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Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors.The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures.Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern.This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

Endoscopic lumbar discectomy has been an alternative for treating lumbar disc herniation. Evidence-based study for the benefit zone of full-endoscopic lumbar discectomy (FELD) is necessary. The study compared the complication risks between the FELD and open discectomy or microdiscectomy.The literature search was from 4 online databases for randomized controlled trials (RCTs) and cohort studies. The meta-analysis of different study designs was conducted separately. Complication rates were considered primary outcomes, and the recurrence and revision rates were considered secondary outcomes.Six RCTs and thirteen cohort studies met the eligibility criteria. The meta-analysis was conducted separately. From the pooled RCT meta-analysis, the overall complication rates of FELD and open discectomy/microdiscectomy were 5.5% and 10.4%, respectively. The moderate-quality evidence suggested that FELD had a lower risk of overall complications (risk ratio [RR] = 0.55, 95% confidence interval [CI] = 0.31-0.98). There was no significant difference in specific complications and recurrence. The analysis of cohort studies revealed no significant difference in overall complications, but there was significant heterogeneity in the results. The risk of dural injury was significantly lower for FELD (RR = 0.46, 95% CI = 0.22-0.96). The pooled meta-analysis from cohort studies suggested a higher risk of transient dysesthesia (RR = 3.70, 95% CI = 1.54-8.89), residual fragment (RR = 5.29, 95% CI = 2.67-10.45), and revision surgeries (RR = 1.53, 95% CI = 1.12-2.08) for FELD.The current evidence showed a lower risk of overall complications for FELD. The quality of evidence was moderate to low, and the risk of bias from the primary literature should be concerned.

(1) Background: Temozolomide (TMZ), an oral alkylating agent, is used to treat malignant gliomas and other difficult-to-treat tumors. TMZ can enter the cerebrospinal fluid p.o. (per os) and does not need hepatic metabolism for activation of its use as a standard chemotherapeutic regimen after surgical resection of malignant glioma of the brain. However, the prognosis remains poor for most patients, and the survival rate is still unsatisfactory. Gallic acid (Ga) is a secondary metabolite existent in numerous plants. Ga shows various bioactivities, including antioxidant, anti-inflammatory, anticancer and antimicrobial effects. In this study, the latent enhanced anti-cancer efficacy of Ga in TMZ-treated U87MG cells (a human glioma line) was evaluated. (2) Methods: The U87MG cell line was cultured for 24 h. The cells were incubated with Ga alone, TMZ alone, or their combination for various time points. Cell viability and the drug combination index were evaluated by an XTT-based analysis and isobologram analysis, respectively. DNA destruction and intracellular reactive oxygen species (ROS) generation were analyzed by flow cytometer. The expression of various proteins was assessed via Western blotting. (3) Results: Compared with the action of TMZ alone or Ga alone, TMZ/Ga combination augmented the inhibition of cellular viability and apoptotic level in the U87MG glioma cell line. This enhanced anti-cancer effect correlated with the decreased expression of Bcl-2 and p-Akt, and corresponded with the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. In addition, Ga suppressed the TMZ-promoted ROS generation. (4) Conclusions: Ga can augment the anti-cancer effect of TMZ via the repression of Bcl-2 expression and Akt activation and the enhancement of the p38 MAPK pathway. Our results offer a novel probable approach for the medical treatment of malignant glioma.

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX, notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy, in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

Background Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief. Method This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging. Result The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness. Conclusion This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief.

Long term success of metallic fusion cages depends on mechanobiological processes through the bone incorporation and rich osseointegration. An optimal configuration of porous titanium-aluminum-vanadium (Ti 6Al 4V) implant fabricated via the additive manufacturing was evaluated in complimentary structure examinations to investigate the growth of autologous osseous at multi-length scales. X-ray microcomputed tomography (micro-CT) and transmission X-ray microscopy (TXM) using newly-built analysis method indicate the porous Ti 6Al 4V is much better for bone ingrowth compared to commercially non-porous titanium (Ti) and porous tantalum (Ta) implants at the ultramicrostructural level. The evolution of bone formation and remodeling acquired by nano X-ray Laue diffraction mapping exhibits the isotropic orientation and low crystallinity of all newly formed bone whereas mature bone in Ti 6Al 4V discloses the preferential alignment and higher crystallinity volumes of constituent hydroxyapatite (HA) crystallites. The high degree in mineral crystallinity of the fully mature bone suggests additive manufactured Ti 6Al 4V pores enhance the collagen-regulated mineralization.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured −34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC), the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

