Double Blind Study Investigating the Effect of Different Voice Prostheses on Ease of Swallowing and Residue Post Laryngectomy.

Voice prostheses have been examined for their effect on voice production but there is little datum on their effect on swallow function. This study investigated the difference between six commonly available voice prostheses in terms of swallowing. Laryngectomy patients had up to six voice prostheses placed in a random order over two visits. Swallowing was evaluated for each prosthesis using FEES (Fibreoptic Endoscopic Evaluation of Swallowing). After each prosthesis trial, patients self-evaluated their experience of swallowing. Three independent experts indicated which prosthesis they considered best for swallowing for each patient and judged residue on the voice prosthesis and in the upper esophagus. Raters were blinded to participant details, voice prosthesis type and scores of other raters. On patient self-evaluation, scores were equally distributed across all prostheses for swallowing. Experts most frequently chose the Blom Singer Low pressure and Blom Singer Classic Indwelling voice prostheses as best for swallowing but consensus was poor for most patients. Experts found that the Blom Singer Classic Indwelling and the Provox Vega had least residue on the voice prosthesis on thin liquid (p ≤ 0.001) and soft (p = 0.001), respectively. Experts also found that the Blom Singer Low Pressure had least residue in the upper esophagus on soft consistency (p ≤ 0.001). While self-evaluation by patients did not identify a consistently preferred prosthesis for swallow, many patients expressed personal preferences, suggesting benefits to involving patients in the choice of prosthesis. Some voice prostheses may be associated with lower levels of residue on the prosthesis and upper esophagus with certain consistencies

Follow-up care for cancer survivors: views of the younger adult

BACKGROUND: Since the launch of the National Cancer Survivorship Initiative, there has been a surge of interest surrounding the value and organisation of long-term follow-up care after cancer treatment. We report the views of 309 adult cancer survivors (aged 18-45 years) on provision of follow-up and preferences for care. METHODS: A total of 207 survivors completed questionnaires before and after routine consultant-led follow-up appointments and 102 were recruited by post. Measures of health status (including late effects, perceived vulnerability to late effects and quality of life), reasons for attending follow-up (clinical and supportive), issues to be discussed at follow-up and preferences for different models of care were assessed. RESULTS: In all, 59% of the survivors reported experiencing one or more cancer-related health problems. Survivors rated clinical reasons for attending follow-up more highly than supportive reasons (P < 0.001), although nutritional advice and counselling were considered useful (60 and 47%, respectively). Those still receiving scheduled follow-up appointments did not discuss the range of issues intended with 'late effects' and 'fertility', which were particularly under-discussed. Hospital rather than GP follow-up was more highly rated. CONCLUSION: Survivors value the clinical reassurance currently provided by consultant-led care. However, supportive needs are not systematically addressed. Multi-disciplinary services are recommended to meet supportive needs in addition to clinical care

Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Factors associated with dental visit and barriers to utilisation of oral health care services in a sample of antenatal mothers in Hospital Universiti Sains Malaysia

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to determine factors associated with dental visit and to describe barriers to utilisation of oral health care services among antenatal mothers attending the Obstetric and Gynaecology Specialist clinic in Hospital Universiti Sains Malaysia.</p> <p>Methods</p> <p>A structured, self-administered questionnaire was used obtain information on the variables of interest pertaining to the current pregnancy from 124 antenatal mothers.</p> <p>Results</p> <p>The majority of the mothers claimed that their oral health status was good (67.0%) or very good (2.4%). On the contrary, most of them admitted of having had at least one oral health problem (59.7%) including cavitated (43.5%) and painful teeth (15.3%), bleeding gum (21.0%), and bad breath (10.5%). However, only 29% of the mothers visited dentist during the current pregnancy. Factors associated with the mothers' dental visit were exposure to oral health education before the pregnancy and awareness of relationship between poor maternal oral health and adverse pregnancy outcomes with odds ratio of 4.06 (95% CI: 1.67-9.78) and 3.57 (95% CI: 1.30-9.77) respectively. Common excuses given by most mothers include perceptions of not having any oral health problems (65.9%), long waiting time at the clinic (71.6%), and no immediate treatment given by the dentist (64.8%).</p> <p>Conclusions</p> <p>Utilisation of oral health care services among antenatal mothers was low. Mothers who reported dental visit were more likely to be those who had received oral health education before the current pregnancy and knew of the association between poor maternal oral health and adverse pregnancy outcomes. Dissatisfaction with the services rendered and perceptions of not having any oral health problems were the main barriers.</p

Role of Pseudomonas aeruginosa Peptidoglycan-Associated Outer Membrane Proteins in Vesicle Formation

Gram-negative bacteria produce outer membrane vesicles (OMVs) that package and deliver proteins, small molecules, and DNA to prokaryotic and eukaryotic cells. The molecular details of OMV biogenesis have not been fully elucidated, but peptidoglycan-associated outer membrane proteins that tether the outer membrane to the underlying peptidoglycan have been shown to be critical for OMV formation in multiple Enterobacteriaceae. In this study, we demonstrate that the peptidoglycan-associated outer membrane proteins OprF and OprI, but not OprL, impact production of OMVs by the opportunistic pathogen Pseudomonas aeruginosa. Interestingly, OprF does not appear to be important for tethering the outer membrane to peptidoglycan but instead impacts OMV formation through modulation of the levels of the Pseudomonas quinolone signal (PQS), a quorum signal previously shown by our laboratory to be critical for OMV formation. Thus, the mechanism by which OprF impacts OMV formation is distinct from that for other peptidoglycan-associated outer membrane proteins, including OprIclose17181

Both habitat change and local lek structure influence patterns of spatial loss and recovery in a black grouse population

The final publication is available at Springer via http://dx.doi.org/10.1007/s10144-015-0484-3Land use change is a major driver of declines in wildlife populations. Where human economic or recreational interests and wildlife share landscapes this problem is exacerbated. Changes in UK black grouse Tetrao tetrix populations are thought to have been strongly influenced by upland land use change. In a long-studied population within Perthshire, lek persistence is positively correlated with lek size, and remaining leks clustered most strongly within the landscape when the population is lowest, suggesting that there may be a demographic and/or spatial context to the reaction of the population to habitat changes. Hierarchical cluster analysis of lek locations revealed that patterns of lek occupancy when the population was declining were different to those during the later recovery period. Response curves from lek-habitat models developed using MaxEnt for periods with a declining population, low population, and recovering population were consistent across years for most habitat measures. We found evidence linking lek persistence with habitat quality changes and more leks which appeared between 1994 and 2008 were in improving habitat than those which disappeared during the same period. Generalised additive models (GAMs) identified changes in woodland and starting lek size as being important indicators of lek survival between declining and low/recovery periods. There may also have been a role for local densities in explaining recovery since the population low point. Persistence of black grouse leks was influenced by habitat, but changes in this alone did not fully account for black grouse declines. Even when surrounded by good quality habitat, leks can be susceptible to extirpation due to isolation

Targeting deficiencies in the TLR5 mediated vaginal response to treat female recurrent urinary tract infection

Abstract The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle