The multiple effects of thyroid disorders on bone and mineral metabolism / Os múltiplos efeitos das disfunções tireoidianas sobre o metabolismo osteomineral

Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.

Diferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT.

Automated assessment of developmental levels of epiphysis by support vector machine / 法医学杂志

OBJECTIVE@#To realize the automated assessment of the levels of epiphysis of distal radius and ulna by support vector machine (SVM).@*METHODS@#The X-ray films of the left wrist joints were taken from 140 teenagers aged from 11 to 19 years old as training samples. The levels of epiphysis of distal radius and ulna were divided into five developmental levels. Each level contained 28 samples. Another 35 cases were selected as independent verifying samples. SVM classification models of the five developmental levels of epiphysis of distal radius and ulna were established. The internal cross validation was made by leave one out cross validation (LOOCV), while the external validation was made by histogram of oriented gradient (HOG), and then the accuracy (PA) of testing results was calculated, respectively.@*RESULTS@#The PA of SVM, LOOCV and HOG of distal radius epiphyseal level were 100%, 78.6%, and 82.8%, respectively; whereas the PA of SVM, LOOCV and HOG of distal ulna epiphyseal level were 100.0%, 80.0% and 88.6%, respectively.@*CONCLUSION@#The SVM-based automatic models of the growth stage of distal ra- dius and ulna appear to have certain feasibility, and may provide a foundation for software development of bone age assessment by forensic medicine.

In vitro effects of caffeine in growth cartilage of rats / Efeitos in vitro da cafeína na cartilagem de crescimento de ratos

OBJETIVO: Avaliar os efeitos in vitro da cafeína na proliferação, apoptose e expressão de transcriptos gênicos de diferenciação condrogênica na cartilagem de crescimento.MÉTODO: As epífises cartilaginosas de fêmures de ratos neonatos foram divididas em dois subgrupos: os tratados com cafeína e o grupo controle, ambos observados nos tempos de 0, 7, 14 e 21 dias. As epífises cartilaginosas de fêmures de cada subgrupo e de cada tempo foram submetidas à histomorfometria, análise imunoistoquímica, técnica de túnel e RT-PCR em tempo real.RESULTADO: A diminuição da atividade proliferativa e o aumento de condroblastos em apoptose aos 21 dias foram encontrados em ambos os subgrupos. Entretanto a diminuição da proliferação celular causada pela cafeína foi menor quando comparada ao grupo controle e aumentou significativamente a expressão de transcriptos gênicos para diferenciação condrogênica, representada pelo SOX-9 e pelo RUNX-2. Entretanto o cultivo in vitro com cafeína demostrou efeitos antagônicos: apesar dos efeitos positivos na proliferação e diferenciação de condroblatos, cafeína aumentou a apoptose, caracterizada pelo aumento da expressão de caspase-3 e do numero de células em apoptose (p< 0.05).CONCLUSÃO: A cafeína apresenta efeitos antagônicos in vitro na cartilagem em crescimento, aumentando a proliferação, diferenciação e apoptose celular. Estudo experimental.

OBJECTIVE: To evaluate the in vitro effetcs of caffeine on proliferation, apoptosis and gene transcripts expression of chondrogenic differentiation in growth cartilage.METHODS: The cartilaginous epiphyses of femurs of newborn rats, which were divided into two subgroups: treated with caffeine and control group, both observed over the time periods of 0, 7, 14 and 21 days. The cartilaginous epiphyses of femurs of each subgroup and each time span were subjected to histomorphometric, immunohistochemical analysis, Tunel technique and RT-PCR in real time.RESULTS: The decrease in proliferative activity and the increase of apoptotic chondroblasts at 21 days were found regardless of the subgroup. However, the decrease in cell proliferation caused by caffeine was lower than in the control group and significantly increased the expression of gene transcripts for chondrogenic differentiation, represented by SOX-9 and RUNX-2. However, the in vitro culture with caffeine revealed antagonistic effects: despite the positive effect on chondroblasts proliferation and differentiation, caffeine increased apoptosis, characterized by increased expression of caspase 3 and of the number of cells undergoing apoptosis (p<0.05).CONCLUSION: Caffeine presents antagonistic effects in vitro on growth cartilage, increasing the proliferation, differentiation and cell apoptosis. Experimental Study.

