75 results on '"Shenvi N"'
Search Results
2. Human milk fortification and intestinal inflammation in very preterm infants
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Salem, A, primary, Ou, J, additional, Lukemire, J, additional, Shenvi, N, additional, Barbian, ME, additional, Rose, A, additional, Hendrickson, J, additional, Easley, KA, additional, Guo, Y, additional, Arthur, C, additional, Stowell, S, additional, Josephson, C, additional, and Patel, RM, additional
- Published
- 2024
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3. P‐IT‐13 | Use of Pulse Oximeter and Pulse Rate Time‐Series Processing to Understand Physiologic Changes Associated with Transfusion in Very Preterm Infants
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Marshall, C., primary, Vale, J. Gabriel De Souza, additional, Newaz, S., additional, Shenvi, N., additional, Josephson, C., additional, Anderson, D., additional, Mangal, R., additional, and Kalamaswaran, R., additional
- Published
- 2023
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4. 735 - Human milk fortification and intestinal inflammation in very preterm infants
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Salem, A, Ou, J, Lukemire, J, Shenvi, N, Barbian, ME, Rose, A, Hendrickson, J, Easley, KA, Guo, Y, Arthur, C, Stowell, S, Josephson, C, and Patel, RM
- Published
- 2024
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5. 664 - Association between diet and fecal calprotectin levels in very preterm infants
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Ou, J, Lukemire, J, Shenvi, N, Salem, A, Barbian, ME, Easley, KA, Guo, Y, Arthur, C, Stowell, S, Josephson, C, and Patel, RM
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- 2024
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6. Reactivation of Replication Competent Cytomegalovirus (CMV) from CMV Seropositive (CMV-SP) Maternal Breast Milk and Infection of Low Birth Weight Infants (LBWIs ≤1500 g): Preliminary Results of a Birth Cohort Transfusion-Transmitted CMV Study: S4-010A
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Josephson, C, Caliendo, A, Hinkes, M, Easley, K A, Frempong, M, Shenvi, N, Grier, K, Matzick, T, Hillyer, C D, and Roback, J D
- Published
- 2011
7. Impact of Hospital‐Acquired Infection on Vitamin D Status in Critically Ill Patients
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Peterson, B, primary, Alvarez, J, additional, Jones, J, additional, Hebbar, G, additional, Griffith, D, additional, Dave, N, additional, Hao, L, additional, Easley, K, additional, Shenvi, N, additional, Tangpricha, V, additional, and Ziegler, T, additional
- Published
- 2015
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8. A rubrerythrin operon and nigerythrin gene in Desulfovibrio vulgaris (Hildenborough)
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Lumppio, H L, primary, Shenvi, N V, additional, Garg, R P, additional, Summers, A O, additional, and Kurtz, D M, additional
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- 1997
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9. SOCIOECONOMIC FACTORS IN ADOLESCENT DELINQUENCY.
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D., Jejurikar N. and S., Shenvi N.
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JUVENILE delinquency ,CONDUCT disorders in adolescence ,SOCIOECONOMIC factors ,HOME environment ,FAMILY size ,NUCLEAR families ,SEX crimes - Abstract
[In Bombay, 371 delinquent boys and girls were interviewed in order to study the various socioeconomic factors. In the majority of the cases, an adverse home environment played a major role. 45% of the boys and 50% of the girls had incurred loss of one or both the parents. Factors like poverty, large family size, nuclear family pattern and illiteracy had a great bearing in causing aberrant behaviour in these children. Involvement in sexual offences in the form of elopement and/or rape were observed in girls. In boys, stealing was a major reason for being in the observation home. 70% of the delinquents did not belong to proper Bombay. With rapid urbanisation, the problem of juvenile delinquency is bound to increase manifold in the next few decades]. [ABSTRACT FROM AUTHOR]
- Published
- 1985
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10. Substituent Ordering and Interpolation in Molecular Library Optimization
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Shenvi, N., Geremia, J. M., and Rabitz, H.
- Abstract
The substituent ordering problem in molecular libraries refers to identifying a rational ordering for molecular moieties such that coarse sampling and interpolation over the full space of possible library molecules may be efficiently performed. A practical solution to the ordering problem is proposed on the bases of (a) coarse sampling of the molecular substituents, (b) radial basis function interpolation over the full space, and (c) the use of genetic algorithms to find rational moiety orderings. The procedure is shown to be extremely effective for a variety of simulated libraries. This algorithm is also used to reorder and predict the glass transition temperature T
g for a combinatorial polymer library.- Published
- 2003
11. Nonlinear Kinetic Parameter Identification through Map Inversion
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Shenvi, N., Geremia, J. M., and Rabitz, H.
- Abstract
A nonlinear method for parameter identification in kinetic systems is presented. Parameter identification is achieved through the use of HDMR (high-dimensional model representation), which can reduce greatly the computational cost of high-dimensional function inversion. The technique is demonstrated in simulations to extract rate constants from concentration data in a linear kinetic system, the reaction of H
2 with Br2 , and the oxidation of formaldehyde. The results of inversion for the latter case are compared with a previously published linear inversion procedure. The new algorithm shows excellent performance in identifying the full distribution of rate constants consitent with the data. The speed and accuracy of the HDMR permits full inversion of all relevant model parameters without the introduction of hidden biases from prior assumptions on the quality of the model parameters.- Published
- 2002
12. Re-engineering the diiron site in rubrerythrin towards that in ribonucleotide reductase
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DeMare, F., Nordlund, P., Gupta, N., Shenvi, N. V., Cui, X., and Kurtz, D. M.
- Published
- 1997
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13. Transmission spectrum of an optical cavity containing N atoms.
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Leslie, S., Stamper-Kurn, D.M., Shenvi, N., Brown, K.R., and Birgitta Whaley, K.
- Published
- 2004
14. A Risk Tool for Evaluating Overuse Injury and Return-to-Play Time Periods in Youth and Collegiate Athletes: Preliminary Study.
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Schley S, Buser A, Render A, Ramirez ME, Truong C, Easley KA, Shenvi N, and Jayanthi N
- Abstract
Background: Overuse injuries in youth athletes are associated with risks, including sports specialization, biological maturation, female sex, and workload measures. As no assessment tool exists to evaluate risk accumulation, we developed a novel risk factor scoring system (Sport Training Assessment of Risk [STAR]) to assess participants' risk of overuse injury and explore association with return-to-play (RTP) time periods., Hypothesis: (1) STAR will reach an acceptable predictive threshold in the assessment of overuse injury in youth athletes. (2) Higher STAR scores will be associated with increased RTP time periods after injury., Study Design: Longitudinal cohort study., Level of Evidence: Level 3., Methods: Youth athletes with an injury sustained during competitive sport completed questionnaires. Association of questionnaire variables with injury risk type was evaluated via logistic regression analyses, and unweighted and weighted versions of a total risk score were developed. RTP was defined by physician clearance per electronic medical record review. Mantel-Haenszel chi-square tests and Kendall's rank correlation coefficients were used to assess the relationship between weighted total risk score and RTP time periods. The weighted STAR model was analyzed with receiver operating characteristic (ROC) curves., Results: The weighted STAR model trended toward an acceptable level of prediction for overuse (nonserious + serious) injury (area under the ROC curve [AUC], 0.66; 95% CI, 0.61-0.71), but was less predictive for serious overuse injury (AUC, 0.63; 95% CI, 0.55-0.71). Weighted total risk score was weakly associated with return to full play (ρ = 0.11; P < 0.01), and potentially with return to modified play (ρ = -0.08; P = 0.04)., Conclusion: STAR may be a feasible tool for assessing overuse injury risk and RTP time periods in youth athletes but requires further development, as it did not reach an acceptable predictive threshold in this preliminary study., Clinical Relevance: Clinicians can use STAR to assess overuse injury risk in youth athletes., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.
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- 2024
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15. T-cell receptor excision circles and postnatal cytomegalovirus infection in very low birth weight infants.