Background Neurovascular compression (NVC) in patients with trigeminal neuralgia (TN) can be a factor of treatment outcome, especially in microvascular decompression and stereotactic radiosurgery. No such effect has been reported in percutaneous radiofrequency rhizotomy (RF). This study aims to investigate whether NVC affects the efficacy of RF in patients with TN. Methods We retrospectively reviewed patients with TN who received RF in our institution. Pretreatment magnetic resonance imaging was performed in every patient, and the presence of NVC was reviewed independently by two physicians. The patients were followed up at least for a year after the treatment. Pain severity was assessed with a numeric rating scale (NRS). Results Sixty-two patients were included in the study. All of the patients had single-sided lesions, and 35 patients had NVC. There were no significant differences between these two groups of patients in terms of gender distribution, age, and pretreatment pain severity. Comparable pain severity improvement was found at 1-year follow-up between these two groups (NRS 7.93 ± 0.492 without compression vs 7.57 ± 0.451 with compression, P = 0.600). No significant difference in posttreatment pain severity at 1 year was found between these two patient groups (NRS 1.37 ± 0.466 without compression vs 1.66 ± 0.458 with compression, P = 0.667). Conclusions For patients with TN treated by RF, the presence or absence of NVC is not likely to affect the 1-year pain control rate.

Spreading depolarization (SD) represents a neurological process characterized by a massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible for neuronal transmembrane currents of SD. However, the explicit role of NMDARs remains ambiguous. This is in part due to the limitation of traditional pharmacological approaches in resolving the contribution of NMDARs in different intercellular and intracellular processes of SD. Here, we applied single-cell blockade and genetic deletion methods to remove functional NMDARs from individual hippocampal CA1 neurons in order to examine the role of NMDARs in the depolarization mechanism without affecting the propagation of SD. We analyzed neuronal membrane potential changes to demonstrate that NMDARs are not required for initiating the depolarization. Consistently, neuronal input resistance (RN) revealed a sharp decline at the start of SD, which was unaffected by blocking NMDARs. Instead, the recovery of both membrane potential and RN during the late phase of SD was facilitated by inhibition of NMDARs, indicating that NMDARs are responsible for sustaining the depolarization. Our results strongly indicate that NMDAR activation is not a determinant of the initiation of depolarization but is important for sustaining transmembrane ion fluxes during SD.

Background: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. Methods: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40%, 60%, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed.Results: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60% and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. Conclusion: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.

Intracranial schwannomas account for 8% of all primary brain tumours [1] and are derived from Schwann cells in the peripheral...

Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.

Microplastics (MPs) pollution has become a serious environmental issue worldwide, but its potential effects on health remain unknown. The administration of polystyrene MPs (PS-MPs) to mice for eight weeks impaired learning and memory behavior. PS-MPs were detected in the brain especially in the hippocampus of these mice. Concurrently, the hippocampus had decreased levels of immediate-early genes, aberrantly enhanced synaptic glutamate AMPA receptors, and elevated neuroinflammation, all of which are critical for synaptic plasticity and memory. Interestingly, ablation of the vagus nerve, a modulator of the gut-brain axis, improved the memory function of PS-MPs mice. These results indicate that exposure to PS-MPs in mice alters the expression of neuronal activity-dependent genes and synaptic proteins, and increases neuroinflammation in the hippocampus, subsequently causing behavioral changes through the vagus nerve-dependent pathway. Our findings shed light on the adverse impacts of PS-MPs on the brain and hippocampal learning and memory.

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. 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. 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. 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.

Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial inflammation in rheumatoid arthritis (RA). Some evidence indicates that particulate matter (PM) in air pollution could contribute to the progression of RA. However, more research is needed to clarify this relationship. Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are implicated in various inflammatory diseases. Resveratrol, a polyphenol found mainly in grapes and red wine, has antioxidant and anti-inflammatory activities. In the present study, we demonstrated that resveratrol reduced PM-induced COX-2/PGE2 expression in human FLSs, and attenuated PM-enhanced NADPH oxidase activity and ROS generation. In addition, PM induced Akt, ERK1/2, or p38 MAPK activation, which was inhibited by resveratrol. Finally, we demonstrated that PM enhanced NF-κB p65 phosphorylation and the NF-κB promoter activity, which were reduced by pretreatment with a ROS inhibitor or resveratrol. Thus, we concluded that resveratrol functions as a suppressor of PM-induced inflammatory signaling pathways by inhibiting COX-2/PGE2 expression.

