Differences in spine growth potential for Sanders maturation stages 7A and 7B have implications for treatment of idiopathic scoliosis.

PURPOSE: This study aimed to clarify the differences in spine and total body height growth and curve progression between Sanders maturation stage (SMS) 7A and 7B in patients with adolescent idiopathic scoliosis (AIS). METHODS: This retrospective case-control study involving patients with AIS at SMS 7 evaluated the differential gains in the spine (T1-S1) and total body height and curve progression between SMS 7A and 7B. A validated formula was used to calculate the corrected height, accounting for height loss due to scoliosis. A multivariable non-linear and logistic regression model was applied to assess the distinct growth and curve progression patterns between the SMS 7 subtypes, adjusting for potential confounders. RESULTS: A total of 231 AIS patients (83% girls, mean age 13.9 ± 1.2 years) were included, with follow-up averaging 3.0 years. Patients at SMS 7A exhibited larger gains in spine height (9.9 mm vs. 6.3 mm) and total body height (19.8 mm vs. 13.4 mm) compared with SMS 7B. These findings remained consistent even after adjustments for curve magnitude. Non-linear regression models showed continued spine and total body height increases plateauing after 2 years, significantly greater in SMS 7A. More SMS 7A patients had curve progression over 10°, with an adjusted odds ratio of 3.31. CONCLUSION: This study revealed that patients staged SMS 7A exhibited more spine and total body growth and a greater incidence of substantial curve progression than those at 7B. These findings imply that delaying brace discontinuation until reaching 7B could be beneficial, particularly for those with larger curves. LEVEL OF EVIDENCE: Level III (Case-control study).

Palmitoylation of the small GTPase Cdc42 by DHHC5 modulates spine formation and gene transcription.

The small GTPase Cdc42 exists in the form of two alternatively spliced variants that are modified by hydrophobic chains: the ubiquitously expressed Cdc42-prenyl and a brain-specific isoform that can be palmitoylated, Cdc42-palm. Our previous work demonstrated that Cdc42-palm can be palmitoylated at two cysteine residues, Cys188 and Cys189, while Cys188 can also be prenylated. We showed that palmitoylation of Cys188 is essential for the plasma membrane localization of Cdc42-palm and is critically involved in Cdc42-mediated regulation of gene transcription and neuronal morphology. However, the abundance and regulation of this modification was not investigated. In the present study, we found that only a minor fraction of Cdc42 undergoes monopalmitoylation in neuroblastoma cells and in hippocampal neurons. In addition, we identified DHHC5 as one of the major palmitoyl acyltransferases that could physically interact with Cdc42-palm. We demonstrate that overexpression of dominant negative DHHC5 mutant decreased palmitoylation and plasma membrane localization of Cdc42-palm. In addition, knockdown of DHHC5 significantly reduced Cdc42-palm palmitoylation, leading to a decrease of Cdc42-mediated gene transcription and spine formation in hippocampal neurons. We also found that the expression of DHHC5 in the brain is developmentally regulated. Taken together, these findings suggest that DHHC5-mediated palmitoylation of Cdc42 represents an important mechanism for the regulation of Cdc42 functions in hippocampus.

Determinación de la maduración ósea según la morfología de las vértebras cervicales, sexo y biotipo facial de niños y adolescentes de Córdoba, Argentina / Determination of bonematurationaccording to the cervical vertebrae morphology, sex, and facial biotype of children and adolescents from Córdoba, Argentina

