Real-world analysis of afatinib as a first-line treatment for patients with advanced stage non-small-cell lung cancer with uncommon EGFR mutations: a multicenter study in Vietnam.

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

Identification and nitric oxide production inhibitory activity of phenolic derivatives from the trunks of Gnetum latifolium.

Phytochemical investigation of the trunks from Gnetum latifolium led to the isolation of a novel phenolic glucoside, 2E-2,4-di-(3,4-dihydroxyphenyl)but-2-en-1-yl-O-ß-D-glucopyranoside (1), along with five known stilbene derivatives (2-6). Their structures were determined mainly using high-resolution electrospray ionisation mass spectrometry and nuclear magnetic resonance spectroscopic analyses, followed by comparisons of observed spectral data with reported values. The novel compound 1 in G. latifolium was found to be useful as a chemotaxonomic marker. Biological evaluation revealed that compound 6 had remarkable inhibitory effects on nitric oxide production, with a half-maximal inhibitory concentration (IC50) value of 4.85 ± 0.20 µM, which was much higher than that of the positive control dexamethasone (IC50 = 14.20 ± 0.54 µM).

The radical scavenging activity of monocaffeoylquinic acids: the role of neighboring hydroxyl groups and pH levels.

Caffeoylquinic acids (CQAs) are well-known antioxidants. However, a key aspect of their radical scavenging activity - the mechanism of action - has not been addressed in detail thus far. Here we report on a computational study of the mechanism of activity of CQAs in scavenging hydroperoxyl radicals. In water at physiological pH, the CQAs demonstrated ≈ 104 times higher HOO˙ antiradical activity than in lipid medium (k(lipid) ≈ 104 M-1 s-1). The activity in the aqueous solution was determined by the hydrogen transfer mechanism of the adjacent hydroxyl group (O6'-H) of the dianion states (Γ = 93.2-95.2%), while the single electron transfer reaction of these species contributed 4.8-6.8% to the total rate constants. The kinetics estimated by the calculations are consistent with experimental findings in water (pH = 7.5), yielding a kcalculated/kexperimental = 2.4, reinforcing the reliability and precision of the computational method and demonstrating its utility for evaluating radical reactions in silico. The results also revealed the pH dependence of the HOO˙ scavenging activity of the CQAs; activity was comparable for all compounds below pH 3, however at higher pH values 5CQA reacted with the HOO˙ with lower activity than 3CQA or 4CQA. It was also found that CQAs are less active than Trolox below pH 4.7, however over pH 5.0 they showed higher activity than the reference. The CQAs had the best HOO˙ antiradical activity at pH values between 5.0 and 8.6. Therefore, in the physiological environment, the hydroperoxyl antiradical capacity of CQAs exhibits similarity to renowned natural antioxidants including resveratrol, ascorbic acid, and Trolox.

The Theoretical and Experimental Insights into the Radical Scavenging Activity of Rubiadin.

Rubiadin (RBD), an anthraquinone derivative, is obtained from Rubia cordifolia, a plant species classified under the Rubiaceae family. Rubiadin has proven beneficial properties, such as anticancer, neuroprotective, anti-inflammatory, and antidiabetic activity. The antioxidant activity of this molecule was suggested by some experimental results but has not been clearly established thus far. In this study, we employ DFT calculations to comprehensively assess the mechanism and kinetics of the HO•/HOO• radical scavenging activity of this compound in relation to solvents. RBD showed moderate HO• radical scavenging activity, with rate constants of 2.95 × 108 and 1.82 × 1010 M-1 s-1 in lipid and polar media, respectively. In the aqueous solution, the compound exhibited remarkable superoxide anion radical scavenging activity (k = 4.93 × 108 M-1 s-1) but modest HOO• antiradical activity. RBD also showed promising antiradical activity against a variety of radicals (CCl3O•, CCl3OO•, NO2, SO4•-, and N3•), while experimental and computational results confirmed that RBD has moderate activity in DPPH/ABTS•+ assays. Thus, RBD is predicted to be a good, albeit selective, radical scavenger.

