SzM protein of Streptococcus equi ssp. zooepidemicus triggers the release of neutrophil extracellular traps depending on GSDMD.

Streptococcus equissp.zooepidemicus (SEZ) is a crucial pathogen and contributes to various infections in numerous animal species. Swine streptococcicosis outbreak caused by SEZ has been reported in several countries in recent years. SzM protein is a cell membrane-anchored protein, which exhibits as an important virulence factor of SEZ. Effects of SzM protein on host innate immune need further study. Here, recombinant SzM (rSzM) protein of the SEZ was obtained, and mice were intraperitoneally injected with rSzM protein. We discovered that rSzM protein can recruit neutrophils into the injected site. In further study, neutrophils were isolated and treated with rSzM protein, NETs release were triggered by rSzM protein independently, and GSDMD protein was promoted-expressed and activated. In order to investigate the role of GSDMD in NETs formation, neutrophils isolated from WT mice and GSDMD-/- mice were treated with rSzM protein. The results showed that GSDMD deficiency suppressed the NETs release. In conclusion, SzM protein of SEZ can trigger the NETs release in a GSDMD-depending manner.

LASS2 suppresses metastasis in multiple cancers by regulating the ferroptosis signalling pathway through interaction with TFRC.

BACKGROUND: As a key enzyme in ceramide synthesis, longevity assurance homologue 2 (LASS2) has been indicated to act as a tumour suppressor in a variety of cancers. Ferroptosis is involved in a variety of tumour processes; however, the role of LASS2 in regulating ferroptosis has yet to be explored. This article explores the potential underlying mechanisms involved. METHODS: Bioinformatics tools and immunohistochemical staining were used to evaluate LASS2 expression, and the results were analysed in relation to overall survival and clinical association in multiple cancers. Coimmunoprecipitation-coupled liquid chromatography-mass spectrometry (co-IP LC-MS) was performed to identify potential LASS2-interacting proteins in thyroid, breast, and liver cancer cell lines. Transcriptomics, proteomics and metabolomics analyses of multiple cancer cell types were performed using MS or LC-MS to further explore the underlying mechanisms involved. Among these tumour cells, the common LASS2 interaction partner transferrin receptor (TFRC) was analysed by protein-protein docking and validated by coimmunoprecipitation western blot, immunofluorescence, and proximity ligation assays. Then, we performed experiments in which tumour cells were treated with Fer-1 or erastin or left untreated, with or without inducing LASS2 overexpression, and assessed the molecular biological and cellular functions by corresponding analyses. RESULTS: Low LASS2 expression is correlated with adverse clinical characteristic and poor prognosis in patients with thyroid cancer, breast cancer or HCC. Multiomics analyses revealed significant changes in the ferroptosis signalling pathway, iron ion transport and iron homeostasis. Our in vitro experiments revealed that LASS2 overexpression regulated ferroptosis status in these tumour cells by affecting iron homeostasis, which in turn inhibited tumour migration, invasion and EMT. In addition, LASS2 overexpression reversed the changes in tumour cell metastasis induced by either Fer-1 or erastin. Mechanistically, LASS2 interacts directly with TFRC to regulate iron homeostasis in these tumour cells. CONCLUSIONS: In summary, our study reveals for the first time that LASS2 can inhibit tumour cell metastasis by interacting with TFRC to regulate iron metabolism and influence ferroptosis status in thyroid, breast, and liver cancer cells, these results suggest potential universal therapeutic targets for the treatment of these cancers.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

Genetic and Phenotypic Analysis of Phage-Resistant Mutant Fitness Triggered by Phage-Host Interactions.

