Osteopontin (OPN) is a multifunctional protein, which has recently been shown to be linked to tumorigenesis, progression and metastasis in different malignancies. Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few predictors of outcome, the purpose of this study was to evaluate if OPN might be involved in NSCLC's biology and therefore represent a prognostic marker and a target for new therapeutic trials. Immunohistochemistry was used to detect OPN expression, evaluated as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumours with low (o20%) from tumours with high (X20%) OPN expression. A statistically significant correlation between high levels of OPN and shorter overall (P ¼ 0.034) and disease-free (P ¼ 0.011) survival in our patients was shown. Our results support the hypothesis that high OPN expression is a significantly unfavourable prognostic factor for the survival of patients with stage I NSCLC. This conclusion has notable importance in terms of the biological characterization of early-stage tumours and therapeutic opportunities.

Longevity is determined by diverse signaling pathways including telomere protection and homeostasis master regulators like FOXO3a. We previously showed that the telomeric repeat binding factor 2 (TRF2) expression decreases with age in human skeletal muscle and that, surprisingly, its loss in myofibers does not trigger telomere deprotection. We reveal here that in TERF2-compromised myotubes, FOXO3a is recruited to telomeres where it acts as a protective factor against ATM-dependent DNA damage activation. Moreover, we show that FOXO3a-telomere association increases with age in human skeletal muscle biopsies. In mitotic fibroblasts, the telomere protective properties of FOXO3a are operative if the cells are treated with bleomycin. The telomere function of FOXO3a does not require its Forkhead DNA binding domain but the CR2C. Overall, these findings demonstrate a direct connection between two key longevity pathways, FOXO3a and telomere protection. This unveils an unexpected higher level of integration in the regulation of longevity signaling pathway.

We described a male child of two years and three months affected by assial hypotonia, psicomotor retardation, muscular distal hypotrophy with hyporeflexia, dystonic movements and deafness. He was born from non‐consanguineous parents by spontaneous caesarian twin delivery at 38 weeks. His sister is healthy. He came to our observation at 16 months of age. Screenings for metabolic diseases and CSF neurotransmitters and lactate were normal, whereas the serum lactate was mildly increased. Brain MRI showed delayed myelination, with the normal lactate at the spectroscopic study. EEG showed interemispheric asymmetry with epileptic discharges. EMG showed a neurogenic pattern. Molecular DNA analysis for Spinal Muscular Atrophy was negative. Muscle biopsy showed neurogenic injury and an absence of ragged red fibers; enzymatic assay showed a severe deficiency of Complex I (2.8 nmol/min/mg protein, n.v. 17–33) and a mild deficiency of Pyruvate Dehydrogenase (PDHC=0.47 nmol/min/mg protein, n.v.0.8‐2). The clinical features of patients with a dysfunction in mitochondrial metabolic pathways are variable. A PDHC deficiency leads to a graduated spectrum of neurological involvement starting from severe forms with death in the neonatal period, Leigh disease and carbohydrate‐induced episodic ataxia. The most common features associated with a PDHC defect are delayed development and hypotonia. Patients with Complex I deficiency show a variable phenotype from fatal infantile encephalomyopathy to adult‐onset myopathy; neurodegenerative disorders are also described: Parkinson's disease, dystonia and Leber's optic neuropathy. A combined PHDC and Complex I deficiency is rarely reported. We can make the hypothesis that a defect of a single enzyme (Complex I) can play a role on the other enzyme deficiency. The presence of a primitive PHDC and Complex I deficiency is unlikely be hypothesized since the parents are not consanguineous and a double genetic defect is improbable.