Changes in the phosphorylation of nucleotide metabolism­associated proteins by leukemia inhibitory factor in mouse embryonic stem cells.

Leukemia inhibitory factor (LIF) is a stem cell growth factor that maintains self­renewal of mouse embryonic stem cells (mESCs). LIF is a cytokine in the interleukin­6 family and signals via the common receptor subunit gp130 and ligand­specific LIF receptor. LIF causes heterodimerization of the LIF receptor and gp130, activating the Janus kinase/STAT and MAPK pathways, resulting in changes in protein phosphorylation. The present study profiled LIF­mediated protein phosphorylation changes in mESCs via proteomic analysis. mESCs treated in the presence or absence of LIF were analyzed via two­dimensional differential in­gel electrophoresis and protein and phosphoprotein staining. Protein identification was performed by matrix­assisted laser desorption/ionization­time of flight mass spectrophotometry. Increased phosphorylation of 16 proteins and decreased phosphorylation of 34 proteins in response to LIF treatment was detected. Gene Ontology terms enriched in these proteins included 'organonitrogen compound metabolic process', 'regulation of mRNA splicing via spliceosome' and 'nucleotide metabolic process'. The present results revealed that LIF modulated phosphorylation levels of nucleotide metabolism­associated proteins, thus providing insight into the mechanism underlying LIF action in mESCs.

Changes in Emberiza bunting communities and populations spanning 100 years in Korea.

The rapid decline of a few Emberiza bunting species is increasing conservation concerns, especially in Asia. However, temporal changes in communities and populations of buntings, ones of the most common migratory songbirds in Korea, have not been quantitatively assessed. To understand how the status of buntings has changed over the past 100 years, we collated abundance data from museum collections and bird-banding records between 1910 and 2019. We also used presence-absence data for buntings collected by a nationwide census scheme between 1997 to 2012. Our analysis showed that bunting communities reconstructed from museum-specimen and bird-banding data were not significantly different; however, community composition differed over time. The Meadow (E. cioides), Yellow-throated (E. elegans), Black-faced (E. spodocephala), Rustic (E. rustica) and Chestnut Buntings (E. rutila), which are still common or were once common species, significantly affected the temporal changes in bunting community composition. There were no recent changes in the presence of Rustic and Chestnut Buntings since 1997, but they caused medium-term changes in the bunting community composition, suggesting that there was a sharp to moderate decline in their numbers in the past. The probability of the presence of six bunting species decreased annually, with the most prominent decline in two common breeders, the Meadow (-2.99%/year) and Yellow-throated Buntings (-1.82%/year). This finding suggests that breeding buntings in Korea are under high pressure, as are the migratory buntings. Moreover, despite its recent population decline, the Yellow-throated Bunting was still a major contributor to the community, suggesting that bunting diversity has also been deteriorating while bunting populations are shrinking. Long-term monitoring schemes across their distribution ranges, international cooperation for identifying major threats and key areas of conservation, and law enforcement against illegal hunting and habitat loss are strongly required to mitigate the on-going decline of buntings in Korea and Asia.

Temporal augmentation with calvarial onlay graft during pterional craniotomy for prevention of temporal hollowing.

BACKGROUND: Atrophy of muscle and fat often contributes to temporal hollowing after pterional craniotomy. However, the main cause is from the bony defect. Several methods to prevent temporal hollowing have been introduced, all with specific limitations. Autologous bone grafts are most ideal for cranial defect reconstruction. The authors investigated the effectiveness of bony defect coverage and temporal augmentation using pterional craniotomy bone flap. METHODS: This study was conducted in 100 patients who underwent brain tumor excision through pterional approach from 2015 to 2016. Group 1 underwent pterional craniotomy with temporal augmentation and group 2 without temporal augmentation. In group 1, after splitting the calvarial bone at the diploic space, the inner table was used for covering the bone defect and as an onlay graft for temporal augmentation. The outcome is evaluated by computed tomography at 1-year follow-up. RESULTS: The mean operative time for temporal augmentation was 45 minutes. The mean follow-up was 12 months. The ratio of temporal thickness of operated side to non-operated side was 0.99 in group 1 and 0.44 in group 2, which was statistically different. The mean visual analogue scale score was 1.77 in group 1 and 6.85 in group 2. CONCLUSION: This study demonstrated a surgical technique using autologous bone graft for successfully preventing the temporal hollowing and improved patient satisfaction.

