Publications by authors named "Chun-Chih Huang"

53 Publications

4-Acetyl-Antroquinonol B Improves the Sensitization of Cetuximab on Both Kras Mutant and Wild Type Colorectal Cancer by Modulating the Expression of Ras/Raf/miR-193a-3p Signaling Axis.

Int J Mol Sci 2021 Jul 14;22(14). Epub 2021 Jul 14.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes. Our previous study revealed the anti-proliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control; SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab; however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the reduction of colony formation, invasion, and tumorsphere generation and of oncogenic KRAS signaling cascade of CRC cells. Thus, inducing cells with 4-AAQB before cetuximab therapy could resensitize KRAS-mutant, but not wild-type, cells to cetuximab. Therefore, we hypothesized that 4-AAQB can inhibit KRAS. In silico analysis of the publicly available GEO (GSE66548) dataset of KRAS-mutated versus KRAS wild-type CRC patients confirmed that miR-193a-3p was significantly downregulated in the former compared with the latter patient population. Overexpression of miR-193a-3p considerably reduced the oncogenicity of both CRC cells. Furthermore, KRAS is a key target of miR-193a-3p. In vivo treatment with the combination of 4-AAQB and cetuximab significantly reduced the tumor burden of a xenograft mice model through the reduction of the expression of oncogenic markers (EGFR) and p-MEK, p-ERK, and c-RAF/p-c-RAF signaling, with the simultaneous induction of miR-193a-3p expression in the plasma. In summary, our findings provide strong evidence regarding the therapeutic effect of 4-AAQB on KRAS-mutant CRC cells. Furthermore, 4-AAQB effectively inhibits Ras singling in CRC cells, through which KRAS-mutant CRC can be resensitized to cetuximab.
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http://dx.doi.org/10.3390/ijms22147508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307961PMC
July 2021

4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells.

Toxicol Appl Pharmacol 2021 07 13;422:115493. Epub 2021 Mar 13.

College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu City 30015, Taiwan; Department of Hematology & Oncology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan. Electronic address:

Background: Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 -) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2- breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells.

Methods: We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment.

Results: High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4.

Conclusion: The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.
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http://dx.doi.org/10.1016/j.taap.2021.115493DOI Listing
July 2021

Maternal morbidity by attempted route of delivery in periviable birth.

J Matern Fetal Neonatal Med 2021 Apr 26;34(8):1241-1248. Epub 2019 Jun 26.

Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC, USA.

Objective: Much of the literature on clinical decision-making regarding the optimal route of delivery for periviable birth, 23 0/7-25 6/7 weeks gestation, has focused on neonatal risks. In fact, routine cesarean delivery at these early gestational ages has not been shown to improve neonatal mortality or neurological outcomes. Neonatal risks associated with the route of delivery are well known. Conversely, there is a paucity of data on maternal morbidity associated with the route of delivery. We examined maternal morbidity according to the attempted route of delivery in women undergoing periviable birth.

Study Design: In a secondary analysis of the Consortium on Safe Labor, a retrospective cohort study, maternal outcomes were compared between attempted vaginal delivery and planned cesarean delivery in women undergoing periviable birth. Analyses were repeated to compare maternal outcomes among actual mode of delivery (vaginal delivery versus cesarean delivery). Multivariable Poisson regression was used to estimate adjusted relative risks (aRR) with 95% confidence intervals (95% CI), controlling for predefined covariates.

Results: Of 678 women who underwent periviable birth, 558 (82.3%) and 120 (17.7%) attempted vaginal delivery and planned cesarean delivery, respectively. Of 558 women who attempted a vaginal delivery, 411 (73.7%) achieved a vaginal delivery. Women who attempted a vaginal delivery compared to those who had a planned cesarean delivery were less likely to have endometritis (3.1 versus 15.0%; aRR 0.18, 95% CI 0.09-0.35). Women who attempted a vaginal delivery compared to those who had a planned cesarean delivery had 7-day shorter total length of hospital stay ( < .001). Comparison of actual mode of delivery showed that women with vaginal had decreased risks of fever (2.9 versus 7.9%; aRR 0.42, 95% CI 0.20-0.90), endometritis (0.5 versus 12.4%; aRR 0.03, 95% CI 0.01-0.13), and maternal thrombosis (0.2 versus 3.0%; aRR 0.08, 95% CI 0.01-0.93) compared to cesarean delivery. Women with vaginal delivery had 3-day shorter total length of hospital stay ( < .001) compared to cesarean delivery.

Conclusion: The majority of women (73.7%) who attempted a vaginal delivery achieved a vaginal delivery. Attempting a vaginal delivery between 23 0/7 and 25 6/7 weeks gestation compared to a planned cesarean delivery was associated with decreased risks of maternal infectious morbidity. Deciding the route of delivery is challenging in women undergoing periviable delivery. Our analysis provides important information on short-term maternal risks when considering the risks and benefits during these discussions.
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http://dx.doi.org/10.1080/14767058.2019.1631792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930981PMC
April 2021

Mycelium and Its Isolated Compound, Erinacine A, Ameliorate High-Fat High-Sucrose Diet-Induced Metabolic Dysfunction and Spatial Learning Deficits in Aging Mice.

J Med Food 2019 May;22(5):469-478

2 Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan.

Aging and lifestyle factors, including high-sugar and high-fat diets, promote a systemic metabolic imbalance that promotes neurodegeneration. has long been used in traditional Chinese medicine. Recently, its functional activities, such as antimetabolic dysfunction, antineuroinflammatory activities, and stimulation of nerve growth factor (NGF) synthesis, have been revealed. This study demonstrated that mycelium (HEM) and an isolated diterpenoid derivative, erinacine A (EA), may reverse spatial learning disabilities in aging mice (15 months old) fed with a high-fat and high-sucrose diet (HFSD). Aging mice were randomly assigned to one of four treatment groups: (1) a chow diet (control), (2) an HFSD, and an HFSD supplemented with either (3) HEM or (4) EA for 18 weeks. The Morris water maze (MWM) and Y-maze were used for behavioral assessments. Both HEM- and EA-treated mice had shorter mean daily escape latencies than HFSD-treated mice in the MWM. In addition, HEM-treated mice had a slightly increased exploratory time and frequency in the novel arm in the Y-maze. Quantitative PCR revealed that both HEM- and EA-treated mice exhibited reduced messenger RNA (mRNA) expression of tumor necrosis factor-, interleukin-1, and HEM-treated mice exhibited increased mRNA expression of NGF and NeuN in the hippocampus. Moreover, HEM and EA also decreased body weight, abdominal fat, plasma glucose, serum and liver total cholesterol, and liver triacylglycerol. Thus, HEM may be a potential health-promoting supplement for minimizing the progression of aging and obesity-induced neurodegeneration by reducing metabolic abnormalities and neuroinflammatory cytokines and increasing neurogenesis factors.
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http://dx.doi.org/10.1089/jmf.2018.4288DOI Listing
May 2019

The Disruption of the β-Catenin/TCF-1/STAT3 Signaling Axis by 4-Acetylantroquinonol B Inhibits the Tumorigenesis and Cancer Stem-Cell-Like Properties of Glioblastoma Cells, In Vitro and In Vivo.

