Probiotics, prebiotics, synbiotics and insulin sensitivity.

Animal studies indicate that the composition of gut microbiota may be involved in the progression of insulin resistance to type 2 diabetes. Probiotics and/or prebiotics could be a promising approach to improve insulin sensitivity by favourably modifying the composition of the gut microbial community, reducing intestinal endotoxin concentrations and decreasing energy harvest. The aim of the present review was to investigate the effects of probiotics, prebiotics and synbiotics (a combination of probiotics and prebiotics) on insulin resistance in human clinical trials and to discuss the potential mechanisms whereby probiotics and prebiotics improve glucose metabolism. The anti-diabetic effects of probiotics include reducing pro-inflammatory cytokines via a NF-κB pathway, reduced intestinal permeability, and lowered oxidative stress. SCFA play a key role in glucose homeostasis through multiple potential mechanisms of action. Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release of glucagon-like peptide-1 and peptide YY resulting in increased insulin and decreased glucagon secretion, and suppressed appetite. SCFA can decrease intestinal permeability and decrease circulating endotoxins, lowering inflammation and oxidative stress. SCFA may also have anti-lipolytic activities in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation of 5'-AMP-activated protein kinase signalling in muscle and liver tissues. Resistant starch and synbiotics appear to have favourable anti-diabetic effects. However, there are few human interventions. Further well-designed human clinical studies are required to develop recommendations for the prevention of type 2 diabetes with pro- and prebiotics.

The preventive effects of lifestyle intervention on the occurrence of diabetes mellitus and acute myocardial infarction in metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. STUDY DESIGN: Observational study on disease occurrence after lifestyle intervention. METHODS: The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. RESULTS: In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644-0.879) and 0.499 (95% CI: 0.251-0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. CONCLUSIONS: Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail.

Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status.

UNLABELLED: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency. INTRODUCTION: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans. METHODS: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip. RESULTS: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites (R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years. CONCLUSION: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis.

Group B streptococcal bacteremia in non-pregnant adults: results from two Korean centers.

Patients with liver cirrhosis (LC) have impaired immunity and are, thus, predisposed to infection. Few studies have attempted to evaluate group B streptococcal (GBS) bacteremia in LC patients. A retrospective study of patients with GBS bacteremia was performed at the Dongguk University Ilsan Hospital and National Health Insurance Service Ilsan Hospital over a 13-year period (October 2000 to July 2013). During the study period, 97 patients with GBS bacteremia were enrolled. The median age of the patients was 67 years and 54 % were men. Among them, 23 (24 %) patients were classified as LC patients. The 30-day mortality rate of LC patients was significantly higher than that of patients with other diseases (26 % vs. 8 %, p = 0.03). The multivariate analysis indicated that LC was associated with an increased risk of 30-day mortality [hazard ratio (HR) 5.0; 95 % confidence interval (CI) 1.53-16.3; p = 0.008], as well as age (HR 1.07; 95 % CI 1.03-1.13; p = 0.02) and high Pitt bacteremia score (HR 1.23; 95 % CI 1.02-1.46; p = 0.03). The probability of survival at day 30 was significantly different for the Child-Pugh class C and the Child-Pugh classes A or B (44 % vs. 93 %, respectively; p = 0.01 by the log-rank test). The mortality rates of LC patients with GBS bacteremia were significantly higher than those of patients with other diseases. The severity of hepatic dysfunction plays an important role in the development of adverse events. Cirrhosis-specific scores such as the Child-Pugh class might be useful for predicting the prognosis of GBS bacteremia in LC patients.

Evaluation of anatomic landmarks for axillary nerve block in the quadrilateral space.

