Identification of Mammalian Mediator Subunits with Similarities to Yeast Mediator Subunits Srb5, Srb6, Med11, and Rox3

The Mediator is a multiprotein coactivator required for activation of RNA polymerase II transcription by DNA binding transactivators. We recently identified a mammalian homologue of yeast Mediator subunit Med8 and partially purified a Med8-containing Mediator complex from rat liver nuclei (Brower, C. S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause, A., Stearman, R., Klausner, R. D., Malik, S., Lane, W. S., Sorokina, I., Roeder, R. G., Conaway, J. W., and Conaway, R. C. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 10353-10358). Analysis of proteins present in the most highly purified Med8-containing fractions by tandem mass spectrometry led to the identification of many known mammalian Mediator subunits, as well as four potential Mediator subunits exhibiting sequence similarity to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3. Here we present direct biochemical evidence that these four proteins are bona fide mammalian Mediator subunits. In addition, we identify direct pairwise binding partners of these proteins among the known mammalian Mediator subunits. Taken together, our findings identify a collection of novel mammalian Mediator subunits and shed new light on the underlying architecture of the mammalian Mediator complex

Federal Cutbacks and Working AFDC Recipients: A Preliminary Impact Analysis in Rural Minnesota.

Prepared by the Center for Urban and Regional Affairs and the Center for Health Services Research, University of Minnesota, with funding from the Bush Foundation, Hennepin County, the Minneapolis Foundation, Minnesota Department of Energy, Planning and D

Predictors of Outcomes of Non-Surgical Management for Acetabular Labral Tears

Objectives: Acetabular labral tears are increasingly recognized as a source of hip pain in the younger, active population. Due to a significant focus on surgical intervention, there has been limited investigation on the predictive factors and natural history of non-surgical management of these injuries. Many reports recommend a trial of non-operative management with a variety of modalities including physical therapy, education, non-steroidal anti-inflammatories (NSAIDs), intra-articular injections, and activity modification. However, there is limited data supporting these claims as few studies have explored non-surgical management. Additionally, the authors were not able to find any studies on factors that portend outcomes of non-operative management. We hypothesized that patients with more significant bony FAI pathology or more severe osteoarthritis would have poorer outcomes. Methods: Eighty patients with acetabular labral tears, confirmed by MRI, receiving a minimum of one year of non-surgical management were identified. Subjects completed baseline patient reported outcome measures (PROMs: mHHS, HOS-ADL, HOS-SS, iHOT-33). Sixty five (81.25%) patients completed the same one-year follow-up functional outcomes measures in addition to a satisfaction questionnaire (37F, 28 M). Chart review was conducted to obtain demographic information and radiographic information (Tonnis grade, alpha angle, center edge angle, chondral damage, cartilage defects, cysts, and subchondral edema). Statistical significance (p55 (cam lesion) resulted in significantly worse outcomes across all PROMs although CEA>40 (pincer lesion) only reached significance for the HOS ADL and SSS. CEA40 0.0684 0.0185 0.0216 0.0838 No 10(14.7) 12(19) 19(30) 20(24) Yes 0.9(13.2) 1(12) -2(22) 3.8(25.2) Alpha>55 0.0001 0.0079 0.001 0.0001 No 12.1(14.1) 13(19) 21(29) 25.1(20.6) Yes -4.0(9.0) -1(14) -4(20) -10.4(17.2) Change in patient reported outcome measures from baseline to follow-up for cartilage status mHHS p value HOS-ADL p value HOS-SSS p value iHOT-33 p value Edema 0.0945 0.8995 0.8333 0.1312 No 10.2 (14.4) 10 (20) 16 (28) 20.4 (21.9) Yes 1.8 (14.7) 10 (14) 14 (37) 4.6 (32.5) Cartilage Degeneration 0.0001 0.0001 0.0001 0.0001 No 18.0 (9.1) 19(17) 29(27) 31.7(17.0) Yes -5.4(9.4) -3(12) -4(22) -4.0(17.9) Cartilage Defect 0.0001 0.0009 0.0089 0.0002 No 12.0(13.3) 14(18) 20(28) 22.7(22.9) Yes -6.4 (11.2) -6 (11) -5 (26) -5.9 (18.4

