Analysis of electrochemical and liver microsomal transformation products of lasalocid by LC/HRMS.

RATIONALE: Lasalocid (LAS), an ionophore, is used in cattle and poultry farming as feed additive for its antibiotic and growth-promoting properties. Literature on transformation products (TP) resulting from LAS degradation is limited. So far, only hydroxylation is found to occur as the metabolic reaction during the LAS degradation. To investigate potential TPs of LAS, we used electrochemistry (EC) and liver microsome (LM) assays to synthesize TPs, which were identified using liquid chromatography high-resolution mass spectrometry (LC/HRMS). METHODS: Electrochemically produced TPs were analyzed online by direct coupling of the electrochemical cell to the electrospray ionization (ESI) source of a Sciex Triple-TOF high resolution mass spectrometer. Then, EC-treated LAS solution was collected and analyzed offline using LC/HRMS to confirm stable TPs and improve their annotation with a chemical structure due to informative MS/MS spectra. In a complementary approach, TPs formed by rat and human microsomal incubation were investigated using LC/HRMS. The resulting data were used to investigate LAS modification reactions and elucidate the chemical structure of obtained TPs. RESULTS: The online measurements identified a broad variety of TPs, resulting from modification reactions like (de-)hydrogenation, hydration, methylation, oxidation as well as adduct formation with methanol. We consistently observed different ion complexations of LAS and LAS-TPs (Na+ ; 2Na+ K+ ; NaNH4 + ; KNH4 + ). Two stable methylated EC-TPs were found, structurally annotated, and assigned to a likely modification reaction. Using LM incubation, seven TPs were formed, mostly by oxidation/hydroxylation. After the identification of LM-TPs as Na+ -complexes, we identified LM-TPs as K+ -complexes. CONCLUSION: We identified and characterized TPs of LAS using EC- and LM-based methods. Moreover, we found different ion complexes of LAS-based TPs. This knowledge, especially the different ion complexes, may help elucidate the metabolic and environmental degradation pathways of LAS.

LC-HRMS-Based Identification of Transformation Products of the Drug Salinomycin Generated by Electrochemistry and Liver Microsome.

The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction.

Efficacy of the Getting Ready Intervention and the Role of Parental Depression.

This study reports the results of a randomized trial of a parent engagement intervention (the Getting Ready Project) on directly observed learning-related social behaviors of children from families of low-income in the context of parent-child interactions. The study explored the moderating effect of parental depression on intervention outcomes. Participants were 204 children and their parents, and 29 Head Start teachers. Semi-structured parent-child interaction tasks were videotaped two times annually over the course of two academic years. Observational codes of child behaviors included agency, persistence, activity level, positive affect, distractibility, and verbalizations. Controlling for gender and disability concerns, relative to children in the control group, those in the treatment condition experienced a significant decline in activity level. Furthermore, compared to children of non-depressed mothers and to control children, those in the experimental condition whose parent reported elevated levels of depression showed greater gains in positive affect and in verbalizations.

GETTING READY: RESULTS OF A RANDOMIZED TRIAL OF A RELATIONSHIP-FOCUSED INTERVENTION ON THE PARENT-INFANT RELATIONSHIP IN RURAL EARLY HEAD START.

The purpose of this study is to investigate the effects of a relational intervention (the Getting Ready intervention) on parenting behaviors supporting the parent-infant relationship for families enrolled in Early Head Start home-based programming. Two-hundred thirty-four parents and their children participated in the randomized study, with 42% of parents reporting education of less than a high-school diploma. Brief, semistructured parent-child interaction tasks were videotaped every 4 months over a16-month intervention period. Observational codes of parent-infant relationship behaviors included quality of three parental behaviors: warmth and sensitivity, support for learning, and encouragement of autonomy; two appropriateness indicators: support for learning and guidance/directives; and one amount indicator: constructive behaviors. Parents who participated in the Getting Ready intervention demonstrated higher quality interactions with their children that included enhanced quality of warmth and sensitivity, and support for their children's autonomy than did parents in the control group. They also were more likely to use appropriate directives with their children and more likely to demonstrate appropriate supports for their young children's learning. Results indicate an added value of the Getting Ready intervention for Early Head Start home-based programming for families of infants and toddlers.