Introducción: Durante el proceso de crecimiento y desarrollo una serie de hechos se suceden con mayor o menor regularidad y similitud en todos los niños desde el nacimiento hasta la adultez. Mediante la radiografía carpal se observaban un gran número de centros secundarios de osificación, considerados "indicadores de madurez", ubicados en la mano, muñeca y epífisis distales del cúbito y radio. Actualmente, los cambios morfológicos de las vértebras cervicales son considerados indicadores de la maduración ósea. Objetivo:Con el objeto de minimizar las radiaciones en pacientes niños y adolescentes al momento de determinar el grado de maduración ósea, se reemplazó la radiografía carpal por la telerradiografía lateral de cráneo, utilizada rutinariamente. Corroborando, además la edad de maduración en nuestra población. Este estudio nos permite, al momento de decidir el plan de tratamiento, el método a utilizar para la resolución del caso clínico: ortopedia, ortodoncia o ambos a la vez.Materiales y métodos: estudiotransversal sin seguimiento del paciente. Se analizaron radiografías laterales del cráneo, ortopantomografías y carpo de 318 niños y adolescentes de ambos sexos de 10 a 16 años con dentición permanente en ambos arcos dentales, con/sin la presencia del 2° molar. El biotipo facial se determinó por el cefalograma de Björk-Jarabak.Resultados: Las edades promedio en los diferentes biotipos faciales no variaron significativamente, observándose valores medios menores en varones, con biotipo dólico y meso con tendencia a braquifacial. En niñas, se observa que la mayoría están relacionadas significativamente (p<0,05) con excepción del biotipo mesofacial entre edades cronológicas con edades óseas vertebrales y edades óseas vertebrales con óseas carpales y dentarias.Mientras que en varones la excepción se da en el biotipo dólicofacial en todas las variables siendo, solamente significativo entre las variables: edades cronológicas con óseas carpales y edades óseas vertebrales con óseas carpales. Por lo tanto, podemos concluir que existe una alta correlación entre las edades óseas vertebral, carpal y dentaria en ambos sexos y biotipos faciales excepto en niñas con biotipo mesofacial

FAM20C plays a critical role in the development of mouse vertebra.

BACKGROUND CONTEXT: Family with sequence similarity 20-member C (FAM20C) is a protein kinase that is responsible for the phosphorylation of many secretory proteins; however, its roles in spine or vertebra development have not be studied. PURPOSE: The aim of this investigation is to analyze the roles of FAM20C in vertebra development. STUDY DESIGN/SETTING: A mouse study of the Fam20c gene using conditional knockout to assess the effects of its inactivation on vertebra development. METHODS: By breeding Sox2-Cre mice with Fam20cflox/flox mice, Sox2-Cre;Fam20cflox/flox mice (abbreviated as cKO mice) are created. X-ray radiography, resin-casted scanning electron microscopy, Hematoxylin and Eosin staining, safranin O staining, Goldner's Masson trichrome staining, Von Kossa staining, tartrate-resistant alkaline phosphatase staining, immunohistochemistry staining, Western Immunoblotting and real-time PCR were employed to characterize the vertebrae of cKO mice compared to the normal control mice. RESULTS: Inactivation of Fam20c in mice results in remarkable spine deformity, severe morphology and mineralization defects, altered levels of osteoblast differentiation markers, reduction of activity of the Wnt/ß-catenin signaling pathway and reduced level of osteoclastogenesis in the vertebrae. CONCLUSIONS: FAM20C plays an essential role in vertebral development; it may regulate vertebral formation through the Wnt/ß-catenin signaling pathway. CLINICAL SIGNIFICANCE: Mutations in the human FAM20C gene are associated with Raine syndrome. The findings of this study provide valuable clues for the clinical management of Raine syndrome regarding spine manifestations in patients.

hox gene expression predicts tetrapod-like axial regionalization in the skate, Leucoraja erinacea.

