Trunk Movement and Sequential Trunk Muscle Activation During Oscillation Exercises Using Flexible Poles.

OBJECTIVES: Oscillatory exercises using flexible poles, such as the Flexi-bar, were recommended as rehabilitation programs to increase trunk muscles strength; however, the strategy to enhance the training effects is under investigations. The aim of this study was to characterize the trunk movements and muscle activation patterns when performing an oscillation exercise with flexible poles in different weights. METHODS: Twelve healthy male participants performed oscillation exercises with flexible poles of different weights. The center of mass, as well as surface electromyography for 10 trunk muscles were assessed while participants performed oscillation exercises. RESULTS: The participants' trunks showed rhythmic anterior-posterior movement during oscillation exercises using flexible poles. The center-of-mass movement distances were 20.32 (6.73) mm, 25.33 (5.31) mm, 32.40 (9.94) mm, and 37.28 (21.59) mm for the Flexi-bar, light pole, medium pole, and heavy pole, respectively. Erector spinae, internal obliques, multifidus, and external obliques revealed significant activation levels during oscillation exercises. The participants who could perform steady and smooth oscillation with heavy pole for 30 seconds revealed phasic sequential muscle activation. CONCLUSION: The present study suggested that oscillation exercises with flexible poles were associated with a concomitant trunk movement in anterior-posterior direction and an effective activation of trunk muscles.

Decreasing recurrence and increasing survival rates in patients of ethmoid or sphenoid intestinal-type adenocarcinomas: Systematic review and meta-analysis with 1126 cases.

BACKGROUND: Ethmoid or sphenoid intestinal-type adenocarcinomas (ITACs) form a distinct subtype of sinonasal adenocarcinomas that occur less than 1 case/100,000/yr. They have obvious exposure relationship to hardwood or leather dusts, infrequent metastasis, but a relatively high local-recurrence rate. They locate at sinuses close to vital structures listed as high-risk areas in surgeries. Even in expert hands, a craniofacial resection is associated with non-negligible mortality and morbidity. Management of these tumors, first or recurrent, needs to weigh these consequences versus the survival, regional-recurrence, and distant-recurrence rates. Due to the rareness of ethmoid or sphenoid ITACs, accurate overall survival and local- or regional-recurrence rates across diverse treatments are unclear. The aim of this study is to report the overall statistics of this cancer and the relationship between enrollment year versus age, recurrence, and survival. METHODS: Systemic review and meta-analysis with 1126 cases across various treatments in the literature. RESULTS: Here, we show that patients of ethmoid or sphenoid ITACs had overall local-, regional-, and distant-recurrence rates of 32.2%, 2.2%, and 10.3%, respectively, with a 5-year overall survival rate of 66.2%. The results present a significant correlation between age, local-recurrent rate, or overall survival rate versus enrollment year. CONCLUSION: This suggests that recent patients of ethmoid or sphenoid ITACs may present at an older mean age, have a lower local-recurrence rate, and have a better 5-year survival rate than before. There was a shifting trend of treating ethmoid ITACs from external approach to endoscopic resection. Clinicians may want to weigh mortality and morbidity rates of external surgeries and these data to share or decide a solution.

Bone Morphogenetic Protein 7 Effect on Human Glioblastoma Cell Transmigration and Migration.

Glioblastoma, World Health Organization-grade IV, is the most malignant glioma type and it is still an incurable tumor due to the high level of heterogeneity and uncontrolled metastatic nature. In addition to the tumorigenicity-suppressing activity, bone morphogenetic protein 7 (BMP7) has recently been found for its invasion-promoting role in glioblastoma. However, the detailed and precise mechanism in this issue should have more elucidation. Thus, in this study, we determined the BMP7 effect on glioblastoma transmigration and migration regulations and the underlying mechanisms. Human LN18/LN229 glioblastoma cells were used in this study. Our results showed a higher BMP7/pSmad5 level in human malignant glioma tissues compared to healthy brain tissues. In addition, it was demonstrated that endogenous and exogenous BMP7 stimulation could increase the transmigration and migration capabilities of human LN18/LN229 glioblastoma cells. Moreover, this event is regulated by Smad5 and p75 neurotrophin receptor (p75NTR) signaling. Furthermore, unexpected data are that the Smad1 gene knockdown could lead to the cell death of human LN18 glioblastoma cells. Overall, the present study finds that the invasion-promoting activity of BMP7 might be an autocrine stimulation of glioblastoma and this effect could be regulated by Smad5-p75NTR signaling.

γ-secretase inhibitors, DAPT and RO4929097, promote the migration of Human Glioma Cells via Smad5-downregulated E-cadherin Expression.

Malignant gliomas are a type of central nervous system cancer with extremely high mortality rates in humans. γ-secretase has been becoming a potential target for cancer therapy, including glioma, because of the involvement of its enzymatic activity in regulating the proliferation and metastasis of cancer cells. In this study, we attempted to determine whether γ-secretase activity regulates E-cadherin to affect glioma cell migration. The human glioma cell lines, including LN18 and LN229, and the γ-secretase inhibitors, including N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) and RO4929097, were used in this study. It was shown that γ-secretase activity inhibition by DAPT and RO4929097 could promote LN18 and LN229 glioma cell migration via downregulating E-cadherin mRNA and protein expressions, but not via affecting E-cadherin protein processing. In addition, γ-secretase activity inhibition was regulated by bone morphogenetic proteins-independent Smad5 activation in glioma cells. Moreover, endogenous Smad1 in glioma cells was found to play an important role in regulating E-cadherin expression and subsequent cell migration but did not affect DAPT-stimulated effects. These results help further elucidate the molecular mechanisms of γ-secretase activity regulation involved in controlling glioma cell malignancy. Information about a potential role for Smad1/5 activity upregulation and subsequent E-cadherin downregulation during inhibition of γ-secretase activity in the development of gliomas is therefore relevant for future research.

The risk of cardiac mortality in patients with status epilepticus: A 10-year study using data from the Centers for Disease Control and Prevention (CDC).

OBJECTIVE: To explore whether status epilepticus affected cardiac mortality. METHODS: We used the 2008-2017 multicause mortality data of the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiological Research. The status epilepticus group included patients whose death certificates mentioned status epilepticus as contributing to death. The non-status epilepticus group included patients whose death certificates mentioned epilepsy, other and unspecified convulsions, febrile convulsions, or post-traumatic seizures, as contributing to death. The outcomes for evaluation were death certificates that indicated that myocardial infarction, arrhythmia, heart failure, or cardiac arrest (CA) was the immediate cause of death. The numbers of deaths and population sizes by categorical demographics were recorded and subjected to multiple logistic regression analysis. RESULTS: Among the 14,487 death certificates in status epilepticus group; 3080 patients (21.3%) died of CA. When clinical records were compared to autopsy data, females were at a lower risk of myocardial infarction (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.51-0.61). Patients aged 45-65 years and older than 65 years were at a higher risk of developing all four cardiac complications. Status epilepticus was associated with higher risks of arrhythmia (OR: 1.55, 95% CI: 1.11-2.15) and CA (OR: 4.34, 95% CI: 3.49-5.39) but a reduced risk of myocardial infarction (OR: 0.42, 95% CI: 0.30-0.57) as the cause of immediate death. CONCLUSION: The frequency of CA in patients with status epilepticus increased between 2008 and 2017. Male and elderly patients were at a higher risk of cardiogenic mortality.

Risk of Cardiac Morbidities and Sudden Death in Patients With Epilepsy and No History of Cardiac Disease: A Population-Based Nationwide Study.