Cancers (Basel) 2018 Dec 5;10(12). Epub 2018 Dec 5.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan.

Background: Glioblastoma (GBM), a malignant form of glioma, is characterized by resistance to therapy and poor prognosis. Accumulating evidence shows that the initiation, propagation, and recurrence of GBM is attributable to the presence of GBM stem cells (GBM-CSCs).

Experimental Approach: Herein, we investigated the effect of 4-Acetylantroquinonol B (4-AAQB), a bioactive isolate of , on GBM cell viability, oncogenic, and CSCs-like activities.

Results: We observed that aberrant expression of catenin is characteristic of GBM, compared to other glioma types ( = 0.0001, log-rank test = 475.2), and correlates with poor prognosis of GBM patients. Lower grade glioma and glioblastoma patients ( = 1152) with low catenin expression had 25% and 21.5% better overall survival than those with high catenin expression at the 5 and 10-year time-points, respectively ( = 3.57e-11, log-rank test = 43.8). Immunohistochemistry demonstrated that compared with adjacent non-tumor brain tissue, primary and recurrent GBM exhibited enhanced catenin expression (~10-fold, < 0.001). Western blot analysis showed that 4-AAQB significantly downregulated β-catenin and dysregulated the catenin/LEF1/Stat3 signaling axis in U87MG and DBTRG-05MG cells, dose-dependently. 4-AAQB⁻induced downregulation of catenin positively correlated with reduced Sox2 and Oct4 nuclear expression in the cells. Furthermore, 4-AAQB markedly reduced the viability of U87MG and DBTRG-05MG cells with 48 h IC of 9.2 M and 12.5 M, respectively, effectively inhibited the nuclear catenin, limited the migration and invasion of GBM cells, with concurrent downregulation of catenin, vimentin, and slug; similarly, colony and tumorsphere formation was significantly attenuated with reduced expression of c-Myc and KLF4 proteins.

Conclusions: Summarily, we show for the first time that 4-AAQB suppresses the tumor-promoting catenin/LEF1/Stat3 signaling, and inhibited CSCs-induced oncogenic activities in GBM in vitro, with in vivo validation; thus projecting 4-AAQB as a potent therapeutic agent for anti-GBM target therapy.
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http://dx.doi.org/10.3390/cancers10120491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315804PMC
December 2018

Early preterm preeclampsia outcomes by intended mode of delivery.

Am J Obstet Gynecol 2019 01 28;220(1):100.e1-100.e9. Epub 2018 Sep 28.

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, MedStar Washington Hospital Center, Washington, DC.

Background: The optimal route of delivery in early-onset preeclampsia before 34 weeks is debated because many clinicians are reluctant to proceed with induction for perceived high risk of failure.

Objective: Our objective was to investigate labor induction success rates and compare maternal and neonatal outcomes by intended mode of delivery in women with early preterm preeclampsia.

Study Design: We identified 914 singleton pregnancies with preeclampsia in the Consortium on Safe Labor study for analysis who delivered between 24 0/7 and 33 6/7 weeks. We excluded fetal anomalies, antepartum stillbirth, or spontaneous preterm labor. Maternal and neonatal outcomes were compared between women undergoing induction of labor (n = 460) and planned cesarean delivery (n = 454) and women with successful induction of labor (n = 214) and unsuccessful induction of labor (n = 246). We calculated relative risks and 95% confidence intervals to determine outcomes by Poisson regression model with propensity score adjustment. The calculation of propensity scores considered covariates such as maternal age, gestational age, parity, body mass index, tobacco use, diabetes mellitus, chronic hypertension, hospital type and site, birthweight, history of cesarean delivery, malpresentation/breech, simplified Bishop score, insurance, marital status, and steroid use.

Results: Among the 460 women with induction (50%), 47% of deliveries were vaginal. By gestational age, 24 to 27 6/7, 28 to 31 6/7, and 32 to 33 6/7, the induction of labor success rates were 38% (12 of 32), 39% (70 of 180), and 54% (132 of 248), respectively. Induction of labor compared with planned cesarean delivery was less likely to be associated with placental abruption (adjusted relative risk, 0.33; 95% confidence interval, 0.16-0.67), wound infection or separation (adjusted relative risk, 0.23; 95% confidence interval, 0.06-0.85), and neonatal asphyxia (0.12; 95% confidence interval, 0.02-0.78). Women with vaginal delivery compared with those with failed induction of labor had decreased maternal morbidity (adjusted relative risk, 0.27; 95% confidence interval, 0.09-0.82) and no difference in neonatal outcomes.

Conclusion: About half of women with preterm preeclampsia who attempted an induction had a successful vaginal delivery. The rate of successful vaginal delivery increases with gestational age. Successful induction has the benefit of preventing maternal and fetal comorbidities associated with previous cesarean deliveries in subsequent pregnancies. While overall rates of a composite of serious maternal and neonatal morbidity/mortality did not differ between induction of labor and planned cesarean delivery groups, women with failed induction of labor had increased maternal morbidity highlighting the complex route of delivery counseling required in this high-risk population of women.
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http://dx.doi.org/10.1016/j.ajog.2018.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605098PMC
January 2019

Choice of Prophylactic Antibiotics and Surgical Site Infections After Cesarean Delivery.

Obstet Gynecol 2018 10;132(4):948-955

Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC; the Department of Biostatistics and Epidemiology, MedStar Health Research Institute, Hyattsville, Maryland; and Georgetown-Howard Universities Center for Clinical and Translational Science and Obstetrics and Gynecology, MedStar Georgetown University Hospital, Washington, DC.

Objective: To examine the rate of surgical site infection according to the choice of antibiotics in women undergoing cesarean delivery.

Methods: We conducted a retrospective cohort study of women undergoing cesarean delivery (labored, unlabored, and scheduled) from 2012 to 2017. Women with chorioamnionitis and those who did not receive any antibiotics were excluded. Our primary outcome was defined a priori as a composite of cellulitis, endometritis, deep wound infection, abdominopelvic abscess, and sepsis. Outcomes were examined according to the choice of antibiotics: cefazolin, a standard alternative (both clindamycin and gentamicin), and inappropriate alternatives (such as clindamycin only). A multivariable logistic regression model was used to calculate the propensity score for each observation, which was the probability of receiving a particular antibiotic regimen. The propensity score-adjusted logistic regression models were conducted to calculate adjusted odds ratios (ORs) and 95% CIs. Firth's penalized likelihood approach was applied to address issues of rare events.

