The aim of our study was to evaluate thoracic vertebrae rotation in patients with pectus excavatum. Moreover, we wanted to assess the prevalence, the severity and relationship between pectus excavatum and adolescent idiopathic scoliosis (AIS).

Vertnin (VRTN) variants are associated with thoracic vertebral number (TVN) in pigs. However, the biological function of VRTN remains poorly understood. Here we first conducted a range of experiments to demonstrate that VRTN is a responsible gene for TVN and two causative variants in the regulatory region of VRTN additively regulate TVN. Then, we show that VRTN is a novel DNA-binding transcription factor as it localizes exclusively in the nucleus, binds to DNA on a genome-wide scale and regulates the transcription of a set of genes that harbor VRTN binding motifs. Next, we illustrate that VRTN is essential for the development of thoracic vertebrae. Vrtn-null embryos display somitogenesis defect with the failure of axial rotation and fewer somites at the thoracic somite stage. Half of Vrtn heterozygous mice show abnormal spinal development with fewer thoracic vertebrae and ribs than their wild-type littermates. Lastly, we reveal that VRTN could modulate somite segmentation via the Notch signaling pathway. The findings advance our understanding of the mechanisms underlying the development of thoracic vertebrate in mammals, and VRTN causative variants provide a robust tool to improve pork production by selecting the alleles increasing the number of thoracic vertebrae and ribs.

The number of vertebrae, especially thoracic vertebrae, is an important economic trait that may influence carcass length and meat production in animals. However, the genetic basis of vertebrae number in sheep is still poorly understood. To detect the candidate genes, 400 increased number of thoracic vertebrae (T14L6) and 200 normal (T13L6) Kazakh sheep were collected. We generated and sequenced 60 pools of genomic DNA (each pool prepared by mixing genomic DNA from 10 sheep with the same thoracic traits), with an average depth of coverage of 25.65×. We identified a total of 42,075,402 SNPs and 11 putatively selected genomic regions, including the VRTN gene and the HoxA gene family that regulate vertebral development. The most prominent areas of selective elimination were located in a region of chromosome 7, including VRTN, which regulates spinal development and morphology. Further investigation indicated that the expression level of the VRTN gene during fetal development was significantly higher in sheep with more thoracic vertebrae than in those with a normal number of thoracic vertebrae. A genome-wide comparison between sheep with increased and normal numbers of thoracic vertebrae showed that the VRTN gene is the major selection locus for the number of thoracic vertebrae in sheep and has the potential to be utilized in sheep breeding in the future.

The aim of this study was to evaluate the clinical and radiographic outcomes of upper thoracic (UT) versus lower thoracic (LT) upper instrumented vertebrae (UIV) for adult scoliosis by meta-analysis. We conducted a literature search in three databases to retrieve related studies up to March 15, 2017. The preliminary screened studies were assessed by two reviewers according to the selection criteria. All analyses were carried out using the statistical software package R version 2.31. Odds ratios (OR) with 95% confidence intervals (CI) were used to describe the results. The I2 statistic and Q statistic test were used for heterogeneity assessment. Egger's test was performed to detect publication bias. To assess the effect of each study on the overall pooled OR or standardized mean difference (SMD), sensitive analysis was conducted. Ten trials published between 2007 and 2015 were eligible and included in our study. Meta-analysis revealed that the UT group was associated with more blood loss (SMD=0.4779, 95%CI=0.3349-0.6209, Z=6.55, P<0.0001) and longer operating time (SMD=0.5780, 95%CI=0.1971-0.958, Z=2.97, P=0.0029) than the LT group. However, there was no significant difference in Oswestry Disability Index, Scoliosis Research Society (SRS) function subscores, radiographic outcomes including sagittal vertical axis, lumbar lordosis, and thoracic kyphosis, length of hospital stay, and revision rates between the two groups. No evidence of publication bias was found between the two groups. Fusion from the lower thoracic spine (below T10) has as advantages a shorter operation time and less blood loss than upper thoracic spine (above T10) in posterior long-segment fixation for degenerative lumbar scoliosis.

Previous reports of neonatal hypoglycemia have been associated with malpositioned umbilical cord artery catheters. Neonatal hypoglycemia in association with normally positioned umbilical artery catheter and responsive to catheter repositioning is reported for the first time.

Computed tomography currently has a prominent role in diagnosis and evaluation of vertebral column. On the other hand, a thorough knowledge about vertebral column property in normal state is prerequisite an accurate diagnosis of different abnormalities in this region.