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Towne A, Patel RM, Shenvi N, Easley KA, Saakadze N, Josephson CD, and Kobrynski L
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- Humans, Infant, Newborn, Female, Receptors, Antigen, T-Cell, Male, Cytomegalovirus immunology, Infant, Premature, Cytomegalovirus Infections diagnosis, Infant, Very Low Birth Weight
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- 2024
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16. The Effects of Injury Type on Health-Related Quality of Life in Youth Athletes: A Cross-Sectional Analysis.
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Verma R, DeMaio E, Render A, Wild J, Hunt D, Cato S, Shenvi N, LaBella C, Stracciolini A, and Jayanthi N
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- Adolescent, Child, Female, Humans, Male, Athletic Injuries epidemiology, Brain Concussion epidemiology, Cross-Sectional Studies, Cumulative Trauma Disorders epidemiology, Fatigue epidemiology, Athletes, Quality of Life
- Abstract
Objective: The relationship between health-related quality of life (HRQoL) and injury type has not been analyzed for young athletes. We hypothesized that there would be no difference in HRQoL between injured athletes, injured nonathletes, and normative data for healthy youth (NDHY) or among athletes with acute, overuse, or concussion injuries., Design: Cross-sectional clinical cohort., Setting: Primary care sports medicine clinics at 3 academic institutions., Participants: Patients aged 8 to 18 years presenting with injury., Independent Variables: Injury type and athletic participation., Main Outcome Measures: Health-related quality of life measured 1 month after injury through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric-25 v2.0 assessed pain interference, peer relationships, depression, fatigue, anxiety, and mobility. One-way analysis of variance was performed with P values of <0.05 considered significant. Concussion Learning Assessment and School Survey (CLASS) evaluated academic performance., Results: Three hundred fifty-seven patients (36% male), with average age of 14.2 years, completed HRQoL and CLASS surveys following injury. There were 196 overuse injuries (55%), 119 acute injuries (33%), and 42 concussions (12%). Ninety-four percent were athletes. Six percent were nonathletes; 90.5% of concussed patients reported grades worsening. Concussed athletes reported more fatigue (P = 0.008) compared with other injury types but no worse than NDHY. Athletes with overuse injuries had lower mobility (P = 0.005) than other injury types and NDHY. Patients with lower HRQoL were female, older age, or required surgery. No other domains had significant differences by injury type nor did HRQoL differ between the athletes, nonathletes, and NDHY., Conclusions: With the exception of injuries requiring surgery, HRQoL of injured young athletes was similar to NDHY in most domains., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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17. Human Immunodeficiency Virus (HIV) Care Continuum Outcomes After Transition to Adult Care Among a Prospective Cohort of Youth With HIV in Atlanta, Georgia.
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Hussen SA, Doraivelu K, Goldstein MH, Shenvi N, Easley KA, Zanoni BC, Camacho-González A, and Del Río C
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- Adult, Humans, Male, Adolescent, Child, Young Adult, Georgia epidemiology, HIV, Prospective Studies, Continuity of Patient Care, Viral Load, Transition to Adult Care, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Background: Healthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting human immunodeficiency virus (HIV) care outcomes after healthcare transition., Methods: We conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age, 24 years) were enrolled up to 3 months before the expected transition and were followed up to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at the baseline and at 6, 12, 18, and 24 months., Results: The majority of our cohort (n = 70) was male (88.6%) and black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% confidence interval, 78%-94%) at 6 months, 76% (66%-86%) at 12 months, and 66% (55%-78%) at 18 and 24 months. Once in adult care, the proportion with viral suppression was stable (73% at baseline and 74%, 77%, 67%, and 78% at 6, 12, 18, and 24 months, respectively)., Conclusions: Although most youth successfully linked to adult care, retention rates decreased over the 24-month follow-up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing this transition for youth with HIV., Competing Interests: Potential conflicts of interest. B. C. Z. reports grants or contracts unrelated to this work from National Institute of Mental Health (grant K23MH114771) and participation as a volunteer member of the CombinADO data and safety monitoring board (UH3HD096926; principal investigator, Elaine Abrams). C. d. R. is a scientific advisor for and reports consulting fees from Resverlogix. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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18. Three-year Outcomes After Conversion From Monthly to Every 2-month Belatacept Maintenance Therapy in Kidney Transplant Recipients: Results From a Randomized Controlled Trial.
- Author
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Johnson AC, Karadkhele GM, Shenvi N, Easley KA, Larsen CP, and Badell IR
- Abstract
Maintenance immunosuppression with belatacept following kidney transplantation results in improved long-term graft function as compared with calcineurin inhibitors. However, broad application of belatacept has been limited, in part related to logistical barriers surrounding a monthly (q1m) infusion requirement., Methods: To determine whether every 2-mo (q2m) belatacept is noninferior to standard q1m maintenance, we conducted a prospective, single-center randomized trial in low-immunologic-risk, stable renal transplant recipients. Here, post hoc analysis of 3-y outcomes, including renal function and adverse events, are reported., Results: One hundred sixty-three patients received treatment in the q1m control group (n = 82) or q2m study group (n = 81). Renal allograft function as measured by baseline-adjusted estimated glomerular filtration rate was not significantly different between groups (time-averaged mean difference of 0.2 mL/min/1.73 m
2 ; 95% confidence interval: -2.5, 2.9). There were no statistically significant differences in time to death or graft loss, freedom from rejection, or freedom from donor-specific antibodies (DSAs). During the extended 12- to 36-mo follow-up, 3 deaths, 1 graft loss occurred in the q1m group, compared with 2 deaths, and 2 graft losses in the q2m group. In the q1m group, 1 patient developed DSAs and acute rejection. In the q2m group, 3 patients developed DSAs and 2 associated with acute rejection., Conclusions: Based on the similar renal function and survival at 36 mo compared with q1m, q2m belatacept is a potentially viable maintenance immunosuppressive strategy in low immunologic risk kidney transplant recipients that may facilitate increased clinical utilization of costimulation blockade-based immunosuppression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)- Published
- 2023
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19. Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization.
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Buetefisch CM, Haut MW, Revill KP, Shaeffer S, Edwards L, Barany DA, Belagaje SR, Nahab F, Shenvi N, and Easley K
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- Humans, Stroke Volume, Brain, Transcranial Magnetic Stimulation, Evoked Potentials, Motor physiology, Motor Cortex, Stroke
- Abstract
Background: After stroke, increases in contralesional primary motor cortex (M1
CL ) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL ) injury, but this has yet to be tested clinically., Objectives: We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke., Methods: Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP-)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test., Results: The extent of M1CL reorganization was related to greater lesion volume in the MEP- group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP- but not MEP+ participants. Absence of an MEP (MEP-), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function., Conclusions: In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence.ClinicalTrials.gov Identifier: NCT02544503.- Published
- 2023
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20. Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy.
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Harper J, Ribeiro SP, Chan CN, Aid M, Deleage C, Micci L, Pino M, Cervasi B, Raghunathan G, Rimmer E, Ayanoglu G, Wu G, Shenvi N, Barnard RJ, Del Prete GQ, Busman-Sahay K, Silvestri G, Kulpa DA, Bosinger SE, Easley KA, Howell BJ, Gorman D, Hazuda DJ, Estes JD, Sekaly RP, and Paiardini M
- Subjects
- Animals, CD4-Positive T-Lymphocytes, Humans, Interleukin-10 genetics, Macaca mulatta, HIV Infections drug therapy, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Immunodeficiency Virus
- Abstract
Interleukin-10 (IL-10) is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper (Tfh) cell differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph nodes (LNs) were induced by infection and not normalized with antiretroviral therapy (ART). During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including Tfh cells, and predicted the frequency of CD4+ Tfh cells and their cell-associated SIV-DNA content during ART, respectively. In ART-treated rhesus macaques, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B cell follicle in proximity to IL-10. Finally, we demonstrated that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques reduced B cell follicle maintenance and, by extension, LN memory CD4+ T cells, including Tfh cells and those expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.
