A Randomized Trial Evaluating Online 3-Dimensional Optical Frequency Domain Imaging-Guided Percutaneous Coronary Intervention in Bifurcation Lesions.
Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P=0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36-0.81]; P=0.003). Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02972489.


Does metoclopramide impair anastomotic healing of the left colon of rats?
To evaluate the effects of metoclopramide on the formation of adhesion and the healing of left colonic anastomoses in rats. Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of metoclopramide (experimental group - E) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). Adhesion was assessed, and a colonic segment containing the anastomosis was removed for analysis of breaking strength and hydroxyproline concentration. There were no deaths or dehiscence on the 3(rd) postoperative day. There was one death and one blocked anastomotic dehiscence in the E7 group. No significant differences between groups were found in the analysis of clinical outcome, intra-cavity adhesion, adhesion to the anastomosis or breaking strength on the 3(rd) and 7(th) postoperative day. Hydroxyproline concentration was higher in the control group on the 3(rd) (p=0.006) but not on the 7(th) postoperative day (p=0.241). Metoclopramide did not have harmful effects on the healing of intestinal anastomoses in rats.


Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65-/- mice.
To investigate the role of the myocyte enhancer factor 2 (Mef2) transcription factor family in retinal diseases, Mef2c expression was assessed during retinal degeneration in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA). Mef2c-dependent expression of photoreceptor-specific genes was further addressed. Expression of Mef2 members was analyzed by oligonucleotide microarray, quantitative PCR (qPCR), and in situ hybridization. Mef2c-dependent transcriptional activity was assayed by luciferase assay in HEK293T cells. Mef2c was the only Mef2 member markedly downregulated during retinal degeneration in Rpe65(-/-) mice. Mef2c mRNA level was decreased by more than 2-fold at 2 and 4 months and by 3.5-fold at 6 months in retinas of Rpe65(-/-) mice. Downregulation of Mef2c at the protein level was confirmed in Rpe65(-/-) retinas. The decrease in Mef2c mRNA levels in the developing Rpe65(-/-) retinas from postnatal day (P) 13 onward was concomitant with the decreased expression of the rod-specific transcription factors Nrl and Nr2e3. Nrl was further shown to drive Mef2c transcriptional activity, supporting a physiological role for Mef2c in the retina. In addition, Mef2c appeared to act as a transcriptional repressor of its own expression and the expression of the retina-specific retinal G-protein coupled receptor (Rgr), rhodopsin, and M-opsin genes. These findings highlight the early altered regulation of the rod-specific transcriptional network in Rpe65-related disease. They also indicate that Mef2c may act as a novel transcription factor involved in the development and the maintenance of photoreceptor cells.


The Results of the Surgical Treatment of Spontaneous Rhinorrhea via Craniotomy and the Contribution of CT Cisternography to the Detection of Exact Leakage Side of CSF.
To share the results of conventional surgery in rhinorrhea and the contribution of computerized tomography (CT) cisternography to determination of the site of cerebrospinal fluid (CSF) leak. Twelve cases treated for spontaneous rhinorrhea were included in this study. All the cases underwent cranial CT and magnetic resonance imaging (MRI). CT cisternography was performed in four patients whose bone defect or leakage site could not be detected by CT and MRI. In order to repair the defect, either the galea or galea together with collagen matrix was used and the procedure was supported with fibrin glue. In the cases, postoperative rhinorrhea was seen in neither the early nor the late follow up period. We observed no complications related to CT cisternography or craniotomy. The leakage area was successfully detected with CT cisternography when the other methods failed. Bone defect can usually be shown by means of CT. However, when bone-defect cannot be shown or the dura in the defective area is intact, CT cisternography is useful to show the CSF leak. Conventional surgery was very succesful in the treatment of spontaneous rhinorrhea but it was cosmetically problematic. In the patients both treated with galea and galea together with collagen matrix, the repair of the defect was successful.


