Heart rate variability in middle-aged adults: Use of Sasang typology to distinguish individuals susceptible to stress.

While stress is known to cause many diseases, there is no established method to determine individuals vulnerable to stress. Sasang typology categorizes humans into four Sasang types (So-Eum, Tae-Eum, So-Yang, and Tae-Yang), which have unique pathophysiologies because of their differential susceptibilities to specific stimuli, including stress. The purpose of this study was to determine if Sasang typology can be used identify individuals who are vulnerable to stress by evaluation of heart rate variability (HRV).This was a cross-sectional study. A total of 399 healthy men and women aged 30 to 49 years were recruited. Physical examinations for stress included HRV measurement and blood tests. The subjects also completed questionnaires about psychological stress, self-awareness, and lifestyle. HRV was analyzed using frequency-domain analysis. Subjects were divided into So-Eum (SE) and non-So-Eum (non-SE) groups according to their diagnosis.The weight and body mass index in the SE group were significantly lower than those in the non-SE group (both, P = .000). There were no significant between-group differences in any other demographic variables. In HRV analysis, the normalized high frequency (nHF) was higher (P = .008) while the normalized low frequency (nLF; P = .008) and LF:HF ratio (LF/HF; P = .002) were lower in the SE group than in the non-SE group.Although there was no difference in variables affecting HRV, HRV values were significantly different between groups. The LF/HF value for the SE group was at the lower limit of the normal range, although there were no associated clinical problems. These findings suggest that individuals with the SE type are more susceptible to stress than those with the other types. Thus, middle-aged individuals who are vulnerable to stress can be identified using Sasang typology.

Roles of T Follicular Helper Cells and T Follicular Regulatory Cells in Autoantibody Production in IL-2-Deficient Mice.

Autoantibodies can result from excessive T follicular helper (Tfh) cell activity, whereas T follicular regulatory (Tfr) cells negatively regulate autoantibody production. IL-2 knockout (KO) mice on the BALB/c background have elevated Tfh responses, produce autoantibodies, and develop lethal autoimmunity. We analyzed Tfh and Tfr cells in IL-2 KO mice on the C57BL/6 (B6) genetic background. In B6 IL-2 KO mice, the spontaneous formation of Tfh cells and germinal center B cells was greatly enhanced, along with production of anti-DNA autoantibodies. IL-2 has been reported to repress Tfr cell differentiation; however, Tfr cells were not increased over wild-type levels in the B6 IL-2 KO mice. To assess Tfh and Tfr cell regulation of autoantibody production in IL-2 KO mice, we generated IL-2 KO mice with a T cell-specific deletion of the master Tfh cell transcription factor Bcl6. In IL-2 KO Bcl6 conditional KO (2KO-Bcl6TC) mice, Tfh cells, Tfr cells, and germinal center B cells were ablated. In contrast to expectations, autoantibody IgG titers in 2KO-Bcl6TC mice were significantly elevated over autoantibody IgG titers in IL-2 KO mice. Specific deletion of Tfr cells with Foxp3-cre Bcl6-flox alleles in IL-2 KO mice led to early lethality, before high levels of autoantibodies could develop. We found IL-2+/+ Tfr cell-deficient mice produce significant levels of autoantibodies. Our overall findings provide evidence that Tfh cells are dispensable for high-level production of autoantibodies and also reveal a complex interplay between Tfh and Tfr cells in autoantibody production and autoimmune disease.

Feasibility and effectiveness assessment of a mobile application for subhealth management: Study protocol for a randomized controlled trial.