The axial skeleton of tetrapods is organized into distinct anteroposterior regions of the vertebral column (cervical, trunk, sacral, and caudal), and transitions between these regions are determined by colinear anterior expression boundaries of Hox5/6, -9, -10, and -11 paralogy group genes within embryonic paraxial mesoderm. Fishes, conversely, exhibit little in the way of discrete axial regionalization, and this has led to scenarios of an origin of Hox-mediated axial skeletal complexity with the evolutionary transition to land in tetrapods. Here, combining geometric morphometric analysis of vertebral column morphology with cell lineage tracing of hox gene expression boundaries in developing embryos, we recover evidence of at least five distinct regions in the vertebral skeleton of a cartilaginous fish, the little skate (Leucoraja erinacea). We find that skate embryos exhibit tetrapod-like anteroposterior nesting of hox gene expression in their paraxial mesoderm, and we show that anterior expression boundaries of hox5/6, hox9, hox10, and hox11 paralogy group genes predict regional transitions in the differentiated skate axial skeleton. Our findings suggest that hox-based axial skeletal regionalization did not originate with tetrapods but rather has a much deeper evolutionary history than was previously appreciated.

Diversity and function of motile ciliated cell types within ependymal lineages of the zebrafish brain.

Motile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain and spine disorders. The development of ciliated cells, their impact on CSF flow, and their function in brain and axial morphogenesis are not fully understood. We have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricles undergo restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs co-exist with monociliated cells and generate directional flow patterns. These ciliated cells have different developmental origins and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from the tela choroida and choroid plexus or global perturbation of multiciliation does not affect overall brain or spine morphogenesis but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.

Marking fin spine of juvenile sturgeon (Acipenseriformes: Acipenseridae) using oxytetracycline and the comparing of growth performance / [Marcação da espinha da nadadeira de esturjão juvenil (Acipenseriformes: Acipenseridae) usando-se oxitetraciclina e comparação do desempenho de crescimento]

This study aimed to describe and validate the formation of the rings in the spine of the pectoral fin and to determine the coherence of the OTC mark with the rings of three species of Caspian Sea sturgeon, the Persian sturgeon (Acipenser persicus), the Starry sturgeon (Acipenser stellatus) and Ship sturgeon (Acipenser nudiventris). Validation was achieved by comparing the total radius of the fin spine of fish of known age after one and two years of growth with the measured radius of the first and second rings in the zone. There was no overlap between the measured radius for the first year and the increase for the second. The Ship sturgeon showed the largest width of the second ring followed by the Persian sturgeon and Stellate sturgeon. The results indicate that the highest growth parameter belongs to the juvenile Ship sturgeon. This research showed that chemically marking the fin spines of juvenile Acipenseridae leads to unbiased estimates and contributes to the knowledge of the population dynamics of these species. The study found that the combination of the dial ring of the pectoral fin spine with growth validated the age estimation in juvenile sturgeon Ship, Persian, and Starry sturgeon.(AU)

O objetivo deste estudo foi descrever e validar a formação dos anéis na espinha da nadadeira peitoral de três espécies de esturjão do mar Cáspio: o esturjão-persa (Acipenser persicus), o esturjão-estrelado (Acipenser stellatus) e o esturjão-de-navio (Acipenser nudiventris), bem como determinar a coerência da marca OTC com os anéis dessas três espécies. A validação foi alcançada comparando-se o raio total da espinha da nadadeira de peixes de idade conhecida, após um e dois anos de crescimento, com o raio medido do primeiro e segundo anéis na zona. Não houve sobreposição entre o raio medido no primeiro ano e o aumento no segundo. O esturjão-de-navio mostrou a maior largura do segundo anel, seguido pelo esturjão-persa e pelo esturjão-estrelado. Os resultados indicam que o maior parâmetro de crescimento pertence ao esturjão-de-navio juvenil. Esta pesquisa mostrou que a marcação química dos espinhos das nadadeiras de juvenis de Acipenseridae leva a estimativas imparciais e contribui para o conhecimento da dinâmica populacional dessas espécies. O estudo descobriu que a combinação do anel do mostrador da barbatana peitoral espinhal com o crescimento validou a estimativa de idade em esturjão-de-navio juvenil, esturjão-persa e esturjão-estrelado.(AU)

Spiny and soft-rayed fin domains in acanthomorph fish are established through a BMP-gremlin-shh signaling network.

