Safety of acupuncture during pregnancy: a retrospective cohort study in Korea.

OBJECTIVE: The present study aimed to analyse the Korean National Health Insurance Service (NHIS) cohort data to examine the safety of acupuncture therapy during pregnancy. DESIGN: Retrospective cohort. SETTING: Korea. POPULATION OR SAMPLE: Women with confirmed pregnancy between 2003 and 2012 from the 2002-13 NHIS sample cohort (n = 20 799). METHODS: Women with confirmed pregnancy were identified and divided into acupuncture or control group for comparison of their outcomes. Differences in other factors such as age, and rate of high-risk pregnancy and multiple pregnancy were examined. In the acupuncture group, the most frequent acupuncture diagnosis codes and the timing of treatment were also investigated. MAIN OUTCOME MEASURES: Incidence of full-term delivery, preterm delivery and stillbirth by pregnancy duration and among the high-risk and multiple pregnancy groups. RESULTS: Of 20 799 pregnant women analysed, 1030 (4.95%) and 19 749 were in the acupuncture and control groups, respectively. Both overall (odds ratio [OR] 1.23; 95% CI 0.98-1.54), and in the stratified analysis of high-risk pregnancies (OR 1.09; 95% CI 0.73-1.64), there was no significant difference between acupuncture and control groups in preterm deliveries. No stillbirths occurred in the acupuncture group and 0.035% of pregnancies resulted in stillbirths in the control group. CONCLUSION: No significant difference in delivery outcomes (preterm delivery and stillbirth) was observed between confirmed pregnancies in the acupuncture and control groups. Therefore, in pregnancy, acupuncture therapy may be a safe therapeutic modality for relieving discomfort without an adverse delivery outcome. TWEETABLE ABSTRACT: In pregnancy, acupuncture therapy may be a safe therapeutic modality for relieving discomfort without an adverse outcome.

Non-local means filter denoising for DEXA images.

Dual high and low energy images of Dual Energy X-ray Absorptiometry (DEXA) suffer from noises due to the use of weak amount of X-rays. Denoising these DEXA images could be a key process to enhance and improve a Bone Mineral Density (BMD) map which is derived from a pair of high and low energy images. This could further improve the accuracy of diagnosis of bone fractures, osteoporosis, and etc. In this paper, we present a denoising technique for dual high and low energy images of DEXA via non-local means filter (NLMF). The noise of dual DEXA images is modeled based on both source and detector noises of a DEXA system. Then, the parameters of the proposed NLMF are optimized for denoising utilizing the experimental data from uniform phantoms. The optimized NLMF is tested and verified with the DEXA images of the uniform phantoms and real human spine. The quantitative evaluation shows the improvement of Signal-to-Noise Ratio (SNR) for the high and low phantom images on the order of 30.36% and 27.02% and for the high and low real spine images on the order of 22.28% and 33.43%, respectively. Our work suggests that denoising via NLMF could be a key preprocessing process for clinical DEXA imaging.

IGF-1 Mediates EphrinB1 Activation in Regulating Tertiary Dentin Formation.

Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system that govern tertiary dentin formation in vitro and in vivo. During tooth development, ephrinB1, and EphB2 were expressed in preodontoblast and odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in odontoblasts and odontoblastic processes until the completion of tooth eruption. In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following tooth injury without pulp exposure, whereas EphB2 was expressed in the center of pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure, ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide aggregate (MTA) showed an increased expression of insulin-like growth factor 1 (IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression, and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor ablation exhibited a reduced tertiary dentin volume, mineral density, and ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1 axis plays significant roles in the early stages of tooth injury. Further research is needed to fully understand the potential of targeting ephrinB1 as a regenerative pulp therapy.

Dietary whole and cracked linseed increases the proportion of oleic and α-linolenic acids in adipose tissues and decreases stearoyl-coenzyme A desaturase, acetyl-coenzyme A carboxylase, and fatty acid synthase gene expression in the longissimus thoracis muscle of Yanbian Yellow cattle.

