Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus.

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP-competitive mitotic kinesin KIF18A inhibitor BTB-1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB-1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran-binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB-1 greatly improved the viability of IAV-infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.

A Repeated Game Freeway Lane Changing Model.

Lane changes are complex safety- and throughput-critical driver actions. Most lane-changing models deal with lane-changing maneuvers solely from the merging driver's standpoint and thus ignore driver interaction. To overcome this shortcoming, we develop a game-theoretical decision-making model and validate the model using empirical merging maneuver data at a freeway on-ramp. Specifically, this paper advances our repeated game model by using updated payoff functions. Validation results using the Next Generation SIMulation (NGSIM) empirical data show that the developed game-theoretical model provides better prediction accuracy compared to previous work, giving correct predictions approximately 86% of the time. In addition, a sensitivity analysis demonstrates the rationality of the model and its sensitivity to variations in various factors. To provide evidence of the benefits of the repeated game approach, which takes into account previous decision-making results, a case study is conducted using an agent-based simulation model. The proposed repeated game model produces superior performance to a one-shot game model when simulating actual freeway merging behaviors. Finally, this lane change model, which captures the collective decision-making between human drivers, can be used to develop automated vehicle driving strategies.

Bioprinting an Artificial Pancreas for Type 1 Diabetes.

PURPOSE OF REVIEW: Pancreatic islet cell transplantation is currently the only curative cell therapy for type 1 diabetes mellitus. However, its potential to treat many more patients is limited by several challenges. The emergence of 3D bioprinting technology from recent advances in 3D printing, biomaterials, and cell biology has provided the means to overcome these challenges. RECENT FINDINGS: 3D bioprinting allows for the precise fabrication of complex 3D architectures containing spatially distributed cells, biomaterials (bioink), and bioactive factors. Different strategies to capitalize on this ability have been investigated for the 3D bioprinting of pancreatic islets. In particular, with co-axial bioprinting technology, the co-printability of islets with supporting cells such as endothelial progenitor cells and regulatory T cells, which have been shown to accelerate revascularization of islets and improve the outcome of various transplantations, respectively, has been achieved. 3D bioprinting of islets for generation of an artificial pancreas is a newly emerging field of study with a vast potential to improve islet transplantation.

Effect of apoptosis-associated speck-like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant.

Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine-induced humoral and cell-mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine-induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC-/- ) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine-immunized ASC-/- mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC-/- mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T-lymphocyte response against influenza vaccine was not induced in ASC-/- mice. Therefore, vaccinated ASC-/- mice did not show effective protection against viral challenge. ASC-/- mice immunized with alum-formulated HPV vaccine showed similar antibody titers and T-cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV-specific antibody titers in ASC-/- mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC-deficient condition.

Randomized, controlled trial of qigong for treatment of prehypertension and mild essential hypertension.

CONTEXT: Hypertension treatments include sodium restriction, pharmacological management, and lifestyle modifications. Although many cases of hypertension can be controlled by medication, individuals may experience side effects or incur out-of-pocket expenses, and some may not comply with the treatment regimen. Although some previous studies have shown a favorable effect for qigong on hypertension, well-designed, rigorous trials evaluating the effect of qigong on hypertension are scarce. OBJECTIVE: This study aimed to evaluate the effect of qigong on prehypertension and mild hypertension and to calculate a sample size for a subsequent randomized, clinical trial (RCT). DESIGN: Participants were randomized to a qigong group or an untreated control group. SETTING: This study was conducted at the Oriental Medical Center of Dongeui University, in the Republic of Korea. PARTICIPANTS: Participants were individuals between the ages of 19 and 65 y with systolic blood pressure (SBP) between 120 and 159 mm Hg and/or diastolic blood pressure (DBP) between 80 and 99 mm Hg. INTERVENTION: The qigong group attended qigong classes 3 ×/wk and performed qigong at home at least 2 ×/wk. Participants in the control group did not receive any intervention for hypertension. OUTCOME MEASURES: Outcome measures for this study were (1) changes in blood pressure (BP); (2) quality of life (QOL) using 2 surveys: the Medical Outcomes Study (MOS) 36-item short form (SF-36) (Korean version) and the Measure Yourself Medical Outcome Profile 2 (MYMOP2); and (3) hormone levels. RESULTS: Of 40 participants, 19 were randomly assigned to the qigong group, and 21 were assigned to the control group. After 8 wk, significant differences were observed between the qigong and the control groups regarding changes in SBP (P = .0064) and DBP (P = .0003). Among the categories of the MYMOP2 questionnaire, only wellbeing was significantly different between the 2 groups (P = .0322). The qigong group showed a significantly greater improvement in the physical component score of the SF-36 compared with the control group (P = .0373). Regarding changes in hormone levels, there was no significant difference between the qigong and the control groups. This pilot study demonstrates that regarding sample size, a RCT evaluating the effect of qigong on hypertension should include 22 participants based on DBP and 285 participants based on SBP in each group, thus allowing for a loss to follow-up rate of 20%. CONCLUSION: The results indicate that qigong may be an effective intervention in reducing BP in prehypertension and mild hypertension. Further studies should include an appropriate sample size and methodology to determine the mechanism of qigong on BP.

