High-Rate Anisotropic Properties in Human Infant Parietal and Occipital Bone.

Computational models of infant head impact are limited by the paucity of infant cranial bone material property data, particularly with regard to the anisotropic relationships created by the trabecular fibers in infant bone. We previously reported high-rate material property data for human infant cranial bone tested perpendicular to trabeculae fiber orientation. In this study, we measure the anisotropic properties of human infant cranial bone by analyzing bending modulus parallel to the trabeculae fibers. We tested human bone specimens from nine donors ranging in age from 32 weeks gestational age to 10 months at strain rates of 12.3-30.1 s-1. Bending modulus significantly increased with donor age (p=0.008) and was 13.4 times greater along the fiber direction compared to perpendicular to the fibers. Ultimate stress was greater by 5.1 times when tested parallel to the fibers compared to perpendicular (p=0.067). Parietal bone had a higher modulus and ultimate stress compared to occipital bone, but this trend was not significant, as previously shown perpendicular to fiber orientation. Combined, these data suggest that the pediatric skull is highly age-dependent, anisotropic, and regionally dependent. The incorporation of these characteristics in finite element models of infant head impact will be necessary to advance pediatric head injury research and further our understanding of the mechanisms of head injury in children.

Maternal Tobacco Smoke Exposure Causes Sex-Divergent Changes in Placental Lipid Metabolism in the Rat.

Maternal tobacco smoke exposure (MTS) affects fetal acquisition of long-chain polyunsaturated fatty acids (LCPUFA) and increases the risk of obesity and cardio-metabolic disease in the offspring. Alterations in fetal LCPUFA acquisition in maternal smoking are mediated by the placenta. The handling of LCPUFA by the placenta involves protein-mediated transfer and storage. Molecular mediators of placental LCPUFA handling include PPARγ and the fatty acid transport proteins. We previously demonstrated, in a rat model, that MTS results in programming of adult-onset obesity and metabolic disease in male, but not female, offspring. In this study, we test the hypothesis that in utero MTS exposure alters placental structure, placental LCPUFA handling, and fetal fatty acid levels, in a sex-divergent manner. We exposed pregnant rats to tobacco smoke from embryonic day 11 to term gestation. We measured placental and fetal fatty acid profiles, the systolic/diastolic ratio (SD ratio), placental histology, and expression of molecular mediators in the placenta. Our primary finding is that MTS alters fatty acid profiles in male, but not female fetuses and placenta, including increasing the ratio of omega-6 to omega-3 fatty acids. MTS also increased SD ratio in male, but not female placenta. In contrast, the expression of PPARγ and FATPs was upregulated in female, but not male placenta. We conclude that MTS causes sex-divergent changes in placental handling of LCPUFA in the rat. We speculate that our results demonstrate an adaptive response to MTS by the female placenta.

Fellowship training in pediatric pathology: a guide for program directors.

ABSTRACT The Accreditation Council for Graduate Medical Education (ACGME) has provided guidance for specialty and subspecialty fellowship training programs by defining 6 core competencies that must be met. Furthermore, the ACGME has defined several program requirements for pathology training, including those applicable to several pathology subspecialties. However, the requirements are broad and lack specific details, particularly as they pertain to the unique nature of pediatric pathology. The Fellowship Committee of the Society for Pediatric Pathology examined the ACGME requirements and interpreted the guidelines with respect to their application to training in pediatric pathology. The Committee worked within the ACGME guidelines to provide an expanded and more comprehensive set of guidelines for use by pediatric pathology fellowship directors and trainees. The resultant document lists the educational goals, core competencies, and program requirements with specific application to pediatric pathology. In addition, methods for assessing and documenting the progress of the individual trainees as they progress through each requirement are provided. It is to be emphasized that many of the guidelines set forthwith are flexible, and allowances should be made for individual differences of each training program.

Recurrence of achondrogenesis type 2 in sibs: Additional evidence for germline mosaicism.