With over 18,000 species, the Acanthomorpha, or spiny-rayed fishes, form the largest and arguably most diverse radiation of vertebrates. One of the key novelties that contributed to their evolutionary success are the spiny rays in their fins that serve as a defense mechanism. We investigated the patterning mechanisms underlying the differentiation of median fin Anlagen into discrete spiny and soft-rayed domains during the ontogeny of the direct-developing cichlid fish Astatotilapia burtoni Distinct transcription factor signatures characterize these two fin domains, whereby mutually exclusive expression of hoxa13a/b with alx4a/b and tbx2b marks the spine to soft-ray boundary. The soft-ray domain is established by BMP inhibition via gremlin1b, which synergizes in the posterior fin with shh secreted from a zone of polarizing activity. Modulation of BMP signaling by chemical inhibition or gremlin1b CRISPR/Cas9 knockout induces homeotic transformations of spines into soft rays and vice versa. The expression of spine and soft-ray genes in nonacanthomorph fins indicates that a combination of exaptation and posterior expansion of an ancestral developmental program for the anterior fin margin allowed the evolution of robustly individuated spiny and soft-rayed domains. We propose that a repeated exaptation of such pattern might underly the convergent evolution of anterior spiny-fin elements across fishes.

Does the Use of Sanders Staging and Distal Radius and Ulna Classification Avoid Mismatches in Growth Assessment with Risser Staging Alone?