Mathematical models of the teenager's skeletal age evaluation based on CT scan and imaging reconstruction of medial clavicular epiphysis / 法医学杂志

OBJECTIVE@#To explore the correlation between CT volume rendering (VR) statistics and living age and to build the mathematical models for skeletal age evaluation based on the growth rules of medial clavicular epiphysis of teenagers in China.@*METHODS@#The thin layer CT scan and VR 3D imaging reconstruction of both sides of sternal ends of clavicles were examined for 684 teenagers aged from 15 to 25 in East and South China. The parameters of sternal end of clavicle including the longest diameter of epiphysis, the longest diameter of metaphysis, their length radio, area of epiphysis, area of metaphysic, their area ratio, and other data were measured and calculated in order to establish mathematical models of skeletal age evaluation. Fifty trained subjects were tested to verify the accuracy of the mathematical models.@*RESULTS@#In the same age group, the length ratio and the area ratio had significant difference in genders (P < 0.05). The established mathematical models showed that the growth rules of medial clavicular epiphysis were highly correlated with the living ages. The accuracies of these models were higher than 70.5% +/- 1.0 year) and 82.5% (+/- 1.5 year).@*CONCLUSION@#The mathematical models have easy operability and high accuracy. It can be used to confirm and sustain the conclusion of atlas method. Meanwhile, it is of great significance to study the other single skeletal age evaluation in the future.

Mathematical models for teenager's living age evaluation based on CT image of medial clavicular epiphysis / 法医学杂志

OBJECTIVE@#To explore the correlation between volume rendering (VR) statistics of medial clavicular epiphysis and living age, and establish the mathematical models for living age evaluation using the CT image of medial clavicular epiphysis based on the growth rules of osteoepiphysis of medial clavicle.@*METHODS@#The CT images of the medial clavicles from 795 teenagers aged 15-25, 387 males and 408 females, were collected in East and South China. VR 3D images were reconstructed from 0.60 mm-thick slice CT images. The epiphyseal diameter, sternal end diameter, and their respective diameter ratio (the left: X1; the right: x3); epiphyseal area, sternal end area, and their respective area ratio (the left: x2; the right: x4), were measured and calculated. All these observations were analyzed using SPSS 19.0 statistical software. The statistical differences in gender and age were analyzed by Mann-Whitney U test. The mathematical models were established using least square. Sixty trained subjects, 30 males and 30 females, were tested to verify the accuracy of the established mathematical models.@*RESULTS@#In the group of same age, x1 showed significant difference in gender; the same results were observed in x2, x3, and x4, which suggested that the growth rules of osteoepiphysis of medial clavicle were highly correlated with living age. The accuracy of these mathematical models were all above 67.6% (+/- 1.0 year) and 78.5% (+/- 1.5 year).@*CONCLUSION@#The mathematical models with reasonable accuracy could be manageable in practice to confirm the conclusion of the atlas method. The current study can contribute to the single skeletal age evaluation.

Bone development trend in the knee joint of Tibetan teenagers in Aba Prefecture of Sichuan Province / 法医学杂志

OBJECTIVE@#To discuss bone development trend in the knee joint of Tibetan teenagers in Sichuan province and to effectively update the database for estimating the living age of Tibetan teenagers in terms of bone age of the knee joint.@*METHODS@#Radiographs including epiphysis of distal femur, proximal tibia and proximal fibula were taken from 483 Tibetan male and female teenagers aged from 14 to 19 years old in Aba prefecture of Sichuan province in order to observe epiphyseal growth situation. The descriptive data of the epiphyseal closure ages of these teenagers' knee joints were statistically analyzed by SPSS 16.0 software.@*RESULTS@#The distal femur epiphyseal closure occurred earliest, while the proximal fibula epiphyseal closure occurred latest. The epiphyseal growth of knee joints of females occurred about one year earlier than that of males.@*CONCLUSION@#The forensic information and data related to Tibetan teenagers' bone age identification should be updated regularly. These results provide potential value for the practice of forensic medicine, anthropology and clinical medicine.

