Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+

We investigated how inhibition of mitochondrial Ca2+ uptake affects stimulation-induced increases in cytosolic [Ca2+] and phasic and asynchronous transmitter release in lizard motor terminals in 2 and 0.5 mM bath [Ca2+]. Lowering bath [Ca2+] reduced the rate of rise, but not the final amplitude, of the increase in mitochondrial [Ca2+] during 50-Hz stimulation. The amplitude of the stimulation-induced increase in cytosolic [Ca2+] was reduced in low-bath [Ca2+] and increased when mitochondrial Ca2+ uptake was inhibited by depolarizing mitochondria. In 2 mM Ca2+, end-plate potentials (epps) depressed by 53% after 10 s of 50-Hz stimulation, and this depression increased to 80% after mitochondrial depolarization. In contrast, in 0.5 mM Ca2+ the same stimulation pattern increased epps by approximately 3.4-fold, and this increase was even greater (transiently) after mitochondrial depolarization. In both 2 and 0.5 mM [Ca2+], mitochondrial depolarization increased asynchronous release during the 50-Hz train and increased the total vesicular release (phasic and asynchronous) measured by destaining of the styryl dye FM2-10. These results suggest that by limiting the stimulation-induced increase in cytosolic [Ca2+], mitochondrial Ca2+ uptake maintains a high ratio of phasic to asynchronous release, thus helping to sustain neuromuscular transmission during repetitive stimulation. Interestingly, the quantal content of the epp reached during 50-Hz stimulation stabilized at a similar level ( approximately 20 quanta) in both 2 and 0.5 mM Ca2+. A similar convergence was measured in oligomycin, which inhibits mitochondrial ATP synthesis without depolarizing mitochondria, but quantal contents fell to <20 when mitochondria were depolarized in 2 mM Ca2+.     

Professional growth of trainees: applying teacher training models to the training of GPs

Study of professional growth is useful for reflective purposes at any time during a career. The concept of known knowns and unknowns with a training twist can be used to summarise the overall stages of any trainee. At the start of vocational training the trainee does not know what they do not know, they have not yet recognised how much they have to learn. This happens in the second stage (that could be equated to survival) when they begin to understand the vast array of skills they must develop to make it look easy. With time and practice they will reach the point where they know what they have to do--not always getting it right but then who does? Finally, and it is particularly important that trainers recognise this, an individual will reach the point where everything is so automatic they are no longer aware of the intricacies of the skills they have acquired. This is where most trainers, both for teachers and GPs, find themselves and this can be frustrating for both trainee and trainer as they find they are unable to communicate effectively. A good trainer will spend time dissecting and 'unlearning' their skills so they are able to teach their trainees successfully. Trainees, meanwhile, must realise that, one day, they will have their own unknown knowns, but they cannot expect it to happen overnight or without substantial effort. In moving forward from our training it is how we deal with repeated survival stages that determines if we can keep doing the job, it is how we deal with the plateau that determines if we will be any good at it--effective on-the-job training leads to lifelong on-the-job learning.     

Long-term prosthetic aftercare of direct vs. indirect attachment incorporation techniques to mandibular implant-supported overdenture

Objective: The aim of this long‐term study was to compare the need for prosthetic aftercare of direct vs. indirect attachment incorporation techniques to mandibular implant‐supported overdenture. Materials and methods: Forty‐five consecutive patients were included (130 implants were placed). Treatment was randomly allocated, resulting in 22 patients (group A) to be treated with direct ball attachment incorporation and 23 patients (group B) to be treated with indirect ball attachment incorporation. All patients were treated by experienced oral‐maxillofacial surgeons/periodontists and experienced prosthodontists/residents. From the first day that the patients visited the clinic up to 20 years after the first treatment session, all surgical or prosthetic therapeutic interventions were recorded. The recorded data for the present study included the number of aftercare visits and dental treatment received (pressure sores relieve, liner changes due to loss of retention and attachment replacement due to wear). Results: The mean follow‐up was 93±57 months. No implants were lost. Statistical analysis revealed a statistically significantly (P<0.001) greater need for prosthetic interventions in group B vs. group A. The mean number of visits dedicated to – pressure sores relieve (7.04±1.4 vs. 3.63±0.84); liner exchange due to loss of retention (3.6±1.3 vs. 1.09±1.06) was significantly higher in group B. Attachment replacement due to wear occurred only in group B (11/23 – 47.8%). Conclusion: The direct technique for attachment incorporation in mandibular implant‐supported overdentures using ball attachments is superior to the indirect technique from the aftercare perspective during a long‐term evaluation period. To cite this article:
Nissan J, Oz‐Ari B, Gross O, Ghelfan O, Chaushu G. Long‐term prosthetic aftercare of direct vs. indirect attachment incorporation techniques to mandibular implant‐supported overdenture.
Clin. Oral Impl. Res. 22 , 2011; 627–630
doi: 10.1111/j.1600‐0501.2010.02026.x     

Early vulnerability to ischemia/reperfusion injury in motor terminals innervating fast muscles of SOD1-G93A mice

In mouse models of familial amyotrophic lateral sclerosis (fALS), motor neurons are especially vulnerable to oxidative stresses in vitro. To determine whether this increased vulnerability also extends to motor nerve terminals in vivo, we assayed the effect of tourniquet-induced ischemia/reperfusion (I/R) injury on motor terminals innervating fast and slow hindlimb muscles in male G93A-SOD1 mice and their wild-type littermates. These mice also expressed yellow fluorescent protein (YFP) in motor neurons. We report that in SOD1-G93A/YFP mice the motor terminals innervating two predominantly fast muscles, extensor digitorum longus (EDL) and plantaris, were more vulnerable to I/R injury than motor terminals innervating the predominantly slow soleus muscle. The mean duration of EDL ischemia required to produce a 50% reduction in endplate innervation in SOD1-G93A/YFP mice was 26 min, compared to 45 min in YFP-only mice. The post-I/R destruction of EDL terminals in SOD1-G93A mice was rapid (<2 h) and was not duplicated by cutting the sciatic nerve at the tourniquet site. The increased sensitivity to I/R injury was evident in EDL muscles of SOD1-G93A/YFP mice as young as 31 days, well before the onset of motor neuron death at approximately 90 days. This early vulnerability to I/R injury may correlate with the finding (confirmed here) that in fALS mice motor nerve terminals innervating fast hindlimb muscles degenerate before those innervating slow muscles, at ages that precede motor neuron death. Early vulnerability of fast motor terminals to I/R injury thus may signal, and possibly contribute to, early events involved in motor neuron death.