Spinal Growth Research Articles

Bilateral rib-to-pelvis growth-friendly spinal surgery for congenital kyphosis in the child with myelomeningocele delays but does not prevent a definitive procedure.

To determine the efficacy of bilateral rib-to-pelvis distraction instrumentation for the growth-friendly surgical treatment of congenital kyphosis in children with myelomeningocele. The clinical courses of nine children (five males, four females), mean age 4.3 years (range 1.4 years-10.0 years), with myelomeningocele and congenital kyphosis treated by the rib-to-pelvis surgical method were studied. Radiographic measurements established the extent of deformity corrections, spinal elongation and growth, and rib levels. Surgical complications were categorized as wound or instrumentation related. The mean follow-up was 5.2years (range, 2.4years-10.4years). Following the index procedure, a mean of seven procedures (range, 4-20), or 1.2 procedures per year, were performed on each child. The mean preoperative, postoperative, and final follow-up kyphotic deformity was 139° (range, 93°-180°), 86°(range, 45°-150°) and 98° (range, 50°-176°) respectively. Eight children lost some of the initial correction and the two youngest lost all correction. Six children were converted to spine-based procedures. The mean growth for the cohort was 0.6cm/year (range, -1.2cm-1.9cm). Twenty-two complications occurred in eight children-14 in the three youngest children. In two children the procedure was abandoned due to ulceration over the gibbus after 2.8 years and 5.6 years of treatment. The bilateral rib-to-pelvis surgical procedure produced modest deformity correction and spinal growth, and prevented deformity progression. It delayed but did not eliminate the need for spine-based deformity correction, and was associated with the significant morbidity of distraction-based growth-friendly spinal surgery. The rib-based technique may have a role in a child with myelomeningocele kyphosis when surgical intervention is required in the very young.

Magnetically controlled growing rods increase 3D true spine length in idiopathic early onset scoliosis patients: results from a multicenter study.

To determine, at 2year follow-up, 3D spine growth for idiopathic early onset scoliosis (iEOS) patients treated with magnetically controlled growing rods (MCGR). From an international EOS registry, patients with iEOS treated with MCGR were identified. Scoliosis, kyphosis, traditional coronal height, and 3D true spine length (3D-TSL) were measured pre-index surgery, post-index, and at 2year follow-up. 135 participants, mean age 8.1years (2.7-15.6) were included. Scoliosis improved from 71° pre-index to 41° post-index (p < 0.001) and remained constant at 2years (43°, p = 0.58). Kyphosis improved from 49° to 36° (p < 0.001); then increased by 2years to 42° (p = 0.002). Traditional T1-S1 height, which reflects both spine growth and changes in deformity, increased from pre-index to post-index (274mm vs. 310mm; p < 0.001), and again at 2years (332mm, p < 0.001). As 3D-TSL reflects growth of the spine, independent of changes in deformity, as expected it did not change perioperatively (335mm vs. 339mm, p = 0.83), but significantly changed by 2years (367mm; p < 0.001). Participants < 5years at surgery increased 22mm (8.2%), 5-10years increased 26mm (7.8%), and > 10 increased 41mm (11.0%). For instrumented levels, mean vertebral growth was 1.3mm/level for < 5years, 1.4mm/level for 5-10years, and 2.2mm/level for > 10years. As kyphosis increased over time, these out of the coronal plane changes justify the use of 3D-TSL for this cohort of patients. For idiopathic EOS patients treated with MCGR, 3D spine length increased by 28mm during the 2year post-operative period.

A comparative analysis of axial and appendicular skeletal maturity staging systems through assessment of longitudinal growth and curve modulation after VBT surgery.