A Comprehensive Study of the Radical Scavenging Activity of Rosmarinic Acid.

Rosmarinic acid (RA) is reported in separate studies to be either an inducer or reliever of oxidative stress, and this contradiction has not been resolved. In this study, we present a comprehensive examination of the radical scavenging activity of RA using density functional theory calculations in comparison with experimental data. In model physiological media, RA exhibited strong HO• radical scavenging activity with overall rate constant values of 2.89 × 1010 and 3.86 × 109 M-1 s-1. RA is anticipated to exhibit excellent scavenging properties for HOO• in an aqueous environment (koverall = 3.18 × 108 M-1 s-1, ≈2446 times of Trolox) following the hydrogen transfer and single electron transfer pathways of the dianion state. The neutral form of the activity is equally noteworthy in a lipid environment (koverall = 3.16 × 104 M-1 s-1) by the formal hydrogen transfer mechanism of the O6(7,15,16)-H bonds. Chelation with RA may prevent Cu(II) from reduction by the ascorbic acid anion (AA-), hence blocking the OIL-1 pathway, suggesting that RA in an aqueous environment also serves as an OIL-1 antioxidant. The computational findings exhibit strong concurrence with the experimental observations, indicating that RA possesses a significant efficacy as a radical scavenger in physiological environments.

Antiradical Activity of Lignans from Cleistanthus sumatranus: Theoretical Insights into the Mechanism, Kinetics, and Solvent Effects.

Sumatranus lignans (SL) isolated from Cleistanthus sumatranus have demonstrated bioactivities, e.g., they were shown to exhibit immunosuppressive properties in previous research. Their structure suggests potential antioxidant activity that has not attracted any attention thus far. Consistently, a comprehensive analysis of the antioxidant activity of these compounds is highly desirable with the view of prospective medical applications. In this work, the mechanism and kinetics of the antiradical properties of SL against hydroperoxyl radicals were studied by using calculations based on density functional theory (DFT). In the lipid medium, it was discovered that SL reacted with HOO• through the formal hydrogen transfer mechanism with a rate constant of 101-105 M-1 s-1, whereas in aqueous media, the activity primarily occurred through the sequential proton loss electron transfer mechanism with rate constants of 102-108 M-1 s-1. In both lipidic and aqueous environments, the antiradical activity of compounds 6 and 7 exceeds that of resveratrol, ascorbic acid, and Trolox. These substances are therefore predicted to be good radical scavengers in physiological environments.

Current Status of Biological Treatment in Ankylosing Spondylitis Patients and Some Related Factors.

Background: Axial spondyloarthritis (axSpA) is a potentially disabling inflammatory arthritis of the spine, usually presenting as chronic back pain typically before the age of 45 years. It is often associated with one or more articular features, including synovitis, enthesitis, and dactylitis. It may also be associated with several non-articular features; these include uveitis, psoriasis, and inflammatory bowel diseases1. Objective: The aim of this article is to describe the status of using biological drugs and some related factors in treating ankylosing spondylitis in Vietnam. Methods: A joint prospective and retrospective cross-sectional descriptive study was conducted on 161 ankylosing spondylitis patients treated with biological drugs at the Centre for Rheumatology between January 2018 and July 2021. Data were collected at the first dose and after 3, 6, 12, 24, and 36 months, including general characteristics, clinical and para-clinical features, drug use status, and related factors. Results: Of the 161 patients, 86.3% were male, with a mean age of 31.1 ± 11.6 years and a mean disease duration of 7.6 ± 6.6 years. Most patients were started on biologics at stage II (46.6%) or III (28.6%). Moreover, 68.9% had active disease based on the Bath Ankylosing Spondylitis Disease Activity Index. The most commonly prescribed first-line therapy was anti-tumor necrosis factor (69.6%), with infliximab the most frequently prescribed drug (44.7%). The rate of biological drug treatment decreased gradually from 100% at the start to 77% after one year and 39.1% after three years. Moreover, 74% of patients changed drugs due to non-response, and 50% discontinued treatment for economic reasons. Age was associated with treatment adherence, and drug change rates were higher in female patients and patients with active disease. Age was significantly associated with drug discontinuation (p < 0.05). Conclusion: Infliximab was the most commonly prescribed first-line drug. The rate of biological therapy gradually decreased after three years. Most patients changed drugs due to non-response, and many discontinued the drugs for economic reasons. Among the individual and clinical factors, age was associated with treatment adherence.