OBJECTIVE: To investigate the impact of epilepsy on secondary cardiac morbidities and sudden death in patients with epilepsy. PATIENTS AND METHODS: The present cohort study evaluated data obtained from a subset of adult patients listed in the Taiwan National Health Insurance Research Database with an International Classification of Diseases, Ninth Revision, diagnosis code of epilepsy from January 1, 1997, to December 31, 2013; the date of epilepsy diagnosis or antiepilepsy drug prescription was defined as the index date. Patients with cardiac disease prior to the index date were excluded, and the remaining patients were categorized into epilepsy and nonepilepsy groups. Frequency matching was performed to balance the covariates across groups for the comparison of outcomes. The development of myocardial infarction (MI) and arrhythmia and/or the occurrence of sudden death were the outcomes for evaluation. A Cox proportional hazards regression model and competing risk analysis were used to compare the risks of cardiac morbidities and sudden death between groups. RESULTS: The final analysis included a total of 5411 patients with epilepsy and 21,644 participants without epilepsy. The epilepsy group had significantly higher risks for development of MI (hazard ratio [HR], 1.71; 95% CI, 1.62 to 1.81; P<.001) and arrhythmia (HR, 2.11; 95% CI, 1.97 to 2.25; P<.001) and the occurrence of sudden death (HR, 1.83; 95% CI, 1.53 to 2.18; P<.001) compared with the nonepilepsy group. CONCLUSION: Our results indicate that the risks for development of MI and arrhythmia and the occurrence of sudden death were higher in patients with epilepsy. These findings support the hypothesis that epilepsy may lead to secondary cardiac dysfunction and increases the risk of sudden death.

Effect of valproic acid on overall survival in patients with high-grade gliomas undergoing temozolomide: A nationwide population-based cohort study in Taiwan.

High-grade gliomas (HGGs) are a rapidly progressive and highly recurrent group of primary brain tumors. Despite aggressive surgical resection with chemoradiotherapy, prognoses remained poor. Valproic acid (VPA), a histone deacetylase inhibitor has shown the potential to inhibit glioma cell growth in vitro through several diverse mechanisms. However clinical studies regarding the effect of VPA on HGGs are limited. This study aimed to investigate whether using VPA in patients with HGGs under temozolomide (TMZ) would lead to a better overall survival (OS).We used the Taiwan National Health Insurance Research database to conduct this population-based cohort study. A total of 2379 patients with HGGs under TMZ treatment were included and were further classified into VPA (n = 1212, VPA ≥ 84 defined daily dose [DDD]) and non-VPA (n = 1167, VPA < 84 DDD) groups. Each patient was followed from 1998 to 2013 or until death. A Cox proportional hazard regression was performed to evaluate the effect of VPA and OS.The VPA group had a longer mean OS time compared with the non-VPA group (OS: 50.3 ±â€Š41.0 vs 42.0 ±â€Š37.2 months, P < .001). In patients between 18 and 40 years old, the difference is most significant (OS: 70.5 ±â€Š48.7 vs 55.1 ±â€Š46.0, P = .001). The adjusted hazard ratio is 0.81 (95% confidence interval, 0.72-0.91) for the VPA group relative to the non-VPA group.VPA at over 84 DDD improved OS in HGGs TMZ treatment.

Intracranial aneurysms formation after radiotherapy for head and neck cancer: a 10-year nationwide follow-up study.

BACKGROUND: Intracranial aneurysms after radiotherapy (RT) have previously been reported. However, the majority of studies were case reports. Therefore, we performed a nationwide study to explore the risk of radiation-induced intracranial aneurysms. METHODS: This study included patients diagnosed with head and neck cancer (ICD9: 140-149, 161). Intracranial aneurysms formation was identified using the following ICD9 codes: nonruptured cerebral aneurysm (ICD9:4373), aneurysm clipping (ICD9:3951). Patients who did not receive curative treatment and those with intracranial aneurysms before the diagnosis of head and neck cancer were excluded. RESULTS: In total, 70,691 patients were included in the final analysis; they were categorized into the following three groups: nasopharyngeal carcinoma (NPC) with RT, non-NPC with RT, and non-NPC without RT. Patients in the NPC with RT group had the highest risk of developing intracranial aneurysms (hazard ratio (HR) 2.57; P <  0.001). In addition, hypertension was also a risk factor of developing intracranial aneurysms (HR 2.14; P <  0.01). The mean time interval from cancer diagnosis to intracranial aneurysm formation in the NPC with RT group was 4.3 ± 3.1 years. CONCLUSIONS: Compared with the non-NPC with RT and the non-NPC without RT groups, patients with NPC who received RT had a higher risk of developing intracranial aneurysms.

