mechanisms that regulate these events are unknown. Here we demonstrate that ligand engagement of the adhesion molecule, CD2, initiates a process of protein segregation, CD2 clustering, and cytoskeletal polarization. Although protein segregation was not dependent on the cytoplasmic domain of CD2, CD2 clustering and cytoskeletal polarization required an interaction of the CD2 cytoplasmic domain with a novel SH3-containing protein. This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

Bridging the Gulf: Phytophthora and Downy Mildews Are Connected by Rare Grass Parasites

Downy mildews and root and foliar rots caused by Phytophthora are among the most destructive plant pathogens and therefore have attracted considerable attention during the past two decades. Although it has been realized that a close phylogenetic relationship exists, so far sharp distinction has been made between the obligate biotrophic downy mildews and the hemibiotrophic Phytophthora. In the study presented here, it is shown that a continuum of character states from hemibiotrophic Phytophthora species to obligate biotrophic downy mildews is present. Intermediate character states between downy mildews and Phytophthora species exist in several rare parasites of grasses, which are not embedded within the major clades of the downy mildews but are placed sister to these, with unresolved affinities to both these clades and to Phytophthora. They still have retained traits hitherto thought to be exclusive for Phytophthora. A careful review of previous research is presented and it is highlighted that uniquely for downy mildews, Poakatesthia may form an intracellular mycelium, growing through several host cells. In addition, scanning electron microscopy reveals that sporangiophore growth is not determinate in Viennotia and that outgrowth from sporangiophores is very similar to Phytophthora infestans. It is concluded that the sharp morphological distinction between downy mildews and Phytophthora species (that are often placed in separate families and even different orders), is rather artificial, since all features thought to be exclusive to Phytophthora or the downy mildews are united in the rare grass-parasitizing down mildew genera Viennotia and Poakatesthia and the enigmatic genus Sclerophthora. Therefore, several paradigms regarding the distinction between Phytophthora and the downy mildews need to be reconsidered

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen