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Two different synthetic approaches to novel heterocyclic hybrid compounds of 4-azapodophyllotoxin were investigated. The obtained products were characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. MTT protocol was then performed to examine the cytotoxic activity of these products against KB, HepG2, A549, MCF7, and Hek-293 cell lines. The cytotoxic assessment indicated that all products displayed moderate to high cytotoxicity against all tested cancer cell lines. The most active compound 13k containing the 2-methoxypyridin-4-yl group exhibited selective cytotoxicity against KB, A549, and HepG2 cell lines with the IC 50 values ranging from 0.23 to 0.27 μM, which were between 5- to 10-fold more potent than the positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) and 13d (HetAr = 5-bromofuran-2-yl) displayed high cytotoxic selectivity for A549 and HepG2 cancer cell lines when compared to the other cancer cell lines and low toxicity to the normal Hek-293 cell line. Molecular docking study was conducted to evaluate the interaction of new synthesized compounds with the colchicine-binding-site of tubulin. Besides that, physicochemical and pharmacokinetic properties of the most active compounds 13h,k were predicted., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: A simple and efficient tool for evaluating ovarian tumors in general hospitals where radiologists without experience in gynecological ultrasound is necessary. This study aims to evaluate the diagnostic performance of IOTA simple rules in initial classification of ovarian tumors by non-experienced examiners who have received simple training., Materials and Method: A prospective single-center study was conducted at Hanoi Obstetrics and Gynecology Hospital. Three resident gynecologists trained themselves for two weeks and then received hands-on practice under the supervision of experts for another two weeks. The examiners performed ultrasound on 424 eligible women scheduled for surgery for ovarian tumors and classified the tumors based on IOTA simple rules. The postoperative pathology of ovarian tumors was used as the gold standard., Results: 90.8 % (385/424) of the tumors were benign. Simple rules were applicable in 399/424 (94.1 %) tumors, with a sensitivity of 84.8 % (95 % CI, 70.2-94.3), specificity of 98.9 % (95 % CI, 97.5-99.7), positive predictive value of 87.5 % (95 % CI, 73.3-95.9), and negative predictive value of 98.6 % (95 % CI, 97.1-99.5). The sensitivity of IOTA simple rules was higher in postmenopausal women (91.7 % vs. 81.0 %), while the specificity was higher in premenopausal women (99.4 % vs. 95.8 %). Accuracy was 100 % in all ten pregnant women were assessed using these rules., Conclusion: In conclusion, in the hands of non-expert examiners who were trained thoroughly, IOTA simple rules are a simple and efficient tool for clinical practice in centers where expert radiologists in gynecology are not always available. The training program is simple and could be applied widely in other clinical centers. Further studies are necessary to evaluate the effectiveness of the IOTA simple rules in assessing ovarian tumors among pregnant women., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Cellulitis is an acute bacterial infection of the skin and subcutaneous tissue. The characteristic symptoms of the disease are an area of skin that is swollen, warmth, redness, pain, unknown borderline, tends to expand, and can lead to tissue necrosis. Hyperbaric Oxygen (HBO) is a non-drug treatment, which has the effect of relieving pain, reducing edema, and accelerating the wound healing process for patients with cellulitis. This study aims to evaluate the results of treating patients with cellulitis by HBO., Materials and Methods: A case-control study was conducted. 89 patients were diagnosed with cellulitis and treated at VINIMAM from January 2022 to December 2023. The study group included 48 patients treated with HBO combined with intravenous antibiotics, wound care. The reference group included 41 patients who were not treated with HBO but were treated with intravenous antibiotics, wound care., Results: The pain relief level of the study group was better than that of the reference group (VAS score after one day of treatment: 4.34 and 5.78, after 2 days: 2.46 and 4.17, after 3 days: 1.28 and 3.35). The time for edema to subside in the study group was shorter than in the reference group. The circumference of the cellulitis area in the study group shrunk better than in the reference group. The average days of treatment in the study group were less than the reference group (8.33 ± 2.67 days and 13.17 ± 4.78 days)., Conclusion: Hyperbaric Oxygen was a good method to treat cellulitis, helped to reduce pain, was anti-inflammatory, reduced edema, and shortened treatment time.

Introduction: COVID-19 vaccination hesitancy is prevalent in underserved communities, and family medicine clinics can combat hesitancy with vaccine education. However, due to general misinformation, physicians hesitate to educate patients because doing so can create conflict., Methods: A series of resident-run, team-based quality improvement projects were conducted at a federally qualified health center every 4 months between June 2021 and May 2022. First, staff documentation of vaccine status was addressed. Second, physician and staff education about COVID-19 vaccines was completed along with motivational interview training to avoid conflict with patients. Third, patient COVID-19 vaccine education was addressed., Results: After Cycle 1, COVID-19 vaccine documentation status increased the number of patients who completed the vaccination series from 1% to 22%. Cycle 2 showed an increase in COVID-19 vaccination rate after health care team education. This reflected an increase from 35% to 76% of residents reporting that they discussed COVID-19 vaccines with unvaccinated patients after the intervention. Cycle 3 fought vaccine misinformation by educating patients. Most patients heard information about COVID-19 vaccines from friends and family (95%), social media (90%), and the news (80%). Physician confidence in providing COVID-19 vaccine education to patients increased from 2.8 (< somewhat confident) to 4.3 (moderately confident) out of 5 over 3 plan-do-study-act cycles., Discussion: Vaccination rates were tracked alongside physician surveys regarding the experience of offering the vaccine to patients. Vaccination rates steadily increased over time, and physicians became more confident in COVID-19 vaccine discussions with patients., Conclusion: Primary care physicians are needed to approach public health concerns, such as vaccination completion, but ongoing education is also needed to promote confidence in health care pathways., Competing Interests: Conflicts of Interest None declared