INTRODUCTION: Mibyeongbogam (MBBG) is a mobile application developed for subhealth status self-management in the Republic of Korea. It aims to assess a user's subhealth status, and then to recommend relevant traditional Korean medicine (TKM)-based health-promoting strategies. The purpose of this study is to evaluate the feasibility and effectiveness of MBBG's employment for the subhealth management of general healthy adults. METHODS: This is a prospective, open-label, parallel group, randomized controlled trial that will seek to enroll 150 healthy adults, aged 30 to 49 years old, from 2 hospitals in the Republic of Korea. The eligible participants will then be randomly allocated to either the MBBG or control group, at a 1:1 allocation ratio. The MBBG group will use the application for 12 weeks, while the control group will undergo no intervention. The awareness of subhealth status will be primarily assessed. Health promoting behaviors, quality of life, TKM-based health questionnaires, and physical examination results will be assessed as secondary outcomes. DISCUSSION: The primary endpoint will be tested with a 2-sample t test, or a Wilcoxon rank sum test. Any other continuous variables will be tested via an analysis of covariance, while categorical variables will be tested by a Chi-squared or Fisher exact test. Repeated measure analysis of variance will be performed to explore any in-group differences. The results will be addressed with a 95% confidence interval. We expect that MBBG will be the 1st TKM-based mobile application to be feasible for primary care in subhealth management. TRIAL REGISTRATION: CRIS (Clinical Research Information Service), KCT0003488, February 11, 2019.

Effect of Traditional East Asian Medicinal herbal tea (HT002) on insomnia: a randomized controlled pilot study.

BACKGROUND: Complementary and alternative medicine treatment for insomnia has been sought due to the possible adverse effects of conventional pharmacotherapies. We performed a preliminary evaluation of the feasibility of using, and of the effect of a herbal tea (HT002), based on Traditional East Asian Medicine, in mild-to-moderate insomnia. METHODS: Patients (n = 40) with mild-to-moderate insomnia were randomized to the HT002 (n = 20) or waitlist (n = 20) groups. The HT002 group consumed HT002 twice daily for 4 weeks. Outcomes were assessed using the Insomnia Severity Scale (ISI), Pittsburgh Sleep Quality Index (PSQI), and 12-item Short Form Health Survey (SF-12) at baseline and after 4 and 8 weeks. RESULTS: The ISI score differences from baseline at weeks 4 and 8 were significantly greater in the HT002 than that in the waitlist group (week 4: -4.0 ± 0.8 vs. -0.4 ± 0.8, p < 0.05; week 8: -4.8 ± 0.7 vs. -0.9 ± 0.7, p < 0.05). Changes in PSQI and SF-12 physical component scores in the HT002 group were significantly greater at weeks 4 and 8 (p < 0.05), while SF-12 mental component scores were only significantly larger at 4 weeks (p < 0.05). HT002 was well-tolerated, with only one (5.0%) dropout, and no significant mean liver and renal function test changes post-treatment. CONCLUSION: Our preliminary results suggest that a 4-week treatment with HT002 may reduce the severity of insomnia symptoms and improve the quality of life. Further studies devoid of the limitations of our protocol may provide stronger conclusions. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0001900.

Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice.

The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH ) cells: Bcl6 promotes and Blimp1 inhibits TFH -cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH -cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH -cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control TFH -cell differentiation independently of Bcl6. However, a population of T follicular regulatory (TFR ) cells developed independently of Bcl6 in dcKO mice. We have also analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found that Bcl6 positively regulates PD-1 expression by inhibiting the ability of T-bet/Tbx21 to repress Pdcd1 transcription. Our data provide a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control TFH -cell differentiation.

Percutaneous transsplenic embolization of jejunal varices in a patient with liver cirrhosis: a case report.

Bleeding jejunal varices are rare and could be life threatening. They are usually found in the presence of portal hypertension and prior history of gastrointestinal surgery. They can be effectively managed by radiological interventions such as transjugular intrahepatic portosystemic shunt or transhepatic embolization of varices. However, in patients with portal vein obstruction, an alternative access is necessary. We report a case of bleeding jejunal varices associated with postoperative adhesion in a patient with portal vein thrombosis which was successfully managed by percutaneous transsplenic embolization.

Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation.

The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.

Comparison of sasang constitutional medicine, traditional chinese medicine and ayurveda.

