Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

Effects of the Mental Health and Welfare Law revision on schizophrenia patients in Korea: an interrupted time series analysis

Background High rates of involuntary hospitalization and long lengths of stay have been problematic in Korea. To address these problems, the Mental Health and Welfare Law was revised in 2016, mainly to protect patient rights by managing involuntary admissions. The aim of this study was to evaluate the impact of the revised Mental Health and Welfare Law on deinstitutionalization by using routinely collected data from hospital admissions and continuity of mental health service use after hospital discharge as proxy measures of deinstitutionalization. Methods We used monthly-aggregated claims-based data with a principal or secondary diagnosis of schizophrenia from 2012 to 2019, collected by the National Health Insurance Service. Outcome variables included rates of first admission; discharges; re-admissions within 7, 30, and 90 days; outpatient visits after discharge within 7 and 30 days; and continuity of visits, at least once a month for 6 months after discharge. Using interrupted time series analysis, we estimated the change in levels and trends of the rates after revision, controlling for baseline level and trend. Results There was no significant change in first admission and discharge rates after the revision. Immediately after the revision, however, the rates of re-admission within 7 and 30 days dropped significantly, by 2.24% and 1.99%, respectively. The slopes of the re-admission rate decreased significantly, by 0.10% and 0.14%, respectively. The slopes of the re-admission rate within 90 days decreased (0.001%). The rates of outpatient visits within 7 and 30 days increased by 1.98% and 2.72%, respectively. The rate of continuous care showed an immediate 4.0% increase. Conclusions The revision had slight but significant effects on deinstitutionalization, especially decreasing short-term re-admission and increasing immediate outpatient service utilization.The study is funded by the Korean NeuroPsychiatric Association: 2018-001

Numb Chin Syndrome with Concomitant Painful Ophthalmoplegia Leading to a Diagnosis of Diffuse Large B Cell Lymphoma

Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease

Translation and validation of the Korean confusion assessment method for the intensive care unit

<p>Abstract</p> <p>Background</p> <p>Delirium is a common problem and associated with poor outcomes in intensive care unit (ICU) patients. Diagnosis of delirium in ICU patients is limited and usually underdiagnosed by physicians. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is one of the most widely used screening methods for detection of ICU delirium. Our goal was to translate and validate the CAM-ICU for use in the Korean ICU setting.</p> <p>Methods</p> <p>Translation of the CAM-ICU was done according to the guidelines suggested by the Translation and Cultural Adaptation Group. For validation and interrater reliability assessment of the Korean CAM-ICU, two nurses independently assessed delirium in ICU patients and the results were compared with the reference evaluation, which was done by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV).</p> <p>Results</p> <p>Twenty-two patients were evaluated by two nurses and one psychiatrist expert independently. During the study period, we have continuously educated study nurses. Based on DSM-IV criteria, 16 out of 22 (72.7%) patients developed delirium. The sensitivities of the two nurses' evaluations using the Korean CAM-ICU were 89.80% for nurse 1 and 77.40% for nurse 2. Their specificities were 72.40% and 75.80% and their overall accuracy was 83.33% and 88.37% respectively. The Korean CAM-ICU was done with reasonable interrater reliability between nurse 1 and nurse 2 (κ = 0.81, <it>p </it>< 0.001).</p> <p>Conclusions</p> <p>The Korean CAM-ICU showed good validity and could be incorporated into clinical practice in Korean ICUs.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN50265663">ISRCTN50265663</a></p

Encoder-decoder multimodal speaker change detection

The task of speaker change detection (SCD), which detects points where speakers change in an input, is essential for several applications. Several studies solved the SCD task using audio inputs only and have shown limited performance. Recently, multimodal SCD (MMSCD) models, which utilise text modality in addition to audio, have shown improved performance. In this study, the proposed model are built upon two main proposals, a novel mechanism for modality fusion and the adoption of a encoder-decoder architecture. Different to previous MMSCD works that extract speaker embeddings from extremely short audio segments, aligned to a single word, we use a speaker embedding extracted from 1.5s. A transformer decoder layer further improves the performance of an encoder-only MMSCD model. The proposed model achieves state-of-the-art results among studies that report SCD performance and is also on par with recent work that combines SCD with automatic speech recognition via human transcription.Comment: 5 pages, accepted for presentation at INTERSPEECH 202

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

How Many High Risk Korean Patients with Osteopenia Could Overlook Treatment Eligibility?