Lithium-ion batteries lay the foundation for satisfying the fast-growing demand of portable electronics and electric vehicles. However, due to the complexity of material syntheses, high fabrication temperature condition, and toxic gas emission, high volume manufacturing of lithium-ion batteries is still challenging. Here, we propose a modified coprecipitation method to synthesize Li 1.0 Ni 0.6 Mn 0.2 Co 0.2 O 2 (NMC622-MCP) as a cathode material in a simple, cost-effective, and environmentally friendly approach. We demonstrate that the proposed method can be operated in a lower temperature environment, with respect to the requirement of conventional synthesis methods. Furthermore, only CO 2 gas is emitted during synthesis. We also employed first-principles simulations to evaluate the crystallinity of the synthesized materials via X-ray diffractometer patterns. During charge/discharge processes, the obtained cathode materials induce outstanding electrochemical performance with a maximum specific capacity of up to 206.9 mAh g -1 at 0.05 C and a retention capacity of 83.22% after 100 cycles. Thus, the simple, cost-effective, environmentally friendly, and highly electrochemical performance of the newly acquired material envisages the modified coprecipitation method as a promising tool to manufacture cathode materials for lithium-ion batteries., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: To evaluate the value of contrast volume/glomerular filtration ratio (Vc/eGFR ratio) and urine Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting the progression contract associated-acute kidney injury (CA-AKI) to chronic kidney disease (CKD) in planned percutaneous coronary intervention (PCI) patients., Patients and Methods: We examined 387 adult patients who had undergone planned percutaneous coronary intervention (PCI). We determined acute kidney injury (AKI) and chronic kidney disease (CKD) using the criteria set by the Kidney Disease: Improving Global Outcomes (KDIGO). We calculated the estimated glomerular filtration rate (eGFR) using the CKD-EPI formula based on serum creatinine levels. To determine the Vc/eGFR ratio, we considered the contrast medium volume and eGFR for each patient. Additionally, we measured urine NGAL levels using the ELISA method., Results: The percentage of CA-AKI patients who developed CKD after planned PCI was 36.36%. Within the CA-AKI to CKD group, the Vc/eGFR ratio was 2.82, and uNGAL levels were significantly higher at 72.74 ng/mL compared to 1.93 ng/mL for Vc/eGFR ratio and 46.57 ng/mL for uNGAL in the recovery CA-AKI group. This difference was statistically significant (p<0.001). Diabetic mellitus, urine NGAL concentration, and Vc/eGFR ratio were found to be independent factors in the progression of CA-AKI to CKD. The Vc/eGFR ratio and uNGAL showed predictive capabilities for progressing CA-AKI to CKD with an AUC of 0.884 and 0.878, respectively. The sensitivity was 81.3% for both, while the specificity was 89.3% for Vc/eGFR ratio and 85.7% for uNGAL., Conclusion: The Vc/eGFR ratio and uNGAL were good predictors for CA-AKI to CKD in planned PCI patients., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Nguyen Duy et al.)

The 11 lytic transglycosylases of Pseudomonas aeruginosa have overlapping activities in the turnover of the cell-wall peptidoglycan. Rare lipoprotein A (RlpA) is distinct among the 11 by its use of only peptidoglycan lacking peptide stems. The spatial localization of RlpA and its interactome within P. aeruginosa are unknown. We employed suppression of introduced amber codons at sites in the rlpA gene for the introduction of the unnatural-amino-acids Ν ζ -[(2-azidoethoxy)carbonyl]-l-lysine (compound 1) and N ζ -[[[3-(3-methyl-3H-diazirin-3-yl)propyl]amino]carbonyl]-l-lysine (compound 2). In live P. aeruginosa, full-length RlpA incorporating compound 1 into its sequence was fluorescently tagged using strained-promoted alkyne-azide cycloaddition and examined by fluorescence microscopy. RlpA is present at low levels along the sidewall length of the bacterium, and at higher levels at the nascent septa of replicating bacteria. In intact P. aeruginosa, UV photolysis of full-length RlpA having compound 2 within its sequence generated a transient reactive carbene, which engaged in photoaffinity capture of neighboring proteins. Thirteen proteins were identified. Three of these proteins-PBP1a, PBP5, and MreB-are members of the bacterial divisome. The use of the complementary methodologies of non-canonical amino-acid incorporation, photoaffinity proximity analysis, and fluorescent microscopy confirm a dominant septal location for the RlpA enzyme of P. aeruginosa, as a divisome-associated activity. This accomplishment adds to the emerging recognition of the value of these methodologies for identification of the intracellular localization of bacterial proteins., (© 2023 The Protein Society.)

Introduction: The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19., Methods: We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital., Results: Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO 2 (34.6%), hypocapnia with reduced PaCO 2 (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.10 9 /l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks., Conclusions: Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19., (© 2023. The Author(s).)

Introduction: Artificial Intelligence (AI) and machine learning (ML) are used extensively in HICs to detect and control antibiotic resistance (AMR) in laboratories and clinical institutions. ML is designed to predict outcome variables using an algorithm to enable "machines" to learn the "rules" from the data. ML is increasingly being applied in intensive care units to identify AMR and to assist empiric antibiotic therapy. This study aimed to evaluate the performance of ML models for predicting AMR bacteria and resistance to antibiotics in two Vietnamese hospitals., Patients and Methods: A cross-sectional study combined with retrospective was conducted from 1st January 2020 to 30th June 2022. Five models were developed to predict antibiotic resistance of bacterial infections of ICU patients. Two datasets were prepared to predict AMR bacteria and antibiotics with ML models. The performance of the prediction models was evaluated by various indicators (sensitivity, specificity, precision, accuracy, F1-score, PRC, AuROC, and NormMCC) to determine the optimal time point for data selection. Python version 3.8 was used for statistical analyses., Results: The accuracy, F1-score, AuROC, and normMMC of LightGBM, XGBoost, and Random Forest models were higher than those of other models in both datasets. In both datasets 1 and 2, accuracy, F1-score, AuROC and normMCC of the XGBoost model were the highest among five models (from 0.890 to 1.000). Only Random Forest models had specificity scores higher than 0.850. High scores of sensitivity, accuracy, precision, F1-score, and normMCC indicated that the models were making accurate predictions for datasets 1 and 2., Conclusion: XGBoost, LightGBM, and Random Forest were the best-performed machine learning models to predict antibiotic resistance of bacterial infections of ICUs patients using the patients' EMRs., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2023 Tran Quoc et al.)

Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain-Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO 2 decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination., (© 2023. The Author(s).)

