Distinct ligand binding sites in integrin alpha3beta1 regulate matrix adhesion and cell-cell contact.

The integrin alpha3beta1 mediates cellular adhesion to the matrix ligand laminin-5. A second integrin ligand, the urokinase receptor (uPAR), associates with alpha3beta1 via a surface loop within the alpha3 beta-propeller (residues 242-246) but outside the laminin binding region, suggesting that uPAR-integrin interactions could signal differently from matrix engagement. To explore this, alpha3-/- epithelial cells were reconstituted with wild-type (wt) alpha3 or alpha3 with Ala mutations within the uPAR-interacting loop (H245A or R244A). Wt or mutant-bearing cells showed comparable expression and adhesion to laminin-5. Cells expressing wt alpha3 and uPAR dissociated in culture, with increased Src activity, up-regulation of SLUG, and down-regulation of E-cadherin and gamma-catenin. Src kinase inhibition or expression of Src 1-251 restored the epithelial phenotype. The H245A and R244A mutants were unaffected by coexpression of uPAR. We conclude that alpha3beta1 regulates both cell-cell contact and matrix adhesion, but through distinct protein interaction sites within its beta-propeller. These studies reveal an integrin- and Src-dependent pathway for SLUG expression and mesenchymal transition

Assessment of Altmetrics and PlumX Metrics Scoring as Mechanisms to Evaluate the Top 100 Trending Hidradenitis Suppurativa Articles on Social Media: Cross-Sectional Study

Background: Dermatologists are increasingly utilizing social media platforms to disseminate scientific information. New tools, such as altmetrics and PlumX metrics, have been made available to rapidly capture the level of scientific article dissemination across social media platforms. However, no studies have been performed to assess the level of scientific article dissemination across social media regarding hidradenitis suppurativa, a disease that is still currently not well understood. Objective: The aim of our study was to evaluate the utility of altmetrics and PlumX metrics by characterizing the top 100 “trending” hidradenitis suppurativa articles in the altmetric database by the altmetric attention score and PlumX score. Methods: Altmetric data components of the top 100 hidradenitis suppurativa articles were extracted from the altmetric database. Article citation count was found using Web of Science. PlumX field-weighted impact scores for each article were collected from the Scopus database. Journal title, open-access status, article type, and study design of original articles were assessed. Additionally, the altmetric attention score, PlumX score, and citation count were log transformed and adjusted by +1 for linear regression, and Spearman correlation coefficients were utilized to determine correlations. Results: Most of the top 100 “trending” hidradenitis suppurativa articles were published in JAMA Dermatology (n=27, 27%). The median altmetric attention score, PlumX score, and citation count were 25.5, 3.7, and 10.5, respectively. The most mentions regarding social media platforms came from Twitter. Although no correlation was observed between the citation count and altmetric attention score (r 2 =0.019, P=.17), positive correlation was observed between the citation count and PlumX score (r 2 =0.469, P\u3c.001). Conclusions: Our research demonstrated that citation count is not correlated with the altmetric attention score, but is strongly correlated with the PlumX score regarding hidradenitis suppurativa articles at this point in time. With the continual increase of social media usage by medical professionals and researchers, this study can help investigators understand the best way to captivate their audience

Total Hip Arthroplasty: COPD and its Effect on Postoperative Complications

Introduction The demand for Total Hip Arthroplasty (THA) has rapidly risen and continues to due to high success rates of this procedure and the growing aging population. Particularly in Chronic Obstructive Pulmonary Disease (COPD), studies have indicated an increased risk of various postoperative complications across several surgery types. Despite the prevalence of COPD, very little has been investigated regarding postsurgical complications in patients with COPD following a THA. The aim of the current study is to utilize the NSQIP database and determine differences in short-term postoperative complications after undergoing THA, comparing patients with and without COPD. Methods In total, 74,814 patients were included in the analysis looking at how COPD contributes to the rates of postoperative complications in primary THA. Data was obtained from the National Surgical Quality Improvement Project Database years 2005-2014, with readmission/reoperation data beginning in 2011. THA cases were selected out of the database using current procedural terminology (CPT) code 27130. On univariate analysis, p-values were calculated using chi-square for categorical variables and one-way ANOVA for continuous variables. On multivariate analysis, logistic regression was used to control for preoperative comorbidities and calculate p-values. Results On multivariate analysis and after controlling for contributing comorbidities, having COPD was found to be an independent predictor of superficial surgical site infection (OR: 1.74), pneumonia (OR: 3.69), reintubation (OR: 2.65) failure to wean (OR: 3.45), urinary tract infection (OR: 1.46), needing a postoperative transfusion (OR: 1.19), and sepsis (OR: 1.97). COPD also independently predicted whether a patient would be discharged home or not (OR: 1.50). Discussion Although COPD has been linked to negative postoperative outcomes across several surgeries, few studies have examined postsurgical complications in patients with COPD following a THA. Our study found patients with COPD to have higher rates of superficial surgical site infection, pneumonia, reintubation, failure to wean, urinary tract infection, needing a postoperative transfusion, and sepsis. COPD also independently predicted whether a patient would be discharged home or not. Managing high-risk surgical patients requires a better understanding of possible complications a patient faces and enhancing perioperative conditions to improve outcomes. Given our study identified certain complications as independent risk factors for patients with COPD, surgeons and other healthcare providers can use this information to more accurately counsel patients and make perioperative adjustments accordingly