Moxibustion for treating knee osteoarthritis: study protocol of a multicentre randomised controlled trial.

BACKGROUND: The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care. METHODS/DESIGNS: This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach. DISCUSSION: This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis. TRIAL REGISTRATION NUMBER: KCT0000130.

The effectiveness of moxibustion for the treatment of functional constipation: a randomized, sham-controlled, patient blinded, pilot clinical trial.

BACKGROUND: Moxibustion is an ancient traditional medicine using burning mugworts to stimulate acupuncture points. The aim of this study was to investigate the safety and efficacy of moxibustion for the treatment of constipation using a randomized, sham-controlled, participant-blinded, pilot trial. METHODS: Twenty-six participants (identified with either qi (vital energy) deficiency or qi excess syndrome) were randomly divided into either a moxibustion or sham group. Participants were treated with real or sham moxibustion at 4 acupuncture points, ST23 and ST27, bilaterally, 3 times per week for four weeks. The primary outcome was the frequency of defecations; secondary outcomes were the Bristol stool form scale (BSS) and the constipation assessment scale (CAS). RESULTS: Of the 26 participants that were randomized, 24 completed the study. Defecation frequency, BSS, and CAS showed no difference between the moxibustion and sham groups. The differences were -0.25 (95% CI: -2.08, 1.58, p = 0.78), -1.22 (95% CI: -2.7, 0.26, p = 0.1), 0.91 (95% CI: -1.46, 3.28, p = 0.44) in defecation frequency, BSS, CAS, respectively. The defecation frequency increased from an average of 3.3 to 4.6 times per week in the moxibustion group (1.5[-0.5, 2], p = 0.06) and from 2.7 to 3.7 stools per week in the sham group (1[-1, 2], p = 0.15) after four weeks of treatment. The difference between participants with a deficiency or an excess syndrome, determined based on assessment of sweat, facial features, pain, body energy, and pulse type, was significant in only defecation frequency. The difference was 3.3 (95% CI: 0.41, 6.19, p = 0.03). CONCLUSION: Moxibustion treatment appears safe, but showed no positive effect on constipation. The effectiveness of moxibustion treatment may depend on the syndrome pattern, and further long-term studies with a larger number of subjects are warranted. TRIAL REGISTRATION: Clinical Research Information Service, KCT0000168.

Effects of Acupuncture on Lowering Blood Pressure in Postmenopausal Women with Prehypertension or Stage 1 Hypertension: A Propensity Score-Matched Analysis.

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120-159 mmHg or diastolic blood pressure 80-99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants' diastolic blood pressure (-9.92 mmHg; p < 0.001) and systolic blood pressure (-10.34 mmHg; p < 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.

A randomized pilot study of acupuncture as an adjunct therapy in adult asthmatic patients.