Evaluation of Cardiac Complications Following Hemorrhagic Stroke Using 5-Year Centers for Disease Control and Prevention (CDC) Database.

Literature regarding cardiac deaths in hemorrhagic stroke patients is few. The aim of this study was to investigate the incidence and risk factors of cardiac death in hemorrhagic stroke patients. We used the multiple causes of death database from the Centers for Disease Control and Prevention Wide-ranging Online Data of the United States. We identified death certificates from 2006 to 2010 with hemorrhagic stroke (International Classification of Disease, Tenth Revision (ICD-10) code I60-62), or ischemic stroke (ICD-10 code I63), and evaluated the frequency and risk factors of reporting MI (ICD-10 code I20-25) or arrhythmias (ICD-10 code I44-45, I47-49) as the main cause of death in these populations. Over the five-year period, 224,359 death certificates that mentioned hemorrhagic stroke were identified, and the cause of death was MI in 8.95% and arrhythmia in 7.28% patients. With autopsy confirmation, the incidences of MI and arrhythmias in the hemorrhagic stroke group were still lower than the ischemic group. The odds ratio of reporting arrhythmias as a cause of death in hospitalized population was higher. A substantial percentage of hemorrhagic stroke patients had cardiac death. Greater efforts are needed to closely monitor high-risk groups such as females and the elderly.

Cell Subpopulations Overexpressing p75NTR Have Tumor-initiating Properties in the C6 Glioma Cell Line.

BACKGROUND/AIM: Glioma is the most common and lethal primary brain tumor. Even with the development of multidisciplinary treatment approaches, results are disappointing because of the unavoidable tumor recurrence, which may be caused by the existence of tumor-initiating cells. The p75 neurotrophin receptor (p75NTR), which belongs to the tumor necrosis factor receptor superfamily, is not only involved in various cellular functions but also related to tumor growth. This study is focused, on the possible role of p75NTR in glioma tumor initiation. MATERIALS AND METHODS: C6 cells with high and low expression of p75NTR were sorted using flow cytometry. The neurosphere characteristics and properties of these two subpopulations were assessed and compared with those of parental cells. Radiation and chemotherapy sensitivity was also analyzed in these cell populations. Finally, in vivo tumorigenicity of cells was tested in a rat model. RESULTS: Cells overexpressing p75NTR (C6p75+++ cells) demonstrated greater ability of neurosphere formation, colony proliferation, and certain stem cell marker overexpression than cells with low p75NTR expression (C6p75+) and parental cells. In addition, following irradiation or temozolomide treatment, more viable C6p75+++ cells remained, and they proliferated into more colonies. In vivo, C6p75+++ cell implantation in Sprague Dawley rats reduced the survival time. CONCLUSION: Cells with p75NTR overexpression demonstrated certain unique characteristics of tumor-initiating cells, such as neurosphere formation, high colony proliferation, and resistance to radio- and chemotherapy. With regard to the heterogeneous composition of glioma cells, p75NTR can be used as an alternative marker to identify a glioma subpopulation with tumor-initiating properties.

Fusion Techniques Are Related to a Lower Risk of Reoperation in Lumbar Disc Herniation: A 5-Year Observation Study of a Nationwide Cohort in Taiwan.