The staging method of sternal end of clavicle epiphyseal growth by thin layer CT scan and imaging reconstruction / 法医学杂志

OBJECTIVE@#To establish a CT staging method of sternal end of clavicle epiphyseal growth for teenagers by thin layer CT scan, multiplanar reconstruction (MPR) and volume reconstruction (VR) technologies.@*METHODS@#The CT imaging characteristics, which collected from 460 teenagers (aged from 15 to 25) in East and South China, were studied through both sternal ends of clavicles' imagings by thin layer coronal CT scan and axial CT scan, MPR and VR technologies. The parameters of sternal end of clavicle including the longest diameter of epiphysis, the longest diameter of metaphysis, their length ratio, area of epiphysis, area of metaphysis, and their area ratio were measured and calculated in order to establish new classification.@*RESULTS@#Based on the staging method of Schmeling, integrating the CT imaging reconstruction information of sternal end of clavicle, the new classification of sternal end of clavicle epiphyseal growth were divided into 1 to 5 stages, and stage 2 and stage 3, respectively, contained a, b and c sub-classification.@*CONCLUSION@#This new classification has merits of large sample size, wide age range and easy operability. By using CT imaging reconstruction techniques and analyzing the data which closely related to sternal end of clavicle epiphyseal growth of teenagers, the feasibility of the staging method could be increased.

Progress in thin layer CT scan technology in estimating skeletal age of sternal end of clavicle / 法医学杂志

It is practical value for determination the teenagers whether the age is full of the legal responsibility age of 18 years old or not by estimating skeletal age of sternal end of clavicle. The traditional methods mainly based on X-ray radiography. However, sternal end of clavicle and adjacent lung, bronchus, sternum, rib, transverse process of thoracic vertebra are overlapped each other. As a result of overlapping, there will be obtained false negative or positive film reading results when according to X-ray observation of epiphyseal growth of sternal end of clavicle, which directly affect the scientificalness and accuracy of estimating of skeletal age. In recent years, the scholars at home and abroad have started to use thin layer CT scan technology to estimate skeletal age of the sternal end of clavicle. With the 2D and 3D CT recombination technology, the accuracy of the film reading distinctly improves by making the shape, size and position of epiphysis displayed clearly. This article reviews the application and research progress of thin layer CT scanning technology in estimating skeletal age of sternal end of clavicle at home and abroad, analyzes the superiority and value of thin layer CT scan technology, which applied to skeletal age of sternal end of clavicle.

Long-term trend of bone development in the contemporary teenagers of Chinese Han nationality / 法医学杂志

OBJECTIVE@#To further improve the accuracy of bone age identification using the time of secondary ossification center appearance and epiphyseal fusion of 7 joints to estimate the age of living individuals.@*METHODS@#DR films were taken from 7 parts including sternal end of clavical and the left side of shoulder, elbow, carpal, hip, knee and ankle joints of 1 709 individuals who came from eastern China, central China and southern China, whose ages were between 11.0 and 20.0 years. From those 7 joints 24 osteal loci were selected as bone age indexes, which could better reflect age growth of teenagers. The characteristics of secondary ossification center appearance and epiphyseal fusion were observed, and the mean and age range of secondary ossification center appearance and epiphyseal fusion were calculated.@*RESULTS@#The fusion time of the 24 epiphyses were advanced at different degrees, the most obvious epiphyses the sternal end of clavicle, scapular acromial end, distal end of the radius, distal end of the ulna, iliac crest, ischial tuberosity, the upper and lower end of tibia and fibula. The appearance time of sternal end of clavicle, scapular acromial end, iliac crest and ischial tuberosity epiphyses were all found to be after the age of 12, and the female's age, approximately 1 year ahead of schedule in comparison with the male's.@*CONCLUSION@#The relevant forensic information and data for bone age identification should be updated every 10-15 years so as to provide accurate and objective evidence for court testimony, conviction and sentencing.

