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Purpose: To study the effect of inhaling a beta-agonist (salbutamol) compared to placebo on skiing and cycling performance in well-trained elite athletes. Methods: Three different exercise protocols were used, all with a cross-over double blind placebo-controlled design. Participants inhaled 800 µg salbutamol or a placebo prior to the test, which was repeated on a following day with the participants inhaling the other substance. Fifteen junior elite skiers performed four free-style high intensity sprints (1100 m/work time 3.5–4.5 min). Twelve elite cyclists carried out a short cycling protocol, starting with two 5 min submaximal workloads followed by a maximal intermittent performance test to exhaustion. Another 12 elite cyclists performed the maximal intermittent performance test to exhaustion after a 150 min long submaximal cycling protocol. Results: Group mean time for the ski sprints increased, with no difference between treatment groups. In the short cycling protocol time to exhaustion was 9.1% (95% CI 52–161) lower after inhaling salbutamol compared to placebo and in the long cycling protocol time to exhaustion was 9.1% (95% CI – 121–267) lower after inhaling salbutamol compared to placebo. Blood lactate, heart rate and ventilation increased during submaximal exercise with salbutamol compared to placebo in the short cycling protocol (p <.05). Conclusion: This study could not confirm any positive performance effects from inhaling 800 µg salbutamol compared to placebo in skiing and high-intensity intermittent cycling performance. Instead, time to exhaustion in the maximal intermittent performance test was lower in both cycling protocols. Highlights There was no difference in performance time between salbutamol and placebo treatment in real-life applicable repeated ski sprints. Time to exhaustion in the maximal intermittent performance test was 9.1% lower after inhaling salbutamol compared to placebo, both when performed after 10 and 150 min of submaximal cycling. [ABSTRACT FROM AUTHOR]

Background: Reducing the time to treatment by means of cardiopulmonary resuscitation (CPR) and defibrillation is essential to increasing survival after cardiac arrest. A novel method of dispatching drones for delivery of automated external defibrillators (AEDs) to the site of a suspected out-of-hospital cardiac arrest (OHCA) has been shown to be feasible, with the potential to shorten response times compared with the emergency medical services. However, little is known of dispatchers' experiences of using this novel methodology., Methods: A qualitative semi-structured interview study with a phenomenological approach was used. Ten registered nurses employed at an emergency medical dispatch centre in Gothenburg, Sweden, were interviewed and the data was analysed by qualitative content analysis. The purpose was to explore dispatcher nurses' experiences of deliveries of AEDs by drones in cases of suspected OHCA., Results: Three categories were formed. Nurses expressed varying compliance to the telephone-assisted protocol for dispatch of AED-equipped drones. They experienced uncertainty as to how long would be an acceptable interruption from the CPR protocol in order to retrieve a drone-delivered AED. The majority experienced that collegial support was important. Technical support, routines and training need to be improved to further optimise action in cases of drone-delivered AEDs handled by dispatcher nurses., Conclusions: Although telephone-assisted routines for drone dispatch in cases of OHCA were available, their use was rare. Registered nurses showed variable degrees of understanding of how to comply with these protocols. Collegial and technical support was considered important, alongside routines and training, which need to be improved to further support bystander use of drone-delivered AEDs. As the possibilities of using drones to deliver AEDs in cases of OHCA are explored more extensively globally, there is a good possibility that this study could be of benefit to other nations implementing similar methods. We present concrete aspects that are important to take into consideration when implementing this kind of methodology at dispatch centres., (© 2024. The Author(s).)

Carbapenem-resistant Enterobacterales (CRE) constitute an urgent threat to worldwide public health. The spread of CRE is facilitated by transmission via the environment. Wastewater treatment plants (WWTPs) are considered to be important sources of antibiotic resistance and hot spots of antibiotic-resistant bacteria (ARB) which can facilitate dissemination of antibiotic resistance genes. In this study, water samples were collected over one year from a WWTP in Jinan, Shandong province, China, from different functional sites in the wastewater treatment process. Carbapenem-resistant Escherichia coli (CREC) were isolated by selective cultivation and whole-genome sequenced to investigate the occurrence and characteristics of CREC in the WWTP. A total of 77 CREC isolates were included in the study and the detection rate of CREC in the WWTP water inlet was found to be 85%. An additional 10 CREC were isolated from a nearby teaching hospital during the sampling period and included for comparison to the environmental isolates. Susceptibility testing showed that all CREC were multidrug-resistant. 6 different carbapenem resistance genes (CRGs) were detected, including bla NDM-5 (n = 75), bla NDM-1 (n = 6), bla NDM-4 (n = 3), bla NDM-6 (n = 1), bla NDM-9 (n = 1), and bla KPC-2 (n = 4). 42 CREC isolates were whole-genome sequenced with Illumina short-read sequencing. 11 of these were also sequenced with Nanopore long-read sequencing. Plasmids carrying CRGs were found to belong to IncX3 (n = 35), IncFII (n = 12), IncFIA (n = 5), IncFIB (n = 2), IncC (n = 1), and IncP6 (n = 1). Clonal dissemination of CREC belonging to ST167, ST448, and ST746 was observed between different parts of the WWTP. Furthermore, isolates from the WWTP, including an isolate belonging to the high-risk ST167 strain, were found to be clonally related to CREC isolated at the hospital. The spread of CRGs is of considerable concern and strategies to prevent environmental dissemination of this contaminant urgently needs to be implemented., 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 © 2023 Elsevier Ltd. All rights reserved.)

