Developmental administration of valproic acid alters DNA methylation and maternal behavior.

Exposure to adversity in early development has powerful and potentially lasting consequences on behavior. Previous work in our laboratory using female Long-Evans rats has demonstrated that exposure to early-life maltreatment manifests into alterations in dam behavior, including a perpetuation of the maltreatment phenotype. These observed behavioral changes coincide with changes in epigenetic activity in the prefrontal cortex (PFC). Further, treating dams with a chromatin modifying agent (Zebularine) normalizes methylation and maltreatment phenotypes, suggesting a link between epigenetic programming and phenotypic outcomes. Here, we sought to investigate if administration of a chromatin modifying agent concurrent with the experience of maltreatment normalizes epigenetic activity associated with maltreatment and alters behavioral trajectories. Administration of valproic acid (VPA) transiently lowered levels of global DNA methylation in the PFC, regardless of exposure to nurturing care or maltreatment. When VPA-exposed animals reached adulthood, they engaged in more adverse behaviors toward their offspring. These data provide further evidence linking epigenetic changes in the developing brain with effects on behavior.

NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells.

NOTCH signaling is required for the arterial specification and formation of hematopoietic stem cells (HSCs) and lympho-myeloid progenitors in the embryonic aorta-gonad-mesonephros region and extraembryonic vasculature from a distinct lineage of vascular endothelial cells with hemogenic potential. However, the role of NOTCH signaling in hemogenic endothelium (HE) specification from human pluripotent stem cell (hPSC) has not been studied. Here, using a chemically defined hPSC differentiation system combined with the use of DLL1-Fc and DAPT to manipulate NOTCH, we discover that NOTCH activation in hPSC-derived immature HE progenitors leads to formation of CD144+CD43-CD73-DLL4+Runx1 + 23-GFP+ arterial-type HE, which requires NOTCH signaling to undergo endothelial-to-hematopoietic transition and produce definitive lympho-myeloid and erythroid cells. These findings demonstrate that NOTCH-mediated arterialization of HE is an essential prerequisite for establishing definitive lympho-myeloid program and suggest that exploring molecular pathways that lead to arterial specification may aid in vitro approaches to enhance definitive hematopoiesis from hPSCs.

The Influence of Force Direction on the Fracture Pattern and Fracture Resistance of Canine Teeth in Dogs.

Biomechanical studies of the elongated canine tooth of animals are few, and thus our understanding of mechanical and physical properties of animal teeth is limited. The objective of the present study was to evaluate the influence of force direction on fracture resistance and fracture pattern of canine teeth in an ex vivo dog cadaver model. Forty-five extracted canine teeth from laboratory beagle dogs were standardized by hard tissue volume and randomly distributed among 3 force direction groups. The teeth were secured within a universal testing machine and a load was applied at different directions based on testing group. The maximum force to fracture and the fracture pattern classification were recorded for each tooth. After correcting for hard tissue cross-sectional area in a multivariate analysis, no significant difference in the amount of force required for fracture was apparent between the different force direction groups. However, the influence of force direction on fracture pattern was significant. The results of this study may allow the clinician to educate clients on possible causal force directions in clinically fractured teeth and, thus, help prevent any contributing behavior in the future.

Reliability of radiographic measures in infants with clubfoot treated with the Ponseti method.

PURPOSE: The aim of this study was two-fold: (1) to determine if radiographic measures can be reliably made in infants being treated with the Ponseti method and (2) to document radiographic changes before and after Achilles tenotomy. METHODS: A retrospective radiographic and chart review was performed on children with clubfoot treated by the Ponseti method at a single institution over a 10-year period. Five independent reviewers measured a series of angles from a lateral forced dorsiflexion radiograph taken prior to and following Achilles tenotomy. These measures were taken in triplicate to determine the intra- and inter-reader reliability of dorsiflexion, tibio-calcaneal, talo-calcaneal, and talo-first metatarsal angles. RESULTS: Thirty-six subjects (56 feet) were treated with the Ponseti method and met the inclusion criteria. The median (range) age of patients at the time of tenotomy was 52 (34-147) days. The intra-reader reliability [intra-rater correlation coefficient (ICC)] for each of the measured angles pre- and post-tenotomy ranged from 0.933 to 0.995 and 0.864 to 0.995, respectively. Similarly, the inter-reader reliabilities (ICC) ranged from 0.727 for the pre-tenotomy (talo-calcaneal) to 0.950 for the post-tenotomy (talo-first metatarsal) angles. The mean differences between pre- and post-tenotomy radiographs were: dorsiflexion increase of 17°, tibio-calcaneal angle increase of 19°, talo-calcaneal angle increase of 9°, and talo-first metatarsal angle increase of 10° (p-value ≤0.001 for all measurements except the talo-first metatarsal angle, with a p-value of 0.001). CONCLUSIONS: Reliable radiographic measures can be made from lateral dorsiflexion radiographs of clubfeet treated with the Ponseti method before and after Achilles tenotomy.

Evaluation of the Natural Crown Convergence Angle of Dog Carnassial Teeth.

A limiting factor in achieving an ideal crown preparation design is the natural morphology, principally the convergence angle, of the tooth. The natural convergence angle of the carnassial teeth in the dog has not been reported. The aim of the study reported here was to establish the natural crown convergence angle of the maxillary fourth premolar and mandibular first molar teeth in the dog. The natural convergence angle of the carnassial teeth in dogs was large and was not significantly associated with patient weight, age, or skull type.

Clinical manifestations and treatment of the pediatric rheumatoid patient.

The management goal of juvenile rheumatoid arthritis (JRA) is to achieve early diagnosis and treatment so that arthritis can be resolved at an early stage, which avoids long-term damage and provides a good outcome of the affected inflammatory joints. This article describes presentation, classification, evaluation, and treatment of JRA as it relates to the foot and ankle. Because the course of JRA is complex and the optimal management is highly variable in each patient, this article can only offer recommendations. Actual treatment should be individualized to meet the conditions of each patient.