BACKGROUND: Although Risser stages are visible on the same radiograph of the spine, Risser staging is criticized for its insensitivity in estimating the remaining growth potential and its weak correlation with curve progression in patients with adolescent idiopathic scoliosis. Risser staging is frequently accompanied by other skeletal maturity indices to increase its precision for assessing pubertal growth. However, it remains unknown whether there is any discrepancy between various maturity parameters and the extent of this discrepancy when these indices are used concurrently to assess pubertal growth landmarks, which are important for the timing of brace initiation and weaning. QUESTIONS/PURPOSES: (1) What is the chronologic order of skeletal maturity grades based on the growth rate and curve progression rate in patients with adolescent idiopathic scoliosis? (2) What are the discrepancies among the grades of each maturity index for indicating the peak growth and start of the growth plateau, and how do these indices correspond to each other? (3) What is the effectiveness of Risser staging, Sanders staging, and the distal radius and ulna classification in assessing peak growth and the beginning of the growth plateau? METHODS: Between 2014 and 2017, a total of 13,536 patients diagnosed with adolescent idiopathic scoliosis were treated at our tertiary clinic. Of those, 3864 patients with a radiograph of the left hand and wrist and a posteroanterior radiograph of the spine at the same visits including initial presentation were considered potentially eligible for this study. Minimum follow-up was defined as 6 months from the first visit, and the follow-up duration was defined as 2 years since initial consultation. In all, 48% (1867 of 3864) of patients were eligible, of which 26% (485 of 1867) were excluded because they were prescribed bracing at the first consultation. These patients visited the subsequent clinics wearing the brace, which might have affected body height measurement. Six percent (117 of 1867) of eligible patients were also excluded as their major coronal Cobb angle reached the surgical threshold of 50° and had undergone surgery before skeletal maturity. Another 21% (387 of 1867) of patients were lost before minimum follow-up or had incomplete data, leaving 47% (878) for analysis. These 878 patients with 1139 skeletal maturity assessments were studied; 74% (648 of 878) were girls. Standing body height was measured in a standardized manner by a wall-mounted stadiometer. Several surgeons measured curve magnitude as per routine clinical consultation, skeletal maturity was measured according to the distal radius and ulna classification, and two raters measured Risser and Sanders stages. Reliability tests were performed with satisfaction. Data were collected for the included patients at multiple points when skeletal maturity was assessed, and only up to when brace wear started for those who eventually had bracing. The growth rate and curve progression rate were calculated by the change of body height and major coronal Cobb angle over the number of months elapsed between the initial visit and next follow-up. At each skeletal maturity grading, we examined the growth rate (in centimeters per month) and curve progression rate (in degrees per month) since the skeletal maturity assessment, as well as the mean age at which this maturity grading occurred. Each patient was then individually assessed for whether he or she was experiencing peak growth and the beginning of growth plateau at each timepoint by comparing the calculated growth rate with the previously defined peak growth rate of ≥ 0.7 cm per month and the beginning of growth plateau rate of ≤ 0.15 cm per month in this adolescent idiopathic scoliosis population. Among the timepoints at which the peak growth and the beginning of growth plateau occurred, the median maturity grade of each maturity index was identified as the benchmark grade for comparison between indices. We used the McNemar test to investigate whether pubertal growth landmarks were identified by specific maturity grades concurrently. We assessed the effectiveness of these skeletal maturity indices by the difference in proportions (%) between two benchmark grades in indicating peak growth and the growth plateau. RESULTS: For girls, the chronological order of maturity grades that indicated peak growth was the radius grade, ulna grade, Sanders stage, and Risser stage. Curve progression peaked between the age of 11.6 and 12.1 years at a similar timing by all maturity indices for girls but was inconsistent for boys. For both sexes, radius (R) grade 6, ulna (U) grade 5, Sanders stage (SS) 3, and Risser stage 0+ were the median grades for peak growth, whereas Risser stage 4, R8/9, U7/8, and SS6/7 indicated the beginning of the growth plateau. The largest discrepancy between maturity indices was represented by Risser stage 0+, which corresponded to six grades of the Sanders staging system (SS2 to SS7) and to R6 in only 41% (62 of 152) of girls in the whole cohort. Despite Risser stage 0+ corresponding to the wide range of Sanders and distal radius and ulna grades, none of the R6, U5, SS3, and Risser stage 0+ was found more effective than another grade in indicating the peak growth in girls. R6 most effectively indicated the peak growth in boys, and Risser stage 0+ was the least effective. For the beginning of the growth plateau in girls, SS6/7 was the most effective indicator, followed by U7/8. Risser stage 4 was the least effective because it indicated 29% (95% CI 21% to 36%; p < 0.001) fewer patients who reached the beginning of the growth plateau than did those with R8/9. Risser stage 4 also indicated 36% (95% CI 28% to 43%; p < 0.001) fewer patients who reached the beginning of the growth plateau than those indicated by U7/8, and it identified 39% fewer patients than SS6/7 (95% CI 32% to 47%; p < 0.001). For boys, similarly, R8/9, U7/8, and SS6/7 were all more effective than Risser stage 4 in identifying when the growth plateau began. CONCLUSION: Risser stage 0+ corresponds to a wide range of Sanders and distal radius and ulna grades. Risser stage 0+ is least effective in indicating the peak growth in boys, and Risser stage 4 is the least effective maturity grade for indicating when the growth plateau starts in both sexes. The concurrent use of R6 and SS3 can be useful for detecting the peak growth, and SS6/7 in conjunction with U7/8 is most effective in indicating the beginning of the growth plateau. Using a combination of specific grades of Sanders staging and the distal radius and ulna classification can indicate pubertal growth landmarks with reduced risk of underestimating or overestimating skeletal maturity. These findings may aid in refining clinical decision-making of brace initiation and weaning at a more precise timing. Among Risser stage 0, the appearance of R6, U5, and SS3 provide the most effective assessment of peak growth that can indicate the most effective bracing period within which curve progression occurs. For initiation of the growth plateau, Risser 4 is not useful, and SS6/7, R8/9 and U7/8 should be used instead. LEVEL OF EVIDENCE: Level III, diagnostic study.

On being the right shape: Roles for motile cilia and cerebrospinal fluid flow in body and spine morphology.

