Investing in early human development: Timing and economic efficiency

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.     

Intrinsic resistance of neural stem cells to toxic metabolites may make them well suited for cell non-autonomous disorders: evidence from a mouse model of Krabbe leukodystrophy

While transplanted neural stem cells (NSCs) have been shown to hold promise for cell replacement in models of a number of neurological disorders, these examples have typically been under conditions where the host cells become dysfunctional due to a cell autonomous etiology, i.e. a 'sick' cell within a relatively supportive environment. It has long been held that cell replacement in a toxic milieu would not likely be possible; donor cells would succumb in much the same way as endogenous cells had. Many metabolic diseases are characterized by this situation, suggesting that they would be poor targets for cell replacement therapies. On the other hand, models of such diseases could prove ideal for testing the capacity for cell replacement under such challenging conditions. In the twitcher (twi ) mouse -- as in patients with Krabbe or globoid cell leukodystrophy (GLD), for which it serves as an authentic model -- loss of galactocerebrosidase (GalC) activity results in the accumulation of psychosine, a toxic glycolipid. Twi mice, like children with GLD, exhibit inexorable neurological deterioration presumably as a result of dysfunctional and ultimately degenerated oligodendrocytes with loss of myelin. It is believed that GLD pathophysiology is related to a psychosine-filled environment that kills not only host oligodendrocytes but theoretically any new cells placed into that milieu. Through the implantation of NSCs into the brains of both neonatal and juvenile/young adult twi mice, we have determined that widespread oligodendrocyte replacement and remyelination is feasible. NSCs appear to be intrinsically resistant to psychosine -- more so in their undifferentiated state than when directed ex vivo to become oligodendrocytes. This resistance can be enhanced by engineering the NSCs to over-express GalC. Some twi mice grafted with such engineered NSCs had thicker white tracts and lived 2-3 times longer than expected. While their brains had detectable levels of GalC, it was probably more significant that their psychosine levels were lower than in twi mice that died at a younger age. This concept of resistance based on differentiation state extended to human NSCs which could similarly survive within the twi brain. Taken together, these results suggest a number of points regarding cellular therapies against degenerative diseases with a prominent cell non-autonomous component: Cell replacement is possible if cells resistant to the toxic environment are employed. Furthermore, an important aspect of successful treatment will likely be not only cell replacement but also cross-correction of host cells to provide them with enzyme activity and hence resistance. While oligodendrocyte replacement alone was not a sufficient treatment for GLD (even when extensive), the replacement of both cells and molecules -- e.g. with NSCs that could both become oligodendrocytes and 'pumps' for GalC -- emerges as a promising basis for a multidisciplinary strategy. Most neurological disease are complex in this way and will likely require multifaceted approaches, perhaps with NSCs serving as the 'glue'.     

The role of the saliva antioxidant barrier to reactive oxygen species with regard to caries development

Objectives: The aim of this study was to evaluate the role of the antioxidant barrier in the saliva of children with caries, and its impact on the colonization of cariogenic bacteria.

Methods: This is a cross-sectional study of 81 children aged 1–5 years. Antioxidant levels and salivary bacterial profiles were measured. Patients were divided into two groups as follows: initial stage decay, termed non-cavitated (1–2 in International Caries Detection and Assessment System (ICDAS)), and extensive decay, termed cavitated lesions (5–6 in ICDAS). The control group includes children without caries.

Results: The linear regression model demonstrated that the GSH, GSSG, GSH/GSSG, and total antioxidant capacity levels are influenced (P?P?Discussion: Our results indicate that the high levels of antioxidants in saliva increase significantly in children in line with the salivary cariogenic bacterial profiles and caries progression.     

Powerful allies: Arts educators and early childhood educators joining forces on behalf of young children

ABSTRACT

Arts educators and early childhood educators espouse similar philosophies and purposes surrounding young children's educational lives, yet continue to function in largely separate worlds. This article calls for the creation of intentional alliances between the two disciplines, by first recognizing and embracing these alignments. In addition, this article provides recommendations for arts educators and early childhood educators to consider as they join forces to ensure that all young children have access to high-quality arts-based education.     

Early childhood arts education in the United States: A special issue of Arts Education Policy Review

ABSTRACT

In this introduction to Early Childhood Arts Education in the United States, a special issue of Arts Education Policy Review, the editors provide a platform for stakeholders' increased awareness and understandings of the need to ensure children's rights to arts education. They summarize the five articles comprising this issue, and invite stakeholders to consider example action steps to apply content from this Issue to arts interactions with young children.     

Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia—A case-control study from Iran

We examined the possible relationship between three RAGE polymorphisms, ?429C/T, ?374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE ?374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.     

How Should Thiopurine Treatment be Monitored?— Methodological Aspects

Monitoring of thiopurine metabolites is important due to a complex metabolism with large interindividual variation, but the suitability of currently used methods has been questioned. The drawbacks include poor reproducibility, the inability to differentiate between the different analytes, as well as the use of a nontarget matrix. Further research should be directed toward measuring thiopurine metabolites in mononuclear cells, measuring the different nucleotides specifically, as well as measuring the incorporation of thioguanine into DNA. The studies should not be limited to thioguanosine nucleotides but include methylthioinosine nucleotides as well.     

Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity,Linking PHIP Variants to Repressed POMC Transcription

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Empathy,home environment,and attitudes toward animals in relation to animal abuse

Abstract

Recent years have seen an increase in interest in the social, behavioral, psychological, and developmental correlates of animal abuse. The current study examined the relationships between empathy, family environment, attitudes toward animals and participation in animal abuse using a self-report methodology among a sample of college students. Within a sample of 286 college students, scores on the Attitudes Toward the Treatment of Animals Scale (ATTAS) were significantly correlated with scores on the Interpersonal Reactivity Index (IRI), a measure of empathy. The Caregiving subscale of the ATTAS was found to significantly differentiate abusers from non-abusers, and to differentiate abusers who reported having first engaged in abuse prior to age 13 years from those who reported having first engaged in abuse at age 13 or later. Abusers scored significantly higher on the IRI Fantasy subscale than did non-abusers. Men who reported a history of sexual abuse were more likely to report participating in animal abuse than were those who reported no history of sexual abuse. Finally, the effect of sexual abuse on animal abuse was found to be independent of individual differences in empathy and attitudes toward animals. The potential roles of trauma and fantasy in the genesis of animal abuse are discussed.