We hypothesized that supplementation of linseed in a beef cattle fattening diet would increase PUFA concentrations in intramuscular adipose tissue and depress (), (), and () gene expression by decreasing () expression. Conversely, supplemental linseed would upregulate expression of () and () in muscle of Yanbian Yellow steers. Thirty steers were assigned at random to 3 groups of 10 steers fed either the basal diet (corn grain and corn silage-based commercial concentrate [CON]), the CON diet plus 8% whole linseed (WLS; DM basis), or the CON diet plus 8% cracked linseed (CLS; DM basis) for 6 mo. The WLS and CLS supplements did not affect carcass weight, backfat thickness, or marbling scores ( > 0.10) but increased rib eye area and fat color (more yellow; < 0.05). The WLS and CLS diets decreased the proportions of 16:0 and 18:0 and increased the proportions of 18:1-9, 18:3-3, -9, -11 conjugated linoleic acid, total MUFA, and total PUFA in intramuscular, intermuscular, and subcutaneous adipose tissues. The WLS and CLS diets increased and gene expression whereas the supplements depressed , , , and gene expression in longissimus thoracis muscle, relative to CON muscle, consistent with our hypothesis. Because the WLS and CLS treatments did not affect any measure of carcass adiposity, these results indicated that linseed supplements promoted uptake of dietary lipids while concurrently depressing de novo fatty acid biosynthesis in adipose tissue.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence.

The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.

Dietary linseed oil with or without malate increases conjugated linoleic acid and oleic acid in milk fat and and gene expression in mammary gland and milk somatic cells of lactating goats.

Supplementary dietary plant oils have the potential to alter milk fatty acid composition in ruminants as a result of changes in the amount and kind of fatty acid precursors. We hypothesized that linseed oil in combination with malate (a key propionate precursor in the rumen) would increase ∆9 unsaturated fatty acids and specific gene expression in somatic cells and mammary glands of lactating goats. Twelve lactating goats were used in a 3 × 3 Latin square design. Treatments included the basal diet (CON), the CON plus 4% linseed oil (LO), and the CON plus 4% linseed oil and 2% -malate (LOM). Relative to CON, the LO and LOM supplements increased the daily intake of palmitic (16:0), stearic (18:0), oleic (18:1-9), linoleic (18:2-6), α-linolenic (18:3-3), and γ-linolenic acids (18:2-6); α-linolenic acid intake was increased over 9-fold, from 6.77 to over 51 g/d ( < 0.02). The LO and LOM supplements increased daily milk yield, milk fat yield, and milk fat percentage ( < 0.05). The LOM supplement also increased milk lactose percentage and daily yield ( = 0.03). Both the LO and LOM supplements increased plasma glucose and total cholesterol and decreased plasma ß-hydroxbutyrate concentrations ( = 0.03). The LO and LOM supplements increased concentrations of stearic acid; -vaccenic acid (TVA; 18:1-11); -9, -11 CLA; -10 -12 CLA; and α-linolenic acid in rumen fluid and increased the concentrations of oleic acid; TVA; -9, -11 CLA; -10, -12 CLA; and α-linolenic acid in plasma lipids and milk fat ( < 0.05). Conversely, the LO and LOM supplements decreased short- and medium-chain SFA, including lauric (12:0), myristic (14:0), and palmitic acids, in plasma and milk fat ( < 0.05). Relative mRNA levels for and () gene expression were increased in somatic cells and mammary gland tissue by LO and LOM ( < 0.05). We conclude that the higher intake and ruminal production of stearic acid promoted SCD gene expression in somatic cells and mammary tissue. Furthermore, milk somatic cells are a suitable substitute for documenting treatment effects of dietary oils on gene expression in goat mammary tissue.

Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 induces immunostimulatory activity in macrophages and immunosuppressed mice.

AIMS: Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its immunostimulating effects were analysed. METHODS AND RESULTS: In this study, we used interferon-γ (IFN-γ)-primed RAW 264·7 macrophages and CD3/CD28-stimulated splenocytes to determine the immunotimulatory activities of PE-EPS. Upon exposure to PE-EPS, IFN-γ-primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE-EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor-κB (NF-κB). Furthermore, PE-EPS enhanced anti-CD3/CD28-specific proliferation and the productions of IL-2 and IFN-γ in primary splenocytes. In cyclophosphamide-induced immunosuppressed mice, pretreatment with PE-EPS (5, 15 or 45 mg kg(-1) day(-1), p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts. CONCLUSION: PE-EPS stimulated the IFN-γ-primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide-induced immunosuppression in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The results in this study improved our understanding of immunostimulating activity of PE-EPS and supported its potential treatment option as a natural immunostimulant.

A phantom model study to identify the most effective manual aspiration thrombectomy for acute deep-vein thrombosis of the lower extremity.

