A QTL Resource and Comparison Tool for Pigs: PigQTLDB

During the past decade, efforts to map quantitative trait loci (QTL) in pigs have resulted in hundreds of QTL being reported for growth, meat quality, reproduction, disease resistance, and other traits. It is a challenge to locate, interpret, and compare QTL results from different studies. We have developed a pig QTL database (PigQTLdb) that integrates available pig QTL data in the public domain, thus, facilitating the use of this QTL data in future studies. We also developed a pig trait classification system to standardize names of traits and to simplify organization and searching of the trait data. These steps made it possible to compare primary data from diverse sources and methods. We used existing pig map databases and other publicly available data resources (such as PubMed) to avoid redundant developmental work. The PigQTLdb was also designed to include data representing major genes and markers associated with a large effect on economically important traits. To date, over 790 QTL from 73 publications have been curated into the database. Those QTL cover more than 300 different traits. The data have been submitted to the Entrez Gene and the Map Viewer resources at NCBI, where the information about markers was matched to marker records in NCBI’s UniSTS database. Having these data in a public resource like NCBI allows regularly updated automatic matching of markers to public sequence data by e-PCR. The submitted data, and the results of these calculations, are retrievable from NCBI via Entrez Gene, Map Viewer, and UniSTS. Efforts were undertaken to improve the integrated functional genomics resources for pigs

Early Growth Response Factor-1 Is Associated With Intraluminal Thrombus Formation in Human Abdominal Aortic Aneurysm

ObjectivesThe goal of this study was to investigate the expression of early growth response-1 (Egr-1), a vascular pathogenic transcription factor, and its potential relationship with tissue factor (TF), a key player during the thrombus formation in the abdominal aortic aneurysm (AAA) wall.BackgroundAlthough intraluminal thrombus is a common finding in human AAA, the molecular mechanism of the thrombus formation has not been studied.MethodsDuring the elective AAA repair, specimens were taken from the thrombus-covered and thrombus-free portions of the aneurysmal wall in each of 16 patients with AAA and analyzed to assess the differential expression of Egr-1 and TF. The proinflammatory and prothrombogenic activities of Egr-1 in vasculature were evaluated in vitro and in vivo by overexpressing it using adenovirus.ResultsThe expression of both Egr-1 and TF was significantly increased in the thrombus-covered wall compared with the thrombus-free wall, in which their up-regulation in the thrombus-covered wall was strongly correlated with each other (p < 0.005, r = 0.717). Adenoviral overexpression of Egr-1 in human vascular smooth muscle and endothelial cells was found to up-regulate the expression of TF and inflammation-related genes. Moreover, Egr-1 overexpression in endothelial cells increased their adhesiveness to monocytes and also substantially promoted the intravascular thrombus formation in vivo, as shown in the inferior vena cava ligation experiment of the rat.ConclusionsThe present study demonstrates the differential up-regulation of Egr-1 in the thrombus-covered wall of human AAA and also suggests its possible contribution to the thrombogenic and inflammatory pathogenesis in human AAA

Pre-hospital i-gel blind intubation for trauma: a simulation study

Objective This study aimed to evaluate the efficacy of i-gel blind intubation (IGI) as a rescue device for definitive airway management in ground intubation for pre-hospital trauma patients. Methods A prospective randomized crossover study was conducted with 18 paramedics to examine intubation performance of two blind intubation techniques through a supraglottic airway devices (IGI and laryngeal mask airway Fastrach), compared with use of a Macintosh laryngoscope (MCL). Each intubation was conducted at two levels of patient positions (ground- and stretcher-level). Primary outcomes were the intubation time and the success rate for intubation. Results The intubation time (sec) of each intubation technique was not significantly different between the two positions. In both patient positions, the intubation time of IGI was shortest among the three intubation techniques (17.9±5.2 at the ground-level and 16.9±3.8 at the stretcher-level). In the analysis of cumulative success rate and intubation time, IGI was the fastest to reach 100% success among the three intubation techniques regardless of patient position (all P<0.017). The success of intubation was only affected by the intubation technique, and IGI achieved more success than MCL (odds ratio, 3.6; 95% confidence interval, 1.1 to 11.6; P=0.03). Conclusion The patient position did not affect intubation performance. Additionally, the intubation time with blind intubation through supraglottic airway devices, especially with IGI, was significantly shorter than that with MCL

Prognostic factors related with outcomes in traumatic out-of-hospital cardiac arrest patients without prehospital return of spontaneous circulation: a nationwide observational study

