Effects of lead exposure on development of heart and spine in zebrafish embryos / 环境与职业医学

Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.

Effect of different Pilates workout endings on the kyphotic and lumbar lordotic angles / Efeito de diferentes finalizações do método Pilates sobre os ângulos de curvatura da coluna lombar e torácica

Abstract Introduction: There are no studies that investigate whether different workout endings of the Pilates method (PM), either prioritizing the activation of powerhouse muscles or the relaxation of muscles trained during the session, affects spinal curvature. Objective: Identify the immediate effect of a PM session that ends with soft tissue mobilization or wall exercises on the kyphotic and lumbar lordotic angles. Methods: A crossover clinical trial with 19 female Pilates practitioners that used a Flexicurve ruler to evaluate thoracic and lumbar spine curvature before and after a PM exercise protocol, and after endings that involved soft tissue mobilization using massage balls or wall exercises. The order of the different endings was chosen by random draw and the study volunteers participated in two interventions, with intervals of seven to ten days between them. Two two-way ANOVAs were performed (one for each postural variable), using the factors "assessment time" (pre-session; post-PE; post-ending) and "type of ending" (soft tissue or wall exercises). Results: There was no significant difference between the assessment times or endings for the kyphotic (p = 0.972; p = 0.747) and lumbar lordotic angles (p = 0.574; p = 0.627), respectively. Conclusion: Pilates instructors can opt for more relaxing or more active endings without affecting the kyphotic and lumbar lordotic angles.

Resumo Introdução: Ainda não há pesquisas que demonstrem se diferentes maneiras de finalização da sessão no método Pilates (MP), priorizando a ativação da musculatura do power house ou o relaxamento da musculatura trabalhada durante a sessão têm efeito sobre os ângulos de curvatura da coluna. Objetivo: Identificar qual é o efeito imediato de uma sessão do MP finalizada com mobilização de tecidos moles ou com exercícios na parede sobre os ângulos das curvaturas da coluna torácica e lombar. Métodos: Trata-se de um ensaio clínico cruzado, composto por 19 mulheres praticantes de Pilates, que avaliou as curvaturas torácica e lombar através do flexicurva antes e após um protocolo de exercícios do MP, e depois as finalizações de mobilização de tecidos moles através de bolas de massagem e de exercícios na parede. A escolha da ordem das diferentes finalizações foi realizada por sorteio e as voluntárias da pesquisa participaram das duas intervenções com intervalos entre sete e dez dias. Para análise, foram realizadas duas ANOVAs two-way (uma para cada variável postural) com os fatores "momento avaliativo" (pré-sessão; pós-PE; pós-finalização) e "tipo de finalização" (tecidos moles e parede). Resultados: Não houve diferença significativa entre os momentos avaliativos e entre o tipo de finalização para os ângulos da cifose dorsal (p = 0,972; p = 0,747) e da lordose lombar (p = 0,574; p = 0,627), respectivamente. Conclusão: Os profissionais podem propor diferentes formas de finalização, optando por uma finalização mais relaxante ou mais ativa, sem que isso interfira no ângulo das curvaturas torácica e lombar da coluna vertebral.

Sindrome de Ehlers-Danlos cifoescoliótico-FKBP14 en una paciente adolescente: primer reporte de caso colombiano / FKBP14 kyphoscoliotic Ehlers-Danlos Syndrome in adolescent patient: the first Colombian report

El síndrome de Ehlers-Danlos es un conjunto de trastornos hereditarios del tejido conectivo, clínica y genéticamente heterogéneos, caracterizados por hiperextensibilidad cutánea, pobre cicatrización, hipermovilidad articular y friabilidad tisular. Desde 1997, se han reportado variantes poco frecuentes del síndrome, entre las cuales se incluye el de tipo cifoescoliótico, causado por mutaciones en el gen PLOD1, caracterizado por hipotonía muscular grave al nacer, cifoescoliosis grave progresiva, osteopenia, ojos frágiles y fragilidad vascular. También ha sido descrita una rara variante recesiva que compromete el gen FKBP14, con hallazgos clínicos adicionales, que incluyen retardo del desarrollo psicomotor, miopatía, hipoacusia y una proporción normal de lisil-piridinolina a hidroxilisil-piridinolina en la orina. Se presenta el primer caso de una paciente colombiana con una mutación FKBP14 c.362dupC, caracterizada por hipotonía generalizada, retardo en el desarrollo de los hitos motores gruesos, hipoacusia, cifoescoliosis progresiva temprana, hipermovilidad articular y deformidades en los pies.

