MEG-based Classification and Grad-CAM Visualization for Major Depressive and Bipolar Disorders with Semi-CNN.

Major depressive disorder (MDD) and bipolar disorder (BD) are two major mood disorders with partly overlapped symptoms but different treatments. However, their misdiagnosis and mistreatment are common based on the DSM-V criteria, lacking objective and quantitative indicators. This study aimed to develop a novel approach that accurately classifies MDD and BD based on their resting-state magnetoencephalography (MEG) signals during euthymic phases. A revisited 3D CNN model, Semi-CNN, that could automatically detect brainwave patterns in spatial, temporal, and frequency domains was implemented to classify wavelet-transformed MEG signals of normal controls and MDD and BD patients. The model achieved a test accuracy of 96.05% and an average of 95.71% accuracy for 5-fold cross-validation. Furthermore, saliency maps of the model were estimated using Grad-CAM++ to visualize the proposed classification model and highlight disease-specific brain regions and frequencies. Clinical Relevance - Our model provides a stable pipeline that accurately classifies MDD, BD, and healthy individuals based on resting-state MEG signals during the euthymic phases, opening the potential for quantitative and accurate brain-based diagnosis for the highly misdiagnosed MDD/BD patients.

Urokinase plasminogen activator induces epithelial-mesenchymal and metastasis of pancreatic cancer through plasmin/MMP14/TGF-ß axis, which is inhibited by 4-acetyl-antroquinonol B treatment.

BACKGROUND: The current standard therapy for metastatic pancreatic cancer is ineffective, necessitating a new treatment approach for prognosis improvement. The urokinase-plasmin activator (uPA) is a critical factor in epithelial-mesenchymal transition (EMT) and cancer metastasis, but its underlying mechanisms in pancreatic cancer remains elusive. METHODS: We investigated uPA expression in our pancreatic cancer cohort. A bioinformatics approach was used to further determine the role of uPA in pancreatic cancer. We employed MiaPaCa-2 and PANC-1 cell lines to investigate how uPA regulates EMT and metastasis in pancreatic cancer and present a novel approach aimed at inhibiting uPA in pancreatic cancer. RESULTS: We observed that higher uPA mRNA expression was significantly associated with overall-poor survival and progression-free survival in pancreatic cancer. uPA was highly expressed in tumor tissue. Gene set enrichment analysis revealed a positive association between uPA mRNA expression and EMT and transforming growth factor ß (TGF-ß) signaling pathways. Moreover, shRNA-mediated uPA gene knockdown reduced plasmin, MMP14, and TGF-ß activation, leading to the inhibition of PANC-1 cells' EMT marker expression, migration, invasion, and cell viability. Notably, 4-acetyl-antroquinonol B (4-AAQB) treatment suppressed MiaPaCa-2 and PANC-1 cell migratory and invasive abilities by inhibiting the uPA/MMP14/TGF-ß axis through upregulation of miR-181d-5p. In the xenograft mouse model of orthotropic pancreatic cancer, 4-AAQB treatment has reduced tumor growth and metastasis rate by deactivating uPA and improving the survival of the mice model. CONCLUSION: Accordingly, to extent of our knowledge and previous studies, we demonstrated that 4-AAQB is an anti Pan-Cancer drug, and may inhibit pancreatic cancer EMT and metastasis and serve as a new therapeutic approach for patients with late-stage pancreatic cancer.

Erinacine A Prevents Lipopolysaccharide-Mediated Glial Cell Activation to Protect Dopaminergic Neurons against Inflammatory Factor-Induced Cell Death In Vitro and In Vivo.

Hericium erinaceus (HE) is a common edible mushroom consumed in several Asian countries and considered to be a medicinal mushroom with neuroprotective effects. Erinacine A (EA) is a bioactive compound in Hericium erinaceus mycelium (HEM) that has been shown to have a neuroprotective effect against neurodegenerative diseases, e.g., Parkinson's disease (PD). Although the etiology of PD is still unclear, neuroinflammation may play an important role in causing dopaminergic neuron loss, which is a pathological hallmark of PD. However, glial cell activation has a close relationship with neuroinflammation. Thus, this study aimed to investigate the anti-neuroinflammatory and neuroprotective effects of EA on lipopolysaccharide (LPS)-induced glial cell activation and neural damage in vitro and in vivo. For the in vitro experiments, glial cells, BV-2 microglial cells and CTX TNA2 astrocytes were pretreated with EA and then stimulated with LPS and/or IFN-γ. The expression of proinflammatory factors in the cells and culture medium was analyzed. In addition, differentiated neuro-2a (N2a) cells were pretreated with EA or HEM and then stimulated with LPS-treated BV-2 conditioned medium (CM). The cell viability and the amount of tyrosine hydroxylase (TH) and mitogen-activated protein kinases (MAPKs) were analyzed. In vivo, rats were given EA or HEM by oral gavage prior to injection of LPS into the substantia nigra (SN). Motor coordination of the rats and the expression of proinflammatory mediators in the midbrain were analyzed. EA pretreatment prevented LPS-induced iNOS expression and NO production in BV-2 cells and TNF-α expression in CTX TNA2 cells. In addition, both EA and HEM pretreatment significantly increased cell viability and TH expression and suppressed the phosphorylation of JNK and NF- κB in differentiated N2a cells treated with CM. In vivo, both EA and HEM significantly improved motor dysfunction in the rotarod test and the amphetamine-induced rotation test and reduced the expression of TNF-α, IL-1ß and iNOS in the midbrain of rats intranigrally injected with LPS. The results demonstrate that EA ameliorates LPS-induced neuroinflammation and has neuroprotective properties.

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.

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.

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

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.

Maternal morbidity by attempted route of delivery in periviable birth.

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 (p < .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 (p < .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.

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

Aging and lifestyle factors, including high-sugar and high-fat diets, promote a systemic metabolic imbalance that promotes neurodegeneration. Hericium erinaceus 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 Hericium erinaceus 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-α, interleukin-1ß, 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.

Early preterm preeclampsia outcomes by intended mode of delivery.

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.

The Disruption of the ß-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.

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 Antrodia cinnamomea, 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 (p = 0.0001, log-rank test = 475.2), and correlates with poor prognosis of GBM patients. Lower grade glioma and glioblastoma patients (n = 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 (p = 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, p < 0.001). Western blot analysis showed that 4-AAQB significantly downregulated ß-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 IC50 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.

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

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.

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.

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.

Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice

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-gamma, IL-4, IL-5, TNF-alfa 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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Universal Rapid Human Immunodeficiency Virus Screening at Delivery: A Cost-Effectiveness Analysis.

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.

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

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.

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

Objective 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. Study Design 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. Results 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]). Conclusion Cervical dilation < 6 cm with any station and 6 to 10 cm with station ≤ -3 were associated with a higher risk of cord prolapse.

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

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 (n = 3324) and no true-positive results. Patients not tested (n = 458) were predominately secondary to physician omission (93.7%) and were more likely to be White (p < 0.01) and older (p < 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.

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

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 (240/7-336/7), late preterm (340/7-366/7), and term (370/7-416/7 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% (p < 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 (p < 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.

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

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.

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

BACKGROUND: The prevalence of morbid obesity (body mass index ≥40 kg/m2) 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.

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

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.