Sonographically Guided Patellar Tendon Fenestration

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135446/1/jum2013325771.pd

Sonography of the Lateral Antebrachial Cutaneous Nerve With Magnetic Resonance Imaging and Anatomic Correlation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135544/1/jum20143381475.pd

Diversity and Tropism of HIV-1 Rebound Virus Populations in Plasma Level After Treatment Discontinuation

Human immunodeficiency virus–infected people discontinuing therapy experience a rebound in the virus level (hereafter, “rebound virus”) from a persistent reservoir. We examined 10 samples from patients in AIDS Clinical Trials Group study A5068 with rebound virus, using single-genome amplification and Primer ID deep sequencing, to assess env genetic diversity of the virus population. Most rebound-virus populations showed significant diversity. All env examined required high levels of CD4 for entry, consistent with selection of replication in CD4+ T cells. These results indicate that most people discontinuing therapy release a diverse population of virus and that this released virus has entry features of virus selected for replication in CD4+ T cells, rather than in myeloid cells

Plasma Interleukin-6 (IL-6), Angiopoietin-2, and C-Reactive Protein Levels Predict Subsequent Type 1 Myocardial Infarction in Persons With Treated HIV Infection

BackgroundHIV infection leads to endothelial activation, promoting platelet adhesion, and accelerating atherosclerosis. Our goal was to determine whether biomarkers of endothelial activation and hemostasis/thrombosis were elevated in people with treated HIV (PWH) before myocardial infarction (MI).MethodsIn a case-control study nested within the CFAR Network of Integrated Clinical Systems (CNICS) cohort, we compared 69 adjudicated cases with type 1 MI with 138 controls matched for antiretroviral therapy regimen. We measured angiopoietin-1, angiopoietin-2 (ANG-2), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), von Willebrand factor, C-reactive protein (CRP), interleukin-6 (IL-6), plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, and apolipoprotein A1 in stored plasma. Conditional logistic regression identified associations with subsequent MI, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores.ResultsHigher IL-6 was associated with MI after adjustment for ASCVD score (adjusted odds ratio [AOR] 1.51, 95% confidence interval [95% CI]: 1.05 to 2.17 per standard-deviation-scaled log 2 increment). In a separate model adjusting for VACS score, higher ANG-2 (AOR 1.49, 95% CI: 1.04 to 2.14), higher CRP (AOR 1.45, 95% CI: 1.06 to 2.00), and higher IL-6 (AOR 1.68, 95% CI: 1.17 to 2.41) were associated with MI. In a sensitivity analysis excluding PWH with viral load ≥400 copies/mL, higher IL-6 remained associated with MI after adjustment for ASCVD score and after adjustment for VACS score.ConclusionsAmong PWH, higher levels of plasma IL-6, CRP, and ANG-2 predict subsequent type 1 MI, independent of conventional risk scores. IL-6 had the most consistent associations with type 1 MI, regardless of viral load suppression

Witten's 2+1 gravity on R x (Klein bottle)

Witten's formulation of 2+1 gravity is investigated on the nonorientable three-manifold R x (Klein bottle). The gauge group is taken to consist of all four components of the 2+1 Poincare group. We analyze in detail several components of the classical solution space, and we show that from four of the components one can recover nondegenerate spacetime metrics. In particular, from one component we recover metrics for which the Klein bottles are spacelike. An action principle is formulated for bundles satisfying a certain orientation compatibility property, and the corresponding components of the classical solution space are promoted into a phase space. Avenues towards quantization are briefly discussed.Comment: 33 pages, REVTeX v3.0, 3 figures in a separate PostScript fil

The Asymmetric Merger of Black Holes

We study event horizons of non-axisymmetric black holes and show how features found in axisymmetric studies of colliding black holes and of toroidal black holes are non-generic and how new features emerge. Most of the details of black hole formation and black hole merger are known only in the axisymmetric case, in which numerical evolution has successfully produced dynamical space-times. The work that is presented here uses a new approach to construct the geometry of the event horizon, not by locating it in a given spacetime, but by direct construction. In the axisymmetric case, our method produces the familiar pair-of-pants structure found in previous numerical simulations of black hole mergers, as well as event horizons that go through a toroidal epoch as discovered in the collapse of rotating matter. The main purpose of this paper is to show how new - substantially different - features emerge in the non-axisymmetric case. In particular, we show how black holes generically go through a toroidal phase before they become spherical, and how this fits together with the merger of black holes.Comment: 28 pages, 10 figures, uses REVTEX. Improved quality figures and additional color images are provided at http://www.phyast.pitt.edu/~shusa/EH

Dynamics of Immune Reconstitution and Activation Markers in HIV+ Treatment-Naïve Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

Background: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. Methods: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. Results: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. Conclusions: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. Trial Registration Clinicaltrials.gov NCT0066097

Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood. Here, we found aging-associated (age ≥61) intrinsic changes in T cell responses when compared to those from individuals aged ≤ 60, even among COVID-positive patients with mild symptoms. Specifically, when stimulated with SARS-CoV-2 peptides in vitro, peripheral blood mononuclear cell (PBMC) CD4+ and CD8+ T cells from individuals aged ≥61 showed a diminished capacity to produce IFN-γ and IL-1β. Although they did not have severe disease, aged individuals also showed a higher frequency of PD-1+ cells and significantly diminished IFN-γ/PD-1 ratios among T lymphocytes upon SARS-CoV-2 peptide stimulation. Impaired T cell IL-1β expression coincided with reduced NLRP3 levels in T lymphocytes. However, the expression of these molecules was not affected in the monocytes of individuals aged ≥61. Together, these data reveal SARS-CoV-2-specific CD4+ and CD8+ T-cell intrinsic cytokine alterations in the individuals older than 61 and may provide new insights into dysregulated COVID-directed immune responses in the elderly

Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures.

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures associated with co-receptor utilization. RESULTS: The accessory protein Tat and the HlV-1 long terminal repeat (LTR) were analyzed with respect to genetic diversity and compared by Jensen-Shannon divergence which resulted in a correlation with both mean genetic diversity as well as the absolute difference in genetic diversity between R5- and X4-genome specific trends. As expected, the V3 domain of the gp120 protein was enriched with statistically divergent positions. Statistically divergent positions were also identified in Tat amino acid sequences within the transactivation and TAR-binding domains, and in nucleotide positions throughout the LTR. We further analyzed LTR sequences for putative transcription factor binding sites using the JASPAR transcription factor binding profile database and found several putative differences in transcription factor binding sites between R5 and X4 HIV-1 genomes, specifically identifying the C/EBP sites I and II, and Sp site III to differ with respect to sequence configuration for R5 and X4 LTRs. CONCLUSION: These observations support the hypothesis that co-receptor utilization coincides with specific genetic signatures in HIV-1 Tat and the LTR, likely due to differing transcriptional regulatory mechanisms and selective pressures applied within specific cellular targets during the course of productive HIV-1 infection