The ability to form synapses is one of the fundamental properties required by the mammalian nervous system to generate network connectivity. Structural and functional diversity among synaptic populations is a key hallmark of network diversity, and yet we know comparatively little about the morphological principles that govern variability in the size, shape and strength of synapses. Using the mouse neuromuscular junction (NMJ) as an experimentally accessible model synapse, we report on the development of a robust, standardized methodology to facilitate comparative morphometric analysis of synapses (‘NMJ-morph’). We used NMJ-morph to generate baseline morphological reference data for 21 separate pre- and post-synaptic variables from 2160 individual NMJs belonging to nine anatomically distinct populations of synapses, revealing systematic differences in NMJ morphology between defined synaptic populations. Principal components analysis revealed that overall NMJ size and the degree of synaptic fragmentation, alongside pre-synaptic axon diameter, were the most critical parameters in defining synaptic morphology. ‘Average’ synaptic morphology was remarkably conserved between comparable synapses from the left and right sides of the body. Systematic differences in synaptic morphology predicted corresponding differences in synaptic function that were supported by physiological recordings, confirming the robust relationship between synaptic size and strength.
The ability to deliver sufficient core anatomical knowledge and understanding to medical students with limited time and resources remains a major challenge for anatomy educators. Here, we report the results of switching from a primarily didactic method of teaching to supported self-directed learning for students studying anatomy as part of undergraduate medicine at the University of Edinburgh. The supported self-directed approach we have developed makes use of an integrated range of resources, including formal lectures and practical sessions (incorporating gross anatomy specimens, medical imaging technologies, anatomical models, clinical scenarios, and surface anatomy workstations). In practical sessions, students are provided with a custom-made workbook that guides them through each session, with academic staff, postgraduate tutors, and near-peer teaching assistants present to deal with misunderstandings and explain more complicated topics. This approach retains many of the best attributes of didactic teaching but blends them with the advantages associated with self-directed learning approaches. The switch to supported self-directed learning-initially introduced in 2005-resulted in a significant improvement in anatomy examination scores over the subsequent period of five years, manifesting as an increase in the average anatomy practical spot examination mark, less students failing to obtain the pass mark and more students passing with distinction. We conclude that the introduction of supported self-directed learning improved students' engagement, leading to deeper learning and better understanding and knowledge of anatomy.
Growth was studied in 89 children with atopic eczema aged 1-16 years. Nine (10%) had a standing height below the 3rd centile. Both boys and girls had significantly reduced sitting height but normal subischial leg length, and both sexes had significantly delayed skeletal maturity scores. Impaired growth was particularly associated with widespread eczema, but also with the presence of asthma and the potency of topical corticosteroid. Six of the 15 patients with a corrected height centile below the 10th centile had been receiving potent (British National Formulary category I or II) topical corticosteroids. This study suggests that impaired linear growth is a feature of atopic eczema. While the causes of the growth impairment are unclear, there is a need for caution in the use of potent topical corticosteroids in children.
Abnormalities in muscle histology have been reported frequently for the cricopharyngeus muscle of patients with oculopharyngeal muscular dystrophy, motor neuron disease and other neurological disorders in which dysphagia is a common clinical sign. However, there are few detailed reports of the normal structure of this muscle nor quantitative baseline data with which to compare the diseased state. In this study, cricopharyngeus muscles from 21 healthy individuals and four patients with motor neuron disease underwent quantitative histological and histochemical examination. In addition to the extensive connective tissue content (40%), comprising abundant elastic fibres, cricopharyngeus muscles from normal individuals possessed small calibre striated muscle fibres (mean narrow diameter 30 microns) of widely varying size (coefficient of variation 41%). The majority of fibres were histochemically type I (82%) and highly oxidative. All muscles comprised numerous muscle fibres with aberrant histological and histochemical features (internalized nuclei, 'ragged red' crescents, splits, degenerating fibres, 'moth-eaten' fibres, or nemaline rods.) The histomorphometric and histopathological features were similar in males and females and some showed a correlation with age. There were increases in fibre size and roundedness and decreases in the numerical density and percentage of type I and split fibres in the specimens from older individuals. Cricopharyngeus muscles from patients with motor neuron disease were not significantly different from the controls for most parameters. It is therefore suggested that previous descriptions of specific cricopharyngeal pathology accompanying neuromuscular disease or dysphagia be interpreted with caution. The importance of obtaining normal structural, morphometric and histopathological data from muscles other than the usually biopsied limb muscles, is emphasized.
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