Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization.

SignificanceSARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus's evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.

Identification and functional characterization of annexin A2 in half-smooth tongue sole (Cynoglossus semilaevis).

Annexin A2 (AnxA2), belonging to the annexin family, plays a crucial role in immune responses. In this study, the cDNA of the AnxA2 gene was identified in half-smooth tongue sole, Cynoglossus semilaevis. The transcript of AnxA2 gene in C. semilaevis (CsAnxA2) showed broad tissue distribution, with the highest expression level observed in the gut. CsAnxA2 expression was significantly up-regulated in the intestine, spleen, and kidney tissues following exposure to Shewanella algae. Immunohistochemical staining revealed that CsAnxA2 was predominantly expressed in epithelial cells and significantly elevated after S. algae challenge. Subcellular localization showed that CsAnxA2 was primarily localized in the cytoplasmic compartment. Moreover, proinflammatory cytokines (IL-6, IL-8 and IL-1ß) exhibited significant upregulation after CsAnxA2 was overexpressed in vivo. One hundred and fifty-eight CsAnxA2-interacting proteins were captured in the intestinal tissue, showing the top two normalized abundance observed for actin beta (ACTB) and protein S100-A10 (p11). Fifty-four high abundance CsAnxA2-interacting proteins (HIPs) were primary enriched in ten pathways, with the top three significantly enriched pathways being Salmonella infection, glycolysis/gluconeogenesis, and peroxisome proliferator-activated receptor (PPAR) signaling pathway. These results provide valuable information for further investigation into the functional mechanism of AnxA2 in C. semilaevis.

A Dielectric MXene-Induced Self-Built Electric Field in Polymer Electrolyte Triggering Fast Lithium-Ion Transport and High-Voltage Cycling Stability.

Quasi-solid polymer electrolyte (QPE) lithium (Li)-metal battery holds significant promise in the application of high-energy-density batteries, yet it suffers from low ionic conductivity and poor oxidation stability. Herein, a novel self-built electric field (SBEF) strategy is proposed to enhance Li+ transportation and accelerate the degradation dynamics of carbon-fluorine bond cleavage in LiTFSI by optimizing the termination of MXene. Among them, the SBEF induced by dielectric Nb4C3F2 MXene effectively constructs highly conductive LiF-enriched SEI and CEI stable interfaces, moreover, enhances the electrochemical performance of the QPE. The related Li-ion transfer mechanism and dual-reinforced stable interface are thoroughly investigated using ab initio molecular dynamics, COMSOL, XPS depth profiling, and ToF-SIMS. This comprehensive approach results in a high conductivity of 1.34 mS cm-1, leading to a small polarization of approximately 25 mV for Li//Li symmetric cell after 6000 h. Furthermore, it enables a prolonged cycle life at a high voltage of up to 4.6 V. Overall, this work not only broadens the application of MXene for QPE but also inspires the great potential of the self-built electric field in QPE-based high-voltage batteries.

RTA dh404 Induces Cell Cycle Arrest, Apoptosis, and Autophagy in Glioblastoma Cells.

RTA dh404 is a novel synthetic oleanolic acid derivative that has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory properties, and exerts therapeutic effects on various cancers. Although CDDO and its derivatives have anticancer effects, the actual anticancer mechanism has not been fully explored. Therefore, in this study, glioblastoma cell lines were exposed to different concentrations of RTA dh404 (0, 2, 4, and 8 µM). Cell viability was evaluated using the PrestoBlue™ reagent assay. The role of RTA dh404 in cell cycle progression, apoptosis, and autophagy was analyzed using flow cytometry and Western blotting. The expression of cell cycle-, apoptosis-, and autophagy-related genes was detected by next-generation sequencing. RTA dh404 reduces GBM8401 and U87MG glioma cell viability. RTA dh404 treated cells had a significant increase in the percentage of apoptotic cells and caspase-3 activity. In addition, the results of the cell cycle analysis showed that RTA dh404 arrested GBM8401 and U87MG glioma cells at the G2/M phase. Autophagy was observed in RTA dh404-treated cells. Subsequently, we found that RTA dh404-induced cell cycle arrest, apoptosis, and autophagy were related to the regulation of associated genes using next-generation sequencing. Our data indicated that RTA dh404 causes G2/M cell cycle arrest and induces apoptosis and autophagy by regulating the expression of cell cycle-, apoptosis-, and autophagy-related genes in human glioblastoma cells, suggesting that RTA dh404 is a potential drug candidate for the treatment of glioblastoma.

Experimental Study on Magnetic Coupling Piezoelectric-Electromagnetic Composite Galloping Energy Harvester.