OBJECTIVE: This trial aimed to evaluate the feasibility of estimating the effectiveness of acupuncture on asthmatic patients under conventional medical management. PARTICIPATIONS AND METHODS: A prospective randomized, patient/assessor-blinded, sham acupuncture-, and waiting list-controlled pilot trial was conducted. Forty-five eligible asthmatic participants underwent a 1-week run-in period and were then randomized into one of three groups: an active acupuncture group, a sham acupuncture group, and a waiting list group. They were instructed to maintain the use of antiasthmatic medications. Needling was administered three times per week for 4 weeks with a 2-week follow-up in the active and sham acupuncture groups. The primary outcome was daily morning peak expiratory flow (PEF) and the secondary outcomes included forced expiratory volume one second (FEV(1)), quality of life questionnaire for adult Korean asthmatics (QLQAKA), transition dyspnea index (TDI), serum eosinophil count, and total serum immunoglobulin E (IgE). RESULTS: No significant differences in the between- or within-group values of weekly average PEF (recorded daily in the morning) and FEV(1) were found. For QLQAKA and TDI, the active acupuncture group showed a significant improvement over the waiting list group at 2, 4, and 6 weeks after randomization. DISCUSSION: Acupuncture as an adjunct therapy to conventional medical care does not seem to affect pulmonary function in asthmatic patients. However, 12 sessions of acupuncture treatment during 4 weeks showed a favorable effect on the quality of life in adult asthmatic patients. Further large trials assessing the effectiveness of acupuncture on the quality of life and symptoms in asthmatic patients are needed.

Body Acupuncture for Nicotine Withdrawal Symptoms: A Randomized Placebo-controlled Trial.

This study evaluated whether improvements in nicotine withdrawal symptoms (NWS), depression and anxiety are greater for body acupuncture than for sham acupuncture. Smoking volunteers from the public were randomized to receive six sessions of either real or sham acupuncture for 2 weeks. The primary outcome measure was NWS measured by the Minnesota Nicotine Withdrawal Score, and the secondary measures were scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Eighty volunteers were randomized into real acupuncture (n = 38) and sham acupuncture (n = 42) groups, of which 46 subjects (22 and 24 in the real and sham acupuncture groups, respectively) completed the treatment and the 2-week follow-up. An intention-to-treat analysis revealed that the NWS did not differ significantly between the real and sham acupuncture groups immediately after the treatment (12.2 ± 9.7 and 12.8 ± 7.7, respectively; mean ± SD) and at the 2-week follow-up (11.7 ± 10.2 and 12.6 ± 7.8). Both groups also showed similar improvements in BDI and BAI scores. These results indicate that the real acupuncture treatment tested in this trial was no more effective than sham acupuncture at reducing NWS, depression and anxiety for smoking cessation.

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.

Association Between Acupuncture and Knee Surgery for Osteoarthritis: A Korean, Nationwide, Matched, Retrospective Cohort Study.

Objectives: The present study was undertaken to investigate the relationship between acupuncture therapy and surgery rate. Design: Matched, retrospective cohort study. Materials and Methods: From nationwide health insurance data (2002-2013 cohort data published by the National Health Insurance Service of Korea), patients with new cases of knee osteoarthritis that occurred between January 1, 2004 and December 31, 2010 were analyzed. Patients were divided into an acupuncture group (AG) and a control group (CG), based on records of acupuncture therapy. Propensity scores were calculated by using gender, age, income level, and Charlson comorbidity index (CCI), with the groups matched at a ratio of 1:3 (AG:CG). The final analysis period was 2 years after the first acupuncture therapy for AG and 2 years after initial diagnosis for CG; surgery rates were compared between the two groups. Stratified analyses were performed based on age, gender, and income level; sensitivity analyses were performed based on the frequency and duration of acupuncture therapy. Results: Propensity score-matched AG and CG included 8,605 and 25,815 subjects, respectively. Post-matching surgery rates were 0.26 and 0.93% in AG and CG, respectively. For all age groups, AG showed a lower surgery rate than CG. In the analysis based on gender, the female group showed a significantly lower hazard ratio of 0.225. In analysis based on income level, the results of the entire group were significant, with the lower income group showing the lowest hazard ratio. In sensitivity analyses, AG tended to show a lower surgery rate than CG. Conclusions: The present study demonstrated that acupuncture therapy is associated with a low rate of surgery for knee osteoarthritis. Additional studies are needed to support this conclusion.

Cervical surgery rate in neck pain patients with and without acupuncture treatment: a retrospective cohort study.