The increasing prevalence of infections caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae strains (CR-hvKP) prompts the question of whether these strains also circulate outside of clinical settings. However, the environmental occurrence and dissemination of CR-hvKP are poorly studied. In the current study, we investigated the epidemiological characteristics, and dissemination dynamics of carbapenem-resistant K. pneumoniae (CRKP) isolated from a hospital, an urban wastewater treatment plant (WWTP), and adjacent rivers in Eastern China during one year of monitoring. A total of 101 CRKP were isolated, 54 were determined to be CR-hvKP harboring pLVPK-like virulence plasmids, which were isolated from the hospital (29 out of 51), WWTP (23 out of 46), and rivers (2 out of 4), respectively. The period with lowest detection rate of CR-hvKP in the WWTP, August, corresponded with the lowest detection rate at the hospital. Comparing the inlet and outlet of the WWTP, no significant reduction of the detection of CR-hvKP and relative abundance of carbapenem resistance genes was observed. The detection rate of CR-hvKP and the relative abundance of carbapenemase genes were significantly higher in the WWTP in colder months compared to warmer months. Clonal dissemination of CR-hvKP clones of ST11-KL64 between the hospital and the aquatic environment, as well as the horizontal spread of IncFII-IncR and IncC plasmids carrying carbapenemase genes, was observed. Furthermore, phylogenetic analysis showed that the ST11-KL64 CR-hvKP strain has spread nationally by interregional transmission. These results indicated transmission of CR-hvKP clones between hospital and urban aquatic environments, prompting the need for improved wastewater disinfection and epidemiological models to predict the public health hazard from prevalence data of CR-hvKP., 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 © 2023. Published by Elsevier Ltd.)

Emergence and dissemination of resistance to last-resort antibiotics such as carbapenem and colistin is a growing, global health concern. Wastewater treatment plants (WWTPs) link human activities and the environment, can act as reservoirs and sources for emerging antibiotic resistance, and likely play a large role in antibiotic resistance transmission. The aim of this study was to investigate occurrence and characteristics of colistin- and carbapenem-resistant Escherichia coli (CCREC) in wastewater and sludge samples collected over a one-year period from different functional areas of an urban WWTP in Jinan city, Shandong, China. A total of 8 CCREC were isolated from 168 samples with selective agar and PCR, corresponding to high prevalence of 4.8%, co-harboring carbapenem resistance genes (bla NDM ) and colistin resistance gene (mcr-1) and subsequently whole-genome sequenced. Additionally, all isolates were multidrug-resistant by antimicrobial susceptibility testing and carried a variety of antibiotic resistance genes. Two isolates carrying virulence genes associated with avian pathogenic E. coli were identified, one belonging to the high-risk clone O101:H9-ST167. Southern blotting was used to characterize CCREC isolates and plasmids carrying bla NDM -genes or mcr-1 could be transferred to a recipient strain E. coli J53 by in vitro conjugation assays. Resistance to other antibiotic classes were sporadically co-transferred to the transconjugant. Transposition of and mcr-1-carrying element from a transferable IncHI2-plasmid was observed among two CCREC clones isolated within 4 days of each other. The occurrence of multidrug-resistant CCREC capable of transferring their antibiotic resistance genotypes via conjugative plasmids is alarming. WWTPs bring bacteria from different sources together, providing opportunities for horizontal exchange of DNA among compatible hosts. Further dissemination of the colistin-, carbapenem-, or both colistin- and carbapenem resistant E. coli could lead to a serious threat to public health., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier., Competing Interests: Declaration of interests A.H., K.H.S.M., K.S., and S.S.E. are employees of deCODE genetics., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.

