Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Linguistic validation and cultural adaptation of an English version of the Evaluation of Daily Activity Questionnaire in rheumatoid arthritis

Background: To linguistically validate and culturally adapt the Evaluation of Daily Activity Questionnaire (EDAQ) for use in rheumatoid arthritis (RA) from Swedish to British English. The EDAQ is a patient reported outcome measure of daily activity ability. It includes 11 activity domains (Eating and Drinking; Personal Care; Dressing; Bathing; Cooking; Moving Indoors; House Cleaning; Laundry; Moving and Transfers; Communication; Moving Outdoors) and was developed for use in rheumatoid arthritis (RA). Methods: The EDAQ was translated from Swedish to English using standard methods. Activity diaries, cognitive debriefing interviews and focus groups were completed with people with RA to: generate new culturally applicable items; identify important items in the Swedish version to retain in the English version; and develop the English EDAQ based on their views of content and layout. Content validity was established by linking the EDAQ to the International Classification of Functioning RA Core Set. Results: The English EDAQ translation was harmonised with the Swedish version to ensure equivalence of meaning. Sixty-one people with RA participated. 156 activities were identified from 31 activity diaries and included in a draft English EDAQ. Following interviews (n=20) and four focus groups, 138 activities were retained and three additional domains added (Gardening/Household Maintenance; Caring; and Leisure/ Social Activities). Most ICF RA Core Set activities are in the EDAQ. Conclusions: The English EDAQ is a detailed self-report measure of ability in RA. with good content validity

Current trends in the surgical management of Dupuytren’s disease in Europe: an analysis of patient charts

Introduction: Dupuytren's disease (DD) causes progressive digital flexion contracture and is more common in men of European descent. Methods: Orthopaedic and plastic surgeons in 12 European countries (the Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, The Netherlands, Poland, Spain, Sweden and the UK) with >3 and <30 years experience reviewed the medical charts of five consecutive patients they had treated surgically for DD in 2008. Descriptive statistics are reported. Results: In total, 3,357 patient charts were reviewed. Mean (standard deviation) patient age was 61.9 (10.2) years; 81% were men. At the time of the procedure, 11% of patients were at Tubiana stage Ia (0-20° total flexion); 30%, stage Ib (21-45°); 34%, stage II (46-90°); 17%, stage III (91-135°); and 5%, stage IV (&135°). Percutaneous needle fasciotomy was performed in 10%, fasciotomy in 13%, fasciectomy in 69% and dermofasciectomy (DF) in 6% of patients. After surgery, fingers improved a mean of 1.9 Tubiana stages, and 54% of patients had no nodules or contracture. The rate of reported complications during the procedure was 4% overall (11% in patients undergoing DF). The most common postoperative complications reported were haematoma (8%), wound healing complications (6%) and pain (6%). No postoperative complications were reported in 77% of patients. Conclusions: In this European study of more than 3,000 patients with DD, most patients were diagnosed at Tubiana stage I or II, the majority received fasciectomy and more than half had no nodules or contracture remaining after surgery

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Impaired Release of Antimicrobial Peptides into Nasal Fluid of Hyper-IgE and CVID Patients

Patients with primary immunodeficiency (PID) often suffer from frequent respiratory tract infections. Despite standard treatment with IgG-substitution and antibiotics many patients do not improve significantly. Therefore, we hypothesized that additional immune deficits may be present among these patients.To investigate if PID patients exhibit impaired production of antimicrobial peptides (AMPs) in nasal fluid and a possible link between AMP-expression and Th17-cells.Nasal fluid, nasopharyngeal swabs and peripheral blood mononuclear cells (PBMCs) were collected from patients and healthy controls. AMP levels were measured in nasal fluid by Western blotting. Nasal swabs were cultured for bacteria. PBMCs were stimulated with antigen and the supernatants were assessed for IL-17A release by ELISA.In healthy controls and most patients, AMP levels in nasal fluid were increased in response to pathogenic bacteria. However, this increase was absent in patients with common variable immunodeficiency (CVID) and Hyper-IgE syndrome (HIES), despite the presence of pathogenic bacteria. Furthermore, stimulation of PBMCs revealed that both HIES and CVID patients exhibited an impaired production of IL-17A.CVID and HIES patients appear to have a dysregulated AMP response to pathogenic bacteria in the upper respiratory tract, which could be linked to an aberrant Th17 cell response