The number of vertebrae (NV), especially the number of thoracic vertebrae (NTV), varies among pig breeds. The NTV is controlled by vertebral segmentation and the number of somites during embryonic development. Although there is a high correlation between the NTV and NV, studies on a fixed NV have mainly considered the absolute numbers of thoracic vertebrae instead of vertebral segmentation. Therefore, this study aimed to discover variants associated with the NTV by considering the effect of the NV in pigs. The NTV and NV of 542 F2 individuals from a Large White × Minzhu pig crossbreed were recorded. All animals were genotyped for VRTN g.19034 A > C, LTBP2 c.4481A > C, and 37 missense or splice variants previously reported in a 951-kb interval on SSC7 and 147 single nucleotide polymorphisms (SNPs) on SSC14. To identify NTV-associated SNPs, we firstly performed a genome-wide association study (GWAS) using the Q + K (population structure + kinship matrix) model in TASSEL. With the NV as a covariate, the obtained data were used to identify the SNPs with the most significant genome-wide association with the NTV by performing a GWAS on a PorcineSNP60K Genotyping BeadChip. Finally, a conditional GWAS was performed by fixing this SNP. The GWAS showed that 31 SNPs on SSC7 have significant genome-wide associations with the NTV. No missense or splice variants were found to be associated with the NTV significantly. A linkage disequilibrium analysis suggested the existence of quantitative trait loci (QTL) in a 479-Kb region on SSC7, which contained a critical candidate gene FOS for the NTV in pigs. Subsequently, a conditional GWAS was performed by fixing M1GA0010658, the most significant of these SNPs. Two SNPs in BMPR1A were found to have significant genome-wide associations and a significant dominant effect. The leading SNP, S14_87859370, accounted for 3.86% of the phenotypic variance. Our study uncovered that regulation variants in FOS on SSC7 and in BMPR1A on SSC14 might play important roles in controlling the NTV, and thus these genetic factors may be harnessed for increasing the NTV in pigs.

[Purpose] The purpose of this study was to examine the relationship between the degree of thoracic deformity (TD) and the angle formed by a line drawn on transverse plane computed tomography (CT) images, connecting the sternum and the spinous process of the vertebrae at the level of the xiphisternum, and the perpendicular line from the floor (ANGLE), in individuals with severe motor and intellectual disorders (SMID). [Subjects] Twenty seven individuals with SMID were examined. [Methods] CT transverse images were acquired at the level of the xiphisternum of each patient. Two protocols were used to measure the anteroposterior (AP) and laterolateral (LL) diameters. The largest AP diameters were measured along a perpendicular line from the floor (protocol 1) and the line from the midline of the sternum to the spinous process of the vertebrae (protocol 2). The largest LL diameters were measured along the lines perpendicular to the AP diameters in each protocol. The ratios of the AP to LL diameters and the difference between the ratios of protocols 1 and 2 (DIFFERENCE) were calculated. [Results] Moderate to good correlation between DIFFERENCE and ANGLE was observed, and DIFFERENCE became larger with increasing ANGLE. [Conclusions] These results show that ANGLE indicates the degree of TD.

Systematic review.

We aimed to clarify the position of the spinal cord relative to the vertebra in patients with Lenke type 1 adolescent idiopathic scoliosis (AIS). In all, 35 patients with Lenke type 1 AIS who underwent posterior spinal fusion using a pedicle screw construct and preoperative computed tomography (CT) after myelography were recruited. The following radiological parameters were measured on preoperative CT myelography: spinal cord-vertebral (SV) angle, entry-spinal cord distance (ESD), ESD-X, ESD-Y, spinal cord-pedicle (SP) angle, and rotation angle (RAsag). The SV and SP angles were the smallest at T9 level, followed by T8 and T7 levels, and tended to increase cranially and caudally. The ESD was the shortest at T9 level, followed by T8 and T10 levels. The ESD-X was the smallest at T9 level, followed by T8 level, while the ESD-Y was the smallest at T10 level, followed by T9 and T8 levels. Mean RAsag increased from T4 to T9 levels and decreased from T9 to T12 levels. The ESD was significantly negatively correlated to RAsag. Among all apical vertebrae, the SV and SP angles were negatively correlated to Cobb angle. The RAsag was positively correlated while the ESD was negatively correlated to the Cobb angle. The spinal cord is close to the vertebrae in the apical vertebral region and far from the vertebrae at the upper and lower thoracic vertebral levels in AIS. Therefore, the potential risk of spinal cord injury by pedicle screw is the highest in the apical vertebral region.