Skeletal age estimation of sternal end of clavicle in Sichuan Han nationality youth using thin-section computed tomography / 法医学杂志

OBJECTIVE@#To explore the growth status of epiphysis of sternal end of clavicle using thin-section computed tomography (CT) and to study the relationship between the status and the chronological age of Sichuan Han nationality youth.@*METHODS@#According to the Schmeling's report and the age range of our samples, the ossification status of medial clavicle epiphysis was classified as four stages. CT films of 565 patients between 15 and 25 years were studied based on the classification and analyzed statistically.@*RESULTS@#There was no statistical difference between the sexes (P > 0.05). The calculated empiric distribution function showed that 100% of stage 1 patients were under 18 years, 75% of stage 2 patients were under 18 years, 94.5% of stage 3 patients were over 18 years, and 100% of the stage 4 patients were over 20 years, respectively.@*CONCLUSION@#The ossification of medial epiphysis of the clavicle for those around 18 years has certain regular. These characteristics can be used for forensic identification of the skeletal age, especially 18 years, which is the criminal responsibility age.

Age determination in girls of Jodhpur Region by epiphyseal union of bones at ankle joint.

There is no statistical data to establish variation in epiphyseal fusion in Western Rajasthan populations. This significant oversight can lead to exclusion of persons of interest in a forensic investigation. Epiphyseal fusion of the distal tibia and fibula in sixty females was analyzed on radiological basis to assess the range of variation of epiphyseal fusion at each age. In the study the X ray films of the subjects were divided into three groups on the basis of degree of fusion. Firstly, those which were showing No Epiphyseal Fusion (N), secondly those showing Partial Union (P), and thirdly those showing Complete Fusion (C). Observations made were compared with the previous studies. Results indicate that complete fusion in females occurs as early as 14 years in the distal tibia and fibula. All females demonstrated complete fusion by 19 years with no significant differences between ancestral groups.

Change in Effective Leg Length after Angular Deformity Correction by Hemiepiphyseal Stapling

BACKGROUND: The hemiepiphyseal stapling has both positive and negative effects on effective leg length. The purpose of this study was to analyze change in effective leg length after angular correction by hemiepiphyseal stapling, and to validate in clinical cases. METHODS: Mathematical analysis of a hemiepiphyseal stapling model was conducted. The induced formula was validated in 6 cases fulfilling the assumptions of the model. Anatomical parameters involved in this formula were measured in additional 21 cases undergoing hemiepiphyseal stapling or hemiepiphysiodesis. RESULTS: Effective leg length increased or decreased according to three parameters in this model: 1) limb length distal to the operated physis (L), 2) width of the operated physis (d), and 3) the amount of angular deformity to be corrected (theta). Actual change in effective leg length of 6 cases similar to this model coincided with the predicted change at least in its direction. L/d ratio was 4.82 +/- 0.51. CONCLUSIONS: Considering the narrow range of the L/d ratio, hemiepiphyseal stapling is likely to decrease effective leg length if the amount of angular correction is less than 10degrees, whereas to increase it if the amount of angular correction is larger than 16degrees. This should be taken into consideration when selecting the surgical method for angular deformity correction in skeletally immature patients.

