Duchenne muscular dystrophy (DMD) is characterized by a severe and progressive destruction of muscle fibers associated with altered Ca homeostasis. We have previously shown that the IP receptor (IPR) plays a role in elevating basal cytoplasmic Ca and that pharmacological blockade of IPR restores muscle function. Moreover, we have shown that the IPR pathway negatively regulates autophagy by controlling mitochondrial Ca levels. Nevertheless, it remains unclear whether IPR is involved in abnormal mitochondrial Ca levels, mitochondrial dynamics, or autophagy and mitophagy observed in adult DMD skeletal muscle. Here, we show that the elevated basal autophagy and autophagic flux levels were normalized when IPR was downregulated in mdx fibers. Pharmacological blockade of IPR in mdx fibers restored both increased mitochondrial Ca levels and mitochondrial membrane potential under resting conditions. Interestingly, mdx mitochondria changed from a fission to an elongated state after IPR knockdown, and the elevated mitophagy levels in mdx fibers were normalized. To our knowledge, this is the first study associating IPR1 activity with changes in autophagy, mitochondrial Ca levels, mitochondrial membrane potential, mitochondrial dynamics, and mitophagy in adult mouse skeletal muscle. Moreover, these results suggest that increased IPR activity in mdx fibers plays an important role in the pathophysiology of DMD. Overall, these results lead us to propose the use of specific IPR blockers as a new pharmacological treatment for DMD, given their ability to restore both autophagy/mitophagy and mitochondrial function.
Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009.
Complete ischemia and reperfusion effects on twitch force (∫(F·t)), twitch latent period (TLP), maximal rate of rise of twitch tension (δF/δt), and twitch maximum relaxation rate (TMRR) were assessed. We divided 36 adult rats into four groups; two control groups (n = 9), a group undergoing 1 hour of ischemia followed by 1 hour of reperfusion (n = 9), and one group exposed to 2 hours of ischemia followed by 1 hour of reperfusion (n = 9). We have induced twitch contractions every 10 minutes in the soleus and the extensor carpi radialis longus (ECRL). Twitch contractions were recorded and then analyzed for ∫(F·t), TLP, (δF/δt), and TMRR. During 1 hour and 40 minutes of ischemia, TLP increased to 179 ± 24% (p < 0.05) in the soleus and to 184 ± 16% (p < 0.05) in the ECRL, an effect that was partially recovered during 1 hour of reperfusion. This increase started after 20 minutes of ischemia in the soleus and after 40 minutes of ischemia in the ECRL. The increase was faster in the ECRL and peaked at the same time for both muscular groups. ∫(F·t) and (δF/δt) decreased during 1 hour of ischemia to 46 ± 7% (p < 0.05) in the soleus and to 40 ± 7% (p < 0.05) in the ECRL. TMRR decreased during 1 hour of ischemia to 39 ± 5% (p < 0.05) in the soleus and to 54 ± 8% (p < 0.05) in the ECRL. During 1 hour of reperfusion all of them recovered close to control values.
Background and objective
There is a shortage of supplies for the protection of professionals during the COVID-19 pandemic. 3D printing offers the possibility to compensate for the production of some of the equipment needed. The objective is to describe the role of 3D printing in a health service during the COVID-19 pandemic, with an emphasis on the process to develop a final product ready to be implemented in the clinical environment.
Methods
A working group was formed between the healthcare administration, clinicians and other public and private institutions in Cantabria, Spain coordinated by the Valdecilla Virtual Hospital. The process included receiving the printing proposals, learning about the printing resources in the region, selecting the devices, creating a team for each project, prototyping, evaluation and redesign, manufacturing, assembly and distribution.
Results
The following supplies are produced: 1) devices that help protect providers: face protection screens (2400 units), personalized accessories for photophores (20 units) and ear-protection forks for face-masks (1200 units); 2) products related to the ventilation of infected patients: connectors for non-invasive ventilation systems; and 3) oral and nasopharyngeal swabs (7500 units) for the identification of coronavirus carriers with the aim of designing action protocols in clinical areas.
Conclusions
3D printing is a valid resource for the production of protective material for professionals whose supply is reduced during a pandemic.
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