Results: Among 6,584 selected women, 6,163 (93.6%), 274 (4.2%), and 147 (2.2%) received cefazolin, a standard alternative, and inappropriate alternatives, respectively. Use of standard alternative antibiotics compared with cefazolin was not associated with increased odds of the primary outcome (crude OR 1.50 [0.92-2.46]; adjusted OR 1.63 [0.97-2.60]) but was associated with increased odds of cellulitis (crude OR 2.07 [1.16-3.70]; adjusted OR 1.93 [1.03-3.31]). Use of inappropriate alternative antibiotics compared with cefazolin was associated with increased odds of the primary outcome (crude OR 4.37 [2.80-6.83]; adjusted OR 4.13 [2.59-6.36]) as well as some components of the composite outcome such as endometritis before discharge (crude OR 6.85 [3.94-11.90]; adjusted OR 6.68 [3.69-11.44]) and cellulitis (crude OR 3.36 [1.78-6.34]; adjusted OR 3.23 [1.63-5.81]).

Conclusion: Both standard alternative and inappropriate alternatives were associated with increased odds of surgical site infections compared with cefazolin.
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http://dx.doi.org/10.1097/AOG.0000000000002863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353631PMC
October 2018

4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 re-Expression.

Cancers (Basel) 2018 Aug 10;10(8). Epub 2018 Aug 10.

Department of Hematology and Oncology, Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored.

Experimental Approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, Western blot, real-time polymerase chain reaction (RT-PCR), and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2.

Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-acetylantroquinonol B (4-AAQB), as evidenced by inhibited cell viability and proliferation, as well as attenuated migration, invasion, and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. Interestingly, 4-AAQB did not affect the viability and proliferation of normal colon cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA, reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates the FOLFOX (folinate (leucovorin), fluorouracil (5FU), and oxaliplatin) anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324, and inhibiting SOD2-mediated tumorigenicity.

Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.
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http://dx.doi.org/10.3390/cancers10080269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116152PMC
August 2018

Risk Factors for Umbilical Cord Prolapse at the Time of Artificial Rupture of Membranes.

AJP Rep 2018 Apr 10;8(2):e89-e94. Epub 2018 May 10.

Department of Obstetrics and Gynecology, MedStar Georgetown University Hospital, Washington, District of Columbia.

 The aim of the study was to examine the association between cervical exam at the time of artificial rupture of membranes (AROM) and cord prolapse.  We conducted a retrospective cohort study using the data from the Consortium on Safe Labor. We included women with cephalic presentation and singleton pregnancies at ≥ 23 weeks' gestation who underwent AROM during the course of labor. Multivariable logistic regression was used to calculate the adjusted odds ratio (aOR) with 95% confidence interval (95% CI), controlling for prespecified covariates.  Of 57,204 women who underwent AROM, cord prolapse occurred in 113 (0.2%). Compared with dilation 6 to 10 cm + station ≥ 0 at the time of AROM, <6 cm + any station and 6-10 cm + station ≤ -3 were associated with increased risks of cord prolapse (<6 cm + station ≤ -3 [aOR, 2.29; 95% CI, 1.02-5.40]; <6 cm + station -2.5 to -0.5 [aOR, 2.34; 95% CI, 1.23-4.97]; <6 cm + station ≥ 0 [aOR, 3.31; 95% CI, 1.39-8.09]; and 6-10 cm + station ≤ -3 [aOR, 5.47; 95% CI, 1.35-17.48]).  Cervical dilation < 6 cm with any station and 6 to 10 cm with station ≤ -3 were associated with a higher risk of cord prolapse.
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http://dx.doi.org/10.1055/s-0038-1649486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945286PMC
April 2018

Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice.

Allergol Immunopathol (Madr) 2018 Jul - Aug;46(4):354-360. Epub 2018 May 5.

Department of Food Science and Technology, HungKuang University, Taichung, Taiwan. Electronic address:

Background: Probiotics could be beneficial to health and some of them have shown to modulate immune responses.

Aim: The aim of this study is to investigate if the probiotic strains including Lactobacillus and Pediococcus strains are able to alleviate allergic reactions in an ovalbumin-induced airway allergy model.

Methods: Lactobacillus multi-species preparation (LMP) was gavaged to BALB/c for total six weeks and BALB/c was challenged with ovalbumin in the last two weeks. A barometric whole-body plethysmography was used to assess enhanced pause (Penh) of airway hyperreactivity (AHR). Immunoglobulins (Ig) such as IgE, IgG1, IgG2a and cytokines such as IL-12, IFN-γ, IL-4, IL-5, TNF-α and IL-13 in bronchoalveolar lavage fluid were assayed using ELISA kits.

Results: The results showed this LMP significantly reduced Th2 cytokines and enhanced Th1 cytokines production. OVA-specific IgE and IgG1 was lower in the probiotics-treated mice whereas IgG2a was increased. Most importantly, this murine model showed LMP supplementation significantly reduced AHR.

Conclusions: Overall, this Lactobacillus multi-species preparation seemed to suppress OVA-sensitized airway hyperreactivity, thus serving as a possible candidate for therapeutic uses for allergic airway symptoms.
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http://dx.doi.org/10.1016/j.aller.2018.02.001DOI Listing
October 2018

Universal Rapid Human Immunodeficiency Virus Screening at Delivery: A Cost-Effectiveness Analysis.

Infect Dis Obstet Gynecol 2018 14;2018:6024698. Epub 2018 Mar 14.

MedStar Health Research Institute (MHRI), Washington, DC, USA.

Objective: To determine the cost-effectiveness of universal maternal HIV screening at time of delivery to decrease mother-to-child transmission (MTCT), by comparing the cost and quality-adjusted life years (QALYs) of universal rapid HIV screening at time of delivery to two current standards of care for prenatal HIV screening in the United States.

Study Design: We conducted a cost-effectiveness analysis to compare the cost and QALY of universal intrapartum rapid HIV screening with two current standards of care: (I) opt-out rapid HIV testing limited to patients without previous third-trimester screening and (II) opt-out rapid HIV testing limited to patients without any prenatal screening. We developed a decision-tree model and performed sensitivity analyses to estimate the impact of variances in QALY, estimated lifetime medical costs, HIV prevalence, and cumulative incidence.

Results: The incremental cost-effectiveness ratio for universal screening was $7,973.45/QALY. The results remained robust to sensitivity analysis, except for annual cumulative incidence. In areas with an annual cumulative incidence rate of <0.02% for reproductive-age women, the incremental cost-effectiveness ratio for the expanded program would exceed $89,926.94/QALY, approaching the commonly applied cost-effectiveness thresholds ($100,000/QALY).

Conclusions: Intrapartum universal rapid HIV screening to decrease MTCT appears cost-effective in populations with high HIV incidence in the United States.
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http://dx.doi.org/10.1155/2018/6024698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872626PMC
January 2019

Implementation of universal rapid human immunodeficiency virus screening on labor and delivery.