- Published
- 2022
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21. Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion.
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Patel RM, Lukemire J, Shenvi N, Arthur C, Stowell SR, Sola-Visner M, Easley K, Roback JD, Guo Y, and Josephson CD
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- Age Factors, Anemia, Neonatal mortality, Bronchopulmonary Dysplasia etiology, Bronchopulmonary Dysplasia mortality, Cohort Studies, Enterocolitis, Necrotizing etiology, Enterocolitis, Necrotizing mortality, Female, Georgia, Humans, Incidence, Infant, Newborn, Male, Middle Aged, Retinopathy of Prematurity etiology, Retinopathy of Prematurity mortality, Sex Factors, Anemia, Neonatal therapy, Blood Donors, Erythrocyte Transfusion adverse effects, Infant, Very Low Birth Weight
- Abstract
Importance: There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions., Objective: To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions., Design, Setting, and Participants: This is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (≤1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020., Exposures: Donor sex and mean donor age., Main Outcomes and Measures: The primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight., Results: In total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased., Conclusions and Relevance: These findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.
- Published
- 2021
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22. A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.
- Author
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Pino M, Abid T, Pereira Ribeiro S, Edara VV, Floyd K, Smith JC, Latif MB, Pacheco-Sanchez G, Dutta D, Wang S, Gumber S, Kirejczyk S, Cohen J, Stammen RL, Jean SM, Wood JS, Connor-Stroud F, Pollet J, Chen WH, Wei J, Zhan B, Lee J, Liu Z, Strych U, Shenvi N, Easley K, Weiskopf D, Sette A, Pollara J, Mielke D, Gao H, Eisel N, LaBranche CC, Shen X, Ferrari G, Tomaras GD, Montefiori DC, Sekaly RP, Vanderford TH, Tomai MA, Fox CB, Suthar MS, Kozlowski PA, Hotez PJ, Paiardini M, Bottazzi ME, and Kasturi SP
- Subjects
- Administration, Inhalation, Administration, Intranasal, Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, COVID-19 immunology, COVID-19 pathology, COVID-19 virology, Cell Line, Cytokines immunology, Humans, Immunoglobulin G immunology, Lung pathology, Macaca mulatta, Male, Protein Binding, Protein Domains, Spike Glycoprotein, Coronavirus immunology, Viral Load, Adjuvants, Immunologic administration & dosage, Alum Compounds administration & dosage, COVID-19 prevention & control, COVID-19 Vaccines, SARS-CoV-2, Saccharomycetales genetics, Spike Glycoprotein, Coronavirus genetics
- Abstract
Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate., (Copyright A(c) 2021, American Association for the Advancement of Science.)
- Published
- 2021
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23. IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques.
- Author
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Harper J, Huot N, Micci L, Tharp G, King C, Rascle P, Shenvi N, Wang H, Galardi C, Upadhyay AA, Villinger F, Lifson J, Silvestri G, Easley K, Jacquelin B, Bosinger S, Müller-Trutwin M, and Paiardini M
- Subjects
- Animals, Antiviral Agents pharmacology, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes virology, Female, Killer Cells, Natural virology, Lymphocyte Activation drug effects, Macaca mulatta, Simian Acquired Immunodeficiency Syndrome virology, Simian Immunodeficiency Virus physiology, Viral Load drug effects, Viremia blood, Viremia drug therapy, Anti-Retroviral Agents pharmacology, Interferon-gamma pharmacology, Interleukins pharmacology, Killer Cells, Natural drug effects, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Immunodeficiency Virus drug effects
- Abstract
Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy, nonpathogenic infections in natural hosts, such African green monkeys, are characterized by a lack of gut microbial translocation and robust secondary lymphoid natural killer cell responses resulting in an absence of chronic inflammation and limited SIV dissemination in lymph node B-cell follicles. Here we report, using the pathogenic model of antiretroviral therapy-treated, SIV-infected rhesus macaques that sequential interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells (NKG2a/c
low CD16+ ) with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides. This is in contrast to control macaques, where less differentiated, interferon gamma-producing natural killer cells predominate. The frequency and activity of terminally differentiated NKG2a/clow CD16+ natural killer cells correlates with a reduction of replication-competent SIV in lymph node during antiretroviral therapy and time to viral rebound following analytical treatment interruption. These data demonstrate that African green monkey-like natural killer cell differentiation profiles can be rescued in rhesus macaques to promote viral clearance in tissues.- Published
- 2021
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24. Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.
- Author
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Strongin Z, Micci L, Fromentin R, Harper J, McBrien J, Ryan E, Shenvi N, Easley K, Chomont N, Silvestri G, and Paiardini M
- Subjects
- Animals, CD4-CD8 Ratio, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, DNA, Viral blood, DNA, Viral immunology, Macaca mulatta, Time Factors, Anti-Retroviral Agents pharmacology, Simian Acquired Immunodeficiency Syndrome blood, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus immunology, Simian Immunodeficiency Virus metabolism, Th17 Cells immunology, Th17 Cells metabolism
- Abstract
Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIV
mac239 -infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <104 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs. IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy., (Copyright © 2020 American Society for Microbiology.)- Published
- 2020
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25. Observational study of cytomegalovirus from breast milk and necrotising enterocolitis.
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Patel RM, Shenvi N, Knezevic A, Hinkes M, Bugg GW, Stowell SR, Roback JD, Easley KA, and Josephson C
- Abstract
Objective: To evaluate the relationship between cytomegalovirus (CMV) exposure from breast milk and risk of necrotising enterocolitis (NEC)., Design: Secondary analysis of a multicentre, observational cohort study. Maternal breast milk and infant serum or urine were serially evaluated by nucleic acid testing at scheduled intervals for CMV. Infants with evidence of congenital infection were excluded. Competing-risks Cox models, with adjustment for confounders, were used to evaluate the relationship between breast milk CMV exposure or postnatal CMV infection and NEC., Setting: Three neonatal intensive care units in Atlanta, Georgia., Patients: Infants with a birth weight≤1500 grams., Exposures: Maximal CMV viral load in breast milk in the first 14 days after birth or postnatal CMV infection. Two different approaches were used to assess the timing of onset of CMV infection (midpoint or early)., Main Outcome Measures: NEC, defined as Bell stage II or greater., Results: Among 596 enrolled infants, 457 (77%) were born to CMV seropositive mothers and 33 developed postnatal CMV infection (cumulative incidence 7.3%, 95% CI 5.0% to 10.1%). The incidence of NEC was 18% (6/33) among infants with CMV infection, compared with 7% (37/563) among infants without infection (adjusted cause-specific HR (CSHR): 2.81; 95% CI 0.73 to 10.9 (midpoint); 6.02; 95% CI 1.28 to 28.4 (early)). Exposure to higher breast milk CMV viral load was associated with a higher risk of NEC (adjusted CSHR per twofold increase 1.28; 95% CI 1.06 to 1.54)., Conclusions: CMV exposure from breast milk may be associated with the development of NEC in very low birth weight infants., Competing Interests: Competing interests: Dr. Patel received travel support from Danone Nutricia to attend the SIGNEC UK meeting., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
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26. The effects of roux en y gastric bypass surgery on neurobehavioral symptom domains associated with severe obesity.