In order to solve the demand for low-power microcomputers and micro-electro-mechanical system components for continuous energy supply, a magnetic coupling piezoelectric-electromagnetic composite galloping energy harvester (MPEGEH) is proposed. It is composed of a piezoelectric energy harvester (PEH) and an electromagnetic energy harvester (EEH) coupled by magnetic force. The bistable nonlinear magnetic coupling structure improves the output power of the MPEGEH. The advantages and output performance of the MPEGEH are analyzed. The prototype of the energy harvester is made, and the nonlinear output characteristics under different load resistances are analyzed. Through the experiment on the key parameters of the composite energy harvester, it is found that the higher the coupling degree of the two parts of the MPEGEH, the stronger the nonlinear characteristics and the better the output characteristics. The results show that the onset wind velocity and output power of the MPEGEH are better than the classic galloping piezoelectric energy harvester (CGPEH). At the same wind speed, with the increase in the distance d0 between magnets A and B, the output power of both the PEH and the EEH decreases. When d0 is 37 mm, the output power of the EEH is the largest. The distance s0 between magnets B and C has little influence on the output power of the PEH but has a great influence on the EEH. When s0 is 23 mm, the EEH has the best output characteristics. Compared with the CGPEH, the onset wind velocity is reduced by 28%, and the output power is increased by 136% when the wind speed is 11 m/s.

The Risk of Trigeminal Neuralgia Following Osteoporosis.

Background and objectives: Managing people with trigeminal neuralgia (TN) and osteoporosis is challenging due to their debilitating conditions. Currently, the exact association between TN and osteoporosis in patients remains unknown, although there is potential overlapping of pathophysiological mechanisms. In response, we calculated TN risk in patients who have osteoporosis. Materials and Methods: 45,393 patients aged over 50 years diagnosed with osteoporosis were matched with 45,393 non-osteoporosis patients aged over 50 years (1:1 ratio) who were used as the control group, using data from 1996 to 2010 from Taiwan's National Health Insurance Research Database. The cumulative incidences of subsequent TN and the hazard ratio were estimated using Cox proportional hazards modeling and the Kaplan-Meier method, respectively. Results: Among the total sample, 333 patients were diagnosed with TN during the follow-up period: 205 in the osteoporosis cohort and 128 in the control cohort. Through covariate adjustment, the overall TN incidence showed a 1.80-fold increase in the osteoporosis cohort in comparison with the control cohort (0.60 vs. 0.18 per 1000 person-years, respectively). The High Charlson Comorbidity Index, hypertension, and migraines were risk factors of TN. Conclusions: Osteoporosis patients had a higher TN risk than that of the control cohort. Therefore, early recognition of pain and symptoms in osteoporotic people may help to identify possible TN patients who need prompt therapy.

Prevention of Compression Fracture in Osteoporosis Patients under Minimally Invasive Trans-Foraminal Lumbar Interbody Fusion with Assistance of Bone-Mounted Robotic System in Two-Level Degenerative Lumbar Disease.

Background and Objectives: Minimally invasive spine surgery reduces destruction of the paraspinal musculature and improves spinal stability. Nevertheless, screw loosening remains a challenging issue in osteoporosis patients receiving spinal fixation and fusion surgery. Moreover, adjacent vertebral compression fracture is a major complication, particularly in patients with osteoporosis. We assessed long-term imaging results to investigate the outcomes of osteoporosis patients with two-level degenerative spine disease receiving minimally invasive surgery with the assistance of a robotic system. Materials and Methods: We retrospectively analyzed consecutive osteoporosis patients who underwent minimally invasive surgery with the assistance of a robotic system at our institution during 2013-2016. All patients were diagnosed with osteoporosis according to the World Health Organization criteria. All patients were diagnosed with two levels of spinal degenerative disease, including L34, L45, or L5S1. The study endpoints included screw-loosening condition, cage fusion, and vertebral body heights of the adjacent, first fixation segment, and second fixation segments before and after surgery, including the anterior, middle, and posterior third parts of the vertebral body. Differences in vertebral body heights before and after surgery were evaluated using the F-test. Results: Nineteen consecutive osteoporosis patients were analyzed. A lower rate of screw loosening was observed in osteoporosis patients in our study. There were no significant differences between the preoperative and postoperative vertebral body heights, including adjacent and fixation segments. Conclusions: According to our retrospective study, we report that minimally invasive surgery with the assistance of a robotic system provided better screw fixation, a lower rate of screw loosening, and a lesser extent of vertebral compression fracture after spinal fixation and fusion surgery in osteoporosis patients.