A randomized trial examining the effects of parent engagement on early language and literacy: the Getting Ready intervention.

Language and literacy skills established during early childhood are critical for later school success. Parental engagement with children has been linked to a number of adaptive characteristics in preschoolers including language and literacy development, and family-school collaboration is an important contributor to school readiness. This study reports the results of a randomized trial of a parent engagement intervention designed to facilitate school readiness among disadvantaged preschool children, with a particular focus on language and literacy development. Participants included 217 children, 211 parents, and 29 Head Start teachers in 21 schools. Statistically significant differences in favor of the treatment group were observed between treatment and control participants in the rate of change over 2 academic years on teacher reports of children's language use (d=1.11), reading (d=1.25), and writing skills (d=0.93). Significant intervention effects on children's direct measures of expressive language were identified for a subgroup of cases where there were concerns about a child's development upon entry into preschool. Additionally, other child and family moderators revealed specific variables that influenced the treatment's effects.

Implementation of a Relationship-Based School Readiness Intervention: A Multidimensional Approach to Fidelity Measurement for Early Childhood.

The implementation efforts of 65 early childhood professionals involved in the Getting Ready project, an integrated, multi-systemic intervention that promotes school readiness through parent engagement for children from birth to age five, were investigated. Digital videotaped records of professionals engaged in home visits with families across both treatment and comparison conditions were coded objectively using a partial-interval recording system to identify and record early childhood professionals' implementation of intervention strategies and their effectiveness in promoting parent engagement and interest in their child. Adherence, quality of intervention delivery, differentiation between groups, and participant responsiveness were assessed as multiple dimensions of fidelity. Early childhood professionals in the treatment group relative to the comparison group demonstrated greater frequency of adherence to some intervention strategies, as well as higher rates of total strategy use. In addition, significant positive relationships were found between years of experience, education and quality of intervention delivery. Quality of intervention delivery was different by program type (Early Head Start versus Head Start). Adherence in the treatment group was correlated with the rate of contact between parent and early childhood professional during the home visit.

Parent Engagement and School Readiness: Effects of the Getting Ready Intervention on Preschool Children's Social-Emotional Competencies.

RESEARCH FINDINGS: Parental engagement with children has been linked to a number of adaptive characteristics in preschool children, and relationships between families and professionals are an important contributor to school readiness. Furthermore, social-emotional competence is a key component of young children's school readiness. This study reports the results of a randomized trial of a parent engagement intervention (Getting Ready) designed to facilitate school readiness among disadvantaged preschool children, with a particular focus on social-emotional outcomes. Two hundred and twenty children were involved over the 4-year study period. Statistically significant differences were observed between treatment and control participants in the rate of change over a 2-year period on teacher reports for certain interpersonal competencies (i.e., attachment, initiative, and anxiety/ withdrawal). In contrast, no statistically significant differences between groups over a 2-year period were noted for behavioral concerns (anger/aggression, self-control, or behavioral problems) as a function of the Getting Ready intervention. PRACTICE OR POLICY: The intervention appears to be particularly effective at building social-emotional competencies beyond the effects experienced as a function of participation in Head Start programming alone. Limitations and implications for future research are reviewed.

Professional Development in Early Childhood Programs: Process Issues and Research Needs.

In light of the current policy context, early childhood educators are being asked to have a complex understanding of child development and early education issues and provide rich, meaningful educational experiences for all children and families in their care. Accountability for outcomes is high, and resources for professional support are limited. As such, the early education field needs well-conducted empirical studies on which to base professional development practices. In this paper, we offer research directions associated with the processes underlying professional development, including areas in need of investigation that can inform the early childhood education field in terms of how professional development efforts exert their influence and produce meaningful change in practitioners' skills, behaviors, and dispositions. The paper highlights representative research from the professional development literature on its various forms/approaches and offers an agenda for research on the professional development process. Broad issues associated with the conduct of research on professional development, including considerations of professional development processes, participant characteristics, relationships, and sustainability are discussed.