A Multicenter Retrospective Study Evaluating Intravenous to Oral Antibiotic Stepdown for Uncomplicated Streptococcal Bacteremia.

Background: The purpose of this study was to compare the efficacy and safety of intravenous (IV) versus oral (PO) stepdown therapy for uncomplicated streptococcal bacteremia.

Methods: This multicenter, retrospective study included adult patients with uncomplicated streptococcal bacteremia between 1 July 2019 and 1 July 2022. Patients who received IV therapy for the full treatment course were compared to patients who transitioned to PO therapy after initial IV therapy.

Transposable Elements in Bats Show Differential Accumulation Patterns Determined by Class and Functionality.

Bat genomes are characterized by a diverse transposable element (TE) repertoire. In particular, the genomes of members of the family Vespertilionidae contain both active retrotransposons and active DNA transposons. Each TE type is characterized by a distinct pattern of accumulation over the past ~40 million years.

Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials.

A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no.

Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1.

The humoral response to invading mucosal pathogens comprises multiple antibody isotypes derived from systemic and mucosal compartments. To understand the contribution of each antibody isotype/source to the mucosal humoral response, parallel investigation of the specificities and functions of antibodies within and across isotypes and compartments is required. The role of IgA against HIV-1 is complex, with studies supporting a protective role as well as a role for serum IgA in blocking effector functions.

Development and application of a multiplex assay for the simultaneous measurement of antibody responses elicited by common childhood vaccines.

Because vaccine co-administration can affect elicited immune responses, it is important to evaluate new vaccines in the context of pre-existing vaccination schedules. This is particularly necessary for new pediatric vaccines, as the World Health Organization's infant immunization program already schedules several vaccines to be administered during the first months of life. To facilitate the assessment of inter-vaccine interference, we developed a pediatric vaccine multiplex assay (PVMA) to simultaneously measure antibodies against vaccines commonly administered to infants, including hepatitis B, Haemophilus influenzae type B, diphtheria, tetanus, pertussis, rubella, and respiratory syncytial virus (RSV).

Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma.

Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood.

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine.

In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59- and alum-adjuvanted HIV envelope vaccines.

Maternal Humoral Immune Correlates of Peripartum Transmission of Clade C HIV-1 in the Setting of Peripartum Antiretrovirals.

Despite the widespread use of antiretrovirals (ARV), more than 150,000 pediatric HIV-1 infections continue to occur annually. Supplemental strategies are necessary to eliminate pediatric HIV infections. We previously reported that maternal HIV envelope-specific anti-V3 IgG and CD4 binding site-directed antibodies, as well as tier 1 virus neutralization, predicted a reduced risk of mother-to-child transmission (MTCT) of HIV-1 in the pre-ARV era U.

Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk.

The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV to the infant. We previously determined that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy-to-neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U.S.

The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.

Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment.

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

Unlabelled: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission.

Programmed evolution for optimization of orthogonal metabolic output in bacteria.

Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization.

The use of the Gail model, body mass index and SNPs to predict breast cancer among women with abnormal (BI-RADS 4) mammograms.

Introduction: Mammography screening results in a significant number of false-positives. The use of pretest breast cancer risk factors to guide follow-up of abnormal mammograms could improve the positive predictive value of screening. We evaluated the use of the Gail model, body mass index (BMI), and genetic markers to predict cancer diagnosis among women with abnormal mammograms.

Orexinergic activity modulates altered vital signs and pituitary hormone secretion in experimental sepsis.

Objectives: Sepsis is a common, lethal poorly understood disorder affecting nearly a million Americans annually. The syndrome is characterized by altered cardiodynamics, respiration, metabolism, pituitary function, arousal, and impaired interaction among organ systems. The immunologic and endocrine systems, which are in part responsible for organ-organ communication, have been studied extensively in sepsis.

Agreement of self-reported hormone receptor status with cancer registry data in young breast cancer patients.

Background: Though breast cancer subtype is a key determinant of treatment choice and prognosis, few studies have assessed breast cancer patients' knowledge of estrogen and progesterone receptor (ER/PR) status.

Methods: Women diagnosed with invasive breast cancer at age 18-64 years in 2007 were recruited from the Pennsylvania Cancer Registry, and mailed a questionnaire that asked respondents to identify their ER/PR status. There were 2191 respondents included in the analysis.

