Dopamine and glutamate regulate striatal acetylcholine in decision-making.

Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making1. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour.

Predicting miRNA-disease associations based on lncRNA-miRNA interactions and graph convolution networks.

Increasing studies have proved that microRNAs (miRNAs) are critical biomarkers in the development of human complex diseases. Identifying disease-related miRNAs is beneficial to disease prevention, diagnosis and remedy. Based on the assumption that similar miRNAs tend to associate with similar diseases, various computational methods have been developed to predict novel miRNA-disease associations (MDAs). However, selecting proper features for similarity calculation is a challenging task because of data deficiencies in biomedical science. In this study, we propose a deep learning-based computational method named MAGCN to predict potential MDAs without using any similarity measurements. Our method predicts novel MDAs based on known lncRNA-miRNA interactions via graph convolution networks with multichannel attention mechanism and convolutional neural network combiner. Extensive experiments show that the average area under the receiver operating characteristic values obtained by our method under 2-fold, 5-fold and 10-fold cross-validations are 0.8994, 0.9032 and 0.9044, respectively. When compared with five state-of-the-art methods, MAGCN shows improvement in terms of prediction accuracy. In addition, we conduct case studies on three diseases to discover their related miRNAs, and find that all the top 50 predictions for all the three diseases have been supported by established databases. The comprehensive results demonstrate that our method is a reliable tool in detecting new disease-related miRNAs.

Predicting miRNA-disease associations based on graph attention networks and dual Laplacian regularized least squares.

Increasing biomedical evidence has proved that the dysregulation of miRNAs is associated with human complex diseases. Identification of disease-related miRNAs is of great importance for disease prevention, diagnosis and remedy. To reduce the time and cost of biomedical experiments, there is a strong incentive to develop efficient computational methods to infer potential miRNA-disease associations. Although many computational approaches have been proposed to address this issue, the prediction accuracy needs to be further improved. In this study, we present a computational framework MKGAT to predict possible associations between miRNAs and diseases through graph attention networks (GATs) using dual Laplacian regularized least squares. We use GATs to learn embeddings of miRNAs and diseases on each layer from initial input features of known miRNA-disease associations, intra-miRNA similarities and intra-disease similarities. We then calculate kernel matrices of miRNAs and diseases based on Gaussian interaction profile (GIP) with the learned embeddings. We further fuse the kernel matrices of each layer and initial similarities with attention mechanism. Dual Laplacian regularized least squares are finally applied for new miRNA-disease association predictions with the fused miRNA and disease kernels. Compared with six state-of-the-art methods by 5-fold cross-validations, our method MKGAT receives the highest AUROC value of 0.9627 and AUPR value of 0.7372. We use MKGAT to predict related miRNAs for three cancers and discover that all the top 50 predicted results in the three diseases are confirmed by existing databases. The excellent performance indicates that MKGAT would be a useful computational tool for revealing disease-related miRNAs.

Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploited a behavioral paradigm in which mice, depending on strain, social experience, and sensory context, either vigorously cover an arena with small urine spots or deposit urine in a few isolated large spots. We refer to these micturition modes as, respectively, high and low territory-covering micturition (TCM) and find that the presence of a urine stimulus robustly induces high TCM in socially isolated mice. Comparison of the brain networks activated by social isolation and by urine stimuli to those upstream of the PMC identified the lateral hypothalamic area as a potential modulator of micturition modes. Indeed, chemogenetic manipulations of the lateral hypothalamus can switch micturition behavior between high and low TCM, overriding the influence of social experience and sensory context. Our results suggest that both inhibitory and excitatory signals arising from a network upstream of the PMC are integrated to determine context- and social-experience-dependent micturition patterns.

Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production.

The mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from the dorsal telencephalon, whereas inhibitory interneurons are generated in its ventral portion. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear whether PRDM16 plays a similar role in neurogenesis in both dorsal and ventral progenitor lineages and, if so, whether it regulates common or unique networks of genes. Here, we show that Prdm16 expression in mouse medial ganglionic eminence (MGE) progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of forebrain GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. PRDM16 regulates convergent developmental gene expression programs in the cortex and MGE, which utilize both common and region-specific sets of genes to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.

Endothelial cell-derived exosomes boost and maintain repair-related phenotypes of Schwann cells via miR199-5p to promote nerve regeneration.

