Environmental responses of virally infected respiratory epithelial cells

Background: Rhinovirus, airborne pollution, and allergens are thought to contribute to epithelial dysfunction in chronic airway disease. Objectives were to determine whether these factors act in synergism to induce inflammation and chronic airway disease. Methods: Respiratory mucosa from chronic rhinosinusitis with nasal polyps (CRSwNP) (n=7) or healthy (n=6) patients were cultured at air-liquid interface (ALI) (culture wells n=204). Cells were infected with rhinovirus, then exposed to combinations of vehicle, diesel particulate matter (DPM), and house dust mite (HDM). Ciliary beating frequency (CBF), interleukin (IL)-6 release, and cytotoxicity were assessed by Sisson-Ammons Video Analysis (SAVA) software, flow cytometry, and LDH assays. Results: Compared with healthy cultures, CRSwNP culture groups had lower baseline CBF. The CBF of virally infected ALI cultures was higher than healthy cultures. Challenges tended to impair CBF more in cells that were also virally infected. There was an elevation in IL-6 with viral infection. Challenge combinations did not cause a different IL-6 or CBF response within groups. Conclusions: An inherent mucosal dysfunction and environmental exposures can worsen sinus disease. Synergism in CBF impairment or IL-6 release was not seen

Becoming and staying physically active in adolescents with cerebral palsy: protocol of a qualitative study of facilitators and barriers to physical activity

<p>Abstract</p> <p>Background</p> <p>Adolescents with cerebral palsy (CP) show a reduced physical activity (PA). Currently there are no interventions for adolescents with CP in this critical life phase that optimise and maintain the individuals' physical activity in the long term. To develop such a program it is important to fully understand the factors that influence physical activity behaviours in adolescents with CP. The aim of this study is to explore what makes it easy or hard for adolescents with CP to be and to become physically active.</p> <p>Methods/Design</p> <p>A qualitative research method is chosen to allow adolescents to voice their own opinion. Because we will investigate the lived experiences this study has a phenomenological approach. Thirty ambulatory and non-ambulatory adolescents (aged 10-18 years) with CP, classified as level I to IV on the Gross Motor Function Classification System and 30 parents of adolescents with CP will be invited to participate in one of the 6 focus groups or an individual interview. Therapists from all Children's Treatment Centres in Ontario, Canada, will be asked to fill in a survey. Focus groups will be audio- and videotaped and will approximately take 1.5 hours. The focus groups will be conducted by a facilitator and an assistant. In preparation of the focus groups, participants will fill in a demographic form with additional questions on physical activity. The information gathered from these questions and recent research on barriers and facilitators to physical activity will be used as a starting point for the content of the focus groups. Recordings of the focus groups will be transcribed and a content analysis approach will be used to code the transcripts. A preliminary summary of the coded data will be shared with the participants before themes will be refined.</p> <p>Discussion</p> <p>This study will help us gain insight and understanding of the participants' experiences and perspectives in PA, which can be of great importance when planning programs aimed at helping them to stay or to become physically active.</p

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (&#8805; 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Transabdominal Preperitoneal Repair for Obturator Hernia

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第889号）・横山隆秀Background A laparoscopic surgical approach for obturator hernia (OH) repair is uncommon. The aim of the present study was to assess the effectiveness of laparoscopic transabdominal preperitoneal (TAPP) repair for OH. Methods From 2001 to May 2010, 659 patients with inguinal hernia underwent TAPP repair at in our institutes. Among these, the eight patients with OH were the subjects of this study. Results Three of the eight patients were diagnosed as having occult OH, and the other five were diagnosed preoperatively, by ultrasonography and/or computed tomography, as having strangulated OH. Bilateral OH was found in five patients (63%), and combined groin hernias, either unilaterally or bilaterally, were observed in seven patients (88%), all of whom had femoral hernia. Of the five patients with bowel obstruction at presentation, four were determined not to require resection after assessment of the intestinal viability by laparoscopy. There was one case of conversion to a two-stage hernia repair performed to avoid mesh contamination: addition of mini-laparotomy, followed by extraction of the gangrenous intestine for resection and anastomosis with simple peritoneal closure of the hernia defect in the first stage, and a Kugel hernia repair in the second stage. There was no incidence of postoperative morbidity, mortality, or recurrence. Conclusions Because TAPP allows assessment of not only the entire groin area bilaterally but also simultaneous assessment of the viability of the incarcerated intestine with a minimum abdominal wall defect, we believe that it is an adequate approach to the treatment of both occult and acutely incarcerated OH. Two-stage hernia repair is technically feasible in patients requiring resection of the incarcerated intestine.ArticleWORLD JOURNAL OF SURGERY. 35(10):2323-2327 (2011)journal articl

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C&gt;A and TT&gt;CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful

