Dynamics of Wolbachia pipientis gene expression across the Drosophila melanogaster life cycle

Symbiotic interactions between microbes and their multicellular hosts have manifold impacts on molecular, cellular and organismal biology. To identify candidate bacterial genes involved in maintaining endosymbiotic associations with insect hosts, we analyzed genome-wide patterns of gene expression in the alpha-proteobacteria Wolbachia pipientis across the life cycle of Drosophila melanogaster using public data from the modENCODE project that was generated in a Wolbachia-infected version of the ISO1 reference strain. We find that the majority of Wolbachia genes are expressed at detectable levels in D. melanogaster across the entire life cycle, but that only 7.8% of 1195 Wolbachia genes exhibit robust stage- or sex-specific expression differences when studied in the "holo-organism" context. Wolbachia genes that are differentially expressed during development are typically up-regulated after D. melanogaster embryogenesis, and include many bacterial membrane, secretion system and ankyrin-repeat containing proteins. Sex-biased genes are often organised as small operons of uncharacterised genes and are mainly up-regulated in adult males D. melanogaster in an age-dependent manner suggesting a potential role in cytoplasmic incompatibility. Our results indicate that large changes in Wolbachia gene expression across the Drosophila life-cycle are relatively rare when assayed across all host tissues, but that candidate genes to understand host-microbe interaction in facultative endosymbionts can be successfully identified using holo-organism expression profiling. Our work also shows that mining public gene expression data in D. melanogaster provides a rich set of resources to probe the functional basis of the Wolbachia-Drosophila symbiosis and annotate the transcriptional outputs of the Wolbachia genome.Comment: 58 pages, 6 figures, 6 supplemental figures, 4 supplemental files (available at https://github.com/bergmanlab/wolbachia/tree/master/gutzwiller_et_al/arxiv

Using a discrete choice experiment to inform the design of programs to promote colon cancer screening for vulnerable populations in North Carolina

BackgroundScreening for colorectal cancer (CRC) is suboptimal, particularly for vulnerable populations. Effective intervention programs are needed to increase screening rates. We used a discrete choice experiment (DCE) to learn about how vulnerable individuals in North Carolina value different aspects of CRC screening programs.MethodsWe enrolled English-speaking adults ages 50–75 at average risk of CRC from rural North Carolina communities with low rates of CRC screening, targeting those with public or no insurance and low incomes. Participants received basic information about CRC screening and potential program features, then completed a 16 task DCE and survey questions that examined preferences for four attributes of screening programs: testing options available; travel time required; money paid for screening or rewards for completing screening; and the portion of the cost of follow-up care paid out of pocket. We used Hierarchical Bayesian methods to calculate individual-level utilities for the 4 attributes’ levels and individual-level attribute importance scores. For each individual, the attribute with the highest importance score was considered the most important attribute. Individual utilities were then aggregated to produce mean utilities for each attribute. We also compared DCE-based results with those from direct questions in a post-DCE survey.ResultsWe enrolled 150 adults. Mean age was 57.8 (range 50–74); 55% were women; 76% White and 19% African-American; 87% annual household income under $30,000; and 51% were uninsured. Individuals preferred shorter travel; rewards or small copayments compared with large copayments; programs that included stool testing as an option; and greater coverage of follow-up costs. Follow-up cost coverage was most frequently found to be the most important attribute from the DCE (47%); followed by test reward/copayment (33%). From the survey, proportion of follow-up costs paid was most frequently cited as most important (42% of participants), followed by testing options (32%). There was moderate agreement (45%) in attribute importance between the DCE and the single question in the post-DCE survey.ConclusionsScreening test copayments and follow-up care coverage costs are important program characteristics in this vulnerable, rural population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-014-0611-4) contains supplementary material, which is available to authorized users

Older adults’ preferences for, adherence to and experiences of two self-management falls prevention home exercise programmes: a comparison between a digital programme and a paper booklet

Background: Fall prevention exercise programmes are known to be effective, but access to these programmes is not always possible. The use of eHealth solutions might be a way forward to increase access and reach a wider population. In this feasibility study the aim was to explore the choice of programme, adherence, and self-reported experiences comparing two exercise programmes – a digital programme and a paper booklet. Methods: A participant preference trial of two self-managed fall prevention exercise interventions. Community-dwelling adults aged 70 years and older exercised independently for four months after one introduction meeting. Baseline information was collected at study start, including a short introduction of the exercise programme, a short physical assessment, and completion of questionnaires. During the four months intervention period, participants self-reported their performed exercises in an exercise diary. At a final meeting, questionnaires about their experiences, and post-assessments, were completed. For adherence analyses data from diaries were used and four subgroups for different levels of participation were compared. Exercise maintenance was followed up with a survey 12 months after study start. Results: Sixty-seven participants, with mean age 77 ± 4 years were included, 72% were women. Forty-three percent chose the digital programme. Attrition rate was 17% in the digital programme group and 37% in the paper booklet group (p = .078). In both groups 50–59% reported exercise at least 75% of the intervention period. The only significant difference for adherence was in the subgroup that completed ≥75% of exercise duration, the digital programme users exercised more minutes per week (p = .001). Participants in both groups were content with their programme but digital programme users reported a significantly higher (p = .026) degree of being content, and feeling supported by the programme (p = .044). At 12 months follow-up 67% of participants using the digital programme continued to exercise regularly compared with 35% for the paper booklet (p = .036). Conclusions: Exercise interventions based on either a digital programme or a paper booklet can be used as a self-managed, independent fall prevention programme. There is a similar adherence in both programmes during a 4-month intervention, but the digital programme seems to facilitate long-term maintenance in regular exercise

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years