Appendicular skeleton markers are commonly used for maturity assessment for Adolescent Idiopathic Scoliosis (AIS) patients. Traditionally, Risser has been a standard skeletal maturity assessment method. More recently, Sanders classification (SSMS), as a more comprehensive system, became popular, especially in decision-making for Vertebral Body Tethering (VBT). Thumb-Ossification Composite Index (TOCI), using ossification of thumb epiphyses, has been claimed to more accurately stage patients around their peak height velocity. However, growth peaks may occur separately at lower limbs and trunk. Hence, Cervical Vertebral Maturity (CVM), using cervical spine morphology, possesses a potential to better estimate spinal growth as it uses axial skeleton markers instead of appendicular skeleton markers. The aim of the study was to compare various axial and appendicular skeletal maturity assessment methods for longitudinal growth and curve modulation after VBT. A retrospective analysis of prospectively collected data was conducted. Skeletal maturity was determined using Risser, SSMS, TOCI and CVM for each patient. Crosstabulations of axial vs. appendicular markers were formed to analyze their concordance and discordance. Logistic and logarithmic regression models were run to assess longitudinal growth (postoperative height gain and leg-length growth) and curve modulation (follow-up instrumented Cobb correction after index operation), respectively. Models were compared using Akaike information criterion (AIC). 34 patients (32F/2M, mean age: 12.8 ± 1.5 years, mean follow-up: 47.7 (24-80) months) were included. The median preoperative maturity stages were: Risser: 1 (-1-4), SSMS: 4 (1-7), TOCI: 6 (1-8) and CVM: 4 (1-6). At latest follow-up, all patients reached skeletal maturity. Concordance and discordance were observed between axial vs. appendicular systems that demonstrated a range of possible distributions of CVM, where trunk peak height velocity occurred before, simultaneously with or after the standing height peak height velocity. R-squared values for Risser, SSMS, TOCI and CVM were 0.701, 0.783, 0.810 and 0.811, respectively, for prediction of final height; 0.759, 0.821, 0.831 and 0.775 for final leg-length, and 0.507, 0.588, 0.668 and 0.673 for curve modulation. Delta AIC values demonstrated that different skeletal maturity assessment methods provided distinctive information regarding follow-up height gain, leg-length growth and curve behavior. Risser score provided considerably less information for all three outcome variables. TOCI and SSMS provided substantial information regarding remaining leg-length assessments, while in terms of assessment of total height gain and curve modulation after surgery, CVM and TOCI offered substantial information and SSMS offered strong information. Mutual use of axial and appendicular markers may provide valuable insight concerning timing of surgery and magnitude of surgical correction.

Structural neural plasticity evoked by rapid-acting antidepressant interventions.

A feature in the pathophysiology of major depressive disorder(MDD), a mood disorder, is the impairment of excitatory synapses in the prefrontal cortex. Intriguingly, different types of treatment with fairly rapid antidepressant effects (within days or a few weeks), such as ketamine, electroconvulsive therapy and non-invasive neurostimulation, seem to converge on enhancement of neural plasticity. However, the forms and mechanisms of plasticity that link antidepressant interventions to the restoration of excitatory synaptic function are still unknown. In this Review, we highlight preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons. We compare the longitudinal effects of various psychoactive drugs on neuronal rewiring, and we highlight rapid onset and sustained time course as notable characteristics for putative rapid-acting antidepressant drugs. Furthermore, we consider gaps in the current understanding of drug-evoked in vivo structural plasticity. We also discuss the prospects of using synaptic remodelling to understand other antidepressant interventions, such as repetitive transcranial magnetic stimulation. Finally, we conclude that structural neural plasticity can provide unique insights into the neurobiological actions of psychoactive drugs and antidepressant interventions.

Reducing the Brace Correction Stress on the Secondary Lumbar Curve Results in Excellent Muscle, Bone, and Disc Mechanical Performance: A Musculoskeletal Finite Element Simulation of AIS Patient With Rigo A3.