BACKGROUND: Schwann cells (SCs) respond to nerve injury by transforming into the repair-related cell phenotype, which can provide the essential signals and spatial cues to promote axonal regeneration and induce target reinnervation. Endothelial cells (ECs) contribute to intraneural angiogenesis contributing to creating a permissive microenvironment. The coordination between ECs and SCs within injury sites is crucial in the regeneration process, however, it still unclear. As the intercellular vital information mediators in the nervous system, exosomes have been proposed to take a significant role in regulating regeneration. Thus, the main purpose of this study is to determine the facilitative effect of ECs-derived exosomes on SCs and to seek the underlying mechanism. RESULTS: In the present study, we collected exosomes from media of ECs. We demonstrated that exosomes derived from ECs possessed the favorable neuronal affinity both in vitro and in vivo. Further research indicated that EC-exosomes (EC-EXO) could boost and maintain repair-related phenotypes of SCs, thereby enhancing axonal regeneration, myelination of regenerated axons and neurologically functional recovery of the injured nerve. MiRNA sequencing in EXO-treated SCs and control SCs indicated that EC-EXO significantly up-regulated expression of miR199-5p. Furthermore, this study demonstrated that EC-EXO drove the conversion of SC phenotypes in a PI3K/AKT/PTEN-dependent manner. CONCLUSION: In conclusion, our research indicates that the internalization of EC-EXO in SCs can promote nerve regeneration by boosting and maintaining the repair-related phenotypes of SCs. And the mechanism may be relevant to the up-regulated expression of miR199-5p and activation of PI3K/AKT/PTEN signaling pathway.

Predicting potential miRNA-disease associations based on more reliable negative sample selection.

BACKGROUND: Increasing biomedical studies have shown that the dysfunction of miRNAs is closely related with many human diseases. Identifying disease-associated miRNAs would contribute to the understanding of pathological mechanisms of diseases. Supervised learning-based computational methods have continuously been developed for miRNA-disease association predictions. Negative samples of experimentally-validated uncorrelated miRNA-disease pairs are required for these approaches, while they are not available due to lack of biomedical research interest. Existing methods mainly choose negative samples from the unlabelled ones randomly. Therefore, the selection of more reliable negative samples is of great importance for these methods to achieve satisfactory prediction results. RESULTS: In this study, we propose a computational method termed as KR-NSSM which integrates two semi-supervised algorithms to select more reliable negative samples for miRNA-disease association predictions. Our method uses a refined K-means algorithm for preliminary screening of likely negative and positive miRNA-disease samples. A Rocchio classification-based method is applied for further screening to receive more reliable negative and positive samples. We implement ablation tests in KR-NSSM and find that the combination of the two selection procedures would obtain more reliable negative samples for miRNA-disease association predictions. Comprehensive experiments based on fivefold cross-validations demonstrate improvements in prediction accuracy on six classic classifiers and five known miRNA-disease association prediction models when using negative samples chose by our method than by previous negative sample selection strategies. Moreover, 469 out of 1123 selected positive miRNA-disease associations by our method are confirmed by existing databases. CONCLUSIONS: Our experiments show that KR-NSSM can screen out more reliable negative samples from the unlabelled ones, which greatly improves the performance of supervised machine learning methods in miRNA-disease association predictions. We expect that KR-NSSM would be a useful tool in negative sample selection in biomedical research.

Predictive value of single-nucleotide polymorphisms in curve progression of adolescent idiopathic scoliosis.

PURPOSE: Genetic diagnosis is a promising approach because several single-nucleotide polymorphisms (SNPs) associated with adolescent idiopathic scoliosis (AIS) progression have been reported. We review the predictive value of SNPs in curve progression of adolescent idiopathic scoliosis. METHODS: We reviewed DNA-based prognostic testing to predict curve progression. Then, the multiple polymorphisms in loci related to AIS progression were also reviewed, and we elucidated the predictive value of SNPs from four functional perspectives, including endocrine metabolism, neuromuscular system, cartilage and extracellular matrix, enzymes, and cytokines. RESULTS: The ScoliScores were less successful predictors than expected, and the weak power of predictive SNPs might account for its failure. Susceptibility loci in ESR1, ESR2, GPER, and IGF1, which related to endocrine metabolism, have been reported to predict AIS progression. Neuromuscular imbalance might be a potential mechanism of scoliosis, and SNPs in LBX1, NTF3, and SOCS3 have been reported to predict the curve progression of AIS. Susceptibility loci in SOX9, MATN1, AJAP1, MMP9, and TIMP2, which are related to cartilage and extracellular matrix, are also potentially related to AIS progression. Enzymes and cytokines play essential roles in regulating bone metabolism and embryonic development. SNPs in BNC2, SLC39A8, TGFB1, IL-6, IL-17RC, and CHD7 were suggested as predictive loci for AIS curve progression. CONCLUSIONS: Many promising SNPs have been identified to predict the curve progression of AIS. However, conflicting results from replication studies and different ethnic groups hamper their reliability. Convincing SNPs from multiethnic populations and functional verification are needed.