How developing and growing organisms attain their proper shape is a central problem of developmental biology. In this review, we investigate this question with respect to how the body axis and spine form in their characteristic linear head-to-tail fashion in vertebrates. Recent work in the zebrafish has implicated motile cilia and cerebrospinal fluid flow in axial morphogenesis and spinal straightness. We begin by introducing motile cilia, the fluid flows they generate and their roles in zebrafish development and growth. We then describe how cilia control body and spine shape through sensory cells in the spinal canal, a thread-like extracellular structure called the Reissner fiber, and expression of neuropeptide signals. Last, we discuss zebrafish mutants in which spinal straightness breaks down and three-dimensional curves form. These curves resemble the common but little-understood human disease Idiopathic Scoliosis. Zebrafish research is therefore poised to make progress in our understanding of this condition and, more generally, how body and spine shape is acquired and maintained through development and growth.

Unveiling the tale of the tail: an illustration of spinal dysraphisms.

Spinal dysraphism is an umbrella term describing herniation of meninges or neural elements through defective neural arch. They can be broadly categorized into open and closed types. MRI is the investigation of choice to study neural abnormalities and to assess the severity of hydrocephalus and Chiari malformation. Knowledge of the embryology of these disorders is valuable in correctly identifying the type of dysraphism. The aim of surgery is untethering and dural reconstruction. Accurate depiction of the abnormal anatomy in cases of spinal dysraphism is of utmost importance for surgical management of these patients. MRI makes this possible due to its excellent soft tissue contrast resolution and multiplanar capability, allowing the radiologist to evaluate the intricate details in small pediatric spinal structures. Imaging enlightens the surgeons about the status of spinal cord and other associated abnormalities and helps detect re-tethering in operated cases. Besides, antenatal surgery to repair myelomeningoceles has made detection of open dysraphisms on fetal MRI and antenatal ultrasound critical. The purpose of this review is to describe the development of spine, illustrate the myriad imaging features of open and closed spinal dysraphisms, and enlist the reporting points the operating surgeon seeks from the radiologist.

Postembryonic screen for mutations affecting spine development in zebrafish.

The spine gives structural support for the adult body, protects the spinal cord, and provides muscle attachment for moving through the environment. The development and maturation of the spine and its physiology involve the integration of multiple musculoskeletal tissues including bone, cartilage, and fibrocartilaginous joints, as well as innervation and control by the nervous system. One of the most common disorders of the spine in human is adolescent idiopathic scoliosis (AIS), which is characterized by the onset of an abnormal lateral curvature of the spine of <10° around adolescence, in otherwise healthy children. The genetic basis of AIS is largely unknown. Systematic genome-wide mutagenesis screens for embryonic phenotypes in zebrafish have been instrumental in the understanding of early patterning of embryonic tissues necessary to build and pattern the embryonic spine. However, the mechanisms required for postembryonic maturation and homeostasis of the spine remain poorly understood. Here we report the results from a small-scale forward genetic screen for adult-viable recessive and dominant zebrafish mutations, leading to overt morphological abnormalities of the adult spine. Germline mutations induced with N-ethyl N-nitrosourea (ENU) were transmitted and screened for dominant phenotypes in 1229 F1 animals, and subsequently bred to homozygosity in F3 families; from these, 314 haploid genomes were screened for adult-viable recessive phenotypes affecting general body shape. We cumulatively found 40 adult-viable (3 dominant and 37 recessive) mutations each leading to a defect in the morphogenesis of the spine. The largest phenotypic group displayed larval onset axial curvatures, leading to whole-body scoliosis without vertebral dysplasia in adult fish. Pairwise complementation testing of 16 mutant lines within this phenotypic group revealed at least 9 independent mutant loci. Using massively-parallel whole genome or whole exome sequencing and meiotic mapping we defined the molecular identity of several loci for larval onset whole-body scoliosis in zebrafish. We identified a new mutation in the skolios/kinesin family member 6 (kif6) gene, causing neurodevelopmental and ependymal cilia defects in mouse and zebrafish. We also report multiple recessive alleles of the scospondin and a disintegrin and metalloproteinase with thrombospondin motifs 9 (adamts9) genes, which all display defects in spine morphogenesis. Our results provide evidence of monogenic traits that are essential for normal spine development in zebrafish, that may help to establish new candidate risk loci for spine disorders in humans.