Background: Hypertension is one of the leading causes of morbidity and mortality globally. It is a major risk factor for major cardiovascular events such as stroke, myocardial infarction, heart failure, kidney failure, and blindness. The aim of this research is to assess the prevalence and some factors related to arterial hypertension on Vietnamese seafarers aboard merchant vessels., Materials and Methods: Seven hundred eight Vietnamese seafarers working aboard merchant ships were examined at the Institute of Marine Medicine before going to sea during the period from January 2022 to December 2022. It was a cross-sectional descriptive epidemiological study. The following parameters were measured: blood pressure, height, weight, waist circumference, buttock circumference to assess the prevalence of hypertension, overweight, and obesity. Seafarers we directly interviewed about workplace on ships and physical exercise, smoking tobacco, alcohol abuse, and anxiety symptoms to identify several factors associated with hypertension., Results: The prevalence of hypertension in seafarers was 32.9%, prehypertension 26.4%, overweight 32.4%, obesity 13.3%, abdominal obesity 47.7%. Factors related to hypertension of seafarers included: job duration at sea > 10 years, odds ratio (OR) = 8.23 (95% confidence interval [CI] 4.34-17.27); non-officers, OR = 2.11 (95% CI 1.45-2.82); engine room crew, OR = 2.11 (95% CI 1.45-3.58); obesity, OR = 3.34 (95% CI 2.15-5.63); abdominal obesity, OR = 9.12 (95% CI 4.23-18.45); current smoking, OR = 1.32 (95% CI 1.02-1.99); irregular exercise, OR =1.43 (95% CI 1.03-2.18); anxiety symptoms, OR = 1.56 (95% CI 1.08-2.27)., Conclusions: Hypertension is a health problem for Vietnamese seafarers. To minimise hypertension, seafarers need to adjust their lifestyle, increase regular exercise and improve psychological issues on board.

Cannabidiol (CBD) is a non-psychoactive cannabinoid purported to reduce symptoms of discomfort. Individuals are now using CBD to treat symptoms of multiple sclerosis, seizures, and chronic pain. Animal models indicate that CBD may be effective at reducing inflammation post fatiguing exercise. However, little evidence is available to evaluate these findings in humans. Therefore, the purpose of this investigation was to evaluate the impact of two doses of CBD oil on inflammation (IL-6), performance, and pain after an eccentric loading protocol. Participants ( n = 4) participated in three conditions (placebo, low dose, and high dose), in this randomized, counterbalanced design. Each condition took 72 hours to complete, with a 1-week washout period between conditions. At the beginning of each week, participants were subjected to a loading protocol of six sets of ten eccentric only repetitions in the single-arm bicep curl. Participants consumed capsules of either a placebo, low dose (2mg/kg) or high dose (10mg/kg) of CBD oil immediately following the session and continued every twelve hours for 48 hours. Venipunctures were taken before exercise and repeated at 24, 48, and 72 hours post exercise. Blood samples were centrifuged for 15 minutes in gel and lithium heparin vacutainers. Plasma was separated from cells and stored at -80° until analysis. Samples were analyzed using an immunometric assay for IL-6 (ELISA). Data were analyzed using a three (condition) by four (time) repeated measure ANOVA. There were no differences in inflammation between conditions (F(2,6) = 0.726, p = 0.522, n p 2 = 0.195) or across time (F(3,9) = 0.752, p = 0.548, n p 2 = 0.200), handgrip strength between conditions (F(2,6) = 0.542, p = 0.607, n p 2 = .153) or across time (F(3,9) = 2.235, p = .153, n p 2 = .427), or bicep curl strength between conditions (F(2,6) = 0.675, p = 0.554, n p 2 = .184) or across time (F(3,9) = 3.513, p = .150, n p 2 = .539). There were no differences in pain between conditions (F(2,6) = 0.495, p = 0.633, n p 2 = .142), but there was a difference across time (F(3,9) = 7.028, p = .010, n p 2 = .701). There were no significant interactions to note. Although there was no statistical significance between conditions (likely due to the low sample size), there was a visible increase in IL-6 48 (4.88 ± 6.53) and 72 hours (3.12 ± 4.26) post exercise in the placebo condition which was not observed in the low (48: 0.35 ± 2.22; 72: 1.34 ± 5.6) and high dose condition (48: 1.34 ± 1.34; 72: -0.79 ± 5.34). Future investigations should consider implementing eccentric resistance training across a larger portion of the body to improve ecological validity of the exercise. A larger sample would reduce risk of researchers committing a type II statistical error and give strength to detecting differences between conditions.

This paper attempts to extend the concept of the equilibrium point to what is called equilibrium space, which can adapt to a system in which there exists an infinite number of equilibrium points. In the context of Lyapunov's linearization method extended for the equilibrium space, this paper proposes a pseudo linearization, from which we can derive a linear representation for a nonlinear system. The equilibrium state of this pseudo linearization and its stability are shown to be the same as that of the original nonlinear system. As an example of the applicability, the proposed pseudo linearization is applied to derive a discrete-time model for a control moment gyroscope system from a nonlinear continuous-time model. Simulation results show that the discrete-time model derived using the proposed pseudo linearization yields responses that are closer to that of the continuous-time model than the discrete-time model derived by the well-known forward-difference method and the conventional pseudo linear representation method, even with a large sampling interval., (© 2022. The Author(s).)

Objectives: Vaginal bleeding is a common symptom of uterine intracavitary pathologies in perimenopausal and postmenopausal women, which leads to anemia. However, findings regarding the relationship between hemoglobin level and sonographic parameters remain limited. The aim of this study was (1) to investigate the histopathological findings of uterine intracavitary pathologies, hemoglobin concentrations and basic sonographic parameters, and (2) to evaluate their correlation among Vietnamese women with perimenopausal and postmenopausal bleeding., Methods: This was a prospective study at Hue University Hospital and Hue Central Hospital from June 2016 to June 2019. The study enrolled 150 women older than 40 years with abnormal uterine bleeding. All patients underwent blood count testing and transvaginal ultrasound., Results: Moderate to severe anemia was observed at a higher frequency in women with perimenopausal bleeding (58.1%) than postmenopausal bleeding (10.0%). The most common abnormality resulting in severe anemia was endometrial hyperplasia (70.8%), which was followed by endometrial cancer (4.2%). The uterine size, intrauterine mass, and endometrial thickness differed substantially between the benign and malignant groups. The study found significantly a weak negative correlation between hemoglobin concentration (g/L) and uterinelength, the anteroposterior diameter of uterine corpus in the overall study (r = -0.37, r = -0.32, respectively, P < 0.05); a moderate negativecorrelation between hemoglobin concentration and the largest diameter of intracavitary mass‑shaped lesion in the perimenopausal group (r = -0.4, P < 0.05)., Conclusion: Overall, histopathological results, hemoglobin concentration and basic sonographic parameters should be combined in evaluating intrauterine abnormalities in women with perimenopausal and postmenopausal bleeding. Ultrasonic indices of uterine size may be used to determine the prognosis of anemia in uterine intracavitary pathologies. However, further studies are needed to confirm these findings., (© 2022 [The Author/The Authors].)

