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BACKGROUND: Young children living in families experiencing social vulnerability, including low income, mental illness, addictions, social isolation, and/or homelessness, are at risk of developmental delay. Two-generation programs can improve outcomes for preschool children, but underlying mechanisms and outcomes for younger children remain unclear. PURPOSE: We explored program facilitation and identified developmental benefits of a two-generation program beginning prenatally. METHODS: In our convergent, concurrent mixed methods study, we interviewed agency staff (n = 10) and held focus groups with parents (n = 14). We compared child (N = 100) development between program intake and exit as measured by the Ages and Stages Questionnaires 3rd edition. RESULTS: Our core category, Engaging From Both Sides, included (a) Mitigating Adversity (focused codes Developing Trust, Letting Go of Fear, and Putting in the Effort); (b) Continual Learning (focused codes Staying Connected, and Taking it to the Community); (c) Fostering Families (focused codes Cultivating Optimism, and Happiness and Love); (d) Unravelling Cycles of Crisis (focused codes Advocating, and Helping Parents' Parent); and (e) Becoming Mainstream (focused codes Knowing Someone Has Your Back, and Managing Stress, Anxiety, and Anger). We found significant improvements in child Fine Motor, Problem-Solving, and Personal-Social domains between program intake and exit. CONCLUSIONS: Our study adds to existing literature regarding mechanisms of two-generation programs beginning prenatally. Mitigating effects of intergenerational adversity was the primary motivation for interaction and engagement of staff and parents in two-generation programming, which improved child development.

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Exposure to a natural disaster in childhood can have serious, long-lasting consequences, impacting physical and mental health, development, and learning. Although many children experience negative effects after a disaster, the majority do not, and what differentiates these groups is not well understood. Some of the factors that influence disaster-related outcomes in the midst of adversity include parents' mental health, the home environment, and socioeconomic status. Furthermore, genetics has also a role to play in how children respond to stressors. We had the opportunity to conduct a natural experiment of disaster recovery following the Alberta 2013 Flood. This paper presents the detailed protocol on prediction of resilience in Albertan families, and validation with cortisol data. In addition, data collection procedures, developing resiliency screening tools, candidate gene identification, genotyping, DNA methylation, and genomic analyses are described to achieve the research objectives. This study produced new knowledge by using pre- and post-disaster information on children's health and development, including children's genetics and responses to stress. This information has been identified as important to governments and other organizations invested in early child development. Our comprehensive research plan generates evidence that can be mobilized population-based approaches to improve child and family resiliency.

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BACKGROUND: Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice. METHOD: In a defined subset (MYC/BCL2 or MYC/BCL2) of AML patients (n=20), we examined expression signature of several genes (n=12) of established prognostic value in AML. RNA expression and MYC/BCL2 protein pattern was correlated with 3 cytogenetic risk groups and overall survival. RESULTS: K-means++ unsupervised clustering defined 2 distinct groups with high and low transcript levels of BAALC/MN1/MLLT11/EVI1/SOCS2 genes (>2.5-fold difference; P<0.001). This mRNA signature trended with higher prevalence of MYC/BCL2 coexpression (P<0.057) and poor overall survival (P<0.036), but did not correlate with conventional cytogenetic risk groups (P<0.084). CONCLUSIONS: This pilot study provides useful data, which may help further refine the prognostic scheme of AML patients outside conventional cytogenetic risk groups. It also presents some biological rationale for future studies to explore the use of novel agents targeting MYC and/or BCL2 genes in combination with conventional chemotherapy protocols for AML.

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Parenting stress has been linked to child development issues in early preterm infants, but less is known about its effects on development in infants born late preterm. We examined relationships between parenting stress of 108 mothers and 108 fathers and development of late preterm infants born at 34 0/7 to 36 6/7 weeks gestation. At 4 months corrected age, mothers and fathers completed the Parenting Stress Index (PSI-3); mothers were primary caregivers in almost all families and completed the Ages and Stages Questionnaire (ASQ-2) on child development. Mothers reported significantly more stress than fathers on the PSI-3 Parent Domain. PSI-3 subscale scores from the Child Domain were significant predictors of mother-reported infant development as measured by the ASQ-2 in regression models: Reinforces Parent predicted Gross Motor, Mood predicted Communication, and Acceptability predicted Communication, Fine Motor, Problem Solving, and Personal -Social development scale scores. Experiences of parenting stress differed for mothers and fathers. Further research is required on specific dimensions of parenting stress related to development of late preterm infants.

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This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell.

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