MIRNA-DISTILLER: A Stand-Alone Application to Compile microRNA Data from Databases

MicroRNAs (miRNA) are small non-coding RNA molecules of ∼22 nucleotides which regulate large numbers of genes by binding to seed sequences at the 3′-untranslated region of target gene transcripts. The target mRNA is then usually degraded or translation is inhibited, although thus resulting in posttranscriptional down regulation of gene expression at the mRNA and/or protein level. Due to the bioinformatic difficulties in predicting functional miRNA binding sites, several publically available databases have been developed that predict miRNA binding sites based on different algorithms. The parallel use of different databases is currently indispensable, but highly uncomfortable and time consuming, especially when working with numerous genes of interest. We have therefore developed a new stand-alone program, termed MIRNA-DISTILLER, which allows to compile miRNA data for given target genes from public databases. Currently implemented are TargetScan, microCosm, and miRDB, which may be queried independently, pairwise, or together to calculate the respective intersections. Data are stored locally for application of further analysis tools including freely definable biological parameter filters, customized output-lists for both miRNAs and target genes, and various graphical facilities. The software, a data example file and a tutorial are freely available at http://www.ikp-stuttgart.de/content/language1/html/10415.as

The Isolated Orbital Floor Fracture from a Transconjunctival or Subciliary Perspective-A Standardized Anthropometric Evaluation

Background: The influence of orbital fractures and their repair on the rate of deformities of the lower eyelid is an ongoing source of discussion in the literature. Most of the present studies include isolated blow-out as well as combined orbital fractures. Material and Methods: We present a retrospective evaluation of a series of 100 patients after isolated blow-out fracture repair using reference anthropometric data on standardized photographs. Analysis included eye fissure width and height, lid sulcus height, upper lid height, upper and lower iris coverage, position of cornea to palpebra inferior, canthal tilt, scleral show, ectropion and entropion. It was clearly distinguished between operated and contralateral eyelid, whether a transconjunctival or a subciliary approach was performed and amount of fracture. Our main interests were changes of the aforementioned parameters with regards to eyelid deformities. Results: Surgery per se did not significantly influence eyelid deformities. However, the surgical approach selected significantly affected eye fissure index, lower iris coverage and rate of scleral show, indicating retraction of the lower eyelid. Conclusions: The standardized measurements described here are accurate and objective to evaluate postoperative results. The subciliary approach included the highest risk of lower lid retraction as compared to transconjunctival approaches

Quality of Postoperative Pain Management after Midfacial Fracture Repair—An Outcome-oriented Study

Objectives There is a lack of literature regarding the procedure-specific quality of acute postoperative pain management after midfacial fracture repair. The purpose of the presented prospective clinical study was to evaluate postoperative pain management after surgical repair of midfacial fractures. Materials and methods Eighty-five adults were evaluated on the first postoperative day following midfacial repair using the questionnaire of the Quality Improvement in Postoperative Pain Management (QUIPS) project. The main outcome measures were patients’ characteristics and clinical- and patient-reported outcome parameters. Results Overall, pain on the first postoperative day was moderate. A significant correlation between process and outcome parameters could be shown. Duration of surgery above the calculated median was significantly associated with higher maximum pain intensity (p = 0.017). Patients requiring opioids in the recovery room presented significantly higher pain on activity (p = 0.029) and maximum pain (p = 0.035). Sleeping impairment (p = 0.001) and mood disturbance (p = 0.008) were significantly more prevalent in patients undergoing repair of a centrolateral midfacial fracture. Conclusions QUIPS is a simple and qualified tool to evaluate the procedure specific quality of acute postoperative pain management. Pain on the first postoperative day following midfacial fracture repair seems overall to be moderate. Nearly a third of the patients showed inadequate postoperative pain management. To prevent inadequate postoperative pain management, it is necessary to establish a continued procedure-specific outcome measurement

Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients

Introduction Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. Material and methods In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. Results In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. Discussion Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings

Special Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters Expression Variability of Absorption, Distribution, Metabolism, Excretion-Related MicroRNAs in Human Liver: Influence of Nongenetic Factors and Association with Gene Ex

