An XYZ-axis Matrix Approach for the Integration of Neuroscience and Neuroethics

The recent, unprecedented advancement in neuroscience has led to new discoveries about the human brain and its function. Yet at the same time, it has spurred novel ethical and regulatory issues, and the field of neuroethics has emerged as an interdisciplinary endeavor to address these issues.Across the globe, extensive efforts have been underway to achieve the integration of neuroscience and Neuroethics, with active engagement not only from academia but also from the government, the public, and industry. However, in some countries, integrating neuroscience and neuroethics has proved to be a particularly challenging task. For example, in South Korea, the government has primarily driven the integration effort, and only a small group of researchers is properly trained for conducting an interdisciplinary evaluation of ethical, legal, social, and cultural implications (ELSCI) of neurotechnology. On the basis of the last few years of experience pursuing a government-funded neuroethics project in South Korea, we developed a new operational framework to provide practical guidance on ELSCI research. This framework consists of the X, Y, and Z axes; the X-axis represents a target neurotechnology, the Y-axis represents different developmental stages of the technology, and the Z-axis represents ELSCI issues that may arise from the development and use of the neurotechnology. Here we also present a step-by-step workflow to apply this matrix framework, from organizing a panel for a target neurotechnology to facilitating stakeholder discussion through public hearings. This framework will enable meaningful integration of neuroscience and neuroethics to promote responsible innovation in neuroscience and neurotechnology.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Tuberculous Osteomyelitis of the First Metatarsophalangeal Joint Misdiagnosed as Gouty Arthritis

A-43-year-old man visited our clinic due to pain and swelling of his left first metatarsophalangeal (MTP) joint since 6-months ago. He was diagnosed as gouty arthritis at private clinic and took hypouricemic agent, but he had progressive pain and swelling. There was swelling, erythema and tenderness and ulceration at base of the left first MTP joint. His laboratory results showed elevated C-reactive protein and normal serum uric acid level. The plain radiograph of foot showed bone destruction of left first MTP joint. MRI revealed joint space narrowing, soft tissue swelling and subchondral cyst. He underwent excisional biopsy and histology demonstrated chronic granulomatous inflammation with caseation necrosis. Tissue polymerase chain reaction for mycobacterium tuberculosis was positive. He was diagnosed as tuberculous osteomyelitis. He started on quadruple anti-tuberculous therapy and his symptom was improved. Early diagnosis and anti-tuberculosis therapy could lead to improve outcomes.

Posttraumatic Intracranial Tuberculous Subdural Empyema in a Patient with Skull Fracture

Intracranial tuberculous subdural empyema (ITSE) is extremely rare. To our knowledge, only four cases of microbiologically confirmed ITSE have been reported in the English literature to date. Most cases have arisen in patients with pulmonary tuberculosis regardless of trauma. A 46-year-old man presented to the emergency department after a fall. On arrival, he complained of pain in his head, face, chest and left arm. He was alert and oriented. An initial neurological examination was normal. Radiologic evaluation revealed multiple fractures of his skull, ribs, left scapula and radius. Though he had suffered extensive skull fractures of his cranium, maxilla, zygoma and orbital wall, the sustained cerebral contusion and hemorrhage were mild. Eighteen days later, he suddenly experienced a general tonic-clonic seizure. Radiologic evaluation revealed a subdural empyema in the left occipital area that was not present on admission. We performed a craniotomy, and the empyema was completely removed. Microbiological examination identified Mycobacterium tuberculosis (M. tuberculosis). After eighteen months of anti-tuberculous treatment, the empyema disappeared completely. This case demonstrates that tuberculosis can induce empyema in patients with skull fractures. Thus, we recommend that M. tuberculosis should be considered as the probable pathogen in cases with posttraumatic empyema.

Overexpressions of Vimentin and Integrins in Human Metastatic Spine Tumors

OBJECTIVE: To comparatively investigate the expression of several integrins in specimens of human bone metastases and degenerative bone tissue. METHODS: Degenerative cancellous tissue was obtained from a sample of human degenerative spine. Thirteen human specimens were obtained from metastatic spine tumors, whose primary cancer was colon cancer (n=3), hepatocellular cancer (n=3), lung cancer (n=4), and breast cancer (n=3). The expression of vimentin and integrins alphav, beta1, and beta3 was assessed in metastatic and degenerative specimens by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Immunohistochemical staining showed that vimentin and integrin alphav was broadly expressed in all tissues examined. By contrast, integrin beta1 was weakly expressed only in 38.4% (5/13) of tissues. Integrin beta3 was consistently negative in all cases examined. qRT-PCR analysis showed that vimentin gene expression was higher in all metastatic specimens, as compared to degenerative bone. The gene expression of integrin alphav in breast specimen was significantly higher than others (p=0.045). The gene expression of integrin beta1 was also higher in all metastatic specimens than in degenerative bone tissue. The gene expression of integrin beta3 was variable. CONCLUSION: Spinal metastatic tumors have mesenchymal characteristics such as increased expression of vimentin. The increased expression of integrin alphav and beta1 in spine metastatic tumors suggests that adhesive molecules such as integrin may have implications for the prevention of spine metastasis.