Study DesignRetrospective study.PurposeTo determine the prevalence of high risk patient with osteopenia requiring pharmacologic treatment and investigate the difference of 10-year fracture probability whether bone mineral density (BMD) include or not in Korean FRAX model.Overview of LiteratureMany people with the fracture have osteopenia rather than osteoporosis, and BMD alone could be considered as a chance to prevent fracture.MethodsThree hundred sixty-nine patients who was diagnosed as osteopenia were divided into two groups according to age (group 1, under 65 years; group 2, over 65 years), and 10-year fracture probabilities were calculated by FRAX algorithm with and without femur neck T-score.ResultsThe high risk patients of the fracture who had above 3% of 10-year hip fracture probability were 15 cases in group 1 and 121 cases in group 2. In 193 patients of group 1, the mean 10-year fracture probability with BMD was significantly higher than the results without BMD (hip fracture: p=0.04, major osteoporotic fracture: p=0.01). Unlike the results of the group 1, the mean 10-year fracture probability without BMD was significantly higher than the results with BMD in 176 patients of group 2 (hip fracture: p=0.01, major osteoporotic fracture: p=0.01).ConclusionsTotal of 136 cases (36.8%) as a high risk of the fracture with osteopenia could be overlooked treatment eligibility in Korean. The Korean FRAX model without BMD could be effective in predicting fracture risk especially in the individuals who were over 65 years

A Case of Superficial Giant Basal Cell Carcinoma with Satellite Lesions on Scalp

Giant basal cell carcinoma (BCC), defined as a lesion greater than 5 cm at its largest diameter, is a rare variant of BCC. In contrast to small BCC, giant BCC develops on skin that is not exposed to sunlight, including the back, shoulder, groin and thigh. Most of the histopathologic subtypes of giant BCC are micronodular, morpheaform and nodular, but the superficial subtype is rare. Giant superficial BCC arising on the scalp is extremely rare. We report the case of giant superficial BCC with four satellite lesions on the scalp in a 53-year-old male without predisposing factors

Clinical and Microbiologic Investigation of an Expedited Peri-implantitis Dog Model: An Animal Study

Background: Animal studies are pivotal in allowing experimentation to identify efficacious treatment protocols for resolution of peri-implantitis. The purpose of this investigation was to characterize an expedited dog peri-implantitis model clinically, radiographically, and microbiologically. Methods: Eight hound dogs underwent extractions (week 0) and implant (3.3 × 8.5 mm) placement with simultaneous surgical defect creation and ligature placement for induction of peri-implantitis (week 10). Ligatures were replaced at 6 weeks (week 16) and removed after 9 weeks (week 19) when supporting bone loss involved approximately 50% of the peri-implant bone. Microbial samples from the defects and healthy control implant sites collected at week 19 were analyzed utilizing a microarray. Clinical measures of inflammation were obtained and radiographic bone loss was measured from periapical radiographs. Radiographic depth and width measurements of bony defect were repeated at weeks 10 (baseline), 16, and 19. Canonical analysis of principal coordinates was used to visualize overall differences in microbial abundance between peri-implantitis and healthy implants. Results: This accelerated disease protocol led to intrabony defect creation with a mean depth and width of 4.3 mm and 3.5 mm, respectively after 9 weeks of ligature placement. Microbial identification revealed 59 total bacteria in peri-implant sites, 21 of which were only present in peri-implant sites as compared to healthy controls. Overall microbial beta diversity (microbial between-sample compositional diversity) differed between peri-implantitis and healthy implants (p = 0.009). Conclusions: Within the limitations of this study, this protocol led to expedited generation of peri-implant defects with a microbial profile indicative of a shift to disease and defect patterns conducive to regenerative treatment. However, the possibility of potential spontaneous resolution of lesions due to the lack of a chronicity interval as compared to chronic disease models need to be further clarified and considered during preclinical peri-implantitis model selection