Lumbar Decompression Surgery: Does Chronic Steroid Use Increase the Risk of Postoperative Infectious Complications? – A Study of the National Surgical Quality Improvement Program (NSQIP) Database

Intro: It has long been established that corticosteroids have a negative impact on the human immune system’s ability to function at an optimal level. Many past studies have shown that patient’s will have higher rates of infection if they are taking chronic steroids. What has yet to be established is just how much of an increased risk patients on chronic steroids have for infection after undergoing lumbar decompression surgeries, of which there are thousands per year. We hypothesize that patients on chronic steroids will have higher rates of surgical site infections and higher rates of other infections (UTI, pneumonia, etc.) after undergoing lumbar decompression surgery of the spine. Methods: To test our hypothesis, we looked at the ACS National Surgical Quality Improvement Program (NSQIP) database data from 2005-2014. Using CPT codes, we selected out all spine surgeries where the purpose of surgery was to decompress an area of the lumbar spine, including herniated discectomies, laminectomies, among others. Chi-square analysis was done to evaluate for differences among the steroid and non-steroid groups for demographics, preoperative comorbidities, and postoperative complications. Binary regression analysis was done to determine if chronic steroid use independently predicts rates of postoperative infections. Results: Though chronic steroid use was not found to increase rates of surgical site infections, chronic steroid use was found to independently predict rates of pneumonia (OR: 3.06, p=0.030) and septic shock (OR: 3.79, p=0.008). Discussion: While steroid use has been established as immunosuppressive, it has not been established to what extent steroid use increases infection rates postoperatively in lumbar decompression surgeries, of which there are thousands each year. Spine surgeons should remain vigilant regarding postoperative infections in patients on chronic steroids, especially as it relates to pneumonia and propensity to decompensate into septic shock as these occur at significantly higher rates than the general population

High Sensitivity Array Observations of the z=1.87 Sub-Millimeter Galaxy GOODS 850-3

We present sensitive phase-referenced VLBI results on the radio continuum emission from the z=1.87 luminous submillimeter galaxy (SMG) GOODS 850-3. The observations were carried out at 1.4 GHz using the High Sensitivity Array (HSA). Our sensitive tapered VLBI image of GOODS 850-3 at 0.47 x 0.34 arcsec (3.9 x 2.9 kpc) resolution shows a marginally resolved continuum structure with a peak flux density of 148 \pm 38 uJy/beam, and a total flux density of 168 \pm 73 uJy, consistent with previous VLA and MERLIN measurements. The derived intrinsic brightness temperature is > 5 \pm 2 x 10^3 K. The radio continuum position of this galaxy coincides with a bright and extended near-infrared source that nearly disappears in the deep HST optical image, indicating a dusty source of nearly 9 kpc in diameter. No continuum emission is detected at the full VLBI resolution (13.2 x 7.2 mas, 111 x 61 pc), with a 4-sigma point source upper limit of 26 uJy/beam, or an upper limit to the intrinsic brightness temperature of 4.7 x 10^5 K. The extent of the observed continuum source at 1.4 GHz and the derived brightness temperature limits are consistent with the radio emission (and thus presumably the far-infrared emission) being powered by a major starburst in GOODS 850-3, with a star formation rate of ~2500 M_sun/yr. Moreover, the absence of any continuum emission at the full resolution of the VLBI observations indicates the lack of a compact radio AGN source in this z=1.87 SMG.Comment: 19 pages, 4 figures, accepted for publication in A