Suicide Attempts in Patients With Amyotrophic Lateral Sclerosis: An Analysis of the Korean National Health Insurance Database.

Objective: The knowledge of the common risk factors for suicide attempts may not be simply applicable to patients with amyotrophic lateral sclerosis (ALS). We aimed to identify risk factors associated with suicide attempts in patients with ALS and to determine the annual prevalence and periods of vulnerability associated with attempts.Methods: This nationwide cohort study was performed using the Korean National Health Insurance Database. All patients with ALS concomitantly registered for the Exempted Calculation of Health Insurance for rare, incurable diseases between 2011 and 2017 were identified. We used the Cox proportional hazards regression model and competing risk model to identify the risk factors for suicide attempts. The multivariable models were adjusted for potential risk factors from the univariate analysis.Results: Among 2,955 incident patients, 47 attempted suicide. After adjusting for sex, previous attempts, and previous psychiatric disorders, the hazard ratios for psychiatric hospitalization before ALS diagnosis were 3.17 (95% confidence interval [CI], 1.31-7.70; P = .01) and 3.02 (95% CI, 1.32-6.90; P = .01) in the Cox regression model and the competing risk model, respectively. The annual prevalence of suicide attempts was 0.29%-1.12%. Twenty (42.6%) and 9 (19.1%) attempts occurred within 3 months and 12-18 months after diagnosis, respectively.Conclusions: Psychiatric hospitalization increased the risk of suicide attempts, which clustered at the early stage or on losing autonomy. Those with a history of psychiatric hospitalization should receive an in-depth evaluation and be cautiously monitored.

A newly developed PLD1 inhibitor ameliorates rheumatoid arthritis by regulating pathogenic T and B cells and inhibiting osteoclast differentiation.

Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline, plays multiple roles in inflammation. We investigated the therapeutic effects of the newly developed PLD1 inhibitors A2998, A3000, and A3773 in vitro and in vivo rheumatoid arthritis (RA) model. A3373 reduced the levels of LPS-induced TNF-α, IL-6, and IgG in murine splenocytes in vitro. A3373 also decreased the levels of IFN-γ and IL-17 and the frequencies of Th1, Th17 cells and germinal-center B cells, in splenocytes in vitro. A3373 ameliorated the severity of collagen-induced arthritis (CIA) and suppressed infiltration of inflammatory cells into the joint tissues of mice with CIA compared with vehicle-treated mice. Moreover, A3373 prevented systemic bone demineralization in mice with CIA and suppressed osteoclast differentiation and the mRNA levels of osteoclastogenesis markers in vitro. These results suggest that A3373 has therapeutic potential for RA.

Serious infections and tuberculosis in psoriasis patients receiving systemic therapy in Korea: a nationwide population-based cohort study.

BACKGROUND: Psoriasis itself, as well as its immunomodulatory drugs, may alter the immune system, increasing the risk of infections. Recent research has indicated that patients with psoriasis are at an increased risk of developing severe infections including tuberculosis. OBJECTIVES: To evaluate and compare the incidence of serious infectious diseases in Korea between patients with psoriasis and participants without psoriasis regarding each treatment modality. MATERIALS & METHODS: This nationwide cohort study utilized claims data based on the National Health Insurance Service between January 2005 and December 2018. RESULTS: In total, 293,073 patients with psoriasis enrolled for the analysis of serious infection and 272,400 patients enrolled for the analysis of tuberculosis. Participants without psoriasis matched by age and sex (1:1 ratio) were also enrolled. For serious infection overall, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.21 (1.20-1.23), 1.23 (1.17-1.28), and 1.33 (1.09-1.63) for the non-systemic, non-biologic systemic, and biologic groups, respectively. For tuberculosis overall, the aHRs were 1.15 (1.10-1.20), 1.32 (1.10-1.57), and 6.72 (4.28-10.56) for the non-systemic, non-biologic systemic, and biologic groups, respectively. CONCLUSION: This study reveals that the risk of serious infection and tuberculosis in patients with psoriasis was significantly higher than in participants without psoriasis. Moreover, patients with psoriasis who received systemic therapy other than phototherapy had a higher risk of these infections compared to those without psoriasis. Also, biologics appeared to increase the risk of tuberculosis in patients with psoriasis. Dermatologists should consider these potential risks when selecting treatment modalities for psoriasis.