ABSTRACT Genes that are important for the detoxification of drugs and other xenobiotics show a high degree of interindividual variation attributable to regulation by diverse genetic, nongenetic, and epigenetic mechanisms including microRNAs (miRNAs). We selected a set of 56 miRNAs predicted to target the 39-untranslated region of absorption, distribution, metabolism, excretion (ADME) genes to assess their hepatic expression levels and interindividual variability in a well-documented human liver tissue cohort (n = 92), together with the well-known hepatic miRNAs miR-122, miR-21, miR-27b, and miR-148a. Quantification by stem-loop real-time reversetranscription polymerase chain reaction confirmed high expression for these microRNAs and revealed particularly strong variability of expression (>1000-fold) for miR-539, miR-200c, miR-31, miR-15a, and miR-22. Association analysis revealed a high degree of correlation among various miRNAs, suggesting coregulation. Statistical analysis considering liver donor meta-data including correction for multiple testing revealed strongly elevated levels of miR-21, miR-34a, miR-130b, and miR-132 in cholestatic liver and of miR-21 and miR-130b during inflammation, as indicated by elevated C-reactive protein levels in serum. Although none of the miRNAs was strongly associated with sex, several miRNAs, including miR-34a and miR-200a/b, were positively correlated with age. Association analysis with ADME gene expression profiles and with cytochrome P450 gene expression phenotypes (mRNA, protein, enzymatic activity) revealed numerous significant correlations. Negatively affected protein and/or activity levels were observed for CYP1A1 (e.g., miR-132, miR-142-3p, miR-21), CYP2A6 (miR-142-3p, miR-21), CYP2C19 (e.g., miR-130b, miR-185, miR-34a), and CYP2E1 (miR-10a, let-7g, miR-200c). These data should be useful to further elucidate regulatory functions of miRNAs in liver pathophysiology and regulation of ADME gene expression

Morphologic outcome of bimaxillary surgery–An anthropometric appraisal

Objectives: To adequately perform orthognathic surgery procedures, it is from basic interest to understand the morphologic changes caused by orthognathic surgery. Anthropometric analyses of standardized frontal view and profile photographs could help to investigate and understand such changes. Study Design: We present a pre- to postoperative evaluation of orthognathic surgery results based on anthropometric indices described by Farkas and cephalometric measurements. 30 Class III patients undergoing maxillary advancement by Le Fort I Osteotomy and mandibular setback by bilateral sagittal split osteotomy were evaluated. Preoperative as well as three and nine months postoperative lateral cephalograms as well as standardized frontal view and profile photographs were taken. On the photographs 21 anthropometric indices given by Farkas were evaluated. In cephalograms SNA and SNB angle as well as Wits appraisal were investigated. Results: The investigated anthropometric indices showed a significant increase of the vertical height of the upper lip without changing the relation of the upper vermilion to the cutaneous upper lip. The lower vermilion height increased relatively to the cutaneous lower lip without vertical changes in the lower lip. Due to maxillary advancement the upper face height increased meanwhile the lower face height decreased due to mandibular setback. SNA and SNB angle and Wits appraisal showed typical changes related to surgery. Conclusions: The investigated photo-assisted anthropometric measurements presented reproducible results related to bimaxillary surgery

Bilateral Sagittal Split Osteotomy-parameters and Correlations of Postoperative Pain Management

Objectives Postoperative pain management is of utmost interest for patients undergoing orthognathic surgery. Currently, there is a lack of information regarding process and outcome parameters of postoperative pain management after bilateral sagittal split osteotomy. Materials and methods In a prospective clinical study, 31 adults were evaluated on the first postoperative day following bilateral sagittal split osteotomy using the standardized questionnaire of the Germany-wide project Quality Improvement in Postoperative Pain Management (QUIPS). It allows a standardized assessment of patients’ characteristics, pain parameters, outcome, and pain therapy process parameters. Results Pain management consisted mainly of premedication with midazolam, sufentanil, and metamizol intraoperatively; piritramide in the recovery room; and metamizol and tramadol on ward. Twenty patients (64.5%) showed inadequate pain management with pain levels ≥4. Patients receiving tramadol as opioid on ward presented significantly higher maximum pain levels (p = .037). Significantly lower satisfaction with postoperative pain intensity (p \u3e .001) and significantly higher desire for additional pain medication (p = .023) were detected, when duration of surgery was above the median of 107.5 min. Conclusions Inadequate pain management on the first postoperative day following bilateral sagittal split osteotomy was widespread on our ward. QUIPS helped us to identify it and thereby gave us the possibility to improve the situation. Prolonged duration of surgery seems to be a predictor of an elevated postoperative pain medication demand. Clinical relevance Only the establishment of an ongoing monitoring of postoperative pain management can help to reduce or even avoid inadequate postoperative pain management. In accordance to the existing literature, we found inadequate postoperative pain management more widespread than thought

