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.

Risk factors for Korean women to develop an isthmocele after a cesarean section.

BACKGROUND: The increase in number of cesarean section (CS) operations has resulted in an increase in cases of isthmocele development. The objective of this study is to determine the risk factors for isthmocele development after CS. METHODS: Isthmocele measurements were taken for 404 women with a history of at least one low transverse CS. The following potential risk factors were investigated: patient's age at CS, cause of CS, weeks of gestation at CS, premature rupture of membrane (PROM), phase of labor, type suture (single/double layer), operation time, uterine flexion (anteversion/retroversion), and blood transfusion during operation. A transvaginal ultrasound was carried out to examine the isthmocele in the uterus after CS, including the shape of the isthmocele, residual myometrial thickness, depth and width of isthmocele, cervical thickness, location of the isthmocele, and clinical characteristics. RESULTS: In our study population, the isthmocele had a prevalence of 73.8%. Most isthmocele had a triangular (65.4%) or semicircular shape (10.4%). The presence of an isthmocele was significantly associated with repeat CS, premature rupture of membrane (PROM), short operation time, and extent of cervix dilatation at CS. The risk of isthmocele was low in women who had placenta previa totalis (PPT), twin, a long operation time, or a transfusion during the operation. CONCLUSIONS: In our study, isthmocele development was significantly associated with repeat CS, PROM, a short operation time, and the extent of cervix dilatation at CS. Therefore, PROM prevention and a more careful uterine closure are needed to reduce the risk of developing an isthmocele after CS.

Retinoic acid directs breast cancer cell state changes through regulation of TET2-PKCζ pathway.

The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARß-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool. Our data reveal that pharmacological concentration of ATRA effectively downregulates PKCζ through activation of miR-200c, leading to a decrease of the stem cell-like populations from non-tumorigenic mammary epithelial cells and non-aggressive breast cancer cells. However, aggressive breast cancer cells that manifest TET2-miR-200c dysregulation sustain a CSC pool highly resistant to ATRA, where inhibition of PKCζ directs the resistant CSCs to the luminal cell-like state and sensitization to tamoxifen, resulting in abrogation of mammary tumor growth and progression. Together, these findings elucidate a novel RARß-TET2-miR-200c-PKCζ signaling pathway that directs cancer cell state changes and also provide previously unidentified therapeutic implications for PKCζ inhibitors in diminishment of breast CSCs to eradicate breast cancer.

Wireless multichannel electroencephalography in the newborn.

OBJECTIVES: First, to determine the feasibility of an ultra-compact wireless device (microEEG) to obtain multichannel electroencephalographic (EEG) recording in the Neonatal Intensive Care Unit (NICU). Second, to identify problem areas in order to improve wireless EEG performance. STUDY DESIGN: 28 subjects (gestational age 24-30 weeks, postnatal age <30 days) were recruited at 2 sites as part of an ongoing study of neonatal apnea and wireless EEG. Infants underwent 8-9 hour EEG recordings every 2-4 weeks using an electrode cap (ANT-Neuro) connected to the wireless EEG device (Bio-Signal Group). A 23 electrode configuration was used incorporating the International 10-20 System. The device transmitted recordings wirelessly to a laptop computer for bedside assessment. The recordings were assessed by a pediatric neurophysiologist for interpretability. RESULTS: A total of 84 EEGs were recorded from 28 neonates. 61 EEG studies were obtained in infants prior to 35 weeks corrected gestational age (CGA). NICU staff placed all electrode caps and initiated all recordings. Of these recordings 6 (10%) were uninterpretable due to artifacts and one study could not be accessed. The remaining 54 (89%) EEG recordings were acceptable for clinical review and interpretation by a pediatric neurophysiologist. Of the recordings obtained at 35 weeks corrected gestational age or later only 11 out of 23 (48%) were interpretable. CONCLUSIONS: Wireless EEG devices can provide practical, continuous, multichannel EEG monitoring in preterm neonates. Their small size and ease of use could overcome obstacles associated with EEG recording and interpretation in the NICU.

Interleukin-1ß increases Angptl4 (FIAF) expression via the JNK signaling pathway in osteoblastic MC3T3-E1 cells.

