Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p.

Success With Extended-Infusion Meropenem After Recurrence of Baclofen Pump-Related Achromobacter Xylosoxidans Meningitis in an Adolescent.

A 13-year-old female experienced a recurrence of baclofen pump-related central nervous system (CNS) infection caused by Achromobacter, despite absence of retained foreign material. Due to the failure of meropenem (120 mg/kg/d in divided doses every 8 hours and infused over 30 minutes) in the initial infection, the dose was infused over 4 hours during the recurrence. Meropenem is an antibiotic for which efficacy is time dependent, and 4-hour versus 30-minute infusions have been shown to prolong the time the concentration of the antibiotic exceeds the minimum inhibitory concentration (MIC) of the organism at the site of infection (T>MIC).

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages.

Effect of reconstruction algorithms on the accuracy of (99m)Tc sestamibi SPECT/CT parathyroid imaging.

The superiority of SPECT/CT over SPECT for (99m)Tc-sestamibi parathyroid imaging often is assumed to be due to improved lesion localization provided by the anatomic component (computed tomography) of the examination. It also is possible that this superiority may be related to the algorithms used for SPECT data reconstruction. The objective of this investigation was to determine the effect of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid imaging.

Migration-related phenotypic divergence is associated with epigenetic modifications in rainbow trout.

Migration is essential for the reproduction and survival of many animals, yet little is understood about its underlying molecular mechanisms. We used the salmonid Oncorhynchus mykiss to gain mechanistic insight into smoltification, which is a morphological, physiological and behavioural transition undertaken by juveniles in preparation for seaward migration. O.

Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents.

Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome.

Clinical guidelines for management of dry eye associated with Sjögren disease.

Purpose: To provide a consensus clinical guideline for management of dry eye disease associated with Sjögren disease by evaluating published treatments and recommending management options.

Design: Consensus panel evaluation of reported treatments for dry eye disease.

Methods: Using the 2007 Report of the International Workshop on Dry Eye (DEWS) as a starting point, a panel of eye care providers and consultants evaluated peer-reviewed publications and developed recommendations for evaluation and management of dry eye disease associated with Sjögren disease.

Expression platforms for producing eukaryotic proteins: a comparison of E. coli cell-based and wheat germ cell-free synthesis, affinity and solubility tags, and cloning strategies.

Vectors designed for protein production in Escherichia coli and by wheat germ cell-free translation were tested using 21 well-characterized eukaryotic proteins chosen to serve as controls within the context of a structural genomics pipeline. The controls were carried through cloning, small-scale expression trials, large-scale growth or synthesis, and purification. Successfully purified proteins were also subjected to either crystallization trials or (1)H-(15)N HSQC NMR analyses.

Antimicrobial prophylaxis for external ventricular drains in pediatric neurosurgical patients.

Background: Our goal was to describe the use of antibiotics for surgical prophylaxis of external ventricular drains (EVDs) in a pediatric neurosurgical population and determine the incidence of EVD-related infections among different antimicrobial prophylaxis strategies.

Main Outcome Measures: This retrospective chart review included patients up to 18 years old who underwent EVD insertion at either of two tertiary care academic hospitals in the same health system between August 1, 2008, and July 31, 2012. Patients were included if they received at least one dose of antibiotics before EVD insertion.

Quantitative genetics of migration-related traits in rainbow and steelhead trout.

Rainbow trout (Oncorhynchus mykiss) exhibit remarkable life history diversity throughout their native range, and among the most evident is variation in migratory propensity. Although some populations and ecotypes will remain resident in freshwater habitats throughout their life history, others have the ability to undertake tremendous marine migrations. Those that migrate undergo a suite of behavioral, morphological, and physiological adaptations in a process called smoltification.

Ontogenetic changes in embryonic and brain gene expression in progeny produced from migratory and resident Oncorhynchus mykiss.

Little information has been gathered regarding the ontogenetic changes that contribute to differentiation between resident and migrant individuals, particularly before the onset of gross morphological and physiological changes in migratory individuals. The aim of this study was to evaluate gene expression during early development in Oncorhynchus mykiss populations with different life histories, in a tissue known to integrate environmental cues to regulate complex developmental processes and behaviours. We sampled offspring produced from migrant and resident parents, collecting whole embryos prior to the beginning of first feeding, and brain tissue at three additional time points over the first year of development.

