A cross-sectional study of ageing at the mouse neuromuscular junction and effects of an experimental therapeutic approach for dynapenia.

Despite prior efforts to understand and target dynapenia (age-induced loss of muscle strength), this condition remains a major challenge that reduces the quality of life in the aged population. We have focused on the neuromuscular junction (NMJ) where changes in structure and function have rarely been systematically studied as a dynamic and progressive process. Our cross-sectional study found neurotransmission at the male mouse NMJ to be biphasic, displaying an early increase followed by a later decrease, and this phenotype was associated with structural changes to the NMJ. A cross-sectional characterization showed that age-induced alterations fell into four age groups: young adult (3-6 months), adult (7-18 months), early aged (19-24 months), and later aged (25-30 months). We then utilized a small molecule therapeutic candidate, GV-58, applied acutely during the later aged stage to combat age-induced reductions in transmitter release by increasing calcium influx during an action potential, which resulted in a significant increase in transmitter release. This comprehensive study of neuromuscular ageing at the NMJ will enable future research to target critical time points for therapeutic intervention. KEY POINTS: Age-induced frailty and falls are the leading causes of injury-related death and are caused by an age-induced loss of muscle strength due to a combination of neurological and muscular changes. A cross-sectional approach was used to study age-induced changes to the neuromuscular junction in a mouse model, and physiological changes that were biphasic over the ageing time course were found. Changes in physiology at the neuromuscular junction were correlated with alterations in neuromuscular junction morphology. An acutely applied positive allosteric gating modifier of presynaptic voltage-gated calcium channels was tested as a candidate therapeutic strategy that could increase transmitter release at aged neuromuscular junctions. These results provide a detailed time course of age-induced changes at the neuromuscular junction in a mouse model and test a candidate therapeutic strategy for weakness.

Sociodemographic determinations of management behavior of diabetic patients attending a diabetic clinic in Alexandria. Part III: Relation between diabetics' sociodemographic background and health belief model variables.

The present work aims to study the relation between patient's health beliefs and psychological perception and demographic variables. The same subjects and methods applied in part I and II was adopted. It was found that a minority (1.7%) had a weak overall perceived susceptibility. However the rest were categorized as having either moderate (36.3%) or strong perception (62.0%). None of the diabetic patients was graded as having a weak overall perceived severity level. The remaining diabetics were graded as having either moderate (50.7%) or strong perception (49.3%). The majority (98.3%) had a strong perception and the rest had a moderate one. None of diabetic patients had weak overall internal cues to action towards their health. They had either moderate (59.7%) or strong cues (40.3%). Age of diabetic patients was linearly associated with the overall perceived severity level (X2 (MH) = 10.49). The younger the patients the more likely that they were classified as having a strong perception. Moreover, a significant linear association was observed between age and exposure to external cues to action (X2(MH) = 8.17), where the older the patients the more likely that they were exposed to external cues to action. It was observed that a significant relation was observed between gender and exposure to external cues to action (X2 = 4.60), where females were more likely to be exposed than males to external cues to action. A statistical significant linear association was observed between the education of diabetics and exposure to external cues to action (X2(MH) = 9.26). Diabetics without any educational certificates were more likely to be exposed to external cues to action. The present study provides data on the level of perception of diabetic patients in order to plan for a diabetic education programme.