Short stature caused by SHOX gene haploinsufficiency: from diagnosis to treatment

Estudos realizados em pacientes portadores de deleções parciais dos cromossomos sexuais permitiram a caracterização do SHOX, gene localizado na região pseudoautossômica no braço curto dos cromossomos sexuais, fundamental na determinação da altura normal. A perda de uma cópia deste gene na síndrome de Turner (ST) explica dois terços da baixa estatura observada nesta síndrome. A haploinsuficiência do SHOX é detectada em 77% dos pacientes com discondrosteose de Leri-Weill, uma forma comum de displasia esquelética de herança autossômica dominante e em 3% das crianças com baixa estatura idiopática (BEI), tornando os defeitos neste gene a principal causa monogênica de baixa estatura. A medida da altura sentada em relação à altura total (Z da AS/AT para idade e sexo) é uma forma simples de identificar a desproporção corpórea e, associada ao exame cuidadoso do paciente e de outros membros da família, auxilia na seleção de pacientes para o estudo molecular do SHOX. O uso de hormônio de crescimento (GH) está bem estabelecido na ST e em razão da causa comum da baixa estatura com o de crianças com defeitos isolados do SHOX o tratamento destes pacientes com GH é também proposto. Neste artigo será revisado os aspectos clínicos, moleculares e terapêuticos da haploinsuficiência do SHOX.Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77% of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3% of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Conformal Field Theory Interpretation of Black Hole Quasi-normal Modes

We obtain exact expressions for the quasi-normal modes of various spin for the BTZ black hole. These modes determine the relaxation time of black hole perturbations. Exact agreement is found between the quasi-normal frequencies and the location of the poles of the retarded correlation function of the corresponding perturbations in the dual conformal field theory. This then provides a new quantitative test of the AdS/CFT correspondence.Comment: 4 pages, RevTeX, references adde

Accessible technologies for kinetic and kinematic analysis of people with disabilities: a literature review/ Tecnologias acessíveis para análise cinética e cinemática da pessoa com deficiência: uma revisão da literatura

Locomotion is the process by which a being moves from one place to another, including stopping, changing speed, changes in direction and adaptation to changes in terrain. Human walking follows a pattern, and it is one of the forms of locomotion that most calls the attention of researchers. Its variation among a group may indicate pathological conditions that influence the treatment and rehabilitation of patients with low mobility. The objective of this article is to carry out a review for the development of a low-cost instrumented treadmill that can assist in the rehabilitation, treatment and follow-up of patients with stroke, and for that, a search of articles related to the topic was carried out in databases such as ScienceDirect, PubMed and others. The results obtained were satisfactory and enabled the creation of a good database. It was possible to conclude that there is a diversity of existing resources and that it is up to the professionals to direct their choice to the one that suits them best

Noonan syndrome: from phenotype to growth hormone therapy

A síndrome de Noonan (SN) é uma síndrome genética comum que constitui importante diagnóstico diferencial em pacientes com baixa estatura, atraso puberal ou criptorquidia. A SN apresenta grande variabilidade fenotípica e é caracterizada principalmente por dismorfismo facial, cardiopatia congênita e baixa estatura. A herança é autossômica dominante com penetrância completa. O diagnóstico é clínico, com base em critérios propostos por van der Burgt, em 1994. Recentemente, diversos genes envolvidos na via de sinalização RAS-MAPK foram identificados como causadores da SN: PTPN11, KRAS, SOS1, RAF1 e MEK1. O tratamento com hormônio de crescimento (hrGH) é proposto para corrigir a baixa estatura observada nestes pacientes. Estudos recentes apontam que pacientes com SN por mutações no gene PTPN11 apresentam pior resposta ao tratamento com hrGH quando comparado com pacientes sem mutações no PTPN11. Este artigo revisará os aspectos clínicos, moleculares e do tratamento da baixa estatura de crianças com SN com hrGH.Noonan Syndrome (NS) is one of the most common genetic syndromes and it is an important differential diagnosis in children with short stature, delayed puberty and cryptorchidism. NS is characterized by dysmorphic facial features, congenital heart defects and short stature, but there is a great variability in phenotype. NS may occur in a pattern consistent with autosomal dominant inheritance with almost complete penetrance. The diagnosis is based on a clinical score system proposed by van der Burgt e cols. in 1994. In recent years, germline mutations in the components of RAS-MAPK (mitogen activated protein kinase) pathway have been shown to be involved in the pathogenesis of NS. Mutations in PTPN11, KRAS, SOS1, RAF1 e MEK1 can explain 60-70% of NS molecular cause. Growth hormone therapy is proposed to correct the short stature observed in these patients. Recent studies suggest that the presence of PTPN11 mutations in patients with NS indicates a reduced growth response to short-term hrGH treatment. In this article, it is reviewed clinical and molecular aspects of NS and hrGH treatment for short stature.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Polarization and Strong Infra-Red Activity in Compressed Solid Hydrogen