Risk of malignancy in patients with psoriasis according to treatment modalities in Korea: a nationwide cohort study.

Intrinsic immunologic disparity of psoriasis itself, along with chronic inflammation and immunomodulatory anti-psoriatic treatments could be associated with increased risk of malignancy. We aimed to estimate the risk of malignancy in patients with psoriasis by treatment modality compared with that in individuals without psoriasis in Korea. We conducted a nationwide cohort study using the claims database of the National Health Insurance Service from January 2005 to December 2018. A total of 255,471 patients with psoriasis, and age- and sex-matched non-psoriasis participants (1:1 ratio) were enrolled. The adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] for malignancy without nonmelanoma skin cancer (NMSC) were 1.10 [1.08-1.12] in patients with psoriasis, 1.13 [1.00-1.27], 1.05 [0.97-1.13], and 1.24 [0.84-1.83] in phototherapy, non-biologic systemics, and biologics cohort, respectively. Among the non-biologic systemics cohort, patients treated with cyclosporin showed higher risk of malignancy without NMSC (aHR [95% CI], 1.20 [1.04-1.39]). The risk of malignancy without NMSC in patients with psoriasis was higher than that in individuals without psoriasis. Phototherapy and biologics were not associated with significant increase of risk; however, cyclosporin appeared to increase its risk. Dermatologists should be vigilant about this potential risk while managing patients with psoriasis.

Anti-arthritic effects of Schisandra chinensis extract in monosodium iodoacetate-induced osteoarthritis rats.

The present study aimed to investigate the therapeutic effects of Schisandra chinensis (SC) extract on clinical symptoms of osteoarthritis and the modulating effect on the mechanisms associated with the progression of osteoarthritis in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Osteoarthritis-induced rats were randomized into four groups: MIA injection control (MC), MIA injection with celecoxib (PC), MIA injection with SC extract 100 mg/kg (SC100), and MIA injection with SC extract 200 mg/kg (SC200). Another healthy group received a saline injection as a negative control (NC). During the treatment, weight-bearing measurements were performed once a week for 4 weeks. Histopathological and biochemical analyses of the joints, blood, and chondrocyte tissue were performed following the completion of treatment. Compared with MC rats, SC rats demonstrated significantly alleviated pain behavior, bone erosion, and cartilage degradation. SC reduced serum levels of matrix metalloproteinases and pro-inflammatory cytokines. SC treatment also reversed the levels of biomarkers such as Collagen II and ADAMTS4 in the cartilage tissue. Moreover, SC administration inhibited the phosphorylation levels of nuclear factor kappa B (NF-κB) and NF-κB Inhibitor alpha. This study demonstrates that SC ameliorated osteoarthritis at in vivo level. Our results suggest that SC might be a potential therapeutic agent for osteoarthritis.

Spadework for Establishing Integrative Enhanced Recovery Program After Spine Surgery: Web-Based Survey Assessing Korean Medical Doctors' Perspectives.

Introduction: Efforts are necessary to promote postoperative patient management to reduce complications or side effects, particularly those adapted to spinal surgery. Considering compatible medical system in Korea, the study objective is to report the opinions of Korean medical doctors regarding integrative enhanced recovery after spine surgery. Methods: From December 2020 to January 2021, members of the Korean Medical Association were asked to complete an online questionnaire regarding an integrative enhanced recovery program after spine surgery. A total of 726 participants responded to the survey. Results: Approximately half of the respondents had more than 10 years of medical experience in the Korean health-care system, and 58.29% were affiliated with primary Korean medical clinics. The majority of respondents were not aware of the ERAS program (N = 412, 79.08%) but said that patient management would be advanced from the establishment of a postoperative medical program that reflected an integrated medical perspective (N = 505, 96.92%). Furthermore, Korean medical professionals believe that Korean medical interventions should play a major role in the pain management and digestive improvement sections of the upcoming postoperative program. Moreover, respondents claimed that Korean traditional medical modalities such as acupuncture, moxibustion, cupping, and herbal decoction should be included in the program. Discussion/Conclusion: Responses collected from the present study can be used as a spadework for future studies. A study on the development of a comprehensive postoperative program that reflects the perspectives of patients and conventional medical doctors is needed.