Cranio-Maxillofacial Reconstruction with Microvascular Radialis Flaps—Parameters and Correlations of Postoperative Pain Management

Objectives Postoperative pain management is of highest interest for patients undergoing maxillofacial surgery including microvascular reconstructive surgery. Currently, there is a lack of information regarding process and outcome of postoperative pain management after microvascular reconstruction. Materials and methods In a prospective clinical study, 31 adults were evaluated on the first postoperative day following microvascular reconstruction with a radial forearm flap using the standardized questionnaire of the Germany-wide project Quality Improvement in Postoperative Pain Management (QUIPS). It enables a standardized assessment of patients’ characteristics, pain parameters, outcome and pain therapy process parameters. Results Pain management consisted predominately of premedication with midazolam, sufentanil and metamizol intraoperatively, piritramid in the intensive care unit and metamizol, tramadol and fentanyl patches on ward. Nineteen patients (61.3 %) showed inadequate pain management with pain levels ≥4. Among other significant relations, patients exhibiting an age below the median presented significant higher levels of pain under strain (p = .041) and maximum pain (p = .006) as well as rate of breathing (p = .009) and mood (p = .006) disturbance. Performance of pain counselling showed specific impact on pain under strain (p = .008), maximum pain (p = .004) and satisfaction with pain intensity (p = .001). Whether microvascular reconstruction was performed with primary or secondary intention or performance of a neck dissection did not show significant influence. Conclusions QUIPS helped us to adequately evaluate the procedure-specific quality of postoperative management following microvascular reconstruction with a radial forearm flap. It helped us to identify a surprisingly high amount of inadequate pain management. Postoperative pain levels seem to be primarily influenced by the performed reconstruction. Clinical relevance Establishment of a continuous and procedure-specific evaluation of postoperative pain levels should help to avoid inadequate pain management, which is widely prevalent according to the literature and our study. Preoperative pain counselling is essential and should be procedure specific to be its best

Long-term optical variability of PKS 2155-304

Aims: The optical variability of the blazar PKS 2155-304 is investigated to characterise the red noise behaviour at largely different time scales from 20 days to O(>10 yrs). Methods: The long-term optical light curve of PKS 2155-304 is assembled from archival data as well as from so-far unpublished observations mostly carried out with the ROTSE-III and the ASAS robotic telescopes. A forward folding technique is used to determine the best-fit parameters for a model of a power law with a break in the power spectral density function (PSD). The best-fit parameters are estimated using a maximum-likelihood method with simulated light curves in conjunction with the Lomb Scargle Periodogram (LSP) and the first-order Structure Function (SF). In addition, a new approach based upon the so-called Multiple Fragments Variance Function (MFVF) is introduced and compared to the other methods. Simulated light curves have been used to confirm the reliability of these methods as well as to estimate the uncertainties of the best-fit parameters. Results: The light curve is consistent with the assumed broken power-law PSD. All three methods agree within the estimated uncertainties with the MFVF providing the most accurate results. The red-noise behaviour of the PSD in frequency f follows a power law with f^-{\beta}, {\beta}=1.8 +0.1/-0.2 and a break towards f^0 at frequencies lower than f_min=(2.7 +2.2/-1.6 yrs)^-1.Comment: 10 pages, 8 figures, the ROTSE-light curve can be downloaded from http://vizier.cfa.harvard.edu/viz-bin/VizieR?-source=J/A+A/531/A12