Oleanane-type triterpenoid sulphates, two new α-glucosidase inhibitors from Elaeocarpus hainanensis.

In connection with our interest in the phytochemical investigation of Elaeocarpus hainanensis Oliv. (Elaeocarpaceae) growing in Vietnam, two new sulphated oleanane triterpenes were obtained herein and structurally identified. Based on the combination of the extensive 1D-, 2D NMR and HR ESI MS spectroscopic data analysis, their chemical structures have been elucidated as 1α,3ß-dihydroxy-olean-18-ene 1-sulphate (1) and 1α,3ß-dihydroxy-olean-12-ene 1-sulphate (2). Notably, compounds 1 and 2 are corroborating the proposition that triterpenoid sulphates serve as chemosystematic markers of the Elaeocarpus genus. Additionally, all these two new compounds 1 and 2 strongly inhibited α-glucosidase in vitro with the respective IC50 values of 3.81 ± 0.33 µM and 21.27 ± 0.48 µM, which were significantly better than that obtained from positive control, acarbose (IC50 247.73 ± 11.85 µM).

The alkoxy radical polymerization of N-vinylpyrrolidone in organic solvents: theoretical insight into the mechanism and kinetics.

Poly(N-vinylpyrrolidone) (PVP) is a polymer with many applications in cosmetic, pharmaceutical, and biomedical formulations due to its minimal toxicity. PVP can be synthesized through radical polymerization in organic solvents; this well-known industrial process is thoroughly characterized experimentally, however, quantum chemical modeling of the process is scarce: the mechanism and kinetics have not been thoroughly investigated yet. In this work, the mechanism and kinetics of the alkoxy radical polymerization of N-vinylpyrrolidone in organic solvents, namely isopropanol (IP) and toluene (TL), were successfully modeled by computational chemistry. The initiator radicals di-tert-butyl peroxide (TBO˙) and dicumyl peroxide (CMO˙) as well as the solvents isopropanol and toluene, were shown to be capable of assisting in the initiation reactions. The rate constant was influenced by the combination of initiators and solvent and the values of the rate constant of propagation were approximately 101-103 M-1 s-1. The radical polymerization of NVP with dicumyl peroxide as an initiator was comparable to that of di-tert-butyl peroxide in all of the examined organic solvents, whereas the solvents had less of an effect.

Four New Stilbene Derivatives Isolated from Gnetum latifolium var. funiculare Markgr. and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.

Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives (1-8) including for new compounds (1-4). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1-3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC50 values ranging from 46.81 to 68.10 µM, compounds 4 and 6 showed weak effects with the IC50 values of 96.57 and 79.46 µM, respectively, compared to that of the positive control compound, dexamethasone (IC50 14.20 µM).

Study of the Mechanism and Kinetics of the Radical Scavenging Activity of 2-Mercaptoimidazole.

2-Mercaptoimidazole (2MI) is related to natural ovothiols that are recognized as powerful radical scavengers. Yet, despite early reports of its potent antioxidant properties, 2MI received little attention. Specifically, its radical scavenging activity against typical free radicals like HO• and HOO• has not yet been studied in terms of its mechanism and kinetics. In this project, density functional theory (DFT) simulations were used to assess the antiradical activity of 2MI. Calculations indicate that 2MI can demonstrate anti-HO• activity in both lipid and aqueous environments (koverall of 1.05 × 1010 and 2.07 × 1010 M-1 s-1, respectively). The calculated kinetics is extremely close to the experimental data in water (pH = 7.0), resulting in a kcalculated/kexperimental ratio of 1.73, validating the accuracy of the computational method and its usefulness for assessing radical scavenging activity in silico. In lipid media, the HOO• radical scavenging activity of 2MI is faster than that of common typical natural scavengers such as ascorbic acid, Trolox, and trans-resveratrol; hence, 2MI is a powerful radical scavenger in nonpolar media.