The potential impact of systemic anti-inflammatory therapies in psoriasis on major adverse cardiovascular events: a Korean nationwide cohort study.

This nationwide population-based cohort study aimed to investigate the impact of systemic anti-inflammatory treatment on the major adverse cardiovascular events (MACE) risk in patients with psoriasis from January 2006 to December 2018, using a database provided by the Korean National Health Insurance Service. Patients were grouped based on the following treatment modalities: biologics, phototherapy, methotrexate, cyclosporine, and mixed conventional systemic agents. Patients who had not received any systemic treatment were assigned to the control cohort. The incidence of MACE per 1000 person-year was 3.5, 9.3, 12.1, 28.4, 39.5, and 14.5 in the biologic, phototherapy, methotrexate, cyclosporine, mixed conventional systemic agents, and control cohorts, respectively. During the 36-month follow-up, the cumulative incidence of MACE in the phototherapy and biologic cohorts remained lower than that of other treatment modalities. Cyclosporine (hazard ratio (HR) = 2.11, 95% confidence interval (CI) = 1.64-2.71) and mixed conventional systemic agents (HR = 2.57, 95% CI = 2.05-3.22) treatments were associated with increased MACE risk. Methotrexate treatment was not associated with MACE. Our finding demonstrates that treatment modalities may affect cardiovascular comorbidities in patients with psoriasis. Thus, an appropriate combination of anti-psoriatic therapies should be considered to manage patients with high cardiovascular risk.IRB approval status: Waiver decision was obtained by the institutional review board, Konkuk University Hospital, Seoul, Republic of Korea (KUH1120107).

Anti-Inflammatory Effects of Fermented Lotus Root and Linoleic Acid in Lipopolysaccharide-Induced RAW 264.7 Cells.

Inflammation is a protective response of the innate immune system. However, aberrant inflammatory responses lead to various diseases. Lotus root, the edible rhizome of Nelumbo nucifera, is a popular traditional herbal medicine in East Asia. In a previous study, we reported that fermented lotus root (FLR) alleviated ethanol/HCl-induced gastric ulcers in rats by modulating inflammation-related genes. However, the mechanisms underlying the anti-inflammatory effects of FLR and its major constituent, linoleic acid (LA), are still largely unknown. In this study, we investigated the anti-inflammatory effects of FLR and LA on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 murine macrophages. We found that FLR inhibited LPS-induced expression of inflammatory mediators through down-regulation of NF-κB activity. Similarly, LA also attenuated LPS-induced inflammatory responses and reduced LPS-induced phosphorylation of proteins associated with NF-κB signaling, such as ERK, JNK, and p38. Overall, our results suggested that FLR and LA may effectively ameliorate inflammatory diseases.

Bone health in neuromyelitis optica: Bone mineral density and fractures.

BACKGROUND: The bone health in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G antibodies (NMOSD-AQP4) have not been fully evaluated. To evaluate the prevalence of fractures and bone loss in patients with NMOSD-AQP4 compared to healthy controls and patients with multiple sclerosis (MS) and to identify the risk factors associated with fractures and low bone mineral density (BMD) in patients with NMOSD-AQP4. METHODS: Seventy-one patients with NMOSD-AQP4 were included. The two control groups consisted of 213 age-, sex-, menopause-, and body mass index (BMI)-matched healthy participants from the Korean National Health and Nutrition Examination Survey (healthy controls) and 41 patients with multiple sclerosis (disease controls). We collected demographic and clinical data related to bone health including BMD and FRAX score. RESULTS: Patients with NMOSD-AQP4 had a higher prevalence of fractures than the healthy control group (OR = 5.40, CI = 2.004-14.524, p = 0.001), with falling, but not steroid use, being associated with an increased risk of fractures after diagnosis with NMOSD-AQP4 (OR = 24.902, CI = 3.086-200.947, p = 0.003). They also had significantly lower BMD than controls (femur neck, p = 0.044; total hip, p < 0.001), which was more prominent in young participants. The BMD in the NMOSD-AQP4 group was associated with cumulative dose of oral steroids, age, sex, BMI, and partly with the prophylactic calcium supplements. Though the patients with NMOSD-AQP4 did not differ significantly from patients with MS in terms of fracture rate and BMD, they had higher risk of fractures as measured by the Fracture Risk Assessment Tool (for major osteoporotic fractures, (p = 0.001; for hip fractures, p = 0.018). CONCLUSION: Patients with NMOSD-AQP4 had a significantly higher risk of fractures that could mostly be attributed to falling. Additionally, low BMD was observed in these patients; it was more prominent among young patients, associated with steroid use, and may partially prevented by the use of prophylactic calcium supplements.