Achondrogenesis Type II (ACG2) is a lethal skeletal disorder caused by a dominant mutation in the type II collagen gene (COL2A1). Familial cases have been reported, suggesting both germline and somatic mosaicism. We report on two pregnancies from the same couple with gross, radiologic, and microscopic findings of ACG2. Molecular analysis of the second infant demonstrated heterozygosity for a c.2303G > A transition (p.Gly768Asp) in exon 33 of the COL2A1 gene. Although this mutation could not be proven by molecular studies in the first infant, identical findings in two affected pregnancies support germline mosaicism as the cause of ACG2 in this family.

Composite pheochromocytoma: a clinicopathologic and molecular comparison with ordinary pheochromocytoma and neuroblastoma.

Composite pheochromocytoma is a rare adrenal tumor composed of ordinary pheochromocytoma and other components, most frequently neuroblastic elements. Little is known about its biologic potential, therefore creating a clinical dilemma on diagnosis. This study investigates the clinical characteristics and N-myc amplification status of 4 cases of composite pheochromocytoma and compares them with selected cases of ordinary pheochromocytoma and neuroblastoma. The age range of the patients with composite pheochromocytoma was 15 to 40 years with an equal M/F ratio, including 2 patients with syndromes. None of these composite pheochromocytomas demonstrated N-myc amplification, none recurred, and there were no deaths. Of the classic pheochromocytomas, none demonstrated N-myc amplification, 2 recurred, and there were no deaths. Of the neuroblastomas, 5 (50%) of 10 showed significant N-myc amplification, and there were 4 known recurrences and 5 known deaths. These findings suggest that composite pheochromocytoma may be regarded as a histologic variant of classic pheochromocytoma.

Mortality and pathological findings in C (Opitz trigonocephaly) syndrome.

Even as a rare multiple congenital anomalies/mental retardation syndrome, the C-syndrome (CS, or Opitz C-trigonoecephaly syndrome) is, at long last, beginning to attract attention because of its developmental and causal complexity. Also, the possibility that the apparently balanced translocation recently described in an affected Japanese boy may soon provide a molecular/causal insight into this disorder. The manifestations recorded in the previously published patients, those autopsied within recent years, and the unpublished instances in our files suggest that the CS is a heterogeneous genetic disorder, predominantly sporadic but with sufficient familial cases (at times with consanguinity) to allow postulation of an entity due to autosomal dominant mutations with a high rate of germinal mosaicism, or due to both autosomal dominant mutations and an autosomal recessive genocopy. In any event, elucidation of cause and pathogenesis of CS will, in due time, shed light on its developmental pleiotropy, rarity in liveborn infants, prevalence in stillborn fetuses, recurrence risk in humans, and occurrence in other animals (e.g., mice) to further understanding of pathogenesis.

Prenatal death in Fraser syndrome.

Cryptophthalmos may be partial or complete, unilateral or bilateral, apparently nonsyndromal or syndromal. A recent study of 2 stillborn infants at the University of Utah prompted an analysis of the developmental aspects of the syndromal form (Fraser syndrome). We conclude that, per se, cryptophthalmos is a developmental field defect on the basis of heterogeneity (autosomal dominant and recessive forms) and phylogeneity (occurrence also in the pheasant, rabbit, pigeon, dog, and mouse). In humans this autosomal recessive disorder maps to 4q21, is homologous to the bleb (bl/bl) mouse, and is due to mutations in the FRAS1 gene that codes for a 4007 amino acid protein 85% identical to the Fras1 gene of the bleb mouse. Commonest anomalies in humans are cryptophthalmos, cutaneous syndactyly of digits, abnormal ears and genitalia, renal agenesis, and congenital heart defects. Almost half of affected infants are stillborn or die in infancy, and mental retardation is common. The pathogenesis evidently involves abnormal epithelial integrity during prenatal life. Older (mostly German) publications, some dating to the 19th century, provide a fascinating historical insight into the process of syndrome delineation.