The biomechanical mechanism of brace intervention on bone, muscle, and disc should be comprehensively considered for AIS patients. We aimed to developmentally construct a musculoskeletal finite element model of adolescent idiopathic scoliosis to simulate the coupling of corrective forces and analyze the mechanical properties of bone, muscle, and disc. Investigateing, more effective clinical interventions to break the vicious cycle of patients during growth. A finite element model, including muscle, bone, and disc, was established using computed tomography data of a patient with RigoA3 adolescent idiopathic scoliosis. The three-point force coupling, antigravity, and bending effects of the Chêneau brace were simulated, and the correction force of the secondary lumbar bend was gradually reduced while observing the mechanical characteristics of bone, muscle, and disc. The correction force in line with symmetrical spine growth was comprehensively evaluated. The correction rate of the main thoracic (MT) curve, the intervertebral space height on the concave side of the vertebrae at the apex, and the stress ratio of the intervertebral discs were optimal when the maximum corrective pressure threshold was reached. However, the proximal thoracic (PT) curve was aggravated and the axial forces on the concave side were unbalanced. At this time, the biomechanical performance of the model is also not optimal. The correction rate of the Cobb Angle of the MT curve decreased with the decrease of the correction pressure in the lumbar region. When reduced to 25% of the maximum threshold, the convex side of disc stress, intervertebral space, and muscle axial force is more in line with the biomechanical mechanism of correction and can avoid sacrificing the PT curve. Downward adjustment of the corrective force to the secondary lumbar curve, using the Chêneau brace, results in better primary thoracic curvature mechanics in the musculoskeletal finite element model, suggesting that breaking the vicious cycle of scoliosis progression to guide benign spinal growth is beneficial.

Pyramidal cell types and 5-HT2A receptors are essential for psilocybin's lasting drug action.

Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses1-4. At the cellular level, psychedelics induce structural neural plasticity5,6, exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells7-9. A key question is how these cellular modifications map onto cell type-specific circuits to produce psychedelics' behavioral actions10. Here, we use in vivo optical imaging, chemogenetic perturbation, and cell type-specific electrophysiology to investigate the impact of psilocybin on the two main types of pyramidal cells in the mouse medial frontal cortex. We find that a single dose of psilocybin increased the density of dendritic spines in both the subcortical-projecting, pyramidal tract (PT) and intratelencephalic (IT) cell types. Behaviorally, silencing the PT neurons eliminates psilocybin's ability to ameliorate stress-related phenotypes, whereas silencing IT neurons has no detectable effect. In PT neurons only, psilocybin boosts synaptic calcium transients and elevates firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolishes psilocybin's effects on stress-related behavior and structural plasticity. Collectively these results identify a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex as playing essential roles for psilocybin's long-term drug action.

Evaluating the Feasibility of Cervical Vertebral Maturation Stages as an Alternative to Risser Sign in Assessing Skeletal Maturity in Adolescent Idiopathic Scoliosis Patients

Radiographic methods for evaluating skeletal maturity traditionally include the Risser sign and the hand-wrist maturation method. While the cervical vertebral maturation (CVM) stage is widely recognized in orthodontics, its application in assessing spinal growth, particularly in adolescent idiopathic scoliosis (AIS), has been less explored. This study explores the correlation between CVM, chronological age, and the Risser sign to evaluate the feasibility of CVM in assessing skeletal development in adolescents. This prospective study included AIS patients and asymptomatic adolescents, aged 7-15years, who underwent full-spine imaging with clear visibility of the cervical and pelvic regions. The correlation between CVM and the Risser sign was analyzed. The height of the cervical C3-7 vertebral body was measured, and its growth trend with age was examined. Differences between AIS patients and asymptomatic adolescents were compared. A total of 85 AIS patients (mean age 11.44 ± 2.36years) and 47 asymptomatic adolescents (mean age 11.48 ± 3.14years) were included. No statistically significant differences were observed in age, Risser sign grading, CVM staging, or C3-7 vertebral body height between the 2 groups. Chronological age showed a stronger correlation with CVM stages than with the Risser sign in both the AIS group (r= 0.93 vs. r= 0.82, P < 0.01) and the asymptomatic group (r= 0.81 vs. r= 0.72, P < 0.01). The CVM stage, which shows a strong correlation with Risser sign grading, could serve as a reliable alternative for assessing skeletal maturity in adolescent subjects, particularly in clinical scenarios where minimizing radiation exposure is a priority.

