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Messenger RNA Vaccine in Mother's Milk-Reply

Hanna, Nazeeh; Clauss, Christie; Krilov, Leonard R
PMID: 36804769
ISSN: 2168-6211
CID: 5433782

Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates

Schiller, Emily A; Cohen, Koral; Lin, Xinhua; El-Khawam, Rania; Hanna, Nazeeh
Neonates born prematurely (<37 weeks of gestation) are at a significantly increased risk of developing inflammatory conditions associated with high mortality rates, including necrotizing enterocolitis, bronchopulmonary dysplasia, and hypoxic-ischemic brain damage. Recently, research has focused on characterizing the content of extracellular vesicles (EVs), particularly microRNAs (miRNAs), for diagnostic use. Here, we describe the most recent work on EVs-miRNAs biomarkers discovery for conditions that commonly affect premature neonates.
PMID: 36768944
ISSN: 1422-0067
CID: 5421072

Detection of Messenger RNA COVID-19 Vaccines in Human Breast Milk

Hanna, Nazeeh; Heffes-Doon, Ari; Lin, Xinhua; Manzano De Mejia, Claudia; Botros, Bishoy; Gurzenda, Ellen; Nayak, Amrita
PMID: 36156636
ISSN: 2168-6211
CID: 5328352

"Impact of the COVID pandemic on the incidence of prematurity: Critical role of gestational age and environment." [Letter]

Weinberger, Barry; Divers, Jasmin; Campbell, Deborah; Ham, Steven; Juliano, Courtney; Kurepa, Dalibor; Lagamma, Edmund; Mally, Pradeep; Nafday, Suhas; Sheri, Nemerofsky; Sridhar, Shanthy; Williams, Kim; Hanna, Nazeeh
PMID: 35218696
ISSN: 1097-6868
CID: 5172662


Abuso, S.; Choi, J. J.; Akerman, M.; El-Khawam, R.; Kamity, R.; Clauss, C.; Hanna, N.; Dumpa, V.
ISSN: 1081-5589
CID: 5243662


Choi, J. J.; Pitter, L.; Hanna, N.; Dumpa, V.
ISSN: 1081-5589
CID: 5243692

Light protection of parenteral nutrition, cholestasis, and other prematurity-related morbidities in premature infants

Clauss, Christie; Tack, Valentyna; Macchiarulo, Maria; Akerman, Meredith; El-Chaar, Gladys; Hanna, Nazeeh; Tiozzo, Caterina
Introduction/UNASSIGNED:Parenteral Nutrition (PN) can lead to intestinal failure associated liver disease (IFALD). There are no human studies to date studying specifically the benefits of light-protection on neonatal IFALD. Recently, the European Medicines Agency and the American Society for Parenteral and Enteral Nutrition (ASPEN) both recommended full light protection of PN to reduce the risk of adverse clinical outcomes. Objective/UNASSIGNED:The primary objective of this study was to evaluate the impact of light-protecting PN on the incidence of cholestasis and peak direct bilirubin levels in premature infants. Study design/UNASSIGNED:Retrospective chart review of preterm infants requiring PN for a minimum of 2 weeks with or without light-protection. After light protection of the PN solution, primary outcomes (including cholestasis and direct bilirubin levels) of both groups were compared. Secondary outcomes include evaluation of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis and mortality. Results/UNASSIGNED:= 0.0223). There was no difference in NEC, ROP, sepsis or mortality. Conclusion/UNASSIGNED:Our study supports that the practice of light-protecting PN may reduce the incidence of IFALD in premature infants. Moreover, there was a trend toward decreased incidence of severe BPD in the light-protection group. Further light protection studies are needed to confirm these findings.
PMID: 35989991
ISSN: 2296-2360
CID: 5338072

Placental extracellular vesicles-associated miRNA-519c mediates endotoxin adaptation in pregnancy