Supplementary Motor Area Syndrome after Removal of an Unusual Extensive Parasagittal Meningioma: Analysis of Twelve Reported Cases.

Background and Objectives: Supplementary motor area (SMA) syndrome is a common post-operation complication in intra-axial brain tumors, such as glioma. Direct damage to parenchyma or scarification of the major vessels during an operation are the main causes. However, it is rarely reported as a postoperative complication in extra-axial tumors. Materials and Methods: We reviewed 11 reported cases of supplementary motor area syndrome after removal of extra-axial meningiomas in the English literature from the PubMed database. We also added our case, which presented as an unusual huge meningioma, to analyze the clinical parameters and outcomes of these 12 reported cases. Results: Recovery time of supplementary motor area syndrome in extra-axial tumors could be within 1-7 weeks, shorter than intra-axial tumors (2-9 weeks). Epilepsy and progressive limb weakness are the most common presentations in 50% of cases. Different degrees of postoperative muscle power deterioration were noted in the first 48 h (from 0-4). Lower limbs (66.6%, 8/12) were slightly predominant compared to upper limbs (58.3%, 7/12). Mutism aphasia was also observed in 41.6% (5/12, including our case), and occurred in tumors which were involved in the dominant side; this recovered faster than limb weakness. Discussion and Conclusions: Our work indicated that SMA syndrome could occur in extra-axial brain tumors presenting as mutism aphasia and limb weakness without any direct brain parenchyma damage. In our analysis, we found that recovery time of postoperative motor function deficit could be within 1-7 weeks. Our study also provides a further insight of SMA syndrome in extra-axial brain tumors.

Valproic Acid Reduces Vasospasm through Modulation of Akt Phosphorylation and Attenuates Neuronal Apoptosis in Subarachnoid Hemorrhage Rats.

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating emergent event associated with high mortality and morbidity. Survivors usually experience functional neurological sequelae caused by vasospasm-related delayed ischemia. In this study, male Sprague-Dawley rats were randomly assigned to five groups: sham (non-SAH) group, SAH group, and three groups with SAH treated with different doses of valproic acid (VPA) (10, 20, 40 mg/kg, once-daily, for 7 days). The severity of vasospasm was determined by the ratio of cross-sectional areas to intima-media thickness of the basilar arteries (BA) on the seventh day after SAH. The BA showed decreased expression of phospho-Akt proteins. The dentate gyrus showed increased expression of cleaved caspase-3 and Bax proteins and decreased expression of Bcl-2, phospho-ERK 1/2, phospho-Akt and acetyl-histone H3 proteins. The incidence of SAH-induced vasospasm was significantly lower in the SAH group treated with VPA 40 mg/kg (p < 0.001). Moreover, all groups treated with VPA showed reversal of the above-mentioned protein expression in BA and the dentate gyrus. Treatment with VPA upregulated histone H3 acetylation and conferred anti-vasospastic and neuro-protective effects by enhancing Akt and/or ERK phosphorylation. This study demonstrated that VPA could alleviate delayed cerebral vasospasm induced neuro-apoptosis after SAH.

Integrating thermodynamic and sequence contexts improves protein-RNA binding prediction.

Predicting RNA-binding protein (RBP) specificity is important for understanding gene expression regulation and RNA-mediated enzymatic processes. It is widely believed that RBP binding specificity is determined by both the sequence and structural contexts of RNAs. Existing approaches, including traditional machine learning algorithms and more recently, deep learning models, have been extensively applied to integrate RNA sequence and its predicted or experimental RNA structural probabilities for improving the accuracy of RBP binding prediction. Such models were trained mostly on the large-scale in vitro datasets, such as the RNAcompete dataset. However, in RNAcompete, most synthetic RNAs are unstructured, which makes machine learning methods not effectively extract RBP-binding structural preferences. Furthermore, RNA structure may be variable or multi-modal according to both theoretical and experimental evidence. In this work, we propose ThermoNet, a thermodynamic prediction model by integrating a new sequence-embedding convolutional neural network model over a thermodynamic ensemble of RNA secondary structures. First, the sequence-embedding convolutional neural network generalizes the existing k-mer based methods by jointly learning convolutional filters and k-mer embeddings to represent RNA sequence contexts. Second, the thermodynamic average of deep-learning predictions is able to explore structural variability and improves the prediction, especially for the structured RNAs. Extensive experiments demonstrate that our method significantly outperforms existing approaches, including RCK, DeepBind and several other recent state-of-the-art methods for predictions on both in vitro and in vivo data. The implementation of ThermoNet is available at https://github.com/suyufeng/ThermoNet.

Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-ΔA146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae.