Ehlers-Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous inherited connective tissue disorders, characterized by skin hyperextensibility, poor wound healing, joint hypermobility and tissue friability. Since 1997 a new spectrum of novel rare EDS-variants has been described, among which is included the EDS kyphoscoliotic type, characterized by severe muscular hypotonia at birth, severe progressive kyphoscoliosis, osteopenia, fragile eyeballs and vascular fragility. This EDS variant is caused by mutations in the PLOD1 gene; however, a rare recessive variant that compromises the FKBP14 gene has been reported, with additional clinical findings that includes gross motor developmental delay, myopathy, hearing impairment and a normal ratio of lysyl pyridinoline to hydroxylysyl pyridinoline in urine. We report the first Colombian patient with a FKBP14 c.362dupC mutation, with clinical features that include generalized hypotonia, delayed gross motor milestones, hearing loss, early-onset progressive kyphoscoliosis, joint hypermobility and foot deformities.

Efficacy and safety of growing rods in the treatment of scoliosis in children under 10 / Eficácia e segurança de hastes de crescimento no tratamento da escoliose em crianças menores de 10 / Eficacia y seguridad de las barras de alargamiento en el tratamiento de escoliosis en niños menores de 10 años

ABSTRACT Objective: To determine the efficacy and safety of growing rods in the treatment of scoliosis in children aged under 10 years. Methods: A retrospective review of medical records of patients under 10 with scoliosis, treated with growing rods from the period between 1997 and 2012. Results: We identified 35 patients treated with growing rods who met the selection criteria. The average age at the start of treatment was 5.9 ± 2.3 years. Most of the patients (51.4%) showed idiopathic etiology scoliosis. Pre-surgery and post-surgery radiographic change showed a 47.7% reduction in Cobb angle (p>0.001). We identified 8 patients with some complication, the most prevalent being instrumentation failure (22.9%). The only predicting factor for post-operative complications was the total number of lengthenings performed (OR=7.03; CI 95% [1.1-45.4]; p=0.040). Conclusions: Treatment of scoliosis with growing rods in patients aged under 10 achieved a significant reduction in the magnitude of the deformity before final bone fusion. However, the rate of complications is rather high, therefore we recommend reducing the frequency of lengthenings to the minimum needed to maintain correction and longitudinal growth of the spine. Level of Evidence IV; Case series.

RESUMO Objetivo: Determinar a eficácia e segurança de hastes de crescimento no tratamento de escoliose em crianças menores de 10 anos. Métodos: Revisão retrospectiva de prontuários de pacientes menores de 10 anos com escoliose, tratados com hastes de crescimento entre 1997 e 2012. Resultados: Identificamos 35 pacientes, que foram tratados com hastes de crescimento, que satisfizeram os critérios de seleção. A idade média no início do tratamento foi de 5,9 ± 2,3 anos. A maioria dos pacientes (51,4%) apresentou escoliose de etiologia idiopática. A alteração radiográfica pré e pós-operatória mostra uma redução de 47,7% do ângulo de Cobb (p> 0,001). Foram identificados 8 pacientes com alguma complicação, sendo falha de instrumentação a mais prevalente (229%). O único fator preditivo para complicações pós-operatórias foi o número total de alongamentos realizados (OR = 7,03; IC95% [1,1-45,4]; p = 0,040). Conclusão: O tratamento para escoliose em pacientes com menos de 10 anos com hastes de crescimento alcançou uma redução significativa na magnitude da deformidade antes da fusão óssea final. No entanto, a frequência de complicações é bastante alta e, para isso, recomendamos reduzir ao mínimo a frequência de alongamentos, a fim de manter a correção e o crescimento longitudinal da coluna. Nível de Evidência IV; Série de casos.

RESUMEN Objetivo: Determinar la eficacia y seguridad de las barras de alargamiento en el tratamiento de la escoliosis en niños menores de 10 años. Métodos: Revisión retrospectiva de registros médicos de pacientes menores de 10 años con escoliosis, tratados mediante barras de alargamiento entre 1997 y 2012. Resultados: Se identificaron 35 pacientes tratados con barras de alargamiento que satisfacían los criterios de selección. El promedio de edad al inicio del tratamiento fue de 5,9 ± 2,3 años. La mayoría de los pacientes (51,4%) tenían escoliosis de etiología idiopática. El cambio radiográfico prequirúrgico y postquirúrgico mostró reducción del 47,7% en el ángulo de Cobb (p > 0,001). Se identificaron 8 pacientes con alguna complicación, siendo el fallo del instrumental más prevalente (22,9%). El único factor predictor de complicaciones postoperatorias fue el número total de alargamientos realizados (OR = 7,03; IC 95% [1,1-45,4]; p = 0,040). Conclusiones: El tratamiento de la escoliosis con barras de alargamiento en pacientes menores de 10 años logró una reducción significativa de la magnitud de la deformidad antes de la fusión ósea definitiva. Sin embargo, la tasa de complicaciones es bastante alta, por lo cual se recomienda disminuir la frecuencia de alargamientos al mínimo necesario para mantener la corrección y el crecimiento longitudinal de la columna vertebral. Nivel de Evidencia IV; Serie de Casos.