Angiopoietin-like protein 4 (Angptl4), also known as fasting-induced adiopogenic factor (FIAF), has recently been reported to influence bone metabolism. However, there have been few studies on regulatory factors other than hypoxia for Angptl4 in bone, and particularly in osteoblasts. Expression of interleukin-1ß (IL-1ß), a proinflammatory cytokine, is increased in serum or bone microenvironments in inflammatory bone diseases or estrogen deficient-conditions. The present study was conducted to determine whether Angptl4 expression in osteoblasts is affected by IL-1ß and investigate its involvement in MAP kinase signaling pathways. Angptl4 RNA levels were increased by IL-1ß treatment in murine MC3T3-E1 osteoblastic cells. Western blotting and immunofluorescent staining showed a corresponding increase in Angptl4 protein. IL-1ß treatment of osteoblasts induced phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular regulated kinases (ERKs), p38, and c-Jun N-terminal kinase (JNK). Furthermore, SP600125, an inhibitor of JNK, significantly blocked the upregulation of Angptl4 by IL-1ß. In contrast, treatment with an inhibitor of p38 MAP kinase (SB203580) or an ERK inhibitor (PD98059) produced responses similar to those seen with the DMSO control. Taken together, these results suggest that IL-1ß increases Angptl4 expression through a mechanism dependent on the JNK-MAPK signaling pathway in MC3T3-E1 cells.

Association between pelvic organ prolapse and bone mineral density in postmenopausal women.

Both pelvic organ prolapse (POP) and osteoporosis are age-related diseases in older aged women. Both POP and bone metabolism may be associated with collagen metabolism. Our study determined the relationship between POP and bone mineral density (BMD) of the lumbar spine and femur neck in postmenopausal women. We selected 554 postmenopausal women (aged 50-79 years) and divided them into two groups (moderate to severe POP and absent to mild POP). We compared the BMDs of the lumbar spine and femur neck between the moderate to severe POP and absent to mild POP groups. Lumbar spine BMD was inversely correlated with POP severity (p = 0.001). However, after adjusting for age, time since menopause, height, weight, body mass index (BMI), and vaginal delivery, the BMDs of both the lumbar spine and femur neck were not significantly different between the moderate to severe POP and absent to mild POP groups (p = 0.583 and p = 0.305, respectively). A lower BMD is associated with increased fracture risk and we postulated that women with severe POP would have an increased risk of osteoporotic fracture.

The association between bone mineral density and periodontitis in Korean adults (KNHANES 2008-2010).

OBJECTIVES: This study investigated the association between bone mineral density (BMD) and periodontitis in a representative sample of Korean adults. MATERIAL AND METHODS: Of 36 188 individuals who participated in the Korea National Health and Nutrition Examination Survey in 2008, 2009, and 2010, 9977 participants aged ≥40 years were included in this cross-sectional study. The associations of BMD of lumbar spine, total femur, and femoral neck with periodontitis were investigated using logistic regression analysis. Additionally, dose-response relationships with BMD divided into quintiles and the association between osteoporosis and periodontitis were investigated. RESULTS: With the set of Community Periodontal Index (CPI) ≥ 3 as a dependent variable, logistic regression analysis revealed that a decrease of BMD was significantly associated with higher odds of periodontitis [range of adjusted odds ratios (AORs); 1.15-1.20, P < 0.001 for all BMD sites]. Similarly, these associations were also found in the CPI 4 model. With regard to dose-response relations, the lower the BMD quintile, the higher the AORs appeared with statistical significance in the CPI ≥ 3 model. (P for trend < 0.001) Participants with osteoporosis had 2.26 and 1.91 times higher odds for CPI ≥ 3 and CPI 4, respectively, than those with normal BMD, indicating a significant association between the two diseases. CONCLUSIONS: Our results suggest that BMD is significantly associated with periodontitis.

Anti-inflammatory effects of Hylomecon hylomeconoides in RAW 264.7 cells.

BACKGROUND AND OBJECTIVES: Papaveraceae serve as a rich source of various alkaloids which have anti-inflammatory effect. MATERIALS AND METHODS: In this study, we investigated the effect of Hylomecon hylomeconoides ethanol extract (HHE) on lipopolysaccharide (LPS)-induced NO and interleukin-6 (IL-6) production in RAW 264.7 cells. RESULTS: HHE inhibited LPS-induced NO and IL-6 production. Moreover, HHE suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW 264.7 in a dose-dependent manner. Furthermore, major constituents, dihydrosanguinarine and 6-methoxydihydrosanguinarine, of the chloroform-soluble extract were analyzed. CONCLUSIONS: Taken together, the results of this study indicate that the anti-inflammatory effects of HHE may occur via the inhibition of NO and IL-6 expression through the down-regulation of MAP kinase (ERK1/2, p38) phosphorylation in RAW 264.7 cells.