Growth-friendly spinal surgery: Review of the effect on truncal growth

BackgroundPediatric spinal deformity surgery affects ultimate spinal height in the growing child. This effect on ultimate spinal height has also been shown to affect pulmonary development and ultimately pulmonary function. There has been an increasing trend toward growth-friendly spinal surgery in early onset scoliosis to minimize the negative consequences of early spinal fusion surgery. Such growth-friendly techniques include VEPTR, MCGR, and Shilla. Which technique allows for the most growth after initial implantation is still not clear. MethodsAn extensive literature review on the topic of pediatric spinal growth was undertaken. Topics reviewed include: normal growth, growth after intervention by various methods, and the effect on pulmonary function. We have summarized the literature for the techniques identified and compared these with normal population data.. ResultsThe data for various surgical techniques were reviewed. These included VEPTR, standard growing rods, and MCGR. The measurement techniques for determining ultimate spinal growth varied based upon the technique for measurement and the timing of initial and final measurements. The results of attained spinal growth were not directly correlated to pulmonary function values. ConclusionsThere is still no standardized ideal time or technique for assessing the best results in this area. We suggest that some of what is called growth from growth-friendly techniques is lengthening from the initial deformity correction. This nomenclature needs to be clarified. In addition, how and when to determine ultimate spinal growth from each surgical technique and by which radiographic technique needs to be standardized.

The Alzheimer's Disease Risk Gene CD2AP Functions in Dendritic Spines by Remodeling F-Actin.

CD2-associated protein (CD2AP) was identified as a genetic risk factor for late-onset Alzheimer's disease (LOAD). However, it is unclear how CD2AP contributes to LOAD synaptic dysfunction underlying AD memory deficits. We have shown that loss of CD2AP function increases β-amyloid (Aβ) endocytic production, but it is unknown whether it contributes to synapse dysfunction. As CD2AP is an actin-binding protein, it may also function in F-actin-rich dendritic spines, which are the excitatory postsynaptic compartments. Here, we demonstrate that CD2AP colocalizes with F-actin in dendritic spines of primary mouse cortical neurons of both sexes. Cell-autonomous depletion of CD2AP specifically reduces spine density and volume, resulting in a functional decrease in synapse formation and neuronal network activity. Postsynaptic reexpression of CD2AP, but not blocking Aβ production, is sufficient to rescue spine density. CD2AP overexpression increases spine density, volume, and synapse formation, while a rare LOAD CD2AP mutation induces aberrant F-actin spine-like protrusions without functional synapses. CD2AP controls postsynaptic actin turnover, with the LOAD mutation in CD2AP decreasing F-actin dynamicity. Our data support that CD2AP risk variants could contribute to LOAD synapse dysfunction by disrupting spine formation and growth by deregulating actin dynamics.

Effect of growth hormone to spinal growth and recombinant human growth hormone to scoliosis.

Growth hormone (GH) plays a key role in human growth and development. In addition to promoting height growth, GH affects bone metabolism, bone size, and bone mineral density (BMD) in children and adolescents by affecting bone formation and resorption. Among them, the effect of GH on spinal growth has been widely concerned. Scoliosis is a three-dimensional structural spinal deformity characterized by lateral curvature of one or more segments of the spine accompanied by vertebral rotation and sagittal imbalance. For children with growth hormone deficiency (GHD), whether GH supplementation leads to scoliosis is still controversial. In recent years, numerous scholars have conducted extensive research to investigate the correlation between recombinant human GH replacement therapy and scoliosis, yielding divergent findings with some even presenting contradictory results. This study aims to investigate the impact of GH on spinal growth and explore the association between recombinant human GH replacement therapy and scoliosis by comprehensively reviewing the effects of GH and insulin-like growth factors 1 (IGF-1) on bone metabolism, bone mass, as well as examining the consequences of GHD on bone health. Additionally, we aim to access the influence of recombinant human GH replacement therapy on adolescent idiopathic scoliosis (AIS).

