Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State: Recommendations for Doctors with Less Expertise at Local Emergency Rooms.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

Novel Postoperative Serum Biomarkers in Atypical Meningiomas: A Multicenter Study.

BACKGROUND: There has been no known serum biomarker to predict the prognosis of atypical meningioma. OBJECTIVE: To investigate the prognostic impact of serum biomarkers in patients newly diagnosed with resected intracranial atypical meningiomas. METHODS: This study enrolled 523 patients with atypical meningioma who underwent surgical resection between 1998 and 2018 from 5 Asian institutions. Serum laboratory data within 1 week after surgery were obtained for analysis. Optimal cutoffs were calculated for each serum marker using the maxstat package of R. RESULTS: Of 523 patients, 19.5% underwent subtotal resection and 29.8% were treated with adjuvant radiation therapy (ART). Among the 523 patients, 454 were included in the multivariate analysis for the progression/recurrence (P/R) rate excluding patients with incomplete histopathologic or laboratory data. On multivariate analysis, tumor size >5 cm, subtotal resection, and postoperative aspartate aminotransferase/alanine transaminase (De Ritis) ratio >2 were associated with higher P/R rates, whereas ART and postoperative platelet count >137 × 10 3 /µL were associated with lower P/R rates. In the subgroup of patients treated with ART, tumor size >5 cm and postoperative neutrophil-to-lymphocyte ratio >21 were associated with higher P/R rates. By contrast, postoperative De Ritis ratio >2 remained an adverse prognosticator in patients not treated with ART. CONCLUSION: Postoperative De Ritis ratio, platelet count, and neutrophil-to-lymphocyte ratio were revealed as a novel serum prognosticator in newly diagnosed atypical meningiomas. Additional studies are warranted to validate its clinical significance and biological background.

Location of Ulnar Nerve Branches to the Flexor Carpi Ulnaris during Surgery for Cubital Tunnel Syndrome.

OBJECTIVE: Cubital tunnel syndrome, the most common ulnar nerve entrapment neuropathy, is usually managed by simple decompression or anterior transposition. One of the concerns in transposition is damage to the nerve branches around the elbow. In this study, the location of ulnar nerve branches to the flexor carpi ulnaris (FCU) was assessed during operations for cubital tunnel syndrome to provide information to reduce operation-related complications. METHODS: A personal series (HJY) of cases operated for cubital tunnel syndrome was reviewed. Cases managed by transposition and location of branches to the FCU were selected for analysis. The function of the branches was confirmed by intraoperative nerve stimulation and the location of the branches was assessed by the distance from the center of medial epicondyle. RESULTS: There was a total of 61 cases of cubital tunnel syndrome, among which 31 were treated by transposition. Twenty-one cases with information on the location of branches were analyzed. The average number of ulnar nerve branches around the elbow was 1.8 (0 to 3), only one case showed no branches. Most of the cases had one branch to the medial head, and one other to the lateral head of the FCU. There were two cases having branches without FCU responses (one branch in one case, three branches in another). The location of the branches to the medial head was 16.3±8.6 mm distal to the medial epicondyle (16 branches; range, 0 to 35 mm), to the lateral head was 19.5±9.5 mm distal to the medial epicondyle (19 branches; range, -5 to 30 mm). Branches without FCU responses were found from 20 mm proximal to the medial condyle to 15 mm distal to the medial epicondyle (five branches). Most of the branches to the medial head were 15 to 20 mm (50% of cases), and most to the lateral head were 15 to 25 mm (58% of cases). There were no cases of discernable weakness of the FCU after operation. CONCLUSION: In most cases of cubital tunnel syndrome, there are ulnar nerve branches around the elbow. Although there might be some cases with branches without FCU responses, most branches are to the FCU, and are to be saved. The operator should be watchful for branches about 15 to 25 mm distal to the medial epicondyle, where most branches come out.

The High-Resolution Structure Reveals Remarkable Similarity in PD-1 Binding of Cemiplimab and Dostarlimab, the FDA-Approved Antibodies for Cancer Immunotherapy.