Antibacterial activity of bark of Alnus pendula against methicillin-resistant Staphylococcus aureus.

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a rapidly growing health problem around the globe. Recently, there has been considerable interest in the use of plant materials as an alternative method to control pathogenic microorganisms. In this study we evaluated the antibacterial activity of bark of Alnus pendula against MRSA. MATERIALS AND METHODS: The MIC determination was done using the microdilution broth method and bacterial growth was determined by measuring optical density using spectrophotometer. RESULTS: Alnus pendula bark EtOH extract and fractions (F-1, -2, -3 and -4) were investigated against MRSA. The most active fractions (F-3 and F-4) led to the isolation of oregonin (ORE) and hirsutanone (HIR). These compounds were active against MRSA strains with minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 microg/ml MIC and 2 MIC of HIR completely inhibited the growth of MRSA. CONCLUSIONS: The bark EtOH extract of Alnus Pendula has potent antibacterial activity against MRSA.

Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses.

BACKGROUND: Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu. OBJECTIVE: To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases. METHODS: Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA). RESULTS: Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis α (TNF-α) and interleukin 6 (IL-6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL-6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll-like receptor 2 (TLR2)-dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon γ (IFN-γ) or IL-17. CONCLUSION: Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2-dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.

Immunohistochemical changes of adenomyosis after heat therapy: comparison of radiofrequency myolysis and endoablation.

PURPOSE: To check the pathologic changes of focal adenomyosis after heat therapy using radiofrequency and to evaluate which approach--endometrial ablation or direct heat therapy--is better for adenomyosis. To evaluate whether the timing of the procedure and the menstrual cycle are related to pathologic outcomes after heat therapy. METHODS: This study included nine women who underwent total hysterectomy for adenomyosis (diameter, > or = 6 cm). Six fresh uteri were excised in the midline and subjected to radiofrequency heat therapy at the center of the adenomyomas (direct heat therapy) and three uteri were subjected to endometrial ablation. Thereafter, 1 cm(3) myometrial tissue was obtained at 1 cm, 2 cm, and 3 cm away from the endometrium. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical analysis using antibodies against cytokerain-19 (CK-19), actin, and estrogen receptor/progesterone receptor (ER/PR) was performed to evaluate CK-19 (endometrial epithelium marker), actin (myometrial marker) and ER/PR (checking the state of the menstrual cycle), respectively. RESULTS: After endometrial ablation, cauterized tissues were not noted 2 cm away from the endometrium. All tissues between the endometruim and center of adenomyosis were cauterized after direct heat therapy. During the uterine proliferative phase, unlike the secretory phase, subendometrial layers were cauterized 10 min after direct cauterization. CONCLUSION: Direct heat therapy is more effective than endometrial ablation in adenomyosis, and heat is conducted effectively when the patients are in the proliferative phase.

Initial dose of vancomycin based on body weight and creatinine clearance to minimize inadequate trough levels in Japanese adults.

Our aims were to elucidate the factors that affected vancomycin (VCM) serum trough levels and to find the optimal initial dose based on creatinine clearance (CrCl) and body weight (BW) to minimize inadequate trough levels in a retrospective observational study among Japanese adults. One hundred and six inpatients, in whom VCM trough levels were measured after completing the third dosing, were consecutively recruited into our study in a tertiary hospital. We considered the frequency of <30% as low. In the generalized linear model, initial VCM total daily dose, CrCl, and BW were independent risk factors of VCM trough levels. In patients with CrCl ≥30 and <50 mL/min, 1 g/day yielded low frequencies of a trough level of ≥20 mcg/mL, regardless of BW. In patients with CrCl ≥50 mL/min, 2 g/day yielded low frequencies of a trough level of <10 mcg/mL in patients weighing <55 kg, but not in patients weighing ≥55 kg. Optimal VCM initial total daily dose may be 1 g/day in patients with CrCl ≥30 and <50 mL/min regardless of BW and 2 g/day in patients weighing <55 kg with CrCl ≥50 mL/min among Japanese adults.

