Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children.

Background: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13.

Methods: We identified patients ≤ 18 years of age with PM at 8 children's hospitals in the United States.

CD8 T cells and Mycobacterium tuberculosis infection.

Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas.

Expression quantitative trait loci (eQTL) mapping in Puerto Rican children.

Background: Expression quantitative trait loci (eQTL) have been identified using tissue or cell samples from diverse human populations, thus enhancing our understanding of regulation of gene expression. However, few studies have attempted to identify eQTL in racially admixed populations such as Hispanics.

Methods: We performed a systematic eQTL study to identify regulatory variants of gene expression in whole blood from 121 Puerto Rican children with (n = 63) and without (n = 58) asthma.

Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era.

Background: Streptococcus pneumoniae is a common cause of otitis media (OM) in children; mastoiditis remains an important complication of OM. Limited data are available on the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal otitis.

Methods: Investigators from 8 children's hospitals in the United States prospectively collected pneumococcal isolates from middle ear or mastoid cultures from children from 2011 to 2013.

Variability in tuberculosis granuloma T cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization.

Lung granulomas are the pathologic hallmark of tuberculosis (TB). T cells are a major cellular component of TB lung granulomas and are known to play an important role in containment of Mycobacterium tuberculosis (Mtb) infection. We used cynomolgus macaques, a non-human primate model that recapitulates human TB with clinically active disease, latent infection or early infection, to understand functional characteristics and dynamics of T cells in individual granulomas.

A genome-wide association study of chronic obstructive pulmonary disease in Hispanics.

Rationale: Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent.

Objectives: We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations.

Methods: We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]).

Are the neuromotor disabilities of bilirubin-induced neurologic dysfunction disorders related to the cerebellum and its connections?

Investigators have hypothesized a range of subcortical neuropathology in the genesis of bilirubin-induced neurologic dysfunction (BIND). The current review builds on this speculation with a specific focus on the cerebellum and its connections in the development of the subtle neuromotor disabilities of BIND. The focus on the cerebellum derives from the following observations: (i) the cerebellum is vulnerable to bilirubin-induced injury; perhaps the most vulnerable region within the central nervous system; (ii) infants with cerebellar injury exhibit a neuromotor phenotype similar to BIND; and (iii) the cerebellum has extensive bidirectional circuitry projections to motor and non-motor regions of the brainstem and cerebral cortex that impact a variety of neurobehaviors.

A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials.

PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis.

Oxazolidinone antibiotics such as linezolid have shown significant therapeutic effects in patients with extensively drug-resistant (XDR) tuberculosis (TB) despite modest effects in rodents and no demonstrable early bactericidal activity in human phase 2 trials. We show that monotherapy with either linezolid or AZD5847, a second-generation oxazolidinone, reduced bacterial load at necropsy in Mycobacterium tuberculosis-infected cynomolgus macaques with active TB. This effect coincided with a decline in 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG PET) imaging avidity in the lungs of these animals and with reductions in pulmonary pathology measured by serial computed tomography (CT) scans over 2 months of monotherapy.

Endoscopic endonasal surgery for sinonasal and skull base lesions in the pediatric population.

Endoscopic endonasal skull base surgical techniques, initially developed in adult patients, are being utilized with increasing frequency in pediatric patients to treat sinonasal and skull base lesions. This article reviews the current state of endoscopic endonasal approaches to the skull base to both treat disease and reconstruct the skull base in pediatric patients. Sinonasal and skull base embryology and anatomy are reviewed as a foundation for understanding the disease processes and surgical techniques.

Brief cognitive and behavioral screening in children with new-onset epilepsy: a pilot feasibility trial.

Background: Minimal work has used psychometrically robust measures in a systematic fashion to identify and monitor children at risk for cognitive and behavioral comorbidities in current epilepsy care. We piloted a computerized cognitive battery and behavioral questionnaire for children with newly diagnosed epilepsy to determine clinical feasibility and acceptability to parents and patients.

Methods: We recruited medication-naïve children (ages 8-17 years) with recent-onset seizures and typical developmental history from an outpatient child neurology clinic.