Development and evolution of the notarium in Pterosauria.

The notarium is the structure formed by fusion of the dorsal vertebrae which occurred independently in pterosaurs and birds. This ankylosis usually involves two to six elements and in many cases, also includes the last cervical vertebra. Fusion can occur in different degrees, uniting the vertebral centra, the neural spines, the transverse processes, the ventral processes, or a combination of these sites. A detailed assessment of the fusion process of pterosaur dorsal vertebrae is still lacking. Here we identify the fusion sequence of pterosaur notarial elements, demonstrating the order of ossification in vertebral bodies and neural spines based on fossils and extant birds. In both Pterosauria and Aves, the notarium generally develops in a antero-posterior direction, but the actual order of each fusion locus may present slight variations. Based on our data, we were able to identify seven developmental stages in the notarium formation, with broad implications for the prediction of ontogenetic stages for the Pterosauria. In addition, we report the occurrence of a notarium in Ardeadactylus longicollum (Kimmeridgian, Southern Germany), the oldest occurrence of this structure in pterosaurs.

Morphological changes in the vertebrae and central canal of rat pups born after exposure to the electromagnetic field of pregnant rats.

Several studies have investigated the effects of the electromagnetic field (EMF) on the central nervous system. However, we encountered no studies of the effects of EMF applied in the prenatal period on the offspring vertebrae. The aim of this study is to investigate the effect of a 900 megahertz (MHz) EMF applied to rat dams in the prenatal period on the vertebrae of rat pups. Female Sprague Dawley rats weighing 180-250 g were used in the experiment. Rats identified as pregnant were divided into two groups, control (n = 3) and EMF (n = 3). No EMF was applied to the control group pregnant rats. EMF was applied to the EMF group rats for 1 h daily on an equal and standard basis on prenatal days 13-21. All newborn rat pups were divided into pup control (n = 6) (PC) and pup EMF (n = 6) (PEMF) groups, and no treatment was performed on either. All animals were decapitated on day 32, and the spinal cord in the upper thoracic region was harvested. Vertebral tissues were subjected to routine histological procedures. Histopathological examination revealed that PEMF group vertebral cartilage had been converted into bone tissue. Comparison of central canal diameter and area values between the PEMF group and the PC group revealed statistically significant increases in the PEMF group (p = 0.000 and p = 0.001, respectively). Statistical analysis revealed no significant difference in mean body weights between the two groups (p > 0.530). Based on these findings, we think that 900 MHz EMF applied in the prenatal period affects the development of the vertebrae. This effect causes pathological changes in the rat pup vertebrae. These findings now raise the question of whether EMF also has an impact on neurological and neurosurgical diseases involving the vertebrae.

Spinal changes after craniospinal irradiation in pediatric patients.

BACKGROUND: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI). PROCEDURE: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated. RESULTS: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis. CONCLUSIONS: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.

Spinal Growth in Patients With Juvenile Idiopathic Scoliosis Treated With Boston Brace: A Retrospective Study.