“In-Round” Labral Repair After Acetabular Recession Using Intermittent Traction

The prevalence of hip arthroscopy has increased exponentially with the advent of arthroscopic labral repair techniques for femoroacetabular impingement. The goal of arthroscopic labral repair is to re-create the anatomic suction seal of the labrum against the femoral head. This important anatomic relationship has been demonstrated in several biomechanical studies. Performing the acetabular recession and evaluating the congruity of labral repairs during surgery is difficult with the application of traction distracting the femoral head from the chondrolabral junction. Additionally, prolonged traction risks nerve injury during hip arthroscopy. The purpose of this technique article is to describe a method of using traction only for central compartment work, and releasing the traction to allow the femoral head to reduce the labrum to its anatomic position for acetabular recession, anchor placement, and suture fixation. In this manner, the presented technique prevents an “out-of-round” or everted repair. This technique re-creates the native anatomy and biomechanics of the hip after acetabular recession and labral repair while decreasing traction time

Puncture Capsulotomy Technique for Hip Arthroscopy: Midterm Functional Outcomes

Background: The most common surgical approaches in hip arthroscopy are interportal and T-capsulotomy. However, these methods may introduce capsular instability. Puncture capsulotomy preserves capsuloligamentous integrity by avoiding iatrogenic transection of the iliofemoral capsular ligament. Purpose: To present minimum 2-year functional outcomes for patients who underwent arthroscopic treatment for acetabular labral tears and concomitant femoroacetabular impingement using the puncture capsulotomy technique. Study design: Case series; Level of evidence, 4. Methods: The authors conducted a retrospective review of prospectively collected data on patients who underwent arthroscopic acetabular labral tear treatment between December 2013 and May 2019. Included were patients aged ≥18 years who underwent hip arthroscopy by a single surgeon and completed a minimum of 2 years of patient-reported outcome measure (PROM) surveys. Intraoperatively, patients underwent hip arthroscopy via puncture capsulotomy to treat labral tears and any concomitant femoroacetabular impingement. Clinical outcome data consisted of PROMs. Results: A total of 163 hips were included; the mean patient follow-up was 30.4 months (range, 24-60 months; 95% CI, 28.5-32.3 months). Patients had a mean age of 37.9 years (range, 36.1-39.6 years), with a mean body mass index of 25.9 (range, 25.2-26.5). There were significant improvements in mean [95% CI] baseline to final follow-up scores for the 33-Item International Hip Outcome Tool (iHOT-33) (39.6 [36.8-42.4] vs 76.1 [72.7-79.6]), Hip Outcome Score-Activities of Daily Living (70.0 [67.0-73.0] vs 89.3 [87.3-91.3]), modified Harris Hip Score (60.1 [57.9-62.4] vs 84.9 [82.5-87.2]), and Hip Outcome Score-Sports Specific Subscale (41.8 [37.9-45.6] vs 75.7 [71.7-79.7]) (P \u3c .001 for all). Additionally, the mean [95% CI] visual analog scale pain scores were noted to significantly improve throughout the duration of the postoperative period (from 6.3 [5.9-6.7] to 2.2 [1.8-2.6]; P \u3c .001). There were no incidences of infection, avascular necrosis of the femoral head, dislocation/instability, or femoral neck fracture. At the 2-year follow-up, 81.0%, 62.0%, and 58.9% of hips achieved previously published clinically meaningful iHOT-33 thresholds for minimally clinically important difference, Patient Acceptable Symptom Score, and substantial clinical benefit, respectively. Conclusion: Puncture capsulotomy demonstrated significantly improved functional and clinically meaningful outcomes at a minimum 2-year follow-up, along with a minimal complication rate