Ther Adv Infect Dis 2018 Mar 23;5(2):47-54. Epub 2018 Jan 23.

MedStar Washington Hospital Center, Washington, DC, USA; MedStar Health Research Institute, Washington, DC, USA.

Background: A case of mother to child transmission (MTCT) of HIV at a medical center in Washington, DC, resulted in the implementation of universal opt-out rapid testing of patients admitted for delivery. This article evaluates the policy's efficacy and implementation.

Methods: We evaluated the implementation using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework.

Results: We could not evaluate decrease in MTCT rate secondary to low sample size ( = 3324) and no true-positive results. Patients not tested ( = 458) were predominately secondary to physician omission (93.7%) and were more likely to be White ( < 0.01) and older ( < 0.01). There was a negative relationship with physician omission over time.

Conclusion: The policy was successfully implemented with decreasing proportions of patients not tested. Earlier inclusion of testing into standard admission orders and nurse-based approach may have expedited adoption. Given the low incidence of new HIV diagnosis in labor, we were unable to assess decrease in MTCT.
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http://dx.doi.org/10.1177/2049936117753012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813856PMC
March 2018

Racial/Ethnic Differences in Labor Induction in a Contemporary US Cohort: A Retrospective Cohort Study.

Am J Perinatol 2018 03 24;35(4):361-368. Epub 2017 Oct 24.

Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, District of Columbia.

Objective: To examine labor induction by race/ethnicity and factors associated with disparity in induction.

Study Design: This is a retrospective cohort study of 143,634 women eligible for induction ≥24 weeks' gestation from 12 clinical centers (2002-2008). Rates of labor induction for each racial/ethnic group were calculated and stratified by gestational age intervals: early preterm (24-33), late preterm (34-36), and term (37-41 weeks). Multivariable logistic regression examined the association between maternal race/ethnicity and induction controlling for maternal characteristics and pregnancy complications. The primary outcome was rate of induction by race/ethnicity. Inductions that were indicated, non-medically indicated, or without recorded indication were also compared.

Results: Non-Hispanic black (NHB) women had the highest percentage rate of induction, 44.6% ( < 0.001). After adjustment, all racial/ethnic groups had lower odds of induction compared with non-Hispanic white (NHW) women. At term, NHW women had the highest percentage rate (45.4%) of non-medically indicated or induction with no indication ( < 0.001).

Conclusion: Compared with other racial/ethnic groups, NHW women were more likely to undergo non-medically indicated induction at term. As labor induction may avoid the occurrence of stillbirth, whether this finding explains part of the increased risk of stillbirth for NHB women at term merits further research.
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http://dx.doi.org/10.1055/s-0037-1607285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842105PMC
March 2018

Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression.

J Ethnopharmacol 2017 Jul 8;207:47-56. Epub 2017 Jun 8.

Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address:

Ethnopharmacological Relevance: The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet.

Aim Of The Study: To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels.

Materials And Methods: A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133 CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed.

Results: Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients.

Conclusion: Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.
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http://dx.doi.org/10.1016/j.jep.2017.06.004DOI Listing
July 2017

Nonmedically indicated induction in morbidly obese women is not associated with an increased risk of cesarean delivery.

Am J Obstet Gynecol 2017 10 31;217(4):451.e1-451.e8. Epub 2017 May 31.

Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC.

Background: The prevalence of morbid obesity (body mass index ≥40 kg/m) in women aged 20-39 years was 7.5% in 2009 through 2010. Morbid obesity is associated with an increased risk of stillbirth compared with normal body mass index, especially >39 weeks' gestation. The data regarding increased risk of cesarean delivery associated with nonmedically indicated induction of labor compared to expectant management in morbidly obese women are limited.

Objective: We sought to compare the cesarean delivery rate of nonmedically indicated induction of labor with expectant management in morbidly obese women without other comorbidity.

Study Design: This was a retrospective cohort study from the Consortium on Safe Labor of morbidly obese women with singleton, cephalic gestations without previous cesarean, chronic hypertension, or gestational or pregestational diabetes between 37 0/7 and 41 6/7 weeks' gestation. We examined maternal outcomes including cesarean delivery, operative delivery, third- or fourth-degree laceration, postpartum hemorrhage, and composite maternal outcome (any of: transfusion, intensive care unit admission, venous thromboembolism). We also examined neonatal outcomes including shoulder dystocia, macrosomia (>4000 g), neonatal intensive care unit admission, and composite neonatal outcome (5-min Apgar score <5, stillbirth, neonatal death, or asphyxia or hypoxic-ischemic encephalopathy). Adjusted odds ratios with 95% confidence intervals were calculated, controlling for maternal characteristics, hospital type, and simplified Bishop score. Analyses were conducted at early and full term (37 0/7 to 38 6/7 and 39 0/7 to 40 6/7 weeks' gestation, respectively). Women who delivered between 41 0/7 and 41 6/7 weeks' gestation were included as expectant management group.

Results: Of 1894 nulliparous and 2455 multiparous morbidly obese women, 429 (22.7%) and 791 (32.2%) had nonmedically indicated induction, respectively. In nulliparas, nonmedically indicated induction was not associated with increased risks of cesarean delivery and was associated with decreased risks of macrosomia (2.2% vs 11.0%; adjusted odds ratio, 0.24; 95% confidence interval, 0.05-0.70) at early term and decreased neonatal intensive care unit admission (5.1% vs 8.9%; adjusted odds ratio, 0.59; 95% confidence interval, 0.33-0.98) at full term compared with expectant management. In multiparas, nonmedically indicated induction compared with expectant management was associated with a decreased risk of macrosomia at early term (4.2% vs 14.3%; adjusted odds ratio, 0.30; 95% confidence interval, 0.13-0.60), cesarean delivery at full term (5.4% vs 7.9%; adjusted odds ratio, 0.64; 95% confidence interval, 0.41-0.98), and composite neonatal outcome (0% vs 0.6%; adjusted odds ratio, 0.10; 95% confidence interval, <.01-0.89) at full term.

Conclusion: In morbidly obese women without other comorbidity, nonmedically indicated induction was not associated with an increased risk of cesarean delivery.
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http://dx.doi.org/10.1016/j.ajog.2017.05.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614804PMC
October 2017

Neonatal outcomes in fetuses with cardiac anomalies and the impact of delivery route.

Am J Obstet Gynecol 2017 10 31;217(4):469.e1-469.e12. Epub 2017 May 31.

Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC.

Background: Congenital fetal cardiac anomalies compromise the most common group of fetal structural anomalies. Several previous reports analyzed all types of fetal cardiac anomalies together without individualized neonatal morbidity outcomes based on cardiac defect. Mode of delivery in cases of fetal cardiac anomalies varies greatly as optimal mode of delivery in these complex cases is unknown.

