Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the selective degeneration of motor neurons in the brain and spinal cord progressively leading to paralysis and death. Current diagnosis of ALS is based on clinical assessment of related symptoms. The clinical manifestations observed in ALS appear relatively late in the disease course after degeneration of a significant number of motor neurons. As a result, the identification and development of disease-modifying therapies is difficult. Therefore, novel strategies for early diagnosis of neurodegeneration, to monitor disease progression and to assess response to existing and future treatments are urgently needed. Factually, many neurological disorders, including ALS, are accompanied by skin changes that often precede the onset of neurological symptoms. Aiming to generate an innovative human-based model to facilitate the identification of predictive biomarkers associated with the disease, we developed a unique ALS tissue-engineered skin model (ALS-TES) derived from patient's own cells. The ALS-TES presents a number of striking features including altered epidermal differentiation, abnormal dermo-epidermal junction, delamination, keratinocyte infiltration, collagen disorganization and cytoplasmic TDP-43 inclusions. Remarkably, these abnormal skin defects, uniquely seen in the ALS-derived skins, were detected in pre-symtomatic C9orf72-linked ALS patients carrying the GGGGCC DNA repeat expansion. Consequently, our ALS skin model could represent a renewable source of human tissue, quickly and easily accessible to better understand the physiopathological mechanisms underlying this disease, to facilitate the identification of disease-specific biomarkers, and to develop innovative tools for early diagnosis and disease monitoring.

A hospitalization is a time when perceived vulnerability to dangers from smoking and quitting motivation may be at their peak. Aim was to determine whether a smoking cessation intervention of moderate intensity would increase the smoking cessation rate in hospitalized smokers. Design was randomized trial, conducted in a university-affiliated cardio-pulmonary tertiary care center. Participants were hospitalized smokers aged < or =70 years. Intervention was a smoking cessation intervention consisting of education and psychological support, with or without pharmacological therapy, associated with follow-up phone calls. Patients assigned to the control group received usual care. Measurement was point prevalence cessation rate at 1-year follow-up. A total of 468 patients were screened; 196 were randomized. Although the smoking cessation rates at 12-month follow-up were higher than expected, we found no significant difference between the study groups (intervention: 30.3%; control: 27.8%). Similar results were obtained in patients whose smoking status was validated by urinary cotinine assay. Length of stay and dependence to nicotine were the only significant predictors of smoking cessation. A smoking cessation intervention of moderate intensity delivered in a tertiary cardio-pulmonary center did not increase the smoking cessation rate at 1-year follow-up. The results of this trial should not divert those who deliver care to inpatients from delivering a brief smoking cessation intervention.

Neurofibromas are the most characteristic feature of neurofibromatosis type 1 (NF1), a multisystemic disorder caused by aberrations in the neurofibromin gene (NF1). Despite significant progress over the last several years in understanding this disease, a suitable in vitro model to better mimic neurofibroma formation and growth has yet to be described. There is therefore a need to establish an in vitro, three dimensional model that allows the incorporation of multicellular lineages and the modulation of the cellular microenvironment—known to be important for cellular crosstalk and distribution of soluble factors—to study neurofibroma biology and morphogenesis. A self‐assembly approach was used to generate tissue‐engineered skins (TES) in which patient‐derived spheroids made of NF1‐associated Schwann cells and fibroblasts were seeded. We describe the first in vitro three dimensional neurofibroma model—directly derived from NF1 patients presenting with histopathological features—having an ECM protein expression profile quite similar to that of a native tumor. We observed efficient incorporation, proliferation, and migration of spheroids within NF1‐TES over time. This biotechnological approach could provide a unique tool for precision medicine targeting NF1 and for assessing the tumorigenic properties of each NF1 gene mutation linked to tumor formation.

No abstract