The emergence of phage-resistant bacterial strains is one of the biggest challenges for phage therapy. However, the emerging phage-resistant bacteria are often accompanied by adaptive trade-offs, which supports a therapeutic strategy called "phage steering". The key to phage steering is to guide the bacterial population toward an evolutionary direction that is favorable for treatment. Thus, it is important to systematically investigate the impacts of phages targeting different bacterial receptors on the fitness of the bacterial population. Herein, we employed 20 different phages to impose strong evolutionary pressure on the host Pseudomonas aeruginosa PAO1 and examined the genetic and phenotypic responses of their phage-resistant mutants. Among these strains with impaired adsorptions, four types of mutations associated with bacterial receptors were identified, namely, lipopolysaccharides (LPSs), type IV pili (T4Ps), outer membrane proteins (OMPs), and exopolysaccharides (EPSs). PAO1, responding to LPS- and EPS-dependent phage infections, mostly showed significant growth impairment and virulence attenuation. Most mutants with T4P-related mutations exhibited a significant decrease in motility and biofilm formation ability, while the mutants with OMP-related mutations required the lowest fitness cost out of the bacterial populations. Apart from fitness costs, PAO1 strains might lose their resistance to antibiotics when counteracting with phages, such as the presence of large-fragment mutants in this study, which may inspire the usage of phage-antibiotic combination strategies. This work provides methods that leverage the merits of phage resistance relative to obtaining therapeutically beneficial outcomes with respect to phage-steering strategies.

Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A.

The leucine-rich repeat-containing family 8 member A (LRRC8A) is an essential subunit of the volume-regulated anion channel (VRAC). VRAC is critical for cell volume control, but its broader physiological functions remain under investigation. Recent studies in the field indicate that Lrrc8a disruption in the brain astrocytes reduces neuronal excitability, impairs synaptic plasticity and memory, and protects against cerebral ischemia. In the present work, we generated brain-wide conditional LRRC8A knockout mice (LRRC8A bKO) using NestinCre -driven Lrrc8aflox/flox excision in neurons, astrocytes, and oligodendroglia. LRRC8A bKO animals were born close to the expected Mendelian ratio and developed without overt histological abnormalities, but, surprisingly, all died between 5 and 9 weeks of age with a seizure phenotype, which was confirmed by video and EEG recordings. Brain slice electrophysiology detected changes in the excitability of pyramidal cells and modified GABAergic inputs in the hippocampal CA1 region of LRRC8A bKO. LRRC8A-null hippocampi showed increased immunoreactivity of the astrocytic marker GFAP, indicating reactive astrogliosis. We also found decreased whole-brain protein levels of the GABA transporter GAT-1, the glutamate transporter GLT-1, and the astrocytic enzyme glutamine synthetase. Complementary HPLC assays identified reduction in the tissue levels of the glutamate and GABA precursor glutamine. Together, these findings suggest that VRAC provides vital control of brain excitability in mouse adolescence. VRAC deletion leads to a lethal phenotype involving progressive astrogliosis and dysregulation of astrocytic uptake and supply of amino acid neurotransmitters and their precursors.

Automatic construction of coronary artery tree structure based on vessel blood flow tracking.

We sought to propose an innovative vessel blood flow tracking (VBFT) method to extract coronary artery tree (CAT) and to assess the effectiveness of this VBFT versus the single-frame method. Construction of a CAT from a segmented artery is the basis of artificial intelligence-aided angiographic diagnosis. However, construction of a CAT using a single frame remains challenging, due to bifurcations and overlaps in two-dimensional angiograms. Overall, 13,222 angiograms, including 28,539 vessels, were retrospectively collected from 3275 patients and were then annotated. Coronary arteries were automatically segmented by a previously established deep neural networks (DNNs), and the skeleton lines were then extracted from segmentation images to construct CAT using the single-frame method and the VBFT method. Additionally, 1322 angiograms with 2201 vessels were used to test these two methods. Compared to the single-frame method, the VBFT method can significantly improve the accuracy of CAT as (84.3% vs. 72.3%; p < 0.001). Overlap (OV) was higher in the VBFT group than that in the Single-Frame group (91.1% vs. 87.5%; p < 0.001). The VBFT method significantly reduced the incidence of the lack of branching (7.30% vs. 13.9%, p < 0.001), insufficient length (6.70% vs. 11.0%, p < 0.001), and redundant branches (1.60% vs. 3.10%, p < 0.001). The VBFT method improved the extraction of a CAT structure, which will facilitate the development of artificial intelligence-aided angiographic diagnosis. Cardiologists can efficiently diagnose CAD using this method.