Normal values for sagittal spinal alignment: a study of Brazilian subjects

OBJECTIVES: The purpose of this study is to investigate the normal values of and chain of correlations between spinopelvic parameters in a Brazilian population. METHODS: This is a prospective observational study including asymptomatic adult subjects who had full spinal radiographs performed. The subjects were stratified by age into 3 groups (18-39 years old, 40-59 years old, and >60 years old), and radiographic parameters were compared across age groups and gender using ANOVA and Student's t-test, respectively. The relationships between various radiographic parameters were evaluated with Pearson correlation coefficients. RESULTS: One hundred and thirty asymptomatic volunteers (mean age, 48 years) met the inclusion criteria. The mean sagittal parameters in a normal Brazilian population were as follows: lumbar lordosis (LL) of 56.8°, pelvic tilt (PT) of 12.4°, pelvic incidence (PI) of 49.4°, PI-LL of -7.4°, T1 pelvic angle (TPA) of 8°, sagittal vertical axis (SVA) of -0.54 cm and T1 slope of 25.2°. Subjects ≥60 years old had significantly higher values of SVA (p=0.024) and TPA (p=0.009) than the two younger age groups. The TPA was significantly correlated with the following spinopelvic parameters: LL (r=-0.172, p=0.005), PT (r=0.776, p<0.001), PI (r=0.508, p<0.001), PI-LL (r=0.717, p<0.001), SVA (r=0.409, p<0.001) and T1 slope (r=0.172, p=0.050). CONCLUSION: This study demonstrated significant physiologic trunk inclination with increasing age. The TPA, an angular parameter of global spinal alignment, presented a chain of correlations with different spinal segments.

Comparación de resultados de osteotomías de Smith-Petersen, osteotomías de sustracción pedicular y vertebrectomía en el tratamiento de desequilibrio sagital / Comparação de resultados de osteotomias de Smith-Petersen, osteotomias de subtração pedicular e vertebrectomias no tratamento do desequilíbrio sagital / Comparison of Smith-Petersen, pedicle subtraction osteotomy and vertebral column resection for the correction of sagittal imbalance

OBJETIVO: Comparar los resultados clínicos y radiológicos de pacientes sometidos a osteotomías de Smith-Petersen (SPO), de sustracción pedicular (PSO) y vertebrectomías (VCR) en pacientes con desequilibrio sagital. MÉTODOS: Estudio observacional y retrospectivo. Se compararon 42 pacientes sometidos a 3 SPO (n=14), 1 PSO (n=16) y 1 VCR (n=12) por desequilibrio sagital fijo en el periodo de 2003-2011. La muestra constó de 71,4% de hombres y la edad promedio fue 43 años (17-74). El tiempo de seguimiento promedio fue 5 años. Se registraron las complicaciones, los resultados del cuestionario SRS-22, el ángulo de cifosis y eje sagital vertical (SVA) en el preoperatorio y a los 2 años postoperatorios. RESULTADOS: El tiempo quirúrgico (min.) fue menor en SPO respecto a PSO y VCR (420±347 vs. 578±459 vs. 533±435) (p<0,00). El sangrado intraoperatorio (cc) fue menor en SPO respecto a PSO y VCR (1341±804 vs. 2364±1459 vs, 2134±1335) (p<0,03). Del total, 38% presentaron complicaciones. No se observaron diferencias en el promedio de corrección en la cifosis segmentaria, pero sí en la corrección del SVA, siendo menor SPO. En el SRS-22, en los tres grupos se presentaron cambios significativos en todos los dominios respecto al preoperatorio, sin diferencias significativas entre grupos. CONCLUSIONES: No se encontraron diferencias en las complicaciones, aunque fueron de mayor gravedad en PSO y VCR. No había diferencias en la corrección de la cifosis segmentaria, pero PSO y VCR obtuvieron mejores resultados en la modificación del SVA. No había diferencias en la calidad de vida.