Under a pressure of ~150 GPa solid molecular hydrogen undergoes a phase transition accompanied by a dramatic rise in infra-red absorption in the vibron frequency range. We use the Berry's phase approach to calculate the electric polarization in several candidate structures finding large, anisotropic dynamic charges and strongly IR-active vibron modes. The polarization is shown to be greatly affected by the overlap between the molecules in the crystal, so that the commonly used Clausius-Mossotti description in terms of polarizable, non-overlapping molecular charge densities is inadequate already at low pressures and even more so for the compressed solid.Comment: To appear in Phys. Rev. Let

Wannier-function description of the electronic polarization and infrared absorption of high-pressure hydrogen

We have constructed maximally-localized Wannier functions for prototype structures of solid molecular hydrogen under pressure, starting from LDA and tight-binding Bloch wave functions. Each occupied Wannier function can be associated with two paired protons, defining a ``Wannier molecule''. The sum of the dipole moments of these ``molecules'' always gives the correct macroscopic polarization, even under strong compression, when the overlap between nearby Wannier functions becomes significant. We find that at megabar pressures the contributions to the dipoles arising from the overlapping tails of the Wannier functions is very large. The strong vibron infrared absorption experimentally observed in phase III, above ~ 150 GPa, is analyzed in terms of the vibron-induced fluctuations of the Wannier dipoles. We decompose these fluctuations into ``static'' and ``dynamical'' contributions, and find that at such high densities the latter term, which increases much more steeply with pressure, is dominant.Comment: 17 pages, two-column style with 14 postscript figures embedded. Uses REVTEX and epsf macro

Relaxation in Conformal Field Theory, Hawking-Page Transition, and Quasinormal/Normal Modes

We study the process of relaxation back to thermal equilibrium in $(1+1)$-dimensional conformal field theory at finite temperature. When the size of the system is much larger than the inverse temperature, perturbations decay exponentially with time. On the other hand, when the inverse temperature is large, the relaxation is oscillatory with characteristic period set by the size of the system. We then analyse the intermediate regime in two specific models, namely free fermions, and a strongly coupled large $\tt k$ conformal field theory which is dual to string theory on $(2+1)$-dimensional anti-de Sitter spacetime. In the latter case, there is a sharp transition between the two regimes in the ${\tt k}=\infty$ limit, which is a manifestation of the gravitational Hawking-Page phase transition. In particular, we establish a direct connection between quasinormal and normal modes of the gravity system, and the decaying and oscillating behaviour of the conformal field theory.Comment: 10 pages, latex, no figure

Use of Lichen and Moss in Assessment of Forest Contamination with Heavy Metals in Praded and Glacensis Euroregions (Poland and Czech Republic)

The concentrations of selected metals—Cr, Ni, Cu, Zn, Cd, and Pb—were determined in the samples of Hypogymnia physodes lichen and Pleurozium schreberi moss collected in Polish and Czech Euroregions Praded and Glacensis. More specifically, the samples were collected in Bory Stobrawskie, Bory Niemodlińskie, and Kotlina Kłodzka (Poland) and in Jeseniki (Czech Republic). The concentration of metals in the samples was measured using the atomic absorption spectrometry (flame AAS technique and electrothermal atomization AAS technique). The results were used to calculate the comparison factor (CF) that quantifies the difference in concentration of a given bioavailable analyte × accumulated in lichens and mosses: CF = 2 (cx,lichen − cx,moss) (cx,lichen + cx,moss)−1. The values of CF greater than 0.62 indicate the most probable location of heavy metals deposited in the considered area. In this work, the method was used to show a significant contribution of urban emissions to the deposition of heavy metals in the area of Bory Stobrawskie and in the vicinity of Kłodzko City