Passive smoking induces rat testicular injury via the FAS/FASL pathway.

The mechanisms by which cigarette smoke (CS) exposure has a detrimental effect on the male reproductive system is still not fully understood. We aimed to elucidate the role of cigarette smoke-induced injury by the Fas/FasL pathway by using a Sprague-Dawley rat model of cigarette smoking exposure. Here, 200 rats were randomaly divided into five groups with different smoking exposure durations. Forty animals per group were further divided into four groups: a control group, and groups exposed to cigarette smoke at doses of 10, 20 or 30 cigarettes/day. The testes were harvested and the effects of CS exposure on the testis were characterized on the basis of morphological changes, oxidative stress, and a significant elevation in the expression of FAS/FASL pathway related genes, such as FAS, FASL, FADD, caspase 8 and caspase 3. Oxidative stress was reflected by significant time-dependent changes in SOD and GSH-Px activity, and MDA content. Taken together, our data suggest that CS exposure induces testis injury, which is related to the increased oxidative stress and activation of the FAS/FASL apoptotic pathway in the testes.

Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.

Excessive activation of mammalian target of rapamycin (mTOR) signaling is epileptogenic in genetic epilepsy. However, the exact role of microglial mTOR in acquired epilepsy remains to be clarified. In the present study, we found that mTOR is strongly activated in microglia following excitatory injury elicited by status epilepticus. To determine the role of microglial mTOR signaling in excitatory injury and epileptogenesis, we generated mice with restrictive deletion of mTOR in microglia. Both male and female mice were used in the present study. We found that mTOR-deficient microglia lost their typical proliferative and inflammatory responses to excitatory injury, whereas the proliferation of astrocytes was preserved. In addition, mTOR-deficient microglia did not effectively engulf injured/dying neurons. More importantly, microglial mTOR-deficient mice displayed increased neuronal loss and developed more severe spontaneous seizures. These findings suggest that microglial mTOR plays a protective role in mitigating neuronal loss and attenuating epileptogenesis in the excitatory injury model of epilepsy.SIGNIFICANCE STATEMENT The mammalian target of rapamycin (mTOR) pathway is strongly implicated in epilepsy. However, the effect of mTOR inhibitors in preclinical models of acquired epilepsy is inconsistent. The broad presence of mTOR signaling in various brain cells could prevent mTOR inhibitors from achieving a net therapeutic effect. This conundrum has spurred further investigation of the cell type-specific effects of mTOR signaling in the CNS. We found that activation of microglial mTOR is antiepileptogenic. Thus, microglial mTOR activation represents a novel antiepileptogenic route that appears to parallel the proepileptogenic route of neuronal mTOR activation. This may explain why the net effect of mTOR inhibitors is paradoxical in the acquired models of epilepsy. Our findings could better guide the use of mTOR inhibitors in preventing acquired epilepsy.

Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Increasing evidence suggests that aberrant expression of circRNAs is associated with the occurrence and progression of many cancers. Here, we investigated the role of circNRIP1 in osteosarcoma and explored its possible underlying mechanisms. Three pairs of osteosarcoma tissues and adjacent normal tissues were applied to the detection of altered expression of circRNAs through circRNAs microarray. And the level of circNRIP1 expression was elevated in osteosarcoma tissues. Compared with that in adjacent normal tissue, circNRIP1 expression level was obviously elevated in 100 osteosarcoma tissues. Besides, circNRIP1 knockdown inhibited proliferation and migration, promoted apoptosis of osteosarcoma cells. Bioinformatic analysis demonstrated circNRIP1 contributed to FOXC2 expression by sponging miR-199a. Furthermore, METTL3 elevated circNRIP1 expression level via m6A modification. In short, METTL3-induced circNRIP1 exerted an oncogenic role in osteosarcoma by sponging miR-199a, which may provide new ideas for the treatment of osteosarcoma.