Methylmercury cycling in sediments on the continental shelf of southern New England

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 70 (2006): 918-930, doi:10.1016/j.gca.2005.10.020.Exposure of humans to monomethylmercury (MMHg) occurs primarily through consumption of marine fish, yet there is limited understanding concerning the bioaccumulation and biogeochemistry of MMHg in the biologically productive coastal ocean. We examined the cycling of MMHg in sediments at three locations on the continental shelf of southern New England in September 2003. MMHg in surface sediments is related positively to inorganic Hg (Hg(II)=total Hg-MMHg), the geographical distribution of which is influenced by organic material. Organic matter also largely controls the sediment-water partitioning of Hg species and governs the availability of dissolved Hg(II) for methylation. Potential gross rates of MMHg production, assayed by experimental addition of 200Hg to intact sediment cores, are correlated inversely with the distribution coefficient (KD) of Hg(II) and positively with the concentration of Hg(II), most probably as HgS0, in 0.2-µm filtered pore water of these low-sulfide deposits. Moreover, the efflux of dissolved MMHg to overlying water (i.e., net production at steady state) is correlated with the gross potential rate of MMHg production in surface sediments. These results suggest that the production and efflux of MMHg from coastal marine sediments is limited by Hg(II), loadings of which presumably are principally from atmospheric deposition to this region of the continental shelf. The estimated diffusive flux of MMHg from the shelf sediments averages 9 pmol m-2 d-1. This flux is comparable to that required to sustain the current rate of MMHg accumulation by marine fish, and may be enhanced by the efflux of MMHg from near-shore deposits contaminated more substantially with anthropogenic Hg. Hence, production and subsequent mobilization of MMHg from sediments in the coastal zone may be a major source of MMHg to the ocean and marine biota, including fishes consumed by humans.This research was supported by a STAR student fellowship (U91591801) and grant (R827635) from the U.S. Environmental Protection Agency, a graduate student fellowship and grant from the Hudson River Foundation for Environmental Research, and the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Doherty Foundation

Proton Pump Inhibitor Use Affects Pseudarthrosis Rates and Influences Patient-Reported Outcomes.

Study Design: Retrospective cohort review. Objectives: Cervical pseudarthrosis is a frequent cause of need for revision anterior cervical discectomy and fusion (ACDF) and may lead to worse patient-reported outcomes. The effect of proton pump inhibitors on cervical fusion rates are unknown. The purpose of this study was to determine if patients taking PPIs have higher rates of nonunion after ACDF. Methods: A retrospective cohort review was performed to compare patients who were taking PPIs preoperatively with those not taking PPIs prior to ACDF. Patients younger than 18 years of age, those with less than 1-year follow-up, and those undergoing surgery for trauma, tumor, infection, or revision were excluded. The rates of clinically diagnosed pseudarthrosis and radiographic pseudarthrosis were compared between PPI groups. Patient outcomes, pseudarthrosis rates, and revision rates were compared between PPI groups using either multiple linear or logistic regression analysis, controlling for demographic and operative variables. Results: Out of 264 patients, 58 patients were in the PPI group and 206 were in the non-PPI group. A total of 23 (8.71%) patients were clinically diagnosed with pseudarthrosis with a significant difference between PPI and non-PPI groups (P = .009). Using multiple linear regression, PPI use was not found to significantly affect any patient-reported outcome measure. However, based on logistic regression, PPI use was found to increase the odds of clinically diagnosed pseudarthrosis (odds ratio 3.552, P = .014). Additionally, clinically diagnosed pseudarthrosis negatively influenced improvement in PCS-12 scores (P = .022). Conclusions: PPI use was found to be a significant predictor of clinically diagnosed pseudarthrosis following ACDF surgery. Furthermore, clinically diagnosed pseudarthrosis negatively influenced improvement in PCS-12 scores