Beneficial Effects of Lactobacillus plantarum Strains on Non-Alcoholic Fatty Liver Disease in High Fat/High Fructose Diet-Fed Rats.

Emerging evidence suggests that probiotics are beneficial in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the effects of two Lactobacillus plantarum strains, ATG-K2 and ATG-K6 (isolated from Korean fermented cabbage), in a rat model of high fat/high fructose (HF/HF) diet-induced NAFLD. Rats with NAFLD were randomized into four groups (HF/HF diet control, (HC); HF/HF diet with silymarin, (PC); HF/HF diet with ATG-K2, (K2); and HF/HF diet with ATG-K6, (K6)) with healthy rats on a normal diet serving as the negative control. After treatment, histopathological and biochemical analyses of the blood and liver tissue were conducted. In addition, fecal microbiota was analyzed using the MiSeq platform. Compared with HC rats, K2 and K6 rats experienced significantly lower body weight gain, displayed decreased hepatic lipid accumulation, had lower serum levels of aspartate aminotransferase and alanine aminotransferase, and showed increased antioxidant enzyme activities. Moreover, de novo lipogenesis-related genes were downregulated following K2 and K6 administration. The fecal microbiota of K2 and K6 rats contained a higher proportion of Bacteriodetes and a lower proportion of Fimicutes than that of HC rats. Taken together, our results suggest that L. plantarum strains ATG-K2 and ATG-K6 are potential therapeutic agents for NAFLD.

The most reliable time point for intact parathyroid hormone measurement to predict hypoparathyroidism after total thyroidectomy with central neck dissection to treat papillary thyroid carcinoma: a prospective cohort study.

PURPOSE: We assessed the optimal time for intact parathyroid hormone (iPTH) measurement for early detection of post-total thyroidectomy (TT) hypocalcemia in patients with papillary thyroid carcinoma (PTC). METHODS: In this single-center prospective cohort study, 143 patients who underwent TT with central neck dissection with or without lateral neck dissection for PTC were included. Biochemical profiles including iPTH, corrected total calcium, and ionized calcium within 24 h after surgery were analyzed. RESULTS: The 4-h postoperative iPTH was the most reliable predictor of post-TT transient or permanent hypoparathyroidism (cutoff for hypocalcemia was 3.75 pg/mL, AUC = 0.885, P < 0.001, sensitivity 81.6%, specificity 86.0%; cutoff for permanent hypocalcemia was 2.48 pg/mL, AUC = 0.819, P < 0.001, sensitivity 100%, specificity 57.8% calculated using ROC curves). CONCLUSIONS: The 4-h postoperative iPTH can most accurately predict hypoparathyroidism after TT with central neck dissection to treat PTC and facilitate the early discharge of low-risk postoperative hypoparathyroidism patients and decrease unnecessary overnight observation and calcium supplementation.

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells.

Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH4) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH4 synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH4-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague-Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH4 synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH4 storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH4 synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH4/NO pathway.

Self-Powered Coiled Carbon-Nanotube Yarn Sensor for Gastric Electronics.