AvBD1 nucleotide polymorphisms, peptide antimicrobial activities and microbial colonisation of the broiler chicken gut

Abstract Background The importance of poultry as a global source of protein underpins the chicken genome and associated SNP data as key tools in selecting and breeding healthy robust birds with improved disease resistance. SNPs affecting host peptides involved in the innate defences tend to be rare, but three non-synonymous SNPs in the avian β-defensin (AvBD1) gene encoding the variant peptides NYH, SSY and NYY were identified that segregated specifically to three lines of commercial broiler chickens Line X (LX), Line Y(LY) and Line Z. The impacts of such amino acid changes on peptide antimicrobial properties were analysed in vitro and described in relation to the caecal microbiota and gut health of LX and LY birds. Results Time-kill and radial immune diffusion assays indicated all three peptides to have antimicrobial properties against gram negative and positive bacteria with a hierarchy of NYH > SSY > NYY. Calcein leakage assays supported AvBD1 NYH as the most potent membrane permeabilising agent although no significant differences in secondary structure were identified to explain this. However, distinct claw regions, identified by 3D modelling and proposed to play a key role in microbial membrane attachment, and permeation, were more distinct in the NYH model. In vivo AvBD1 synthesis was detected in the bird gut epithelia. Analyses of the caecal gut microbiota of young day 4 birds suggested trends in Lactobacilli sp. colonisation at days 4 (9% LX vs × 30% LY) and 28 (20% LX vs 12% LY) respectively, but these were not statistically significant (P > 0.05). Conclusion Amino acid changes altering the killing capacity of the AvBD1 peptide were associated with two different bird lines, but such changes did not impact significantly on caecal gut microbiota

The burden of physical activity on type 2 diabetes public healthcare expenditures among adults: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Determinants of public healthcare expenditures in type 2 diabetics are not well investigated in developing nations and, therefore, it is not clear if higher physical activity decreases healthcare costs. The purpose of this study was to analyze the relationship between physical activity and the expenditures in public healthcare on type 2 diabetes mellitus treatment.</p> <p>Methods</p> <p>Cross-sectional study carried out in Brazil. A total of 121 type 2 diabetics attended to in two Basic Healthcare Units were evaluated. Public healthcare expenditures in the last year were estimated using a specific standard table. Also evaluated were: socio-demographic variables; chronological age; exogenous insulin use; smoking habits; fasting glucose test; diabetic neuropathy and anthropometric measures. Habitual physical activity was assessed by questionnaire.</p> <p>Results</p> <p>Age (r = 0.20; p = 0.023), body mass index (r = 0.33; p = 0.001) and waist-to-hip ratio (r = 0.20; p = 0.025) were positively related to expenditures on medication for the treatment of diseases other than diabetes. Insulin use was associated with increased expenditures. Higher physical activity was associated with lower expenditure, provided medication for treatment of diseases other than diabetes (OR = 0.19; p = 0.007) and medical consultations (OR = 0.26; p = 0.029).</p> <p>Conclusions</p> <p>Type 2 diabetics with higher enrollment in physical activity presented consistently lower healthcare expenditures for the public healthcare system.</p

Drive counts as a method of estimating ungulate density in forests: mission impossible?

Although drive counts are frequently used to estimate the size of deer populations in forests, little is known about how counting methods or the density and social organization of the deer species concerned influence the accuracy of the estimates obtained, and hence their suitability for informing management decisions. As these issues cannot readily be examined for real populations, we conducted a series of ‘virtual experiments’ in a computer simulation model to evaluate the effects of block size, proportion of forest counted, deer density, social aggregation and spatial auto-correlation on the accuracy of drive counts. Simulated populations of red and roe deer were generated on the basis of drive count data obtained from Polish commercial forests. For both deer species, count accuracy increased with increasing density, and decreased as the degree of aggregation, either demographic or spatial, within the population increased. However, the effect of density on accuracy was substantially greater than the effect of aggregation. Although improvements in accuracy could be made by reducing the size of counting blocks for low-density, aggregated populations, these were limited. Increasing the proportion of the forest counted led to greater improvements in accuracy, but the gains were limited compared with the increase in effort required. If it is necessary to estimate the deer population with a high degree of accuracy (e.g. within 10% of the true value), drive counts are likely to be inadequate whatever the deer density. However, if a lower level of accuracy (within 20% or more) is acceptable, our study suggests that at higher deer densities (more than ca. five to seven deer/100 ha) drive counts can provide reliable information on population size