Mitochondrial dysfunction caused by aberrant Complex I assembly and reduced activity of the electron transport chain is pathogenic in many genetic and age-related diseases. Mice missing the Complex I ...subunit NADH dehydrogenase ubiquinone iron-sulfur protein 4 (NDUFS4) are a leading mammalian model of severe mitochondrial disease that exhibit many characteristic symptoms of Leigh Syndrome including oxidative stress, neuroinflammation, brain lesions, and premature death. NDUFS4 knockout mice have decreased expression of nearly every Complex I subunit. As Complex I normally contains at least 8 iron-sulfur clusters and more than 25 iron atoms, we asked whether a deficiency of Complex I may lead to iron perturbations, thereby accelerating disease progression. Consistent with this, iron supplementation accelerates symptoms of brain degeneration in these mice, while iron restriction delays the onset of these symptoms, reduces neuroinflammation, and increases survival. NDUFS4 knockout mice display signs of iron overload in the liver including increased expression of hepcidin and show changes in iron-responsive element-regulated proteins consistent with increased cellular iron that were prevented by iron restriction. These results suggest that perturbed iron homeostasis may contribute to pathology in Leigh Syndrome and possibly other mitochondrial disorders.
Neuro-orthopedic disorders are common in patients with disorders of consciousness (DOC) and can lead to potential pain. However, the patients' inability to communicate makes pain detection and ...management very challenging for clinicians. In this crossover randomized double-blind placebo-controlled study, we investigated the effects of an analgesic treatment on the presence of nociception-related behaviors. At baseline, the Nociception Coma Scale-Revised (NCS-R) was performed in 3 conditions: a non-noxious stimulation, a noxious stimulation, and during a physiotherapy session. Patients with a NCS-R total score during physiotherapy equal or above the score observed after the noxious stimulation could participate to the clinical trial, as well as patients with a score above 5. They received an analgesic treatment and a placebo on 2 consecutive days in a randomized order followed by an assessment with the NCS-R. Of the 18 patients, 15 displayed signs of potential pain during physiotherapy. Patients showed higher NCS-R scores during physiotherapy compared with the other conditions, suggesting that mobilizations were potentially painful. Of these 15 patients, 10 met the criteria to participate in the placebo-controlled trial. We did not find any effect of analgesic treatment on the NCS-R scores. This study highlights that physiotherapy may be potentially painful for patients with DOC, while analgesic treatments did not reduced NCS-R scores. Therefore, careful monitoring with appropriate assessment and treatment before and during mobilization should become a priority in clinical settings. Future studies should focus on the development of assessment tools sensitive to analgesic dosage to manage pain in DOC.
This paper investigates the interest of synchronous pulsed plasmas to etch silicon in HBr/O2 chemistries. Using mass spectrometry, ellipsometry and angle resolved X-ray photoelectron spectroscopy, we ...demonstrate that the radical concentration in the plasma, the etch rate and formation of passivation layers, can be controlled by the RF pulse parameters (frequency and duty cycle). Accordingly, pattern profiles are improved, selectivity to the mask is increased and the silicon recess is reduced from 4 to 0.8 nm when the HBr/O2 plasma lands on thin silicon oxide.
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