Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h

Antiviral roles of natural killer (NK) cell subsets were examined in C57BL/6 mice infected with murine cytomegalovirus (MCMV) and other viruses, including lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and mouse hepatitis virus (MHV). Each virus vigorously induced an NK cell infiltrate into the peritoneal cavity and liver, causing some redistributions of NK cell subsets defined by monoclonal antibody (mAb) directed against Ly49A, C/I, D, and G2. Striking results were seen with a mAb (1F8) reactive with the positively signaling molecule Ly49H, present in MCMV-resistant C57BL/6 mice. mAb 1F8 also stains Ly49 C and I, but exclusion of those reactivities with mAb 5E6, which recognizes Ly49 C and I, indicated that Ly49H+ cells infiltrated the peritoneal cavity and liver and were particularly effective at synthesizing interferon γ. Depletion of 1F8+ but not 5E6+ cells in vivo by mAb injections enhanced MCMV titers by 20-1,000-fold in the spleen and approximately fivefold in the liver. Titers of LCMV or VV were not enhanced. These anti-MCMV effects were attributed to prototypical NK1.1+CD3− NK cells and not to NK1.1+CD3+ “NK/T” cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset

Relationship of Proteinases and Proteinase Inhibitors with Microbial Presence in Chronic Lung Disease of Prematurity

Background: A proteolytic imbalance has been implicated in the development of “classical” chronic lung disease of prematurity (CLD). However, in “new” CLD this pattern has changed. This study examines the longitudinal relationship between neutrophil proteinases and their inhibitors in ventilated preterm infants and their relationship to microbial colonisation. Methods: Serial bronchoalveolar lavage fluid was obtained from ventilated newborn preterm infants. Neutrophil elastase (NE) activity, cell counts, metalloproteinase (MMP)-9, MMP-9/TIMP-1 complex, SerpinB1 concentration and percentage of SerpinB1 and α1-antitrypsin (AAT) in complex with elastase were measured. The presence of microbial genes was examined using PCR for 16S rRNA genes. Results: Statistically more infants who developed CLD had NE activity in at least one sample (10/20) compared with infants with resolved respiratory distress syndrome (RDS) (2/17). However, NE activity was present in a minority of samples, occurring as episodic peaks. Peak levels of MMP-9, MMP-9/TIMP-1 complex, percentage of AAT and SerpinB1 in complex and cell counts were all statistically greater in infants developing CLD than in infants with resolved RDS. Peak values frequently occurred as episodic spikes and strong temporal relationships were noted between all markers. The peak values for all variables were significantly correlated to each other. The presence of bacterial 16S rRNA genes was associated with the development of CLD and with elevated elastase and MMP-9. Conclusion: NE activity and MMP-9 appear to be important in the development of “new” CLD with both proteinase and inhibitor concentrations increasing episodically, possibly in response to postnatal infection

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium

Introduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels

BioPAN: a web-based tool to explore mammalian lipidome metabolic pathways on LIPID MAPS.

Lipidomics increasingly describes the quantification using mass spectrometry of all lipids present in a biological sample.  As the power of lipidomics protocols increase, thousands of lipid molecular species from multiple categories can now be profiled in a single experiment.  Observed changes due to biological differences often encompass large numbers of structurally-related lipids, with these being regulated by enzymes from well-known metabolic pathways.  As lipidomics datasets increase in complexity, the interpretation of their results becomes more challenging.  BioPAN addresses this by enabling the researcher to visualise quantitative lipidomics data in the context of known biosynthetic pathways.  BioPAN provides a list of genes, which could be involved in the activation or suppression of enzymes catalysing lipid metabolism in mammalian tissues

Relationship Between Operator Volume and Adverse Outcome in Contemporary Percutaneous Coronary Intervention Practice An Analysis of a Quality-Controlled Multicenter Percutaneous Coronary Intervention Clinical Database