[Design and Implementation of Medical Equipment Rational Deployment Information System Based on ASP.NET].

Based on ASP.NET framework, The Intelligent Estimated System for Rational Deployment of Medical Equipment (MERDIS) is designed and developed with SQL Server 2012 database and C# language. The system is used to realize the rational deployment suggestions and evaluation of medical equipment in hospitals. The system input the data of hospital medical equipment and clinical pathway into the database, and then feedback the deployment information to users which are calculated by big data information, so as to achieve the purpose of giving rational deployment of hospital medical equipment.

Corticostriatal plasticity in the nucleus accumbens core.

Small fluctuations in striatal glutamate and dopamine are required to establish goal-directed behaviors and motor learning, while large changes appear to underlie many neuropsychological disorders, including drug dependence and Parkinson's disease. A better understanding of how variations in neurotransmitter availability can modify striatal circuitry will lead to new therapeutic targets for these disorders. Here, we examined dopamine-induced plasticity in prefrontal cortical projections to the nucleus accumbens (NAc) core. We combined behavioral measures of male mice, presynaptic optical studies of glutamate release kinetics from prefrontal cortical projections, and postsynaptic electrophysiological recordings of spiny projection neurons within the NAc core. Our data show that repeated amphetamine promotes long-lasting but reversible changes along the corticoaccumbal pathway. In saline-treated mice, coincident cortical stimulation and dopamine release promoted presynaptic filtering by depressing exocytosis from glutamatergic boutons with a low-probability of release. The repeated use of amphetamine caused a frequency-dependent, progressive, and long-lasting depression in corticoaccumbal activity during withdrawal. This chronic presynaptic depression was relieved by a drug challenge which potentiated glutamate release from synapses with a low-probability of release. D1 receptors generated this synaptic potentiation, which corresponded with the degree of locomotor sensitization in individual mice. By reversing the synaptic depression, drug reinstatement may promote allostasis by returning corticoaccumbal activity to a more stable and normalized state. Therefore, dopamine-induced synaptic filtering of excitatory signals entering the NAc core in novice mice and paradoxical excitation of the corticoaccumbal pathway during drug reinstatement may encode motor learning, habit formation, and dependence.

Does Three-dimensional Printing Plus Pedicle Guider Technology in Severe Congenital Scoliosis Facilitate Accurate and Efficient Pedicle Screw Placement?

BACKGROUND: Three-dimensional (3-D) printing offers the opportunity to create patient-specific guides for pedicle screw placement based on CT-generated models. This technology might allow for more-accurate placement of pedicle screws in patients with severe congenital scoliosis who have rotated vertebrae and small pedicles, but to our knowledge, this premise has not been tested. QUESTIONS/PURPOSES: (1) Is the use of 3-D printing and pedicle guider technology as or more accurate than the use of the freehand technique for pedicle-screw placement in patients with severe congenital scoliosis? (2) Does surgical time differ with the use of these guiders? (3) Are complications less common in patients treated with this new approach to pedicle-screw placement? METHODS: A prospective controlled study was conducted of patients with severe congenital scoliosis (major curve ≥ 90°) from June 2016 to June 2018. During this period, we treated 93 patients with congenital scoliosis; 32 had severe scoliosis with a major curve ≥ 90°. The patients were divided into a pedicle guider group (n = 15) and a control group (n = 17) based on their willingness to use pedicle guider technology, which was considered a research technology. With the numbers available, there were no between-group differences in terms of age, sex, BMI, or parameters related to curve severity or flexibility, and all patients in both groups had severe curves. Preoperative and postoperative low-dose CT scans were performed in the two groups. In the pedicle guider group, custom software was used to design the pedicle guider, and a 3-D printer was used to print a physical spinal model and pedicle guiders. The pedicle guiders were tested on the surface of the physical spinal model before surgery to ensure proper fit, and then used to assist pedicle screw placement during surgery. A total of 244 screws were implanted with the help of 127 pedicle guiders (254 guiding tunnels) during surgery in the PG group. Five predesigned pedicle guiders were abandoned due to an unstable match, and the success rate of assisted screw placement using a pedicle guider was 96% (244 of 254). The freehand technique was used in the control group, which relied on anatomic localization to place pedicle screws. The accuracy of pedicle screw placement was evaluated with CT scans, which revealed whether screws had broken through the pedicle cortex. We compared the groups in terms of accuracy (defined as unanticipated breaches less than 2 mm), surgical time, time to place pedicle screws, and screw-related complications. RESULTS: A higher proportion of the screws placed using pedicle guider technology were positioned accurately than were in the control group (93% [227 of 244] versus 78% [228 of 291]; odds ratio, 3.69 [95% CI, 2.09-6.50]; p<0.001). With pedicle guider use, operative time (296 ± 56 versus 360 ± 74; 95% CI, -111 to -17; p = 0.010), time to place all screws (92 ± 17 versus 118 ± 21; 95% CI, -39 to -12; p = 0.001), and mean time to place one screw (6 ± 1 versus 7 ± 1; 95% CI, -2 to 0; p = 0.011) decreased. One patient in the pedicle guider group and four in the control group experienced screw-related complications; the sample sizes and small number of complications precluded statistical comparisons. CONCLUSIONS: In this small, preliminary study, we showed that the accuracy of the surgical technique using spinal 3-D printing combined with pedicle guider technology in patients with severe congenital scoliosis was higher than the accuracy of the freehand technique. In addition, the technique using pedicle guider technology appeared to shorten operative time. If these findings are confirmed in a larger study, pedicle guider technology may be helpful for situations in which intraoperative CT or O-arm navigation is not available. LEVEL OF EVIDENCE: Level II, therapeutic study.