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Musselman D, Shenvi N, Manatunga A, Miller AH, Lin E, and Gletsu-Miller N
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- Adipokines blood, Adiposity physiology, Adult, Affect, Blood Glucose metabolism, Cognition, Depression psychology, Female, Humans, Interleukin-6 blood, Middle Aged, Subcutaneous Fat pathology, Suicidal Ideation, Young Adult, Anastomosis, Roux-en-Y psychology, Obesity, Morbid psychology, Obesity, Morbid surgery
- Abstract
Background: Neurobehavioral symptoms and cognitive dysfunction related to mood disorders are present in individuals with severe obesity. We sought to determine acute improvements in these symptoms and relationships with adiposity, inflammation, and insulin sensitivity after roux-en-y gastric bypass (RYGB) surgery., Methods: The self-report Zung Depression Rating (ZDRS) and Neurotoxicity Rating (NRS) scales were administered before, and at 6-months after RYGB surgery in severely obese women (body mass index > 35 kg/m
2 ; N = 19). Symptom domains corresponding to depressed mood/suicide ideation, anxiety, cognitive, somatic, and neurovegetative symptoms were assessed. Biologic measures were of adiposity [leptin, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue], inflammation [IL-6, C-reactive protein (CRP)], and insulin sensitivity (Si). Spearman correlations and linear regression (adjusted for biologic measures) assessed relationships between changes in biologic measures and changes in neurobehavioral domains., Results: By 6-months after RYGB, VAT, SAT, Si, CRP, and IL-6 had improved (p < .05). Anxiety, somatic, and neurovegetative symptoms domains improved (p < .05), but depressed mood/suicidal ideation and cognitive domains did not. Reductions in VAT were associated with decreases in neurovegetative symptoms (beta = 295 ± 85, p < .01). We also found significant positive longitudinal associations between IL-6 concentrations and minor changes in cognitive symptoms., Conclusion: Anxiety, somatic and neurovegetative symptoms, improved within 6 months after RYGB, but depressed mood/suicidal ideation and cognitive symptoms did not improve. Associations between visceral adiposity, IL-6 concentrations and neurovegetative and cognitive symptoms support links between obesity, inflammation and distinct neurobehavioral symptoms., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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27. Enteral iron supplementation, red blood cell transfusion, and risk of bronchopulmonary dysplasia in very-low-birth-weight infants.
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Patel RM, Knezevic A, Yang J, Shenvi N, Hinkes M, Roback JD, Easley KA, and Josephson CD
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- Adult, Blood Transfusion, Cohort Studies, Female, Humans, Infant, Infant, Newborn, Infant, Very Low Birth Weight, Iron, Lung Injury prevention & control, Male, Multicenter Studies as Topic, Multivariate Analysis, Pregnancy, Prospective Studies, Reproducibility of Results, Retrospective Studies, Risk Factors, Bronchopulmonary Dysplasia drug therapy, Bronchopulmonary Dysplasia therapy, Erythrocyte Transfusion methods
- Abstract
Background: Enteral iron supplementation and RBC transfusions are routinely administered to very-low-birth-weight (VLBW) infants, although the potential risks of these exposures have not been adequately quantified. This study evaluated the association between the cumulative dose of enteral iron supplementation, total volume of RBCs transfused, and risk of bronchopulmonary dysplasia (BPD) in VLBW infants., Study Design and Methods: Retrospective, multicenter observational cohort study in Atlanta, Georgia. Cumulative supplemental enteral iron exposure and total volume of RBCs transfused were measured until the age at assessment of BPD. Multivariable generalized linear models were used to control for confounding, and the reliability of the factors was assessed in 1000 bootstrap models., Results: A total of 598 VLBW infants were studied. In multivariable analyses, a greater cumulative dose of supplemental enteral iron exposure was associated with an increased risk of BPD (adjusted relative risk per 50-mg increase, 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.002). Similarly, a greater volume of RBCs transfused was associated with a higher risk of BPD (adjusted relative risk per 20-mL increase, 1.05; 95% CI, 1.02-1.07; p < 0.001). Both factors were reliably associated with BPD (>50%). Volume of RBCs transfused was similar to gestational age in reliability as a risk factor for BPD (present in 100% of models) and was more reliable than mechanical ventilation at 1 week of age., Conclusion: The cumulative dose of supplemental enteral iron exposure and total volume of RBC transfusion are both independently associated with an increased risk of BPD in VLBW infants., (© 2019 AABB.)
- Published
- 2019
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28. Platelet transfusions and mortality in necrotizing enterocolitis.
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Patel RM, Josephson CD, Shenvi N, Maheshwari A, Easley KA, Stowell S, Sola-Visner M, and Ferrer-Marin F
- Subjects
- Birth Weight, Enterocolitis, Necrotizing metabolism, Enzyme-Linked Immunosorbent Assay, Female, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Very Low Birth Weight, Male, Neuropeptide Y metabolism, Risk Factors, Enterocolitis, Necrotizing mortality, Enterocolitis, Necrotizing therapy, Platelet Transfusion
- Abstract
Background: Prior studies have suggested an association between platelet transfusions (PTXs) and worse outcomes among infants with necrotizing enterocolitis (NEC), potentially mediated by proinflammatory factors released by platelets. However, the effects of storage on platelet proinflammatory factor release and the confounding role of illness severity on NEC outcomes have not been determined., Study Design and Methods: First, neuropeptide Y (a potent splanchnic vasoconstrictor released by platelets) was measured by enzyme-linked immunosorbent assay in fresh frozen plasma and in the supernatant of leukoreduced apheresis-derived platelets at different times during storage. Next, we evaluated the relationship between PTX rates and death in a multicenter cohort of very-low-birth-weight infants with NEC, adjusting for illness severity., Results: Neuropeptide Y levels increased over time in the supernatant of leukoreduced apheresis-derived platelets and were 4.4-fold and 8.9-fold higher than in fresh frozen plasma on Days 2 and 3 of storage, respectively (p < 0.001). Among 598 very-low-birth-weight infants, 44 developed NEC. In unadjusted analysis, PTX rate was 30.3 (95% confidence interval [CI], 11.5-80.1) per 100 infant-days among infants who died, compared to 6.0 (95% CI, 3.2-11.2) among survivors (incidence rate ratio, 5.1; 95% CI, 1.6-16.2; p = 0.006). In multivariable analysis, there was no association between PTX rate and mortality (incidence rate ratio, 3.0; 95% CI, 0.6-15.0; p = 0.18), although estimation was imprecise., Conclusion: Proinflammatory mediators accumulate in platelet suspensions during storage. Although PTX rates were not associated with increased mortality among infants with NEC in our study, our estimates suggest the potential for such an association that needs evaluation in larger studies., (© 2018 AABB.)
- Published
- 2019
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29. Medicaid Payer Status Is Associated with Increased 90-Day Morbidity and Resource Utilization Following Primary Total Hip Arthroplasty: A Propensity-Score-Matched Analysis.
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Shau D, Shenvi N, Easley K, Smith M, Bradbury T, and Guild G 3rd
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- Aged, Facilities and Services Utilization statistics & numerical data, Female, Health Resources statistics & numerical data, Humans, Male, Middle Aged, Morbidity, Propensity Score, Time Factors, United States, Arthroplasty, Replacement, Hip economics, Medicaid, Postoperative Complications epidemiology
- Abstract
Background: Medicaid payer status has been shown to affect risk-adjusted outcomes and resource utilization across multiple medical specialties. The purpose of this study was to examine resource utilization via readmission rates, length of stay, and total cost specific to Medicaid payer status following primary total hip arthroplasty., Methods: The Nationwide Readmissions Database (NRD) was utilized to identify patients who underwent total hip arthroplasty in 2013 as well as corresponding "Medicaid" or "non-Medicaid" payer status. Demographic data, 14 individual comorbidities, readmission rates, length of stay, and direct cost were evaluated. A propensity-score-based matching model was utilized to control for baseline confounding variables between payer groups. Following propensity-score matching, the chi-square test was used to compare readmission rates between the 2 payer groups. The relative risk (RR) with 95% confidence interval (CI) was estimated to quantify readmission risk. Length of stay and total cost comparisons were evaluated using the Wilcoxon signed-rank test., Results: A total of 5,311 Medicaid and 144,814 non-Medicaid patients managed with total hip arthroplasty were identified from the 2013 NRD. A propensity score was estimated for each patient on the basis of the available baseline demographics, and 5,311 non-Medicaid patients were matched by propensity score to the 5,311 Medicaid patients. Medicaid versus non-Medicaid payer status yielded significant differences in overall readmission rates of 28.8% versus 21.0% (p < 0.001; RR = 1.37 [95% CI, 1.28 to 1.46]) and 90-day hip-specific readmission rates of 2.5% versus 1.8% (p = 0.01; RR = 1.38 [95% CI, 1.07 to 1.78]). Mean length of stay was greater in the Medicaid group than in the non-Medicaid group at 4.5 versus 3.3 days (p < 0.0001), as was the mean total cost at $71,110 versus $65,309 (p < 0.0001)., Conclusions: This study demonstrates that Medicaid payer status is independently associated with increased resource utilization, including readmission rates, length of stay, and total cost following primary total hip arthroplasty. Providers may have a disincentive to treat patient populations who require increased resource utilization following surgery. Risk adjustment models accounting for Medicaid payer status are necessary to avoid decreased access to care for this patient population and to avoid financial penalty for physicians and hospitals alike., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
- Published
- 2018
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30. High-resolution plasma metabolomics analysis to detect Mycobacterium tuberculosis-associated metabolites that distinguish active pulmonary tuberculosis in humans.