Incremental impact of breast cancer SNP panel on risk classification in a screening population of white and African American women.

Breast cancer risk prediction remains imperfect, particularly among non-white populations. This study examines the impact of including single-nucleotide polymorphism (SNP) alleles in risk prediction for white and African American women undergoing screening mammogram. Using a prospective cohort study, standard risk information and buccal swabs were collected at the time of screening mammography.

Effective analgesia using physical interventions for infant immunizations.

Background: To measure the analgesic effectiveness of the 5 S's (swaddling, side/stomach position, shushing, swinging, and sucking) alone and combined with sucrose, during routine immunizations at 2 and 4 months.

Methods: We conducted a prospective, randomized, placebo-controlled trial with 2- and 4-month-old infants during well-child visits. Patients were assigned into 4 groups (2 × 2) receiving either 2 mL of water or 2 mL of 24% oral sucrose and then either standard-of-care comfort measures by parents or intervention with the 5 S's immediately postvaccination.

Potential barriers to adherence in pediatric dermatology.

This study sought to identify barriers to treatment in children with chronic inflammatory skin disease, particularly those with atopic dermatitis, psoriasis, and acne vulgaris. Caregivers of 101 patients seen in the Children's Specialty Group Division of Dermatology, Children's Hospital of The King's Daughters, Norfolk, Virginia, completed an 11-item Likert scale questionnaire. This survey addressed complexity and time requirements for treatment, medication cost, vehicle formulation, perceived safety, and caregiver understanding of chronicity of skin disorders.

Abdominal migraine: an under-diagnosed cause of recurrent abdominal pain in children.

Objective: Our objective was to demonstrate that, despite recognition by both the gastroenterology and headache communities, abdominal migraine (AM) is an under-diagnosed cause of chronic, recurrent, abdominal pain in childhood in the USA.

Background: Chronic, recurrent abdominal pain occurs in 9-15% of all children and adolescents. After exclusion of anatomic, infectious, inflammatory, or other metabolic causes, "functional abdominal pain" is the most common diagnosis of chronic, idiopathic, abdominal pain in childhood.

Most frequently missed fractures in the emergency department.

This study quantified the types of extremity fractures most commonly missed on plain radiographs by pediatric emergency medicine specialists after an initial emergency department (ED) encounter. From February 2006 to June 2009, extremity radiographs obtained in a pediatric ED in which a radiologist categorized the ED attendings' read of normal as incorrect were tabulated. The authors also counted the total number of each type of radiograph completed when radiologists were unavailable.

Analyzing factors associated with major complications after adenotonsillectomy in 4776 patients: comparing three tonsillectomy techniques.

Objective: To compare the rates of major complications (postoperative hemorrhage requiring return to the operating room or cauterization in the emergency department and dehydration requiring intravenous fluids or readmission) in a large cohort of children undergoing adenotonsillectomy by three different techniques.

Study Design: Case series with chart review, case-controlled study.

Setting: Regional children's hospital.

Fever phobia: a survey of caregivers of children seen in a pediatric emergency department.

Background: Fever continues to be the most common complaint of children seen in a Pediatric Emergency Department (PED). Previous studies have assessed the prevalence of fever phobia in various populations. This study aims to document the incidence of fever phobia in a PED.

Alternative dosage of zidovudine in infants exposed to maternal human immunodeficiency virus infection.

As part of the 076 protocol, ZDV was given to HIV-exposed neonates for the first 6 weeks of life. The dosage was 2 mg/kg every 6 hours. Frequent dosing can be a deterrent to regimen adherence.

Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease.

Background & Aims: The IBD5 locus on chromosome 5q31 is a confirmed Crohn's disease (CD) susceptibility locus in adults. Recently, two polymorphisms in the organic cation transporter (OCTN) gene cluster within the IBD5 locus have been found to be associated with CD. Although the original report of significant linkage to IBD5 was in families with at least one case of early age at onset CD, there are no published reports on the role of OCTN genes in pediatric onset CD.

Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn's disease.

Background: Despite a large body of literature on the subject of Crohn's disease (CD), very little information is available on racial/ethnic differences related to disease presentation, clinical course, and genetics. The first identified CD susceptibility gene, CARD15, seems to be present in up to 40% of white children with CD. However, the frequency of this gene among patients with CD of other racial/ethnic groups in the United States is not known.