Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Extending conceptual understanding : how interprofessional education influences affective domain development

Background: Interprofessional learning (IPL) can influence affective domain development of students, through teaching activities that facilitate learning with, from and about other professions. Current quantitative evidence offers limited explanation of how this learning is achieved within IPL programmes. This original paper tests a conceptual framework drawn from theories on IPL and affective domain development (attitudes, values and behaviours) to explain what works for whom, when and in what circumstances. Methods: The objectives of the study were twofold: to evaluate the impact of the IPL programme on the student’s attitudes and values, and identify behaviour changes in clinical practice towards interprofessional working. Using an action research approach, based in practice, an IPL programme was delivered over six weeks. Students from five professional disciplines: nursing, radiography, physiotherapy, social work, and podiatry (n=63) participated over the two action research cycles and in semi structured focus groups (n=37). Results: The recorded personal experiences of the IPL activities on the students were examined in relation to the: type of activity; impact on the affective domain of learning (attitude, value, or behaviour) and self-reported outcome on application to their practice. Modification in affective domain development was measured to identification or internalisation stage for 30 of the students. Self-reported outcomes on application to practice included direct impact on patient care, personal resilience building, improved communication and ability to challenge practice. Conclusion: This paper presents a conceptual framework not evident in current research, in regards to what IPL works for whom, in what circumstances and when. IPL Activities that address a personal reward or incentive and are delivered over 4 weeks, imitating ‘circles of care,’ that explore self-assessment, team building and reflection can lead to sustained change in values, attitudes and behaviours. Keywords: Action Research, Interprofessional Education, Interprofessional learning, Health and Social care, Collaboration

Onchocerciasis transmission in Ghana: biting and parous rates of host-seeking sibling species of the Simulium damnosum complex

Background: Ghana is renowned for its sibling species diversity of the Simulium damnosum complex, vectors of Onchocerca volvulus. Detailed entomological knowledge becomes a priority as onchocerciasis control policy has shifted from morbidity reduction to elimination of infection. To date, understanding of transmission dynamics of O. volvulus has been mainly based on S. damnosum sensu stricto (s.s.) data. We aim to elucidate bionomic features of vector species of importance for onchocerciasis elimination efforts. Methods: We collected S. damnosum sensu lato from seven villages in four Ghanaian regions between 2009 and 2011, using standard vector collection, and human- and cattle-baited tents. Taxa were identified using morphological and molecular techniques. Monthly biting rates (MBR), parous rates and monthly parous biting rates (MPBR) are reported by locality, season, trapping method and hour of collection for each species. Results: S. damnosum s.s./S. sirbanum were collected at Asubende and Agborlekame, both savannah villages. A range of species was caught in the Volta region (forest-savannah mosaic) and Gyankobaa (forest), with S. squamosum or S. sanctipauli being the predominant species, respectively. In Bosomase (southern forest region) only S. sanctipauli was collected in the 2009 wet season, but in the 2010 dry season S. yahense was also caught. MBRs ranged from 714 bites/person/month at Agborlekame (100% S. damnosum s.s./S. sirbanum) to 8,586 bites/person/month at Pillar 83/Djodji (98.5% S. squamosum). MBRs were higher in the wet season. In contrast, parous rates were higher in the dry season (41.8% vs. 18.4%), resulting in higher MPBRs in the dry season. Daily host-seeking activity of S. damnosum s.s./S. sirbanum was bimodal, whilst S. squamosum and S. sanctipauli had unimodal afternoon peaks. Conclusions: The bionomic differences between sibling species of the S. damnosum complex need to be taken into account when designing entomological monitoring protocols for interventions and parameterising mathematical models for onchocerciasis control and elimination