Fultonmoesgaard7356

The AOSpine sacral classification scheme was recently described. It demonstrated substantial interobserver and excellent intraobserver agreement in the study describing it; however, an independent assessment has not been performed.

To perform an independent inter- and intraobserver agreement evaluation of the AOSpine sacral fracture classification system.

Agreement study.

Complete computerized tomography (CT) scans, including axial images, with coronal and sagittal reconstructions of 80 patients with sacral fractures were selected and classified using the morphologic grading of the AOSpine sacral classification system by six evaluators (from three different countries). Neurological modifiers and case-specific modifiers were not assessed. After a four-week interval, the 80 cases were presented to the same raters in a random sequence for repeat assessment. We used the Kappa coefficient (κ) to establish the inter- and intraobserver agreement.

The interobserver agreement was substantial when considering the fracture severity types (A, B, or C), with κ=0.68 (0.63-0.72), but moderate when considering the subtypes κ=0.52 (0.49-0.54). The intraobserver agreement was substantial considering the fracture types, with κ=0.69 (0.63-0.75), and considering subtypes, κ=0.61 (0.56-0.67).

The sacral classification system allows adequate interobserver agreement at the type level, but only moderate at the subtypes level. Future prospective studies should evaluate whether this classification system allows surgeons to decide the best treatment and to establish prognosis in patients with sacral fractures.

The sacral classification system allows adequate interobserver agreement at the type level, but only moderate at the subtypes level. Future prospective studies should evaluate whether this classification system allows surgeons to decide the best treatment and to establish prognosis in patients with sacral fractures.

Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF.

To evaluate FGF9 expression and function in human LF with and without hypertrophy.

This study employed a basic research study design utilizing human LF tissue for histological analyses.

Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery.

LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using roliferation and migration.

The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.

The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.

The recommended primary treatment for type III odontoid fractures (OFx) is external immobilization, except for patients having major displacement of the odontoid fragment. The bony fusion rate of type III OFx has been reported to be >85%. High compliance to treatment recommendations is favorable only if the treatment leads to a good outcome.

The primary aim of this study was to determine the long-term outcome after conservative and surgical treatment of type III OFx and to reaffirm that primary external immobilization is the best treatment for most type III fractures.

Retrospective study based on a prospective database.

Two hundred twelve consecutive patients with type III OFx treated at Oslo University Hospital over an 8-year period (2009-2017).

Long-term rates of bony fusion, crossover from primary conservative treatment to surgical fixation, new onset spinal cord injury (SCI), severe persistent neck pain (visual analogue scale - VAS), and persistent disability measured with Neck Disability ind4% had an OFx related SCI. Primary treatment was external immobilization alone in 95.3% and open surgical fixation in 4.7%. learn more Patients treated with primary external immobilization alone presented with significantly less translation of the odontoid fragment (p<.001) and less angulation of the odontoid fragment (p=.025) than patients treated with primary surgery. Subsequent crossover to surgical fixation was performed in 5.4%. At long-term follow-up, 95.7% of patients had bony fusion of the OFx, 80.5% had minimal/no neck pain, and none developed new onset SCI. There was no significant difference in long-term follow-up VAS (p=.444) or NDI (p=.562) between the primary external immobilization group and the primary surgical group.

This study reaffirms that nonsurgical treatment remains the preferable option in the majority of patients with type III OFx.

This study reaffirms that nonsurgical treatment remains the preferable option in the majority of patients with type III OFx.Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy in Spinocerebellar Ataxia type 2 (SCA2). Intermediate size expansions carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression in ALS. Although ATXN2 interacts directly with RNA, and in ALS pathogenesis there is a crucial role of RNA toxicity, the affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse model with Atxn2-CAG100-KnockIn for a first definition of molecular mechanisms in spinal cord pathology. Neurophysiology of lower limbs detected sensory neuropathy rather than motor denervation. Triple immunofluorescence demonstrated cytosolic ATXN2 aggregates sequestrating TDP43 and TIA1 from the nucleus. In immunoblots, this was accompanied by elevated CASP3, RIPK1 and PQBP1 abundance. RT-qPCR showed increase of Grn, Tlr7 and Rnaset2 mRNA versus Eif5a2, Dcp2, Uhmk1 and Kif5a decrease. These SCA2 findings overlap well with known ALS features. Similar to other ataxias and dystonias, decreased mRNA levels for Unc80, Tacr1, Gnal, Ano3, Kcna2, Elovl5 and Cdr1 contrasted with Gpnmb increase. Preterminal stage tissue showed strongly activated microglia containing ATXN2 aggregates, with parallel astrogliosis. Global transcriptome profiles from stages of incipient motor deficit versus preterminal age identified molecules with progressive downregulation, where a cluster of cholesterol biosynthesis enzymes including Dhcr24, Msmo1, Idi1 and Hmgcs1 was prominent. Gas chromatography demonstrated a massive loss of crucial cholesterol precursor metabolites. Overall, the ATXN2 protein aggregation process affects diverse subcellular compartments, in particular stress granules, endoplasmic reticulum and receptor tyrosine kinase signaling. These findings identify new targets and potential biomarkers for neuroprotective therapies.