A survey of pediatric CT doses in the Shanghai metropolitan area.

The purpose of this study was to evaluate computed tomography (CT) doses in child examinees at different ages throughout the Shanghai metropolitan area. The head and body CT dose indices (CTDIs) of 50 CT scanners were tested by phantom measurements using standard imaging protocols. The values of CTDIw, CTDIvol and dose length product (DLP) were calculated and saved in a table along with the parameters of routine head and chest scans for different age groups of children and adults. The effective doses were estimated from the K-factors by age and DLP. The CTDIvol, DLP and effective dose for multi-detector row CT (MDCT) in children during routine head scans were larger than those for single-detector row CT (SDCT) and dual-detector row CT (DDCT). The CTDIvol, DLP and effective dose for MDCT and DDCT in children during routine chest scans were lower than those for SDCT. Radiation risks are higher for children in CT examinations compared to adults.

Naringenin inhibits osteoclastogenesis through modulation of helper T cells-secreted IL-4.

Naringenin (NAR) is a natural predominant flavanone and has a wide range of pharmacological activities. The aim of this study was to investigate the protective mechanisms of NAR on RANKL-induced osteoclastogenesis and osteoclast bone resorption. T cells were divided into four groups under different concentrations of NAR (0, 25, 50, 100 µM). CD4+ T cell subsets in different groups were evaluated by flow cytometry. TRAP staining, pit formation assays and F-actin ring immunofluorescent staining were performed. In addition, gene expression of osteoclast-specific markers was analyzed by qPCR and Western blot. Our results showed that compared with the control group, there were relatively fewer Th1 and Th17 cells and more Th2 cells and Treg cells in the NAR groups. Besides, the number of TRAP-positive multinucleated osteoclasts, the areas of bone resorption pits and the size and number of F-actin rings were notably decreased in the bone marrow macrophages (BMMs) treated with T-cell supernatant containing NAR. Moreover, NAR treatment dramatically reduced the expressions of cathepsin K, c-Fos, DC-STAMP, NFATc1, TRAP, and V-ATPase d2 at mRNA and protein levels. However, these effects were abolished by adding a neutralizing antibody against IL-4. In conclusion, NAR suppressed RANKL-induced osteoclastogenesis and osteoclast bone resorption by promoting the release of IL-4 from T cells.

Knockdown of lncRNA BDNF-AS suppresses neuronal cell apoptosis via downregulating miR-130b-5p target gene PRDM5 in acute spinal cord injury.