Objective: Many clinical and imaging characteristics can influence the prognosis of multilevel cervical spondylotic myelopathy (M-CSM). This study investigated the factors that influence surgical outcomes among patients with M-CSM., Patients and Methods: This prospective study included 30 patients who underwent surgical treatment for M-CSM from June 2019 to June 2021., Results: The average age was 62.29 years, and the average follow-up time was 13.13 months. Preoperative, postoperative, and follow-up Modified Japanese Orthopaedic Association (mJOA) scores were 10.17, 13.53, and 16.17, respectively. The average postoperative and follow-up recovery rates were 45.46% and 76.69%, respectively. Patients older than 60 years (p = 0.04), male patients (p = 0.023), and smokers (p = 0.027) had lower preoperative mJOA scores than other groups. Patients with symptoms duration longer than 6 months had lower recovery rates (p = 0.021) than those with shorter symptom duration. Patients with intramedullary hyperintensity in ≤ 2 vertebra (p = 0.041) or anterior surgery (p = 0.022) had better postoperative recovery rates than their counterparts. A shorter period of hyperintensity in the intramedullary region on sagittal T2-weighted magnetic resonance imaging (T2W MRI) was significantly associated with faster discharge (p = 0.044). Patients with type 3 (discrete focal) hyperintensity in the intramedullary region on axial T2W MRI had a 6.75-fold increase in experiencing less than 50% postoperative recovery compared with other groups (odds ratio: 6.75, 95% confidence interval: 2.73-16.67)., Conclusions: Good prognostic factors for a shorter recovery included hyperintensity in the intramedullary region for ≤ 2 levels, shorter period of hyperintensity in the intramedullary region on sagittal T2W MRI, and an anterior surgical approach. A duration of symptoms longer than 6 months and discrete hyperintensity in the intramedullary region on axial T2W MRI were poor prognostic indicators associated with a longer recovery period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (Covid-19), has uncontrollable effects on many organs. A great number of previously published scientific reports have revealed that patients with diabetes mellitus face a more severe form of Covid-19 with a higher death rate. Here we present the case of a 13-year-old unvaccinated boy who was admitted to an intensive care unit (ICU) with a history of fever, cough, dyspnea, throat pain, nausea, and confusion that progressed to lethargy after 24 h. On clinical examination, he was in a coma with Kussmaul's breathing, and was anuric. His blood biochemical analysis demonstrated hyperglycemia, severe metabolic acidosis, kidney failure, electrolyte disturbances, and inflammation. Chest x-ray showed pneumonia and a pleural effusion. The results of the SARS-CoV-2 real-time polymerase chain reaction were positive. The patient was diagnosed with Covid-19-induced acute respiratory distress syndrome associated with multisystem inflammatory syndrome in children secondary to his acute respiratory failure, acute kidney injury, and new-onset type 1 diabetes mellitus with diabetic ketoacidosis. He was intubated for invasive mechanical ventilation and received a normal saline infusion and continuous insulin infusion (0.1 IU/kg/h) for the treatment of his diabetic ketoacidosis. He was also treated with methylprednisolone, aspirin, and heparin, and underwent continuous renal replacement therapy for acute renal failure for 9 days. The patient was discharged from ICU on day 16 and was followed up regularly as an outpatient with daily treatment, including subcutaneous insulin injection (30 IU/day) and a calcium channel blocker for hypertension (nifedipine 20 mg/day)., (© 2022. The Author(s).)

The present environmental crisis prompts the search for renewable energy sources such as solar-driven production of hydrogen from water. Herein, we report an efficient hybrid photocatalyst for water oxidation, consisting of a ruthenium polypyridyl complex covalently grafted on core/shell Fe@FeO x nanoparticles via a phosphonic acid group. The photoelectrochemical measurements were performed under 1 sun illumination in 1 M KOH. The photocurrent density of this hybrid photoanode reached 20 μA/cm 2 (applied potential of +1.0 V vs reversible hydrogen electrode), corresponding to a turnover frequency of 0.02 s -1 . This performance represents a 9-fold enhancement of that achieved with a mixture of Fe@FeO x nanoparticles and a linker-free ruthenium polypyridyl photosensitizer. This increase in performance could be attributed to a more efficient electron transfer between the ruthenium photosensitizer and the Fe@FeO x catalyst as a consequence of the covalent link between these two species through the phosphonate pendant group.

Introduction: Prenatal ethanol exposure (PEE) has been shown to alter the level and function of receptors in the brain, one of which is GABA a receptors (GABA a R), the major inhibitory ligand gated ion channels that mediate neuronal inhibition. High dose PEE in animals resulted in the upregulation of GABA a R, but the effects of low and moderate dose PEE at early gestation have not been investigated. This study aimed at examining GABA a R density in the adult mouse brain following PEE during a period equivalent to the first 3 to 4 weeks in human gestation. It was hypothesized that early moderate PEE would cause alterations in brain GABA a R levels in the adult offspring., Methods: C57BL/6J mice were given 10% v/v ethanol during the first 8 gestational days. Male offspring were studied using in-vivo Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI), biodistribution, in-vitro autoradiography using [ 18 F]AH114726, a novel flumazenil analogue with a high affinity for the benzodiazepine-binding site, and validated using immunohistochemistry., Results: In vivo PET and biodistribution did not detect alteration in brain tracer uptake. In vitro radiotracer studies detected significantly reduced GABA a R in the olfactory bulbs. Immunohistochemistry detected reduced GABA a R in the cerebral cortex, cerebellum and hippocampus, while Nissl staining showed that cell density was significantly higher in the striatum following PEE., Conclusion: Early moderate PEE may induce long-term alterations in the GABA a R system that persisted into adulthood., (Copyright © 2020 Elsevier Inc. All rights reserved.)

From the MeOH extract of the Vietnamese sea cucumber Holothuria edulis , eight triterpene glycosides ( 1 - 8 ), including one new compound namely holothurin A 5 ( 1 ), were isolated by using various chromatographic separations. Their structures were established by spectroscopic experiments including 1D, 2D NMR and HR-ESI-MS. Holothurin A 5 ( 1 ) has a hydroperoxy group at C-25. To the best of our knowledge, this is the first report of this group in triterpene saponins obtained from sea cucumbers to date. In addition, the in vitro cytotoxicity against five human cancer cell lines (HepG2, KB, LNCaP, MCF7 and SK-Mel2) of all isolated compounds was also evaluated using SRB assays.