Tiozzo, Caterina; Bustoros, Mark; Lin, Xinhua; Manzano de Mejia, Claudia; Gurzenda, Ellen; Chavez, Martin; Hanna, Iman; Aguiari, Paola; Perin, Laura; Hanna, Nazeeh
BACKGROUND:Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring a balance between immunosuppression, which is essential for the maintenance of a semi-allogeneic fetus, and pro-inflammatory host defense to protect the maternal-fetal interface from invading organisms. Adaptation to repeated inflammatory stimuli (endotoxin tolerance) may be critical in preventing inflammation-induced preterm birth resulting from exaggerated maternal inflammatory responses to mild/moderate infections that are common during pregnancy. However, the exact mechanisms contributing to the maintenance of tolerance to repeated infections are not completely understood. miRNAs play important roles in pregnancy, with several miRNAs implicated in gestational tissue function, as well as in pathologic pregnancy conditions. miRNA-519c, a member of the C19MC cluster, is a human-specific miRNA mainly expressed in the placenta. However, its role in pregnancy is largely unknown. OBJECTIVES/OBJECTIVE:To explore the role of "endotoxin tolerance" failure in the pathogenesis of an exaggerated inflammatory response often seen in inflammation-mediated preterm birth. In this study, we investigated the role of miRNA-519c, a placenta-specific miRNA, as a key regulator of endotoxin tolerance at the maternal-fetal interface. STUDY DESIGN/METHODS:-trimester placentas were treated with LPS. After 24 hours, the conditioned media was collected for analysis, and the placental explants were re-exposed to repeated doses of LPS for 3 days. The supernatant was analyzed for inflammatory markers, presence of extracellular vesicles (EVs) and microRNAs. To study the possible mechanism of action of the microRNAs, we evaluated the phosphodiesterase 3 B (PDE3B) pathway involved in TNF-α production using a miRNAs mimic and PDE3B siRNA transfection. Finally, we analyzed human placental samples from different gestational ages and from women affected by inflammation-associated pregnancies. RESULTS:Our data showed that repeated exposure of the human placenta to endotoxin challenges induced a tolerant phenotype characterized by decreased TNF-α and upregulated IL-10 levels. This reaction was mediated by the placenta-specific miRNA-519c packaged within placental EVs. LPS treatment increased the EVs that were positive for the exosome tetraspanin markers, namely CD9, CD63, and CD81, and secreted primarily by trophoblasts. Primary human trophoblast cells transfected with miR-519c mimic decreased PDE3B. While lack of PDE3B, achieved by siRNA transfection, resulted in a decreased TNF-α production. These data supported the hypothesis that the anti-inflammatory action of miRNA-519c was mediated by a downregulation of the phosphodiesterase 3 B pathway, leading to inhibition of TNF-α production. Furthermore, human placentas from normal and inflammation-associated pregnancies demonstrated that decreased placental miRNA-519c level was linked to infection-induced inflammatory pathologies during pregnancy. CONCLUSION/CONCLUSIONS:We identified miRNA-519c, a human placenta-specific miRNA, as a novel regulator of immune adaptation associated with infection-induced preterm birth at the maternal-fetal interface. Our study can serve as a basis for future experiments to explore the potential use of miRNA-519c as a biomarker for infection-induced preterm birth.
PMID: 34181894
ISSN: 1097-6868
CID: 4926282

Underestimation of SARS-CoV-2 infection in placental samples [Letter]

Hanna, Nazeeh; Lin, Xinhua; Thomas, Kristen; Vintzileos, Anthony; Chavez, Martin; Palaia, Thomas; Ragolia, Louis; Verma, Sourabh; Khullar, Poonam; Hanna, Iman
PMID: 34297970
ISSN: 1097-6868
CID: 4954872

Application of Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling in Preterm Neonates to Guide Gentamicin Dosing Decisions and Predict Antibacterial Effect

Neeli, Harshith; Hanna, Nazeeh; Abduljalil, Khaled; Cusumano, Jaclyn; Taft, David R
Clinical studies in preterm neonates are rarely performed due to ethical concerns and difficulties associated with trials and recruitment. Consequently, dose selection in this population is primarily empirical. Scaling neonatal doses from adult doses does not account for developmental changes and may not accurately predict drug kinetics. This is especially important for gentamicin, a narrow therapeutic index aminoglycoside antibiotic. While gentamicin's bactericidal effect is associated with its peak plasma concentration, keeping trough concentrations below 1 μg/mL prevents toxicity and also helps counteracting adaptive resistance in bacteria such as Escherichia coli. In this study, physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling was used to support and/or guide dosing decisions, and to predict the antibacterial effect in preterm neonates. A gentamicin PBPK model was successfully verified in healthy adults and preterm neonates across all gestational ages. Clinical data from a neonatal intensive care unit at NYU Langone Long Island hospital was used to identify dosing regimens associated with increased incidence of elevated gentamicin trough concentrations in different preterm patient cohorts. Model predictions demonstrated that a higher dose with an extended-dosing interval (Q36h) in neonates with a postmenstrual age of 30-34 weeks and ≥ 35 weeks, with postnatal age 8-28 days and 0-7 days, respectively, were more likely to have a trough < 1 μg/mL when compared with once-daily (Q24h) dosing. PBPK-PD modeling suggested that a higher dose administered Q36h may provide effective antibacterial therapy. This article is protected by copyright. All rights reserved.
PMID: 33945155
ISSN: 1552-4604
CID: 4873962