Objective To evaluate the prognostic factors associated with the sustained return of spontaneous circulation (ROSC) and survival to hospital discharge in traumatic out-of-hospital cardiac arrest (TOHCA) patients without prehospital ROSC. Methods We analyzed Korean nationwide data from the Out-of-Hospital Cardiac Arrest Surveillance, and included adult TOHCA patients without prehospital ROSC from January 2012 to December 2016. The primary outcome was sustained ROSC (>20 minutes). The secondary outcome was survival to discharge. Multivariate analysis was performed to investigate factors associated with the outcomes of TOHCA patients. Results Among 142,905 cases of OHCA, 8,326 TOHCA patients were investigated. In multivariate analysis, male sex (odds ratio [OR], 1.326; 95% confidence interval [CI], 1.103–1.594; P=0.003), and an initial shockable rhythm (OR, 1.956; 95% CI, 1.113–3.439; P=0.020) were significantly associated with sustained ROSC. Compared with traffic crash, collision (OR, 1.448; 95% CI, 1.086–1.930; P=0.012) was associated with sustained ROSC. Fall (OR, 0.723; 95% CI, 0.589–0.888; P=0.002) was inversely associated with sustained ROSC. Male sex (OR, 1.457; 95% CI, 1.026–2.069; P=0.035) and an initial shockable rhythm (OR, 4.724; 95% CI, 2.451–9.106; P<0.001) were significantly associated with survival to discharge. Metropolitan city (OR, 0.728; 95% CI, 0.541–0.980; P=0.037) was inversely associated with survival to discharge. Compared with traffic crash, collision (OR, 1.745; 95% CI, 1.125–2.708; P=0.013) was associated with survival to discharge. Conclusion Male sex, an initial shockable rhythm, and collision could be favorable factors for sustained ROSC, whereas fall could be an unfavorable factor. Male sex, non-metropolitan city, an initial shockable rhythm, and collision could be favorable factors in survival to discharge

A Randomized Comparison Simulating Face to Face Endotracheal Intubation of Pentax Airway Scope, C-MAC Video Laryngoscope, Glidescope Video Laryngoscope, and Macintosh Laryngoscope

Objectives. Early airway management is very important for severely ill patients. This study aimed to investigate the efficacy of face to face intubation in four different types of laryngoscopes (Macintosh laryngoscope, Pentax airway scope (AWS), Glidescope video laryngoscope (GVL), and C-MAC video laryngoscope (C-MAC)). Method. Ninety-five nurses and emergency medical technicians were trained to use the AWS, C-MAC, GVL and Macintosh laryngoscope with standard airway trainer manikin and face to face intubation. We compared VCET (vocal cord exposure time), tube pass time, 1st ventilation time, VCET to tube pass time, tube pass time to 1st ventilation time, and POGO (percentage of glottis opening) score. In addition, we compared success rate according to the number of attempts and complications. Result. VCET was similar among all laryngoscopes and POGO score was higher in AWS. AWS and Macintosh blade were faster than GVL and C-MAC in total intubation time. Face to face intubation success rate was lower in GVL than other laryngoscopes. Conclusion. AWS and Macintosh were favorable laryngoscopes in face to face intubation. GVL had disadvantage performing face to face intubation

Aldosterone Upregulates Connective Tissue Growth Factor Gene Expression via p38 MAPK Pathway and Mineralocorticoid Receptor in Ventricular Myocytes

The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pattern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each pathway revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/AimsThe aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.MethodsOne hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.ResultsAccording to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.ConclusionsSerum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction

Transcript characterization in the region of the mouse neuromuscular mutationmnd2.

The mouse mutation mnd2 provides an experimental model for studying human neuromuscular and neurodegenerative disease. In order to identify the mnd2 gene, a positional cloning approach was taken. Linkage analysis demonstrated that mnd2 maps to a 0.2 $\pm$ 0.1 cM nonrecombinant interval in the central region of mouse chromosome 6, a region corresponding to human chromosome 2p13. To span this region, a contig of seven BAC clones and seven P1 clones was generated. The physical size of the nonrecombinant interval was between 360 kb and 500 kb. Four previously known genes were mapped to the nonrecombinant region: dynactin 1, smooth muscle gamma-actin, rhotekin, and p62Dok. Five novel genes in the region were identified by exon amplification, cross-species conservation, direct genomic sequencing, and mouse/human comparative sequence analysis. These are: a new member of the semaphorin gene family, semaphorin M; a new member of the WD-repeat gene family, D6Mm3e; a lysyl oxidase-related gene, Lor2; the evolutionary conserved gene, Aup1; and a novel gene, Gene7. Six genes were eliminated as candidates for mnd2 based on normal mRNA size, abundance, and coding sequence. The remaining three genes--semaM, Lor2, and Gene7--are under continued investigation. The gene order in the mnd2 region between the flanking markers D6Mit164 and D6Mit128 is: centromere - semaphorin M - Gene7 - p62\rm\sp{Dok} - Lor2 - Aup1 - rhotekin - D6Mm3e - dynactin1 - smooth muscle $\gamma$ - actin - telomere. Comparison of different gene identification strategies showed that direct genomic sequencing is the most efficient gene-identification method for this gene-rich chromosomal region. Continued application of the strategy described here is expected to result in identification of the gene that causes the mnd2 phenotype. Elucidation of the molecular defect and its consequences for the pathophysiology of mnd2 mice will broaden our knowledge of molecular mechanisms involved in development and maintenance of the neuromuscular system.Ph.D.Biological SciencesGeneticsMolecular biologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131232/2/9840562.pd