MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. Recent evidence indicates that miRNAs can function both as tumor suppressors and as oncogenes. It has been demonstrated that in glioblastoma multiforme miR-21 and 221 are upregulated whereas miR-128 and 181 are downregulated. Expression of miR-21, 221, 128a, 128b, 128c, 181a, 181b, 181c was studied using real-time quantitative reverse transcriptase polymerase chain reaction and northern blotting for human astrocytic tumors with different grade of malignancy. miR-21 and 221 were overexpressed in glioma samples, whereas miRNA 181b was downregulated compared with normal brain tissue. miRNA-21 was hyperexpressed in all tumor samples whereas higher levels of miRNA-221 were found in high-grade gliomas. This study is the first analysis of miRNAs in astrocytic tumor at different stages of malignancy. The different expression pattern observed in tumors at different stages of malignancy is probably dependent on the cell-specific repertoire of target genes of tumors sharing different molecular pathways activity and suggests miRNAs may have also a place in diagnosis and staging of brain tumors.

Background: Despite great technical advances in imaging, such as multidetector computed tomography and magnetic resonance imaging (MRI), diagnosing pancreatic solid lesions correctly remains challenging, due to overlapping imaging features with benign lesions. We wanted to evaluate functional MRI to differentiate pancreatic tumors, peritumoral inflammatory tissue, and normal pancreatic parenchyma by means of dynamic contrast-enhanced MRI (DCE-MRI)-, diffusion kurtosis imaging (DKI)-, and intravoxel incoherent motion model (IVIM) diffusion-weighted imaging (DWI)-derived parameters. Methods: We retrospectively analyzed 24 patients, each with histopathological diagnosis of pancreatic tumor, and 24 patients without pancreatic lesions. Functional MRI was acquired using a 1.5 MR scanner. Peritumoral inflammatory tissue was assessed by drawing regions of interest on the tumor contours. DCE-MRI, IVIM and DKI parameters were extracted. Nonparametric tests and receiver operating characteristic (ROC) curves were calculated. Results: There were statistically significant differences in median values among the three groups observed by Kruskal–Wallis test for the DKI mean diffusivity (MD), IVIM perfusion fraction (fp) and IVIM tissue pure diffusivity (Dt). MD had the best results to discriminate normal pancreas plus peritumoral inflammatory tissue versus pancreatic tumor, to separate normal pancreatic parenchyma versus pancreatic tumor and to differentiate peritumoral inflammatory tissue versus pancreatic tumor, respectively, with an accuracy of 84%, 78%, 83% and area under ROC curve (AUC) of 0.85, 0.82, 0.89. The findings were statistically significant compared with those of other parameters ( p value < 0.05 using McNemar’s test). Instead, to discriminate normal pancreas versus peritumoral inflammatory tissue or pancreatic tumor and to differentiate normal pancreatic parenchyma versus peritumoral inflammatory tissue, there were no statistically significant differences between parameters’ accuracy ( p > 0.05 at McNemar’s test). Conclusions: Diffusion parameters, mainly MD by DKI, could be helpful for the differentiation of normal pancreatic parenchyma, perilesional inflammation, and pancreatic tumor.

BackgroundAs lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.MethodsWe carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.ResultsOf 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.ConclusionsThe present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.Trial registrationClinicalTrials.gov identifier: NCT00927550

Geminiviruses are single-stranded DNA (ssDNA) viruses that infect a wide range of plants. To promote viral replication, geminiviruses manipulate the host cell cycle. The viral protein Rep is essential to reprogram the cell cycle and then initiate viral DNA replication by interacting with a plethora of nuclear host factors. Even though many protein domains of Rep have been characterized, little is known about its nuclear targeting. Here, we show that one conserved lysine in the N-terminal part of Rep is pivotal for nuclear localization of the Rep protein from Tomato yellow leaf curl virus (TYLCV), with two other lysines also contributing to its nuclear import. Previous work had identified that these residues are essential for Rep from Tomato golden mosaic virus (TGMV) to interact with the E2 SUMO-conjugating enzyme (SCE1). We here show that mutating these lysines leads to nuclear exclusion of TYLCV Rep without compromising its interaction with SCE1. Moreover, the ability of TYLCV Rep to promote viral DNA replication also depends on this highly conserved lysine independently of its role in nuclear import of Rep. Our data thus reveal that this lysine potentially has a broad role in geminivirus replication, but its role in nuclear import and SCE1 binding differs depending on the Rep protein examined. IMPORTANCE Nuclear activity of the replication initiator protein (Rep) of geminiviruses is essential for viral replication. We now define that one highly conserved lysine is important for nuclear import of Rep from three different begomoviruses. To our knowledge, this is the first time that nuclear localization has been mapped for any geminiviral Rep protein. Our data add another key function to this lysine residue, besides its roles in viral DNA replication and interaction with host factors, such as the SUMO E2-conjugating enzyme.