OBJECTIVE: Lumbar disc herniation (LDH) is a common spinal problem, with reoperation rates of 6%-24%. Although different surgical techniques are used for treatment, there is still debate regarding whether fusion techniques can reduce the reoperation rate in patients with LDH. METHODS: This retrospective study used a 5-year nationwide database to analyze reoperation rates in Taiwan. Patient age groups (≥20 and <90 years) treated by index surgery and reoperation for LDH were identified. Four surgical procedures were included in the analysis: discectomy (DC), anterior lumbar fusion with DC (FA + DC), posterior lumbar fusion (FP), and posterior lumbar fusion with DC (FP + DC). RESULTS: There were 1743 index surgeries between 2008 and 2012, with 184 (10.56%) reoperations. Index surgery DC had the highest reoperation rate (n = 121, 20%). The reoperation risk was significantly lower for patients undergoing fusion procedures (FA + DC vs. DC [hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.12-0.47; P < 0.01], FP versus DC [HR, 0.17; 95% C, 0.09-0.33; P <0.01], FP + DC versus DC [HR, 0.31; 95% CI, 0.22-0.44; P < 0.01]). Fusion procedures had significantly higher treatment costs compared with DC (FA + DC vs. FP vs. FP + DC vs. DC: 5851.74 ± 4808.94 vs. 5116.88 ± 3428.97 vs. 4782.16 ± 2902.19 vs. 3846.79 ± 3584.45 U.S. dollars/patient, respectively; P < 0.0001). CONCLUSIONS: Among surgical procedures for LDH, fusion techniques are related to lower reoperation rates compared with discectomy, but at the expense of higher medical costs.

Percutaneous dorsal root ganglion block for treating lumbar compression fracture-related pain.

BACKGROUND: The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. METHODS: We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. RESULTS: Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. CONCLUSIONS: PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

Endocrine dysfunction following traumatic brain injury: a 5-year follow-up nationwide-based study.

Post-traumatic endocrine dysfunction is a complication of traumatic brain injury (TBI). However, there is lack of long-term follow-up and large sample size studies. This study included patients suffering from TBI registered in the Health Insurance Database. Endocrine disorders were identified using the ICD codes: 244 (acquired hypothyroidism), 253 (pituitary dysfunction), 255 (disorders of the adrenal glands), 258 (polyglandular dysfunction), and 259 (other endocrine disorders) with at least three outpatient visits within 1 year or one admission diagnosis. Overall, 156,945 insured subjects were included in the final analysis. The 1- and 5-year incidence rates of post-traumatic endocrinopathies were 0.4% and 2%, respectively. The risks of developing a common endocrinopathy (p < 0.001) or pituitary dysfunction (P < 0.001) were significantly higher in patients with a TBI history. Patients with a skull bone fracture had a higher risk of developing pituitary dysfunction at the 1-year follow up (p value < 0.001). At the 5-year follow up, the association between intracranial hemorrhage and pituitary dysfunction (p value: 0.002) was significant. The risk of developing endocrine dysfunction after TBI increased during the entire 5-year follow-up period. Skull bone fracture and intracranial hemorrhage may be associated with short and long-term post-traumatic pituitary dysfunction, respectively.

Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma.

The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life­threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague­Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma.

Charge collection enhancement by incorporation of gold-silica core-shell nanoparticles into P3HT:PCBM/ZnO nanorod array hybrid solar cells.

In this work, gold-silica core-shell (Au@silica) nanoparticles (NPs) with various silica-shell thicknesses are incorporated into P3HT:PCBM/ZnO nanorod (NR) hybrid solar cells. Enhancement in the short-circuit current density and the efficiency of the hybrid solar cells is attained with the appropriate addition of Au@silica NPs regardless of the silica-shell thickness. Compared to the P3HT:PCBM/ZnO NR hybrid solar cell, a 63% enhancement in the efficiency is achieved by the P3HT:PCBM/Au@silica NP/ZnO NR hybrid solar cell. The finite difference time domain simulations indicate that the strength of the Fano resonance, i.e., the electric field of the quasi-static asymmetric quadrupole, on the surface of Au@silica NPs in the P3HT:PCBM/ZnO NR hybrid significantly decreases with increasing thickness of the silica shell. Raman characterization reveals that the degree of P3HT order increases when Au@silica NPs are incorporated into the P3HT:PCBM/ZnO NR hybrid. The charge separation at the interface between P3HT and PCBM as well as the electron transport in the active layer are retarded by the electric field of the Fano resonance. Nevertheless, the prolongation of the electron lifetime and the reduction of the electron transit time in the P3HT:PCBM/ZnO NR hybrid solar cells, which result in an enhancement of electron collection, are achieved by the addition of Au@silica NPs. This may be attributed to the improvement in the degree of P3HT order and connectivity of PCBM when Au@silica NPs are incorporated into the P3HT:PCBM active layer.

