Articles: function.
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There is growing evidence for increased levels of pain and reduced health-related quality of life in survivors of critical illness. Recent studies showed marked small nerve fiber pathology in critically ill patients, which may contribute to chronic pain states and reduced physical recovery after ICU discharge. Primary objective of this study was the comparison of somatosensory functions between survivors of critical illness 6 months after ICU discharge and controls. In post hoc analyses, we aimed to identify associations between small fiber deficits, pain, health-related quality of life, and clinical data. ⋯ A large portion of former critically ill patients show small fiber deficits which seem to be associated with increased pain and reduced physical health-related quality of life. Screening of somatosensory functions in the (post-) acute setting could possibly help to identify patients at risk of long-term impairments.
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Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin-dependent intracellular mitochondrial transport. ⋯ HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.
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In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. ⋯ In mice surviving lipopolysaccharide challenge, the natural recovery of cardiac contractility was associated with the up-regulation of cardiomyocyte calcium handling above baseline levels, indicating the presence of an active myocardial recovery process, which included sarcoplasmic reticulum calcium pump activation, the down-regulation of phospholamban, and sodium/calcium exchange inhibition.