Ten briarane-type diterpenoids ( 1 - 10 ), including one new stereoisomer 17- epi -junceellolide B ( 1 ), were isolated from the MeOH extract of the Vietnamese gorgonian Junceella fragilis . Their structures were elucidated by spectroscopic experiments including 1D and 2D NMR, and HR-QTOF-MS. In addition, the in vitro cytotoxic activity against eight human cancer cell lines (LNCaP, HepG2, KB, MCF-7, SK-Mel2, HL-60, LU-1 and SW480) of all isolated compounds was evaluated by SRB assays.

A cross-sectional study was conducted among 171 doctors and nurses in a National Dermatology hospital using the Karasek's Job Content Questionnaire which has been validated in Vietnamese (JCQ-V), to assess the prevalence of occupational stress and to explore the association with some associated factors among them. The result showed that doctors and nurses with occupational stress accounted for 6.4%. This proportion was higher among nurse compared to doctor (8.0% vs. 2.2%); among those with diploma literacy compared to bachelor and above (10.6% and 2.3%). This rate was also higher in health workers under 30 years old (12.9%), health workers under 5 years at work (12.1%), working night shift from 3-4 nights (33.3%), temporary employment (12.8%), heavy workload occasionally (12.5%), and working hard occasionally (17.2%) compared to those in the comparison groups with p value <0,05. This prevalence concentrated in some departments such as surgery (11.9%), internal medicine (6.7%), dermatology, and others (1.5%). The study has not found the significant association between the prevalence of occupational stress and heavy workload and skill level. Therefore, it is essential for hospital should conduct screening all doctors, nurses, and medical staffs to identify subjects having occupational stress and give appropriate intervention., (Copyright © 2020 Nguyen Ngoc, Le Thi Thanh, Le Thi, Vu Tuan and Nguyen Van.)

Background: This study investigated the effects of early moderate prenatal ethanol exposure (PEE) on the brain in a mouse model that mimics a scenario in humans, whereby moderate daily drinking ceases after a woman becomes aware of her pregnancy., Methods: C57BL/6J pregnant mice were given 10% v/v ethanol from gestational day 0-8 in the drinking water. The male offspring were used for imaging. Anatomical and diffusion Magnetic Resonance Imaging were performed in vivo at postnatal day 28 (P28, adolescence) and P80 (adulthood). Micro-Computed Tomography was performed on fixed whole heads at P80. Tensor-based morphometry (TBM) was applied to detect alterations in brain structure and voxel-based morphometry (VBM) for skull morphology. Diffusion tensor and neurite orientation dispersion and density imaging models were used to detect microstructural changes. Neurofilament (NF) immunohistochemistry was used to validate findings by in vivo diffusion MRI., Results: TBM showed that PEE mice exhibited a significantly smaller third ventricle at P28 (family-wise error rate (FWE), p < 0.05). All other macro-structural alterations did not survive FWE corrections but when displayed with an uncorrected p < 0.005 showed multiple regional volume reductions and expansions, more prominently in the right hemisphere. PEE-induced gross volume changes included a bigger thalamus, hypothalamus and ventricles at P28, and bigger total brain volumes at both P28 and P80 (2-sample t-tests). Disproportionately smaller olfactory bulbs following PEE were revealed at both time-points. No alterations in diffusion parameters were detected, but PEE animals exhibited reduced NF positive staining in the thalamus and striatum and greater bone density in various skull regions., Conclusion: Our results show that early moderate PEE can cause alterations in the brain that are detectable during development and adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The improvement in adsorption/desorption of hydrofluorocarbons has implications for many heat transformation applications such as cooling, refrigeration, heat pumps, power generation, etc. The lack of chlorine in hydrofluorocarbons minimizes the lasting environmental damage to the ozone, with R134a (1,1,1,2-tetrafluoroethane) being used as the primary industrial alternative to commonly used Freon-12. The efficacy of novel adsorbents used in conjunction with R134a requires a deeper understanding of the host-guest chemical interaction. Metal-organic frameworks (MOFs) represent a newer class of adsorbent materials with significant industrial potential given their high surface area, porosity, stability, and tunability. In this work, we studied two benchmark MOFs, a microporous Ni-MOF-74 and mesoporous Cr-MIL-101. We employed a combined experimental and simulation approach to study the adsorption of R134a to better understand host-guest interactions using equilibrium isotherms, enthalpy of adsorption, Henry's coefficients, and radial distribution functions. The overall uptake was shown to be exceptionally high for Cr-MIL-101, >140 wt% near saturation while >50 wt% at very low partial pressures. For both MOFs, simulation data suggest that metal sites provide preferable adsorption sites for fluorocarbon based on favorable C-F ··· M + interactions between negatively charged fluorine atoms of R134a and positively charged metal atoms of the MOF framework.

Fate modelling of artificial radionuclides (ARs) in top soils are necessary to assess the radiological effects to population. Among ARs, 137 Cs, 90 Sr and 131 I are very important since the large abundances in the environment. In this study, the fates of 137 Cs, 90 Sr and 131 I in the surface soil layers were simulated by the soil model which was developed by the Canadian Centre for Environmental Modelling and Chemistry (CEMC). The scenario that 137 Cs, 90 Sr and 131 I contaminated in topsoil in the exclusion of Fukushima Daiichi nuclear power plant (NPP) accident was evaluated. The results show the expected time for the minimum hazardous level of exposure. It is 115.5 days after the exposure, when the total effective dose is 1 mSv y -1 in which 0.46 mSv y -1 from ingestion and 0.54 mSv y -1 from gamma exposure. Hazard levels due to exposure progresses are varied in order gamma exposure (82.14%) > ingestion (17.47%) > inhalation (0.39%). The hazard levels from radionuclides are varied in order 137 Cs (63.34%) >  131 I (33.48%) >  90 Sr (3.18%)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The use of ECMO for cardiovascular support continues to increase in the United States and around the world. It is not a benign endeavor as serious complications may occur. We present our experience of two second generation CentriMag ® (Abbott formerly Thoratec Inc.) console failures that occurred while transporting the patients to other areas of the hospital. In each incident, the patients were immediately placed on back-up units and the transport continued. No patient complications could be attributed to the failures. An investigation by Abbott engineers traced the failure to a static build-up and discharge caused by a non-manufacturer-approved metal rod that was utilized to mount the external monitor. The static discharge caused a disruption of electrical continuity between the control system and the motor, stopping the motor as well as the monitoring system. Removal of the mounting rod prevented replication of the situation in the lab. We have removed the rod from our clinical units and have not experienced any other pump failures.

