Relation between active mediation,exposure to Daniel Tiger’s Neighborhood,and US preschoolers’ social and emotional development

This study explored the relationship between active mediation, exposure to Daniel Tiger’s Neighborhood, and key indicators of preschoolers’ social and emotional development. One hundred and twenty-seven children aged 2–6 either watched or did not watch 10 episodes of Daniel Tiger’s Neighborhood over a two-week period. Results revealed that preschoolers who watched the program exhibited higher levels of empathy, self-efficacy, and emotion recognition when their regular TV-watching experiences are frequently accompanied by active mediation. This was especially true for younger preschoolers and preschoolers from low-income families. Implications for policy-makers, parents, producers of prosocial programming, and educators are discussed.     

Preclinical safety and biodistribution of adenovirus-based cancer vaccines after intradermal delivery

The recombinant adenoviral (Ad) vector is being considered as a cancer vaccine platform because it efficiently induces immune responses to tumor antigens by intradermal immunization. The aims of this study were to evaluate the potential toxicities and biodistribution after a single dose or six weekly intradermal doses of Ad2/gp100v2 and Ad2/MART-1v2, which encode tumor-associated antigens gp100 and MelanA/MART-1, respectively. The only dose-related toxicities associated with intradermal administration of these Ad vectors were inflammatory cell infiltrates in the draining lymph nodes and injection sites that persisted 83 days after administration. The biodistribution of Ad DNA as detected by real-time polymerase chain reaction was largely confined to the injection sites and draining lymph nodes of mice treated with either a single dose or multiple doses of Ad vector and in the spleens of mice treated with multiple doses of Ad vector. Adenoviral DNA was transiently detected in the bone marrow, lung, or blood of only one animal for each site and was below the limit of assay quantification (<10 copies/microg DNA). The vector persisted in the skin and lymph nodes as long as 92 days after the last dose. We conclude that Ad vectors delivered by intradermal administration provide a safe, genetic vaccine delivery platform that induces desirable immune responses at the immunization sites and the lymph nodes that, ultimately, result in immune responses specific to the tumor antigens.     

Hypoglycemia Prediction Using Machine Learning Models for Patients With Type 2 Diabetes

Background:Minimizing the occurrence of hypoglycemia in patients with type 2 diabetes is a challenging task since these patients typically check only 1 to 2 self-monitored blood glucose (SMBG) readings per day.Method:We trained a probabilistic model using machine learning algorithms and SMBG values from real patients. Hypoglycemia was defined as a SMBG value < 70 mg/dL. We validated our model using multiple data sets. In addition, we trained a second model, which used patient SMBG values and information about patient medication administration.Results:The optimal number of SMBG values needed by the model was approximately 10 per week. The sensitivity of the model for predicting a hypoglycemia event in the next 24 hours was 92% and the specificity was 70%. In the model that incorporated medication information, the prediction window was for the hour of hypoglycemia, and the specificity improved to 90%.Conclusions:Our machine learning models can predict hypoglycemia events with a high degree of sensitivity and specificity. These models—which have been validated retrospectively and if implemented in real time—could be useful tools for reducing hypoglycemia in vulnerable patients.     

Sleep Evaluation in the Assessment of Pediatric Attention Deficit Disorders

Introduction

Examining the impact of appropriate sleep evaluation on diagnosis of attention deficit disorders can improve the standard of care in pediatrics. This quality improvement project examined current practice and subsequent implementation of a validated standardized sleep evaluation tool in the assessment of children with symptoms of attention deficit.

Epithelial-specific and stage-specific functions of insulin-like growth factor-I during postnatal mammary development

Postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. IGF-I is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. However, little is known about how local expression of IGF-I in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. The goal of this study was to investigate the mechanisms of IGF-I actions in the postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal and epithelial compartments has distinct functions. We established mouse lines with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP mice with mouse lines expressing Cre recombinase under the control of either the mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in deficits in ductal branching. In contrast, heterozygous reduction of IGF-I throughout the gland decreased expression of cyclins A2 and B1 during pubertal growth and resulted in alterations in proliferation of the alveolar epithelium and milk protein levels during pregnancy-induced differentiation. Reduction in epithelial IGF-I at either of these stages had no effect on these indices. Taken together, our results support distinct roles for IGF-I expressed in epithelial and stromal compartments in mediating growth of the postnatal mammary gland.     

Diagnosis of alpha-1-antitrypsin deficiency: An algorithm of quantification, genotyping, and phenotyping

BACKGROUND: Laboratory testing in suspected alpha-1-antitrypsin (A1AT) deficiency involves analysis of A1AT concentrations and identification of specific alleles by genotyping or phenotyping. The purpose of this study was to define and evaluate a strategy that provides reliable laboratory evaluation of A1AT deficiency. METHODS: Samples from 512 individuals referred for A1AT phenotype analysis were analyzed by quantification, phenotype, and genotype. A1AT concentrations were measured by nephelometry. Phenotype analysis was performed by isoelectric focusing electrophoresis. The genotype assay detected the S and Z deficiency alleles by a melting curve analysis. RESULTS: Of the 512 samples analyzed, 2% of the phenotype and genotype results were discordant. Among these 10 discordant results, 7 were attributed to phenotyping errors. On the basis of these data we formulated an algorithm, according to which we analyzed samples by genotyping and quantification assays, with a reflex to phenotyping when the genotype and quantification results were not concordant. Retrospective analyses demonstrated that 4% of samples submitted for genotype and quantitative analysis were reflexed to phenotyping. Of the reflexed samples, phenotyping confirmed the genotype result in 85% of cases. In the remaining 15%, phenotyping provided further information, including identifying rare deficiency alleles and suggesting the presence of a null allele, and allowed for a more definitive interpretation of the genotype result. CONCLUSIONS: The combination of genotyping and quantification, with a reflex to phenotyping, is the optimal strategy for the laboratory evaluation of A1AT deficiency.