Objective: To study clinical outcome and risk factors associated with extended-spectrum β-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) in community-onset bloodstream infections (CO-BSI)., Methods: This was a population-based cohort study including patients with pheno- and genotype-matched ESBL-producing E. coli and non-ESBL- E. coli in urine and blood samples collected in 2009-2018 in southeast Sweden. Seventy-seven episodes of ESBL-UPEC satisfying the inclusion criteria were matched 1:1 with 77 non-ESBL-UPEC for age, gender, and year of culture., Results: The most common ST-type and ESBL gene was ST131 (55%), and blaCTX-M-15 (47%), respectively. Risk factors for ESBL-UPEC were: previous genitourinary invasive procedure (RR 4.66; p = 0.005) or history of ESBL-producing E. coli (RR 12.14; p = 0.024). There was significant difference between ESBL-UPEC and non-ESBL-UPEC regarding time to microbiologically appropriate antibiotic therapy (27:15 h vs. 02:14 h; p = <0.001) and hospital days (9 vs. 5; p = <0.001), but no difference in 30-day mortality (3% vs. 3%; p = >0.999) or sepsis within 36 hours (51% vs. 62%; p = 0.623) was observed., Conclusion: The predominant risk factors for ESBL-UPEC were history of ESBL-Ec infection and history of genitourinary invasive procedure. The overall mortality was low and the delay in appropriate antibiotic therapy did not increase the risk for 30-day mortality or risk for sepsis within 36 hours among patients infected with ESBL UPEC. However, these results must be regarded with some degree of caution due to the small sample size., Competing Interests: The authors have declared that no competing interests exist.

Animal farms have become one of the most important reservoirs of carbapenem-resistant Klebsiella spp. (CRK) owing to the wide usage of veterinary antibiotics. "One Health"-studies observing animals, the environment, and humans are necessary to understand the dissemination of CRK in animal breeding areas. Based on the concept of "One-Health," 263 samples of animal feces, wastewater, well water, and human feces from 60 livestock and poultry farms in Shandong province, China were screened for CRK. Five carbapenem-resistant Klebsiella pneumoniae (CRKP) and three carbapenem-resistant Klebsiella quasipneumoniae (CRKQ) strains were isolated from animal feces, human feces, and well water. The eight strains were characterized by antimicrobial susceptibility testing, plasmid conjugation assays, whole-genome sequencing, and bioinformatics analysis. All strains carried the carbapenemase-encoding gene bla NDM-5 , which was flanked by the same core genetic structure (IS 5 - bla NDM-5 - ble MBL - trpF - dsbD -IS 26 -IS Kox3 ) and was located on highly related conjugative IncX3 plasmids. The colistin resistance gene mcr-8.1 was carried by three CRKP and located on self-transmissible IncFII(K)/IncFIA(HI1) and IncFII(pKP91)/IncFIA(HI1) plasmids. The genetic context of mcr-8.1 consisted of IS 903 - orf - mcr-8.1-copR-baeS-dgkA - orf -IS 903 in three strains. Single nucleotide polymorphism (SNP) analysis confirmed the clonal spread of CRKP carrying- bla NDM-5 and mcr-8.1 between two human workers in the same chicken farm. Additionally, the SNP analysis showed clonal expansion of CRKP and CRKQ strains from well water in different farms, and the clonal CRKP was clonally related to isolates from animal farms and a wastewater treatment plant collected in other studies in the same province. These findings suggest that CRKP and CRKQ are capable of disseminating via horizontal gene transfer and clonal expansion and may pose a significant threat to public health unless preventative measures are taken., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Han, Berglund, Zou, Gu, Zhao, Meng, Zhang, Ma and Li.)

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae&#95;RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

To date, carbapenem-resistant Enterobacteriaceae have been found predominantly in clinical settings worldwide. Raoultella belongs to the Enterobacteriaceae family which can cause hospital-acquired infections, and carbapenem-resistant Raoultella spp. (CRR) is sporadically reported in the environment. We investigated the distribution and underlying resistance mechanisms of CRR in a wastewater treatment plant (WWTP) from eastern China between January 2018 and February 2019. A total of 17 CRR were isolated from 324 environmental samples, including Raoultella ornithinolytica (n = 15) and Raoultella planticola (n = 2). The detection of CRR was more frequent in the water inlet compared to anaerobic tank, aerobic tank, sludge thickener, activated sludge, mud cake storage area, and water outlet, and CRR was detected in mud cake stacking area. All CRR were resistant to imipenem, meropenem, ampicillin, piperacillin-tazobactam, cefotaxime, ceftazidime, trimethoprim-sulfamethoxazole and fosfomycin. Four different carbapenemase genes were identified, including bla KPC-2 (n = 13), bla NDM-1 (n = 8), bla NDM-5 (n = 1), bla IMP-4 (n = 1). Interestingly, isolated R. ornithinolytica from the WWTP were closely related to those reported from human samples in China. Plasmid analysis indicated that IncFII(Yp), IncP6, and IncU mediated bla KPC-2 spread, IncX3 and IncN2 mediated bla NDM spread in the environment. The core structure of the Tn3-ISKpn27-bla KPC-2 -ISKpn6, ISAba125-bla NDM -ble MBL -trpF-dsbD were identified. The study provides evidence that Raoultella spp. may spread alarming carbapenem resistance in the environment and, therefore, the continuous surveillance for carbapenem resistance in the WWTP should be conducted, especially sludge., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (10 9  CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1 β and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT 7 R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Yiqiu Fei et al.)

