Characteristics of Posterior Ethmoidal Artery and Its Relationship with Anterior Ethmoidal Artery and Skull Base on CT Scan.

Objective: Investigation of the anterior and posterior ethmoidal arteries on computed tomography (CT) scans of the sinuses before and during surgery is important, especially for inexperienced surgeons. The aim of this study was to examine the anatomical characteristics of the posterior ethmoid artery in Vietnamese and the distance from the posterior ethmoid artery to the anterior ethmoid artery and the skull base on CT scan. Methods: A cross-sectional study was conducted involving patients aged ≥18 years who underwent CT scan imaging at the Ear, Nose and Throat Hospital of Ho Chi Minh City from February 2023 to July 2023. Results: There were 100 patients in this study, of whom 51% (51/100) were female and 49% (49/100) were male. Patient ages ranged from 20 to 84 years. Their average age was 40.92±14.65 years. The distance on CT scan between the posterior and anterior ethmoidal arteries was 13.98±1.95 mm (9.3 to 18.6 mm). This distance in males was significantly higher than female (p=0.001). However, there is no difference in this distance between the left and right side (p=0.67). The distance between the posterior ethmoid artery and skull base ranged from 0 to 5.4 mm. The average distance between the posterior ethmoidal artery and skull base on CT scan was 0.95±0.94 mm. The diameter of the posterior ethmoid artery was 0.57-0.91 mm. The average diameter of the posterior ethmoidal artery on CT scan was 0.76±0.09 mm. Conclusion: The characteristics of the posterior ethmoid artery should be considered when examining the CT scan. Distance from the posterior ethmoid This study provides useful information on the characteristics of the posterior ethmoid artery on CT scans, which can be applied in endoscopic sinus surgery and skull base surgery.

A theoretical study of the oxidation of benzene by manganese oxide clusters: formation of quinone intermediates.

Manganese oxides (MnxOy) have been widely applied in various chemical industrial processes owing to their long lifetime, low cost and high abundance. They have been used as co-reactants for the elimination of volatile organic compounds (VOCs); however, their oxidation mechanism is not clearly established. In this theoretical study, interaction capacities between benzene (C6H6) and MnxOy clusters, which were modeled with MnO2 and Mn2O3 molecules, were investigated by quantum chemical computations using density functional theory (DFT) with the PBE-D3 functional. The interaction capacity between C6H6 and MnxOy was evaluated, and the probing of the initial stage of the C6H6 oxidation at a molecular level offers an in-depth oxidation reaction path. Interaction energies computed in several spin states, along with the analysis of the electron distribution using the quantum theory of atoms in molecules, natural bond orbital and Wiberg bond index techniques as well as local softness values and MO energies of fragments, point out that the interaction between C6H6 and Mn2O3 is stronger than that with MnO2, amounting to -43 and -35 kcal mol-1, respectively, and the metal atom is identified as the primary active site. During the oxide cluster-assisted oxidation, benzene firstly undergoes an oxidation reaction by active oxygen to generate intermediates such as hydroquinone and benzoquinone. The pathway involving p-benzoquinone as the product (noted as PR1) is the most energetically favored one through a transition structure lying at 19 kcal mol-1, below the energy reference of the reactants, leading to an energy barrier significantly lower than that of 36 kcal mol-1 found for the gas phase oxidation reaction with molecular oxygen without the assistance of the oxide clusters. Potential energy profiles illustrating the reaction paths and molecular mechanisms were described in detail.

Green extraction of phenolics and flavonoids from black mulberry fruit using natural deep eutectic solvents: optimization and surface morphology.

This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants.

Producing bacterial cellulose from industrial recycling paper waste sludge.

