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  1. Article: Comparison of methods to quantify inducible HIV-1 outgrowth.

    Enick, P Nathan / Brooker, Joseph P / Tumiotto, Camille M / Staines, Brittany T / Eron, Joseph J / McMahon, Deborah K / Gandhi, Rajesh T / Mellors, John W / Sobolewski, Michele D

    Journal of virus eradication

    2021  Volume 7, Issue 2, Page(s) 100043

    Abstract: The quantitative viral outgrowth assay (qVOA) is the gold standard for measuring inducible, replication-competent HIV-1. Using MOLT4-R5 and SupT1-R5 cell lines instead of allogeneic blasts and HIV-1 RNA detection rather than p24 enzyme-immunoassay (EIA) ... ...

    Abstract The quantitative viral outgrowth assay (qVOA) is the gold standard for measuring inducible, replication-competent HIV-1. Using MOLT4-R5 and SupT1-R5 cell lines instead of allogeneic blasts and HIV-1 RNA detection rather than p24 enzyme-immunoassay (EIA) has been proposed to improve the sensitivity of the qVOA. It is unclear, however, how these alternative approaches affect qVOA performance. We compared three qVOAs methods across 15 persons with HIV-1 on suppressive antiretroviral therapy and found that the MOLT4-R5 method yielded a significantly higher proportion of p24-positive wells (42%) than both the allogeneic blast (29%) and SupT1-R5 (32%) assays. Additionally, 5 of 7 qVOAs that were negative by p24 EIA showed viral outgrowth by HIV-1 RNA quantification (>10-fold increase within 7 days). These findings reveal the potential for underestimation of the latent, inducible reservoir by qVOA depending on the target cells used and the measure of viral outgrowth. Use of MOLT4-R5 cells with both p24 EIA and HIV-1 RNA to detect viral outgrowth was the most sensitive method.
    Language English
    Publishing date 2021-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2868549-0
    ISSN 2055-6659 ; 2055-6640
    ISSN (online) 2055-6659
    ISSN 2055-6640
    DOI 10.1016/j.jve.2021.100043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antibody Responses After mRNA-Based COVID-19 Vaccination in Residential Older Adults: Implications for Reopening.

    Nace, David A / Kip, Kevin E / Mellors, John W / Peck Palmer, Octavia M / Shurin, Michael R / Mulvey, Katie / Crandall, Melissa / Sobolewski, Michele D / Enick, P Nathan / McCormick, Kevin D / Jacobs, Jana L / Kane, April L / Lukanski, Amy / Kip, Paula L / Wells, Alan

    Journal of the American Medical Directors Association

    2021  Volume 22, Issue 8, Page(s) 1593–1598

    Abstract: Objective: COVID-19 disproportionately impacts residents in long-term care facilities. Our objective was to quantify the presence and magnitude of antibody response in vaccinated, older adult residents at assisted living, personal care, and independent ... ...

    Abstract Objective: COVID-19 disproportionately impacts residents in long-term care facilities. Our objective was to quantify the presence and magnitude of antibody response in vaccinated, older adult residents at assisted living, personal care, and independent living communities.
    Design: A cross-sectional quality improvement study was conducted March 15 - April 1, 2021 in the greater Pittsburgh region.
    Setting and population: Participants were older adult residents at assisted living, personal care, and independent living communities, who received mRNA-based COVID-19 vaccine. Conditions that impair immune responses were exclusionary criteria.
    Methods: Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels, and blinded evaluation of SARS-CoV-2 pseudovirus neutralization titers. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis evaluated relationships between factors potentially associated with antibody levels. Spearman correlations were calculated between antibody levels and neutralization titers.
    Results: All participants (N = 70) had received two rounds of vaccination and were found to have antibodies with wide variation in relative levels. Antibody levels trended lower in males, advanced age, current use of steroids, and longer length of time from vaccination. Pseudovirus neutralization titer levels were strongly correlated (P < .001) with Beckman Coulter antibody levels [D614 G NT50, r
    Conclusions and implications: Higher functioning, healthier, residential older adults mounted detectable antibody responses when vaccinated with mRNA-based COVID-19 vaccines. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects remain to be determined in larger studies as clinical protection is afforded by ongoing adaptive immunity, which is known to be decreased in older adults. This study provides important preliminary results on level of population risk in older adult residents at assisted living, personal care, and independent living communities to inform reopening strategies, but are not likely to be translatable for residents in nursing homes.
    MeSH term(s) Aged ; Antibody Formation ; COVID-19 ; COVID-19 Vaccines ; Cross-Sectional Studies ; Humans ; Male ; RNA, Messenger ; SARS-CoV-2 ; Vaccination
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger
    Language English
    Publishing date 2021-06-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171030-2
    ISSN 1538-9375 ; 1525-8610
    ISSN (online) 1538-9375
    ISSN 1525-8610
    DOI 10.1016/j.jamda.2021.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Synthesis, Osteoblast, and Osteoclast Viability of Amorphous and Crystalline Tri-Magnesium Phosphate.