The transcription factor, T-bet, primes intestine transplantation rejection and is associated with disrupted mucosal homeostasis.

Background: The transcription factor, t-bet, promotes inflammatory polarization and intestinal homing of many inflammatory cells. In previous studies, the t-bet and granulysin genes were upregulated in peripheral blood before and after intestine transplantation (ITx) rejection, but not during rejection, possibly because of sequestration in allograft mucosa. Mucosal sequestration of t-bet and granulysin may also explain the presence of inflammatory CD14+ monocyte-derived macrophages (MDM) and immunoglobulin G+ B-cell lineage cells, and loss of mature non-inflammatory CD138+ plasma cells in allograft mucosa during ITx rejection in these previous studies.

Airway ciliary dysfunction and sinopulmonary symptoms in patients with congenital heart disease.

Rationale: Patients with congenital heart disease with heterotaxy exhibit a high prevalence of abnormal airway ciliary motion and low nasal nitric oxide, characteristics associated with primary ciliary dyskinesia, a reflection of the role of motile cilia in airway clearance and left-right patterning.

Objectives: To assess the potential broader clinical significance of airway ciliary dysfunction in congenital heart disease, we assessed the prevalence of ciliary dysfunction versus respiratory symptoms in patients with congenital heart disease with or without heterotaxy.

Methods: Patients with a broad spectrum of congenital heart disease were recruited (n = 218), 39 with heterotaxy.

Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise.

Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at-risk infants, while frequently showing increased T1-signal in these regions, may give false-positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy.

Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared.

c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate.

myc(-/-) rat fibroblasts (KO cells) differ from myc(+/+) (WT) cells and KO cells with enforced Myc re-expression (KO-Myc cells) with respect to mitochondrial structure and function, utilization of glucose and glutamine as energy-generating substrates, and ATP levels. Specifically, KO cells demonstrate low levels of glycolysis and oxidative phosphorylation, dysfunctional mitochondria and electron transport chain complexes, and depleted ATP stores. We examined here how these cells adapt to their energy-deficient state and how they differ in their uptake and utilization of long- and medium-chain fatty acids such as palmitate and octanoate, respectively.

Deliberate apprenticeship in the Pediatric Emergency Department improves experience for third-year students.

Introduction: The Pediatric Emergency Department (PED) provides medical students with learning in a high-volume, fast-paced environment; characteristics that can be stressful for new students. Shadowing can improve transitioning, yet this alone does not facilitate students' development of independent medical care competencies. This study evaluates if third-year medical students' deliberate apprenticeship with senior residents increases students' comfort and patient exposure in the PED.

Bartonella henselae endocarditis and glomerulonephritis with dominant C3 deposition in a 21-year-old male with a Melody transcatheter pulmonary valve: case report and review of the literature.

We report a case of a 21-year-old young man with underlying congenital heart disease who developed Bartonella henselae endocarditis of the right ventricular outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary valve (TPV), with an initial presentation of glomerulonephritis with a dominant C3 pattern, with renal failure and circulating cryoglobulins. There are few reports of a glomerulonephritis with a dominant C3 pattern presenting as a manifestation of B. henselae endocarditis.

Improving speech outcomes after failed palate repair: evaluating the safety and efficacy of conversion Furlow palatoplasty.

Background: Velopharyngeal insufficiency occurs in a nontrivial number of cases following cleft palate repair. We hypothesize that a conversion Furlow palatoplasty allows for long-term correction of VPI resulting from a failed primary palate repair, obviating the need for pharyngoplasty and its attendant comorbidities.

Methods: A retrospective review of patients undergoing a conversion Furlow palatoplasty between 2003 and 2010 was performed.

Trends in hospitalizations and mortality from asthma in Costa Rica over a 12- to 15-year period.

Background: Little is known about trends in morbidity and/or mortality due to asthma in Latin America.

Objective: To examine trends in hospitalizations and mortality due to asthma from 1997-2000 to 2011 in Costa Rica.

Methods: The rates of hospitalization due to asthma were calculated for each sex in 3 age groups from 1997 to 2011.