This study aimed to produce bacterial cellulose from paper waste sludge (PWS) as a method of utilizing the cellulose source from the remaining pulp in the material. Initially, PWS was hydrolyzed by sulfuric acid to create an enriched-reducing sugar hydrolysate. One-factor experiments were conducted with a fixed amount of PWS (5 g) to investigate the influence of hydrolysis conditions, including water, sulfuric acid addition, temperature, and retention time, on the production yield of reducing sugars. Based on these results, the Box-Behnken model was designed to optimize the hydrolysis reaction. The optimal hydrolysis conditions were 10 ml/g of the sulfuric acid solution (30.9%) at 105.5 °C for 90 min of retention time 0.81 (gGE/g PWS), corresponding to a conversion yield of 40.5%). Subsequently, 100 ml of the filtered and neutralized PWS hydrolysate was used as the culture to produce the bacterial cellulose (BC) using Acetobacter xylinum, which produced 12 g/L of bacterial cellulose. The conversion yield of bacterial cellulose calculated as the ratio of the weight of produced bacterial cellulose to that of cellulose in PWS reached 33.3%. The structure of the obtained BC was analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD) to indicate the formation of nano-cellulose fiber networks. This research proposed a combined method to convert paper waste sludge into bacterial cellulose, demonstrating the potential for waste utilization and sustainable production of paper industries for added-value products.

P38 kinase in gastrointestinal cancers.

Gastrointestinal cancers are a leading cause of cancer morbidity and mortality worldwide with 4.2 million new cases and 3.2 million deaths estimated in 2020. Despite the advances in primary and adjuvant therapies, patients still develop distant metastases and require novel therapies. Mitogen­activated protein kinase (MAPK) cascades are crucial signaling pathways that regulate many cellular processes, including proliferation, differentiation, apoptosis, stress responses and cancer development. p38 Mitogen Activated Protein Kinases (p38 MAPKs) includes four isoforms: p38α (MAPK14), p38ß (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). p38 MAPK was first identified as a stress response protein kinase that phosphorylates different transcriptional factors. Dysregulation of p38 pathways, in particular p38γ, are associated with cancer development, metastasis, autophagy and tumor microenvironment. In this article, we provide an overview of p38 and p38γ with respect to gastrointestinal cancers. Furthermore, targeting p38γ is also discussed as a potential therapy for gastrointestinal cancers.

Targeting fat mass and obesity-associated protein mitigates human colorectal cancer growth in vitro and in a murine model.

Introduction: Colorectal cancer (CRC) remains a significant cause of cancer related mortality. Fat mass and obesity-associated protein (FTO) is a m6A mRNA demethylase that plays an oncogenic role in various malignancies. In this study we evaluated the role of FTO in CRC tumorigenesis. Methods: Cell proliferation assays were conducted in 6 CRC cell lines with the FTO inhibitor CS1 (50-3200 nM) (± 5-FU 5-80 mM) and after lentivirus mediated FTO knockdown. Cell cycle and apoptosis assays were conducted in HCT116 cells (24 h and 48 h, 290 nM CS1). Western blot and m6A dot plot assays were performed to assess CS1 inhibition of cell cycle proteins and FTO demethylase activity. Migration and invasion assays of shFTO cells and CS1 treated cells were performed. An in vivo heterotopic model of HCT116 cells treated with CS1 or with FTO knockdown cells was performed. RNA-seq was performed on shFTO cells to assess which molecular and metabolic pathways were impacted. RT-PCR was conducted on select genes down-regulated by FTO knockdown. Results: We found that the FTO inhibitor, CS1 suppressed CRC cell proliferation in 6 colorectal cancer cell lines and in the 5-Fluorouracil resistant cell line (HCT116-5FUR). CS1 induced cell cycle arrest in the G2/M phase by down regulation of CDC25C and promoted apoptosis of HCT116 cells. CS1 suppressed in vivo tumor growth in the HCT116 heterotopic model (p< 0.05). Lentivirus knockdown of FTO in HCT116 cells (shFTO) mitigated in vivo tumor proliferation and in vitro demethylase activity, cell growth, migration and invasion compared to shScr controls (p< 0.01). RNA-seq of shFTO cells compared to shScr demonstrated down-regulation of pathways related to oxidative phosphorylation, MYC and Akt/ mTOR signaling pathways. Discussion: Further work exploring the targeted pathways will elucidate precise downstream mechanisms that can potentially translate these findings to clinical trials.