Clinical outcome of proton therapy for patients with chordomas.

PURPOSE: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. MATERIALS AND METHODS: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and diseasespecific survival (DSS) rates were calculated by the Kaplan-Meier method. RESULTS: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. CONCLUSION: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

Effectiveness of Temporal Augmentation Using a Calvarial Onlay Graft during Pterional Craniotomy.

Temporal hollowing occurs to varying degrees after pterional craniotomy. The most common cause of temporal hollowing is a bony defect of the pterional and temporal regions due to the resection of the sphenoid ridge and temporal squama for adequate exposure without overhang. The augmentation of such bony defects is important in preventing craniofacial deformities and postoperative hollowness. Temporal cranioplasty has been performed using a range of materials, such as acrylics, porous polyethylene, bone cement, titanium, muscle flaps, and prosthetic dermis. These methods are limited by the risk of damage to adjacent tissue and infection, a prolonged preparation phase, the possibility of reabsorption, and cost inefficiency. We have developed a method of temporal augmentation using a calvarial onlay graft as a single-stage neurosurgical reconstructive operation in patients requiring craniotomy. In this report, we describe the surgical details and review our institutional outcomes. The patients were divided into pterional craniotomy and onlay graft groups. Clinical temporal hollowing was assessed using a visual analog scale (VAS). Temporal soft tissue thickness was measured on preoperative and postoperative computed tomography (CT) studies. Both the VAS and CT-based assessments were compared between the groups. Our review indicated that the use of an onlay graft was associated with a lower VAS score and left-right discrepancy in the temporal contour than were observed in patients undergoing pterional craniotomy without an onlay graft.

Transfacial Surgical Approaches to Secure Wide Exposure of the Skull Base.

BACKGROUND: Treatment of skull base tumors is challenging due to limited access and presence of important neurovascular structures nearby. The success of a complete tumor resection depends on the extent of tumor exposure and secure field of view. While these tumors are often removed by transcranial endoscopic access, transfacial approach is sometimes required depending on the location and size of the tumor. This study describes various transfacial approaches in patients undergoing skull base tumor resection. METHODS: From March to November 2013, 15 patients underwent skull base tumor resection via transfacial accesses at a tertiary institution. Data were reviewed for patient demographics, type of access used, completeness of tumor resection, surgical outcome, and postoperative complications. RESULTS: Two clivus tumor patients underwent transmaxillary approach; three tuberculum- sellae and suprasellar-hypothalamus tumor patients underwent transbasal approach; three clinoid and retrobulbar intraconal orbital tumor patients underwent orbitozygomatic approach; and seven petroclival-area, pons, cavernous sinus, and lateral-sphenoid-wing tumor patients underwent zygomatic approach. In all cases, the upper and lower margins of the tumor were visible. Complete tumor removal consisted of 10 cases, and partial tumor removal in 5. There were no immediate major complications observed for the transfacial portion of the operations. The overall cosmetic results were satisfactory. CONCLUSION: Plastic surgeons can use various transfacial approaches according to the location and size of skull base tumors to secure a sufficient field of view for neurosurgeons.

Cochlear line: a novel landmark for hearing preservation using the anterior petrosal approach.

OBJECT: The goal of this study was to develop a practical landmark for the safe and easy identification of the cochlea when performing anterior petrosectomy based on cadaver dissection results. METHODS: The cochlear line was defined as the line drawn from the crossing point between the greater superficial petrosal nerve (GSPN) and the petrous internal carotid artery to the line drawn over the apex of the superior circumference of the dura of the internal auditory canal at a right angle. The validity of the cochlear line marking the anteromedial perimeter of the cochlea at the angle of the GSPN and the internal acoustic canal as a practical landmark were evaluated using 5 cadaver heads. RESULTS: The mean distance (± SD) measured from the cochlear line to the margin of the cochlear cavity was 2.25 ± 0.51 mm (range 1.50-3.00 mm). CONCLUSIONS: Anterior petrosectomy can be performed more efficiently by using the cochlear line as a key landmark to preserve the cochlea.