Transitional vertebrae at the thoracolumbar region are called thoracolumbar transitional vertebrae (TLTV) and retain physical features from the thoracic and lumbar regions. Since TLTV were first classified 40 years ago, there has been much discrepancy regarding its features, identification and clinical relevance. Vertebral body levels are used in the medical field as a frame of reference to locate specific organs, vessels, nerves or landmarks. Any numeric variation or deviation in the vertebral column may lead to clinical errors. Previous findings have suggested a high association between numeric variation and the presence of TLTV. Therefore, the aim of this study was to identify the types of TLTV observed and to identify any possible associated numeric variation in the vertebral column. This study also aimed to validate the established technique to quantitatively differentiate TLTV from T12 and L1 at the thoracolumbar junction using skeletal remains from a South African population group. Skeletal remains (n = 187) remains from the Pretoria bone collection were assessed. Measurements were taken of the angle of the superior zygapophyseal processes of the last thoracic vertebra (T12), the first lumbar (L1), and identified TLTV. The results indicate a TLTV prevalence of 35% (n = 66/187). The results show that each vertebral type (T12, L1, TLTV) fall into independent confidence intervals: T12 is 188° ± 9.22 (CI: 187° < μ < 189.6°), 110° ± 7.52 (CI: 109.2° < μ < 111.3°) in L1, and 135° ± 24.51 (CI: 130.4° < μ < 139.1°) in the TLTV. This study observed that 70% of cases with TLTV was associated with numeric variation in the spine, both homeotic and meristic and that TLTV has a 35% prevalence. The results clearly show that quantitative morphometric analysis can effectively differentiate TLTV from other vertebral types at the thoracolumbar junction in skeletal remains.

Mammals almost always have seven cervical vertebrae. The strong evolutionary constraint on changes in this number has been broken in sloths and manatees. We have proposed that the extremely low activity and metabolic rates of these species relax the stabilizing selection against changes in the cervical count. Our hypothesis is that strong stabilizing selection in other mammals is largely indirect and due to associated pleiotropic effects, including juvenile cancers. Additional direct selection can occur due to biomechanical problems (thoracic outlet syndrome). Low metabolic and activity rates are thought to diminish these direct and indirect effects. To test this hypothesis within the primates, we have compared the number of cervical vertebrae of three lorisid species with particularly low activity and metabolic rates with those of more active primate species, including with their phylogenetically closest active relatives, the galagids (bushbabies). In support of our hypothesis, we found that 37.6% of the lorisid specimens had an abnormal cervical count, which is a higher percentage than in the other nine primate families, in which the incidence varied from zero to 2.2%. We conclude that our data support the importance of internal selection in constraining evolvability and of a relaxed stabilizing selection for increasing evolvability. Additionally, we discuss that there is no support for a role of the muscularized diaphragm in the evolutionary constraint.

Disorders of the spine are among the most common indications for neurosurgical and orthopedic surgical interventions. Spinal fixation in the form of pedicle screw placement is a common form of instrumentation method in the lower cervical, thoracic, and lumbar spine. A vital principle to understand for the safe and accurate placement of pedicle screws is the palpable difference between the cortical and cancellous bone, both of which have different material properties and compositions. Probing and palpation of the hard cortical bone, also known as the "ventral lamina", covering the neural elements of the spinal canal during screw placement provides manual feedback to the surgeon, indicating an impending breach if continued directional force is applied. Generally, this practice is learned at the expense of patients in live operating room scenarios. Currently, there is a paucity of human vertebra simulation designs that have been validated based on the in vivo ultrastructure and physical properties of human cortical and cancellous bone. In this study, we examined the feasibility of combining three-dimensionally printed thermoplastic polymers with polymeric foam to replicate both the vertebral corticocancellous interface and surface anatomy for procedural education.

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 analysıs 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.

We managed to establish three-dimensional digitized visible model of human thoracic structures and to provide morphological data for imaging diagnosis and thoracic and cardiovascular surgery. With Photoshop software, the contour line of lungs and mediastinal structures including heart, aorta and its ramus, azygos vein, superior vena cava, inferior vena cava, thymus, esophagus, diaphragm, phrenic nerve, vagus nerve, sympathetic trunk, thoracic vertebrae, sternum, thoracic duct, and so forth were segmented from the Chinese Visible Human (CVH)-1 data set. The contour data set of segmented thoracic structures was imported to Amira software and 3D thorax models were reconstructed via surface rendering and volume rendering. With Amira software, surface rendering reconstructed model of thoracic organs and its volume rendering reconstructed model were 3D reconstructed and can be displayed together clearly and accurately. It provides a learning tool of interpreting human thoracic anatomy and virtual thoracic and cardiovascular surgery for medical students and junior surgeons.

Quantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions.