Cerebral infarction is a common cause of disability. Malignant large infarction (MLI) is a catastrophic event, and there is no effective medical treatment. This study aimed to assess the outcome predictors of MLI and to analyze the impact of decompressive craniectomy (DC) on the functional outcome of survivors.This study comprised 213 MLI cases. Outcome was evaluated with modified Rankin Scale (mRS) at 1-year follow-up, and various parameters were tested for MLI outcome predictors. The impact of DC on functional outcome was examined after being further stratified into good survival (mRS score = 0, 1, 2, 3), poor survival (mRS score = 4, 5), and mortality (mRS score = 6) groups.Standard medical treatment only was used in 106 cases, and both medical treatment and DC were used in 107 cases. With multiple logistic regression analysis, age, motor response at deterioration/operation, and DC were identified as independent outcome predictors of MLI (P = 0.027, P0.001, P0.001). Compared with the sole standard medical treatment, additional DC resulted in a better outcome (odds ratio [OR] =19.95; 95% confidence interval [CI], 7.61-52.27; P0.001). Further analysis of functional outcome revealed that DC significantly increased the chance of good survival as opposed to poor survival (OR = 20.04; 95% CI, 6.05-66.32; P0.001) and death (OR = 43.72; 95% CI, 13.21-144.72; P0.001).In this study, DC performed on a young patient with motor response of localizing pain or better was linked with a better outcome. DC not only reduced mortality and increased the number of good survivals but also, most importantly, decreased the number of poor functional outcome survivals.

Summary Background/introduction The predominant cause of typical trigeminal neuralgia (TN) is the compression of the trigeminal nerve by an artery at the root entry zone. Arachnoid adhesion or venous contact with the trigeminal nerve has been infrequently identified during microvascular decompression (MVD). Purpose/aim This study aimed to elucidate the role of different types of vascular compression and arachnoid thickening in MVD for treating typical TN. Methods Patients with typical TN refractory to treatment with medications and scheduled for MVD were enrolled. Arterial compression of the trigeminal nerve was relieved using Teflon, whereas adhesiolysis was performed for arachnoid thickening. For a conflicting vein, a nearby artery was searched instead of coagulation and division of the vein. The postoperative outcomes were rated as excellent (complete resolution of pain), good (> 75% reduction in pain), poor (25–75% reduction in pain), and failure ( Results Between June 2000 and April 2015, a total of 27 patients undergoing MVD were enrolled in this study; one patient was lost to follow-up. The mean age of the remaining 26 patients was 57.4 ± 11.4 years (38–79 years), whereas the average duration of postoperative symptoms was 5.9 years (0.5–30 years). Significant differences in postoperative outcomes were noted for the arachnoid and artery compared with those for the vein as the conflicting structure, as evidenced by excellent and good outcomes ( p = 0.005). Two operative complications were observed: cerebrospinal fluid rhinorrhea and deep wound infection. No mortality or cerebellar hemorrhage was observed during the follow-up period. Conclusion The tightness of the junction between the offending artery and the trigeminal nerve may represent a major factor affecting different postoperative outcomes following MVD. An offending artery may be attached to the arachnoid thickening, resulting in a neurovascular compressive effect, whereas the role of venous contact as a cause of TN remains debatable.

Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved.Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E2 (PGE2) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry.Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-κB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice.Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future.

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 ± 41.0 vs 42.0 ± 37.2 months, P < .001). In patients between 18 and 40 years old, the difference is most significant (OS: 70.5 ± 48.7 vs 55.1 ± 46.0, 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.

The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry, the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood&ndash, brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs), mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.

Perfusion-diffusion mismatch in magnetic resonance imaging (MRI) represents the non-core hypoperfused area in acute ischemic stroke. The mismatch has been used to predict clinical response after thrombolysis in acute ischemic stroke, but its role for predicting early neurological deterioration (END) in acute ischemic stroke without thrombolysis has not been clarified yet. In this study, we prospectively recruited 54 patients with acute non-lacunar ischemic stroke in anterior circulation without thrombolysis. All patients received the first perfusion MRI within 24 hours from stroke onset. Target mismatch profile was defined as a perfusion-diffusion mismatch ratio ≥ 1.2. END was defined as an increase of ≥ 4 points in the National Institute of Health Stroke Scale (NIHSS) score within 72 hours. There were 13 (24.1%) patients developing END, which was associated with larger infarct growth (p = 0.002), worse modified Rankin Scale (p = 0.001) and higher mortality rate at 3 months (p = 0.025). Target mismatch profiles measured by T(max) ≥ 4, 5 and 6 seconds were independent predictors for END after correcting initial NIHSS score. Among the 3 T(max) thresholds, target mismatch measured by T(max) ≥ 6 seconds had the highest odd's ratio in predicting END (p < 0.01, odd's ratio = 17), with an 80% sensitivity and a 79.5% specificity. In conclusion, perfusion-diffusion mismatch could identify the patients at high risk of early clinical worsening in acute ischemic stroke without thrombolysis.

