Team-based, problem-solving exercises using studies of diarrhea and oral rehydration encourage students to integrate knowledge of systems physiology.

We describe an inquiry activity that aims to develop students' ability to interpret findings that span whole body systems and so encourage the integration of knowledge. The scenario we choose was the physiological challenge posed by diarrhea and the physiological mechanisms that underpin oral rehydration therapy. Before the staff-facilitated inquiry activity, students engage with an online information resource and complete a formative, but mandatory, prelaboratory quiz. These tasks encourage students to develop some mastery of the relevant physiology before the timetabled inquiry activity. The 3-h inquiry activity is driven by a paper workbook containing data from published studies, mainly from veterinary physiology, of the various consequences of diarrhea. Figures from published data are arranged so that, initially, the impact of dehydration on a single system (the cardiovascular system) could be appreciated. Integration with other systems (respiratory and renal systems) is then introduced progressively through the activity. The exercise is designed as a team-based inquiry activity that emphasizes the value of discussion to identify appropriate features for interpretation of the data. Students are obliged to complete a postlaboratory quiz within 5 days of the inquiry activity, serving to consolidate the students' learning and provide staff with feedback on the attainment of intended learning outcomes. Marks from formative pre- and postlaboratory quizzes typically have a median mark in excess of 80% (pass mark is 50%), and qualitative feedback suggests that the majority of students recognized the value of the activity, despite simultaneously reporting that it was intellectually demanding.

Using singing to nurture children's hearing? A pilot study.

This article reports a pilot study of the potential benefits of a sustained programme of singing activities on the musical behaviours and hearing acuity of young children with hearing impairment (HI). Twenty-nine children (n=12 HI and n=17 NH) aged between 5 and 7 years from an inner-city primary school in London participated, following appropriate ethical approval. The predominantly classroom-based programme was designed by colleagues from the UCL Institute of Education and UCL Ear Institute in collaboration with a multi-arts charity Creative Futures and delivered by an experienced early years music specialist weekly across two school terms. There was a particular emphasis on building a repertoire of simple songs with actions and allied vocal exploration. Musical learning was also supported by activities that drew on visual imagery for sound and that included simple notation and physical gesture. An overall impact assessment of the pilot programme embraced pre- and post-intervention measures of pitch discrimination, speech perception in noise and singing competency. Subsequent statistical data analyses suggest that the programme had a positive impact on participant children's singing range, particularly (but not only) for HI children with hearing aids, and also in their singing skills. HI children's pitch perception also improved measurably over time. Findings imply that all children, including those with HI, can benefit from regular and sustained access to age-appropriate musical activities.

Developing a palliative care service for children in the Queen Elizabeth Central Hospital, Blantyre, Malawi.

There are too few palliative care services for children in resource poor countries. Health carers are overwhelmed with cases of acute illness that need their urgent attention, and chronically ill children with life-limiting diseases have been sidelined. The HIV epidemic in southern Africa revealed the huge needs in our own hospital, and in 2002, we started a hospital-based paediatric palliative care service. It was the first in Africa. We describe here how it developed and expanded in the ensuing years and how it has affected our staff, the children and their families in our care.

S-nitrosylation of syntaxin 1 at Cys(145) is a regulatory switch controlling Munc18-1 binding.

Exocytosis is regulated by NO in many cell types, including neurons. In the present study we show that syntaxin 1a is a substrate for S-nitrosylation and that NO disrupts the binding of Munc18-1 to the closed conformation of syntaxin 1a in vitro. In contrast, NO does not inhibit SNARE {SNAP [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein] receptor} complex formation or binding of Munc18-1 to the SNARE complex. Cys(145) of syntaxin 1a is the target of NO, as a non-nitrosylatable C145S mutant is resistant to NO and novel nitrosomimetic Cys(145) mutants mimic the effect of NO on Munc18-1 binding in vitro. Furthermore, expression of nitrosomimetic syntaxin 1a in living cells affects Munc18-1 localization and alters exocytosis release kinetics and quantal size. Molecular dynamic simulations suggest that NO regulates the syntaxin-Munc18 interaction by local rearrangement of the syntaxin linker and H3c regions. Thus S-nitrosylation of Cys(145) may be a molecular switch to disrupt Munc18-1 binding to the closed conformation of syntaxin 1a, thereby facilitating its engagement with the membrane fusion machinery.