Emerging roles of connexin hemichannels in gastrointestinal and liver pathophysiology

Connexin hemichannels have long been considered as mere structural precursors for gap junctions. In the last decade, it has become clear that they also act as individual channels, connecting the intracellular compartment and the extracellular environment. Impairement of connexin hemichannel functionality may result in disturbance of homeostasis, as exemplified in the current paper for the intestine and the liver. Research in this field still has a number of shortcomings, of which some are also discussed here.     

Spondyloarthropathies: An independent cardiovascular risk factor?

An increase in cardiovascular mortality and morbidity has been convincingly documented in rheumatoid arthritis. Data on spondyloarthropathies are more limited. Here, we discuss published studies indicating that patients with spondyloarthropathies are at increased risk for cardiovascular disease. The excess risk is probably multifactorial, being related both to chronic systemic inflammation and to high prevalences of conventional cardiovascular risk factors. Cardiovascular risk management in patients with spondyloarthropathies requires optimal control of disease activity combined with interventions targeting conventional cardiovascular risk factors.     

Helping women make choices about mammography screening: An online randomized trial of a decision aid for 40-year-old women

Objective

To evaluate the effect of a decision aid (DA) on women's knowledge of the benefits and harms of screening and on their ability to make an informed decision.

Methods

An online randomized controlled trial among 321 women aged 38-45 years was conducted. Participants were randomized to either immediate or delayed access to the online DA which (i) explained the benefits and harms, (ii) included a values clarification exercise and a worksheet to support decision making. The primary outcome, knowledge of benefits and harms of screening, and secondary outcomes, informed choice (composite of knowledge, values and intention), anxiety and acceptability of the DA were measured using online questionnaires.

Results

Women in the intervention group were more knowledgeable (mean score out of 10, 7.35 vs 6.27, p < 0.001) and were more likely to have made a decision (82% vs 61% p < 0.001). Of those who made a decision, women in the intervention group were less likely to start screening now (52% vs 65% p = 0.05). There was no significant difference in the proportion of women who made an informed choice (71% intervention group vs 64% control group, p = 0.24). The DA was helpful, balanced and clear, and did not make women anxious.

Conclusions

The DA increased knowledge and reduced indecision, without increasing feelings of anxiety.

Practice Implications

This decision aid is easy to access online and could be an inexpensive way of supporting women aged 40 who are considering whether to start screening now, or wait until they are 50. The results of this study demonstrate the potential of DAs to help inform women about both the benefits and risks of screening at this age and to support women and clinicians in this decision making process.     

Overexpression of activated murine Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mammary tumors

The mouse mammary tumor virus (MMTV) provirus was found to target the Notch1 gene, producing insertional mutations in mammary tumors of MMTV/neu transgenic (Tg) mice. In these mammary tumors, the Notch1 gene is truncated upstream of the transmembrane domain, and the resulting Notch1 intracellular domain (Notch1(intra)), deleted of most extracellular sequences, is overexpressed. Although Notch1(intra) transforms mammary epithelial cells in vitro, its role in mammary gland tumor formation in vivo was not studied. Therefore, we generated MMTV/Notch1(intra) Tg mice that overexpress murine Notch1(intra) in the mammary glands. We observed that MMTV/Notch1(intra) Tg females were unable to feed their pups because of impaired ductal and lobulo-alveolar mammary gland development. This was associated with decreased proliferation of ductal and alveolar epithelial cells during rapid expansion at puberty and in early pregnancy, as well as decreased production of beta-casein. Notch1(intra) repressed expression of the beta-casein gene promoter, as assessed in vitro with a beta-casein/luciferase reporter construct. The MMTV/Notch1(intra) Tg females developed mammary gland tumors, confirming the oncogenic potential of Notch1(intra) in vivo. Furthermore, MMTV/Notch3(intra) Tg mice exhibited a very similar phenotype. Thus, these Tg mice represent novel models for studying the role of Notch1 or Notch3 in the development and transformation of the mammary gland.