Biology subjects

Levesque, M.

Publications and source records attributed to Levesque, M..

2 recordsLinked to original sources

bioRxiv2019

Clinically significant acute pain disturbs motor cortex intracortical inhibition and facilitation in orthopedic trauma patients: A TMS study

ObjectivePrimary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity. MethodsEighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls) performed a single transcranial magnetic stimulation (TMS) session over M1 (resting motor threshold (rMT); short-intracortical inhibition (SICI); intracortical facilitation (ICF); long-interval cortical inhibition (LICI)). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain). ResultsReduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures. DiscussionThese findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities.

neuroscience↗

bioRxiv2019

Multi-site clonality analyses uncovers pervasive subclonal heterogeneity and branching evolution across melanoma metastases

Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naive patient and by leveraging the analytical power of multi-sample analyses, we reveal that metastatic cells may depart the primary tumour very early in the disease course and follow a branched pattern of evolution. Truncal UV-induced mutations that often swamp downstream analyses of heterogeneity, were found to be replaced by APOBEC-associated mutations in the branches of the evolutionary tree. Multi-sample analyses from a further 7 patients confirmed that branched evolution was pervasive, representing an important mode of melanoma dissemination. Our analyses illustrate that combining cancer cell fraction estimates across multiple metastases provides higher resolution phylogenetic reconstructions relative to single sample analyses and highlights the limitations of accurately inferring inter-tumoural heterogeneity from a single biopsy.

genomics↗