The strong peristaltic contraction of the stomach facilitates mixing and emptying of ingested food, which occurs rhythmically at approximately 3 cycles/min (cpm) in humans. Generally, most patients with gastroparesis show gastric electrical dysrhythmia that is disrupted electrical signals controlling gastric contractions. For treatment of gastric electrical dysrhythmia, in vivo electrical impulses to the stomach via an implanted gastric stimulator have been known to restore these gastric deformations. Nevertheless, improved sensors to monitor gastric contractions are still needed in current gastric stimulators. Recently, we have developed a new technology converting mechanical motion to electrical energy by using stretch-induced capacitance changes of a coiled carbon-nanotube (CNT) yarn. For its potential use as a gastric deformation sensor, the performance of a coiled CNT yarn was evaluated in several biological fluids. For a sinusoidal stretch to 30%, the peak-to-peak open-circuit voltage (OCV) was consistently generated at frequencies below 0.1 Hz. This sinusoidal variation in OCV augmented as the strain increased from 10 to 30%. In an in vitro artificial gastric system, the OCV was approximately linearly proportional to the balloon volume, which can monitor periodic deformations of the balloon at 2, 3, and 4 cpm as shown for human gastric deformations. Moreover, stretchy coiled yarns generate the peak electrical voltage and power when deformed. The present study shows that a self-powered CNT yarn sensor can not only monitor the changes in frequency and amplitude of volumetric change but also generate electrical power by periodic deformations of the balloon. Therefore, it seems possible to automatically deliver accurate electrical impulses according to real-time evaluation of a patient's gastric deformation based on information on the frequency, amplitude, and rate of the OCV from CNT yarn.

Changing patterns of multiple sclerosis in Korea: Toward a more baseline MRI lesions and intrathecal humoral immune responses.

BACKGROUND: The environmental risks of multiple sclerosis (MS), including adolescent obesity and vitamin D deficiency, are increasing in Korea. We aimed to determine whether the patterns and/or severity of MS in Korea can change according to the year of birth or disease onset. METHODS: Two hundred and sixty-six patients with adult-onset MS, including 164 with an available baseline magnetic resonance imaging (MRI), were retrospectively included from 17 nationwide referral hospitals in Korea. The demographics, MRI T2 lesion burden at disease onset, cerebrospinal fluid markers, and prognosis were assessed. RESULTS: The birth year, time from disease onset to first MRI, and female sex were associated with a higher number of baseline MRI T2 lesions. The birth year was also associated with the presence of oligoclonal band in the cerebrospinal fluid and high immunoglobin G index. An increased female/male ratio was observed among those with a more recent year of birth and/or disease onset. CONCLUSIONS: In Korea, the disease pattern of adult-onset MS may be changing toward a more baseline T2 MRI lesions, intrathecal humoral immune responses, and also higher female ratio.

Zebrafish extracellular matrix improves neuronal viability and network formation in a 3-dimensional culture.

Mammalian central nervous system (CNS) has limited capacity for regeneration. CNS injuries cause life-long debilitation and lead to $50 billion in healthcare costs in U.S. alone each year. Despite numerous efforts in the last few decades, CNS-related injuries remain as detrimental as they were 50 years ago. Some functional recovery can occur, but most regeneration are limited by an extracellular matrix (ECM) that actively inhibits axonal repair and promotes glial scarring. In most tissues, the ECM is an architectural foundation that plays an active role in supporting cellular development and regenerative response after injury. In mammalian CNS, however, this is not the case - its composition is not conducive for regeneration, with various molecules restricting plasticity and neuronal growth. In fact, the CNS ECM alters its composition dramatically following injury to restrict regeneration and to prioritize containment of injury as well as preservation of intact neural circuitry. This leads us to hypothesize that the inhibitory extracellular environment needs be modified or supplemented to be more regeneration-permissive for significant CNS regeneration. Mammalian nervous tissue cannot provide such ECM, and synthesizing it in a laboratory is beyond current technology. Evolutionarily lower species possess remarkably regenerative neural tissue. For example, small fresh-water dwelling zebrafish (Danio rerio) can regenerate severed spinal cord, re-gaining full motor function in a week. We believe their ECM contributes to its regenerative capability and that it can be harnessed to induce more regeneration in mammalian CNS. This study shows that ECM derived from zebrafish brains promotes more neuronal survival and axonal network formation than the widely studied and available ECM derived from mammalian tissues such as porcine brains, porcine urinary bladder, and rat brains. We believe its regenerative potential, combined with its affordability, easy handling, and fast reproduction, will make zebrafish an excellent candidate as a novel ECM source.