Clinical efficacy and therapeutic value of delayed surgery in patients with symptomatic old thoracolumbar fractures.

BACKGROUND: To investigate the clinical efficacy and therapeutic value of posterior decompression reduction, bone grafting fusion, and internal fixation for treatment of symptomatic old thoracolumbar fractures. METHOD: Retrospective analysis was conducted for 14 patients (9 men, 5 women; average age 40.1 years) with old thoracolumbar fractures who underwent posterior operation. American Spinal Injury Association (ASIA) scores were used to evaluate neurologic function. Vertebral body height, Cobb angle in the sagittal plane, spinal canal volume ratio (%) and bone graft fusion were analyzed by radiography and computed tomography on different follow-up times. RESULTS: Mean follow-up was 27.1 months (23-36 months). Of three patients with ASIA grade A, 2 had improved postoperative urination and defecation, although no classification change. Preoperative ASIA score for eight patients with incomplete injury was grade B; four patients recovered to grade C at final follow-up. Preoperative ASIA score was C in three patients, increased to D in two patients and returned to normal E in one patient. Preoperative results showed average injured vertebra height loss rate decreased from 50.4 to 8.9%; average Cobb angle on the sagittal plane recovered from 39.6 to 6.9°; and the average spinal canal volume ratio recovered from 33.8 to 5.9%. Bony fusion was achieved; local lumbago and leg pain were relieved to some extent. No patients exhibited loosening of the fracture treated by internal fixation, pseudoarthrosis, or other related serious complications. CONCLUSION: Treatment of old thoracolumbar fractures by posterior decompression reduction, bone grafting fusion, and internal fixation can relieve spinal cord compression, improve neurologic function of some patients (ASIA grades B-C), effectively relieve pain, correct deformity, restore biomechanical stability, and significantly improve quality of life.

Unsupervised Trademark Retrieval Method Based on Attention Mechanism.

Aiming at the high cost of data labeling and ignoring the internal relevance of features in existing trademark retrieval methods, this paper proposes an unsupervised trademark retrieval method based on attention mechanism. In the proposed method, the instance discrimination framework is adopted and a lightweight attention mechanism is introduced to allocate a more reasonable learning weight to key features. With an unsupervised way, this proposed method can obtain good feature representation of trademarks and improve the performance of trademark retrieval. Extensive comparative experiments on the METU trademark dataset are conducted. The experimental results show that the proposed method is significantly better than traditional trademark retrieval methods and most existing supervised learning methods. The proposed method obtained a smaller value of NAR (Normalized Average Rank) at 0.051, which verifies the effectiveness of the proposed method in trademark retrieval.

Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance.

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

Engineering Aptamer with Enhanced Affinity by Triple Helix-Based Terminal Fixation.

The affinity of aptamers relies on their adaptive folding, but the excessive flexibility of the aptamer backbone usually hampers the folding process. Thus, there is an urgent need to engineer aptamers with more stable and defined structures. Herein, we report a postselection strategy for stabilizing aptamer structures, by fixing both termini of the aptamer with a length-optimized triple helix structure. An anti-lysozyme aptamer was engineered in this way, and its affinity was enhanced by almost 10-fold. An electrochemical aptasensor was designed based on this engineered aptamer, assisted by a DNA tetrahedron as a spacer to orient the aptamer. The aptasensor achieved a 180-fold lower limit of detection than that achieved by the aptasensor without termini-fixed aptamer and exhibited high sensitivity and selectivity toward lysozyme in real red wine samples. This work sheds light on engineering aptamers to achieve enhanced affinity and on the application of aptasensors in complex matrices.

Substrate-rigidity dependent migration of an idealized twitching bacterium.

Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a "twitcher", a cell driven by extension-retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a "sticky" substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells on a sticky substrate.

Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency-modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic-shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one-third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3-turn crossover design rhombic-shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force-controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties.