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Collins JM, Walker DI, Jones DP, Tukvadze N, Liu KH, Tran VT, Uppal K, Frediani JK, Easley KA, Shenvi N, Khadka M, Ortlund EA, Kempker RR, Blumberg HM, and Ziegler TR
- Subjects
- Adult, Carrier State blood, Cross-Sectional Studies, Family Characteristics, Humans, Lysophospholipids analysis, Middle Aged, Phosphatidylglycerols analysis, Tandem Mass Spectrometry, Tuberculosis, Pulmonary blood, Young Adult, Biomarkers blood, Carrier State diagnosis, Metabolomics methods, Mycobacterium tuberculosis metabolism, Tuberculosis, Pulmonary diagnosis
- Abstract
Introduction: Pulmonary tuberculosis (TB) is a major worldwide health problem that lacks robust blood-based biomarkers for detection of active disease. High-resolution metabolomics (HRM) is an innovative method to discover low-abundance metabolites as putative blood biomarkers to detect TB disease, including those known to be produced by the causative organism, Mycobacterium tuberculosis (Mtb)., Methods: We used HRM profiling to measure the plasma metabolome for 17 adults with active pulmonary TB disease and 16 of their household contacts without active TB. We used a suspect screening approach to identify metabolites previously described in cell culture studies of Mtb based on retention time and accurate mass matches., Results: The association of relative metabolite abundance in active TB disease subjects compared to their household contacts predicted three Mtb-associated metabolites that were significantly increased in the active TB patients based on accurate mass matches: phosphatidylglycerol (PG) (16:0_18:1), lysophosphatidylinositol (Lyso-PI) (18:0) and acylphosphatidylinositol mannoside (Ac1PIM1) (56:1) (p<0.001 for all). These three metabolites provided excellent classification accuracy for active TB disease (AUC = 0.97). Ion dissociation spectra (tandem MS/MS) supported the identification of PG (16:0_18:1) and Lyso-PI (18:0) in the plasma of patients with active TB disease, though the identity of Ac1PIM1 could not be definitively confirmed., Conclusions: Presence of the Mtb-associated lipid metabolites PG (16:0_18:1) and Lyso-PI (18:0) in plasma accurately identified patients with active TB disease. Consistency of in vitro and in vivo data suggests suitability for exploring these in future studies for possible development as TB disease biomarkers., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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31. Social Capital, Depressive Symptoms, and HIV Viral Suppression Among Young Black, Gay, Bisexual and Other Men Who Have Sex with Men Living with HIV.
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Hussen SA, Easley KA, Smith JC, Shenvi N, Harper GW, Camacho-Gonzalez AF, Stephenson R, and Del Rio C
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Depression diagnosis, Depression ethnology, HIV Infections therapy, Homosexuality, Male ethnology, Humans, Male, Microbial Viability, Prejudice psychology, Sexual Behavior statistics & numerical data, Social Stigma, Young Adult, Black People psychology, Depression psychology, HIV Infections psychology, Homosexuality, Male psychology, Sexual and Gender Minorities psychology, Social Capital, Viral Load
- Abstract
Social capital, the sum of an individual's resource-containing social network connections, has been proposed as a facilitator of successful HIV care engagement. We explored relationships between social capital, psychological covariates (depression, stigma and internalized homonegativity), and viral suppression in a sample of young Black gay, bisexual and other men who have sex with men (YB-GBMSM). We recruited 81 HIV-positive YB-GBMSM 18-24 years of age from a clinic setting. Participants completed a cross-sectional survey, and HIV-1 viral load (VL) measurements were extracted from the medical record. Sixty-five percent (65%) were virally suppressed (HIV-1 VL ≤ 40 copies/ml). Forty-seven percent (47%) had a positive depression screen. Depressive symptoms affected viral suppression differently in YB-GBMSM with lower vs. higher social capital (p = 0.046, test for statistical interaction between depression and social capital). The odds of viral suppression among YB-GBMSM with lower social capital was 93% lower among those with depressive symptoms (OR 0.07, p = 0.002); however, there was no association between depressive symptoms and viral suppression among those with higher social capital. Our results suggest that social capital may buffer the strong negative effects of depressive symptoms on clinical outcomes in YB-GBMSM living with HIV. In addition to treating depression, there is a role for interventions to augment social capital among YB-GBMSM living with HIV as a strategy for enhancing care engagement.
- Published
- 2018
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32. Medicaid is associated with increased readmission and resource utilization after primary total knee arthroplasty: a propensity score-matched analysis.
- Author
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Shau D, Shenvi N, Easley K, Smith M, and Guild G 3rd
- Abstract
Background: Medicaid payer status has been shown to affect resource utilization across multiple medical specialties. There is no large database assessment of Medicaid and resource utilization in primary total knee arthroplasty (TKA), which this study sets out to achieve., Methods: The Nationwide Readmissions Database was used to identify patients who underwent TKA in 2013 and corresponding "Medicaid" or "non-Medicaid" payer statuses. Demographics, 15 individual comorbidities, readmission rates, length of stay, and direct cost were evaluated. A propensity score-based matching model was then used to control for baseline confounding variables between payer groups. A chi-square test for paired proportions was used to compare readmission rates between the 2 groups. Length of stay and direct cost comparisons were evaluated using the Wilcoxon signed-rank test., Results: A total of 8372 Medicaid and 268,261 non-Medicaid TKA patients were identified from the 2013 Nationwide Readmissions Database. A propensity score was estimated for each patient based on the baseline demographics, and 8372 non-Medicaid patients were propensity score matched to the 8372 Medicaid patients. Medicaid payer status yielded a statistically significant increase in overall readmission rates of 18.4% vs 14.0% ( P < .0001, relative risk = 1.31, 95% confidence interval [1.23-1.41]) with non-Medicaid status and 90-day readmission rates of 10.0% vs 7.4%, respectively ( P < .001, relative risk = 1.35, 95% confidence interval [1.22-1.48]). The mean length of stay was longer in the Medicaid group compared with the non-Medicaid group at 4.0 days vs 3.3 days ( P < .0001) as well as the mean total cost of $64,487 vs $61,021 ( P < .0001)., Conclusions: This study demonstrates that Medicaid payer status is independently associated with increased resource utilization, including readmission rates, length of stay, and total cost after TKA.
- Published
- 2018
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33. Peritransplantation Red Blood Cell Transfusion Is Associated with Increased Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
- Author
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Hosoba S, Waller EK, Shenvi N, Graiser M, Easley KA, Al-Kadhimi Z, Andoh A, Antun AG, Barclay S, Josephson CD, Koff JL, Khoury HJ, Langston AA, Zimring JC, Roback JD, and Giver CR
- Subjects
- Adult, Aged, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Male, Middle Aged, Perioperative Care adverse effects, Perioperative Care methods, Platelet Transfusion, Retrospective Studies, Risk, Survival Analysis, Transplantation, Homologous adverse effects, Young Adult, Erythrocyte Transfusion adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day -7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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34. T-cell receptor activator of nuclear factor-κB ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts.