ObjectivesThe aim of our study was to evaluate the volume-outcome relationship in a large, quality-controlled, contemporary percutaneous coronary interventions (PCI) database.BackgroundWhether the relationship between physician volume of PCI and outcomes still exists in the era of coronary stents is unclear.MethodsData on 18,504 consecutive PCIs performed by 165 operators in calendar year 2002 were prospectively collected in a regional consortium. Operators' volume was divided into quintiles (1 to 33, 34 to 89, 90 to 139, 140 to 206, and 207 to 582 procedures/year). The primary end point was a composite of major adverse cardiovascular events (MACE) including death, coronary artery bypass grafting, stroke or transient ischemic attack, myocardial infarction, and repeat PCI at the same site during the index hospital stay.ResultsThe unadjusted MACE rate was significantly higher in quintiles one and two of operator volume when compared with quintile five (7.38% and 6.13% vs. 4.15%, p = 0.002 and p = 0.0001, respectively). A similar trend was observed for in-hospital death. After adjustment for comorbidities, patients treated by low volume operators had a 63% increased odds of MACE (adjusted odds ratio [OR] 1.63, 95% confidence interval [CI] 1.29 to 2.06, p < 0.0001 for quintile [Q]1; adjusted OR 1.63, 95% CI 1.34 to 1.90, p < 0.0001 for Q2 vs. Q5), but not of in-hospital death. Overall, high volume operators had better outcomes than low volume operators in low-risk and high-risk patients.ConclusionsAlthough the relationship between operator volume and in-hospital mortality is no longer significant, the relationship between volume and any adverse outcome is still present. Technological advancements have not yet completely offset the influence of procedural volume on proficiency of PCIs

Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV

Pion-nucleus elastic scattering at energies above the Delta(1232) resonance is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies, and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment

Automated Grading of Radiographic Knee Osteoarthritis Severity Combined with Joint Space Narrowing

The assessment of knee osteoarthritis (KOA) severity on knee X-rays is a central criteria for the use of total knee arthroplasty. However, this assessment suffers from imprecise standards and a remarkably high inter-reader variability. An algorithmic, automated assessment of KOA severity could improve overall outcomes of knee replacement procedures by increasing the appropriateness of its use. We propose a novel deep learning-based five-step algorithm to automatically grade KOA from posterior-anterior (PA) views of radiographs: (1) image preprocessing (2) localization of knees joints in the image using the YOLO v3-Tiny model, (3) initial assessment of the severity of osteoarthritis using a convolutional neural network-based classifier, (4) segmentation of the joints and calculation of the joint space narrowing (JSN), and (5), a combination of the JSN and the initial assessment to determine a final Kellgren-Lawrence (KL) score. Furthermore, by displaying the segmentation masks used to make the assessment, our algorithm demonstrates a higher degree of transparency compared to typical "black box" deep learning classifiers. We perform a comprehensive evaluation using two public datasets and one dataset from our institution, and show that our algorithm reaches state-of-the art performance. Moreover, we also collected ratings from multiple radiologists at our institution and showed that our algorithm performs at the radiologist level. The software has been made publicly available at https://github.com/MaciejMazurowski/osteoarthritis-classification

Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection

Emerging studies increasingly demonstrate the importance of the throat and salivary glands as sites of virus replication and transmission in early COVID-19 disease. SARS-CoV-2 is an enveloped virus, characterized by an outer lipid membrane derived from the host cell from which it buds. While it is highly sensitive to agents that disrupt lipid biomembranes, there has been no discussion about the potential role of oral rinsing in preventing transmission. Here, we review known mechanisms of viral lipid membrane disruption by widely available dental mouthwash components that include ethanol, chlorhexidine, cetylpyridinium chloride, hydrogen peroxide, and povidone-iodine. We also assess existing formulations for their potential ability to disrupt the SARS-CoV-2 lipid envelope, based on their concentrations of these agents, and conclude that several deserve clinical evaluation. We highlight that already published research on other enveloped viruses, including coronaviruses, directly supports the idea that oral rinsing should be considered as a potential way to reduce transmission of SARS-CoV-2. Research to test this could include evaluating existing or specifically tailored new formulations in well-designed viral inactivation assays, then in clinical trials. Population-based interventions could be undertaken with available mouthwashes, with active monitoring of outcome to determine efficacy. This is an under-researched area of major clinical need

The Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) Collaborative Quality Improvement Initiative in Percutaneous Coronary Interventions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72388/1/j.1540-8183.2002.tb01071.x.pd