MiR-351-5p regulation of CPEB3 affecting aluminium-induced learning and memory impairment in SD rats

Aluminium exposure has been found to impair learning and memory abilities; however, the underlying molecular mechanisms remain unclear. In this study we conducted a double luciferase reporter assay to determine whether miR-351-5p regulates cytoplasmic polyadenylation element binding protein (CPEB) 3 mRNA. To this end, we overexpressed and inhibited miR-351-5p via stereotaxic microinjections of adeno-associated virus (AAV) into the hippocampus of Sprague Dawley rats in a sub-chronic aluminium exposure model to examine learning and memory ability using Morris water maze. Ultrastructural electron microscopy and Golgi staining were used to examine morphological changes in hippocampal neurons. In addition, we examined the levels of synaptic plasticity-related proteins (PRPs) and CPEB3 to determine the involvement of the miR-351-5P/CPEB3/PRPs pathway in aluminium neurotoxicity. Sub-chronic aluminium exposure reduced the spatial learning and memory ability of rats. Overexpression of AAV-miR-351-5P in the hippocampus aggravated the impairment of spatial learning and memory abilities of aluminium-treated rats, whereas inhibition of AAV-miR-351-5p expression alleviated it. Western blotting suggested that sub-chronic aluminium exposure increased miR-351-5p levels and reduced the expression of CPEB3 and PRPs in the hippocampus. Treatment with an AAV-miR-351-5p inhibitor partially recovered CPEB3 and PRPs. Double luciferase reporter assay results showed that CPEB3 was a direct target of miR-351-5p, while electron microscopy suggested that aluminium could damage mitochondria and synapses in the CA1 of the hippocampus. Golgi staining results indicated that aluminium could reduce the number of dendritic spines in hippocampal neurons. Inhibition of miR-351-5p restored the synaptic structure and growth of dendritic spines in the hippocampus. The involvement of the miR-351-5P/CPEB3/RPPs pathway in aluminium neurotoxicity was confirmed. Our findings suggest that inhibition of miR-351-5p can alleviate learning and memory impairments by increasing CPEB3 and PRPs.

Development of a chronic compression spinal cord injury model in neonatal and adult rats.

Spinal cord injury presents a significant burden globally, with traumatic spinal cord injury being the predominant cause historically. However, nontraumatic spinal cord injury (NTSCI) is emerging as a significant contributor, particularly in developed nations, yet it remains poorly understood due to underreporting and misclassification. NTSCI, spanning various etiologies such as bony growths, vascular conditions, infections, neoplastic conditions, and immune disorders, poses unique challenges in diagnosis and treatment, often resulting in lifelong morbidity. This study addresses the lack of suitable animal models for NTSCI research, especially in neonatal animals. Utilizing a solid spacer approach, we developed a compression NTSCI model applicable to both neonatal and adult Sprague-Dawley rats. Through anatomical measurements and invivo experiments, we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects. The versatility of this model lies in its adaptability to different ages of rats, offering a cost-effective and reproducible means to induce graded injuries. Moreover, behavioral assessments demonstrated observable hindlimb function, validating the model's utility for studying functional outcomes. Although challenges persist, particularly in accounting for spinal column growth in neonatal animals, this model fills a crucial gap in pediatric NTSCI research. By providing a platform to investigate pathophysiological mechanisms and test potential treatments, it offers promising avenues for advancing our understanding and management of pediatric NTSCI.

Decreased functional connectivity is associated with increased levels of Cerebral Spinal Fluid soluble-PDGFRβ, a marker of blood brain barrier breakdown, in older adults.

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-β (CSF sPDGFRβ, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRβ in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.e. Default Mode Network, DMN). Our study aimed to investigate the relationship between these two markers in older individuals that were cognitively normal and had cognitive impairment. Eighty-nine older adults without dementia from the University of Southern California were selected from a larger cohort. Region of interest (ROI) to ROI analyses were conducted using DMN seed regions. Linear regression models measured significant associations between BOLD FC strength among seed-target regions and sPDGFRβ values, while covarying for age and sex. Comparison of a composite ROI created by averaging FC values between seed and all target regions among cognitively normal and impaired individuals was also examined. Using CSF sPDGFRβ as a biomarker of BBB breakdown, we report that increased breakdown correlated with decreased functional connectivity in DMN areas, specifically the PCC, and while the hippocampus exhibited an interaction effect using CDR score, this was an exploratory analysis that we feel can lead to further research. Ultimately, we found that BBB breakdown, as measured by CSF sPDGFRβ, is associated with neural networks, and decreased functional connections.