OBJECTIVE: The present study was designed to investigate the molecular mechanism and biological roles of lncRNA brain-derived neurotrophic factor antisense (lncRNA BDNF-AS) in acute spinal cord injury (ASCI). METHODS: The rat model of ASCI and hypoxic cellular model were established to detect the expression of BDNF-AS, miR-130b-5p, PR (PRDI-BF1 and RIZ) domain protein 5 (PRDM5) and cleaved caspase 3 (c-caspase 3) using qRT-PCR and western blot. Basso, Beattie and Bresnahan (BBB) score was carried out to assess neurological function. Flow cytometry was used to determine the apoptosis of neuronal cells. The association among BDNF-AS, miR-130b-5p and PRDM5 were disclosed by RNA immunoprecipitation (RIP) assay, RNA pull-down assay and dual-luciferase reporter assay. RESULTS: BDNF-AS, PRDM5 and c-caspase 3 expression were significantly upregulated, while miR-130b-5p was suppressed in the ASCI group and neuronal cells following hypoxia treatment. BDNF-AS knockdown inhibited neuronal cell apoptosis. Further studies indicated that BDNF-AS functioned as a competing endogenous RNA (ceRNA) by sponging miR-130b-5p in neuronal cells. Further investigations demonstrated that PRDM5 was a target of miR-130b-5p and BDNF-AS knockdown exerted anti-apoptotic effects via miR-130b-5p/PRDM5 axis. CONCLUSION: The lncRNA BDNF-AS/miR-130b-5p/PRDM5 axis might be a promising therapeutic target for ASCI.

Application for oxytetracycline wastewater pretreatment by Fe-C-Ni catalytic cathodic-anodic-electrolysis granular fillers from rare-earth tailings.

Fe-C-Ni catalytic cathodic-anodic-electrolysis granular fillers (REGF) coupled with a reactor was studied for oxytetracycline (OTC) wastewater pretreatment. In this study, the REGF were manufactured from the rare-earth tailing (RET), powdered activated carbon (PAC), scrap iron and nickel by balling and calcining. The REGF was characterized by X-Ray Diffraction and Scanning Electron Microscope analysis. The influences of pH value (2-7), OTC concentrations, hydraulic retention time and aeration on the removal efficiency of OTC and total organic carbon (TOC) were studied. This system had good removal efficiency of TOC of 80.0% and OTC of 98.2% under the optimal conditions, which were influent pH of 3, aeration rate of 0 mg L-1, and HRT of 3 h. After running for 50 d, the REGF did not become hardened and the ability of reaction was more lasting. The system was back-washed by acid solution (pH = 1) in the 25th day. The removal mechanisms were electrophoresis, redox and flocculation. The nickel, which was as the catalyst, was added into REGF to enhance the reduction of pollution with the absorbed atomic hydrogen. This paper provides a way for the recycle of the rare earth tailings and an effective application for wastewater.

Intensified nutrients removal in constructed wetlands by integrated Tubifex tubifex and mussels: Performance and mechanisms.

The synergy of Tubifex tubifex (T. tubifex) and mussels on SFCWs (named SFCW-MT) performance was well studied in laboratory throughout a year. The SFCW-MT were steady operated with high TN and TP treatment, with the removal efficiencies of 37.85 ±â€¯5.22% and 39.26 ±â€¯5.20% even in winter. The mussels had excellent NH4-N removal efficiency, and avoid the shortage of NH4-N removal with T. tubifex in winter. Simultaneously, the SFCW-MT improved the NO3-N treatment by 51% than that in control group. The plant growth was improved in SFCW-MT, which reflected in the improvement of total chlorophyll contents and plant heights. The N and P absorbed by wetland plants and adsorbed by substrate were both increased with mussels. Microbial analysis results revealed that, the mussels could keep the abundance of nitrifiers despite the negative effect of T. tubifex. On that basis, the improved proportions of denitrifiers (Firmicutes) have a significantly recognized role in NO3-N transformation in SFCW-MT. The gut and membrane sections of mussels, as well as T. tubifex, also has proportions of denitrifiers and part of nitrifiers, and thus changed the microbial community in substrate. This evidence indicated that the co-existence of T. tubifex and mussels have potential application for simultaneous removal of NH4-N and NO3-N in CWs.

Comparison of low density and high density pedicle screw instrumentation in Lenke 1 adolescent idiopathic scoliosis.