Is percutaneous kyphoplasty the better choice for minimally invasive treatment of neurologically intact osteoporotic Kümmell's disease? A comparison of two minimally invasive procedures.

PURPOSE: The purpose of this study was to compare and evaluate the safety and efficacy of percutaneous vertebroplasty at a hyperextension position (PVPHP) and percutaneous kyphoplasty at a hyperextension position (PKPHP) for the treatment of osteoporotic Kümmell's disease. METHODS: This study was a retrospective, single-centre study. There were 35 patients with osteoporotic Kümmell's disease who were analyzed. Twenty-two of them underwent PVPHP and the other 13 patients underwent PKPHP from January 2013 to January 2015. The volume of bone cement injection and operation costs were compared. We compared the visual analogue score (VAS) and vertebral Cobb's angle at pre-operation, the second day after operation, and the final follow-up. We compared the Oswestry disability index (ODI) score at the pre-operation and the final follow-up. RESULTS: There were no significant differences in gender, age, course of disease, bone mineral density (BMD), and mean follow-up time between the two groups (P > 0.05). Regarding the costs of the operation, the PKPHP group was significantly higher than the PVPHP group (P < 0.05). Compared with the pre-operation (P < 0.05), the post-operative ODI score, VAS, and Cobb's angle of the two groups were improved significantly. Even though the correction of Cobb's angle in the PKPHP group was slightly better than the PVPHP position group, there were no significant differences between two groups (P > 0.05). At the final follow-up, the Cobb's angle was increased in both groups, but there was no significant difference (P > 0.05). There was no significant difference in the bone cement leakage rate between the two groups (P > 0.05). CONCLUSION: For the treatment of Kümmell's disease, PVPHP and PKPHP are both safe and effective, but PVPHP is more economical and can be considered a preferred method of treatment.

Cigarette smoke induces rat testicular injury via mitochondrial apoptotic pathway.

An understanding of the causative mechanisms of the harmful effects of cigarette smoke on the male reproductive system remains incomplete. Here, we investigated three different inhaled cigarette smoke doses over five different exposure durations to identify how the testis is affected. The effects of cigarette smoke exposure on testicular germ cells were characterized by morphological changes and a significant elevation in the number of apoptotic cells. Caspase 3 activation increased dramatically after cigarette smoke exposure, accompanied by significant time-dependent expression of the pro-apoptotic proteins Bak (B cell lymphoma/leukemia 2 [Bcl-2] homologous antagonist killer), Bcl2l11 (a BH3 domain-only protein related to Bcl-2), Apaf1 (Apoptotic protease-activating factor-1), and Caspase 9. Conversely, the abundance of anti-apoptotic Bcl2l2 decreased. Taken together, our findings suggest that extensive inhalation of cigarette smoke damages testicular germ cells through the induction of the mitochondrial apoptotic pathway through the Bcl-2 protein family.

A Comparison of the Mini-Open Wiltse Approach with Pedicle Screw Fixation and the Percutaneous Pedicle Screw Fixation for Neurologically Intact Thoracolumbar Fractures.

BACKGROUND The thoracolumbar AO type A3 fracture is an incomplete burst fracture, which affects one vertebral body endplate. The objective of this study was to determine which of two minimal invasive techniques was more suitable for A3 fractures based on clinical and radiographic results. MATERIAL AND METHODS We studied 112 patients with A3 subtype fractures without neurological deficits. A total of 63 patients received percutaneous pedicle screw fixation (PPSF), and 49 patients were treated using mini-open Wiltse approach with pedicle screw fixation (MWPSF). The clinical outcomes, surgery-related results, and the pre-operative and post-operative radiological findings were compared between the two groups. RESULTS The length of incision, intra-operative blood loss, post-operative hospitalization time, visual analog score (VAS), Oswestry disability index (ODI), and accuracy rate of pedicle screw placement were compared between the PPSF and MWPSF groups, with no significant differences found (p>0.05). However, the vertebral body angle (VBA) and Cobb's angle in the MWPSF group was much better than in the PPSF group (p<0.05). The operating time and C-arm exposure time of the MWPSF group were significantly lower than the PPSF group (p<0.05). The operative and post-operative costs of the PPSF group were significantly higher than the MWPSF group (p<0.05). CONCLUSIONS Our study found no significant differences in some clinical outcomes between the two groups. Both treatments were safe and effective for A3 subtype fractures. Nevertheless, given the radiation exposure, reduction of kyphosis, special equipment required, learning curve and hospitalization costs associated with PPSF, we concluded that MWPSF was a better choice for A3 subtype fractures.