Inhibitory effect of GBH on platelet aggregation through inhibition of intracellular Ca2+ mobilization in activated human platelets.

Geiji-Bokryung-Hwan (GBH) was studied on antiplatelet activity in human platelet suspensions. GBH consists of the 5 herbs Cinnamomi Ramulus, Poria Cocos, Mountan Cortex Radicis, Paeoniae Radix, and Persicae Semen, which have been used in herbal medicine for thousands of years for atherosclerosis. The mechanism involved in the antiplatelet activity of GBH in human platelet suspensions was investigated. GBH inhibited platelet aggregation and Ca2+ mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. GBH had no inhibitory effect on thromboxane B2 (TXB2) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca2+ mobilization is regulated by phospholipase C-2 (PLC-gamma2) activation. We evaluated the effect of GBH on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP3). GBH at concentrations that inhibited platelet aggregation and Ca2+ mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP3 induced by CRP. Similar results were obtained with thrombin-induced platelet activation. GBH inhibited platelet aggregation and Ca2+ mobilization induced by thrombin without affecting the production of IP3. We then evaluated the effect of GBH on the binding of IP3 to its receptor. GBH at high concentrations partially blocked the binding of IP3 to its receptor. Therefore, the results suggested that GBH suppresses Ca2+ mobilization at a step distal to IP3 formation. GBH may provide a good tool for investigating Ca2+ mobilization.

Two indices affecting the directions of the sylvian fissure dissection in middle cerebral artery bifurcation aneurysms.

OBJECTIVE: This study proposes more objective methods for deciding the appropriate direction of the sylvian fissure dissection during surgical clipping in middle cerebral artery (MCA) bifurcation aneurysms. METHODS: We reviewed data of 36 consecutive patients with MCA bifurcation aneurysms. We measured 2 indices preoperatively on 3-dimensional computed tomography angiography (3D-CTA). Analysis of the calculated data allowed us to select the appropriate direction of sylvian fissure dissection for ease of proximal control of M1. Statistically, Mann-Whitney test was used. RESULTS: We classified subjects into 2 groups based on the technical level of M1 exposure during surgical clipping. When it was difficult to expose M1, subjects were assigned to Group I, and Group II were subjects in whom M1 exposure was easy. The mean difference between the distances extending from the limbus sphenoidale (LS) line to the internal carotid artery bifurcation and extending from the LS line to the MCA bifurcation was 1.00 ± 0.42 mm in group I and 4.39 ± 2.14 mm in group II. The mean M1 angle was 9.36 ± 3.73° in the group I and 34.05 ± 16.71° in the group II (M1 slope gap p < 0.05, M1 angle p < 0.05). CONCLUSION: We have found an objective method for preoperatively verifying ease of exposure of M1 artery during surgical clipping. Therefore, we suggest use of the preoperative M1 slope gap and M1 angle as indicators in 3D-CTA selecting the direction of sylvian fissure dissection for easy proximal control of M1.

Effectiveness of nicardipine for blood pressure control in patients with subarachnoid hemorrhage.

OBJECTIVE: The purpose of the study is to determine the effectiveness and safety of nicardipine infusion for controlling blood pressure in patients with subarachnoid hemorrhage (SAH). METHODS: We prospectively evaluated 52 patients with SAH and treated with nicardipine infusion for blood pressure control in a 29 months period. The mean blood pressure of pre-injection, bolus injection and continuous injection period were compared. This study evaluated the effectiveness of nicardipine for each Fisher grade, for different dose of continuous nicardipine infusion, and for the subgroups of systolic blood pressure. RESULTS: The blood pressure measurement showed that the mean systolic blood pressure / diastolic blood pressure (SBP/DBP) in continuous injection period (120.9/63.0 mmHg) was significantly lower than pre-injection period (145.6/80.3 mmHg) and bolus injection period (134.2/71.3 mmHg), and these were statistically significant (p < 0.001). In each subgroups of Fisher grade and different dose, SBP/DBP also decreased after the use of nicardipine. These were statistically significant (p < 0.05), but there was no significant difference in effectiveness between subgroups (p > 0.05). Furthermore, controlling blood pressure was more effective when injecting higher dose of nicardipine in higher SBP group rather than injecting lower dose in lower SBP group, and it also was statistically significant (p < 0.05). During the infusion, hypotension and cardiogenic problems were transiently combined in five cases. However, patients recovered without any complications. CONCLUSION: Nicardipine is an effective and safe agent for controlling acutely elevated blood pressure after SAH. A more systemic study with larger patients population will provide significant results and will bring solid evidence on effectiveness of nicardipine in SAH.