Motor outcome of deep intracerebral haemorrhage in diffusion tensor imaging: comparison of data from different locations along the corticospinal tract.

OBJECTIVES: Although diffusion tensor imaging (DTI) is widely studied to assess the motor outcome after ischaemic stroke, there is paucity of data regarding outcomes of intracerebral haemorrhage (ICH). The aim of this study was to determine the DTI data from different locations along the corticospinal tract (CST) and association to motor outcome. METHODS: We prospectively recruited patients with deep ICH admitted to our hospital from November 2010 to July 2012.Diffusion tensor imaging was performed within 14  days after the onset of ICH. Fractional anisotropy (FA) was measured along the CST at corona radiata, perihaematomal oedema, cerebral peduncle and pons. Corticospinal tract integrity was classified into three types by diffusion tensor tractography (DTT): type A with preserved CST, type B with partially interrupted CST and type C with completely interrupted CST. Motor outcome was assessed by Motricity index (MI) at admission, after 1 and 3  months. RESULTS: Forty-eight patients were enrolled with a mean age of 62  years. The median time interval from onset of ICH to DTI study was 7  days. The patients in type C had significantly worse MI at admission (P < 0.001), after 1  month (P < 0.001) and after 3  months (P < 0.001) as compared to those with type A and type B. Lower rFA at the corona radiata was significantly correlated with poorer motor outcome at admission, after 1  month and after 3  months. DISCUSSION: Clinical motor outcome of ICH within 2  weeks can be identified with a statistically significant decrease in rFA at the corona radiata.

Modulation of p75 neurotrophin receptor under hypoxic conditions induces migration and invasion of C6 glioma cells.

p75 neurotrophin receptor (p75NTR) has been reported to play important roles in various cancer types. However, the exact mechanism of tumorigenesis involving p75NTR is unknown. In this study, we investigated the relationship between the expression of p75NTR in malignant glioma and the impact on tumor cell migration and invasion. p75NTR and hypoxia-inducible factor-1α (HIF-1α) expression was down-regulated by short-hairpin RNA and up-regulated with expression vectors. By immunohistochemical staining and Western blot analysis, we found that p75NTR was expressed in both human and rat malignant gliomas. Knockdown of p75NTR increased the expression of vimentin, vascular endothelial growth factor, Matrix metalloproteinase 9, and TWIST, and enhanced the invasion and migration abilities assessed by transwell assay in the C6 tumor cells. Inverse expressions of p75NTR and HIF-1α were detected in glioma cell lines under hypoxic conditions, while increased HIF-1α significantly downregulated the expression of p75NTR, suggesting a HIF-1α-p75NTR-EMT pathway that may regulate glioma cells invasion and migration. Downregulation of p75NTR increased phosphorylation of Src, focal adhesion kinase (FAK) and paxillin. Knockdown of p75NTR also dysregulated ß-catenin-mediated cell junctions, and up-regulated the expressions of fibronectin and L1CAM in the cell-cell junctions, thus suggesting that p75NTR knockdown contributed to a more aggressive migration phenotype via FAK signaling pathway. Our studies suggested that modulation of p75NTR under hypoxic condition could enhance C6 cells migration and invasion by induction of EMT, and activation of the FAK pathway. The HIF-1α-p75NTR-EMT axis may play a central role in glioma tumorigenesis.

Is preoperative brain midline shift a determinant factor for neurological improvement after cranioplasty?