Comparison of Accuracy of Pedicle Screw Insertion Among 4 Guided Technologies in Spine Surgery.

BACKGROUND As an available new tool for spinal surgery, robotic technology holds great potential and has been demonstrated to have better clinical outcomes compared with traditional techniques. However, it has not been compared with other assisted tools for the treatment of lumbar degenerative disease. This article focused on studying such variances. MATERIAL AND METHODS A total of 176 pedicle screws were inserted in 39 patients using a spine robot (group 1), 134 screws were implanted in 28 patients using navigational template (group 2), 234 screws were implanted in 51 patients by O-arm-based navigation (group 3), and 346 screws were implanted in 72 patients by fluoroscopy-guided assistance (group 4). The screw position was evaluated using postoperative scans according to Rampersaud A to D classification, and other secondary data were also collected. RESULTS "Perfect" pedicle screw insertion (Grade A) was 90.34%, 91.79%, 84.19%, and 65.03% of groups 1-4, respectively. "Clinically acceptable" screw implantation (Grade A+B) was 94.32%, 95.52, 90.60%, and 78.03% in groups 1-4, respectively. Deviation sagittal (°) respectively was 3±9, 2±10, 4±7, and 10±8° in groups 1-4, respectively. Deviation transversal (°) screw insertion was 3±8, 3±7, 4±9, and 8±13° in groups 1-4, respectively. Statistical analysis showed group 1 had no significant difference in the accuracy of "Perfect and Clinical acceptable" as well as deviation sagittal or transversal, respectively, compared with groups 2 and 3 but not group 4. CONCLUSIONS Robotic-assistance technology no clear advantage in terms of accuracy compared to the navigation template or O-arm systems for screw implantation, but it significantly reduced adverse events, fluoroscopy time per screw, postoperative stay, and blood loss.

Rapamycin Inhibition of mTOR Reduces Levels of the Na+/H+ Exchanger 3 in Intestines of Mice and Humans, Leading to Diarrhea.

BACKGROUND & AIMS: The immunosuppressant rapamycin frequently causes noninfectious diarrhea in organ transplant recipients. We investigated the mechanisms of this process. METHODS: We performed a retrospective analysis of renal transplant recipients treated with rapamycin from 2003 through 2010 at Albany Medical College, collecting data on serum levels of rapamycin. Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from patients who did and did not receive rapamycin (controls), in ileum tissues from rats or mice given rapamycin, and in mice with intestine-specific disruption of mammalian target of rapamycin (Mtor) (mTOR(f/f):Villin-cre mice) or Atg7 (Atg7(flox/flox); Villin-Cre). Exchange activity and intestinal water absorption were measured using a pH-sensitive dye and small intestine perfusion, respectively. RESULTS: Episodes of noninfectious diarrhea occurred in organ recipients after increases in serum levels of rapamycin. The expression of NHE3 was reduced in the ileal brush border of patients with diarrhea. In rats and mice, continuous administration of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed in mice with intestinal deletion of ATG7, indicating that autophagy is required for the reduction. Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). The intestines of mice with intestine-specific deletion of mTOR were dilated and contained large amounts of liquid stools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice. We observed a significant reduction in Na(+)/H(+) exchange activity in ileum tissues from these mice. CONCLUSIONS: Rapamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tissues of patients and rodents. This process appears to require the autophagic activity mediated by ATG7. Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patients undergoing rapamycin therapy.