Sasang constitutional medicine (SCM), traditional Chinese medicine (TCM) and Ayurveda are three different forms of Asian traditional medicine. Although these traditions share a lot in common as holistic medicines, the different philosophical foundations found in each confer distinguishing attributes and unique qualities. SCM is based on a constitution-based approach, and is in this way relatively more similar to the Ayurvedic tradition than to the TCM, although many of the basic SCM theories were originally derived from TCM, a syndrome-based medicine. SCM and TCM use the same botanical materials that are distributed mainly in the East Asian region, but the basic principles of usage and the underlying rationale are completely different from each other. Meanwhile, the principles of the Ayurvedic use of botanical resources are very similar to those seen in SCM, but the medicinal herbs used in Ayurveda generally originate from the West Asian region which displays a different spectrum of flora.

Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma.

Previous studies have shown that Th2 cytokine genes on mouse chromosome 11 are coordinately regulated by the Th2 locus control region (LCR). To examine the in vivo function of Th2 LCR, we generated CD4-specific Th2 LCR-deficient (cLCR KO) mice using Cre-LoxP recombination. The number of CD4 T cells in the cLCR KO mouse was comparable to that in wild-type mice. The expression of Th2 cytokines was dramatically reduced in in vitro-stimulated naïve CD4 T cells. Deletion of the LCR led to a loss of general histone H3 acetylation and histone H3-K4 methylation, and demethylation of DNA in the Th2 cytokine locus. Upon ovalbumin challenge in the mouse model of allergic asthma, cLCR KO mice exhibited marked reduction in the recruitment of eosinophils and lymphocytes in the bronchoalveolar lavage fluid, serum IgE level, lung airway inflammation, mucus production in the airway walls, and airway hyperresponsiveness. These results directly demonstrate that the Th2 LCR is critically important in the regulation of Th2 cytokine genes, in chromatin remodeling of the Th2 cytokine locus, and in the pathogenesis of allergic asthma.

HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-kappaB pathway.

To explore whether bacterial secreted 4-hydroxy-2-alkylquinolines (HAQs) can regulate host innate immune responses, we used the extracts of bacterial culture supernatants from a wild-type (PA14) and two mutants of Pseudomonas aeruginosa that have defects in making HAQs. Surprisingly, the extract of supernatants from the P. aeruginosa pqsA mutant that does not make HAQs showed strong stimulating activity for the production of innate cytokines such as tumour necrosis factor-alpha and interleukin-6 in the J774A.1 mouse monocyte/macrophage cell line, whereas the extract from the wild-type did not. The addition of 4-hydroxy-2-heptylquinoline (HHQ) or 2-heptyl-3,4-dihydroxyquinoline (PQS, Pseudomonas quinolone signal) to mammalian cell culture media abolished this stimulating activity of the extracts of supernatants from the pqsA mutant on the expression of innate cytokines in J774A.1 cells and in the primary bronchoalveolar lavage cells from C57BL/6 mice, suggesting that HHQ and PQS can suppress the host innate immune responses. The pqsA mutant showed reduced dissemination in the lung tissue compared with the wild-type strain in a mouse in vivo intranasal infection model, suggesting that HHQ and PQS may play a role in the pathogenicity of P. aeruginosa. HHQ and PQS reduced the nuclear factor-kappaB (NF-kappaB) binding to its binding sites and the expression of NF-kappaB target genes, and PQS delayed inhibitor of kappaB degradation, indicating that the effect of HHQ and PQS was mediated through the NF-kappaB pathway. Our results suggest that HHQ and PQS produced by P. aeruginosa actively suppress host innate immune responses.

Sasangin diagnosis questionnaire: test of reliability.

BACKGROUND: The concept of Sasang Constitutional Medicine (SCM) has been in existence in Traditional Korean Medicine for more than 100 years. It is of great importance that the Sasang constitution type be determined accurately before any therapeutic treatment. OBJECTIVES: Reliability analyse were carried out to evaluate the Sasangin Diagnosis Questionnaire (SDQ). DESIGN: The data were collected through multi-center research in collaboration with the Departments of SCM in the nine Korean Colleges of Oriental Medicine. The internal consistency test and the test-retest method were applied in the reliability analysis. SUBJECTS: The test-retest data of 88 respondents were used to analyze the reliability. The internal consistency reliability analysis was carried out using the data collected from 423 respondents. RESULTS: The test-retest reliability was examined using the Pearson's correlation coefficients, which ranged from 0.44 to 0.74. The chi-square test results showed that there were five independent items in the retest that demanded careful attention. The Cronbach's alpha coefficient showed that all items were acceptable. CONCLUSIONS: All the categories of SDQ can be accepted as being reliable scales.

Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: analysis of the pattern and risk factors.

PURPOSE: To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We studied 62 patients with 72 HCCs (< or =4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0-49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. RESULTS: The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin (p<0.05). A multivariate stepwise Cox hazard model showed that the measurement of a tumor diameter >3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR (p<0.05). CONCLUSION: Intrahepatic recurrence after percutaneous RF ablation is common. Large HCC (>3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence.

Clinical trial of herbal formula on weight loss in obese Korean children.

A traditional Korean herbal formula (KH), which is based on Taeumjowi-tang, is currently the most widely used herbal formula in Korea. In this study, KH was administered to obese children for 30 days, and was found to be clinically safe and effective. The subjects were children admitted to hospital to be treated for obesity with relative body weights (%RBW) of 20% or more. Originally, there were 31 subjects, but nine dropped out during the experiment. There were eight girls and 14 boys, whose average age was 11.00 +/- 2.62 years, average weight was 53.37 +/- 17.29 kg, and average period (30-day amount) of KH dosage was 51.18 +/- 22.58 days. The short-term effects of KH on obese children were the reduction of their BMI from 24.34 +/- 3.10 to 23.26 +/- 3.00 kg/m2, of %RBW from 34.41 +/- 10.90 to 25.94 +/- 11.18% (p < 0.01), of body fat mass from 17.99 +/- 5.37 to 16.50 +/- 4.82 kg, and of body fat from 34.16 +/- 3.75 to 32.08 +/- 3.15% (p < 0.01). Concerning anthropometrical measurements, abdominal skin-fold decreased from 26.16 +/- 9.08 to 22.90 +/- 8.35 mm, as did subscapular skin-fold from 20.86 +/- 5.20 to 18.46 +/- 5.31 mm (p < 0.01). In terms of serum lipid levels, which are indices of heart disease, their total cholesterol decreased from 195.38 +/- 31.39 to 183.25 +/- 33.27 mg/dl, the arteriosclerosis index from 4.100 +/- 0.81 to 3.84 +/- 0.64 mg/dl (p < 0.05), and serum leptin level from 14.91 +/- 6.59 to 12.24 +/- 4.98 ng/ml (p < 0.01). Concerning the safety of KH, there were no significant changes in the subjects' livers, hearts, or kidneys. Nor were there any short-term signs of clinically serious side effects or withdrawal symptoms observed. The short-term effects of KH on obese children are weight loss and a decrease in obesity.

Bronchobiliary fistula after radiofrequency thermal ablation of hepatic tumor.

A broad spectrum of complications can occur after radiofrequency (RF) ablation of hepatic tumors, even though it has been accepted as a safe and effective technique for unresectable hepatic tumors. Recently, the rare complication of brochobiliary fistula was encountered after RF ablation in a patient with a metastatic tumor from stomach cancer. It was assumed to have developed from collateral damage to the adjacent diaphragm and lung base as well as biloma formation at the ablation zone. Symptomatic improvement was achieved by conservative management with an external drainage catheter, but the fistula was still persistent on a 2-month follow-up image.

Extrapelvic and extraperitoneal spread of recurrent stomach cancer: two case reports.

We report two cases of unusual combined extrapelvic and extraperitoneal extension of recurrent gastric adenocarcinoma and describe the imaging findings of the preferential anatomic pathway of disease spread. Extrapelvic and extraperitoneal extension of recurrent gastric adenocarcinoma is rare, and its symptoms may be vague and nonspecific. If patients with a surgical history of gastrointestinal neoplasm present with diffuse abdominal pain or painful swelling of the lower extremities, disease spread to the extrapelvic and extraperitoneal spaces should be suspected.