Integrated pest management of Hypsipyla robusta shoot-tip borer (Lepidoptera: Pyralidae) in Chukrasia tabularis (Sapindales: Meliaceae).

Chukrasia tabularis A. Juss produces a valuable timber but plantations are susceptible to attack by the shoot-tip borer Hypsipyla robusta Moore. An integrated pest management (IPM) approach is desirable to limit the extent of damage. Therefore, this study was undertaken to evaluate the deployment of IPM measures in plantations in Vietnam. Data on tree damage and the biology of H. robusta were gathered in 4 provinces over one year and used to build an investigation schedule. Two preliminary IPM trials were then established in which Bacillus thuringiensis and Metarhizium anisopliae were applied to the foliage when the damage incidence (P%) was in the range 5-10%; and insecticides (Carbaryl, Carbosulfan) were applied when the P% exceeded 10%. In addition, larvae and pupae were removed manually over time. In the first trial, the combination of manual and biological control methods reduced the damage index (DI) of trees from 4 tolerant families by 82% compared to the untreated control plots. In the second trial using standard planting stock, application of insecticides was required to reduce the DI by 83%. Six extended IPM trials were undertaken using the same IPM protocols and these reduced the DI to the same extent as in the preliminary trials. Over an 18-month period, the deployment of IPM increased height growth by 19-22% and diameter growth by 38-41% compared to the controls. These findings highlight the value of planting improved seed and the benefit of adopting an IPM approach to manage the shoot-tip borer.

Evidence of widespread endemic populations of highly multidrug resistant Klebsiella pneumoniae in hospital settings in Hanoi, Vietnam: a prospective cohort study.

BACKGROUND: Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum ß-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing. METHODS: We did a prospective cohort study of 69 patients in intensive care units (ICUs) from two hospitals in Hanoi, Viet Nam. Patients were included if they were aged 18 years or older, admitted for longer than the mean length of stay in their ICU, and cultured K pneumoniae from their clinical samples. Longitudinally collected samples from patients (collected weekly) and the ICU environment (collected monthly) were cultured on selective media, and whole-genome sequences from K pneumoniae colonies analysed. We did phylogenetic analyses and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K pneumoniae. FINDINGS: Between June 1, 2017, and Jan 31, 2018, 69 patients were in the ICUs and eligible for inclusion, and a total of 357 K pneumoniae isolates were cultured and successfully sequenced. 228 (64%) of K pneumoniae isolates carried between two and four different ESBL-encoding and carbapenemase-encoding genes, with 164 (46%) isolates carrying genes encoding both, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM-1 in 46·6% of samples from the globally successful ST15 lineage. Despite being physically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. INTERPRETATION: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K pneumoniae in ICUs in Viet Nam. Through studying K pneumoniae ST15 in detail, we showed how important resistance genes are contained within these strains that are carried broadly by patients entering the two hospitals directly or through referral. FUNDING: Medical Research Council Newton Fund, Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Feruloylmonotropeins: promising natural antioxidants in Paederia scandens.

Paederia scandens (Lour.) is a widely used medicinal herb in Vietnam, China, India, and Japan for the treatment of a variety of conditions, including toothache, chest pains, piles, and spleen inflammation. There is broad interest in identifying the composition of its extracts and confirming their numerous biological activities, including anti-nociceptive, antiviral, and anticancer properties. Two iridoid glucosides obtained from the MeOH extract of P. scandens, 6'-O-E-feruloylmonotropein (6-FMT) and 10'-O-E-feruloylmonotropein (10-FMT), are potential antioxidants based on their structure. In this study, the hydroperoxyl scavenging activity of 6-FMT and 10-FMT was examined in silico by using density functional theory. These FMTs are predicted to be weak antioxidants in non-polar environments, whereas a good HOO˙ scavenging activity is expected in polar environments (pH = 7.4) with k overall = 3.66 × 107 M-1 s-1 and 9.45 × 106 M-1 s-1, respectively. This activity is better than many common antioxidants such as trolox and nearly equivalent to ascorbic acid and resveratrol. The hydroperoxyl scavenging activity was exerted mainly by the di-anion form of FMTs in water at physiological pH following the single electron transfer mechanism. The results suggest that FMTs are promising natural antioxidants in aqueous physiological environments.