Expression of Heat Shock Proteins and Cytokines in Response to Ethanol Induced Damage in the Small Intestine of ICR Mice

BACKGROUND/AIMS: Ethanol administration causes intestinal epithelial cell damage by increasing intestinal permeability and the translocation of endotoxins from intestinal bacterial flora. Heat shock proteins (HSPs) are associated with recovery and protection from cell damage. The aim of the current study was to investigate differences in the expression of HSPs in the small intestine and the biochemical changes attributable to ethanol-induced intestinal damage. METHODS: Ethanol (20%) was injected intraperitoneally (2.75 g/kg, 5.5 g/kg, 8.25 g/kg) in ICR mice and the same volume of saline was administered to controls. After 1 hour, the proximal, middle, and distal segments were taken from the small intestine and the degree of damage was analyzed. In each segment, the expression of HSPs was analyzed by western blotting. The expression of inflammatory mediators including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and antioxidant enzyme such as glutathione-S-transferase were compared using real-time polymerase chain reaction assays. RESULTS: In the control group, HSP70 increased in all segments of small intestine. Additionally, increases in the expression of HSP40 and HSP90 in the distal regions and an increase in HSP32 in the middle regions were observed. After ethanol treatment, greater histological damage was observed in the distal small intestine and significant decreases in HSPs were observed generally. Increased expression of IL-1beta, TNF-alpha, and COX-2 was observed in small intestinal tissues exposed to ethanol-induced damage. However, there was no significant difference in the expression of an antioxidant enzyme. CONCLUSIONS: Significant differences in the expression of HSPs in different intestinal regions were observed. These differences may have been attributable to the distribution of intestinal bacteria.

Pure Spinal Epidural Cavernous Hemangioma with Intralesional Hemorrhage: A Rare Cause of Thoracic Myelopathy

Although cavernous hemangiomas occur frequently in the intracranial structures, they are rare in the spine. Most of spinal hemangiomas are vertebral origin and "pure" epidural hemangiomas not originating from the vertebral bone are very rare. Our spinal hemangioma case is extremely rare because of its "pure" epidural involvement and intralesional hemorrhage. A 64-year-old man presented with progressive paraparesis from two months ago. His motor weakness was rated as grade 4/5 in bilateral lower extremities. He also complained of decreased sensation below the T4 sensory dermatome, which continuously progressed to the higher dermatome level. Magnetic resonance imaging demonstrated thoracic spinal tumor at T3-T4 level. The tumor was located epidural space compressing thoracic spinal cord ventrally. The tumor was not involved with the thoracic vertebral bone. We performed T3-5 laminectomy and removed the tumor completely. The tumor was not infiltrating into intradural space or vertebral bone. The histopathologic study confirmed the epidural tumor as cavernous hemangioma. Postoperatively, his weakness improved gradually. Four months later, his paraparesis recovered completely. Here, we present a case of pure spinal epidural cavernous hemangioma, which has intralesional hemorrhage. We believe cavernous hemangioma should be included in the differential diagnosis of the spinal epidural tumors.

Pilomatricoma: An Unusual Presentation

No abstract available.

Analysis of Human Tissue Management Models for Medical Research: Preparation for Implementation of the 2012 Revision of the Bioethics and Safety Act of Korea

Efficient management of human tissue samples is a critical issue; the supply of samples is unable to satisfy the current demands for research. Lack of informed consent is also an ethical problem. One of the goals of the 2012 revision of Korea's Bioethics and Safety Act was to implement regulations that govern the management of human tissue samples. To remain competitive, medical institutions must prepare for these future changes. In this report, we review two tissue management models that are currently in use; model 1 is the most common system utilized by hospitals in Korea and model 2 is implemented by some of the larger institutions. We also propose three alternative models that offer advantages over the systems currently in use. Model 3 is a multi-bank model that protects the independence of physicians and pathologists. Model 4 utilizes a comprehensive single bioresource bank; although in this case, the pathologists gain control of the samples, which may make it difficult to implement. Model 5, which employs a bioresource utilization steering committee (BUSC), is viable to implement and still maintains the advantages of Model 4. To comply with the upcoming law, we suggest that physicians and pathologists in an institution should collaborate to choose one of the improved models of tissue management system that best fits for their situation.

Embryonal Rhabdomyosarcoma Arising from a Mediastinal Teratoma: An Unusual Case Report

We report an unusual case of 9.5-cm-sized embryonal rhabdomyosarcoma arose from a mediastinal mature teratoma in a 46-yr-old man. A man presented with chest trauma as a result of an accident at 10 September 2011. On chest X-ray, an anterior mediastinal mass was detected. To obtain further information, chest computed tomography (CT) with contrast enhancement was performed, revealing an anterior mediastinal mass. Complete surgical excision was performed and entire specimen was evaluated. Pathologic diagnosis was embryonal rhabdomyosarcoma arising in mature cystic teratoma. After surgical excision, two cycles of dactinomycin-based chemotherapy were performed. Lung metastasis was detected on follow up CT in September 2012, and wedge resection was performed. Pathological finding of the lung lesion showed same feature with that of primary rhabdomyosarcoma.

Proposal for the development of a human biological material management system for research hospitals

In this paper, the authors suggest more effective conditions for human tissue preparation in research hospitals. Because recent genetic and molecular studies have contributed to the rapid development of molecular and genetic medicine, human tissue is now again being considered as a valuable research resource. Basically, high-quality research-oriented tissue bank organizations are a very important part of a research hospital. The current management system for human tissue, however, is not very effective from either legal or practical perspectives. In this article, the authors propose some improvements on the human tissue management system. The laws on human tissue such as the Bioethics and Safety Act should be changed to contain suitable language applying on-site and efficient multi-dimensional information. Informed consent should be an essential requirement before surgery. Pathologists should be supported as the essential manpower of human tissue banks by law. A committee composed of a clinician, researcher, pathologist, information manager, and coordinator should be established to manage human tissue banks in hospitals. The Institutional Review Board should pay more attention to preventing the leakage of the private information of donors, and researchers should know about the review process and guidelines. This suggestion will create a more stable and effective system for the management of human tissue banks, and it will also create a complete and integrated system for research institutions. Therefore, human tissue banks can play an important role in improving research hospitals' competitiveness by providing a valuable collection of material for research.

Primary aldosteronism due to right adrenal adenoma case report / 대한내분비학회지

No abstract available.