- Author
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Titanji K, Vunnava A, Foster A, Sheth AN, Lennox JL, Knezevic A, Shenvi N, Easley KA, Ofotokun I, and Weitzmann MN
- Subjects
- Adult, CD4 Lymphocyte Count, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Male, Middle Aged, Staining and Labeling, Bone Diseases, Metabolic pathology, HIV Infections complications, Osteoprotegerin analysis, RANK Ligand analysis, T-Lymphocytes chemistry
- Abstract
Objective: Higher incidence of osteopenia and osteoporosis underlie increased rates of fragility fracture in HIV infection. B cells are a major source of osteoprotegerin (OPG), an inhibitor of the key osteoclastogenic cytokine receptor activator of nuclear factor-κB ligand (RANKL). We previously showed that higher B-cell RANKL/OPG ratio contributes to HIV-induced bone loss. T-cell OPG production in humans, however, remains undefined and the contribution of T-cell OPG and RANKL to HIV-induced bone loss has not been explored., Design: We investigated T-cell OPG and RANKL production in ART-naive HIV-infected and uninfected individuals in relation to indices of bone loss in a cross-sectional study., Methods: T-cell RANKL and OPG production was determined by intracellular staining and flow cytometry, and plasma levels of bone resorption markers were determined by ELISA., Results: We demonstrate for the first time in-vivo human T-cell OPG production, which was significantly lower in HIV-infected individuals and was coupled with moderately higher T-cell RANKL production, resulting in a significantly higher T-cell RANKL/OPG ratio. T-cell RANKL/OPG ratio correlated significantly with BMD-derived z-scores at the hip, lumbar spine and femur neck in HIV-infected individuals with CD4 T-cell counts at least 200 cells/μl but not in those with lower counts., Conclusion: Our data suggest that T cells may be a physiologically relevant source of OPG and T-cell RANKL/OPG imbalance is associated with HIV-induced bone loss in CD4 T-cell-sufficient patients. Both B and T lymphocytes may thus contribute to HIV-induced bone loss.
- Published
- 2018
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35. The impact of diabetes on CD4 recovery in persons with HIV in an urban clinic in the United States.
- Author
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Zuniga JA, Easley KA, Shenvi N, Nguyen ML, and Holstad M
- Subjects
- Adult, Ambulatory Care Facilities, Female, HIV Infections diagnosis, HIV Infections ethnology, HIV-1 isolation & purification, Humans, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Urban Population, Black or African American statistics & numerical data, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Diabetes Mellitus, Type 2 ethnology, HIV Infections drug therapy, HIV Infections immunology, HIV-1 drug effects
- Abstract
The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV-T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV-T2DM cohort ( p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV-T2DM African American women and 28 ± 7 cells/µl/year in HIV-T2DM African American men ( p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV-T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13-47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.
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- 2018
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36. Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants.
- Author
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Patel RM, Knezevic A, Shenvi N, Hinkes M, Keene S, Roback JD, Easley KA, and Josephson CD
- Subjects
- Anemia blood, Anemia therapy, Anti-Bacterial Agents administration & dosage, Birth Weight, Enterocolitis, Necrotizing epidemiology, Female, Georgia, Gestational Age, Hemoglobin A analysis, Humans, Incidence, Infant, Newborn, Infant, Very Low Birth Weight, Intensive Care Units, Neonatal, Male, Proportional Hazards Models, Prospective Studies, Risk Factors, Anemia complications, Enterocolitis, Necrotizing etiology, Erythrocyte Transfusion adverse effects
- Abstract
Importance: Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures., Objective: To determine the relationship between RBC transfusion, severe anemia, and NEC., Design, Setting, and Participants: In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC., Exposures: The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals., Main Outcomes and Measures: Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk., Results: Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001)., Conclusions and Relevance: Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.
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- 2016
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37. Macronutrient intake and body composition changes during anti-tuberculosis therapy in adults.
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Frediani JK, Sanikidze E, Kipiani M, Tukvadze N, Hebbar G, Ramakrishnan U, Jones DP, Easley KA, Shenvi N, Kempker RR, Tangpricha V, Blumberg HM, and Ziegler TR
- Subjects
- Adult, Antitubercular Agents administration & dosage, Body Mass Index, Body Weight, Dietary Carbohydrates administration & dosage, Dietary Carbohydrates analysis, Dietary Fats administration & dosage, Dietary Fats analysis, Dietary Proteins administration & dosage, Dietary Proteins analysis, Dose-Response Relationship, Drug, Double-Blind Method, Electric Impedance, Female, Humans, Linear Models, Male, Middle Aged, Nutrition Assessment, Tuberculosis, Multidrug-Resistant drug therapy, Vitamin D administration & dosage, Vitamin D analysis, Young Adult, Antitubercular Agents therapeutic use, Body Composition, Energy Intake, Malnutrition blood, Tuberculosis, Multidrug-Resistant complications
- Abstract
Background: Malnutrition is common in patients with active tuberculosis (TB), yet little information is available on serial dietary intake or body composition in TB disease., Objective: To evaluate macronutrient intake and body composition in individuals with newly diagnosed TB over time., Design: Adults with active pulmonary TB (n = 191; 23 with multidrug resistant TB (MDR-TB) and 36 culture-negative household contacts (controls) enrolled in a clinical trial of high-dose cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index (BMI; kg/m(2)) and bioelectrical impedance analysis (BIA) to estimate fat mass and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes over time and linear regression were used., Results: At baseline, mean daily energy, protein, fat and carbohydrate (CHO) intakes were significantly higher, and body weight, BMI, fat-free mass and fat mass were significantly lower, between TB subjects and controls. These remained significant after adjusting for age, gender, employment status and smoking. In all TB subjects, baseline mean daily intakes of energy, fat and protein were adequate when compared to the US Dietary Reference Intakes and protein significantly increased over time (p < 0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB patients exhibited lower body weight and fat-free mass over time, despite similar daily intake of kcal, protein, and fat., Conclusions: Macronutrient intake was higher in TB patients than controls, but TB-induced wasting was evident. As macronutrient intake of TB subjects increased over time, there was a parallel increase in BMI, while body composition proportions were maintained. However, individuals with MDR-TB demonstrated concomitantly decreased body weight and fat-free mass over time versus drug-sensitive TB patients, despite increased macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient intake, likely reflecting the catabolic effects of TB., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
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- 2016
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38. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.
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Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley KA, Shenvi N, Kempker RR, Frediani JK, Mirtskhulava V, Alvarez JA, Lomtadze N, Vashakidze L, Hao L, Del Rio C, Tangpricha V, Blumberg HM, and Ziegler TR
- Subjects
- Adolescent, Adult, Antitubercular Agents adverse effects, Calcifediol blood, Cholecalciferol adverse effects, Cholecalciferol metabolism, Cholecalciferol therapeutic use, Cohort Studies, Double-Blind Method, Female, Georgia (Republic), Humans, Intention to Treat Analysis, Longitudinal Studies, Male, Middle Aged, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Patient Dropouts, Sputum drug effects, Sputum immunology, Sputum microbiology, Tuberculosis, Pulmonary complications, Tuberculosis, Pulmonary immunology, Tuberculosis, Pulmonary microbiology, Vitamin D Deficiency blood, Vitamin D Deficiency complications, Vitamin D Deficiency immunology, Young Adult, Antitubercular Agents therapeutic use, Cholecalciferol administration & dosage, Dietary Supplements adverse effects, Mycobacterium tuberculosis immunology, Tuberculosis, Pulmonary drug therapy, Vitamin D Deficiency diet therapy
- Abstract
Background: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy., Objective: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease., Design: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative., Results: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99)., Conclusion: A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086., (© 2015 American Society for Nutrition.)
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- 2015
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39. Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis: Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.
