Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Sex and Diet-Related Disparities in Low Handgrip Strength among Young and Middle-Aged Koreans: Findings Based on the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2017.

"Possible sarcopenia" may be defined as a low muscle strength assessed by handgrip strength (HGS) by sex. We examined the sex-specific association between low handgrip strength (LGS) and dietary factors for the prevention of sarcopenia in young and middle-aged Koreans. We used data from the 2014-2017 Korea National Health and Nutrition Examination Survey of 11,635 Korean adults with LGS and normal handgrip strength (NGS). The relationship between dietary factors, e.g., nutrients, foods, and dietary patterns, and HGS was evaluated by multivariate logistic regression analyses. In men, the LGS group had a higher proportion of energy from carbohydrates and a lower proportion of energy from proteins than the NGS group. The LGS group had lower protein, niacin, phosphorus, and iron densities in their diet than the NGS group. The odds of having LGS increased as intake of vitamin B1 (odds ratio (OR) 2.916, 95% confidence interval (CI) 1.265-6.719), niacin (OR 2.286, 95% CI 1.095-4.774), phosphorus (OR 2.731, 95% CI 1.036-7.199), and iron (OR 2.591, 95% CI 1.102-6.088) decreased. In women with LGS, the odds of insufficient protein intake (OR 1.976, 95% CI 1.248-3.127) was significantly higher. This study suggests that adequate intake of protein, vitamin B1, niacin, phosphorus, and iron is beneficial for maintaining HGS.

Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study.

OBJECTIVE: Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). METHODS: This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. RESULTS: A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. CONCLUSION: The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. METHODS: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. RESULTS: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. CONCLUSIONS: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

Risk of cancer in patients with recurrent aphthous stomatitis in Korea: A nationwide population-based study.

ABSTRACT: The relationship between recurrent aphthous stomatitis (RAS), a common mucosal lesion, and cancer has not been demonstrated. This study investigated the risk for developing cancer in patients with RAS, based on data from Korea's National Health Insurance Sharing Service (NHISS). Nationwide population-based cohort data from 2005 to 2009 provided by the NHISS was used. The group diagnosed with RAS for 5 years and an undiagnosed control group were constructed through 1:1 propensity score matching (PSM). The experimental design compared the incidence rate of a cancer diagnosis from 2010 to 2015 between these 2 groups. After identifying 13,808 people that met our inclusion criterion from a 1 million cohort group, 13,808 controls were included in the study through PSM. Among all cancers, pancreatic cancer had an adjusted hazard ratio of 1.26 (95% confidence interval: 1.01-1.57, P < .041). For the rest of the cancers, there was no significant incidence rate. RAS was associated with an increased risk of pancreatic cancer in the analysis using large population-based cohort data. Further long-term follow-up studies are needed.

A multicenter retrospective analysis of the antifungal susceptibility patterns of Candida species and the predictive factors of mortality in South Korean patients with candidemia.

As detection rates of non-albicans Candida species are increasing, determining their pathogen profiles and antifungal susceptibilities is important for antifungal treatment selection. We identified the antifungal susceptibility patterns and predictive factors for mortality in candidemia.A multicenter retrospective analysis of patients with at least 1 blood culture positive for Candida species was conducted. Candida species were classified into 3 groups (group A, Candia albicans; group B, Candida tropicalis, and Candida parasilosis; group C, Candida glabrata and Candida krusei ) to analyze the susceptibility patterns, first-line antifungal administered, and mortality. Univariate and multivariate comparisons between outcomes were performed to identify mortality risk factors.In total, 317 patients were identified, and 136 (42.9%) had recorded mortality. Echinocandin susceptibility was higher for group A than group B (111/111 [100%] vs 77/94 [81.9%], P < .001). Moreover, group A demonstrated higher fluconazole susceptibility (144/149 [96.6%] vs 39/55 [70.9%], P < .001) and lower mortality (68 [45.3%] vs 34 [61.8%], P = .036) than those of group C. In the multivariate analysis, the sequential organ failure assessment score (odds ratio OR 1.351, 95% confidence interval 1.067-1.711, p = 0.013) and positive blood culture on day 7 of hospitalization (odds ratio 5.506, 95% confidence interval, 1.697-17.860, P = .004) were associated with a higher risk of mortality.Patients with higher sequential organ failure assessment scores and sustained positive blood cultures have an increased risk of mortality.

Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway.

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

Changes in the utilization patterns of antifungal agents, medical cost and clinical outcomes of candidemia from the health-care benefit expansion to include newer antifungal agents.

OBJECTIVES: In 2014, South Korea expanded its national health insurance coverage to include newer antifungal agents, such as echinocandins. This study aimed to investigate the effects of policy change on the prescription patterns of antifungals, medical costs and clinical outcomes of candidemia. METHODS: This retrospective cohort enrolled hospitalized patients with candidemia at three tertiary care hospitals in South Korea from January 2012 to December 2015. The utilization of antifungal agents, medical costs, length of hospital stay (LOS), and mortality before and after the health-care benefit expansion were compared, and the factors associated with all-cause 28-day mortality during the study period were analyzed. RESULTS: A total of 769 candidemia cases were identified. The incidence of candidemia did not significantly vary during the study period (P = 0.253). The proportion of echinocandins, as the initial antifungal agent, and medical costs associated with candidemia significantly increased since the change in insurance coverage (P < 0.001). There was no significant difference in LOS and mortality associated with candidemia before and after the health-care benefit expansion (P = 0.696 and 0.931, respectively). Multivariate logistic regression analysis showed that initial treatment with caspofungin was associated with decreased mortality (adjusted odds ratio: 0.784; 95% confidence interval: 0.681-0.902; reference: fluconazole). CONCLUSIONS: Although the utilization of newer antifungal agents and medical cost for candidemia has significantly increased since the health-care benefit expansion, there has been no change in the outcome of candidemia. However, the further increased use of newer antifungals may improve the outcome of candidemia in this country.

Intravenous sustained-release nifedipine ameliorates nonalcoholic fatty liver disease by restoring autophagic clearance.

Obesity and overweight, the most serious health problems, are associated with chronic metabolic complications such as type 2 diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). However, current pharmacological therapies for obesity are challenged by potential side effects, low effectiveness, and low aqueous solubility, which limit their clinical application. Here, we develop nifedipine-loaded nanoparticles (NFD-NPs) that alleviate obesity-related metabolic dysfunction to be used as instruments for translational medicine. Nanoparticles (NPs) composed of poly (lactic-co-glycolic acid) (PLGA) not only enhance water solubility of hydrophobic nifedipine (NFD), a calcium channel blocker, without modifying the chemical structure of NFD for intravenous administration, but also allow prolonged release of NFD in vivo. NFD-NPs do not show cytotoxicity and reduce palmitate-induced protein inclusions and endoplasmic reticulum stress in human hepatoma HepG2 cells. Importantly, tail-vein injection of NFD-NPs into diet-induced obese mice results in sustained retention of NFD-NPs in the liver and suppression of metabolic derangements associated with NAFLD by enhancing autophagic clearance through Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylation, consequently decreasing diet-induced insulin resistance and improving glucose tolerance. Our findings offer new clinical tools for NP-mediated pharmaceutical strategies to treat NAFLD and its related metabolic dysfunction.

Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea.

BACKGROUND: Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS: Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by -3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by -15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by -0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION: Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Therapeutic Response for Functional Abdominal Pain in Children with Occult Constipation: Laxatives versus Prokinetic Drugs.

The relationship between functional abdominal pain (FAP) and occult constipation (OC) in children who did not meet the Rome III criteria for constipation has rarely been reported. This study aimed to estimate the prevalence of OC in patients with FAP and to compare the effectiveness of prokinetic drugs and laxatives for FAP and OC. Pediatric outpatients (n = 212; aged 4-15 years) who satisfied the Rome III criteria for childhood FAP were divided into 2 groups based on Leech scores: group 1 < 8; group 2 ≥ 8. Group 2 received either prokinetic drugs or laxatives and pain severity was assessed after 2 weeks, 1 month, and 3 months. A total 52.4% (111/212) of patients had OC in this study. More patients who received laxatives had reduced pain scores compared with those who received prokinetic drugs. Those treated with laxatives in group 2 had a better response than those treated with prokinetic drugs throughout the study period (P < 0.001, P < 0.001, and P = 0.002 after 2 weeks, 1 month, and 3 months, respectively). OC was frequently encountered in children with FAP. Laxatives can be more effective than prokinetic drugs for relieving symptoms of FAP in children with a Leech score ≥ 8 and suspected OC.