Modern breeding schemes for livestock species accumulate a large amount of genotype and phenotype data which can be used for genome-wide association studies (GWAS). Many chromosomal regions harboring effects on quantitative traits have been reported from these studies, but the underlying causative mutations remain mostly undetected. In this study, we combine large genotype and phenotype data available from a commercial pig breeding scheme for three different breeds (Duroc, Landrace, and Large White) to pinpoint functional variation for a region on porcine chromosome 7 affecting number of teats (NTE). Our results show that refining trait definition by counting number of vertebrae (NVE) and ribs (RIB) helps to reduce noise from other genetic variation and increases heritability from 0.28 up to 0.62 NVE and 0.78 RIB in Duroc. However, in Landrace, the effect of the same QTL on NTE mainly affects NVE and not RIB, which is reflected in reduced heritability for RIB (0.24) compared to NVE (0.59). Further, differences in allele frequencies and accuracy of rib counting influence genetic parameters. Correction for the top SNP does not detect any other QTL effect on NTE, NVE, or RIB in Landrace or Duroc. At the molecular level, haplotypes derived from 660K SNP data detects a core haplotype of seven SNPs in Duroc. Sequence analysis of 16 Duroc animals shows that two functional mutations of the Vertnin (VRTN) gene known to increase number of thoracic vertebrae (ribs) reside on this haplotype. In Landrace, the linkage disequilibrium (LD) extends over a region of more than 3 Mb also containing both VRTN mutations. Here, other modifying loci are expected to cause the breed-specific effect. Additional variants found on the wildtype haplotype surrounding the VRTN region in all sequenced Landrace animals point toward breed specific differences which are expected to be present also across the whole genome. This Landrace specific haplotype contains two missense mutations in the ABCD4 gene, one of which is expected to have a negative effect on the protein function. Together, the integration of largescale genotype, phenotype and sequence data shows exemplarily how population parameters are influenced by underlying variation at the molecular level.

Thoracic ossification of the ligamentum flavum (TOLF) causes serious spinal canal stenosis. The underlying aetiology may relate to genetic and inflammatory factors. DNA methylation plays a critical role in osteogenesis and inflammation, whereas there is no genome-wide DNA methylation analysis about TOLF. The two subtypes of TOLF (single-level and multiple-level) have distinct clinical features. Using micro-computed tomography (micro-CT), we showed the ossification arose from the joint between two vertebrae at one/both sides of ligament flavum. With Illumina Infinium Human Methylation 850 BeadChip arrays, genome-wide DNA methylation profile was measured in ligament flavum of eight healthy and eight TOLF samples. Only 65 of the differentially methylated cytosine-phosphate-guanine dinucleotides were found in both subtype groups. Principal component analysis and heat map analysis showed a different methylation pattern in TOLF samples, and methylation patterns of two subtypes are also distinct. The Gene Ontology enrichment analysis was significantly enriched in differentiation and inflammation. Pyrosequencing analysis and quantitative real-time polymerase chain reaction were performed to validate the arrays results and expression levels, to test six differentially methylated genes (SLC7A11, HOXA10, HOXA11AS, TNIK, homeobox transcript antisense RNA, IFITM1), using another independent samples (P < 0.05). Our findings first demonstrated an altered Genome-wide DNA methylation profile in TOLF, and implied distinct methylated features in two subtypes.

Vertebral compression fractures (VCFs) occur in 1 to 1.5 million patients in the US each year and are associated with pain, disability, altered pulmonary function, secondary vertebral fracture, and increased mortality risk. A better understanding of VCFs and their management requires preclinical models that are both biomechanically analogous and accessible. We conducted a study using twelve spinal vertebrae (T12-T14) from porcine specimens. We created mathematical simulations of vertebral compression fractures (VCFs) using CT scans for reconstructing native anatomy and validated the results by conducting physical axial compression experiments. The simulations accurately predicted the behavior of the physical compressions. The coefficient of determination for stiffness was 0.71, the strength correlation was 0.88, and the failure of the vertebral bodies included vertical splitting on the lateral sides or horizontal separation in the anterior wall. This finite element method has important implications for the preventative, prognostic, and therapeutic management of VCFs. This study also supports the use of porcine specimens in orthopedic biomechanical research.

To investigate the association between radiotherapy (RT) and thoracic vertebral fractures in esophageal squamous cell carcinoma (ESCC) and explore the risk factors of thoracic vertebral fracture in ESCC who underwent RT. This retrospective cohort study including 602 consecutive ESCC patients examined the association between RT and thoracic vertebral fractures using multivariable Cox proportional hazard models and relevant risk factors of thoracic vertebral fractures based on clinical and RT parameters in patients with ESCC. Followed for a median follow-up of 24 months, 54 patients had thoracic vertebral fractures. The multivariable analysis revealed RT as an independent risk factor after adjusting for clinical risk factors. Univariable analyses associated a 5-Gy increase in vertebral dose to single vertebrae and a 1-time increase in RT fraction with higher risk of vertebral fracture. Adding RT factors (vertebral dose and fraction) and mean vertebral hounsfield unit to the Cox models containing conventional clinical risk factors significantly improved the χ2 value for predicting vertebral fractures (all P < .001). This study revealed RT, as well as increased vertebral dose and RT fractions, as a significant, consistent, and strong vertebral fracture predictor in ESCC. Combined vertebral dose, RT fractions, and vertebral hounsfield unit provided optimal risk stratification for ESCC patients.