Association between metabolic syndrome and serum leptin levels in postmenopausal women.

Menopausal status is associated with weight gain, increased central fat mass, abnormal lipid metabolism, insulin resistance and susceptibility to metabolic syndrome (MetS). Leptin is synthesised and secreted by adipocytes. Serum leptin levels are highly correlated with fat mass. We determined the association between MetS and serum leptin levels in 153 postmenopausal women. The difference in serum leptin level between MetS and non-MetS groups showed a statistical significance after adjusting for body mass index (BMI; 19.9 ± 9.5 vs 12.1 ± 5.9 ng/ml, p = 0.013). The indicator of abdominal obesity, waist-to-hip ratio (WHR) and visceral fat area (VFA), had a positive correlation with serum leptin level in non-obese subjects after adjusting for BMI (p = 0.017, p < 0.001, respectively). Of the components of MetS, abdominal obesity and the number of MetS components had a positive correlation with serum leptin level (p < 0.05, p < 0.001, respectively).

Clinical efficacy of different doses of rituximab in the treatment of pemphigus: a retrospective study of 27 patients.

BACKGROUND: The treatment of pemphigus is still challenging and some patients with pemphigus are unresponsive to conventional immunosuppressive treatments. Rituximab, a chimeric monoclonal anti-CD20 antibody, binds to the CD20 antigen on the surface of B cells and has been reported to be effective for the treatment of recalcitrant pemphigus. OBJECTIVE: To compare the efficacy of different doses of rituximab in patients with pemphigus who were unresponsive to conventional therapies. METHODS: Twenty-seven patients with pemphigus who received different doses of rituximab (375 mg m(-2) per infusion weekly) were analysed retrospectively. We divided the patients into two groups: group 1 (n = 12) received two infusions of rituximab and group 2 (n = 15) received three or more infusions of rituximab at 1-week intervals. The number of infusions was determined by the choice of each patient. The endpoints of the study were time to disease control, partial remission (PR) and complete remission (CR). RESULTS: There was no significant difference in time to achieve PR between the two groups (147 vs. 135 days, P = 0·65). However, group 2 demonstrated better outcomes than group 1 in time to CR (443 vs. 149 days, P = 0·06) and relapse rate (0% vs. 67%, P < 0·01). CONCLUSIONS: We conclude that three or more infusions of rituximab are more effective than two infusions for the treatment of pemphigus.

Differential expression of gastrointestinal glutathione peroxidase (GI-GPx) gene during mouse organogenesis.

Gastrointestinal glutathione peroxidase (GI-GPx) is an antioxidant enzyme that has been known to be restricted to the gastrointestinal tract in rodents. In an effort to determine the expression pattern of GI-GPx mRNA during organogenesis, quantitative real-time PCR and in situ hybridization for GI-GPx mRNA were conducted in whole embryos or each developing organ of mice. GI-GPx mRNA was expressed more abundantly in the extraembryonic tissues, including placenta than in embryos on embryonic days (EDs) 7.5-18.5 (P < 0.05). When compared with the expression levels of cytosolic GPx (cGPx) mRNA, GI-GPx mRNA levels were low in the embryos, but relatively high in the extraembryonic tissues (P < 0.05). According to the results of whole mount in situ hybridizations, GI-GPx mRNA was principally expressed in the ectoplacental cone, neural tube and fold, and primitive heart at EDs 7.5-8.5. At EDs 9.5-12.5, GI-GPx mRNA was abundantly expressed in nervous tissues such as the telencephalon, mesencephalon and dorsal neural tube and was also detected in the forelimb and hindlimb at EDs 10.5-12.5. In the sectioned embryos after ED 13.5, GI-GPx mRNA levels were high in the cerebral cortex, metanephric corpuscle, pancreatic ducts, surface epithelia of the skin, inner ear, and nasal conchae, gastrointestinal tract, liver, urinary bladder, airway passages of lung, and whisker follicles. These findings indicate that GI-GPx is not only spatiotemporally expressed in a variety of embryonic organs during organogenesis but also may perform a mutual compensatory role with the cGPx in the protection of embryos and extraembryonic tissues against the reactive oxygen species generated in ontogenetic periods.

Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation.

BACKGROUND: Recently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD. METHODS: Extracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects. RESULTS: The in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects. CONCLUSION: These results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.