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Cribbs SK, Tse C, Andrews J, Shenvi N, and Martin GS
- Subjects
- APACHE, Adult, Age Factors, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cross Infection complications, Female, HIV Infections drug therapy, Hospital Mortality, Humans, Intensive Care Units, Male, Middle Aged, Outcome Assessment, Health Care, Pneumonia complications, Prospective Studies, Sepsis mortality, Socioeconomic Factors, HIV Infections complications, Sepsis complications
- Abstract
Objectives: Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to affect outcomes. We hypothesized that HIV-infected patients with severe sepsis would have worse outcomes compared with their HIV-uninfected counterparts in a large safety-net hospital where access to healthcare is low and delivery of critical care is delayed., Design: Secondary analysis of an ongoing prospective observational study between 2006 and 2010., Setting: Three adult ICUs (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital, Atlanta, GA., Patients: Adult patients with severe sepsis in the ICU., Interventions: Baseline patient characteristics and clinical outcomes were collected. HIV-infected and HIV-uninfected patients with sepsis were compared using t tests, chi-square tests, and logistic regression; p values less than 0.05 indicated significance., Measurements and Main Results: Of 1,095 patients with severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200. HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01). HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of mortality by multivariate regression modeling after adjusting for age, history of pneumonia, history of hospital-acquired infection, and history of sepsis., Conclusions: HIV-infected patients with severe sepsis continue to suffer worse outcomes compared with HIV-uninfected patients in a large urban safety-net hospital caring for patients with limited access to medical care. Further studies need to be done to investigate the effect of socioeconomic status and mitigate healthcare disparities among critically ill HIV-infected patients.
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- 2015
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40. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study.
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Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, Patel RM, Hillyer CD, and Roback JD
- Subjects
- Cohort Studies, Female, Humans, Infant, Newborn, Male, Proportional Hazards Models, Prospective Studies, Risk Factors, Cytomegalovirus isolation & purification, Cytomegalovirus Infections transmission, Infant, Newborn, Diseases etiology, Infant, Very Low Birth Weight, Milk, Human microbiology, Transfusion Reaction
- Abstract
Importance: Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized., Objective: To estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk., Design, Setting, and Participants: A prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤ 1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death., Exposures: Blood transfusion and breast milk feeding., Main Outcomes and Measures: Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT., Results: The seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%)., Conclusions and Relevance: Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection., Trial Registration: clinicaltrials.gov Identifier: NCT00907686.
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- 2014
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41. Tensor hypercontracted ppRPA: reducing the cost of the particle-particle random phase approximation from O(r(6)) to O(r(4)).
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Shenvi N, van Aggelen H, Yang Y, and Yang W
- Abstract
In recent years, interest in the random-phase approximation (RPA) has grown rapidly. At the same time, tensor hypercontraction has emerged as an intriguing method to reduce the computational cost of electronic structure algorithms. In this paper, we combine the particle-particle random phase approximation with tensor hypercontraction to produce the tensor-hypercontracted particle-particle RPA (THC-ppRPA) algorithm. Unlike previous implementations of ppRPA which scale as O(r(6)), the THC-ppRPA algorithm scales asymptotically as only O(r(4)), albeit with a much larger prefactor than the traditional algorithm. We apply THC-ppRPA to several model systems and show that it yields the same results as traditional ppRPA to within mH accuracy. Our method opens the door to the development of post-Kohn Sham functionals based on ppRPA without the excessive asymptotic cost of traditional ppRPA implementations.
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- 2014
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42. A culture-specific nutrient intake assessment instrument in patients with pulmonary tuberculosis.
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Frediani JK, Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley KA, Shenvi N, Ramakrishnan U, Tangpricha V, Blumberg HM, and Ziegler TR
- Subjects
- Adult, Diet Records, Diet Surveys, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Dietary Proteins administration & dosage, Female, Georgia (Republic), Humans, Male, Pilot Projects, Randomized Controlled Trials as Topic, Reproducibility of Results, Socioeconomic Factors, Surveys and Questionnaires, Trace Elements administration & dosage, Vitamins administration & dosage, Energy Intake ethnology, Nutrition Assessment, Tuberculosis, Pulmonary diet therapy
- Abstract
Background & Aim: To develop and evaluate a culture-specific nutrient intake assessment tool for use in adults with pulmonary tuberculosis (TB) in Tbilisi, Georgia., Methods: We developed an instrument to measure food intake over 3 consecutive days using a questionnaire format. The tool was then compared to 24 h food recalls. Food intake data from 31 subjects with TB were analyzed using the Nutrient Database System for Research (NDS-R) dietary analysis program. Paired t-tests, Pearson correlations and intraclass correlation coefficients (ICC) were used to assess the agreement between the two methods of dietary intake for calculated nutrient intakes., Results: The Pearson correlation coefficient for mean daily caloric intake between the 2 methods was 0.37 (P = 0.04) with a mean difference of 171 kcals/day (p = 0.34). The ICC was 0.38 (95% CI: 0.03-0.64) suggesting the within-patient variability may be larger than between-patient variability. Results for mean daily intake of total fat, total carbohydrate, total protein, retinol, vitamins D and E, thiamine, calcium, sodium, iron, selenium, copper, and zinc between the two assessment methods were also similar., Conclusions: This novel nutrient intake assessment tool provided quantitative nutrient intake data from TB patients. These pilot data can inform larger studies in similar populations., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
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- 2013
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43. The tensor hypercontracted parametric reduced density matrix algorithm: coupled-cluster accuracy with O(r(4)) scaling.
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Shenvi N, van Aggelen H, Yang Y, Yang W, Schwerdtfeger C, and Mazziotti D
- Abstract
Tensor hypercontraction is a method that allows the representation of a high-rank tensor as a product of lower-rank tensors. In this paper, we show how tensor hypercontraction can be applied to both the electron repulsion integral tensor and the two-particle excitation amplitudes used in the parametric 2-electron reduced density matrix (p2RDM) algorithm. Because only O(r) auxiliary functions are needed in both of these approximations, our overall algorithm can be shown to scale as O(r(4)), where r is the number of single-particle basis functions. We apply our algorithm to several small molecules, hydrogen chains, and alkanes to demonstrate its low formal scaling and practical utility. Provided we use enough auxiliary functions, we obtain accuracy similar to that of the standard p2RDM algorithm, somewhere between that of CCSD and CCSD(T).
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- 2013
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44. Comparison of low-rank tensor expansions for the acceleration of quantum chemistry computations.
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Hoy EP, Shenvi N, and Mazziotti DA
- Abstract
Low-rank spectral expansion and tensor hypercontraction are two promising techniques for reducing the size of the two-electron excitation tensor by factorizing it into products of smaller tensors. Both methods can potentially realize an O(r(4)) quantum chemistry method where r is the number of one-electron orbitals. We compare the two factorizations in this paper by applying them to the parametric 2-electron reduced density matrix method with the M functional [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)]. We study several inorganic molecules, alkane chains, and potential curves as well as reaction and dissociation energies. The low-rank spectral expansion, we find, is typically more efficient than tensor hypercontraction due to a faster convergence of the energy and a smaller constant prefactor in the energy optimization. Both factorizations are applicable to the acceleration of a wide range of wavefunction and reduced-density-matrix methods.
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- 2013
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45. Reference values for renal size obtained from MAG3 scintigraphy.