    Ostrowski, Nicole / Lee, Boeun / Hong, Daeho / Enick, P Nathan / Roy, Abhijit / Kumta, Prashant N

    ACS biomaterials science & engineering

    2014  Volume 1, Issue 1, Page(s) 52–63

    Abstract: Magnesium phosphate implants may be used for bone void filling applications, potentially replacing traditionally studied bioceramics, which suffer from limited resorption and inferior mechanical properties compared to natural bone. In this study, ... ...

    Abstract Magnesium phosphate implants may be used for bone void filling applications, potentially replacing traditionally studied bioceramics, which suffer from limited resorption and inferior mechanical properties compared to natural bone. In this study, amorphous and crystalline trimagnesium phosphates were synthesized and characterized utilizing a variety of analytical methods. In vitro solubility and cytotoxicity of the corresponding amorphous and crystalline phosphates were also analyzed. Amorphous magnesium phosphate was shown to be more soluble than the crystalline counterpart in vitro while inducing mineralization of an amorphous phosphate phase mimicking hydroxyapatite-type characteristic morphology on the substrate surface. The rapid mineralization of the amorphous magnesium phosphate was found to promote the proliferation and differentiation of osteoblast-like cells in comparison to the crystalline phase. Both magnesium phosphates hindered the differentiation of monocytes into osteoclasts. The combined effects of the spontaneous serum-mediated apatite-like mineralization, increased osteoblast differentiation and suspended osteoclast formation indicate that the amorphous magnesium phosphates may be promising bioactive materials for bone void repair applications.
    Language English
    Publishing date 2014-12-12
    Publishing country United States
    Document type Journal Article
    ISSN 2373-9878
    ISSN (online) 2373-9878
    DOI 10.1021/ab500073c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Immunogenicity of COVID-19 Vaccination in Immunocompromised Patients: An Observational, Prospective Cohort Study Interim Analysis

    Haidar, Ghady / Agha, Mounzer / Lukanski, Amy / Linstrum, Kelsey / Troyan, Rachel / Bilderback, Andrew / Rothenberger, Scott / McMahon, Deborah K / Crandall, Melissa / Enick, P Nathan / Sobolewksi, Michelle / Collins, Kevin / Schwartz, Marc B / Dueker, Jeffrey M / Silveira, Fernanda P / Keebler, Mary E / Humar, Abhinav / Luketich, James D / Morrell, Matthew R /
    Pilewski, Joseph M / McDyer, John F / Pappu, Bhanu / Ferris, Robert L / Marks, Stanley M / Klamar-Blain, Cynthia / Parikh, Urvi M / Heaps, Amy / Kip, Paula L / Wells, Alan / Minnier, Tami / Angus, Derek / Mellors, John W

    medRxiv

    Abstract: Objectives: Immunocompromised patients were excluded from COVID-19 vaccine clinical trials. The objectives of the study were to measure antibody responses, levels, and neutralization capability after COVID-19 vaccination among immunocompromised patients ... ...

    Abstract Objectives: Immunocompromised patients were excluded from COVID-19 vaccine clinical trials. The objectives of the study were to measure antibody responses, levels, and neutralization capability after COVID-19 vaccination among immunocompromised patients and compare these variables to those of immunocompetent healthcare workers. Methods This is an interim analysis of an ongoing observational, prospective cohort study which launched on April 14, 2021 across Western Pennsylvania. Participants were healthy healthcare workers (HCW) and immunocompromised patients who had completed their COVID-19 vaccination series. Individuals with a history of COVID-19 were not eligible. Serum was collected to measure for the presence of IgG against the SARS-CoV-2 Spike protein using a semi-quantitative assay; antibody levels were available for comparisons. A quasi-random subset of patients was selected for pseudovirus neutralization assays. Seropositivity with 95% Clopper-Pearson exact confidence intervals and distribution of antibody levels were measured. To identify risk factors for seronegativity, clinical characteristics were univariately compared between antibody reactive and non-reactive individuals within the immunocompromised group. Results: 107 HCW and 489 immunocompromised patients were enrolled. Compared to HCWs, seropositivity was significantly lower (p<.001) among immunocompromised patients with Solid organ transplant (SOT), autoimmune, hematological malignancies, and solid tumors (HCW=98.1%; SOT=37.2%; autoimmune=83.8%; hematological malignancies=54.7%; and solid tumor=82.4%, p < 0.05). Over 94% of patients with Human Immunodeficiency Virus were seropositive. Among seropositive patients, antibody levels were much lower among SOT (4.5 [2.1,13.1], p=.020). Neutralization titers tightly correlated with antibody levels (Spearman r = 0.91, p < 0.0001). Conclusion: Our findings demonstrate the heterogeneity of the humoral immune response to COVID-19 vaccines based on underlying immunosuppressive condition and highlight an urgent need to optimize and individualize COVID-19 prevention in these patients. These findings also have implications on public health guidance, particularly given revised Centers for Disease Control and Prevention recommendations permitting vaccinated individuals to abandon masking and social distancing in most settings. Future studies are warranted to determine assessment of cellular immunity, longitudinal measurement of immune responses, and the safety and efficacy of revaccination.
    Keywords covid19
    Language English
    Publishing date 2021-06-30
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.06.28.21259576
    Database COVID19

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