Treatment of fecal retention is important in the management of overactive bladder in children.

AIMS: The investigation of fecal retention using objective and patient-friendly tools, rather than the diagnosis of constipation, might be important in the management of overactive bladder (OAB) in children. The present study aimed to evaluate the incidence and grade of fecal retention in children with OAB and to determine the effectiveness of laxative treatment for fecal retention in the management of OAB in children. METHODS: This study included 88 children with OAB aged 5-15 years. Fecal retention was defined as type 1/2 feces (Bristol stool form scale) or a Leech score above eight points, and constipation was determined according to the ROME III criteria. Among the 88 children, 71 with fecal retention or constipation were treated with oral laxatives (polyethylene glycol 3,350/4,000 or lactulose) for 2 weeks, and the responses to the treatment were assessed. RESULTS: Among the 88 children, 63 (71.6%) had a Leech score above eight points as assessed by plain abdominal radiography, 52 (59.1%) had type 1/2 feces (Bristol stool form scale), 24 (27.3%) had functional constipation and only 6 (6.8%) had none of either. Among the 71 children who received laxative treatment for 2 weeks, 58 (81.7%) reported an improvement in OAB symptoms. Additionally, the number of children with a Leech score above eight points was significantly higher in the good response group than in the poor response group (P = 0.014). CONCLUSION: Investigation of fecal retention with the Leech scoring system and laxative treatment might be helpful in the management of OAB in children. Neurourol. Urodynam. 36:490-494, 2017. © 2016 Wiley Periodicals, Inc.

Clinical factors associated with acquisition of resistance to levofloxacin in Stenotrophomonas maltophilia.

PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in ≥3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.

Vitamin D deficiency in infants aged 1 to 6 months.

PURPOSE: The aim of this study was to recognize the state of vitamin D among healthy infants aged 1 to 6 months in South Korea, and also to identify the risk factors affecting the level of vitamin D. METHODS: A total of 117 infants were enrolled in this study for 12 months, from March 1, 2011 to February 29, 2012. Serum levels of 25-hydroxyvitamin D (25[OH]D), calcium, phosphorus, and alkaline phosphatase were measured and data including birth weight, body weight, sex, feeding pattern, delivery mode, siblings and maternal age and occupation were collected. Data was mainly analyzed with independent t-test model. RESULTS: We determined that the prevalence of vitamin D deficiency (serum 25[OH]D<20 ng/mL [50 mmol/L]) was 48.7% in the population investigated. Particularly in breastfed infants, the prevalence of vitamin D deficiency was strikingly high (90.4%). The mean serum level of 25(OH)D in breastfed infants was lower than that of formula fed infants (9.35 ng/mL vs. 28.79 ng/mL). Also female infants showed lower mean serum level of 25(OH)D than male. Mean serum values of calcium and phosphorus had positive correlation with vitamin D state (P<0.001). CONCLUSION: Vitamin D deficiency was found to be very common in infants aged 1 to 6 months in South Korea, and breast feeding was the most critical risk factor of vitamin D deficiency. Therefore we suggest to start vitamin D supplementation in South Korea, as soon as possible, to all infants, including breastfed and female infants.

Capillary electrophoretic method for the determination of diterpenoid isomers in Acanthopanax species.

Acanthoic, continentalic and kaurenoic acids are bioactive diterpenoids that are structural isomers isolated from Acanthopanax species. Due to the interest in their potent biological activity, an analytical method of diterpenoids was developed for the quality control and the classification of Acanthopanax species. Capillary electrophoresis was used to separate and quantify the isomers. The three compounds were successfully separated from each other and from the matrices in the extracts of leaves, stems and roots of Acanthopanax species. The contents of acanthoic, continentalic and kaurenoic acids showed taxonomical differences in Acanthopanax species. Relatively higher concentrations of diterpenoids were found from A. koreanum and A. trifoliatus, while only trace amounts were found from the four other species tested: A. senticosus, A. senticosus f. inermis, A. chiisanensis, and A. divaricatus var. albeofructus. The contents of diterpenoids in association with lignans and triterpenoids in the Acanthopanax species could provide a chemotaxonomical index able to be used in the classification and discrimination of the species.