BACKGROUND: Axillary nerve block (ANB) was recently introduced along with suprascapular nerve block as an alternative to inter-scalene brachial plexus block for post-operative pain control. However, the methods for performing ANB are variable. We studied the relationship between surface anatomy and the location of the axillary nerve in the quadrilateral space to ensure a technically safe and simple ANB. METHODS: Eighty-eight shoulders were included. All measurements were performed with the subjects seated and the shoulders in a neutral position. We located the posterior circumflex humeral artery (PCHA) using a vascular Doppler system and named this point 'AN'. We used this point to locate the axillary nerve, since this nerve is generally present with the PCHA in the quadrilateral space. We then examined the relationship between surface anatomic landmarks and AN. The depth of the medial side of the humerus at the AN (AN depth), which is at the lateral border of the quadrilateral space, was measured using ultrasonography. RESULTS: AN was located on the line between the posterolateral corner of the acromion (Ac) and the axillary fold (Axf) (Ac-Axf) in 77% of shoulders. The ratio of the distance from Ac to AN (Ac-AN) to Ac-Axf in all shoulders was 0.6 [standard deviation (SD), 0.1]. AN depth was 4.0 (SD, 0.5) cm in men and 3.6 (SD, 0.4) cm in women. CONCLUSION: Knowledge of the relationship between surface anatomy and AN, as well as estimated AN depth may aid in locating the axillary nerve in the quadrilateral space.

Written informed consent for living kidney donors: practices and compliance with CMS and OPTN requirements.

We sought to assess how written informed consent practices for candidate living kidney donors have changed over the last 5 years and to assess compliance with Centers for Medicare and Medicaid (CMS) and Organ Procurement and Transplantation Network (OPTN) regulations that took effect in 2007. We requested evaluation consent forms from US centers that performed >5 living kidney transplants during the prior year (n = 184). We received 148 consent forms; each was reviewed for information provided and inclusion of CMS- and OPTN-required elements. We found that nearly all transplant centers now obtain written consent for living kidney donor evaluation. However, most centers' evaluation consent forms do not include all CMS and OPTN requirements. Multiple items balancing donor and recipient interests and confidentiality were omitted. In addition, information about payment for routine follow-up care, complications related to surgery and other health problems following surgery were highly variable and frequently ambiguous. As centers revise their consent forms to address the 2013 OPTN policies, our findings may help them identify areas of potential deficiency. We propose that UNOS develop a uniform donor evaluation consent form to improve the clarity, consistency and efficiency of living donor consent.

Needs regarding care and factors associated with unmet needs in disease-free survivors of surgically treated lung cancer.

BACKGROUND: To evaluate the long-term needs of lung cancer survivors and to explore factors associated with unmet need. PATIENTS AND METHODS: We recruited lung patients treated with curative surgery from 2001 through 2006 at two centers in Korea. Needs in the domains of information, supportive care, education and counseling, and socioeconomic support were measured. We selected the four most frequently reported items of unmet need among 19 items in four domains. RESULTS: The most frequently reported unmet needs were Complementary and alternative medicine (CAM) and folk remedies (59.8%) in the Information domain, Counseling and treatment of depression and anxiety (63.5%) in the Supportive care domain, diet, exercise and weight control (55.1%) in the Education and counseling domain and Financial support (90.4%) in the socioeconomic support domain. Unmet needs for psychological treatment was significantly greater in participants who were employed (adjusted odds ratio [aOR], 2.25; 95% confidential interval [CI], 1.12 to 4.53). Unmet needs for diet, exercise and weight control were significantly greater in participants who had not received chemotherapy (aOR, 1.76; 95% CI, 1.09 to 2.85). Unmet need for financial support was greater in participants who were married (aOR, 4.14, 95%CI, 1.12 to 15.22) and those who had not received chemotherapy (aOR, 5.91, 95%CI, 1.91 to 18.31). CONCLUSION: There were substantial unmet needs for information regarding psychological support, education for diet and exercise, and financial support among lung cancer survivors.

Effect of complementary and alternative medicine on the survival and health-related quality of life among terminally ill cancer patients: a prospective cohort study.

