Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

Chronic inflammation in CF airways - a persistent issue for A20

Cystic Fibrosis (CF) is characterised by prolonged and exaggerated airways inflammation. Despite recent developments to overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to reduce the inflammatory response. The NF-kB regulator A20 is a key target to normalise the inflammatory response and is reduced in CF. Here, we describe the plethora of functions of A20 as they apply to innate immune function within the airways. Pharmacological compounds can enhance A20 mRNA and protein expression, but we observed a blunted effect in CF primary epithelial cells. In CF cells pre-treatment with gibberellic acid (GA3) shows anti-inflammatory effects only in some patients. We show that cells with higher basal p38 expression respond with an increase in pro-inflammatory cytokines. Furthermore, all CF PNECs show increased p38 mRNA when stimulated in the presence of GA3. Our results suggest that those patients may benefit from therapeutics targeting p38.

Behavior change theory, content and delivery of interventions to enhance adherence in chronic respiratory disease: A systematic review

Background: We sought to describe the theory used to design treatment adherence interventions, the content delivered, and the mode of delivery of these interventions in chronic respiratory disease. Methods: We included randomized controlled trials of adherence interventions (compared to another intervention or control) in adults with chronic respiratory disease (8 databases searched; inception until March 2015). Two reviewers screened and extracted data: post-intervention adherence (measured objectively); behavior change theory, content (grouped into psychological, education and self-management/supportive, telemonitoring, shared decision-making); and delivery. “Effective” studies were those with p < 0.05 for adherence rate between groups. We conducted a narrative synthesis and assessed risk of bias. Results: 12,488 articles screened; 46 included studies (n = 42,91% in OSA or asthma) testing 58 interventions (n = 27, 47% were effective). Nineteen (33%) interventions (15 studies) used 12 different behavior change theories. Use of theory (n = 11,41%) was more common amongst effective interventions. Interventions were mainly educational, self-management or supportive interventions (n = 27,47%). They were commonly delivered by a doctor (n = 20,23%), in face-to-face (n = 48,70%), one-to-one (n = 45,78%) outpatient settings (n = 46,79%) across 2–5 sessions (n = 26,45%) for 1–3 months (n = 26,45%). Doctors delivered a lower proportion (n = 7,18% vs n = 13,28%) and pharmacists (n = 6,15% vs n = 1,2%) a higher proportion of effective than ineffective interventions. Risk of bias was high in >1 domain (n = 43, 93%) in most studies. Conclusions: Behavior change theory was more commonly used to design effective interventions. Few adherence interventions have been developed using theory, representing a gap between intervention design recommendations and research practice.