Multiple tumors have responded well to immunotherapies, which use monoclonal antibodies to block the immune checkpoint proteins and reactivate the T-cell immune response to cancer cells. Significantly, the anti-PD-1 antibodies pembrolizumab and nivolumab, which were approved in 2014, have revolutionized cancer therapy, demonstrating dramatic improvement and longer duration. The US FDA authorized the third anti-PD-1 medication, cemiplimab, in 2018 for use in patients with cutaneous squamous cell carcinoma. To further understand the molecular mechanism of the antibody drug, we now reveal the intricate structure of PD-1 in complex with the cemiplimab Fab at a resolution of 1.98 Å. The cemiplimab-PD-1 interaction preoccupies the space for PD-L1 binding with a greater binding affinity than the PD-1/PD-L1 interaction, which is the basis for the PD-1 blocking mechanism. The structure reveals that cemiplimab and dostarlimab are significantly similar in PD-1 binding, although the precise interactions differ. A comparative investigation of PD-1 interactions with the four FDA-approved antibodies reveals that the BC, C'D, and FG loops of PD-1 adopt distinct conformations for optimal interaction with the antibodies. The structural characteristics in this work could be helpful information for developing more potent anti-PD-1 biologics against cancer.

An Experimental Study on the Biomechanical Effectiveness of Bone Cement-Augmented Pedicle Screw Fixation with Various Types of Fenestrations.

OBJECTIVE: To analyze the effects of the number and shape of fenestrations on the mechanical strength of pedicle screws and the effects of bone cement augmentation (BCA) on the pull-out strength (POS) of screws used in conventional BCA. METHODS: For the control group, a conventional screw was defined as C1, a screw with cannulated end-holes was defined as C2, a C2 screw with six pinholes was defined as C3, and the control group type was set. Among the experimental screws, T1 was designed using symmetrically placed thru-hole type fenestrations with an elliptical shape, while T2 was designed with half-moon (HM)-shaped asymmetrical fenestrations. T3 and T4 were designed with single HM-shaped fenestrations covering three pitches and five pitches, respectively. T5 and T6 were designed with 0.6-mm and 1-mm wider fenestrations than T3. BCA was performed by injecting 3 mL of commercial bone cement in the screw, and mechanical strength and POS tests were performed according to ASTM F1717 and ASTM F543 standards. Synthetic bone (model #1522-505) made of polyurethane foam was used as a model of osteoporotic bone, and radiographic examinations were performed using computed tomography and fluoroscopy. RESULTS: In the fatigue test, at 75% ultimate load, fractures occurred 7781 and 9189 times; at 50%, they occurred 36122 and 82067 times; and at 25%, no fractures occurred. The mean ultimate load for each screw type was 219.1±52.39 N for T1, 234.74±15.9 N for T2, 220.70±59.23 N for T3, 216.45±32.4 N for T4, 181.55±54.78 N for T5, and 216.47±29.25 N for T6. In comparison with C1, T1, T2, T3, T4, and T6 showed significantly different ultimate load values (p<0.05). However, when the values for C2 and the fenestrated screws were evaluated with an unpaired t test, the ultimate load value of C2 significantly differed only from that of T2 (p=0.025). The ultimate load value of C3 differed significantly from those of T1 and T2 (C3 vs. T1 : p=0.048; C3 vs. T2 : p<0.001). Linear correlation analysis revealed a significant correlation between the fenestration area and the volume of bone cement (Pearson's correlation coefficient r=0.288, p=0.036). The bone cement volume and ultimate load significantly correlated with each other in linear correlation analysis (r=0.403, p=0.003). CONCLUSION: Fenestration yielded a superior ultimate load in comparison with standard BCA using a conventional screw. In T2 screws with asymmetrical two-way fenestrations showed the maximal increase in ultimate load. The fenestrated screws can be expected to show a stable position for the formation of the cement mass.

Adjuvant Radiotherapy Versus Surveillance for Grade 2 Intracranial Meningiomas: A Multi-Institutional Propensity Score-Matched Study.

Purpose: We aimed to compare the outcomes of adjuvant radiotherapy (ART) and surveillance in patients with grade 2 meningiomas (MNG2) who underwent surgical resection. Materials and Methods: Data from four hospitals, in which patients aged ≥18 years underwent Simpson grade 1-4 surgical resection for newly diagnosed MNG2 between 1998 and 2018, were examined in this multicenter retrospective cohort study. Patients receiving ART with conventional fractionation were compared with those undergoing surveillance. Progression-free survival (PFS), progression/recurrence (P/R) were evaluated. Results: This study included 518 patients, 158 of whom received ART. The median follow-up duration was 64.9 months. In the total cohort, ART was independently associated with significantly improved PFS (HR, 0.35; 95% CI, 0.23-0.55; P<0.001) and P/R (HR, 0.30; 95% CI, 0.18-0.48; P<0.001). In the propensity score-matched cohort (n=143 in each group), the 5-year PFS rates were 80.8% and 57.7% (P=0.004), and the 5-year P/R rates were 16.5% and 40.0% (P=0.002) in the ART and surveillance groups, respectively. After gross total resection, the 5-year PFS (85.0% vs. 64.7%; P=0.020) and P/R rates (15.2% vs. 32.0%; P=0.035) were significantly better in the ART group than in the surveillance group. A model for P/R was developed using recursive partitioning analysis with surgical extent, tumor size, and Ki-67 index. ART reduced the risk of P/R in the low- (P=0.069), intermediate- (P=0.044), and high-risk groups (P<0.001). Local control was also significantly enhanced by ART among all the risk groups (all P<0.05). Conclusions: ART significantly improved PFS and P/R in patients with MNG2, irrespective of the surgical extent, and can be recommended after gross total resection. A prognostic model may guide decision-making for the use of ART.