Assessing Statistically Significant Heavy-Metal Concentrations in Abandoned Mine Areas via Hot Spot Analysis of Portable XRF Data.

To develop appropriate measures to prevent soil contamination in abandoned mining areas, an understanding of the spatial variation of the potentially toxic trace elements (PTEs) in the soil is necessary. For the purpose of effective soil sampling, this study uses hot spot analysis, which calculates a z-score based on the Getis-Ord Gi* statistic to identify a statistically significant hot spot sample. To constitute a statistically significant hot spot, a feature with a high value should also be surrounded by other features with high values. Using relatively cost- and time-effective portable X-ray fluorescence (PXRF) analysis, sufficient input data are acquired from the Busan abandoned mine and used for hot spot analysis. To calibrate the PXRF data, which have a relatively low accuracy, the PXRF analysis data are transformed using the inductively coupled plasma atomic emission spectrometry (ICP-AES) data. The transformed PXRF data of the Busan abandoned mine are classified into four groups according to their normalized content and z-scores: high content with a high z-score (HH), high content with a low z-score (HL), low content with a high z-score (LH), and low content with a low z-score (LL). The HL and LH cases may be due to measurement errors. Additional or complementary surveys are required for the areas surrounding these suspect samples or for significant hot spot areas. The soil sampling is conducted according to a four-phase procedure in which the hot spot analysis and proposed group classification method are employed to support the development of a sampling plan for the following phase. Overall, 30, 50, 80, and 100 samples are investigated and analyzed in phases 1-4, respectively. The method implemented in this case study may be utilized in the field for the assessment of statistically significant soil contamination and the identification of areas for which an additional survey is required.

Th17 and IL-17 Cause Acceleration of Inflammation and Fat Loss by Inducing α2-Glycoprotein 1 (AZGP1) in Rheumatoid Arthritis with High-Fat Diet.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints. High-fat diet (HFD) is a risk factor for RA and is related to inflammation but responds minimally to medication. Given the association between HFD and inflammation, it is important to understand the function of inflammation-related T cells in RA with HFD. Collagen-induced arthritis (CIA), a model of RA, was induced in HFD mice by injection of collagen II, and metabolic markers and T cells were analyzed. The metabolic index and IgG assay results were higher in HFD-CIA mice than in nonfat diet-CIA mice. Numbers of inflammation-related T cells and macrophages, such as Th1 and Th17 cells and M1 macrophages, were higher in spleens of HFD-CIA mice. HFD-CIA mice had a high level of α2-glycoprotein 1 (Azgp1), a soluble protein that stimulates lipolysis. To examine the association between Azgp1 and Th17 cells, the reciprocal effects of Azgp1 and IL-17 on Th17 differentiation and lipid metabolism were measured. Interestingly, Azgp1 increased the Th17 population of splenocytes. Taken together, our data suggest that the acceleration of fat loss caused by Azgp1 in RA with metabolic syndrome is related to the increase of IL-17. Mice injected with the Azgp1-overexpression vector exhibited more severe CIA compared with the mock vector-injected mice.

Effect of peripheral nerve tetanic stimulation on the inter-trial variability and accuracy of transcranial motor-evoked potential in brain surgery.

OBJECTIVES: The aim of this study was to evaluate and compare the advantages of post-tetanic motor-evoked potential (p-MEP) and conventional motor-evoked potential (c-MEP) in terms of MEP inter-trial variability and accuracy. METHODS: c-MEP and p-MEP were quantified in subjects who underwent brain surgery. c-MEP was generated by transcranial electrical stimulation (TES). p-MEP was generated using a preconditioning process involving tetanic stimulation at the left tibial nerve followed by TES. The presence of significant MEP deterioration was monitored during major surgical process. An additional 5-8 MEP obtained after major surgical process were used to analyze amplitude parameters such as mean, standard deviation, range, coefficient of variation (CV), and range to mean ratio. RESULTS: When only irreversible MEP deteriorations were considered as positive results, the false-positive rate was identical for p-MEP and c-MEP. When total MEP deteriorations were considered as positive results, the false-positive rate of p-MEP was lower and p-MEP had higher specificity than c-MEP. The mean amplitude of p-MEP was significantly higher than that of c-MEP. The CV and range to mean ratio of p-MEP were less than those of c-MEP. CONCLUSION: The p-MEP technique is useful for augmenting MEP amplitude and reducing inter-trial variability. SIGNIFICANCE: p-MEP has clinical significance as a useful technique for intraoperative monitoring.