ZBP1 enhances cell polarity and reduces chemotaxis.
The interaction of beta-actin mRNA with zipcode-binding protein 1 (ZBP1) is necessary for its localization to the lamellipod of fibroblasts and plays a crucial role in cell polarity and motility. Recently, we have shown that low ZBP1 levels correlate with tumor-cell invasion and metastasis. In order to establish a cause and effect relationship, we expressed ZBP1 in a metastatic rat mammary adenocarcinoma cell line (MTLn3) that has low endogenous ZBP1 levels and delocalized beta-actin mRNA. This leads to localization of beta-actin mRNA, and eventually reduces the chemotactic potential of the cells as well as their ability to move and orient towards vessels in tumors. To determine how ZBP1 leads to these two apparently contradictory aspects of cell behavior--increased cell motility but decreased chemotaxis--we examined cell motility in detail, both in cell culture and in vivo in tumors. We found that ZBP1 expression resulted in tumor cells with a stable polarized phenotype, and reduced their ability to move in response to a gradient in culture. To connect these results on cultured cells to the reduced metastatic ability of these cells, we used multiphoton imaging in vivo to examine tumor cell behavior in primary tumors. We found that ZBP1 expression actually reduced tumor cell motility and chemotaxis, presumably mediating their decreased metastatic potential by reducing their ability to respond to signals necessary for invasion.


Post-transcriptional exon shuffling events in humans can be evolutionarily conserved and abundant.
In silico analyses have established that transcripts from some genes can be processed into RNAs with rearranged exon order relative to genomic structure (post-transcriptional exon shuffling, or PTES). Although known to contribute to transcriptome diversity in some species, to date the structure, distribution, abundance, and functional significance of human PTES transcripts remains largely unknown. Here, using high-throughput transcriptome sequencing, we identify 205 putative human PTES products from 176 genes. We validate 72 out of 112 products analyzed using RT-PCR, and identify additional PTES products structurally related to 61% of validated targets. Sequencing of these additional products reveals GT-AG dinucleotides at >95% of the splice junctions, confirming that they are processed by the spliceosome. We show that most PTES transcripts are expressed in a wide variety of human tissues, that they can be polyadenylated, and that some are conserved in mouse. We also show that they can extend into 5' and 3' UTRs, consistent with formation via trans-splicing of independent pre-mRNA molecules. Finally, we use real-time PCR to compare the abundance of PTES exon junctions relative to canonical exon junctions within the transcripts from seven genes. PTES exon junctions are present at <0.01% to >90% of the levels of canonical junctions, with transcripts from MAN1A2, PHC3, TLE4, and CDK13 exhibiting the highest levels. This is the first systematic experimental analysis of PTES in human, and it suggests both that the phenomenon is much more widespread than previously thought and that some PTES transcripts could be functional.


Hirsutism and body mass index in a representative sample of Iranian people.
Hirsutism is the condition of excessive terminal hair growth in women with a typical male pattern distribution. Hirsutism is a common disorder that affects about 5% -10% of women of reproductive age. Adipose tissue contributes up to 50% of the circulating testosterone in premenopausal women Because of excessive androgen production in fat tissue. Therefore, it seems that hirsutism must be more common in people with simple obesity but controversy exist regarding this subject. The aim of this study is to evaluate the relation between Body Mass Index and hirsutism in a representative sample of Iranian woman. This is a cross sectional case control clinical trial. The study involved 800 individuals; 400 hirsute females and 400 healthy women as control group. The mean age of the participants was 28 ± 6.2 years. Hirsutism was determined by the Ferriman-Gallwey scoring system. Height and weight were measured by a Seca scale, Body Mass Index was calculated as weight/height² (kg/m²), and collected data were analyzed by SPSS software version 18 using T-test and chi-square statistical test. There were no significant differences between the two groups regarding age and height. However, Body Mass Index and weight were significantly higher in the case group than the control group. The chi square test revealed significant differences between the case and control groups regarding Body Mass Index (P < 0.001). In the current study hirsutism was more common in patients with a higher Body Mass Index. The increased frequency of hirsutism in overweight women could be explained by increased insulin resistance and more androgen production by adipose tissue.