Signal flow in the NMDA receptor-dependent phosphoproteome regulates postsynaptic plasticity for aversive learning.

Structural plasticity of dendritic spines in the nucleus accumbens (NAc) is crucial for learning from aversive experiences. Activation of NMDA receptors (NMDARs) stimulates Ca2+-dependent signaling that leads to changes in the actin cytoskeleton, mediated by the Rho family of GTPases, resulting in postsynaptic remodeling essential for learning. We investigated how phosphorylation events downstream of NMDAR activation drive the changes in synaptic morphology that underlie aversive learning. Large-scale phosphoproteomic analyses of protein kinase targets in mouse striatal/accumbal slices revealed that NMDAR activation resulted in the phosphorylation of 194 proteins, including RhoA regulators such as ARHGEF2 and ARHGAP21. Phosphorylation of ARHGEF2 by the Ca2+-dependent protein kinase CaMKII enhanced its RhoGEF activity, thereby activating RhoA and its downstream effector Rho-associated kinase (ROCK/Rho-kinase). Further phosphoproteomic analysis identified 221 ROCK targets, including the postsynaptic scaffolding protein SHANK3, which is crucial for its interaction with NMDARs and other postsynaptic scaffolding proteins. ROCK-mediated phosphorylation of SHANK3 in the NAc was essential for spine growth and aversive learning. These findings demonstrate that NMDAR activation initiates a phosphorylation cascade crucial for learning and memory.

Achievements and complications related to final fusion surgery in early onset scoliosis at the end of "traditional dual growing rod mission".

Retrospective cohort study. Assess the outcomes of final fusion in early onset scoliosis patients treated with TDGR, particularly with acceptable coronal and sagittal alignment at the end of their growing age. Early onset scoliosis (EOS) poses challenges due to the need for managing spinal deformities while accommodating trunk growth. The dual growing rod (TDGR) technique, a traditional approach, aims to address these concerns by periodic lengthening until spinal growth ceases. Recent shifts propose observation without immediate implant removal after achieving spinal alignment, raising questions about the necessity of final fusion surgery. This retrospective study included 22 EOS patients treated with TDGR who underwent final fusion surgery. Clinical and radiological data were analyzed, including pre- and post-surgery measurements, complications, surgical approaches, and screw density. Patients (average initial surgery age: 6.9years) exhibited significant reductions in main curve angle (preoperative: 65.8°, pre-fusion: 49.1°, post-fusion: 36.3°) and thoracic kyphosis (preoperative: 47°, pre-fusion: 46.6°, post-fusion: 38.7°). Complications included one surgical site infection and four transient intraoperative neuro-monitoring Impairment. High screw density correlated with lower total correction. Final fusion surgery post-TDGR treatment shows promise in correcting EOS-associated deformities. Surgeons and parents should be aware of the procedure's complexity and potential complications.

Competitive processes shape multi-synapse plasticity along dendritic segments

Neurons receive thousands of inputs onto their dendritic arbour, where individual synapses undergo activity-dependent plasticity. Long-lasting changes in postsynaptic strengths correlate with changes in spine head volume. The magnitude and direction of such structural plasticity - potentiation (sLTP) and depression (sLTD) - depend upon the number and spatial distribution of stimulated synapses. However, how neurons allocate resources to implement synaptic strength changes across space and time amongst neighbouring synapses remains unclear. Here we combined experimental and modelling approaches to explore the elementary processes underlying multi-spine plasticity. We used glutamate uncaging to induce sLTP at varying number of synapses sharing the same dendritic branch, and we built a model incorporating a dual role Ca2+-dependent component that induces spine growth or shrinkage. Our results suggest that competition among spines for molecular resources is a key driver of multi-spine plasticity and that spatial distance between simultaneously stimulated spines impacts the resulting spine dynamics.

