World Health Organization Classification of Tumours

Pathology and genetics of tumors of soft tissue and bone

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Little consistency has been manifest among investigators in choosing an appropriate experimental model for maxillofacial bone research. In an effort to develop a protocol for the experimental analysis of maxillofacial nonunions, previous studies using calvarial and mandibular defects as models were reviewed. The creation of nonunions in animals within the calvaria and mandible was size dependent. Defects of a size that will not heal during the lifetime of the animal may be termed critical size defects (CSDs). A rationale was postulated for testing bone repair materials (BRMs) using CSDs in a hierarchy of animal models. This rationale suggests that testing should be initiated in the calvaria of the rat and rabbit, followed by testing in the mandibles of dogs and monkeys. While calvarial CSDs have been established in the rat, rabbit, and dog, further research is necessary to determine the CSD in the calvaria of the monkey, as well as the mandibles of dogs and monkeys.

https://apps.dtic.mil/dtic/tr/fulltext/u2/a154625.pdf

The critical size defect as an experimental model for craniomandibulofacial nonunions.

A Metodologia Cientifica, mais do que uma disciplina, que em principio desperta a ideia de uma linha puramente teorica, deve ser encarada como um conjunto de procedimentos sistematicos e racionais, base da formacao tanto do estudioso quanto do profissional. Ambos atuam, alem da pratica, no mundo das ideias, ou seja, suas linhas basicas caminham pelo campo teorico, porem, o acumulo do conhecimento cientifico teorico, permite a sua aplicacao pratica no desenvolvimento tecnologico, alem de sua utilizacao nas atividades profissionais. Pode-se afirmar que a pratica nasce da concepcao sobre o que deve ser realizado e qualquer tomada de decisao fundamenta-se naquilo que se afigura como o mais logico, racional, eficiente e eficaz. Desta forma, deve-se encarar a Pesquisa Cientifica e o Metodo Cientifico, que fornece os subsidios para a sua realizacao, como fundamentais para o modelo de sociedade que estamos inseridos. Os alunos devem compreender a Metodologia da Pesquisa Cientifica como um instrumento que deve auxilia a humanidade a encontrar as respostas para os problemas que surgem em nossa vida cotidiana, alem da sua importância para a elaboracao do Trabalho Cientifico, que deve ser apresentado ao final do curso de Pos-Graduacao. Para atingir este objetivo, os alunos deverao produzir um resumo cientifico.

Metodologia da pesquisa científica

Static footprints were obtained from 672 healthy white subjects ranging in age from newborn to 15 years. The length of the footprint was measured and the medial longitudinal arch was evaluated. The findings showed that the feet grew most rapidly up to 3 years of age. From age 3 onward, the feet maintained an almost constant growth rate, which was the same for both sexes until age 12 years, when girls' feet stopped growing, but boys' feet exhibited further growth. From birth up to 2 years of age, there was a higher incidence of flat feet. Rapid progression of plantar arch development was observed between 2 and 6 years of age.

Footprint analysis during the growth period.

Purpose
The aim of this study was to establish ranges of angular variation in lordotic and kyphotic curves in normal male and female children and adolescents.

/pdf/development-and-evaluation-of-thoracic-kyphosis-and-lumbar-4unjcbnytc.pdf

Development and evaluation of thoracic kyphosis and lumbar lordosis during growth

Background: Calcaneal apophysitis in children is a self-limited condition that may interfere with walking and physical performance in sports, thus causing concern to the patient and parents. There is still controversy about the significance of the radiographic changes in children with heel pain, since the report of Sever in 1912. One of the reasons is that normal children may display a consid- erable variation in the radiographic aspects of the sec- ondary ossification center of the calcaneus at different ages. Methods: In this investigation, the developmental aspects of primary and secondary ossification centers of the calcaneus were studied in radiographs obtained from healthy boys and from boys with calcaneal apophysitis. The normal population comprised 392 children and ado- lescents ranging in age from 6 to 15 years. There were 69 individuals with calcaneal apophysitis ranging in age from 8 to 14 years. Lateral standard radiographs were ob- tained of both heels, and a copper step wedge was used as a calibration to determine bone density. The following pa- rameters were analyzed on the plain films: time of ap- pearance, fusion and number of fragments of the sec- ondary nucleus, area and bone densitometry of the pri- mary and secondary ossification centers of the calcaneus. Results: In the normal population, the ossification of the secondary nucleus began at 7 years of age, and at 15 years of age, the nucleus was fused in all individuals. In the apophysitis group, the secondary ossification center was present and not fused in all individuals. Both secondary nuclei increased in size with age with no difference be- tween the two groups. Regarding bone density, both the primary and secondary nuclei were less dense in the apophysitis group than their counterparts in the normal population. The most significant difference between the two populations referred to the degree of fragmentation, which was greater in the apophysitis group. Conclusion: Our data showed that the sclerotic aspect of the secondary nucleus of the calcaneus is a normal feature and, there- fore, should not be used to establish the diagnosis of Sever's disease. The most consistent difference between the normal and apophysitis group was related to the more fragmented aspect of the secondary nucleus in the latter individuals, which may suggest a mechanical etiology for that condition.

Calcaneal apophysitis: a quantitative radiographic evaluation of the secondary ossification center

Summary: An inherited tendency to hypercoagulability has been suggested as a cause of vascular thrombosis resulting in Legg-Calve-Perthes disease (LCPD). Here we carried out an investigation of the most common inherited risk factors for hypercoagulability including the mutation in the factor V gene (factor V Leiden), the transition 20.210 G→A in the prothrombin gene, and also the homozygosity for the 677C→T transition in the methylenetetrahydrofolate reductase gene (MTHFR). The investigation was carried out among 61 Brazilian children with LCPD, who were compared with 296 individuals from the general population. The prevalence of the factor V Leiden mutation was higher in LCPD patients than in the controls (4.9 vs. 0.7%; p = 0.03). However, no patient had the prothrombin gene variant, and no difference was found between patients and controls when homozygosity for MTHFR-T (3.2 vs. 2.6%; p = 0.64) was determined. These data suggest that in our population, the heterozygosity for factor V Leiden was the only inherited risk factor associated with the development of LCPD.

José Batista Volpon

Papers

Footprint analysis during the growth period.

Development and evaluation of thoracic kyphosis and lumbar lordosis during growth

Calcaneal apophysitis: a quantitative radiographic evaluation of the secondary ossification center

Inherited risk factors for thrombophilia among children with Legg-Calvé-Perthes disease.

Osteoid osteomas with chromosome alterations involving 22q.