Diagnosis of 9q22.3 microdeletion syndrome in utero following identification of craniosynostosis, overgrowth, and skeletal anomalies.

9q22.3 microdeletion syndrome is a well-described contiguous deletion syndrome with features of Gorlin syndrome and other manifestations. Commonly reported findings in addition to those of Gorlin syndrome include metopic craniosynostosis, hydrocephalus, intellectual disability, and minor facial anomalies.

Acid-Suppressing Agents and Risk for Clostridium difficile Infection in Pediatric Patients.

Background: Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population.

Methods: This was a retrospective case-control study.

Implementing extended-infusion cefepime as standard of care in a children's hospital: a prospective descriptive study.

Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children.

Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population.

Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children's hospital.

Beyond implementation: sustaining family-centered rounds.

Family-centered care encourages patients and families to participate in the planning and delivery of care based on personal preferences and individual needs. For pediatric patients and families, family-centered rounds (FCRs) represent a standard of care that involves patients and families partnering with the healthcare team to share information and make decisions about care. Our healthcare team strongly believes that FCRs are critical to providing excellence in care.

Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion.

Familial hemophagocytic lymphohistiocytosis (F-HLH) and Griscelli syndrome type 2 (GS) are life-threatening immunodeficiencies characterized by impaired cytotoxic T lymphocyte (CTL) and natural killer (NK) cell lytic activity. In the majority of cases, these disorders are caused by biallelic inactivating germline mutations in genes such as RAB27A (GS) and PRF1, UNC13D, STX11, and STXBP2 (F-HLH). Although monoallelic (ie, heterozygous) mutations have been identified in certain patients, the clinical significance and molecular mechanisms by which these mutations influence CTL and NK cell function remain poorly understood.

Genetic and morphological divergence in three strains of brook trout Salvelinus fontinalis commonly stocked in Lake Superior.

Fitness related traits often show spatial variation across populations of widely distributed species. Comparisons of genetic variation among populations in putatively neutral DNA markers and in phenotypic traits susceptible to selection (QST FST analysis) can be used to determine to what degree differentiation among populations can be attributed to selection or genetic drift. Traditionally, QST FST analyses require a large number of populations to achieve sufficient statistical power; however, new methods have been developed that allow QST FST comparisons to be conducted on as few as two populations if their pedigrees are informative.

Health worker perceptions of integrating mobile phones into community case management of malaria in Saraya, Senegal.

Background: Although community case management of malaria increases access to life-saving care in isolated settings, it contends with many logistical challenges. Mobile phone health information technology may present an opportunity to address a number of these barriers.

Methods: Using the wireless adaptation of the technology acceptance model, this study assessed availability, ease of use, usefulness, and job relevance of mobile phones by health workers in Saraya, Senegal.

Optimized antimicrobial dosing strategies: a survey of pediatric hospitals.

Background: Extended-interval aminoglycoside (EIAG) and extended- and continuous-infusion β-lactam (EIBL and CIBL) dosing strategies are increasingly used in adults, but pediatric literature is limited.

Objective: The objective of this study was to describe the use of EIAG, EIBL, and CIBL dosing in pediatric hospitals in the USA.

Study Design, Setting, And Participants: A national survey of children's hospitals was conducted.

Cinacalcet administration by gastrostomy tube in a child receiving peritoneal dialysis.

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient's therapy.

Overexpression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD) provides protection against AZT- or 3TC-induced endothelial dysfunction.

Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the backbone of current combination therapies for HIV. These therapies have significantly decreased mortality and morbidity in HIV-infected patients, but some are associated with cardiovascular complications, including endothelial dysfunction, an early marker for atherosclerosis. Our prior studies demonstrated that co-treatment of cells with an antioxidant therapy reversed NRTI-induced endothelial injury.

Parent decision-making around the genetic testing of children for germline TP53 mutations.

Background: Li-Fraumeni syndrome is a rare genetic cancer predisposition syndrome caused by germline TP53 mutations. Up to 20% of mutation carriers develop cancer during childhood. The benefits of TP53 mutation testing of children are a matter of debate and knowledge of parent decision-making around such testing is limited.

Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study.

Introduction: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.

Methods: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100).