BACKGROUND/PURPOSE: In patients with traumatic brain injury, the degree of brain midline shift is related to prognosis. In this study, we evaluated the impact of the presence of a preoperative brain midline shift on the Glasgow Coma Scale (GCS) scores and muscle power (MP) improvement after cranioplasty. METHODS: In this 6-year retrospective cohort study, we compared cranioplasty patients from Taiwan with and without a preoperative brain midline shift. We assigned the patients to the following two groups: the midline shift group and the nonmidline shift group. The GCS score and MP contralateral to the lesion site were recorded and analyzed both prior to and 1 year after the operation. RESULTS: We enrolled 56 cranioplasty patients (35 patients with a midline shift and 21 without a midline shift) and analyzed their complete clinical characteristics. There were significant improvements in the GCS (p = 0.0078), arm MP (p = 0.0056), and leg MP (p = 0.0006) scores after cranioplasty. There was also a significant improvement in the GCS score in the brain midline shift group (0.4 ± 0.149 in the brain midline shift group vs. 0.05 ± 0.48 in the nonmidline shift group, p = 0.03). CONCLUSION: For patients who underwent craniectomy, an improvement in neurological function 1 year after cranioplasty was observed. The patients with brain midline shift showed more improvement in consciousness after cranioplasty than those without a brain midline shift. The presence of a preoperative brain midline shift may be an isolated determinant for the prediction of the outcome after cranioplasty.

Mutual effect of rs688 and rs5925 in regulating low-density lipoprotein receptor splicing.

Analysis of the low-density lipoprotein receptor (LDLR) gene based on the rs688 and rs5925 genetic polymorphisms has provided evidence suggesting that haplotypes related to rs688 and rs5925 are associated with ischemic cerebrovascular diseases. Both rs688 and rs5925 have been empirically identified as exon-splicing enhancers in silico, and rs688 has been shown to be a functional polymorphism that modulates LDLR exon 12 splicing efficiency both in vitro and in vivo. The aim of this study was to evaluate whether rs688 and rs5925 and their haplotypes may alter the splicing efficiency of exons 12 and 13 both in vivo and in vitro. When the minigenes were evaluated for splicing efficiency, we found that converting rs688C to the T allele reduced exon 12 splicing efficiency. In parallel, converting rs688T to the C allele increased the efficiency of exon 12 inclusion. The apparent difference in splicing efficiency was 9.36%±2.58% between the C and T alleles. When rs688C existed in the minigene, the major and minor rs5925 alleles were also sufficient to account for the differences in splicing efficiency of LDLR involving exon 13. The apparent splicing efficiency difference was 5.43%±2.87%. Sequential mutations of rs688 and rs5925 were performed to generate four different haplotypes in the LDLR minigene system. The splicing efficiencies for the haplotypes CC, CT, TC, and TT were 79.60%±1.38%, 76.68%±0.85%, 69.02%±1.79%, and 68.54%±1.38%, respectively. The splicing efficiency of the four haplotype groups differed significantly. In vivo analysis of human leukocyte samples was also compatible with in vitro analysis, indicating a mutual effect between rs688 and rs5925 in regulating LDLR splicing efficiency.

Percutaneous dorsal root ganglion lysis with phenol for the treatment of pain associated with thoracic compression fracture.

BACKGROUND: Symptomatic thoracic compression fracture is one of the most common causes of back pain in elderly. Although vertebroplasty is widely utilized in patients when conservative treatment fails, we introduced an alternative percutaneous technique for the treatment of thoracic compression pain. METHODS: This in a retrospective study. The analysis was performed on 28 consecutive patients who underwent undergoing percutaneous dorsal root ganglion lysis with phenol for the treatment of pain associated with thoracic compression fracture. An acceptable treatment outcome was operationally defined as a pain intensity numerical rating scale (NRS) score of 3 or lower or EQ-5D index of 0.672 or higher. The primary outcome was pain relief and acceptable treatment outcome at 1 day, 1 week, 1 month, and 1 year. RESULTS: Of the 28 cases treated with our procedures, the change in mean NRS score between baseline and one day was -2.5 (95 % CI -1.6 ~ -3.4, p < 0.001), between baseline and one week was -4.7 (-4.1 to -5.3, p < 0.001), between baseline and one month was -5.8 (-5.2 to -6.5, p < 0.001), and between baseline and one year was -6.3 (-5.6 to -7.1, p < 0.001). An acceptable treatment outcome was 14 % one day after the procedure, 46 % at one week, 72 % at one month, and 84 % at one year. Complication rate was 3.6 %. CONCLUSIONS: For thoracic compression fracture patients, percutaneous dorsal root ganglion lysis with phenol is an effective, and safe alternative treatment method worth considering. Pain relief is fast and persists for one year.