Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.

BACKGROUND: microRNAs (miRs) are small non-coding RNAs involved in the fine regulation of several cellular processes by inhibiting their target genes at post-transcriptional level. Osteosarcoma (OS) is a tumor thought to be related to a molecular blockade of the normal process of osteoblast differentiation. The current paper explores temporal transcriptional modifications comparing an osteosarcoma cell line, Saos-2, and clones stably transfected with CD99, a molecule which was found to drive OS cells to terminally differentiate. METHODS: Parental cell line and CD99 transfectants were cultured up to 14 days in differentiating medium. In this setting, OS cells were profiled by gene and miRNA expression arrays. Integration of gene and miRNA profiling was performed by both sequence complementarity and expression correlation. Further enrichment and network analyses were carried out to focus on the modulated pathways and on the interactions between transcriptome and miRNome. To track the temporal transcriptional modification, a PCA analysis with differentiated human MSC was performed. RESULTS: We identified a strong (about 80 %) gene down-modulation where reversion towards the osteoblast-like phenotype matches significant enrichment in TGFbeta signaling players like AKT1 and SMADs. In parallel, we observed the modulation of several cancer-related microRNAs like miR-34a, miR-26b or miR-378. To decipher their impact on the modified transcriptional program in CD99 cells, we correlated gene and microRNA time-series data miR-34a, in particular, was found to regulate a distinct subnetwork of genes with respect to the rest of the other differentially expressed miRs and it appeared to be the main mediator of several TGFbeta signaling genes at initial and middle phases of differentiation. Integration studies further highlighted the involvement of TGFbeta pathway in the differentiation of OS cells towards osteoblasts and its regulation by microRNAs. CONCLUSIONS: These data underline that the expression of miR-34a and down-modulation of TGFbeta signaling emerge as pivotal events to drive CD99-mediated reversal of malignancy and activation of differentiation in OS cells. Our results describe crucial and specific interacting actors providing and supporting their relevance as potential targets for therapeutic differentiative strategies.

Late micronutrient deficiency and neurological dysfunction after laparoscopic sleeve gastrectomy: a case report.

Although the micronutrient deficiencies and the related neurological manifestations are widely reported after malabsorbitive weight loss surgery, little is known about cerebral dysfunction secondary to micronutrient impairment in subjects undergoing restrictive interventions (that is, sleeve gastrectomy). We describe a case of a 27-year-old woman with a late development of a Wernicke's encephalopathy (WE) and of severe polyneuropathy following a sleeve gastrectomy without any sleeve stenosis. The impact of WE after bariatric surgery is significantly underestimated. Such a risk should be taken into consideration also after restrictive weight loss surgery. Thus, surgeon/clinicians involved in bariatric patients management must be aware of neurological sequelae related to this intervention.

Topiramate in refractory partial-onset seizures in children, adolescents and young adults: a multicentric open trial.

PURPOSE: This study was to evaluate the efficacy and safety of topiramate (TPM) in refractory partial epilepsy in children, adolescents and young adults. METHODS: We performed a prospective open label add-on study in 55 patients (age 2-30 years, mean 15 years) with refractory partial seizures. Topiramate was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency. RESULTS: TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24h, up to a maximum daily dose of 12 mg/kg. After 9 months of treatment, 11 patients (20%) had 100% fewer seizures and 25 patients (45%) had a more than 50% seizure reduction. TPM appeared to be effective both in cryptogenic (76.2%) and symptomatic (58.8%) partial epilepsies. Mild to moderate adverse events were present in 25 patients (45.4%), mostly represented by drowsiness, nervousness and hyporexia with or without weight loss. CONCLUSION: TPM was an overall effective and safe add-on drug both in cryptogenic and symptomatic childhood refractory partial seizures, the adverse reactions being generally mild or moderate.

Pre-symptomatic neurological involvement in Behcet's disease: the diagnostic role of magnetic transcranial stimulation.

Twenty Behcet's disease (BD) patients with or without neurologic signs and symptoms were studied by means of magnetic transcranial stimulation. The most frequent abnormalities were an increase of motor evoked potential latency and a delay of central motor conduction time (CMCT). In 5 out of 9 BD patients with pyramidal signs central motor conduction changes were present. Furthermore, 2 out of 7 patients without neurologic signs and symptoms showed an increased threshold and a prolonged CMCT. The data obtained suggest that this technique is useful not only to confirm the neurologic impairment but also to reveal subclinical or pre-symptomatic central motor involvement in BD subjects.

[Peripheral nerve damage in HIV infection]. / Il danno neuroperiferico nella infezione da HIV.

A critical review of the literature concerning PNS involvement in HIV infection was carried out. This complication was detected a short time ago (1982) and therefore a common classification is not yet available. The authors, through an analysis of the cases reported in literature, suggest a nosographic classification of this pathology.