CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate,Lymph Node Metastasis Rate,and Associated Predictive Variables

Annals of Surgical Oncology - The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess...     

A New Bracket System for Lingual Orthodontic Treatment Part 1: Theoretical Background and Development

Background and Method: This paper presents a new lingual bracket system differing fundamentally both in design and in manufacturing methods from existing appliances. Using state-of-the-art CAD/CAM technology, the two normally separate processes of bracket production and bracket positioning are fused into one unit. In this process, the demand for maximum individuality with simultaneously minimized space requirements is put consistently into practice. Results and Conclusion: Improved patient comfort, simplified rebonding in the event of bracket loss, and enhanced finishing precision are the improvements resulting for the course of treatment. In addition, bracket manufacture by a Rapid Prototyping technique permits direct transfer to clinically purposeful further developments. Zusammenfassung Hintergrund und Methode: In diesem Artikel wird ein neues linguales Bracketsystem vorgestellt, das sich von den bekannten Apparaturen sowohl in der Konzeption als auch in der Herstellung grundlegend unterscheidet. Die beiden gewöhnlich separat ablaufenden Prozesse der Bracketfertigung und Bracketpositionierung werden mit Hilfe moderner CAD/CAM-Technologie zur einer Einheit verschmolzen. Die Forderung nach maximaler Individualität bei gleichzeitig minimalem Platzbedarf wird dabei konsequent umgesetzt. Ergebnisse und Schlussfolgerung: Verbesserter Patientenkomfort, einfacheres Nachkleben im Falle eines Bracketverlustes und präziseres Finishing sind die für den Behandlungsverlauf resultierenden Verbesserungen. Die Bracketherstellung in einem Rapid-Prototyping-Verfahren ermöglicht zudem die unmittelbare Umsetzung klinisch sinnvoller Weiterentwicklungen.     

Symptom occurrence, symptom distress, and quality of life in renal transplant recipients.

The growing number of persons who have successful renal transplants and the challenges they undergo as they adjust to changed lifestyles increases the need for knowledge of the recipient's view of the changes resulting from the transplantation process. One area for exploration is the recipient's perception of the symptoms that occur after transplantation. The purpose of this study was to determine symptom occurrence and symptom distress following renal transplantation and their relationships to quality of life in patients with renal transplants.     

An Evaluation of a Mixed-Gender Sexual Assault Prevention Program

This study evaluated the short-term effectiveness of a mixed-gender sexual assault prevention program developed for college students. Program participants (n = 177) were compared to non-program participants (n = 132) prior to the program and during a 2-week follow-up period on measures of rape myths, victim empathy, perceived negative consequences and estimated likelihood of committing rape, sexual communication, sexual assault awareness, and risky dating behavior. The prevention program was effective at increasing men’s victim empathy and decreasing their adherence to rape myths but ineffective at changing women’s assault-related knowledge, participation in risky dating behaviors, and sexual communication strategies. Limitations of the study and directions for future research in sexual assault prevention are addressed. Editors’ Strategic Implications: This study provides an important example of the limitations of a single session prevention programming approach (even if it is well designed and executed) in addressing a systemic and pervasive problem like sexual assault on college campuses.     

Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block

Background: Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block.

Methods: Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 [mu]g/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function.

Results: Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min.     

DNA polymerase mu gene expression in B-cell non-Hodgkin's lymphomas: an analysis utilizing in situ hybridization

DNA polymerase mu (pol mu) is a novel error-prone DNA repair enzyme bearing significant structural homology with terminal deoxynucleotidyltransferase. Whereas other human error-prone DNA polymerases identified thus far show no preferential lymphoid tissue distribution, the highest levels of pol mu mRNA have been detected in peripheral lymphoid tissues, particularly germinal center B cells. Conceivably, up-regulation of the pol mu gene may be biologically significant in lymphomagenesis, especially in the development of B-cell non-Hodgkin's lymphomas (B-NHLs), because of enhanced error-prone DNA repair activities. To explore this possibility, we generated a digoxigenin-labeled riboprobe to pol mu mRNA and used the probe and in situ hybridization to examine the expression pattern of the pol mu gene in formalin-fixed, paraffin-embedded tissue sections of 37 B-NHLs. This included eight chronic lymphocytic leukemia/small lymphocytic lymphomas, six mantle cell lymphomas, seven follicular lymphomas, nine diffuse large B-cell lymphomas, three splenic marginal zone lymphomas, two Burkitt's lymphomas, and two precursor B-lymphoblastic lymphomas. We also correlated the pol mu mRNA expression levels with the tumor proliferation index, which was assessed in each case by image analysis of Ki-67 immunostained slides. Nineteen of 21 (90%) B-NHLs arising from postgerminal center B cells (follicular lymphomas, diffuse large B-cell lymphomas, splenic marginal zone lymphomas, and Burkitt's lymphomas) exhibited high expression of pol mu mRNA. In contrast, only 2 of 16 (13%) B-NHLs arising from pregerminal center B cells (chronic lymphocytic leukemia/small lymphocytic lymphomas, mantle cell lymphomas, and precursor B-lymphoblastic lymphomas) expressed significant levels of pol mu mRNA. Pol mu gene expression did not seem to correlate with the proliferation index, especially because a significant level of pol mu mRNA was not detected in either case of precursor B-lymphoblastic lymphomas. In conclusion, pol mu gene expression is highly associated with B-NHLs of postgerminal center B-cell derivation. Furthermore, the expression level is independent of the proliferation rate and thus is unrelated to the biological aggressiveness of the tumors. These findings, along with the error-prone nature of the enzyme, suggest that up-regulation of pol mu gene expression may be a contributing factor to the pathogenesis of a subset of B-NHLs through DNA repair-associated genomic instability.