OBJETIVO: Comparar os resultados clínicos e radiológicos de pacientes submetidos a osteotomias de Smith-Petersen (SPO), de subtração pedicular (PSO) e vertebrectomias (VCR) em pacientes com desequilíbrio sagital fixo. MÉTODOS: Estudo retrospectivo observacional. Foram comparados 42 pacientes submetidos a 3 SPO (n = 14), 1 PSO (n = 16) e 1 VCR (n = 12) por desequilíbrio sagital no período 2003-2011. A amostra é constituída por 71,4% do sexo masculino e a média de idade é de 43 anos (17-74). O tempo médio de acompanhamento foi de 5 anos. Registraram-se as complicações, os resultados do questionário SRS-22, ângulos de cifose e SVA no pré-operatório e no pós-operatório, aos 2 anos. RESULTADOS: O tempo de cirurgia (minutos) foi menor em SPO comparado com PSO e VCR (420 ± 347 vs. 578 ± 459 vs. 533 ± 435) (p < 0,00). As perdas sanguíneas intraoperatórias (cc) foram menores em SPO quando comparadas com SPO PSO e VCR (1341 ± 804 vs. 2364 ± 1.459 vs. 2134 ± 1335) (p < 0,03). Do total, 38% apresentaram complicações. Não houve diferenças na correção média da cifose segmentar, mas sim na correção SVA, sendo menor SPO. No SRS-22, os três grupos apresentaram mudanças significativas em todas as áreas, em comparação com o pré-operatório, sem diferenças significativas entre os grupos. CONCLUSÕES: Não houve diferenças nas complicações, embora tenham sido mais graves em PSO e VCR. Não se verificaram diferenças na correção da cifose segmentar, mas PSO e VCR obtiveram melhores resultados na modificação do SVA. Não havia diferenças na qualidade de vida.

OBJECTIVE: To compare the clinical and radiological results of Smith-Petersen osteotomy (SPO), Pedicle Subtraction Osteotomy (PSO) and Vertebral Column Resection (VCR) on sagittal imbalance. METHODS: Retrospective cohort study. We compared 42 patients submitted to 3 SPO (n=14), 1 PSO (n=16) and 1 VCR (n=12) for fixed sagittal imbalance in the period 2003 to 2011. The sample consisted of 71.4% males, and the mean age was 43 years (17-74). The mean follow-up was 5 years. The complications, results of the SRS-22 questionnaire, sagittal Cobb angle and sagittal vertical axis (SVA) prior to surgery and 2 years after surgery were recorded. RESULTS: Mean operating time (min) was lower in SPO vs PSO and VCR (420 ± 347 vs. 578 ± 459 vs. 533 ± 435) (p<0.00). Average blood loss (cc) was lower in SPO vs PSO and VCR (1341 ± 804 vs. 2364 ± 1.459 vs. 2134 ± 1335) (p<0.03). The overall rate of complications was 38%. There were no differences in the mean segmental kyphosis correction achieved, but in the correction of SVA differences were observed, with SPO being lower. In SRS-22, the three groups showed significant differences in all areas, compared with the preoperative results, where there were no differences between the groups. CONCLUSIONS: there were no differences in complications, although these were more severe in PSO and VCR. No differences were found in correction of segmental kyphosis, but PSO and VSR achieved better results in terms of modifying the SVA. There was no difference in quality of life.

The Comparison of Sagittal Spinopelvic Parameters between Young Adult Patients with L5 Spondylolysis and Age-Matched Control Group

OBJECTIVE: To compare spinopelvic parameters in young adult patients with spondylolysis to those in age-matched patients without spondylolysis and investigate the clinical impact of sagittal spinopelvic parameters in patients with L5 spondylolysis. METHODS: From 2009 to 2012, a total of 198 young adult male patients with spondylolysis were identified. Eighty age-matched patients without spondylolysis were also selected. Standing lateral films that included both hip joints were obtained for each subject. Pelvic incidence (PI), sacral slope (SS), pelvic tilt, lumbar lordosis angle, sacral inclination, lumbosacral angle, and sacral table angle were measured in both groups. A comparative study of the spinopelvic parameters of these two groups was performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). RESULTS: Among the aforementioned spinopelvic parameters, PI, SS and STA were significantly different between patients with spondylolysis and those without spondylolysis. PI and SS were higher in the spondylolysis group than in the control group, but STA was lower in the spondylolysis group than in the control group. CONCLUSION: PI and SS were higher in the spondylolysis group than in the control group, but STA was lower in the spondylolysis group than in the control group. Patients with spondylolysis have low STA at birth, which remains constant during growth; a low STA translates into high SS. As a result, PI is also increased in accordance with SS. Therefore, we suggest that STA is an important etiologic factor in young adult patients with L5 spondylolysis.