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Taylor AT, Shenvi N, Folks RD, Garcia EV, Baruch BS, and Manatunga A
- Subjects
- Adult, Body Height, Body Mass Index, Body Weight, Female, Humans, Kidney Diseases diagnostic imaging, Male, Organ Size, Radionuclide Imaging, Reference Values, Kidney diagnostic imaging, Kidney pathology, Technetium Tc 99m Mertiatide
- Abstract
Purpose: The purposes of this study were to establish reference values for renal size determined from 99mTc-MAG3 renal scintigraphy and to derive regression equations to predict normal limits., Methods: The study population consisted of 106 subjects evaluated for kidney donation who underwent 99mTc-MAG3 renal scintigraphy. Renal length, width, and area were determined from the pixel length and area of whole-kidney regions of interest and correlated with patient sex, height, weight, body mass index, and body surface area (BSA). Reference values were obtained based on estimation of the lower and upper percentiles via quantile regression., Results: The mean (SD) left and right kidney lengths was 12.2 (1.0) and 12.1 (1.0) in male and 11.9 (0.9) and 11.8 (0.9) in female patients, respectively. Sex was not a significant factor in the quantile regression models. Regression equations defining the lower and upper limits of renal length (cm) and area (cm) are as follows: left kidney length (5th percentile), 8.2+1.3×BSA; left kidney length (95th percentile), 9.1+2.3×BSA; right kidney length (5th percentile), 8.8+1.0×BSA; right kidney length (95th percentile), 11.1+1.4×BSA; left kidney area (5th percentile), 32.5+9.6×BSA; left kidney area (95th percentile), 12.6+31.7×BSA; right kidney area (5th percentile), 16.1+18.5×BSA; right kidney area (95th percentile), 32.6+22.2×BSA., Conclusions: Regression equations have been developed, which define the upper and lower limits of renal size from 99mTc-MAG3 images and may assist in the detection of unsuspected bilateral increases or decreases in renal size.
- Published
- 2013
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46. Achieving partial decoherence in surface hopping through phase correction.
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Shenvi N and Yang W
- Abstract
Fewest-switches surface hopping is one of the simplest and most popular methods for the computational study of nonadiabatic processes. Recently, a very simple phase correction was introduced to the traditional surface hopping algorithm, substantially improving its accuracy with essentially no associated computational cost [N. Shenvi, J. E. Subotnik, and W. Yang, J. Chem. Phys. 135, 024101 (2011)]. In this paper, we show that we can modify our phase-corrected algorithm slightly such that it takes into account one type of decoherence, again with no additional computational cost. We apply our algorithm to two existing model problems, demonstrating that it can indeed capture one particular type of decoherence without any of the sophisticated machinery of alternative algorithms.
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- 2012
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47. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study.
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Ofotokun I, Sheth AN, Sanford SE, Easley KA, Shenvi N, White K, Eaton ME, Del Rio C, and Lennox JL
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- Acquired Immunodeficiency Syndrome immunology, CD4 Lymphocyte Count, Drug Administration Schedule, Drug Therapy, Combination, Female, Follow-Up Studies, HIV Protease Inhibitors pharmacology, Humans, Lipids immunology, Lopinavir pharmacology, Male, Middle Aged, Pilot Projects, Prospective Studies, Pyrrolidinones pharmacology, RNA, Viral immunology, Raltegravir Potassium, Ritonavir pharmacology, Treatment Outcome, Viral Load, Acquired Immunodeficiency Syndrome drug therapy, HIV Protease Inhibitors administration & dosage, HIV-1, Lopinavir administration & dosage, Pyrrolidinones administration & dosage, Ritonavir administration & dosage
- Abstract
A nucleoside reverse transcriptase inhibitor (NRTI) backbone is a recommended component of standard highly active antiretroviral therapy (sHAART). However, long-term NRTI exposure can be limited by toxicities. NRTI class-sparing alternatives are warranted in select patient populations. This is a 48-week single-center, open-label pilot study in which 60 HIV-infected adults with plasma HIV-1 RNA (<50 copies/ml) on sHAART were randomized (2:1) to lopinavir/ritonavir (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch (LPV-r/RAL arm) or to continue on sHAART. The primary endpoint was the proportion of subjects with HIV-RNA<50 copies/ml at week 48. Secondary efficacy and immunologic and safety endpoints were evaluated. Demographics and baseline lipid profile were similar across arms. Mean entry CD4 T cell count was 493 cells/mm(3). At week 48, 92% [95% confidence interval (CI): 83-100%] of the LPV-r/RAL arm and 88% (95% CI: 75-100%) of the sHAART arm had HIV-RNA<50 copies/ml (p=0.70). Lipid profile (mean ± SEM, mg/dl, LPV-r/RAL vs. sHAART) at week 24 was total-cholesterol 194 ± 5 vs. 176 ± 9 (p=0.07), triglycerides 234 ± 30 vs. 133 ± 27 (p=0.003), and LDL-cholesterol 121 ± 6 vs. 110 ± 8 (p=0.27). There were no serious adverse events (AEs) in either arm. Regimen change occurred in three LPV-r/RAL subjects (n=1, due to LPV-r/RAL-related AEs) vs. 0 in sHAART. There were no differences between arms in bone mineral density, total body fat composition, creatinine clearance, or CD4 T cell counts at week 48. In virologically suppressed patients on HAART, switching therapy to the NRTI-sparing LPV-r/RAL combination produced similar sustained virologic suppression and immunologic profile as sHAART. AEs were comparable between arms, but the LPV-r/RAL arm experienced higher triglyceridemia.
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- 2012
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48. Multiquantum vibrational excitation of NO scattered from Au(111): quantitative comparison of benchmark data to ab initio theories of nonadiabatic molecule-surface interactions.
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Cooper R, Bartels C, Kandratsenka A, Rahinov I, Shenvi N, Golibrzuch K, Li Z, Auerbach DJ, Tully JC, and Wodtke AM
- Abstract
Surface phenomena: measurements of absolute probabilities are reported for the vibrational excitation of NO(v=0→1,2) molecules scattered from a Au(111) surface. These measurements were quantitatively compared to calculations based on ab initio theoretical approaches to electronically nonadiabatic molecule-surface interactions. Good agreement was found between theory and experiment (see picture; T(s) =surface temperature, P=excitation probability, and E=incidence energy of translation)., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
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49. Nonadiabatic dynamics at metal surfaces: independent electron surface hopping with phonon and electron thermostats.
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Shenvi N and Tully JC
- Abstract
Independent Electron Surface Hopping (IESH) is a computational method for accounting for nonadiabatic electronic transitions in simulations of molecular motion at metal surfaces. IESH is applicable in cases of strong coupling where the electronic friction model is suspect, and has been demonstrated to accurately reproduce the results of detailed molecular beam experiments on vibrationally inelastic scattering of nitric oxide from the (111) surface of gold. However, in its original form, IESH represents a closed system without energy flow outside the local region of explicitly included substrate atoms. In this paper we propose two "thermostats" for introducing energy flow to the bulk, one for phonons and the other for electronic excitations.
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- 2012
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50. The Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) Is a Reliable and Valid Tool for Evaluating Motor Imagery in Stroke Populations.
- Author
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Butler AJ, Cazeaux J, Fidler A, Jansen J, Lefkove N, Gregg M, Hall C, Easley KA, Shenvi N, and Wolf SL
- Abstract
Mental imagery can improve motor performance in stroke populations when combined with physical therapy. Valid and reliable instruments to evaluate the imagery ability of stroke survivors are needed to maximize the benefits of mental imagery therapy. The purposes of this study were to: examine and compare the test-retest intra-rate reliability of the Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) in stroke survivors and able-bodied controls, examine internal consistency of the visual and kinesthetic items of the MIQ-RS, determine if the MIQ-RS includes both the visual and kinesthetic dimensions of mental imagery, correlate impairment and motor imagery scores, and investigate the criterion validity of the MIQ-RS in stroke survivors by comparing the results to the KVIQ-10. Test-retest analysis indicated good levels of reliability (ICC range: .83-.99) and internal consistency (Cronbach α: .95-.98) of the visual and kinesthetic subscales in both groups. The two-factor structure of the MIQ-RS was supported by factor analysis, with the visual and kinesthetic components accounting for 88.6% and 83.4% of the total variance in the able-bodied and stroke groups, respectively. The MIQ-RS is a valid and reliable instrument in the stroke population examined and able-bodied populations and therefore useful as an outcome measure for motor imagery ability.
- Published
- 2012
- Full Text
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