Aspectos histológicos da epífise de crescimento ósseo em resposta ao exercício físico extenuante em camundongos / Histologic aspects of bone growth epiphysis after strenuous physical exercise in mice

Procurou-se identificar se existe alteração histológica na epífise de crescimento ósseo de camundongos submetidos a exercício físico extenuante. Para tanto, foi realizada uma pesquisa experimental com uma amostra de 8 camundongos, que ficaram em condições ambientes em um biotério, alimentados com água e ração comum, ad libitum. A ninhada foi dividida em dois grupos, um grupo controle e um grupo experimental, sendo que, o grupo experimental foi submetido a um exercício físico extenuante, caracterizado pelo aumento do nível de ácido láctico sanguíneo, realizado por 40 minutos/dia, durante 20 dias ininterruptos. Ao final da intervenção, foram confeccionadas lâminas histológicas, com cortes longitudinais do fêmur dos camundongos e analisadas em um microscópio óptico. Os dados obtidos mostraram alteração na estrutura epifisária do grupo experimental com aparente diminuição da zona proliferativa do disco epifisário, articulação mais desenvolvida e aumento das espículas ósseas com diminuição das trabéculas, sugerindo uma maturação precoce da epífise de crescimento. Através da análise dos resultados, conclui-se que o exercício físico extenuante modifica a estrutura da epífise de crescimento ósseo em camundongos.

The aim of this study was to identify histological alterations in bone growth epiphysis of mice submitted to a tiring physical exercise. For so, it was carried out an experimental research with a sample of 8 mice that stayed in environment conditions, fed with water and common feed, ad libitum. The brood was divided in two groups, a control group and an experimental group, being the experimental group submitted to a tiring physical exercise, characterized by the increasing of blood lactate level, carried out by 40 minutes/day, during 20 days uninterrupted. At the end of the intervention, were confectioned histological slides corresponding to the bone growth epiphysis of the femur of the mice and analyzed in an light microscope. Data showed an alteration in the epiphysis structure in the experimental group, with apparent decrease of the proliferation zone of epiphysis disc, an articulation more evolution and an increase of bone specula’s with a decrease of trabeculaes, what suggests an early maturation, accelerating the substitution of cartilaginous woven by bone weave. Through the analysis of the results, it was concluded that the tiring physical exercise modifies the structure of bone growth epiphysis in mice.

Effects of glucosamine on the tibial epiphyseal disk of ovariectomized rats: morphologic and morphometric analysis

OBJECTIVE: The aim of this study was to analyze the effect of glucosamine sulfate on the tibial epiphyseal disk of the ovariectomized rats. METHODS: After ovariectomy (OVx), 28 female rats were randomly divided into 4 experimental groups with 7 animals each, treated as follows: OVx 21 - vehicle (NaCl 0.9 percent) 0.5 mL/day) for 21 days; OVx GS21 - 230 mg/kg/day glucosamine sulphate for 21 days; OVx 45 - treated with NaCl 0.9 percent as above for 45 days; and OVx - GS45230 mg/kg/day glucosamine sulphate for 45 days. Seven intact animals in the proestrous phase were used as controls (CG). Upon treatment completion, the animals were sacrificed and the left knee joint was dissected and prepared for histological analysis. RESULTS: The percentage of remaining cartilage in new bone of the CG; that found in THE OVx GS45 group was significantly less than that of the OVx 21, OVx GS21, and OVx 45 groups. The percentage of trabecular bone in proestrous animals was the highest. The OVx GS45 group showed higher values compared with the other ovariectomized groups. These results were paralleled by the findings regarding the cells of the proliferative zone, since the CG had the highest values, and the values of the OVx GS45 group were greater than those of the OVx 21, OVx GS21, and OVx 45 groups. CONCLUSION: Our studies suggested that glucosamine may stimulate tibial cartilage and bone growth after ovariectomy in rats.