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.

Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) has been an effective treatment modality for medically refractory trigeminal neuralgia. Our group has established a protocol for this procedure that includes intraoperative computed tomography (iCT) navigation. The depth of the puncture needle in our protocol was based on cadaveric studies, and anatomical localization was mainly by electric stimulation test. The limitation of the invisibility of the trigeminal cistern on CT imaging and bias from the patient’s subjective expression during neurophysiologic stimulation might affect the accuracy of the needle tip and the treatment effect.This study aimed to evaluate the feasibility and preliminary results of the application of magnetic resonance imaging (MRI) and iCT fusion imaging in RF-TR. The study included 13 patients who received RF-TR with iCT navigation and with recurrence within 3 years. Repeated RF-TR was performed with real-time guidance by MRI and iCT fusion imaging. A pain-free or partial satisfactory response was reported with 12 patients (92 %). There was a statistically significant difference in the depth of the needle tip before and after application of MRI and iCT fusion imaging. This preliminary study demonstrated that the application of MRI and iCT fusion could help with anatomical localization of the trigeminal cistern intraoperatively. The improvement in neuronavigation provides a choice in the treatment of recurrent or persistent trigeminal neuralgia after previous intervention. Long-term follow-up of the result is necessary to evaluate the benefit in terms of durability of therapeutic efficacy.

Summary A 56-year-old female patient experienced mild back pain, which radiated to her legs, as well as intermittent claudication for 5 years. The symptoms became more pronounced on sitting and walking, and conservative therapy was ineffective in relieving pain. Preoperative whole-spine X-ray scans revealed degenerative lumbar kyphoscoliosis. Asymmetrical pedicle subtraction osteotomy was performed and a convex-sided posterolateral wedge osteotomy was applied to correct the scoliosis and restore sagittal balance. Pre- and postoperative sagittal balance was measured using a C7 plumb line for both scans, and the difference was calculated. Lumbar scoliosis was measured using the Cobb angle. The degree of correction required to restore sagittal alignment was 25°, which was determined on the basis of the full-balance-integrated technique. The operative time and blood loss were 365 minutes and 1620 mL, respectively. Postoperatively, the lumbar scoliosis decreased from 10.2° to 2.0°, and the sagittal vertical axis decreased from 7.6 cm to 3.3 cm. The visual analog scale and Oswestry disability index scores indicated that the patient was relieved of the symptoms after the surgery. No complications were observed during the follow-up period.

Summary A 54-year-old male patient underwent an L3–4 and L4–5 microdiscectomy. Two days after this operation, he suffered from acute abdominal pain accompanied by nausea and vomiting. A plain upright abdominal radiograph demonstrated multiple dilated small bowel loops with air-fluid levels. Abdominal computed tomography demonstrated diffuse dilatation of the small bowel loops with collapsed colon lumen. Laparoscopic laparotomy was performed after 4 days of conservative therapy without improvement. A 2–3 cm transmesenteric hernia, an uncommon type of internal hernia, and a short segment of entrapped jejunum were observed 40 cm from the ileocecal junction. The entrapped jejunum was viable and removed from the mesenteric defect without resection, and the defect was repaired; the patient recovered after laparoscopic repair. Small bowel obstruction caused by a congenital defect in the intestinal mesentery following microscopic discectomy has never been reported.

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.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.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.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.

Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD. Moreover, we systematically evaluated the effects of multiple anti-epileptic drugs (AEDs) on SD-induced epileptiform activity. Among the drugs that are known to inhibit voltage-gated sodium channels, carbamazepine, phenytoin, valproate, lamotrigine, and zonisamide reduced the frequency of PDSs and the overriding firing bursts in 20–25 min after the induction of SD. The GABA uptake inhibitor tiagabine exhibited moderate effects and partially limited the incidence of PDSs after SD. AEDs including gabapentin, levetiracetam, ethosuximide, felbamate, and vigabatrin, had no significant effect on SD-induced epileptic activity. Taken together, these results demonstrate the effects of AEDs on SD and the related epileptiform activity at the cellular level.