Adolescent Idiopathic Scoliosis: A 71 Cases Study Ascertaining that Straightening Is Possible, and a New Etiological Hypothesis

STUDY DESIGN: Seventy-one children (23 boys and 48 girls, aged 6 to 18 year-old) with adolescent idiopathic scoliosis (AIS) between 11degrees and 62degrees, without braces, have been treated manually, only at the level of the neck. PURPOSE: To ascertain that non-surgical straightening of AIS is possible (without brace). OVERVIEW OF LITERATURE: So far no disease modifying treatment for AIS existed. Braces can only slow down worsening (and this can only be achieved if they are worn 23 hours a day). Surgery is not without important risks. METHODS: All patients have been treated exclusively with a manual therapy called Brachy-Myotherapy. This method treats spasmed (contractured) muscles by placing them in a shortening position according to a specific protocol. RESULTS: An average straightening of 8degrees of AIS was observed, with a maximum of 25degrees. 94% of cases improved, 67 out of 71. The worst prognosis was, the better results. The more advanced AIS was, the better the results. CONCLUSIONS: A simple and reliable treatment of AIS is possible. AIS seems to be a compensation mechanism of the body, with the aim of keeping the ears, and thus the labyrinths, at a horizontal level for correct equilibrium. When lasting post-traumatic neck muscle contractures causing a permanent side-bending of the skull have been treated, this compensation mechanism becomes irrelevant and scoliosis tends to subside.

Avaliação da coluna vertebral: relação entre gibosidade e curvas sagitais por método não-invasivo / Spine evaluation: Determination of the relationship between thoracic spinal deformity and sagittal curves by a noninvasive method

Os objetivos do estudo foram avaliar o alinhamento, no plano sagital, da coluna de indivíduos com alterações na medida da gibosidade, comparando com um grupo sem alterações; testar a confiabilidade do instrumento utilizado e verificar se existem correlações entre as medidas da gibosidade e os valores das curvaturas vertebrais. Foram avaliados 40jovens, divididos em grupo controle ? ausência ou presença de gibosidades inferiores a 0,5 cm na curvatura torácica e 0,7 cm na lombar (n=20) e, grupo experimental ? gibosidades superiores às descritas (n=20). A gibosidade e as curvaturas no plano sagital foram mensuradascom um instrumento adaptado a um nível d?água e o teste de Adams. As coletas foram realizadas em duas datas distintas, nos dois grupos. Após aplicação do teste Mann- Whitney não foi encontrada diferença entre as ocasiões de coletas e, emparelhando-se os grupos, foi encontrada diferença apenas na medida cervical. Na verificação de existênciade relação entre as medidas coletadas, foi encontrada correlação linear (Spearmann) no grupo controle ? curvatura torácica e gibosidade torácica; em ambos os grupos ? curvaturas torácica e lombar; e no grupo experimental ? gibosidade torácica e as curvaturas lombar esacral e, curvatura sacral e curvaturas torácica e lombar. Pôde-se concluir que a medida da gibosidade tem relações com as curvaturas no plano sagital. Por ser um método confiável, simples e acessível, pode ser reproduzido sem altos custos financeiros e sem causar prejuízoà saúde do paciente.

The objectives of this study were to compare sagittal plane alignment between subjects with spinal deformities and a group presenting no changes; to test the reliability of the tool used, and to determine the existence of correlations between spinal deformity and sagittal curvaturemeasures. Forty young subjects were divided into two groups: a control group (n=20) presenting no changes or spinal deformity less than 0.5 cm in the dorsal curvature and 0.7 cm in the lumbar curvature, and an experimental group (n=20) with spinal deformities greater than those described for the control group. Spinal deformity and sagittal plane curvatures were measured using a water level-based tool and by the Adams test. Data were collected from the two groups on two distinctoccasions. The Mann-Whitney test showed no difference between sampling times. A significant difference between the two groups was only observed in terms of cervical curvature. Spearman?s test revealed a linear correlation between dorsal curvature and dorsal spinal deformity in thecontrol group, between dorsal and lumbar curves in the two groups, and between dorsal spinal deformity and lumbar and sacral curves and between sacral curvature and dorsal and lumbar curves in the experimental group. In conclusion, spinal deformity measurement is associated with sagittal plane curvatures. The method proposed here is reliable, simple and accessible and can be reproduced without high costs and damage to the patient?s health.