Cellulose Nanocrystals-Incorporated Thermosensitive Hydrogel for Controlled Release, 3D Printing, and Breast Cancer Treatment Applications.

In situ-gel-forming thermoresponsive copolymers have been widely exploited in controlled delivery applications because their critical gel temperature is similar to human body temperature. However, there are limitations to controlling the delivery of biologics from a hydrogel network because of the poor networking and reinforcement between the copolymer networks. This study developed an in situ-forming robust injectable and 3D printable hydrogel network based on cellulose nanocrystals (CNCs) incorporated amphiphilic copolymers, poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA). In addition, the physicochemical and mechanical properties of injectable hydrogels were controlled by physically incorporating CNCs with amphiphilic PCLA copolymers. CNCs played an unprecedented role in physically reinforcing the PCLA copolymers' micelle network via intermicellar bridges. Apart from that, the free-flowing closely packed rod-like CNCs incorporated PCLA micelle networks at low temperature transformed to a stable viscoelastic hydrogel network at physiological temperature. CNC incorporated PCLA copolymer sols effectively coordinated with hydrophobic doxorubicin and water-soluble lysozyme by a combination of hydrophobic and hydrogen bonding interaction and controlled the release of biologics. As shown by the 3D printing results, the biocompatible PCLA hydrogels continuously extruded during printing had good injectability and maintained high shape fidelity after printing without any secondary cross-linking steps. The interlayer bonding between the printed layers was high and formed stable 3D structures up to 10 layers. Subcutaneous injection of free-flowing CNC incorporated PCLA copolymer sols to BALB/c mice formed a hydrogel instantly and showed controlled biodegradation of the hydrogel depot without induction of toxicity at the implantation sites or surrounding tissues. At the same time, the in vivo antitumor effect on the MDA-MB-231 tumor xenograft model demonstrated that DOX-loaded hydrogel formulation significantly inhibited the tumor growth. In summary, the CNC incorporated biodegradable hydrogels developed in this study exhibit a prolonged release with special release kinetics for hydrophobic and hydrophilic biologics.

Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment.

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 µg/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs.

Mechanistic insights into the dehydrogenation of formaldehyde, formic acid and methanol using the Pt4 cluster as a promising catalyst.

Reaction mechanisms of the dehydrogenation of formaldehyde, formic acid and methanol on the Pt4 cluster were computationally investigated using density functional theory (DFT) with the B3LYP functional in the conjunction with the aug-cc-pVTZ basis sets for H, C and O atoms, and the cc-pVDZ-PP basis set for Pt. Herein, the key mechanistic aspects of three possible pathways of the dehydrogenation of these compounds are summarized. The results indicate that the formation of H2 and CO or CO2 molecules is more energetically favorable than the generation of H and H2O, HCHO products. Generally, the formation of H2 molecule in the presence of catalysts is more favorable than the direct decomposition of either HCHO, HCOOH or CH3OH molecule. The use of Pt4 catalyst significantly reduces the energy barriers for C-H and O-H bond cleavage of all three compounds to 14, 9 and 12 kcal/mol, respectively. The decomposition of HCOOH is found to be the most energetically favorable. In addition, the mechanistic insights of the reactions confirm the reduction of the energy barriers of the gas-phase dehydrogenation by 67-82 kcal/mol and bring it to the values smaller than 14 kcal/mol in the presence of the Pt4 catalysts.

Inhibition of de novo pyrimidine synthesis augments Gemcitabine induced growth inhibition in an immunocompetent model of pancreatic cancer.