Objective: We sought to determine rates of neonatal outcomes for fetal cardiac anomalies and examine the role of attempted route of delivery on neonatal morbidity.

Study Design: Gravidas with fetal cardiac anomalies and delivery >34 weeks, excluding stillbirths and aneuploidies (n = 2166 neonates, n = 2701 cardiac anomalies), were analyzed from the Consortium on Safe Labor, a retrospective cohort study of electronic medical records. Cardiac anomalies were determined using International Classification of Diseases, Ninth Revision codes and organized based on morphology. Neonates were assigned to each cardiac anomaly classification based on the most severe cardiac defect present. Neonatal outcomes were determined for each fetal cardiac anomaly. Composite neonatal morbidity (serious respiratory morbidity, sepsis, birth trauma, hypoxic ischemic encephalopathy, and neonatal death) was compared between attempted vaginal delivery and planned cesarean delivery for prenatal and postnatal diagnosis. We used multivariate logistic regression to calculate adjusted odds ratio for composite neonatal morbidity controlling for race, parity, body mass index, insurance, gestational age, maternal disease, single or multiple anomalies, and maternal drug use.

Results: Most cardiac anomalies were diagnosed postnatally except hypoplastic left heart syndrome, which had a higher prenatal than postnatal detection rate. Neonatal death occurred in 8.4% of 107 neonates with conotruncal defects. Serious respiratory morbidity occurred in 54.2% of 83 neonates with left ventricular outflow tract defects. Overall, 76.3% of pregnancies with fetal cardiac anomalies underwent attempted vaginal delivery. Among patients who underwent attempted vaginal delivery, 66.1% had a successful vaginal delivery. Women with a fetal cardiac anomaly diagnosed prenatally were more likely to have a planned cesarean delivery than women with a postnatal diagnosis (31.7 vs 22.8%; P < .001). Planned cesarean delivery compared to attempted vaginal delivery was not associated with decreased composite neonatal morbidity for all prenatally diagnosed (adjusted odds ratio, 1.67; 95% confidence interval, 0.85-3.30) or postnatally diagnosed (adjusted odds ratio, 0.99; 95% confidence interval, 0.77-1.27) cardiac anomalies.

Conclusion: Most fetal cardiac anomalies were diagnosed postnatally and associated with increased rates of neonatal morbidity. Planned cesarean delivery for prenatally diagnosed cardiac anomalies was not associated with less neonatal morbidity.
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http://dx.doi.org/10.1016/j.ajog.2017.05.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793863PMC
October 2017

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

Toxicol Appl Pharmacol 2017 06 10;325:48-60. Epub 2017 Apr 10.

Department of Hematology and Oncology, Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. Electronic address:

Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy.
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http://dx.doi.org/10.1016/j.taap.2017.04.003DOI Listing
June 2017

Inhibitory Effects of Probiotic Lactobacillus on the Growth of Human Colonic Carcinoma Cell Line HT-29.

Molecules 2017 Jan 10;22(1). Epub 2017 Jan 10.

Department of Food Science and Technology, Hungkuang University, Taichung City 43302, Taiwan.

This study was conducted to investigate the inhibitory effect of cells and supernatants on the growth of the human colon cancer cell line HT-29. Our study results indicated that the PM153 strain exhibits the best adhesion ability and the highest survival in the gastrointestinal tract simulation experiment. Furthermore, after an 8-h co-culture of PM153 and HT-29 cells, the PM153 strain can induce the secretion of nitric oxide from the HT-29 cells. In addition, after the co-culture of the BCRC17010 strain (10⁸ cfu/mL) and HT-29 cells, the Bax/Bcl-2 ratio in the HT-29 cells was 1.19, which showed a significant difference from the other control and LAB groups ( < 0.05), which therefore led to the inference that the BCRC17010 strain exerts a pro-apoptotic effect on the HT-29 cells. Upon co-culture with HT-29 cells for 4, 8 and 12 h, the BCRC14625 strain (10⁸ cfu/mL) demonstrated a significant increase in lactate dehydrogenase (LDH) activity ( < 0.05), causing harm to the HT-29 cell membrane; further, after an 8-h co-culture with the HT-29 cells, it induced the secretion of nitric oxide (NO) from the HT-29 cells. Some lactic acid bacteria (LAB) strains have ability to inhibit the growth of the colorectal cancer cell line HT-29 Bax/Bcl-2 pathway or NO production. In summary, we demonstrated that the BCRC17010 strain, good abilities of adhesion and increased LDH release, was the best probiotic potential for inhibition of HT-29 growth amongst the seven LAB strains tested in vitro.
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http://dx.doi.org/10.3390/molecules22010107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155858PMC
January 2017

Stabilized Wide Bandgap Perovskite Solar Cells by Tin Substitution.

Nano Lett 2016 12 21;16(12):7739-7747. Epub 2016 Nov 21.

Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195-2120, United States.

Wide bandgap MAPb(IBr) perovskites show promising potential for application in tandem solar cells. However, unstable photovoltaic performance caused by phase segregation has been observed under illumination when y is above 0.2. Herein, we successfully demonstrate stabilization of the I/Br phase by partially replacing Pb with Sn and verify this stabilization with X-ray diffractometry and transient absorption spectroscopy. The resulting MAPbSn(IBr) perovskite solar cells show stable photovoltaic performance under continuous illumination. Among these cells, the one based on MAPbSn(IBr) perovskite shows the highest efficiency of 12.59% with a bandgap of 1.73 eV, which make it a promising wide bandgap candidate for application in tandem solar cells. The engineering of internal bonding environment by partial Sn substitution is believed to be the main reason for making MAPbSn(IBr) perovskite less vulnerable to phase segregation during the photostriction under illumination. Therefore, this study establishes composition engineering of the metal site as a promising strategy to impart phase stability in hybrid perovskites under illumination.
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http://dx.doi.org/10.1021/acs.nanolett.6b03857DOI Listing
December 2016

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

Molecules 2016 Oct 31;21(11). Epub 2016 Oct 31.

New Bellus Enterprises Co., Ltd. No. 48, Industrial Rd., Erh Chen Vil., Kuan Tien Dist., Tainan 72042, Taiwan.

The aim of the present study was to determine whether (LS) and (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.
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http://dx.doi.org/10.3390/molecules21111456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274176PMC
October 2016

Duration of Oxytocin and Rupture of the Membranes Before Diagnosing a Failed Induction of Labor.

Obstet Gynecol 2016 08;128(2):373-380

Departments of Obstetrics and Gynecology, MedStar Washington Hospital Center and MedStar Georgetown University Hospital, and the Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC; the Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, Hyattsville, Maryland; and the Department of Maternal Fetal Medicine, Christiana Care Health System, Newark, Delaware.

Objective: To compare maternal and neonatal outcomes based on length of the latent phase during induction with rupture of membranes before 6 cm dilation.