The syntheses of nine new 5-iodosalicylic acid-based 1,3,4-oxadiazoline derivatives starting from methyl salicylate are described. These compounds are 2-[4-acetyl-5-methyl-5-(3-nitrophenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6a), 2-[4-acetyl-5-methyl-5-(4-nitrophenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6b), 2-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-iodophenyl acetate, C 19 H 17 IN 2 O 4 (6c), 2-[4-acetyl-5-(4-fluorophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate, C 19 H 16 FIN 2 O 4 (6d), 2-[4-acetyl-5-(4-chlorophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate, C 19 H 16 ClIN 2 O 4 (6e), 2-[4-acetyl-5-(3-bromophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6f), 2-[4-acetyl-5-(4-bromophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6g), 2-[4-acetyl-5-methyl-5-(4-methylphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6h) and 2-[5-(4-acetamidophenyl)-4-acetyl-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6i). The compounds were characterized by mass, 1 H NMR and 13 C NMR spectroscopies. Single-crystal X-ray diffraction studies were also carried out for 6c, 6d and 6e. Compounds 6c and 6d are isomorphous, with the 1,3,4-oxadiazoline ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C-H...O, C-H...π and I...π interactions. For 6e, the 1,3,4-oxadiazoline ring is almost planar. In the packing, Cl...π interactions are observed, while the I atom is not involved in short interactions. Compounds 6d, 6e, 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep-G2, with IC 50 values of 0.9-4.5 µM.

In the title compound, C 15 H 14 IN 3 O 2 ·CH 3 OH, two aromatic rings are linked by an N -substituted hydrazide function. The dihedral angle between the aromatic rings is 10.53 (8)°. The stereochemistry about the imine function is E . The methanol mol-ecule forms an O-H⋯O hydrogen bond to the hydrazide O atom. In the crystal, chains of mol-ecules running along the c -axis direction are formed by O-H⋯O hydrogen bonds. Adjacent chains are linked through N-H⋯O hydrogen bonds and π-π stacking inter-actions. The inter-molecular inter-actions in the crystal packing were investigated using Hirshfeld surface analysis, which indicated that the most significant contacts are H⋯H (38.2%), followed by C⋯H/H⋯C (20.6%), O⋯H/H⋯O (11.1%) and I⋯H/H⋯I (9.7%).

The purpose of this article is to systematically collate effort-reward imbalance (ERI) rates among health workers internationally and to assess gender differences. The effort-reward (ER) ratio ranges quite widely from 0.47 up to 1.32 and the ERI rate from 3.5% to 80.7%. Many studies suggested that health workers contribute more than they are rewarded, especially in Japan, Vietnam, Greece, and Germany-with ERI rates of 57.1%, 32.3%, 80.7%, and 22.8% to 27.6%, respectively. Institutions can utilize systems such as the new appraisal and reward system, which is based on performance rather than the traditional system, seniority, which creates a more competitive working climate and generates insecurity. Additionally, an increased workload and short stay patients are realities for workers in a health care environment, while the structure of human resources for health care remains inadequate. Gender differences within the ER ratio can be explained by the continued impact of traditional gender roles on attitudes and motivations that place more pressure to succeed for men rather than for women. This systematic review provides some valued evidence for public health strategies to improve the ER balance among health workers in general as well as between genders in particular. An innovative approach for managing human resources for health care is necessary to motivate and value contributions made by health workers., (Copyright © 2018 John Wiley & Sons, Ltd.)

Using various chromatographic separations, six ergostane-type steroids, including one new compound sinubrassione (1), and two pregnene-type steroid glycosides, including one new compound sinubrassioside (7), were isolated from methanol extract of the Vietnamese soft coral Sinularia brassica. The structure elucidation was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-MS. The cytotoxic activities of all the isolated compounds against three human cancer cell lines were also evaluated using MTT-based colorimetric assays.

Six pregnane steroids including one new compound namely 15β-hydroxypregna-4,20-dien-3-one (1), were isolated and structurally elucidated from the octocoral Carijoa riisei. The cytotoxic activity against a panel of eight human cancer cell lines of isolated compounds was also evaluated by SRB method. As the results, 18-acetoxypregna-1,4,20-trien-3-one (5) showed significant cytotoxicity against all the tested cell lines with the IC 50 values from 22.29 ± 1.47 to 48.73 ± 3.93 μM, whereas 15β-acetoxypregna-1,4,20-trien-3-one (3) and 20R-acetoxypregna-1,4-dien-3-one (6) only exhibited weak effect on KB cell line with IC 50 values of 93.62 ± 7.32 and 71.38 ± 5.45 μM, respectively.

A series of arsenic remediation tests were conducted using a washing method with biodegradable organic acids, including oxalic, citric and ascorbic acids. Approximately 80% of the arsenic in one sample was removed under the effect of the ascorbic and oxalic acid combination, which was roughly twice higher than the effectiveness of the ascorbic and citric acid combination under the same conditions. The soils treated using biodegradable acids had low remaining concentrations of arsenic that are primarily contained in the crystalline iron oxides and organic matter fractions. The close correlation between extracted arsenic and extracted iron/aluminum suggested that arsenic was removed via the dissolution of Fe/Al oxides in soils. The fractionation of arsenic in four contaminated soils was investigated using a modified sequential extraction method. Regarding fractionation, we found that most of the soil contained high proportions of arsenic (As) in exchangeable fractions with phosphorus, amorphous oxides, and crystalline iron oxides, while a small amount of the arsenic fraction was organic matter-bound. This study indicated that biodegradable organic acids can be considered as a means for arsenic-contaminated soil remediation., Competing Interests: The authors declare no conflict of interest.

Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain. To this end, we discovered a newly described NG2-expressing cell that we isolated from a distinct pericyte subtype found abundantly in cultures derived from peripheral muscle. In this work, we show the translational significance of these peripherally derived neural-like stem cells (NLSC) and their potential to migrate toward tumors and act as therapeutic carriers. We demonstrate that these NLSCs exhibit in vitro and in vivo GBM tropism. Furthermore, NLSCs did not promote angiogenesis or transform into tumor-associated stromal cells, which are concerns raised when using other common stem cells, such as mesenchymal stem cells and induced neural stem cells, as therapeutic carriers. We also demonstrate the potential of NLSCs to express a prototype therapeutic, tumor necrosis factor α-related apoptosis-inducing ligand and kill GBM cells in vitro. These data demonstrate the therapeutic potential of our newly characterized NLSC against GBM. Stem Cells Translational Medicine 2017;6:471-481., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: Community health workers (CHWs) provide critical services to underserved populations in low and middle-income countries, but maintaining CHW's clinical knowledge through formal continuing medical education (CME) activities is challenging and rarely occurs. We tested whether a Short Message Service (SMS)-based mobile CME (mCME) intervention could improve medical knowledge among a cadre of Vietnamese CHWs (Community Based Physician's Assistants-CBPAs) who are the leading providers of primary medical care for rural underserved populations., Methods: The mCME Project was a three arm randomized controlled trial. Group 1 served as controls while Groups 2 and 3 experienced two models of the mCME intervention. Group 2 (passive model) participants received a daily SMS bullet point, and were required to reply to the text to acknowledge receipt; Group 3 (interactive model) participants received an SMS in multiple choice question format addressing the same thematic area as Group 2, entering an answer (A, B, C or D) in their response. The server provided feedback immediately informing the participant whether the answer was correct. Effectiveness was based on standardized examination scores measured at baseline and endline (six months later). Secondary outcomes included job satisfaction and self-efficacy., Results: 638 CBPAs were enrolled, randomized, and tested at baseline, with 592 returning at endline (93.7%). Baseline scores were similar across all three groups. Over the next six months, participation of Groups 2 and 3 remained high; they responded to >75% of messages. Group 3 participants answered 43% of the daily SMS questions correctly, but their performance did not improve over time. At endline, the CBPAs reported high satisfaction with the mCME intervention, and deemed the SMS messages highly relevant. However, endline exam scores did not increase over baseline, and did not differ between the three groups. Job satisfaction and self-efficacy scores also did not improve. Average times spent on self-study per week did not increase, and the kinds of knowledge resources used by the CBPAs did not differ between the three groups; textbooks, while widely available, were seldom used., Conclusions: The SMS-based mCME intervention, while feasible and acceptable, did not result in increased medical knowledge. We hypothesize that this was because the intervention failed to stimulate lateral learning. For an intervention of this kind to be effective, it will be essential to find more effective ways to couple SMS as a stimulus to promote increased self-study behaviors., Trial Registration: ClinicalTrials.gov NCT02381743., Competing Interests: The authors have declared that no competing interests exist.

Heavy metal contamination of soil and sediment in estuaries warrants study because a healthy estuarine environment, including healthy soil, is important in order to achieve ecological balance and good aquaculture production. The Ba Lat estuary of the Red River is the largest estuary in northern Vietnam and is employed in various land uses. However, the heavy metal contamination of its soil has not yet been reported. The following research was conducted to clarify contamination levels, supply sources, and the effect of land use on heavy metal concentrations in the estuary. Soil samples were collected from the top soil layer of the estuary, and their arsenic (As), chromium (Cr), cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) concentrations were analyzed, as were other soil properties. Most soils in the estuary were loam, silt loam, or sandy loam. The pH was neutral, and the cation exchange capacity ranged from 3.8 to 20 cmol·kg -1 . Manganese and iron concentrations averaged 811 µg·g -1 and 1.79%, respectively. The magnitude of the soil heavy metal concentrations decreased in the order of Zn > Pb > Cr > Cu > As > Cd. The concentrations were higher in the riverbed and mangrove forest than in other land-use areas. Except for As, the mean heavy metal concentrations were lower than the permissible levels for agricultural soils in Vietnam. The principal component analyses suggested that soil As, Pb, Zn, Cd, and Cu were of anthropogenic origin, whereas Cr was of non-anthropogenic origin. The spatial distribution of concentration with land use indicated that mangrove forests play an important role in preventing the spread of heavy metals to other land uses and in maintaining the estuarine environment., Competing Interests: The authors declare no conflict of interest.

A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5'-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM.

Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.

The acquisition of endocrine therapy resistance in estrogen receptor α (ERα) breast cancer patients represents a major clinical problem. Notch signalling has been extensively linked to breast cancer especially in patients who fail to respond to endocrine therapy. Following activation, Notch intracellular domain is released and enters the nucleus where activates transcription of target genes. The numerous steps that cascade after activation of the receptor complicate using Notch as biomarker. Hence, this warrants the development of reliable indicators of Notch activity. DMXL2 is a novel regulator of Notch signalling not yet investigated in breast cancer. Here, we demonstrate that DMXL2 is overexpressed in a subset of endocrine therapy resistant breast cancer cell lines where it promotes epithelial to mesenchymal transition through hyper-activation of Notch signalling via V-ATPase dependent acidification. Following DMXL2 depletion or treatment with Bafilomycin A1, both EMT targets and Notch signalling pathway significantly decrease. We show for the first time that DMXL2 protein levels are significantly increased in ERα positive breast cancer patients that progress after endocrine therapy. Finally, we demonstrate that DMXL2 is a transmembrane protein with a potential extra-cellular domain. These findings identify DMXL2 as a novel, functional biomarker for ERα positive breast cancer.

Previous investigations identified 2'-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity. However, the 7-fluoro analogue of 1 displayed good potency with a promising cytotherapeutic margin., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study was undertaken to investigate combined toxic and genotoxic effects of cadmium (Cd) and arsenic (As) on white clover, a pollutant sensitive plant frequently used as environmental bioindicator. Plants were exposed to soil spiked with increasing concentrations of cadmium sulfate (20, 40 and 60 mg Kg-1) or sodium arsenite (5, 10 and 20 mg Kg-1) as well as with their combinations. Metal(loid) bioavailability was assessed after soil contamination, whereas plant growth, metal(loid) concentration in plant organs and DNA damage were measured at the end of plant exposition. Results showed that individual and joint toxicity and genotoxicity were related to the concentration of Cd and As measured in plant organs, and that As concentration was the most relevant variable. Joint effects on plant growth were additive or synergistic, whereas joint genotoxic effects were additive or antagonistic. The interaction between Cd and As occurred at both soil and plant level. In soil the presence of As limited the bioavailability of Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless only As biovailability determined the amount of As absorbed by plants. The amount of Cd absorbed by plant was not linearly correlated with the fraction of bioavailable Cd in soil suggesting the involvement of additional factors, such as plant uptake mechanisms. These results reveal that the simultaneous presence in soil of Cd and As, although producing an additive or synergistic toxic effect on Trifolium repens L. growth, generates a lower DNA damage.