Leflunomide (Lef) is an agent used in autoimmune disorders that interferes with DNA synthesis. De Novo pyrimidine synthesis is a mechanism of Gemcitabine (Gem) resistance in pancreatic cancer. This study aims to assess the efficacy and changes in the tumor microenvironment of Lef monotherapy and in combination with Gem, in a syngeneic mouse model of pancreatic cancer. Methods: MTS proliferation assays were conducted to assess growth inhibition by Gem (0-20 nM), Lef (0-40 uM) and Gem+Lef in KPC (KrasLSL.G12D/+;p53R172H/+; PdxCretg/+) cells in vitro. An in vivo heterotopic KPC model was used and cohorts were treated with: PBS (control), Gem (75 mg/kg/q3d), Lef (40 mg/kg/d), or Gem+Lef. At d28 post-treatment, tumor burden, proliferation index (Ki67), and vascularity (CD31) were measured. Changes in the frequency of peripheral and intratumoral immune cell subsets were evaluated via FACS. Liquid chromatography-mass spectrometry was used for metabolomics profiling. Results: Lef inhibits KPC cell growth and synergizes with Gem in vitro (P<0.05; Combination Index 0.44 (<1 indicates synergy). In vivo, Lef alone and in combination with Gem delays KPC tumor progression (P<0.001). CTLA-4+T cells are also significantly decreased in tumors treated with Lef, Gem or in combination (Gem+Lef) compared to controls (P<0.05). Combination therapy also decreased the Ki67 and vascularity (P<0.01). Leflunomide inhibits de novo pyrimidine synthesis both in vitro (p<0.0001) and in vivo (p<0.05). Conclusions: In this study, we demonstrated that Gem+Lef inhibits pancreatic cancer growth, decrease T cell exhaustion, vascularity and as proof of principle inhibits de novo pyrimidine synthesis. Further characterization of changes in adaptive immunity are necessary to characterize the mechanism of tumor growth inhibition and facilitate translation to a clinical trial.

Effects of Mucoadhesive Polymers on Released Particles and Drug Release in Solid Lipid Particle-Based Buccal Tablets.

BACKGROUND: Mucoadhesive polymers play a critical role in controlled-release tablets for buccal drug delivery. OBJECTIVE: This research aimed to investigate the characterization and mechanisms of solid lipid particle-based tablets with different mucoadhesive polymers for buccal delivery. METHODS: Prednisolone (PSL)-loaded Solid Lipid Particles (SLPs) were conventionally prepared by ultrasonication. The freeze-drying method was used to convert the SLP suspension into a solid dosage form for buccal delivery by using mucoadhesive polymers. RESULTS: All formulations showed over 80% drug release after 6h, which followed immediate and sustained release patterns depending on the SLP type. However, the different polymers in the formulations resulted in different mucoadhesion times and drug release and drug permeability profiles. HPMC 4000 showed higher drug permeation (3327 µg vs. 2589 µg after 6h) but a shorter mucoadhesion time than Carbopol (197 min vs. 361 min). In addition, surface morphology, swelling and erosion, particle size and zeta potential were also noted for the different mechanisms for buccal tablet design with different controlled release profiles. CONCLUSION: The results of this work indicate a good strategy for the selection of mucoadhesive polymers for SLP-based tablets in improving the bioavailability of poorly water-soluble drugs.

Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer.

Baicalein is a Chinese herbal compound extracted from Scutellaria baicalensis that has anti-tumor properties. The aim of this study was to elucidate the mechanisms of action of baicalein against human colorectal cancer cell lines and to assess whether the anti-proliferative effects of baicalein may be amplified with autophagy inhibition. Human colon cancer cell lines (HT-29, HCT-116, SW480, and SW620) were treated with baicalein alone and in combination with the autophagy inhibitor chloroquine (CQ). Baicalein reduced cell viability in all four colon cancer lines in a dose-dependent fashion. Combination treatment of baicalein and the autophagy inhibitor CQ significantly decreased cell viability compared with baicalein alone in HT-29 and HCT-116 cell lines. Western blot analysis of the HCT-116 cell line treated with both baicalein and CQ demonstrated increased expression of LC3-II, a component of autophagy. The combination of baicalein with CQ culminated in activation of caspase-3-mediated apoptosis. These findings demonstrate that inhibition of autophagy enhanced apoptotic cell death induced by baicalein treatment in colon cancer cell lines. Future work will assess other targetable apoptotic pathways activated by baicalein and autophagy inhibition.