Delayed Cerebral Toxoplasmosis in a Kidney Transplant Patient: a Case Report.

Cerebral toxoplasmosis is often life-threatening in an immunocompromised patient due to delayed diagnosis and treatment. Several differential diagnoses could be possible only with preoperative brain images of cerebral toxoplasmosis which show multiple rim-enhancing lesions. Due to the rarity of cerebral toxoplasmosis cases in Korea, the diagnosis and treatment are often delayed. This paper concerns a male patient whose cerebral toxoplasmosis was activated 21 years post kidney transplantation. Brain open biopsy was decided to make an exact diagnosis. Cerebral toxoplasmosis was confirmed by immunohistochemistry and PCR analyses of the tissue samples. Although cerebral toxoplasmosis was under control with medication, the patient did not recover clinically and died due to sepsis and recurrent gastrointestinal bleeding.

Differences in Brain Morphology between Hydrocephalus Ex Vacuo and Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: The distinction between idiopathic normal pressure hydrocephalus (iNPH) and hydrocephalus ex vacuo caused by encephalic volume loss remains to be established. This study aims to investigate radiological parameters as clinically useful tools to discriminate iNPH from hydrocephalus ex vacuo caused by Alzheimer's disease (AD). METHODS: A total of 54 patients with ventriculomegaly (iNPH, 25; hydrocephalus ex vacuo, 29) were recruited in this study. Consequently, nine radiological parameters were compared between iNPH and hydrocephalus ex vacuo using magnetic resonance imaging (MRI). RESULTS: A small callosal angle (CA), the Sylvian fissure dilatation, and absence of narrowing of superior parietal sulci discriminated the iNPH group from the hydrocephalus ex vacuo group (p<0.05). The final binary logistic regression model included narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure after controlling for age and global Clinical Dementia Rating (CDR). The composite score made from these three indicators (narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure) was statistically different between iNPH and hydrocephalus ex vacuo. CONCLUSION: The narrowing of the CA, dilatation of the Sylvain fissure, and narrowing of superior parietal sulci may be used as radiological key indices and noninvasive tools for the differential diagnosis of iNPH from hydrocephalus ex vacuo.

High-resolution structure of the vWF A1 domain in complex with caplacizumab, the first nanobody-based medicine for treating acquired TTP.

von Willebrand factor (vWF) is a huge oligomeric glycoprotein involved in blood homeostasis. However, this protein is also implicated in acquired thrombotic thrombocytopenic purpura (TTP). The blocking of its binding with platelets has been recognized as an attractive therapeutic strategy for treating acquired TTP. Caplacizumab, a bivalent single-domain antibody (VHH), is the first FDA-approved nanobody drug against vWF for the treatment of acquired TTP. Here, we describe the crystal structure of the A1 domain of vWF in complex with the caplacizumab nanobody at the resolution of 1.60 Å. This structure elucidates the precise epitope and binding mode of caplacizumab. Unexpectedly, caplacizumab binds to the bottom face of the vWF A1 domain and does not create any steric clash with platelet-receptor glycoprotein Ib (GPIb) bound to vWF. However, its binding can stabilize the different conformation within the N-terminus and α1ß2 loop from the GPIb bound structure, suggesting that the mechanisms of caplacizumab would not be the direct competition of GPIb binding to vWF A1 domain but the conformational arrestment of vWF in an inappropriate state to platelet adhesion. This high-resolution structure would provide helpful information for the design of improved anti-vWF therapeutics for the treatment of acquired TTP.

Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Inducing Reduction in IL-17A/Th17 Via Upregulation of SOCS3.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), a demyelinating autoimmune disease caused by the infiltration of a harmful autoreactive Th1 and Th17 cells. To mitigate MS, which is impossible to cure with medication only, immunomodulatory interventions that prevent Th17 cell activation are ideal. The objective of the present study was to analyze the effect of Toxoplasma gondii infection on the onset of EAE. Our results found that Toxoplasma gondii infection in the brain increases SOCS3 expression and decreases the phosphorylation of STAT3, resulting in reducing IL-17A and IL-23, which suppress the differentiation and expansion of pathogenic Th17 cells, an important factor in MS development. These immune responses resulted in a reduction in the clinical scoring of EAE induced by myelin oligodendrocyte glycoprotein 35-55 immunization. In the EAE group with T. gondii infection (Tg + EAE group), Th17-related immune responses that exacerbate the onset of EAE were reduced compared to those in the EAE group. This study suggests that the alleviation of EAE after T. gondii infection is regulated in a SOCS3/STAT3/IL-17A/blood-brain barrier integrity-dependent manner. Although parasite infection would not be permitted for MS treatment, this study using T. gondii infection identified potential targets that contribute to disease attenuation.

Crystal structure of CD38 in complex with daratumumab, a first-in-class anti-CD38 antibody drug for treating multiple myeloma.

Multiple myeloma is a blood cancer characterized by the plasma cell malignancy in the bone marrow, resulting in the destruction of bone tissue. Recently, the US FDA approved two antibody drugs for the treatment of multiple myeloma, daratumumab and isatuximab, targeting CD38, a type II transmembrane glycoprotein highly expressed in plasma cells and multiple myeloma cells. Here, we report the crystal structure of CD38 in complex with the Fab fragment of daratumumab, providing its exact epitope on CD38 and the structural insights into the mechanism of action of the antibody drug. Daratumumab binds to a specific discontinuous region on CD38 that includes residues located opposite to the active site of CD38. All the six complementarity determining regions of daratumumab are involved in the CD38 interaction. The epitopes of daratumumab and isatuximab do not overlap at all and their bindings to CD38 induce different structural changes within the CD38 protein. This structural study can facilitate the design of improved biologics or effective combination therapies for the treatment of multiple myeloma.

Erratum to: Milk Containing BF-7 Enhances the Learning and Memory, Attention, and Mathematical Ability of Normal Persons.

[This corrects the article DOI: 10.5851/kosfa.2009.29.2.278.].

Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy.

Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front ß-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy.

Patient-specific Hemodynamics of Severe Carotid Artery Stenosis Before and After Endarterectomy Examined by 4D Flow MRI.

Carotid endarterectomy (CEA) influences the carotid endoluminal anatomy, which results in hemodynamic changes before and after surgery. We investigated the hemodynamics of severe carotid artery stenosis before and after conventional endarterectomy with/without patch repair. An in vitro experiment utilizing carotid phantoms, which underwent a procedure that emulated CEA with/without the patch repair, was performed with a high-spatiotemporal resolution using 4D flow MRI. We evaluated an abnormal region of carotids, which consists of the normalized time-averaged wall shear stress (NTA|WSS|) and the oscillatory shear index (OSI), to account for continuous high-shear regions (high NTA|WSS| and low OSI) and chaotic low-shear regions, i.e., stenosis-prone regions (low NTA|WSS| and high OSI). The use of normalized hemodynamic parameters (e.g., NTA|WSS|) allowed comparison of diverse cases with different conditions of hemodynamics and vessel geometry. We observed that the stenosis-prone regions of the carotids with patches were noticeably larger than the corresponding regions in no-patch carotids. A large recirculating flow zone found in the stenosis-prone region of the internal carotid artery (ICA) of the postoperative carotids with patches partially blocks the flow path into ICA, and consequently the flow rate was not recovered after surgery unlike an expectation.

Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution.

OBJECTIVE: A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution. METHODS: Ninety-two patients with petroclival meningiomas were treated surgically at the authors' institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1-368 months) and 105 months (range 1-348 months), respectively. RESULTS: A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively. CONCLUSIONS: The authors' preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology.

Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), cemiplimab (Libtayo®), atezolizumab (Tecentriq®), durvalumab (Imfinzi®), and avelumab (Bavencio®), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology.

Increase in the nuclear localization of PTEN by the Toxoplasma GRA16 protein and subsequent induction of p53-dependent apoptosis and anticancer effect.