Reactions of nicotine and the hydroxyl radical in the environment: Theoretical insights into the mechanism, kinetics and products.

Nicotine (NCT) is a prevalent and highly poisonous tobacco alkaloid found in wastewater discharge. Advanced oxidative processes (AOP) are radical interactions between harmful pollutants and ambient free radicals that, theoretically, result in less toxic compounds. For a better understanding of the chemical transformations and long-term environmental effects of toxic discharges, the study of these processes is crucial. Here, quantum chemical calculations are used to investigate the AOP of the NCT in aqueous and lipidic environments. It was found that NCT interacted with HO• in polar and nonpolar media, with an overall rate constant koverall = 106 - 1010 M-1 s-1. The computed kinetic data are reasonably accurate as seen by the comparison with the experimental rate constant in water (pH = 7.0), which results in a kcalculated/kexperimetal ratio of 1.4. The hydrogen transfer (C7, C9, C12)-single electron transfer pathways are the main mechanisms for the HO• + NCT reaction in pentyl ethanoate solvent to form the cations as the primary products of the two-step reaction. However, in aqueous environments, the degradation of NCT by HO• radicals increases with increasing pH levels. It is predicted that oxidation products are less toxic than nicotine itself, especially in an aqueous environment with a pH < 7.0.

Diagnostic Value in Screening Severe Depression of the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory Scale, and Zung's Self-Rating Anxiety Scale Among Patients with Recurrent Depression Disorder.

Background: Depression is a widespread and incapacitating mental health disorder that impacts millions of people worldwide, playing a substantial role in the overall global health challenges. Depression has a big impact on a person's quality of life, cognitive and social functioning, risk of suicide, risk of heart disease and other illnesses, as well as death from all causes. Objective: It may be challenging to choose the best tools to screen for severe depression in patients with recurrent depression disorder (PRD) considering the diversity of psychological scales in Vietnam. The aim of this study was to evaluate diagnostic value for detect severe depression of four psychological scales including Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory Scale (BECK), and Zung's Self-Rating Anxiety Scale (SAS) by genders and age groups among PRD in Vietnam. Methods: This study was conducted at National Institute of Mental Health, Bach Mai Hospital, Vietnam, from 2020 to 2021. There were 109 PRD evaluated with HAM-D, HAM-A, BECK, and SAS by qualified psychiatrists. By analysing Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC) curve, we determined sensitivity, specificity and cut points of four above scales. Results: Among four scales, the BECK scale had the best diagnostic effect with the most optimal sensitivity and specificity (61.64% and 75%, respectively). We proposed the new cut-off of HAM-D, HAM-A, BECK, and SAS for detecting severe depression among PRD were 20, 34, 30, and 45, respectively. By genders, the cut points for the HAM-D, HAM-A, BECK, and SAS in males were 20, 27, 34, and 44, respectively, while those figure in females were 14, 34, 30, and 46, respectively. By age groups, adults had cut values for four above scales of 20, 34, 27, and 45, respectively, whereas those for the elderly were 16, 17, 35, and 44, respectively. Conclusion: We highly recommended that BECK is the most optimal method to screen severe depression in PRD in Vietnam. It is essential to utilize varied cut values of HAM-D, HAM-A, BECK, and SAS for different genders and age groups.

The radical scavenging activity of glycozolidol in physiological environments: a quantum chemical study.