Effects of T-2 and deoxynivalenol mycotoxins on mouse spinal bone growth and integrity

Kashin-Beck Disease (KBD), an osteoarticular disorder, is influenced by various factors, including exposure to Deoxynivalenol (DON) and T-2 mycotoxins. This study systematically explored the impact of these mycotoxins on the development and structural resilience of spinal structures in mice, examining both isolated and combined effects. The experiment involved 72 male mice divided into nine groups, each subjected to varying concentrations of T-2, DON, or their combinations over four weeks. Rigorous monitoring included body weight, key indicators of bone metabolism, and cellular activities essential to bone health. Comprehensive evaluations using biomechanical analysis, x-ray, and micro-computed tomography (micro-CT) were conducted to assess alterations in spinal structure.The findings revealed a pivotal aspect: mice exhibited a dose-dependent decline in body weight when exposed to individual mycotoxins, while simultaneous exposure produced an unanticipated antagonistic effect. Moreover, decreases were noted in levels of calcium, phosphorus, and vitamin D, coupled with changes in the activities of osteoblasts (increased) and osteoclasts (decreased), all intricately tied to the toxins' dosages and combinations. Notably, variations in the biomechanical properties corresponded with the mycotoxin dosage and blend, showing a decline in biomechanical strength. Micro-CT analyses further substantiated the profound toxic impact of the toxin dosage and mixtures on both the cortical and trabecular components of the spinal structures.In summary, this investigation unequivocally illuminates the dose- and ratio-dependent deleterious impacts of DON and T-2 mycotoxins on the growth and structural soundness of spinal structures in mice. These findings highlight the urgent need for a comprehensive understanding of the potential hazards these toxins pose to bone health, providing invaluable guidance for future toxicological research and public health strategies.

Neural Development and Repair Induced by Femtosecond Laser Stimulation.

Dendritic spines function as postsynaptic sites, receiving excitatory signals from presynaptic axons. The synaptic plasticity of spines underlies the refinement of neuronal circuits. Neural cognitive disorders are commonly associated with the impairment and elimination of dendritic spines. In this study, we report an all-optical method to activate dendritic spine growth and regeneration by a single short flash of femtosecond laser stimulation. The inhibited development and loss of spines can be rescued by a transient illumination of the laser inside a micrometer region of the soma by activating the extracellular signal-regulated kinase (ERK) signaling pathway. The rescued neurons exhibit function. Hence we provide a potential noninvasive method for the regeneration of dendritic spines.

Pediatric spinal alignment and spinal development

BackgroundKnowledge of the growth spurt and remaining growth is essential for managing musculoskeletal diseases in children. Accurate prediction of curve progression and timely interventions are crucial, particularly for conditions like adolescent idiopathic scoliosis (AIS). MethodsThis study conducted a comprehensive review and synthesis of existing literature on spinal growth, skeletal maturity classifications, and the evolution of sagittal alignment parameters during childhood and adolescence. Key anatomical elements involved in spinal development, natural history of spinal growth, and skeletal maturity assessment systems were analyzed. ResultsThe analysis highlighted that key parameters such as Pelvic incidence (PI), Pelvic tilt (PT), and Lumbar lordosis (LL) increase significantly with growth, especially during the pubertal growth spurt. In contrast, Sacral slope (SS) remains relatively constant, and Thoracic kyphosis (TK) shows a slight increase. Additionally, there is a posterior shift in the center of gravity as children grow, reflecting progressive postural maturation. The study also reviewed and compared various maturity classification systems, noting the reliability and clinical implications of systems like the Sanders Maturity Stage (SMS) and Tanner-Whitehouse III. ConclusionsReliable maturity classification systems, such as the Sanders Maturity Stage (SMS) and Tanner-Whitehouse III, allow for tailored treatments to individual growth patterns. Integrating these classification systems into clinical practice enables precise prediction of curve progression and timely therapeutic interventions. This includes options from bracing to surgical techniques like growing rods or vertebral body tethering (VBT), with growth modulation being a key factor in achieving successful outcomes.

Homeostatic Shrinkage of Dendritic Spines Requires Melatonin Type 3 Receptor Activation During Sleep.

High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.