This study investigated the efficacy of Toxoplasma GRA16, which binds to herpes virus-associated ubiquitin-specific protease (HAUSP), in anticancer treatment, and whether the expression of GRA16 in genetically modified hepatocellular carcinoma (HCC) cells (GRA16-p53-wild HepG2 and GRA16-p53-null Hep3B) regulates PTEN because alterations in phosphatase and tensin homologue (PTEN) and p53 are vital in liver carcinogenesis and the abnormal p53 gene appears in HCC. For this purpose, we established the GRA16 cell lines using the pBABE retrovirus system, assessed the detailed mechanism of PTEN regulation in vitro and established the anticancer effect in xenograft mice. Our study showed that cell proliferation, antiapoptotic factors, p-AKT/AKT ratio, cell migration and invasive activity were decreased in GRA16-stable HepG2 cells. Conversely, the apoptotic factors PTEN and p53 and apoptotic cells were elevated in GRA16-stable HepG2 cells but not in Hep3B cells. The change in MDM2 was inconspicuous in both HepG2 and Hep3B; however, the PTEN level was remarkably elevated in HepG2 but not in Hep3B. HAUSP-bound GRA16 preferentially increased p53 stabilization by the nuclear localization of PTEN rather than MDM2-dependent mechanisms. These molecular changes appeared to correlate with the decreased tumour mass in GRA16-stable-HepG2 cell-xenograft nude mice. This study establishes that GRA16 is a HAUSP inhibitor that targets the nuclear localization of PTEN and induces the anticancer effect in a p53-dependent manner. The efficacy of GRA16 could be newly highlighted in HCC treatment in a p53-dependent manner.

Delayed Trochlear Nerve Palsy Following Traumatic Subarachnoid Hemorrhage: Usefulness of High-Resolution Three Dimensional Magnetic Resonance Imaging and Unusual Course of the Nerve.

Cranial nerve palsies are relatively common after trauma, but trochlear nerve palsy is relatively uncommon. Although traumatic trochlear nerve palsy is easy to diagnose clinically because of extraocular movement disturbances, radiologic evaluations of this condition are difficult to perform because of the nerve's small size. Here, we report the case of a patient with delayed traumatic trochlear nerve palsy associated with a traumatic subarachnoid hemorrhage (SAH) and the related radiological findings, as obtained with high-resolution three-dimensional (3D) magnetic resonance imaging (MRI). A 63-year-old woman was brought to the emergency room after a minor head trauma. Neurologic examinations did not reveal any focal neurologic deficits. Brain computed tomography showed a traumatic SAH at the left ambient cistern. The patient complained of vertical diplopia at 3 days post-trauma. Ophthalmologic evaluations revealed trochlear nerve palsy on the left side. High-resolution 3D MRI, performed 20 days post-trauma, revealed continuity of the trochlear nerve and its abutted course by the posterior cerebral artery branch at the brain stem. Chemical irritation due to the SAH and the abutting nerve course were considered causative factors. The trochlear nerve palsy completely resolved during follow-up. This case shows the usefulness of high-resolution 3D MRI for evaluating trochlear nerve palsy.

Effects of Antioxidants in Reducing Accumulation of Fat in Hepatocyte.

The progress of the hepatic steatosis (HS), a clinicopathological status, is influenced by cellular oxidative stress, lipogenesis, fatty acid (FA) oxidation, and inflammatory responses. Because antioxidants are gaining attention as potent preventive agents for HS, we aimed to investigate anti-lipogenic effects of the antioxidants vitamin C (VC), N-acetylcysteine (NAC), and astaxanthin (ATX) using hepatocytes. For this, we established an in vitro model using 1 mM oleic acid (OA) and human liver hepatocellular carcinoma (HepG2) cells; 10 µM antioxidants were evaluated for their ability to reduce fat accumulation in hepatocytes. Our results showed that all three antioxidants were effective to reduce fat accumulation for the molecular targets such as reduction in lipid droplets, triglyceride (TG) concentration, reactive oxygen species (ROS) production, and cell apoptosis, as well as in gene expressions of endoplasmic reticulum (ER) stress-related effectors, lipogenesis, and inflammatory cytokines. There were simultaneous increases in diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, cell survival, AMPK phosphorylation, NRF2-related gene expression for cellular defense, and FA ß-oxidation. However, among these, ATX more effectively inhibited ER stress and lipogenesis at the intracellular level than VC or NAC. Consequently, ATX was also more effective in inhibiting cell death, lipotoxicity, and inflammation. Our result emphasizes that ATX achieved greater lipotoxicity reduction than VC and NAC.