Factors supporting long-term culture of bovine male germ cells.

Spermatogonial stem cells (SSCs) are unipotent in nature, but mouse SSCs acquire pluripotency under the appropriate culture conditions. Although culture systems are available for rodent and human germ-cell lines, no proven culture system is yet available for livestock species. Here, we examined growth factors, matrix substrates and serum-free supplements to develop a defined system for culturing primitive germ cells (gonocytes) from neonatal bovine testis. Poly-L-lysine was a suitable substrate for selective inhibition of the growth of somatic cells and made it possible to maintain a higher gonocyte:somatic cell ratio than those maintained with gelatin, collagen or Dolichos biflorus agglutinin (DBA) substrates. Among the serum-free supplements tested in our culture medium, knockout serum replacement (KSR) supported the proliferation and survival of gonocytes better than the supplements B-27 and StemPro-SFM after sequential passages of colonies. Under our optimised culture conditions consisting of 15% KSR supplement on poly-L-lysine-coated dishes, the stem-cell and germ-cell potentials of the cultured gonocytes were maintained with normal karyotype for more than 2 months (over 13 passages). The proposed culture system, which can maintain a population of proliferating bovine germ stem cells, could be useful for studying SSC biology and germline modifications in livestock animals.

Anthocyanin Extracted from Black Soybean Seed Coats Prevents Autoimmune Arthritis by Suppressing the Development of Th17 Cells and Synthesis of Proinflammatory Cytokines by Such Cells, via Inhibition of NF-κB.

INTRODUCTION: Oxidative stress plays a role in the pathogenesis of rheumatoid arthritis (RA). Anthocyanin is a plant antioxidant. We investigated the therapeutic effects of anthocyanin extracted from black soybean seed coats (AEBS) in a murine model of collagen-induced arthritis (CIA) and human peripheral blood mononuclear cells (PBMCs) and explored possible mechanisms by which AEBS might exert anti-arthritic effects. MATERIAL AND METHODS: CIA was induced in DBA/1J mice. Cytokine levels were measured via enzyme-linked immunosorbent assays. Joints were assessed in terms of arthritis incidence, clinical arthritis scores, and histological features. The extent of oxidative stress in affected joints was determined by measuring the levels of nitrotyrosine and inducible nitric oxide synthase. NF-κB activity was assayed by measuring the ratio of phosphorylated IκB to total IκB via Western blotting. Th17 cells were stained with antibodies against CD4, IL-17, and STAT3. Osteoclast formation was assessed via TRAP staining and measurement of osteoclast-specific mRNA levels. RESULTS: In the CIA model, AEBS decreased the incidence of arthritis, histological inflammation, cartilage scores, and oxidative stress. AEBS reduced the levels of proinflammatory cytokines in affected joints of CIA mice and suppressed NF-κB signaling. AEBS decreased Th17 cell numbers in spleen of CIA mice. Additionally, AEBS repressed differentiation of Th17 cells and expression of Th17-associated genes in vitro, in both splenocytes of naïve DBA/1J mice and human PBMCs. In vitro, the numbers of both human and mouse tartrate-resistant acid phosphatase+ (TRAP) multinucleated cells fell, in a dose-dependent manner, upon addition of AEBS. CONCLUSIONS: The anti-arthritic effects of AEBS were associated with decreases in Th17 cell numbers, and the levels of proinflammatory cytokines synthesized by such cells, mediated via suppression of NF-κB signaling. Additionally, AEBS suppressed osteoclastogenesis and reduced oxidative stress levels.