STUDY DESIGN: Retrospective comparative cohort. OBJECTIVE: The aim of this study was to determine whether spinal growth is restricted by brace treatment in patients with juvenile idiopathic scoliosis (JIS). SUMMARY OF BACKGROUND DATA: Spinal fusion can negatively affect spinal growth if performed before the growth spurt. Brace treatment is often given in this young population to control the spinal deformity while allowing spinal growth. It is unknown whether the applied pressure of brace treatment on spine results in growth restriction. The aim of the study is to evaluate spinal growth in braced JIS patients. METHODS: A total of 49 JIS patients treated with Boston brace were retrospectively selected from a scoliosis database. T1-T12/T1-S1 perpendicular and freehand (height following the curvature of the spine) height were measured on radiographs of patients that had reached skeletal maturity and were matched with 49 controls without scoliosis. Spinal growth was calculated from brace initiation until cessation and was compared with normal spinal growth values as reported by Dimeglio. RESULTS: The mean age of diagnosis was 7.4 years. The age of the braced scoliosis patients at skeletal maturity was 17.5 years. The average T1-T12 and T1-S1 freehand height measured by following the curvature of the scoliosis was 29.3 cm (±2.4) and 47.2cm (±4.0), respectively, and was not significant different from the control group. Brace treatment was initiated at a mean age of 11.2 and the mean age of cessation was 14.8. Spinal growth (freehand) during brace treatment was 1.10 cm/year for the thoracic spine and 1.78 cm/year for the full spine and was not significant different from normal values. CONCLUSION: No significant influence of bracing on spinal growth could be detected in this cohort of JIS patients. The spinal height measurements at skeletal maturity were similar to matched controls. In addition, spinal growth did not significantly differ from Dimeglio normal growth data, indicating that the effect of bracing on spinal growth is absent or minimal. LEVEL OF EVIDENCE: 3.

Anterior Vertebral Body Growth-Modulation Tethering in Idiopathic Scoliosis: Surgical Technique.

The management of idiopathic scoliosis in the skeletally immature patient can be challenging. Posterior spinal fusion and instrumentation is indicated for severe scoliosis deformities. However, the skeletally immature patient undergoing posterior fusion and instrumentation is at risk for developing crankshaft deformities. Moreover, bracing treatment remains an option for patients who are skeletally immature, and although it was found to be effective, it does not completely preclude deformity progression. Recently, fusionless treatment options, such as anterior vertebral body growth modulation, have been developed to treat these patients while avoiding the complications of posterior rigid fusion. Good results have been shown in recent literature with proper indications and planning in the skeletally immature patient.

Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates.

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a-/- mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a-/- mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the 'Hox code' via Polycomb regulation during axial patterning.

The Role of Gene Expression Changes in ceRNA Network Underlying Ossification of Ligamentum Flavum Development.

We aimed at exploring the role of gene expression changes regulated by non-coding RNAs in ossification of ligamentum flavum (OLF). Three microarray datasets, including long non-coding RNA (lncRNA)/mRNA expression profile (GSE106253), circular RNA (circRNA) expression profile (GSE106255), and microRNA (miRNA) expression profile (GSE106256), were downloaded from the public Gene Expression Omnibus repository. The differentially expressed (DE) mRNAs, lncRNAs, miRNAs, and circRNAs in OLF tissues were analyzed, compared with normal tissues. Two competing endogenous RNA (ceRNA) networks with lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interactions were constructed, separately. Random walk with the restart model was applied to calculate the correlations of mRNAs with the published OLF-related genes. The top 50 mRNAs were subjected to function enrichment analysis and active small-molecule prediction. Total 2323 DE mRNAs, 1168 lncRNAs, 336 circRNAs, and 29 miRNAs were identified based on the microarray datasets. The LncRNA-related ceRNA network was constructed with 614 lncRNA-miRNA, 494 miRNA-mRNA, and 2099 lncRNA-mRNA interaction pairs; the circRNA-related ceRNA network was constructed with 153 circRNA-miRNA, 190 miRNA-mRNA, and 210 circRNA-mRNA interaction pairs. There were 17 OLF-related genes retrieved from previous literature, such as NPPS, COL6A1, and COL11A2, among which COL6A1 was the overlapped gene with mRNAs in the ceRNA network. Subsequently, top 50 mRNAs that closely correlated with COL6A1 in the ceRNA network were captured and these genes were closely related with the collagen catabolic process, regulation of cell growth, and neuronal action potential. DRD1 and COL6A1 were predicted to be the targets by small active molecule drugs. The collagen catabolic process may be implicated in OLF development. COL6A1 and DRD1 may be the candidate targets for OLF. However, further validations were needed.