Methods: This is a retrospective cohort study using data from the Consortium of Safe Labor study, including 9,763 nulliparous and 8,379 multiparous women with singleton, term pregnancies undergoing induction at 2 cm dilation or less with rupture of membranes before 6 cm dilation after which the latent phase ended. Outcomes were evaluated according to duration of oxytocin and rupture of membranes.

Results: At time points from 6 to 18 hours of oxytocin and rupture of membranes, the rates of nulliparous women remaining in the latent phase declined (35.9-1.4%) and the rates of vaginal delivery for those remaining in the latent phase at these time periods decreased (54.1-29.9%) Nulliparous women remaining in the latent phase for 12 hours compared with women who had exited the latent phase had significantly increased rates of chorioamnionitis (12.1% compared with 4.1%) and endometritis (3.6% compared with 1.3%) and increased rates of neonatal intensive care unit admission (8.7% compared with 6.3%). Similar patterns were present for multiparous women at 15 hours.

Conclusion: Based on when neonatal morbidity increased, in an otherwise uncomplicated induction of labor with rupture of membranes, a latent phase after initiation of oxytocin of at least 12 hours for nulliparous women and 15 hours in multiparous women is a reasonable criterion for diagnosing a failed induction.
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http://dx.doi.org/10.1097/AOG.0000000000001527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959965PMC
August 2016

Induction of Labor in Women with Oligohydramnios: Misoprostol Compared with Prostaglandin E2.

Am J Perinatol 2017 01 11;34(2):204-210. Epub 2016 Jul 11.

Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

 To compare perinatal outcomes in women with oligohydramnios and an unfavorable cervix undergoing labor induction with misoprostol to prostaglandin E2.  We conducted a secondary analysis of women with oligohydramnios undergoing labor induction in the Consortium on Safe Labor study (2002-2008). Oligohydramnios was recorded in the medical chart. We evaluated perinatal outcomes. We limited the analysis to women with an unfavorable cervix defined by simplified Bishop score ≤ 4. Misoprostol was compared with prostaglandin E2. Women could have received oxytocin, underwent mechanical dilation, or had artificial rupture of membranes, but women who underwent induction with both misoprostol and prostaglandin E2 were excluded. We calculated adjusted odds ratios with 95% confidence intervals, controlling for maternal age, maternal body mass index (kg/m), parity, and mechanical dilation.  Among women with oligohydramnios and an unfavorable cervix who underwent induction of labor, 141 (39.4%) received misoprostol and 217 (60.6%) received prostaglandin E2. There were no significant differences in cesarean delivery, chorioamnionitis, postpartum hemorrhage, transfusion, neonatal intensive care unit (NICU) admission, NICU stay > 72 hours, mechanical ventilation, and neonatal sepsis.  In women with oligohydramnios and an unfavorable cervix, induction of labor with misoprostol was comparable to prostaglandin E2.
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http://dx.doi.org/10.1055/s-0036-1585418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226930PMC
January 2017

Indications for primary cesarean delivery relative to body mass index.

Am J Obstet Gynecol 2016 Oct 20;215(4):515.e1-9. Epub 2016 May 20.

Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC.

Background: Obesity is a known risk factor for cesarean delivery. Limited data are available regarding the reasons for the increased rate of primary cesarean in obese women. It is important to identify the factors leading to an increased risk of cesarean to identify opportunities to reduce the primary cesarean rate.

Objective: We evaluated indications for primary cesarean across body mass index (kg/m(2)) classes to identify the factors contributing to the increased rate of cesarean among obese women.

Study Design: In the Consortium of Safe Labor study from 2002 through 2008, we calculated indications for primary cesarean including failure to progress or cephalopelvic disproportion, nonreassuring fetal heart tracing, malpresentation, elective, hypertensive disease, multiple gestation, placenta previa or vasa previa, failed induction, HIV or active herpes simplex virus, history of uterine scar, fetal indication, placental abruption, chorioamnionitis, macrosomia, and failed operative delivery. For women with primary cesarean for failure to progress or cephalopelvic disproportion, dilation at the last recorded cervical examination was evaluated. Women were categorized according to body mass index on admission: normal weight (18.5-24.9), overweight (25.0-29.9), and obese classes I (30.0-34.9), II (35.0-39.9), and III (≥40). Cochran-Armitage trend test and χ(2) tests were performed.

Results: Of 66,502 nulliparous and 76,961 multiparous women in the study population, 19,431 nulliparous (29.2%) and 7329 multiparous (9.5%) women underwent primary cesarean. Regardless of parity, malpresentation, failure to progress or cephalopelvic disproportion, and nonreassuring fetal heart tracing were the common indications for primary cesarean. Regardless of parity, the rates of primary cesarean for failure to progress or cephalopelvic disproportion increased with increasing body mass index (normal weight, overweight, and classes I, II, and III obesity in nulliparous women: 33.2%, 41.6%, 46.4%, 47.4%, and 48.9% [P < .01] and multiparous women: 14.5%, 20.3%, 22.8%, 27.2%, and 25.3% [P < .01]), whereas the rates for malpresentation decreased (normal weight, overweight, and classes I, II, and III obesity in nulliparous women: 23.7%, 17.2%, 14.6%, 12.0%, and 9.1% [P < .01] and multiparous women: 35.6%, 30.6%, 26.5%, 24.3%, and 22.9% [P < .01]). Rates of primary cesarean for nonreassuring fetal heart tracing were not statistically different for nulliparous (P > .05) or multiparous (P > .05) women. Among nulliparous women who had a primary cesarean for failure to progress or cephalopelvic disproportion, rates of cesarean prior to active labor (6 cm) increased as body mass index increased, accounting for 39.3% of women with class I, 47.1% of women with class II, and 56.8% of women with class III obesity compared to 35.2% for normal-weight women (P < .01).

Conclusion: Similar to normal-weight women, the indication of cesarean for failure to progress or cephalopelvic disproportion was the major factor contributing to the increase in primary cesarean in obese women, but was even more prevalent with increasing obesity class. The rates of intrapartum primary cesarean prior to achieving active labor increased with increasing obesity class in nulliparous women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045770PMC
http://dx.doi.org/10.1016/j.ajog.2016.05.023DOI Listing
October 2016

Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats.

Int J Med Sci 2016 30;13(4):277-85. Epub 2016 Mar 30.

4. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;; 11. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;; 12. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.

High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats.
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http://dx.doi.org/10.7150/ijms.14769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829540PMC
December 2016

Lack of Agreement on Distal Radius Fracture Treatment.