Contact dermatitis and other skin conditions in instrumental musicians

BACKGROUND: The skin is important in the positioning and playing of a musical instrument. During practicing and performing there is a permanent more or less intense contact between the instrument and the musician's skin. Apart from aggravation of predisposed skin diseases (e.g., atopic eczema or psoriasis) due to music-making, specific dermatologic conditions may develop that are directly caused by playing a musical instrument. METHODS: To perform a systematic review on instrument-related skin diseases in musicians we searched the PubMed database without time limits. Furthermore we studied the online bibliography "Occupational diseases of performing artist. A performing arts medicine bibliography. October, 2003" and checked references of all selected articles for relevant papers. RESULTS: The most prevalent skin disorders of instrumental musicians, in particular string instrumentalists (e.g., violinists, cellists, guitarists), woodwind players (e.g., flautists, clarinetists), and brass instrumentalists (e.g., trumpeters), include a variety of allergic contact sensitizations (e.g., colophony, nickel, and exotic woods) and irritant (physical-chemical noxae) skin conditions whose clinical presentation and localization are usually specific for the instrument used (e.g., "fiddler's neck", "cellist's chest", "guitar nipple", "flautist's chin"). Apart from common callosities and "occupational marks" (e.g., "Garrod's pads") more or less severe skin injuries may occur in musical instrumentalists, in particular acute and chronic wounds including their complications. Skin infections such as herpes labialis seem to be a more common skin problem in woodwind and brass instrumentalists. CONCLUSIONS: Skin conditions may be a significant problem not only in professional instrumentalists, but also in musicians of all ages and ability. Although not life threatening they may lead to impaired performance and occupational hazard. Unfortunately, epidemiological investigations have exclusively been performed on orchestra musicians, though the prevalence of instrument-related skin conditions in other musician groups (e.g., jazz and rock musicians) is also of interest. The practicing clinician should be aware of the special dermatologic problems unique to the musical instrumentalist. Moreover awareness among musicians needs to be raised, as proper technique and conditioning may help to prevent affection of performance and occupational impairment

Genome of <i>Leptomonas pyrrhocoris</i>:a high-quality reference for monoxenous trypanosomatids and new insights into evolution of <i>Leishmania</i>

Many high-quality genomes are available for dixenous (two hosts) trypanosomatid species of the genera Trypanosoma, Leishmania, and Phytomonas, but only fragmentary information is available for monoxenous (single-host) trypanosomatids. In trypanosomatids, monoxeny is ancestral to dixeny, thus it is anticipated that the genome sequences of the key monoxenous parasites will be instrumental for both understanding the origin of parasitism and the evolution of dixeny. Here, we present a high-quality genome for Leptomonas pyrrhocoris, which is closely related to the dixenous genus Leishmania. The L. pyrrhocoris genome (30.4 Mbp in 60 scaffolds) encodes 10,148 genes. Using the L. pyrrhocoris genome, we pinpointed genes gained in Leishmania. Among those genes, 20 genes with unknown function had expression patterns in the Leishmania mexicana life cycle suggesting their involvement in virulence. By combining differential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified several additional proteins potentially involved in virulence, including SpoU methylase and U3 small nucleolar ribonucleoprotein IMP3. The population genetics of L. pyrrhocoris was also addressed by sequencing thirteen strains of different geographic origin, allowing the identification of 1,318 genes under positive selection. This set of genes was significantly enriched in components of the cytoskeleton and the flagellum

Outlier SNPs detect weak regional structure against a background of genetic homogeneity in the Eastern Rock Lobster, Sagmariasus verreauxi

Genetic differentiation is characteristically weak in marine species making assessments of population connectivity and structure difficult. However, the advent of genomic methods has increased genetic resolution, enabling studies to detect weak, but significant population differentiation within marine species. With an increasing number of studies employing high resolution genome-wide techniques, we are realising that the connectivity of marine populations is often complex and quantifying this complexity can provide an understanding of the processes shaping marine species genetic structure and to inform long-term, sustainable management strategies. This study aims to assess the genetic structure, connectivity, and local adaptation of the Eastern Rock Lobster (Sagmariasus verreauxi), which has a maximum pelagic larval duration of 12 months and inhabits both subtropical and temperate environments. We used 645 neutral and 15 outlier SNPs to genotype lobsters collected from the only two known breeding populations and a third episodic population—encompassing S. verreauxi's known range. Through examination of the neutral SNP panel, we detected genetic homogeneity across the three regions, which extended across the Tasman Sea encompassing both Australian and New Zealand populations. We discuss differences in neutral genetic signature of S. verreauxi and a closely related, co-distributed rock lobster, Jasus edwardsii, determining a regional pattern of genetic disparity between the species, which have largely similar life histories. Examination of the outlier SNP panel detected weak genetic differentiation between the three regions. Outlier SNPs showed promise in assigning individuals to their sampling origin and may prove useful as a management tool for species exhibiting genetic homogeneity