Salmonella-mediated therapy targeting indoleamine 2, 3-dioxygenase 1 (IDO) activates innate immunity and mitigates colorectal cancer growth.

Patients with colon cancer remain largely refractory to current immunotherapeutic strategies. This is, in part, due to the overexpression of the immune checkpoint protein indoleamine 2,3-dioxygenase 1 (IDO). IDO is an important enzyme contributing to tumor-mediated immunosuppression and also correlates with poor prognosis in colon cancer patients. The aim of this study was to assess the therapeutic efficacy of attenuated Salmonella typhimurium delivering an shRNA plasmid targeting IDO (shIDO-ST) in two mouse models of colorectal cancer. In vitro, the CT26 and MC38 murine colon cancer cell lines were shown to upregulate IDO expression following stimulation with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Transfection of both cell lines with shIDO plasmid reduced IDO protein expression and function. In vivo, shIDO-ST treatment significantly delayed CT26 and MC38 tumor progression compared to mice treated with scrambled shRNA control (shScr-ST) or the clinically tested IDO inhibitor epacadostat. Increased tumor infiltration of neutrophils was found to be the primary immune cell population associated with shIDO-ST treatment, suggesting robust activation of innate immunity. Although increased tumor expression of IDO is associated with resistance to antibody therapy against programed cell death-1 (anti-PD1), co-administration of anti-PD1 with shIDO-ST did not provide additional tumor growth control in either model of colorectal cancer. Altogether, we demonstrate that treatment with shIDO-ST markedly delays tumor growth in two immunocompetent colorectal mouse models and this appears to be a superior therapeutic strategy compared to epacadostat or blocking anti-PD1 antibody therapy in colon cancer.

Assessment of cost of illness and quality of life in chronic rhinosinusitis patients with surgical treatment.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a popular and tiring disease with significant impacts on the economy and on the Health-related Quality of Life (HRQOL) of patients. This study aims to estimate the cost of illness (COI) and to assess the Health-related Quality of Life (HRQOL) in patients with CRS who underwent surgery in Vietnam and to analyse the relationship between socio-demographic characteristics and the COI as well as the HRQOL. METHODS: A cross-sectional study was conducted in Ear, Nose, Throat Hospital in Ho Chi Minh City (ENT Hospital HCMC), Vietnam between August and October 2018. The direct medical and non-medical costs, the indirect costs (productivity loss), and the HRQOL of patients with CRS were measured. A subjective assessment of quality of life (QOL) using EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) was used to evaluate the health status of these patients after surgery. Characteristics related with the COI and the HRQOL were identified by multiple regression. RESULTS: A total of 264 inpatients with CRS participated in the study. The mean COI for inpatients with CRS was $812.83 and direct costs accounted for a major proportion (89.32%) of the total cost. In addition, the surgery represented the most significant direct medical cost with 58.57% of the total cost. Most of the patients reported no problems with mobility (89.1%), self-care (93.9%), usual activities (77.2%), and anxiety/depression (64.0%). The mean EQ-5D-5L utility score was 0.76 (SD = 0.17), and the mean Visual Analogue Scale (EQ-VAS) score was 76.57 (SD = 13.34). The results of multiple regression showed that gender, occupations, monthly income, prior surgery and family history of CRS affected the total cost while the HRQOL of patients were related to education, smoking behaviour, exercise behaviour and family history of CRS. CONCLUSIONS: This study showed that although endoscopic sinus surgery (ESS) accounted for the largest expense in the COI, this surgical treatment helped to improve the HRQOL in patients with CRS. The findings provided a reference for policy makers in CRS management as well as for adjustment of costs for patients so as to reduce disease burden and to enhance their QOL.

A mathematical model to investigate the key drivers of the biogeography of the colon microbiota.