Glycozolidol was isolated from the root of Glycosmis pentaphylla (6-hydroxy-2-methoxy-3-methylcarbazole, GLD). This molecule attracted considerable interest due to its beneficial biological activities that likely stem from its antioxidant activity; yet, the radical scavenging action of GLD has not been investigated thus far. In this study, DFT calculations were used to estimate the radical scavenging activity of GLD against a variety of biologically significant radical species in physiological environments. The findings demonstrated that GLD exerts significant antiradical activity in water at pH = 7.40 and in pentyl ethanoate (as a model of lipidic media) with k overall = 8.23 × 106 and 3.53 × 104 M-1 s-1, respectively. In aqueous solution, the sequential proton-loss electron transfer mechanism made the highest contribution to the activity, whereas in nonpolar solvents the formal hydrogen transfer mechanism dominated the activity. GLD is predicted to have strong antiradical activity against CH3O˙, CH3OO˙, CCl3OO˙, NO2, SO4˙-, DPPH and ABTS+˙ k app ≈ 109 M-1 s-1 and k f ≈ 106 M-1 s-1. The results suggest that GLD is a good radical scavenger in physiological environments.

Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

The Gut Microbiota at Different Developmental Stages of Apis cerana Reveals Potential Probiotic Bacteria for Improving Honeybee Health.

Honeybees play a vital role in the ecological environment and agricultural economy. Increasing evidence shows that the gut microbiome greatly influences the host's health. Therefore, a thorough understanding of gut bacteria composition can lead to the development of probiotics specific for each development stage of honeybees. In this study, the gut microbiota at different developmental stages (larvae, pupae, and adults) of the honeybees Apis cerana in Hanoi, Vietnam, was assessed by sequencing the V3-V4 region in the 16S rRNA gene using the Illumina Miseq platform. The results indicated that the richness and diversity of the gut microbiota varied over the investigated stages of A. cenara. All three bee groups showed relative abundance at both phylum and family levels. In larvae, Firmicutes were the most predominant (81.55%); however, they decreased significantly along with the bee development (33.7% in pupae and 10.3% in adults) in favor of Proteobacteria. In the gut of adult bees, four of five core bacteria were found, including Gilliamella apicola group (34.01%) Bifidobacterium asteroides group (10.3%), Lactobacillus Firm-4 (2%), and Lactobacillus Firm-5 (1%). In contrast, pupae and larvae lacked almost all core bacteria except G. apicola (4.13%) in pupae and Lactobacillus Firm-5 (4.04%) in larvae. This is the first report on the gut microbiota community at different developmental stages of A. cerana in Vietnam and provides potential probiotic species for beekeeping.

Synthesis and evaluation of the antioxidant activity of 3-pyrroline-2-ones: experimental and theoretical insights.

The heterocyclic γ-lactam ring 2-pyrrolidinone has four carbon atoms and one nitrogen atom. Among the group of derivatives of 2-pyrrolidinones, 1,5-dihydro-2H-pyrrol-2-ones, also known as 3-pyrroline-2-ones, play a significant structural role in a variety of bioactive natural compounds. In this study, three-component reactions were used to successfully synthesize six polysubstituted 3-hydroxy-3-pyrroline-2-one derivatives. The antioxidant activity of the compounds was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, identifying 4-ethoxycarbonyl-3-hydroxy-5-(4-methylphenyl)-1-phenyl-3-pyrroline-2-one (4b) as the most promising radical scavenger. Quantum chemistry calculations of the thermodynamics and kinetics of the radical scavenging activity also suggest that 4b is an effective HO˙ radical scavenger, with k overall values of 2.05 × 109 and 1.54 × 1010 M-1 s-1 in pentyl ethanoate and water, respectively. On the other hand, 4b could not scavenge hydroperoxyl radicals in either media. The ability of 4b to scavenge hydroxyl radicals in polar and non-polar environments is comparable to that of conventional antioxidants such as melatonin, gallic acid, indole-3-carbinol, ramalin, or Trolox. Thus 4b may be classed as a promising HO˙ radical scavenger in the physiological environment.