Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas

PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas of the ovary. PPP2R1A encodes the α-isoform of the scaffolding subunit of the serine/threonine protein phosphatase 2A (PP2A) holoenzyme. This putative tumour suppressor complex is involved in growth and survival pathways. Through targeted sequencing of PPP2R1A, we identified somatic missense mutations in 40.8% (20/49) of high-grade serous endometrial tumours, and 5.0% (3/60) of endometrial endometrioid carcinomas. Mutations were also identified in ovarian tumours at lower frequencies: 12.2% (5/41) of endometrioid and 4.1% (2/49) of clear cell carcinomas. No mutations were found in 50 high-grade and 12 low-grade serous carcinomas. Amino acid residues affected by these mutations are highly conserved across species and are involved in direct interactions with regulatory B-subunits of the PP2A holoenzyme. PPP2R1A mutations in endometrial high-grade serous carcinomas are a frequent and potentially targetable feature of this disease. The finding of frequent PPP2R1A mutations in high-grade serous carcinoma of the endometrium but not in high-grade serous carcinoma of the ovary provides clear genetic evidence that these are distinct diseases.     

Agreement of the clinician's choice of archwire selection on conventional and virtual models

Objectives:To compare archwire selection on dental casts with archwire selection using a three-dimensional (3D) software program (OrthoAid) and assess agreement between clinicians.Materials and Methods:The best-fitting archwires were selected for dental casts of 100 patients with malocclusion using two approaches by three orthodontists. The first method was to visually determine the fitness of five preformed nickel titanium archwires to the arch form on a dental cast (subjective method). The second method was archwire selection on a virtual image of the same cast by means of 3D software (objective method). Agreement between selections performed by the orthodontists was calculated using Kappa statistics. The accuracy of fit of the archwires to the curves fitted to the arch form was also calculated or reversely assessed by means of the root mean square (RMS) for both methods using the Dahlberg formula.Results:The mean RMS of the distances between the patient arch forms and the archwires for the subjective method was 1.163–1.366 mm. The agreement of selections between orthodontists was 42%–58% (Kappa ranged from .074 to .382). Using the 3D software (objective method), the mean RMS decreased to 0.966–1.171 mm, and agreement increased to 47% to 84% (Kappa ranged from .444 to .747).Conclusions:The use of 3D computer software for archwire selection in patients with malocclusion provided better adaptation and interexaminer reliability.     

Expression Analysis of lncRNAs in Refractory and Non-Refractory Epileptic Patients

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the pathogenesis of neuropsychiatric disorders such as epilepsy. In the current study, we evaluated expression of eight lncRNAs in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal individual using quantitative real-time PCR. Bayesian regression model showed significant higher expression of UCA1 in both refractory and non-refractory groups compared with controls (posterior beta of relative expression (RE) =?2.03, P value?=?0.003, and posterior beta of RE?=?4.05, P value?<?0.0001, respectively). Besides, expression of UCA1 was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?2.008, P value?=?0.019). When repeating statistical analyses in a gender-based manner, differences in expression of UCA1 were significant in all subgroup analyses except for male non-refractory vs. refractory subgroups analysis. Expression levels of NKILA and ANRIL were higher in both refractory and non-refractory groups compared with controls (posterior beta of RE?=?1.565, P value?=?0.018, and posterior beta of RE?=?1.902, P value?=?0.006 for NKILA; posterior beta of RE?=?1.304, P value?<?0.0001, and posterior beta of RE?=?1.603, P value?=?0.019 for ANRIL, respectively). However, expression levels of these two lncRNAs were not different between refractory and non-refractory groups. Gender-based analysis for these two lncRNAs revealed similar results except for lack of difference in ANRIL expression between male refractory group and controls. Expression of THRIL was significantly lower in both refractory and non-refractory groups compared with controls (posterior beta of RE?=???0.842, P value?=?0.044 and posterior beta of RE?=???1.969, P value?<?0.0001, respectively). Furthermore, expression of this lncRNA was lower in non-refractory patients compared with refractory ones (posterior beta of RE?=???1.129, P value?=?0.002). However, no significant difference was detected between non-refractory and refractory patients either in males or females. The interactions between gender and relative expressions of PACER, DILC, and MALAT1 were significant, so the results were assessed in gender-based manner. In females, expression of DILC was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?0.959, P value?=?0.044). Expression of MALAT1 was lower in female non-refractory patients compared with controls and in female non-refractory patients compared with refractory ones (posterior beta of RE?=???1.35, P value?=?0.002, and posterior beta of RE?=???0.942, P value?=?0.045, respectively). Finally, expression of PACER was higher in refractory patients vs. controls and non-refractory patients vs. controls in both male and female subgroups. However, comparison between non-refractory and refractory patients revealed significant results only among females. Expression of none of the assessed lncRNAs was correlated with age of study participants. There were robust correlations between expression levels of lncRNAs. The most robust correlations were detected between UCA1 and PACER (r?=?0.84, P?<?0.0001) and between UCA1 and ANRIL (r?=?0.75, P?<?0.0001). Taken together, our study demonstrated dysregulation of lncRNAs in peripheral blood of epileptic patients and potentiated them as biomarkers for this neurologic condition.