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest: spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities.

Severe Obesity and Sleep-Disordered Breathing as Risk Factors for Emergence Agitation in Pediatric Ambulatory Surgery.

PURPOSE: Sleep-disordered breathing (SDB) may be a critical risk factor for emergence agitation (EA). We hypothesized that SDB diagnosis is a predictor of EA in children after general anesthesia for ambulatory surgery. DESIGN: Prospective, observational, cohort study. METHODS: Children aged 4 to 17 years were assessed for the occurrence of EA. Differences in probability of EA were assessed using multivariable logistic regression analyses. FINDINGS: Of 1,076 children, 66 (6.1%) had EA. Compared with those without EA, children with EA were younger (P < .001), more likely to have had mask induction (P < .001) and a preoperative diagnosis of SDB (P = .008). On multivariable analysis, SDB, severe obesity, decreasing age in years, increasing first arousal pain score, and intraoperative use of sevoflurane were independently associated with EA. CONCLUSIONS: SDB and severe obesity may be critical independent predictors of EA in children. Mechanisms underlying these observations deserve further elucidation.

Violation of Bans on Tobacco Advertising and Promotion at Points of Sale in Viet Nam: Trend from 2009 - 2015.

Comprehensive bans on tobacco advertising and promotion were introduced through tobacco control legislation in Viet Nam, but it has been established that violations of the bans are very common. This study was conducted to explore the trend in violations of bans on tobacco advertising and promotion at points of sale in Viet Nam in the past six years and to explore any differences in the violation situations before and after the Law on Tobacco Control came into effect on 1st May 2013. Quantitative data were collected through observation of violations of the bans on tobacco advertising and promotion at points of sale in 10 provinces throughout Viet Nam in four survey rounds (2009, 2010, 2011, and 2015). Variation in violation prevalence over time was examined by chi-square test using a Bonferini method. Binary logistic regression was employed to identify the factors that may have influences on different types of violation. A level of significance of p<0.05 was used for all tests in this article. The most common form of violation was the display of more than one pack/one carton of a cigarette brand. Violation of bans on tobacco advertising increased while violations on promotion ban and on displaying tobacco decreased through time. Some factors associated with the tobacco advertising and promotion bans included surveyed years, types of points of sale, regions and areas where the points of sale were located. The enforcement of the bans did not improve even after the issuance and the enactment of the Law on Tobacco Control. This suggests that the monitoring and enforcement of bans on tobacco advertising and promotion at points of sale should be strengthened. Penalties should be strictly applied for violators as indicated in the current tobacco control legislation.

Activation of inflammasome by attenuated Salmonella typhimurium in bacteria-mediated cancer therapy.

Escherichia coli and attenuated Salmonella both naturally accumulate in a tumor mass, yet have distinct therapeutic efficacy: the E. coli K-12 strain (MG1655) cannot induce as significant a tumor suppression as attenuated Salmonella typhimurium, despite similar levels of accumulation in the tumor. To elucidate the mechanism of the robust antitumor effect of S. typhimurium, the cytokine profiles elicited by bacterial colonization in tumors were analyzed. C57BL/6 mice bearing MC38 tumors were injected with Salmonella or MG1655 in the tail vein. Tumors were collected 3 days post-infection and homogenized. Inflammasome-related signals were measured by real-time PCR, ELISA and western blot analysis. Only attenuated Salmonella triggered significant levels of the inflammatory cytokine IL-1ß in the tumor, whereas tumor growth was significantly suppressed. In addition, transcript levels of the core molecules of inflammasome signaling, IPAF, NLRP3 and P2X7, were significantly elevated only in Salmonella-treated tumors. Upon direct interaction between Salmonella and BMDM, BMDM expressed inflammasome-related proteins such as NLRP3, IPAF and caspase-1 p10, and secreted a significant amount of IL-1ß in supernatants. Coincubation assays with BMDM and Salmonella-treated MC38 cells (damaged cancer cells) revealed secretion of IL-1ß only when TLR4 and inflammasome were activated by both LPS and damaged cancer cells. ATP released from damaged cancer cells was also identified as a mechanism of NLRP3 activation. In conclusion, Salmonella activate the inflammasome pathway using damage signals released from cancer cells and through direct interaction with macrophages.

