Histone Deacetylases Regulate Gonadotropin-Releasing Hormone I Gene Expression via Modulating Otx2-Driven Transcriptional Activity

BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I) from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs) play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA) and valproic acid (VPA) promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg) family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases

Three lateral osteotomy designs for bilateral sagittal split osteotomy: biomechanical evaluation with three-dimensional finite element analysis

<p>Abstract</p> <p>Background</p> <p>The location of the lateral osteotomy cut during bilateral sagittal split osteotomy (BSSO) varies according to the surgeon's preference, and no consensus has been reached regarding the ideal location from the perspective of biomechanics. The purpose of this study was to evaluate the mechanical behavior of the mandible and screw-miniplate system among three lateral osteotomy designs for BSSO by using three-dimensional (3-D) finite element analysis (FEA).</p> <p>Methods</p> <p>The Trauner-Obwegeser (TO), Obwegeser (Ob), and Obwegeser-Dal Pont (OD) methods were used for BSSO. In all the FEA simulations, the distal segments were advanced by 5 mm. Each model was fixed by using miniplates. These were applied at four different locations, including along Champy's lines, to give 12 different FEA miniplate fixation methods. We examined these models under two different loads.</p> <p>Results</p> <p>The magnitudes of tooth displacement, the maximum bone stress in the vicinity of the screws, and the maximum stress on the screw-miniplate system were less in the OD method than in the Ob and TO methods at all the miniplate locations. In addition, Champy's lines models were less than those at the other miniplate locations.</p> <p>Conclusions</p> <p>The OD method allows greater mechanical stability of the mandible than the other two techniques. Further, miniplates placed along Champy's lines provide greater mechanical advantage than those placed at other locations.</p

Performance of a precast concrete beam-to-beam connection subject to reversed cyclic loading

This study was performed as one phase of an extensive research program focusing on the seismic behaviour of precast connections carried out in Middle East Technical University. The primary objective of the research program was to observe and investigate the seismic behaviour of the connection detail proposed by the collaborating company and the specimens with improved details, in order to develop a 11 moment resisting precast concrete beam-to-beam connection". In this study, six beam-beam connection subassemblies were tested under reversed cyclic loading simulating severe earthquake action. The first specimen was a monolithic specimen used as a reference specimen and tested to define the reference behaviour. The second specimen was a precast specimen, which was detailed by a company specializing in precast concrete production. The remaining specimens were modified according to the results of the formerly tested specimens. All of the specimens were identical in dimensions. All test specimens were 1/2.5 scaled models of the improved connection details used in the highly critical earthquake zones. The behaviour of the precast members was compared with that of the reference one and with the others. In order to improve the seismic performance of the connection, several recommendations for future research and practices are also given in the context of the paper

Cyclic Performance of Precast Concrete Columns Using Steel Box Connection

© 2017, Iran University of Science and Technology. This paper presents an evaluation on lateral cyclic behaviors of precast concrete columns using a steel box connection through experimental investigation. The test consisted of one monolithic reinforced concrete column as a reference and five precast concrete columns. All specimens had identical dimensions of 0.25 × 0.25 m 2 cross-sectional area and 1.7 m height with a longitudinal reinforcement ratio of 0.0152. Materials used for all specimens were also from the same batch. The study was aimed at understanding the design concept of the steel connecting box and detailing of column reinforcement for avoiding the brittle failure of precast concrete frame buildings. The experimental results show that without premature failure in welding or nut slipping, depending largely on the reinforcement details, the precast system with a steel box connection can be effectively used. Flexural failure mode with a ductile mechanism can be achieved to resemble the monolithic one. With a higher relative stiffness and capacities of the designed connecting box, the precast columns show a higher capacity as the failure section was shifted to an upper level. Hence, it can be said that the proper details of precast concrete columns contain acceptable seismic performances, e.g. ultimate capacity, stiffness, energy dissipation, and capacity degradation under repeated loading

Postoperative pain and bleeding after adenotonsillectomy versus adenotonsillotomy in pediatric obstructive sleep apnea an RCT

PURPOSE: Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain. METHODS: A double-blinded RCT including 79 children, aged 2-6 years, with moderate to severe OSA, randomized to either ATE (n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes (parent and child grading pain at different levels, days of analgesic use and return to normal diet). Peri- and postoperative bleeding were also registered. RESULTS: 63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free (p = 0.021, Log Rank Test), and first day the caregiver estimated pain VAS ≤ 5 (p = 0.007, Log Rank Test). Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group. CONCLUSIONS: The results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbidity between the surgical methods were minor the clinical significance is uncertain. TRIAL REGISTRATION: This study was approved by the Swedish Regional Ethics Board in Stockholm, Sweden (Dnr 2011/925-32 and 2013/2274-32) and registered at ClinicalTrials.gov (Trial registration number NCT01676181)