The fusion protein DnaJ-ΔA146Ply could induce cross-protective immunity against pneumococcal infection via mucosal and subcutaneous immunization in mice in the absence of additional adjuvants. DnaJ and Ply are both Toll-like receptor 4 (TLR4) but not TLR2 ligands. However, we found that TLR2-/- mice immunized subcutaneously with DnaJ-ΔA146Ply showed significantly lower survival rates and higher bacterial loads in nasal washes than did wild-type (WT) mice after being challenged with pneumococcal strain D39 or 19F. The gamma interferon (IFN-γ) level in splenocytes decreased in TLR2-/- mice, indicating that Th1 immunity elicited by DnaJ-ΔA146Ply was impaired in these mice. We explored the mechanism of protective immunity conferred by DnaJ-ΔA146Ply and the role of TLR2 in this process. DnaJ-ΔA146Ply effectively promoted dendritic cell (DC) maturation via TLR4 but not the TLR2 signaling pathway. In a DnaJ-ΔA146Ply-treated DC and naive CD4+ T cell coculture system, the deficiency of TLR2 in DCs resulted in a significant decline of IFN-γ production and Th1 subset differentiation. The same effect was observed in adoptive-transfer experiments. In addition, TLR2-/- DCs showed remarkably lower levels of the Th1-polarizing cytokine IL-12p70 than did WT DCs, suggesting that TLR2 was indispensable for DnaJ-ΔA146Ply-induced IL-12 production and Th1 proliferation. Thus, our findings illustrate that dendritic cell expression of TLR2 is essential for optimal Th1 immune response against pneumococci in mice immunized subcutaneously with DnaJ-ΔA146Ply.

Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner.

Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases. Streptococcus pneumoniae endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis of Streptococcus pneumoniae and Staphylococcus aureus by peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time- and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)-NF-κB signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci and Staphylococcus aureus.

A Case of Leptomeningeal Dissemination of Pilocytic Astrocytoma in a Child.

We present the case of a 2-year-old boy with progressive left-sided weakness and a cranial magnetic resonance imaging (MRI) scan showing a lesion with a cystic component in the right thalamus and basal ganglia. The lesion was subtotally resected and diagnosed as a pilocytic astrocytoma by histopathology. Tumor seeding along the surgical tract was seen on MRI 16 days and 10 weeks after surgery. The patient received vincristine and carboplatin, and MRI performed 4 months after chemotherapy revealed no additional or residual lesions. This case illustrated that a World Health Organization grade I astrocytoma could disseminate along the surgical tract.

IL-27 enhances innate immunity of human pulmonary fibroblasts and epithelial cells through upregulation of TLR4 expression.

Lung tissue cells play an active role in the pathogenesis of pulmonary inflammatory diseases by releasing a variety of cytokines and chemokines. However, how lung tissue cells respond to microbial stimuli during pulmonary infections remains unclear. In this study, we found that patients with community-acquired pneumonia displayed increased IL-27 levels in bronchoalveolar lavage fluid and serum. We subsequently examined the immunopathological mechanisms for the activation of primary human lung fibroblasts and bronchial epithelial cells by IL-27. We demonstrated that IL-27 priming enhanced LPS-induced production of IL-6 and IL-8 from lung fibroblasts and bronchial epithelia cells via upregulating Toll-like receptor-4 (TLR4) expression. IL-27 upregulated TLR4 expression in lung fibroblasts through activation of Janus-activated kinase (JAK) and Jun NH2-terminal kinase (JNK) signaling pathways, and inhibition of the JAK pathway could partially decrease IL-27-induced TLR4 expression, while inhibition of JNK pathway could completely suppress IL-27-induced TLR4 expression. Our data suggest that IL-27 modulates innate immunity of lung tissue cells through upregulating TLR4 expression during pulmonary infections.

Traumatic Brain Injury and Substance Related Disorder: A 10-Year Nationwide Cohort Study in Taiwan.

Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000-2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events.

Toona sinensis leaf extract has antinociceptive effect comparable with non-steroidal anti-inflammatory agents in mouse writhing test.