OBJECTIVE: Surgical treatment of neck pain often entails high costs and adverse events. The present cohort study investigated whether utilisation of acupuncture in neck pain patients is associated with a reduced rate of cervical surgery. METHODS: The Korean National Health Insurance Service National Sample Cohort (NHIS-NSC) database was retrospectively analysed to identify the 2 year incidence of cervical surgery in Korean patients suffering neck pain from 2004 to 2010. The incidence was calculated and compared between patients receiving and not receiving acupuncture treatment using Cox proportional hazards models. Cumulative survival rates were compared using Kaplan-Meier survival analysis. RESULTS: The acupuncture and control groups included 50 171 and 128 556 neck pain patients, respectively. A total of 50 161 patients were selected in each group following propensity score matching with regard to sex, age, income and Charlson comorbidity index. The hazard ratio (HR) for surgery within 2 years was significantly lower in the acupuncture group compared with the control group (HR 0.397, 95% CI 0.299 to 0.527). In addition, subgroup analyses according to gender, age and income revealed consistent results for both men (HR 0.337, 95% CI 0.234 to 0.485) and women (HR 0.529, 95% CI 0.334 to 0.836); the results were consistently observed across all age and income strata. Sensitivity analysis with varying numbers of acupuncture treatments and treatment course duration also consistently indicated lower HRs for surgery within 2 years in the acupuncture group compared with the control group. CONCLUSIONS: A significantly lower HR for cervical surgery was observed in neck pain patients following acupuncture treatment. Acupuncture treatment may therefore be an effective method for managing neck pain, and has the potential to mitigate unnecessary surgery. These findings need to be confirmed by prospective studies.

Effects of acupuncture in postmenopausal women with prehypertension or stage 1 hypertension: study protocol for a prospective, comparative, interventional cohort study.

BACKGROUND: Hypertension is a major cause of cardiovascular disease and associated mortality, and postmenopausal women are at a high risk of hypertension. We aim to investigate the hypotensive effect and safety of acupuncture, focusing on postmenopausal women with prehypertension and stage 1 hypertension. In addition, we aim to investigate whether the effect of acupuncture treatment differed, depending on Sasang Constitution and cold-heat pattern. METHODS: This study is designed as an intervention cohort study. Two hundred postmenopausal women aged <65 years with prehypertension or stage 1 hypertension living in Daejeon city in Korea will be recruited, and randomly assigned to either an acupuncture or no-treatment control group. The intervention will consist of four sessions; one session will include acupuncture performed 10 times for 4 weeks. There will be a 20-week observation period after each session, and the total study duration will be 96 weeks. Acupuncture will be applied at the bilateral Fengchi (GB20), Quchi (LI11), Zusanli (ST36), and Sameumgyo (SP6) acupoints. The effect of acupuncture will be evaluated by comparing the change in systolic and diastolic blood pressure between the acupuncture and control groups every 4 weeks until the end of the study. DISCUSSION: To evaluate the success of blood pressure management, long-term observation is required, but no long-term studies have been conducted to evaluate the effect of acupuncture on blood pressure in postmenopausal women. To our knowledge, this study will be the first long-term study to investigate this issue for more than 6-8 weeks.

Impact of acupuncture treatment on the lumbar surgery rate for low back pain in Korea: A nationwide matched retrospective cohort study.

INTRODUCTION: Low back pain (LBP) is a globally prevalent disorder with high social significance. Invasive surgical procedures are increasingly being used to treat LBP despite a lack of solid evidence supporting their long-term benefits. This nationwide retrospective cohort study investigated the association between acupuncture treatment and lumbar surgery rate in patients with LBP. METHODS: Using the National Health Insurance Service Sample Cohort Database for 2002-2013, we identified newly diagnosed LBP patients in Korea between 2004 and 2010 and divided them into an acupuncture group and control group according to whether or not they received acupuncture. Propensity scores based on age, sex, income, and Charlson Comorbidity Index were matched between the two study groups. The lumbar surgery rate in the two years following the first visit (control group) or the first acupuncture session (acupuncture group) was calculated. In addition to the overall analysis, stratified analyses were also conducted in different age, sex, and income strata. Sensitivity analyses were further performed using varying definitions of acupuncture treatment. RESULTS: After matching, 130,089 subjects were included in each study group. The lumbar surgery rate was significantly lower in the acupuncture group than in the control group (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.576-0.696). Decrease in HR was consistently observed in the acupuncture group for all age strata, except for patients in their 20s (HR 1.031, 95% CI 0.804-1.323). HR for lumbar surgery tended to be further reduced in the older age groups upon acupuncture treatment, with no apparent sex-related differences. Lowered HR in the acupuncture group was continuously observed across all income groups; the higher income group showed a tendency of greater decrease. Sensitivity analyses showed that the number of acupuncture sessions had no major impact on the likelihood of lumbar surgery, but also that more intensive acupuncture treatment was associated with further reduction in lumbar surgery rates. CONCLUSION: The present results found that administration of acupuncture treatment is associated with lower lumbar surgery rates for LBP patients in Korea. Prospective studies are warranted in the future to further investigate the effect of acupuncture treatment on lumbar surgery incidence.

Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans.

Paraoxonase-1 (PON1) is an enzyme associated with HDL in blood and it is considered as an anti-oxidant factor due to its capability to prevent lipid oxidation. In vivo mouse studies also have shown that PON1 is one of the genetic risk factors contributing to atherosclerosis. In this study, we evaluated the serum PON1 activities of sex-age matched Korean healthy control and ischemic stroke patients, and investigated the association of PON1 activity with other metabolic parameters. Statistical analyses revealed that PON1 activity and HDL_cholesterol (HDL_C) in stroke patients were significantly decreased when compared with those of healthy control. Additionally, PON1 activity was negatively correlated with age, whereas it was positively correlated with HDL_C in a stroke group. Overall, the results of this study indicated that decreased serum PON1 activity should be considered as a risk factor for ischemic stroke in Koreans.

Immunomodulatory Potential of Weissella cibaria in Aged C57BL/6J Mice.

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; 1 × 108 CFU/mouse) or high dosage (JW15-H; 1 × 109 CFU/mouse), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Twomonth- old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-γ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.

IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation.

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a multicenter, nonblinded, randomized controlled trial.

BACKGROUND: The causes of chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) are not clearly known, and there are no definitive treatments for them. Therefore, patients with CFS and ICF are interested in Oriental medicine or complementary and alternative medicine. For this reason, the effectiveness of complementary and alternative treatments should be verified. We investigated the effectiveness of two forms of acupuncture added to usual care for CFS and ICF compared to usual care alone. METHODS: A three-arm parallel, non-blinded, randomized controlled trial was performed in four hospitals. We divided 150 participants into treatment and control groups at the same ratio. The treatment groups (Group A, body acupuncture; Group B, Sa-am acupuncture) received 10 sessions for 4 weeks. The control group (Group C) continued usual care alone. The primary outcome was the Fatigue Severity Scale (FSS) at 5 weeks after randomization. Secondary outcomes were the FSS at 13 weeks and a short form of the Stress Response Inventory (SRI), the Beck Depression Inventory (BDI), the Numeric Rating Scale (NRS), and the EuroQol-5 Dimension (EQ-5D) at 5 and 13 weeks. RESULTS: Group A showed significantly lower FSS scores than Group C at 5 weeks (P = 0.023). SRI scores were significantly lower in the treatment groups than in the control group at 5 (Group A, P = 0.032; B, P <0.001) and 13 weeks (Group A, P = 0.037; B, P <0.001). Group B showed significantly lower BDI scores than Group C at 13 weeks (P = 0.007). NRS scores from the treatment groups were significantly reduced compared to control at 5 (Group A and B, P <0.001) and 13 weeks (Group A, P = 0.011; B, P = 0.002). CONCLUSIONS: Body acupuncture for 4 weeks in addition to usual care may help improve fatigue in CFS and ICF patients. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0000508; Registered on 12 August 2012.

Utilization of hierarchical, stochastic relationship modeling for Hangul character recognition.

In structural character recognition, a character is usually viewed as a set of strokes and the spatial relationships between them. Therefore, strokes and their relationships should be properly modeled for effective character representation. For this purpose, we propose a modeling scheme by which strokes as well as relationships are stochastically represented by utilizing the hierarchical characteristics of target characters. A character is defined by a multivariate random variable over the components and its probability distribution is learned from a training data set. To overcome difficulties of the learning due to the high order of the probability distribution (a problem of curse of dimensionality), the probability distribution is factorized and approximated by a set of lower-order probability distributions by applying the idea of relationship decomposition recursively to components and subcomponents. Based on the proposed method, a handwritten Hangul (Korean) character recognition system is developed. Recognition experiments conducted on a public database show the effectiveness of the proposed relationship modeling. The recognition accuracy increased by 5.5 percent in comparison to the most successful system ever reported.