J Am Board Fam Med 2016 Mar-Apr;29(2):218-25

From the Department of Human Science, Georgetown University School of Nursing and Health Studies, Washington, DC (KKB); the Department of Family Medicine, Georgetown University Medical Center, Washington, DC (DJM, TPT); Georgetown University School of Medicine, Washington, DC (MVN, JRB, ACP); the Orthopaedic Foot & Ankle Center of Washington, Falls Church, VA (SKN); the Department of Orthopaedics, MedStar Georgetown University Hospital, Washington, DC (MJP); the Department of Biostatistics and Epidemiology, MedStar Health Research Institute, Hyattsville, MD (C-CH); and the Department of Health Systems Administration, Georgetown University School of Nursing and Health Studies, Washington, DC (RBF).

Introduction: Variation in clinical practice resulting from the absence of evidence-based treatment protocols has negative implications on both the cost and the quality of medical care. The objective of this study was to assess whether a standard of care for the treatment of extra-articular nondisplaced distal radius fracture has developed despite the lack of a conclusive recommendation from the American Academy of Orthopaedic Surgeons.

Methods: A case-vignette survey was conducted. Treatment type and duration of casting selections were analyzed. The cost implications of responses were assessed. Participants were practicing orthopedists primarily in the mid-Atlantic region of the United States. Orthopedists (n = 494) were recruited via E-mail and at the American Academy of Orthopaedic Surgeons Annual Meeting held in Chicago in March 2013. Inclusion criteria required that participants be graduates of an accredited medical school and be practicing orthopedists at the time of survey distribution. The main outcome measure was surgical or nonsurgical intervention.

Results: Nonsurgical treatment was selected by 60% of respondents, with surgery preferred by 37%. Duration of casting responses varied from 2 to 12 weeks. Among nonsurgical responses, 69% indicated 6 weeks as their preferred duration of casting (95% confidence interval, 64.9-73.1%). Surgery imposes a 76% greater total cost to society than nonsurgical treatments.

Conclusions: Our findings suggest the absence of a consensus strategy for the treatment of extra-articular nondisplaced distal radius fractures. Implications of variance in treatment on cost and quality support the need for established, evidence-based guidelines or further clinical trials to assist in the management of this common fracture.
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http://dx.doi.org/10.3122/jabfm.2016.02.150233DOI Listing
December 2016

Maternal and Neonatal Outcomes by Attempted Mode of Operative Delivery From a Low Station in the Second Stage of Labor.

Obstet Gynecol 2015 Dec;126(6):1265-1272

Departments of Obstetrics and Gynecology, MedStar Washington Hospital Center and MedStar Georgetown University Hospital, Washington, DC, and the University of Texas Health Sciences Center at San Antonio, San Antonio, Texas; and the Department of Biostatistics and Epidemiology, MedStar Health Research Institute, Hyattsville, Maryland.

Objective: To evaluate maternal and neonatal outcomes by attempted mode of operative delivery from a low station in the second stage of labor.

Methods: Retrospective study of 2,518 women carrying singleton fetuses at 37 weeks of gestation or greater who underwent attempted forceps-assisted delivery, attempted vacuum-assisted vaginal delivery, or cesarean delivery from a low station in the second stage of labor. Primary outcomes were stratified by parity and included a maternal adverse outcome composite (postpartum hemorrhage, transfusion, endometritis, peripartum hysterectomy, or intensive care unit admission) and a neonatal adverse outcome composite (5-minute Apgar score less than 4, respiratory morbidity, neonatal intensive care unit admission, shoulder dystocia, birth trauma, or sepsis).

Results: In nulliparous patients, the maternal adverse composite was not significantly different between women who underwent attempted forceps (12.1% compared with 10.8%, adjusted odds ratio [OR] 0.77, 95% confidence interval [CI] 0.40-1.34) or vacuum (8.3% compared with 10.8%, adjusted OR 0.68, 95% CI 0.40-1.16) delivery compared with cesarean delivery. Among parous women, the maternal adverse composite was not significantly different with attempted forceps (10.7% compared with 12.5%, adjusted OR 0.40, 95% CI 0.09-1.71) or vacuum (11.3% compared with 12.5%, adjusted OR 0.44, 95% CI 0.11-1.72) compared with cesarean delivery. Compared with neonates delivered by cesarean, the neonatal adverse composite was significantly lower among neonates born to nulliparous women who underwent attempted forceps (9.4% compared with 16.7%, adjusted OR 0.44, 95% CI 0.27-0.72) but not among those who underwent vacuum delivery (11.9% compared with 16.7%, adjusted OR 0.68, 95% CI 0.44-1.04). Among parous women, the neonatal adverse composite was not significantly different after attempted forceps (4.1% compared with 12.5%, adjusted OR 0.28, 95% CI 0.06-1.35) or vacuum (12.5% compared with 12.5%, adjusted OR 1.03, 95% CI 0.28-3.87) compared with cesarean delivery.

Conclusion: A trial of forceps delivery from a low station compared with cesarean delivery was associated with decreased neonatal morbidity among neonates born to nulliparous women.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0000000000001156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683158PMC
December 2015

Pregnancy Outcomes Among Obese Women and Their Offspring by Attempted Mode of Delivery.

Obstet Gynecol 2015 Nov;126(5):987-993

Divisions of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, MedStar Washington Hospital Center and MedStar Georgetown University Hospital, Washington, DC, and the University of Illinois at Chicago, Chicago, Illinois; and MedStar Health Research Institute, Hyattsville, Maryland.

Objective: To compare maternal and neonatal morbidities among obese women and their offspring by attempted delivery approach.

Methods: We performed a retrospective cohort study of 47,372 obese women at delivery (body mass index 30 or greater) eligible for vaginal delivery who were carrying singleton vertex fetuses at 37 weeks of gestation or greater. Prior cesarean delivery, congenital anomalies, and antepartum stillbirth were exclusion criteria. We analyzed outcomes by attempted delivery route and stratified by parity. The composite maternal outcome included intensive care admission, death, hemorrhage, transfusion, or thromboembolism. The neonatal composite included intensive care unit admission, death, seizure, ventilator use, birth injury, or asphyxia. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated using Poisson regression.

Results: Among nulliparous women attempting vaginal delivery (n=15,268), the success rate was 72.6% and among parous women (n=23,426), it was 93.7%. The maternal composite outcome rate was not statistically higher among nulliparous women (7.7% compared with 4.2% [adjusted RR 1.58, 95% CI 0.96-2.59]) but it was among parous women (7.6% compared with 2.5% [adjusted RR 2.45, 95% CI 1.23-4.90]) attempting vaginal delivery related to hemorrhage, blood transfusion, or both. In contrast, the neonatal composite outcome rate was lower in parous women (6.0% compared with 11.6% [adjusted RR 0.65, 95% CI 0.51-0.83]) but not in nulliparous women (10.2% compared with 12.4% [adjusted RR 0.91, 95% CI 0.74-1.12]) parous.

Conclusion: In obese nulliparous women, attempted vaginal delivery was not associated with increased composite maternal or neonatal morbidity. In obese parous women, attempted vaginal delivery was associated with increased composite maternal morbidity and lower composite neonatal morbidity.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0000000000001084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648353PMC
November 2015

Adverse Maternal and Neonatal Outcomes in Adolescent Pregnancy.