Intracranial dural arteriovenous fistulas: clinical characteristics and management based on location and hemodynamics.

OBJECTIVE: A dural arteriovenous fistula (DAVF) generally refers to a vascular malformation of the wall of a major venous sinus. These lesions have diverse symptoms according to the location and venous drainage, and require multidisciplinary treatment. We report on our experience and analyze the treatment outcome of intracranial DAVFs for a nine-year period. METHODS: Between January 2000 and December 2008, 95 patients with intracranial DAVFs were enrolled in this study. A retrospective review of clinical records and imaging studies of all patients was conducted. Endovascular embolization, surgical interruption, gamma knife stereotactic radiosurgery (GKS), or combinations of these treatments were performed based on clinical symptoms, lesion location, and venous drainage pattern. RESULTS: Borden type I, II, and III were 34, 48, and 13 patients, respectively. Aggressive presentation was reported in 6% of Borden type I, 31% of Borden type II, and 77% of Borden type III DAVFs, respectively, and DAVFs involving transverse, sigmoid, and superior sagittal sinus. Overall, the rate of complete obliteration was 68%. The complete occlusion rates with a combination treatment of endovascular embolization and surgery, surgery alone, and endovascular embolization were 89%, 86%, and 80%, respectively. When GKS was used with embolization, the obliteration rate was 83%, although it was only 54% in GKS alone. Spontaneous obliteration of the DAVF occurred in three patients. There were a few complications, including hemiparesis (in microsurgery), intracranial hemorrhage (in endovascular embolization), and facial palsy (in GKS). CONCLUSION: The hemorrhagic risk of DAVFs is dependent on the location and hemodynamics of the lesions. Strategies for treatment of intracranial DAVFs should be decided according to the characteristic of the DAVFs, based on the location and drainage pattern. GKS can be used as an optional treatment for intracranial DAVFs.

Endoscope-assisted microsurgical removal of an epidermoid tumor within the cavernous sinus.

Epidermoid tumor of the cavernous sinus is rare. The aim of this case report is to discuss the role of neuroendoscopes in the removal of such lesions. A 21-year-old man presented with 6-year history of progressive headache, diplopia, and visual disturbance. Work-up revealed an epidermoid tumor located in the right cavernous sinus. An extradural transcavernous approach was utilized via a traditional frontotemporal craniotomy with endoscopic assistance. The postoperative course was uneventful with immediate improvement of the patient's headache. Postoperative magnetic resonance imaging demonstrated complete removal of the tumor. There were no signs of recurrence during a 2-year follow-up period. The endoscope is a useful tool for removing epidermoid tumors from the cavernous sinus and enhances visualization of areas that would otherwise be difficult to visualize with microscopes alone. Endoscopes also help minimize the retraction of neurovascular structures.

Meningeal layers around anterior clinoid process as a delicate area in extradural anterior clinoidectomy : anatomical and clinical study.