OBJETIVO: O alvo deste estudo foi analisar o efeito do sulfato de glicosamina no disco epifisário da tíbia em ratas ooforectomizadas. MÉTODOS: Após a ooforectomia (OVx), 28 ratas foram aleatoriamente divididas em 4 grupos experimentais de 7 animais cada, tratados da seguinte maneira: OVx 21 - veículo (0,5ml de NaCl 0.9 por cento ip uma vez ao dia) por 21 dias; OVx GS21 230 - mg/kg peso corporal por dia de sulfato de glicosamina, 21 dias; OVx 45 - tratados com NaCl 0.9 por cento igual ao grupo OVx 21, por 45 dias; e OVx GS45 - 230 mg/kg peso corporal por dia com sulfato de glicosamina, 45 dias. Sete animais intactos, na fase de proestro, foram usados como controle (CG). Ao completar o tratamento, os animais foram sacrificados e a articulação do joelho esquerdo foi dissecada e preparada para análise histológica. RESULTADOS: A porcentagem de cartilagem remanescente no novo osso do CG foi a menor. Os achados no grupo OVx GS45 foi significantemente menor do que no grupo OVx 21, OVx GS21 e OVx 45. A porcentagem de osso trabecular nos animais em pró-estro foi a maior. O grupo OVx GS45 mostrou valores maiores em relação aos outros grupos ooforectomizados. Esses resultados foram correspondentes aos achados em relação às células da zona proliferativa, desde que o CG teve os maiores valores e os valores do grupo OVx GS45 foram superiores aos dos grupos OVx 21, OVx GS21 e OVx 45. CONCLUSÃO: Nossos estudos sugerem que a glicosamina pode estimular o crescimento da cartilagem e do osso tibial após a ooforectomia em ratas.

Fixation of 16 years of age by radiological study of shoulder joint (a Jaipur based study).

Estimation of reasonably accurate age, plays a pivotal role in civil/criminal cases like personal identification, fixing of criminal responsibility, judicial punishment. The present study has been undertaken to explore the pattern of diaphysis-epiphyseal union in the bones of shoulder joint in growing population of Jaipur region.

Criterios de manejo de las lesiones fisarias en el Hospital Angeles del Pedregal / Criteria for treatment of physeal injuries in Hospital Angeles del Pedregal

Este es un estudio prospectivo, realizado en el periodo comprendido del 1º de enero de 1997 al 28 de febrero de 1998, en el servicio de urgencias de nuestro hospital. Fueron capturados los datos de todos los pacientes que ingresaron con una lesión fisaria de las extremidades; en total fueron 20 pacientes, 15 hombres y cinco mujeres. Se utilizó la clasificación de Salter y Harris, encontrando a dos pacientes en el tipo I, once pacientes en el tipo II, cinco en el tipo III y dos en el tipo IV. A todos los pacientes de los tipos I, II y III se les manejó con manipulación cerrada e inmovilización; a los dos pacientes con lesión tipo IV fueron ingresados para cirugía, realizando reducción abierta y fijación con clavillos de Kirschner. En la evaluación a los seis meses, se encontraron sin dolor 18 pacientes (90 pacientes) y el resto, sólo con dolor leve. Dieciocho pacientes tuvieron movilidad articular completa; un caso de lesión tipo II distal de radio tuvo limitación de 10 grados en la flexión de muñeca y otro paciente con lesión de la fisis de la epitróclea tuvo 10 grados de limitación en la extensión de codo. No hubo casos de acortamiento ni angulación. Es de importancia recalcar, que aunque la frecuencia de lesiones fisarias es baja en nuestro medio, se debe de efectuar una correcta evaluación y tratamiento para evitar complicaciones. El seguimiento del paciente se debe llevar a cabo hasta la fase final del crecimiento

Idade do aparecimento radiológico do núcleo epifisário proximal do fêmur / Age in which the proximal femoral center of ossification can be seen radiologically

Os autores avaliam radiologicamente a idade de aparecimento do núcleo epifisário femoral proximal em crianças com quadris normais,instáveis e luxados. Foram revisadas 369 radiografias de crianças de zero a 12 meses, acompanhadas no serviço de Ortopedia e Traumatologia da PUCRS pelo Grupo de Ortopedia Infantil (GOI) nos últimos dez anos. Comparam os dados com a literatura mundial e propöem um padräo médio