AIM: To identify the most effective manual aspiration thrombectomy (MAT) method for the initial endovascular management of acute deep-vein thrombosis (DVT) in the lower extremity using a phantom model. MATERIALS AND METHODS: An acute DVT phantom model was created by infusing a bovine acute thrombus in a 20-mm diameter, 120-cm long plastic tube with banding of the distal portion. A total of 32 types of aspiration methods using combinations of two aspiration catheters (8 and 10 Fr), four syringes (10, 20, 40, and 50 ml), and four different aspiration methods (I, II, III, and IV) were performed. Each method was performed 10 times. The total weight of the aspirated thrombus was measured and compared among the 32 aspiration methods. The aspiration methods were classified based on the length of the dynamic catheter withdrawal (0 cm [method I], 15 cm [II], 30 cm [III], or >45 cm [IV]) while maintaining continuous negative pressure using a syringe. Analysis of variance and Student's t-test were used for statistical analysis. RESULTS: There were no statistically significant differences in the total amount of aspirated thrombus among the various types of aspiration catheters and syringes; however, different aspiration methods showed significantly different results. Acute thrombus was most effectively aspirated by method IV irrespective of the catheter and syringe used. The longer the length of dynamic catheter withdrawal, the greater the amount of total thrombi that could be aspirated, irrespective of the type of aspiration catheter and syringe used (IV > III > II > I; p<0.05). CONCLUSION: MAT can be performed most effectively using method IV. Effective MAT relies on the length of the dynamic catheter withdrawal while maintaining continuous negative pressure using a syringe in the initial endovascular management of acute DVT in the lower extremity.

HMGB1 in the pathogenesis of ultraviolet-induced ocular surface inflammation.

High-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein as well as a crucial cytokine that regulates inflammation. This study demonstrated that secretion of HMGB1 due to ultraviolet (UV) radiation inducing ocular surface inflammation-mediated reactive oxygen species (ROS) production. After treating conjunctival epithelial cells with UV radiation, HMGB1 was translocated from the nucleus to the cytoplasm and then eventually to the extracellular space. HMGB1 played a crucial role in UV-induced conjunctival neutrophil infiltration, which subsided when mice were pretreated with the HMGB1 inhibitors soluble receptor for advanced glycation endproducts (sRAGEs) and HMGB1 A box protein. In case of using ROS quencher, there was decrease in UV-induced HMGB1 secretion in conjunctival epithelial cells and mice. Considering that UV-induced chronic inflammation causes ocular surface change as pterygium, we have confirmed high HMGB1 translocation and ROS expression in human pterygium. Our findings therefore revealed a previously unknown mechanism of UV-induced ocular inflammation related to ROS and HMGB1 suggesting a new medical therapeutic target.

Association between information provision and decisional conflict in cancer patients.

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response.

Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets.

Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen-free (DPF) miniature pigs and infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti-thymocyte globulin (ATG) induction and maintenance with anti-CD154 monoclonal antibody and low-dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90-110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow-up period showed excellent glucose disposal capacity and porcine C-peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.

Upregulated Polo-Like Kinase 1 Expression Correlates with Inferior Survival Outcomes in Rectal Cancer.

BACKGROUND: Human polo-like kinase 1 (PLK1) expression has been associated with inferior outcomes in colorectal cancer. Our aims were to analyse PLK1 in rectal cancer, and its association with clinicopathological variables, overall survival as well as tumour regression to neoadjuvant treatment. METHODS: PLK1 expression was quantified with immunohistochemistry in the centre and periphery (invasive front) of rectal cancers, as well as in the involved regional lymph nodes from 286 patients. Scores were based on staining intensity and percentage of positive cells, multiplied to give weighted scores from 1-12, dichotomised into low (0-5) or high (6-12). RESULTS: PLK1 scores in the tumour periphery were significantly different to adjacent normal mucosa. Survival analysis revealed that low PLK1 score in the tumour periphery had a hazard ratio of death of 0.59 in multivariate analysis. Other predictors of survival included age, tumour depth, metastatic status, vascular and perineural invasion and adjuvant chemotherapy. There was no statistically significant correlation between PLK1 score and histological tumour regression in the neoadjuvant cohort. CONCLUSION: Low PLK1 score was an independent predictor of superior overall survival, adjusting for multiple clinicopathological variables including treatment.