Salmonella typhimurium Suppresses Tumor Growth via the Pro-Inflammatory Cytokine Interleukin-1ß.

Although strains of attenuated Salmonella typhimurium and wild-type Escherichia coli show similar tumor-targeting capacities, only S. typhimurium significantly suppresses tumor growth in mice. The aim of the present study was to examine bacteria-mediated immune responses by conducting comparative analyses of the cytokine profiles and immune cell populations within tumor tissues colonized by E. coli or attenuated Salmonellae. CT26 tumor-bearing mice were treated with two different bacterial strains: S. typhimurium defective in ppGpp synthesis (ΔppGpp Salmonellae) or wild-type E. coli MG1655. Cytokine profiles and immune cell populations in tumor tissue colonized by these two bacterial strains were examined at two time points based on the pattern of tumor growth after ΔppGpp Salmonellae treatment: 1) when tumor growth was suppressed ('suppression stage') and 2) when they began to re-grow ('re-growing stage'). The levels of IL-1ß and TNF-α were markedly increased in tumors colonized by ΔppGpp Salmonellae. This increase was associated with tumor regression; the levels of both IL-1ß and TNF-α returned to normal level when the tumors started to re-grow. To identify the immune cells primarily responsible for Salmonellae-mediated tumor suppression, we examined the major cell types that produce IL-1ß and TNF-α. We found that macrophages and dendritic cells were the main producers of TNF-α and IL-1ß. Inhibiting IL-1ß production in Salmonellae-treated mice restored tumor growth, whereas tumor growth was suppressed for longer by local administration of recombinant IL-1ß or TNF-α in conjunction with Salmonella therapy. These findings suggested that IL-1ß and TNF-α play important roles in Salmonella-mediated cancer therapy. A better understanding of host immune responses in Salmonella therapy may increase the success of a given drug, particularly when various strategies are combined with bacteriotherapy.

A combination of FSH and dibutyryl cyclic AMP promote growth and acquisition of meiotic competence of oocytes from early porcine antral follicles.

Growing porcine oocytes from early antral follicles (1.2-1.5 mm in diameter) do not mature to metaphase II (MII, 4%) under culture conditions which supported maturation (MII, 95%) of fully grown oocytes from large (4-6 mm) antral follicles. We hypothesized that FSH and dbcAMP supported growth and acquisition of meiotic competence. Growing oocytes (113.0 ± 0.4 µm, mean ± SEM) were cultured for 5 d in medium supplemented with 1 mM dbcAMP, 0.01 IU/mL FSH or both; in these media, oocytes reached, 120.5 ± 0.4, 123.5 ± 0.4 and 125.7 ± 0.2 µm, respectively, after 5 d, and then were matured in vitro for 48 h. Oocytes remained enclosed by cumulus cells when cultured with FSH (82%) or both FSH and dbcAMP (80%), but not with dbcAMP alone (0%). Furthermore, oocytes cultured with FSH maintained trans-zonal projections of cumulus cells. Oocytes remained at the GV stage at higher rates when cultured with dbcAMP and FSH (99%), or dbcAMP (97%), than with FSH (64%), or without either (75%). Following in vitro maturation, oocytes reached MII after in vitro growth with dbcAMP (19%), FSH (11%), or both (68%). When oocytes were cultured with both FSH and dbcAMP, activation of Cdc2 and MAP kinases in growing oocytes was similar to fully grown oocytes. In conclusion, growing porcine oocytes grew and acquired meiotic competence in medium supplemented with dbcAMP and FSH; the former maintained oocytes in meiotic arrest, whereas the latter maintained trans-zonal projections of cumulus cells to oocytes during in vitro growth culture.