BACKGROUND: The antinociceptive effect of an aqueous extract from the leaves of Toona sinensis (TS, [A. Juss., M. Roem.]) was studied using the writhing test in mice. METHODS: Different extraction fractions from TS leaf extracts (TSL1 to TSL5) were administered orally 1 h before intraperitoneal injection of acetic acid. RESULTS: After treatment with TSL1, TSL2, TSL3, TSL4, and TSL5 at a dose of 1 g/kg, the respective writhing responses were 39.9% (P < 0.001), 19.9% (P < 0.05), 11.7% (P = 0.052), 8.1% (P = 0.188), and 11.4% (P = 0.057) lower than the control group. Mice treated with TSL1 at 1 g/kg (39.9%, P < 0.001), 0.3 g/kg (38.0%, P < 0.001), 0.1 g/kg (46.9%, P < 0.001), and 0.03 g/kg (31.1%, P < 0.001) had significantly lower writhing responses compared with control mice. A time-course experiment was performed, which involved oral administration of TSL1 (0.1 g/kg) at 0, 0.5, 1, 2, and 6 h before acetic acid intraperitoneal injection. The most effective dose of TSL1 was 0.1 g/kg orally, with the effect beginning 30 min before treatment and persisting until 6 h. CONCLUSIONS: This study showed that TS has anti-visceral pain properties comparable with those of rofecoxib (a cyclooxygenase-2 inhibitor) and diclofenac, which suggests promise for the treatment of intractable visceral pain in humans.

[Identification of a point mutation in the promoter region of cps operon responsible for capsular polysaccharide deficiency in Streptococcus pneumniae SPY1].

OBJECTIVE: To determine if the point mutation of nt313713 T --> C in the promoter region of capsular polysaccharide biosynthesis (cps) operon is responsible for the deficiency of capsular polysaccharide in S. pneumoniae SPY1 strain. METHODS: Western blot was used to compare the amounts of capsular polysaccharide between the wild-type strain and SPY1 strain. Real-time quantitative PCR was used to determine transcription levels of the first four genes of cps operon , cps2A, cps2B, cps2C and cps2D. The lacZ gene was used as a reporter gene to report the strength of the promoters on cps transcription. The cps promoter was amplified by PCR from the wild-type strain or SPY1 strain. The amplified fragments were cloned into shuttle vector pEVP3, transformed into S. pneumoniae D39 or SPY1 strain. The transcription activities of the promoters on capsular polysaccharide biosynthesis were determined by using ß-galactosidase as the reporter. Transmission electron microscopy and the Neufeld test were used to reveal the changes in capsule. RESULTS: Compared to that in the wild-type strain, mRNA levels of the cps genes were significantly decreased in SPY1 strain. The amount of CPS was also decreased in SPY1 strain. ß-galactosidase activities in SPY1-pEVP3-cps promoter(SPY1) and D39-pEVP3-cps promoter(SPY1) were decreased by about 79% and 76%, respectively, compared to that of the control. Transmission electron microscopy showed that the amount of the capsular polysaccharide of SPY1-pEVP3-cps promoter(D39) strain was restored to the wild-type level. In addition, capsular polysaccharide was absent in the D39-pEVP3-cps promoter(SPY1) (NC_008533. 1 313713 T --> C) strain as determined by Neufeld test. CONCLUSION: The point mutation of nt313713 T --> C in the cps promoter region results in a significantly reduced transcription of the cps genes, which is responsible for the significant reduction or even absence of the biosynthesis of capsular polysaccharide in SPY1 strain.

Lack of efficacy of motor cortex stimulation for the treatment of neuropathic pain in 14 patients.

OBJECTIVES: Motor cortex stimulation has been reported as an effective treatment for medically resistant neuropathic pain. The goal of this study is to review the efficacy of this treatment in a series of 14 patients. MATERIALS AND METHODS: The records of a consecutive series of 14 patients undergoing MCS for neuropathic pain at Stanford University Hospital and Clinics between 2002 and 2010 were retrospectively analyzed. The primary outcome measure was a visual analogue scale, which patients completed prior to surgery and following each programming session. The motor cortex was localized using 1) MR image guidance, 2) intraoperative somatosensory evoked potentials and motor response to stimulation, and 3) postoperative imaging. All patients underwent extensive stimulator programming. RESULTS: Five patients exhibited a transient improvement of >50%. Of these, only two patients maintained >50% improvement to their last clinic visit. One of these patients died of unrelated causes, and the other complained of variable response at home. The median time from best to final VAS was 50 days. Average postoperative follow-up was 55.5 weeks. Postoperative imaging demonstrated appropriate lead placement in 12 patients. The other two patients did not undergo postoperative imaging. CONCLUSIONS: In our cohort of 14 patients with neuropathic pain, motor cortex stimulation failed to produce acceptable long-term benefit. Possible reasons for this failure are discussed in the context of a small retrospective study.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring.

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40-60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

Transforming growth factor-beta 1 (TGF-ß1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-ß1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-ß1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-ß1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-ß1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-ß1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-ß1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-ß1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-ß1 might be useful as a tumor marker for astrocytomas.