J Pediatr Adolesc Gynecol 2016 Apr 29;29(2):130-6. Epub 2015 Aug 29.

Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC.

Study Objective: To investigate the outcomes of adolescent pregnancy.

Design: Retrospective cohort study from the Consortium on Safe Labor between 2002 and 2008.

Setting: Twelve clinical centers with 19 hospitals in the United States.

Participants: Nulliparous women (n = 43,537) younger than 25 years of age, including 1189 younger adolescents (age ≤ 15.9 years), 14,703 older adolescents (age 16-19.9 years), and 27,645 young adults (age 20-24.9 years).

Interventions: Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated, controlling for maternal characteristics and pregnancy complications (young adults as a reference group).

Main Outcome Measures: Maternal, neonatal outcomes, cesarean indications, and length of labor.

Results: Younger adolescents had an increased risk of maternal anemia (aOR = 1.25; 95% CI, 1.07-1.45), preterm delivery at less than 37 weeks of gestation (aOR = 1.36; 95% CI, 1.14-1.62), postpartum hemorrhage (aOR = 1.46; 95% CI, 1.10-1.95), preeclampsia or hemolysis, increased liver enzyme levels, and low platelet syndrome (aOR = 1.44; 95% CI, 1.17-1.77) but had a decreased risk of cesarean delivery (aOR = 0.49; 95% CI, 0.42-0.59), chorioamnionitis (aOR = 0.63; 95% CI, 0.47-0.84), and neonatal intensive care unit admission (aOR = 0.80; 95% CI, 0.65-0.98). Older adolescents had an increased risk of maternal anemia (aOR = 1.15; 95% CI, 1.09-1.22), preterm delivery at less than 37 weeks of gestation (aOR = 1.16; 95% CI, 1.08-1.25), and blood transfusion (aOR = 1.21; 95% CI, 1.02-1.43), but had a decreased risk of cesarean delivery (aOR = 0.75; 95% CI, 0.71-0.79), chorioamnionitis (aOR = 0.83; 95% CI, 0.75-0.91), major perineal laceration (aOR = 0.82; 95% CI, 0.71-0.95), and neonatal intensive care unit admission (aOR = 0.89; 95% CI, 0.83-0.96). Older adolescents were less likely to have a cesarean delivery for failure to progress or cephalopelvic disproportion (aOR = 0.89; 95% CI, 0.81-0.98). For adolescents who entered spontaneous labor, the second stage of labor was shorter (P < .01).

Conclusion: Adolescents were less likely to have a cesarean delivery. Failure to progress or cephalopelvic disproportion occurred less frequently in older adolescents. Adolescents who entered spontaneous labor had a shorter second stage of labor.
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http://dx.doi.org/10.1016/j.jpag.2015.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886236PMC
April 2016

4-Acetylantroquinonol B inhibits colorectal cancer tumorigenesis and suppresses cancer stem-like phenotype.

Toxicol Appl Pharmacol 2015 Oct 30;288(2):258-68. Epub 2015 Jul 30.

Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan. Electronic address:

4-Acetylantroquinonol B (4-AAQB), closely related to the better known antroquinonol, is a bioactive isolate of the mycelia of Antrodia camphorata, a Taiwanese mushroom with documented anti-inflammatory, hypoglycemic, vasorelaxative, and recently demonstrated, antiproliferative activity. Based on its traditional use, we hypothesized that 4-AAQB may play an active role in the suppression of cellular transformation, tumor aggression and progression, as well as chemoresistance in colorectal carcinoma (CRC). In this study, we investigated the antiproliferative role of 4-AAQB and its underlying molecular mechanism. We also compared its anticancer therapeutic potential with that of antroquinonol and the CRC combination chemotherapy of choice - folinic acid, fluorouracil and oxaliplatin (FOLFOX). Our results showed that 4-AAQB was most effective in inhibiting tumor proliferation, suppressing tumor growth and attenuating stemness-related chemoresistance. 4-AAQB negatively regulates vital oncogenic and stem cell maintenance signal transduction pathways, including the Lgr5/Wnt/β-catenin, JAK-STAT, and non-transmembrane receptor tyrosine kinase signaling pathways, as well as inducing a dose-dependent downregulation of ALDH and other stemness related factors. These results were validated in vivo, with animal studies showing 4-AAQB possessed comparable tumor-shrinking ability as FOLFOX and potentiates ability of the later to reduce tumor size. Thus, 4-AAQB, a novel small molecule, projects as a potent therapeutic agent for monotherapy or as a component of standard combination chemotherapy.
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http://dx.doi.org/10.1016/j.taap.2015.07.025DOI Listing
October 2015

Risk factors for retained placenta.

Am J Obstet Gynecol 2015 Dec 29;213(6):864.e1-864.e11. Epub 2015 Jul 29.

Department of Obstetrics and Gynecology, MedStar Georgetown University Hospital, Washington, DC; Division of Maternal Fetal Medicine, MedStar Georgetown University Hospital, Washington, DC.

Objective: Retained placenta complicates 2-3% of vaginal deliveries and is a known cause of postpartum hemorrhage. Treatment includes manual or operative placental extraction, potentially increasing risks of hemorrhage, infections, and prolonged hospital stays. We sought to evaluate risk factors for retained placenta, defined as more than 30 minutes between the delivery of the fetus and placenta, in a large US obstetrical cohort.

Study Design: We included singleton, vaginal deliveries ≥24 weeks (n = 91,291) from the Consortium of Safe Labor from 12 US institutions (2002-2008). Multivariable logistic regression analyses estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) for potential risk factors for retained placenta stratified by parity, adjusting for relevant confounding factors. Characteristics such as stillbirth, maternal age, race, and admission body mass index were examined.

Results: Retained placenta complicated 1047 vaginal deliveries (1.12%). Regardless of parity, significant predictors of retained placenta included stillbirth (nulliparous adjusted OR, 5.67; 95% CI, 3.10-10.37; multiparous adjusted OR, 4.56; 95% CI, 2.08-9.94), maternal age ≥30 years, delivery at 24 0/7 to 27 6/7 compared with 34 weeks or later and delivery in a teaching hospital. In nulliparous women, additional risk factors were identified: longer first- or second-stage labor duration, whereas non-Hispanic black compared with non-Hispanic white race was found to be protective. Body mass index was not associated with an increased risk.

Conclusion: Multiple risk factors for retained placenta were identified, particularly the strong association with stillbirth. It is plausible that there could be something intrinsic about stillbirth that causes a retained placenta, or perhaps there are shared pathways of certain etiologies of stillbirth and a risk of retained placenta.
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http://dx.doi.org/10.1016/j.ajog.2015.07.039DOI Listing
December 2015
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