Treatment of Thoracolumbar Fracture

The most common fractures of the spine are associated with the thoracolumbar junction. The goals of treatment of thoracolumbar fracture are leading to early mobilization and rehabilitation by restoring mechanical stability of fracture and inducing neurologic recovery, thereby enabling patients to return to the workplace. However, it is still debatable about the treatment methods. Neurologic injury should be identified by thorough physical examination for motor and sensory nerve system in order to determine the appropriate treatment. The mechanical stability of fracture also should be evaluated by plain radiographs and computed tomography. In some cases, magnetic resonance imaging is required to evaluate soft tissue injury involving neurologic structure or posterior ligament complex. Based on these physical examinations and imaging studies, fracture stability is evaluated and it is determined whether to use the conservative or operative treatment. The development of instruments have led to more interests on the operative treatment which saves mobile segments without fusion and on instrumentation through minimal invasive approach in recent years. It is still controversial for the use of these treatments because there have not been verified evidences yet. However, the morbidity of patients can be decreased and good clinical and radiologic outcomes can be achieved if the recent operative treatments are used carefully considering the fracture pattern and the injury severity

Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners.

Objectives. Kabuki syndrome (KS) is a rare genetic disorder characterized by developmental delay, retarded growth, and cardiac, gastrointestinal, neurocognitive, renal, craniofacial, dental, and skeletal defects. KS is caused by mutations in the genes encoding histone H3 lysine 4 methyltransferase (KMT2D) and histone H3 lysine 27 demethylase (KDM6A), which are core components of the complex of proteins associated with histone H3 lysine 4 methyltransferase SET1 (SET1/COMPASS). Using single-cell RNA data, we examined the expression profiles of Kmt2d and Kdm6a in the mouse dental pulp. In the incisor pulp, Kmt2d and Kdm6a colocalize with other genes of the SET1/COMPASS complex comprised of the WD-repeat protein 5 gene (Wdr5), the retinoblastoma-binding protein 5 gene (Rbbp5), absent, small, and homeotic 2-like protein-encoding gene (Ash2l), nuclear receptor cofactor 6 gene (Ncoa6), and Pax-interacting protein 1 gene (Ptip1). In addition, we found that Kmt2d and Kdm6a coexpress with the downstream target genes of the Wingless and Integrated (WNT) and sonic hedgehog signaling pathways in mesenchymal stem/stromal cells (MSCs) at different stages of osteogenic differentiation. Taken together, our results suggest an essential role of KMT2D and KDK6A in directing lineage-specific gene expression during differentiation of MSCs

Association of Plasma Retinol-Binding Protein 4, Adiponectin, and High Molecular Weight Adiponectin with Insulin Resistance in Non-Diabetic Hypertensive Patients

∙The authors have no financial conflicts of interest. Purpose: The aim of this study was to determine whether retinol-binding protein 4 (RBP4), adiponectin and high molecular weight (HMW) adiponectin are associated with insulin resistance (IR) and metabolic parameters in non-diabetic hypertensive patients. Also, we sought to compare the predictive values of these adipocytokines for IR in non-diabetic hypertensive patients. Materials and Methods: Analyses of RBP4, adiponectin, and HMW adiponectin were performed on 308 non-diabetic hypertensives (148 males, age 58 ± 10 years, 189 non-metabolic syndrome and 119 metabolic syndrome). The homeostasis model assessment (HOMA) index for IR, lipid profiles, and anthropometric measure-ments were assessed. Results: There was no significant difference in RBP4 levels according to the presence of metabolic syndrome, although adiponectin and HMW adiponectin were significantly lower in metabolic syndrome. Correlation analysis of log RBP4 with IR and metabolic indices revealed that there was no significant correlation of RBP4 with wais

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis

FusorSV: an algorithm for optimally combining data from multiple structural variation detection methods.

Comprehensive and accurate identification of structural variations (SVs) from next generation sequencing data remains a major challenge. We develop FusorSV, which uses a data mining approach to assess performance and merge callsets from an ensemble of SV-calling algorithms. It includes a fusion model built using analysis of 27 deep-coverage human genomes from the 1000 Genomes Project. We identify 843 novel SV calls that were not reported by the 1000 Genomes Project for these 27 samples. Experimental validation of a subset of these calls yields a validation rate of 86.7%. FusorSV is available at https://github.com/TheJacksonLaboratory/SVE . Genome Biol 2018 Mar 20; 19(1):38

Body mass index affecting ticagrelor monotherapy vs. ticagrelor with aspirin in patients with acute coronary syndrome: A pre-specified sub-analysis of the TICO randomized trial

BackgroundAlthough ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) results in a significantly greater net clinical benefit over that with ticagrelor-based 12-month DAPT in patients with acute coronary syndrome (ACS), it remains uncertain whether this effect is dependent on body mass index (BMI). We aimed to evaluate the BMI-dependent effect of these treatment strategies on clinical outcomes.MethodsThis was a pre-specified subgroup analysis from the TICO trial (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome), evaluating the interaction between BMI and treatment strategies for the primary outcome [composite of major bleeding and adverse cardiac and cerebrovascular events (MACCE): death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization]. The secondary outcomes were major bleeding and MACCE.ResultsBased on a pre-specified BMI threshold of 25 kg/m2, 3,056 patients were stratified. Patients with BMI <25 kg/m2 had a higher risk of primary and secondary outcomes than those with BMI ≥25 kg/m2. Regardless of the BMI subgroup, the effects of ticagrelor monotherapy after 3-month DAPT on the primary outcome (pint = 0.61), major bleeding (pint = 0.76), and MACCE (pint = 0.80) were consistent without significant interaction compared with ticagrelor-based 12-month DAPT. The treatment effects according to the BMI quartiles and age, sex, and diabetic status were also consistent without significant interaction.ConclusionThe BMI-dependent impact of ticagrelor monotherapy after 3-month DAPT compared with 12-month DAPT on clinical outcomes was not heterogeneous in patients with ACS.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02494895]

An extension of a first-order language and its applications

http://deepblue.lib.umich.edu/bitstream/2027.42/7575/5/bad2105.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/7575/4/bad2105.0001.001.tx