Gain of function (GOF) mutations in the CTNNB1 gene are one of the most frequent genetic events in hepatocellular carcinoma (HCC). T-box transcription factor 3 (TBX3) is a liver-specific target of the Wnt/β-catenin pathway and thought to be an oncogene mediating activated β-catenin-driven HCC formation.

We evaluated the expression pattern of TBX3 in human HCC specimens. Tbx3 was conditionally knocked out in murine HCC models by hydrodynamic tail vein injection of Cre together with c-Met and ΔN90-β-catenin (c-Met/β-catenin) in Tbx3

mice. TBX3 was overexpressed in human HCC cell lines to investigate the functions of TBX3 invitro.

A bimodal expression pattern of TBX3 in human HCC samples was detected high expression of TBX3 in GOF CTNNB1 HCC and downregulation of TBX3 in non-CTNNB1 mutant tumors. High expression of TBX3 was associated with increased differentiation and decreased expression signatures of tumor growth. Using Tbx3

mice, we found that ablation of Tbx3 significantly accelerates c-Met/β-catech increase TBX3 expression and/or activities may be effective for HCC treatment.

TBX3 is a liver-specific target of the Wnt/β-catenin pathway and thought to be an oncogene in promoting liver cancer development. Herein, we demonstrate that TBX3 is in fact a tumor suppressor gene that restricts liver tumor growth. Strategies which increase TBX3 expression and/or activities may be effective for HCC treatment.The term non-alcoholic fatty liver disease (NAFLD) was originally coined to describe hepatic fat deposition as part of the metabolic syndrome. However, a variety of rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders and drugs may underlie, mimic, or aggravate NAFLD. In contrast to primary NAFLD, therapeutic interventions are available for many secondary causes of NAFLD. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of patients with fatty liver disease, and treatment of the underlying disease should be started to halt disease progression. Common genetic variants in several genes involved in lipid handling and metabolism modulate the risk of progression from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma development in NAFLD, alcohol-related liver disease and viral hepatitis. Hence, we speculate that genotyping of common risk variants for liver disease progression may be equally useful to gauge the likelihood of developing advanced liver disease in patients with secondary fatty liver disease.Cadmium (Cd) was a serious heavy metal pollutant. Cd exposure will cause damage to reproductive organs. It was largely unknown whether Cd exposure caused inflammation and apoptosis in epididymis. In this study, we established models of Cd exposure in swine, and the apoptotic level of epididymis was detected by in situ TUNEL fluorescence staining assay, the results showed that Cd exposure significantly increased TUNEL-apoptosis index. Furthermore, the results of qRT-PCR and Western blot showed that Cd activated the proto-oncogenic serine/threonine kinase-1 (RAF1)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signal pathway (RAF1/MEK/ERK) and led to the subsequent up-regulation of the nuclear factor-κB (NF-κB), tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), caused inflammation in epididymis. NF-κB inflammation pathway also mediated the tumor protein P53 (P53) and indirectly activated the Cytochrome c (Cytc), B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X protein (Bax), Caspase 3, Caspase 9. In summary, we believed that the RAF1/MEK/ERK pathway came into play in the apoptosis of epididymal tissues exposed to Cd by activating the NF-κB Inflammation pathway, followed by activation of the mitochondrial apoptotic pathway. This study provides more abundant data for exploring the reproductive toxicity of Cd.