OBJECTIVE: Removal of the anterior clinoid process (ACP) is an essential process in the surgery of giant or complex aneurysms located near the proximal internal carotid artery or the distal basilar artery. An extradural clinoidectomy must be performed within the limits of the meningeal layers surrounding the ACP to prevent morbid complications. To identify the safest method of extradural exposure of the ACP, anatomical studies were done on cadaver heads. METHODS: Anatomical dissections for extradural exposure of the ACP were performed on both sides of seven cadavers. Before dividing the frontotemporal dural fold (FTDF), we measured its length from the superomedial apex attached to the periorbita to the posterolateral apex which connects to the anterosuperior end of the cavernous sinus. RESULTS: The average length of the FTDF on cadaver dissections was 7 mm on the right side and 7.14 mm on the left side. Cranial nerves were usually exposed when cutting FTDF more than 7 mm of the FTDF. CONCLUSION: The most delicate area in an extradural anterior clinoidectomy is the junction of the FTDF and the anterior triangular apex of the cavernous sinus. The FTDF must be cut from the anterior side of the triangle at the periorbital side rather than from the dural side. The length of the FTDF incision must not exceed 7 mm to avoid cranial nerve injury.

An early comparative analysis of the use of autograft versus allograft in anterior cervical discectomy and fusion.

OBJECTIVE: The purpose of this study is to verify the usefulness of autograft versus allograft in the radiographic and clinical outcome in early period after the surgery. METHODS: We performed a retrospective review of 38 patients who had undergone one- or two-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation from March 2006 to May 2009. Interbody graft materials were iliac autograft (n=17) or with allograft (n=21). Fusion rate and graft collapse rate were assessed by radiographic analysis and clinical outcome was based on Odom's criteria. RESULTS: In autograft group, 13 patients achieved successful bone fusion (65%), whereas 7 patients (31.8%) in allograft group. There was statistically significant between two groups (p<0.05). Comparing immediate postoperative radiograph with last follow-up, the mean graft collapse was noted 1.3mm(15.5% change) in autograft group, whereas 2.0mm(24.7% change) in allograft group. There was no statistically significant collapse rate in autograft group (p>0.05), but statistically significant in allograft group (p<0.05). Clinical outcome was excellent or good in 94.1% in autograft group, and 90.5% in allograft group. CONCLUSION: In study, anterior cervical interbody fusion with an allograft got a result of lower fusion rate and higher collapse rate compared with autograft in early period after surgery, and clinical outcome showed similar results in both groups.

Surgical results and risk factors for recurrence of lumbar disc herniation.

OBJECTIVE: Recurrent lumbar disc herniation has been defined as disc herniation at the same level, regardless of ipsilateral or contralateral herniation, with a pain-free interval greater than 6 months. The aim of this study is to analyze outcomes and identify the potential risk factors for recurrent lumbar disc herniation. METHODS: The authors retrospectively reviewed the cases of 178 patients who underwent open discectomy for single-level lumbar disc herniation. Visual analogue scales and modified Macnab criteria were used to compare the clinical outcomes between the recurrent group and the non-recurrent group. Sex, age, discectomy level, degree of disc degeneration, type of disc herniation, pain-free interval after first-operation, smoking status, and trauma were investigated as potential recurrence risk factors. RESULTS: Of the 178 patients for whom the authors were able to definitely assess symptomatic recurrence status, 18 patients (10.1%) underwent revision surgery for recurrent disc herniation. The most common level involved was L4-L5 (61%) and the mean period of time to recurrence was 18.7 months (6-61 months). There were 17 cases of ipsilateral herniation and 1 case of contralateral herniation. The types of herniation for which revision surgery was done were protrusion (3 cases), and transligamentous extrusion (14 cases). There were five excellent, eight good, and two fair results. CONCLUSION: Repeated discectomy for recurrent disc herniation produced unsatisfactory outcomes. Factors such as sex, type of disc herniation and traumatic events were found to be significant risk factors.

Spontaneous cervical epidural hematoma causing brown-sequard syndrome.

Spontaneous cervical epidural hematoma (SCEH) is a rare clinical entity and has a varied etiology. Urgent surgical decompression should be done to prevent serious permanent neurologic deficits. We describe a 59-year-old female who presented with Brown-Sequard syndrome due to spontaneous cervical epidural hematoma. Initially, she was misdiagnosed as cerebrovascular accident. Cervical magnetic resonance imaging revealed epidural hematoma to the right of the spinal cord extending from C3 to C6. She later underwent surgical evacuation and had complete restoration of neurologic function. The outcome in SCEH is essentially determined by the time taken from onset of the symptom to operation. Therefore, early and precise diagnosis such as careful history taking and MRI evaluation is mandatory.