Publications by authors named "Betsy Herold"

Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time.

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Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical challenge in selecting empiric antimicrobials for pediatric infections. We implemented nasal MRSA polymerase chain reaction (nMRSA PCR) screening as a diagnostic tool and evaluated its impact on empiric antibiotic use and clinical outcomes.

Methods: A retrospective single-center study of patients hospitalized with infections who were empirically prescribed anti-MRSA antibiotics was conducted prior to and following the initiation of nMRSA PCR screening.

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Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned.

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Article Synopsis
  • - Bacterial vaginosis (BV) affects Black and Hispanic women more than others, leading to higher risks of HIV, STIs, and preterm birth, but the link between genetic ancestry and BV risk is unclear.
  • - A study used data from the Women's Interagency HIV Study to analyze genetic markers in relation to BV status, finding that both self-reported race and genetic ancestry influenced BV risk, with specific gene polymorphisms related to mucosal defense identified across all groups.
  • - The findings highlight the significance of genes involved in immune response and inflammation in BV, indicating a need for further research on the condition's causes and potential treatments.
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Objectives: Evaluate the safety of Ovaprene, an investigational nonhormonal vaginal contraceptive designed for monthly use.

Study Design: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment-emergent adverse events, systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids.

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The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, clinical and epidemiological studies to understand the pathophysiology of this new family of viruses, which continues to evolve with the emergence of new genetic variants. One of the earliest clinical observations that provided a framework for the research was the finding that, in contrast to most other respiratory viruses, children developed less severe acute and post-acute disease compared to adults.

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Immunoglobulin (Ig) bacterial coating has been described in the gastrointestinal tract and linked to inflammatory bowel disease; however, little is known about Ig coating of vaginal bacteria and whether it plays a role in vaginal health including bacterial vaginosis (BV). We examined Ig coating in 18 women with symptomatic BV followed longitudinally before, 1 week, and 1 month after oral metronidazole treatment. Immunoglobulin A (IgA) and/or immunoglobulin G (IgG) coating of vaginal bacteria was assessed by flow cytometry, and Ig coated and uncoated bacteria were sorted and characterized using 16S rRNA sequencing.

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Antibody-dependent cellular cytotoxicity (ADCC) is associated with protection against neonatal herpes. We hypothesized that placental transfer of ADCC-mediating herpes simplex virus (HSV) immunoglobulin G (IgG) is influenced by antigenic target, function, glycans, gestational age, and maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Maternal and cord blood were collected from HSV-seropositive (HSV+) mothers pre-COVID and HSV+/SARS-CoV-2+ mothers during the pandemic.

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Herpes simplex viruses (HSV) cause chronic infections with significant morbidity. Prior vaccines, designed to generate neutralizing antibodies (nAbs) targeting glycoprotein D (gD), failed to provide durable protection. We adopted a different strategy and evaluated a single-cycle virus deleted in gD (ΔgD-2).

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Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.

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Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency.

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Background: This study investigated the incidences and risk factors associated with new-onset persistent type-2 diabetes during COVID-19 hospitalization and at 3-months follow-up compared to influenza.

Methods: This retrospective study consisted of 8216 hospitalized, 2998 non-hospitalized COVID-19 patients, and 2988 hospitalized influenza patients without history of pre-diabetes or diabetes in the Montefiore Health System in Bronx, New York. The primary outcomes were incidences of new-onset in-hospital type-2 diabetes mellitus (I-DM) and persistent diabetes mellitus (P-DM) at 3 months (average) follow-up.

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There is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, but for HSV this strategy has proven ineffective. Preclinical studies with a candidate HSV vaccine strain, ΔgD-2, demonstrated that non-neutralizing antibodies that activate Fcγ receptors (FcγRs) to mediate antibody-dependent cellular cytotoxicity (ADCC) provide active and passive protection against HSV-1 and HSV-2.

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Although HSV-1 has been implicated in facial palsy for a long time, testing and treating for HSV is not routine. The lack of a meaningful demonstration of how HSV-1 would cause facial palsy has limited progress in this field. Herein we demonstrate that the depth of the lip HSV-1 infection defines the course of the disease, with deeper subcutaneous infection allowing virus access to the facial nerve and causing facial palsy.

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Herpes simplex virus (HSV) receptor engagement activates phospholipid scramblase triggering Akt translocation to the outer leaflet of the plasma membrane where its subsequent phosphorylation promotes viral entry. We hypothesize that this previously unrecognized outside-inside signaling pathway is employed by other viruses and that cell-impermeable kinase inhibitors could provide novel antivirals. We synthesized a cell-impermeable analog of staurosporine, CIMSS, which inhibited outer membrane HSV-induced Akt phosphorylation and blocked viral entry without inducing apoptosis.

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Article Synopsis
  • The study investigated the safety and efficacy of a new intravaginal ring (IVR) combining tenofovir (TFV) and levonorgestrel (LNG) for preventing sexually transmitted infections and unintended pregnancies among women.
  • 47 women participated, using either the active IVR or a placebo for 90 days, with results showing no serious adverse effects and maintained mucosal health.
  • TFV was found to achieve high local concentrations and significantly inhibited HIV replication, although users experienced higher rates of anovulation and some changes in cervical mucus quality.
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There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19.

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Background: The glycoprotein D (gD)/AS04 vaccine failed to prevent herpes simplex virus (HSV) 2 in clinical trials. Failure was recapitulated in mice, in which the vaccine elicited neutralizing antibody but not antibody-dependent cell-mediated cytotoxicity (ADCC) responses. Preclinical findings suggest that ADCC is important for protection, but the clinical data are limited.

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Objective: In children with appendicitis, rupture of the appendix is associated with a significant increase in morbidity. We sought to characterize the spectrum of illness in children with complicated appendicitis and to define those factors associated with a longer hospital stay.

Study Design: We conducted a retrospective review of 132 children, 18 years of age or younger at a large urban teaching hospital in the Bronx, NY between October 2015 and April 2018 with an intraoperative diagnosis of perforated appendix.

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Background: HIV-uninfected persons being evaluated for sexually transmitted infections (STIs) may be good HIV pre-exposure prophylaxis (PrEP) candidates. We measured PrEP use in a sentinel STI patient population.

Design: Cross-sectional study, New York City Sexual Health Clinics (January 2019-June 2019).

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Article Synopsis
  • In New York City, a study found that 91% of STI clinic patients who reported using preexposure prophylaxis (PrEP) had detectable levels of PrEP in their blood.
  • The self-reported data showed 80% sensitivity and 96% specificity, indicating a strong correlation between what patients said and what was measured.
  • These results suggest that self-reporting is a reliable way to assess PrEP uptake among patients.
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There are urinary tract infection (UTI) guidelines for treatment of patients <2 years old, but there is a paucity of data for other pediatric age groups including the potential role for stewardship to reduce prescription of broad-spectrum antibiotics. We assessed practice patterns for the diagnosis and empiric treatment of UTI for outpatient and school health sites affiliated with a large urban pediatric medical center. We hypothesized that outpatient providers under-utilize narrow-spectrum antibiotics, such as first-generation cephalosporins, for uncomplicated UTI.

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