2H,3'H-Spiro[benzofuran-3,2'-naphthoquinones], constituting a new spiroheterocyclic skeleton, were synthesized starting from 2-aryloxymethyl-1,4-naphthoquinones by means of a palladium(II)-catalyzed reaction, which is a new spirocyclic transformation. Under optimal conditions, i.e. 10 mol % of palladium(II) acetate, 15 mol % of 3,5-dichloropyridine, and 5 mol % of trifluoroacetic acid in acetic acid at 110 °C, various 2H,3'H-spiro[benzofuran-3,2'-naphthoquinones] were synthesized in yields strongly dependent on the substitution pattern of the aryloxy group. Unsubstituted or ortho-substituted 2-aryloxymethyl-1,4-quinones were found to rearrange toward the corresponding 2-(4-hydroxyaryl)-1,4-quinones upon treatment with trifluoroacetic acid.

We report a detailed computer simulation study of methanol adsorption in graphitic slit-like micropores to investigate the effects of temperature and pore size on the adsorptive capacity and the configurations of methanol molecules in a confined space. Simulation results show that in the temperature range studied (273-422 K) the amount adsorbed increases gradually with pressure in 0.65 and 0.8 nm pores (where only one molecular layer can be accommodated), while for pores having widths greater than 1.0 nm the adsorption isotherms exhibit a sharp jump at low temperatures which becomes gradual as temperature is increased above the critical pore temperature, which increases with pore width. For a given pore size, the pressure at which a large uptake of adsorption occurs, increases and the excess amount adsorbed, decreases with temperature. The interaction between adsorbate molecules and a pore was studied via the solvation pressure, which exhibits oscillations with pore size. The peaks of this oscillation correspond to pores that have an integer number of layers of methanol molecules. At low loadings snapshots showed methanol molecules in isolated clusters of four or five molecules which maximise the hydrogen bonding within each cluster, in the same way as they do on an open surface. At high loadings, the isolated cluster configuration changes to molecular chains in small pores (0.65 and 0.8 nm), which become more distorted by inter-layer interactions in larger pores. The positions of the first peaks of the O-O and O-H radial distributions for the confined methanol are the same as those for bulk liquid for all pore sizes. However, for confined methanol in pores with an integer number of molecular layers, the amplitude of the first peaks of the O-O and O-H radial distributions are higher than for the bulk liquid, and the positions of the second peaks are slightly shifted to the left. In the incommensurate pores the amplitude of the first peaks and the positions of the second peaks of the O-O and O-H radial distributions are similar to those of liquid methanol. Our simulation results agree well with the experimental results of Ohkubo et al., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Carbonaceous materials with some degree of flexibility in their physical structure can expand or contract under the influence of the forces exerted by adsorbed molecules. To gain insight into how adsorption of non-polar and polar fluids could deform a carbon solid, we present GCMC simulations of sub- and supercritical adsorption of methane and methanol in slit-shaped pores whose walls are made of graphene layers. Our extensive simulation study shows that there is a strong correlation between solvation pressure and solid deformation, and that the expansion or contraction of the pore strongly depends on adsorbate loading, temperature and pore size., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) infection remains a major public health problem in Vietnam. Recent studies have found that prevalence of current HBV infection (HBsAg+) ranges from 10% to 20% in the general population and 20% to 40% among injecting drug users and HIV+ patients. However, HBV prevention and control in Vietnam relies heavily on universal infant vaccination program and HBsAg screening for blood donors. Currently, HBV prevention and control is underfunded by the government and receives little support from international agencies. HBV-related liver disease will continue to create a heavy burden for public health in Vietnam in the next several decades unless appropriate interventions are undertaken urgently. Establishment of a national strategy for HBV prevention and control is crucial to develop and implement effective interventions.

In 1991, WHO recognized the resurgence of tuberculosis as a global health problem. Although modern chemotherapy is effective against the causative pathogen Mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. The success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs. Benzo[j]phenanthridine-7,12-diones, tetracyclic derivatives of the natural product benz[g]isoquinoline-5,10-dione, were conveniently synthesized via palladium-catalyzed intramolecular cyclization of N-methanesulfonyl-3-bromo-2-(arylamino)methyl-1,4-naphthoquinones. Here we report on the bioactivity of eight benzo[j]phenanthridine-7,12-dione derivatives as candidate drug molecules against M. tuberculosis and on their cytotoxicity on C3A human hepatocytes. The strongest antimicrobial activity (as detected by growth inhibition of bacteria, using luminometry and BACTEC 460-TB) and lowest cytotoxicity was found for 3-methylbenzo[j]phenanthridine-7,12-dione 5e, which was also effective in targeting intracellular M. tuberculosis (in murine J774 macrophages) and was not genotoxic for C3A hepatocytes., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Human FSH exists as two major glycoforms designated, tetra-glycosylated and di-glycosylated hFSH. The former possesses both alpha- and beta-subunit carbohydrates while the latter possesses only alpha-subunit carbohydrate. Western blotting differentiated the glycosylated, 24,000 M(r) hFSHbeta band from the non-glycosylated 21,000 M(r) FSHbeta band. Postmenopausal urinary hFSH preparations possessed 75-95% 24,000 M(r) hFSHbeta, while pituitary hFSH immunopurified from 21- to 43-year-old females and 21-43-year-old males possessed only 35-40% 24,000 M(r) hFSHbeta. The pituitary hFSH from a postmenopausal woman on estrogen replacement was 75% 21,000 M(r) hFSHbeta. Other immunopurified postmenopausal pituitary hFSH preparations possessed 50-60% 21,000 M(r) hFSHbeta. Gel filtration removed predominantly 21,000 M(r) free hFSHbeta and reduced its abundance to 13-22% in postmenopausal pituitary hFSH heterodimer preparations. A major regulatory mechanism for FSH glycosylation involves control of beta-subunit N-glycosylation, possibly by inhibition of oligosaccharyl transferase. Two primate species exhibited the same all-or-none pattern of pituitary FSHbeta glycosylation.