BACKGROUND: We evaluated whether complementary and alternative medicine (CAM) use influenced outcomes [survival and health-related quality of life (HRQOL)] of cancer patients whose condition had just been judged terminal. PATIENTS AND METHODS: From July 2005 to October 2006, we conducted a prospective cohort study of 481 terminally ill cancer patients at 11 university hospitals and the National Cancer Center in Korea. We assessed how the use of CAM affected HRQOL and survival. RESULTS: In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased cases. On multivariate analyses, CAM users did not have better survival compared with nonusers [adjusted hazard ratio (aHR), 0.91; 95% confidence interval (CI) 0.74-1.10]. Among mind-body interventions, prayer showed significantly worse survival (aHR, 1.56; 95% CI, 1.00-2.43). Clinically, CAM users reported significantly worse cognitive functioning (-11.6 versus -1.3; P < 0.05) and fatigue (9.9 versus -1.0; P < 0.05) than nonusers. Compared with nonusers in subgroup analysis, users of alternative medical treatments, prayer, vitamin supplements, mushrooms, or rice and cereal reported clinically significant worse changes in some HRQOL subscales. CONCLUSION: While CAM did not provide any definite survival benefit, CAM users reported clinically significant worse HRQOLs.

Replication of Caucasian loci associated with bone mineral density in Koreans.

SUMMARY: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. INTRODUCTION: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. METHODS: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. RESULTS: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). CONCLUSION: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery.

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.

Economic burden attributable to Clostridioides difficile infections in South Korea: a nationwide propensity score-matched study.

BACKGROUND: Clostridioides (Clostridium) difficile is an important pathogen that causes diarrhoea in patients who take antibacterial drugs. Considering the limited medical resources, it is necessary to prioritize the management of threats caused by antibiotic use and the spread of germs, but there are little available data, especially for C. difficile infections in South Korea. AIMS: In this study, we analysed the hospital length of stay (LOS) and the increase in medical costs due to C. difficile infections. METHODS: Propensity score-matched experimental (hospitalized patients with C. difficile infection)-control (hospitalized patients without C. difficile infection) studies were conducted to estimate the increase in the LOS and medical costs associated with C. difficile infections. The data were obtained from the National Health Insurance Service-National Sample Cohort from 2006 to 2015. Reliable results were obtained by actively calibrating various confounding variables of demographic characteristics, disease severity, and information on healthcare facilities. FINDINGS: The C. difficile-attributable increase in LOS and hospitalization costs were 36.9 days and 8298 USD, respectively, per infection case. CONCLUSION: This study quantified the considerable burden associated with C. difficile infections in South Korea.

Nanotechnology: 'buckypaper' from coaxial nanotubes.

Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.

The relative position of ilioinguinal and iliohypogastric nerves in different age groups of pediatric patients.

BACKGROUND: Ilioinguinal nerve (IIN) and iliohypogastric nerve (IHN) blocks provide good perioperative pain relief for children undergoing inguinal procedures such as inguinal hernia repair, orchiopexy, and hydrocelectomy. The aim of this ultrasound imaging study is to compare the relative anatomical positions of IIN and IHN in different age groups of pediatrics. METHODS: Two-hundred children (aged 1-82 months, ASA I or II) undergoing day-case surgery were consecutively included in this study. Following the induction of general anesthesia, an ultrasonographic exam was performed using a high-frequency linear probe that was placed on an imaginary line connecting the anterior superior iliac spine (ASIS) to the umbilicus. RESULTS: There were significant differences in ASIS-IIN (distance from ASIS to IIN), ASIS-IHN (distance from the ASIS to the IHN), and IIN-IHN (distance between IIN and IHN) between the age groups: <12 months (n=84), 12-36 months (n=80), and >37 months (n=36). However, IIN-Peritoneum (distances from IIN to peritoneum), skin-IIN, and skin-IHN (depth of IIN and IHN relative to skin) were similar in three groups. ASIS-IIN and ASIS-IHN showed significantly positive correlations with age. CONCLUSIONS: Age should be considered when placing a needle in landmark techniques for pediatric II/IH nerve blocks. However, needle depth should be confirmed by the fascial click due to the lack of predictable physiologic factors.

Increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells is an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (NKTCL) is a clinically heterogeneous disease with a poor prognosis, requiring risk-stratified management in affected patients. Recently, tumor microenvironment including regulatory T cells (Tregs) has been implicated as a prognostic marker in certain types of lymphoma. PATIENTS AND METHODS: We collected 64 NKTCL cases and numerically quantified the amount of tumor-infiltrating FOXP3-positive Tregs by automated slide scanning and image analysis program after immunohistochemical staining using anti-FOXP3 antibody. RESULTS: Patients were able to be classified into two end groups by their level of Tregs. Twenty-eight (44%) patients had Tregs <50/0.40 mm(2), while 36 (56%) had Tregs > or =50/0.40 mm(2) within the tumor. The decreased number of Tregs (<50/0.40 mm(2)) was more common in patients with poor performance status or in those presented in non-upper aerodigestive tract. However, the level of Tregs was not associated with other prognostic factors, including stage, lactate dehydrogenase level, International Prognostic Index, and NKTCL Prognostic Index. Importantly, patients with increased numbers of Tregs (> or =50/0.40 mm(2)) showed prolonged overall and progression-free survival (P = 0.0005 and P = 0.0079, respectively). The number of FOXP3-positive Tregs was an independent prognostic factor (P = 0.001) by multivariate analysis. CONCLUSION: Increased quantity of tumor-infiltrating Tregs predicted improved clinical outcome in NKTCL patients.

MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with various genetic alterations. The aim was to investigate MYC, Bcl-2 and Bcl-6 translocations and copy number changes in adult DLBCLs to evaluate their clinicopathological features and prognostic implications. METHODS AND RESULTS: Gene status was examined using fluorescence in situ hybridization (FISH), and the results were analysed in the context of germinal centre B-cell (GCB) and non-GCB type of DLBCL based on immunohistochemistry. MYC translocation was observed in 9% (14 of 156), and an increased copy number (ICN) in 7.1% (11 of 156). MYC translocation was more common in GCB type (22%) than in non-GCB type (4.9%), and associated with advanced International Prognostic Index (IPI). MYC aberration, i.e. translocation or increased copy number (ICN), was significantly associated with shorter overall survival, especially for the GCB type. Bcl-2 translocation was rare (3.4%, five of 145), and ICN was observed in 11.7% (17 of 145), more frequently in non-GCB type (16%) than in GCB type (2.5%). Bcl-2 aberration tended to have an adverse effect on survival. In multivariate analysis, MYC ICN was an independent poor prognostic factor. CONCLUSIONS: Analyses of MYC and Bcl-2 status, i.e. translocation and ICN, in the context of DLBCL phenotype might help predict prognosis and determine therapeutic strategies.

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.

Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by ß3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo ß3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and ß3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling.

The effect of oxidative stress on structural transitions of human erythrocyte ghost membranes.

Differential scanning microcalorimetry was used to study the effect of oxidative stress induced by cumene hydroperoxide (CHP) and Fe2+ on structural transitions of membranes of human erythrocyte ghosts. The CHP homolysis was shown to cause: (a) reduction of the intensity of all structural transitions with the disappearance of B1- and D-transitions; (b) decrease in the enthalpy of oxidized membrane denaturation; (c) negative slope of thermograms; (d) anomalous growth of heat absorption by membranes above 72 degreesC. All these changes occurred until the ratio Fe2+/CHP/membranes<0.02:0.05:1 was reached, i.e., prior to the moment of maximal level of TBA-RS in membrane ghosts. We interpret changes in the character of heat absorption by oxidized membranes as perturbations in the structural organization and interactions inside the spectrin-actin-protein 4.1 domains, the spectrin-protein 4.2 domain, as well as inside the domain of spectrin-ankyrin-cdB3 and the domain formed by the msdB3. These perturbations are associated mainly with the decrease in the concentration of native protein in the domains because of oxidative aggregation of proteins, as evidenced by SDS electrophoresis of oxidized membranes. Preincubation of membranes with tocopherol did not block the aggregation of proteins in electrophoresis and the decrease in the intensity of structural transitions, whereas it blocked completely the formation of TBA-RS, changes in the thermogram slope and the sharp rise in the heat absorption above 72 degreesC. This proves that these processes are determined by the thermotropic properties of the oxidized lipid bilayer of membranes and also provides evidence that the degradation of PUFA of phospholipids modifies both the structure of protein domains and the physical properties of the lipid bilayer of membranes.