In vitro and in vivo immunostimulatory activity of an exopolysaccharide-enriched fraction from Bacillus subtilis.

AIMS: The aim of this study was to investigate the immunostimulatory effects of an exopolysaccharide-enriched fraction obtained from Bacillus subtilis J92 (B-EPS). METHODS AND RESULTS: To determine the immunostimulatory activities of B-EPS, we used IFN-γ-primed RAW 264.7 macrophages and CD3/CD28-stimulated splenocytes. Increases in the levels of NO and many cytokines, such as, TNF-α, IL-6, and IL-1ß, were observed in IFN-γ-primed RAW 264.7 macrophages by Griess reaction and ELISAs respectively. Using Western blotting and qRT-PCR, we found that B-EPS increased the protein and mRNA expressions of iNOS and the mRNA expressions of TNF-α, IL-6, and IL-1ß. A reporter gene assay and EMSA revealed that B-EPS up-regulated the transcriptional activity of NF-κB by increasing its DNA binding and nuclear translocation. Pretreatment with NF-κB inhibitors, that is, BAY11-7082 and PDTC, decreased NO production in IFN-γ-primed RAW 264.7 macrophages by B-EPS. Furthermore, B-EPS increased the proliferation of and cytokine (IL-2 and IFN-γ) production by CD3/CD28-stimulated splenocytes. In a cyclophosphamide-induced immunosuppressed mouse model, B-EPS (5, 15 or 45 mg kg(-1) , p.o.) restored thymus and spleen indices. B-EPS also inhibited cyclophosphamide-induced reductions in neutrophil and lymphocyte numbers. CONCLUSIONS: B-EPS improves immune function by regulating immunological parameters in IFN-γ-primed macrophages, CD3/CD28-stimulated splenocytes, and in cyclophosphamide-induced immunosuppressed mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the exopolysaccharides secreted by B. subtilis J92 could be used as immune stimulants.

Predictive markers of radiotherapy-induced rectal cancer regression.

Patients with locally advanced rectal cancer receive preoperative radiotherapy to reduce the probability of recurrence and to possibly improve overall survival. However, this appears dependent on the extent of histological tumour regression seen in the resected bowel, which can be highly variable between individuals. No predictive marker that can stratify patient management in this regard is currently available. Experimental data implicates a variety of factors that are involved in the DNA damage response following radiation injury, tumour tissue oxygenation, autoimmune antitumour response triggered by radiotherapy and in the pathogenesis of colorectal cancer, as potential indicators of radiation sensitivity. These details are presented in this review, which may serve as targets for clinical validation studies aiming to find predictors of radiotherapy response in rectal cancer.

The pharmacokinetics, pharmacodynamics and safety of oral doses of ilaprazole 10, 20 and 40 mg and esomeprazole 40 mg in healthy subjects: a randomised, open-label crossover study.

BACKGROUND: Ilaprazole, a proton pump inhibitor (PPI) currently in clinical use, may provide improved acid suppression vs. other PPIs. AIM: To compare the pharmacodynamic and pharmacokinetic profiles of ilaprazole and esomeprazole. METHODS: A phase 1, randomised, open-label, single-centre, 4-period crossover study was conducted in 40 healthy volunteers. Ilaprazole 10, 20 or 40 mg or esomeprazole 40 mg was administered once daily for 5 days with ≥5-day washout intervals. Pharmacokinetic blood samples and intragastric pH measurements were collected at scheduled timepoints for 24 h after dosing on Days 1 and 5. RESULTS: Esomeprazole 40 mg provided significantly better pH control during the initial hours (0-4 h) after a single dose, but ilaprazole (particularly 20 and 40 mg) provided significantly better pH control for the entire 24-h period and during evening and overnight hours after single and multiple doses. Increasing ilaprazole doses resulted in dose-proportional increases in peak plasma concentration and area under the plasma concentration vs. time curve following single and multiple doses. Ilaprazole was safe and generally well tolerated; an unexpectedly high incidence of allergic eye and skin reactions were observed but were not specific to any dosing regimen. Plasma gastrin concentrations did not increase proportionately with increasing ilaprazole dose. CONCLUSIONS: Ilaprazole provided significantly better pH control over 24 h and during evening and overnight hours compared with esomeprazole in healthy volunteers, which may translate to greater relief of night-time heartburn in the clinical setting for patients with gastric acid-related disorders.