BACKGROUND: The correlation between implant density and deformity correction has not yet led to a precise conclusion in adolescent idiopathic scoliosis (AIS). The aim of this study was to evaluate the effects of low density (LD) and high density (HD) pedicle screw instrumentation in terms of the clinical, radiological and Scoliosis Research Society (SRS)-22 outcomes in Lenke 1 AIS. METHODS: We retrospectively reviewed 62 consecutive Lenke 1 AIS patients who underwent posterior spinal arthrodesis using all-pedicle screw instrumentation with a minimum follow-up of 24 months. The implant density was defined as the number of screws per spinal level fused. Patients were then divided into two groups according to the average implant density for the entire study. The LD group (n = 28) had fewer than 1.61 screws per level, while the HD group (n = 34) had more than 1.61 screws per level. The radiographs were analysed preoperatively, postoperatively and at final follow-up. The perioperative and SRS-22 outcomes were also assessed. Independent sample t tests were used between the two groups. RESULTS: Comparisons between the two groups showed no significant differences in the correction of the main thoracic curve and thoracic kyphosis, blood transfusion, hospital stay, and SRS-22 scores. Compared with the HD group, there was a decreased operating time (278.4 vs. 331.0 min, p = 0.004) and decreased blood loss (823.6 vs. 1010.9 ml, p = 0.048), pedicle screws needed (15.1 vs. 19.6, p < 0.001), and implant costs ($10,191.0 vs. $13,577.3, p = 0.003) in the LD group. CONCLUSIONS: Both low density and high density pedicle screw instrumentation achieved satisfactory deformity correction in Lenke 1 AIS patients. However, the operating time and blood loss were reduced, and the implant costs were decreased with the use of low screw density constructs.

Influence of screw density on thoracic kyphosis restoration in hypokyphotic adolescent idiopathic scoliosis.

BACKGROUND: Previous studies have reported that rod composition and diameter, as well as the correction technique are key factors associated with thoracic kyphosis (TK) restoration. However, few study has analyzed the correlation between screw density and TK restoration in hypokyphotic adolescent idiopathic scoliosis (AIS). METHODS: Fifty-seven thoracic AIS patients with preoperative TK < 10° treated with all pedicle screw fixation with a minimum 2-year follow-up were recruited. Preoperative and postoperative radiographic measurements, and information of posterior instrumentation were reviewed. Pearson and Spearman correlation coefficient analysis were used to assess relationships between change in TK and number of variables. Then, the included patients were classified into two groups (Group 1: postoperative TK ≥ 20°; Group 2: postoperative TK < 20°) to evaluate the influence factors of TK restoration. RESULTS: The average preoperative TK was 4.75°, which was significantly restored to 17.30° (P < 0.001). Significant correlations were found between change in TK and flexibility of major thoracic curve (r = 0.357, P = 0.006), preoperative TK (r = -0.408, P = 0.002), and screw density of concave side (r = 0.306, P = 0.021), respectively. In the subgroup comparison, 17 patients (29.8%) maintain the postoperative TK ≥ 20°, increased flexibility of major thoracic curve (P < 0.001), screw number of concave side (P = 0. 029), and cobalt chromium rods (P = 0.041) were found in the group of postoperative TK ≥ 20°. CONCLUSIONS: TK restoration remains a challenge for AIS patients with hypokyphosis, especially for the poor flexibility ones. Except for thicker and cobalt chromium rods, screw density of concave side might be another positive predictor of restoring normal kyphosis, which provides a stronger corrective force on the sagittal plane with more pedicle screws.

Lanthanum Chloride Attenuates Osteoclast Formation and Function Via the Downregulation of Rankl-Induced Nf-κb and Nfatc1 Activities.

The biological activities of lanthanum chloride (LaCl3 ) and the molecular mechanisms of action underlying its anti-inflammatory, anti-hyperphosphatemic, and osteoblast-enhancing effects have been studied previously, but less is known about the effects of LaCl3 on osteoclasts. The present study used in vivo and in vitro approaches to explore the effects of LaCl3 on osteoclasts and osteolysis. The results indicated that LaCl3 concentrations that were non-cytotoxic to mouse bone marrow-derived monocytes attenuated receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis, bone resorption, mRNA expression of osteoclastogenic genes in these cells, including cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAP). Further, LaCl3 inhibited RANKL-mediated activation of the nuclear factor-κB (NF-κB) signaling pathway, and downregulated mRNA and protein levels of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), and c-fos. In vivo, LaCl3 attenuated titanium (Ti) particle-induced bone loss in a murine calvarial osteolysis model. Histological analyses revealed that LaCl3 ameliorated bone destruction and decreased the number of TRAP-positive osteoclasts in this model. These results demonstrated that LaCl3 inhibited osteoclast formation, function, and osteoclast-specific gene expression in vitro, and attenuated Ti particle-induced mouse calvarial osteolysis in vivo, where the inhibition of NF-κB signaling and downregulation of NFATc1 and c-fos played an important role.