The presence of exopolysaccharides (EPS), a type of biomacromolecules, on the surface of probiotics play an important role in mucoadhesion, and it can be severely influenced by environments during gastrointestinal transit. In this study, the impact of gastrointestinal factors on surface properties of two probiotics ( Lactobacillus rhamnosus GG and Pediococcus pentosaceus LI05) was investigated. Probiotic suspensions had relatively high viscosities and exhibited pronounced shear-thinning behavior due to the presence of EPS. The ζ-potential of both probiotics was relatively low and was not believed to play an important role in mucoadhesion. Compared to the control, the adhesive forces tended to decrease in the presence of gastric acids but increase in the presence of bile salts, since bile salts led to a thicker more open EPS layer compared to gastric acids. Although the functional groups of EPS in both probiotics are similar according to the study by FT-IR spectroscopy, the molecular weight of purified EPS in LI05 was much higher, ranging from 10,112 Da to 477,763 Da, which may contribute to higher rupture length in LI05 group. These results suggest that probiotic-mucin interactions are governed by the compositions and changes in the EPS of the probiotics in different gastrointestinal conditions, which contribute to a better understanding of the mucoadhesive behavior of the probiotics in the GIT., 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., (© 2022 Published by Elsevier B.V.)

The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) constitute a major global health problem. The environment plays an important role in the dissemination of CRE, but large-scale studies on CRE in groundwater environments in animal breeding areas are scarce. The aim of this study was to investigate CRE occurrence and environmental transmission of carbapenem resistance genes in large animal breeding areas in northern China. In total, 280 well water and 102 animal feces samples in large animal breeding areas in six counties from the two provinces Inner Mongolia and Shandong in China, were screened for CRE. A total of 39 CRE were isolated and characterized with next-generation sequencing. 5.3% of well water samples were contaminated with CRE. The well water in chicken farms had the highest number of detections of CRE (15.9%). More than half of the isolates carried closely related, conjugative IncX3 plasmids with bla NDM -genes from multiple geographic areas, indicating that this kind of plasmid plays an important role in dissemination of carbapenem resistance determinants. The clonal expansion of various CRE isolates in well water and animal feces were demonstrated; clonally related CRE were isolated from different wells within the same county, from different counties in the same province, and even from different provinces. In addition to harboring various ARGs, two closely related K. pneumoniae belonging to ST11 isolated from well water carried genetic hypervirulence determinants on a virulence plasmid, highlighting the potential health risk posed by further dissemination of this strain. These findings suggest that groundwater may be an underappreciated reservoir and source of dissemination of CRE, from which resistance genes may disseminate among different bacterial strains and over large geographic distances. Further research and multi-sectorial monitoring, with a "One health" perspective, is urgently needed to investigate the need for interventions aimed at preventing CRE dissemination., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The global increase in carbapenem-resistant Enterobacteriaceae (CRE) is a growing health concern. Infections caused by CRE are associated with increased mortality and length of hospital stay, emphasising the health and economic burden posed by these pathogens. Although CRE can inhabit the human gut asymptomatically, colonisation with CRE is associated with an increased risk of CRE infection and mortality. In this study, we investigated the occurrence and characteristics of CRE in faecal samples from healthy persons in 12 villages in Shandong Province, China., Methods: Screening for CRE in faecal samples was performed by selective cultivation. Minimum inhibitory concentrations (MICs) of meropenem were determined by the agar dilution method. Multilocus sequence typing (MLST) and carbapenemase gene carriage of the isolates were determined by whole-genome sequencing. Genetic relatedness of Escherichia coli isolates was determined by core genome MLST., Results: CRE carriage increased from 2.4% in 2015 to 13.4% in 2017. Most CRE isolates (93.0%) were E. coli and all carried NDM-type carbapenemases. Sequence types (STs) among the E. coli isolates were diverse. The single most common ST was the highly epidemic strain ST167, which was only observed in 2017., Conclusion: We report a rapid increase in occurrence of CRE (from 2.4% to 13.4%) among faecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. Colonisation with CRE is known to increase the risk of CRE infection, and the worrying deterioration of the epidemiological situation in the region reported here indicates a need for further monitoring and possible interventions., Competing Interests: Competing interests None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio of Firmicutes / Bacteroides and the abundance of Lactobacillus genera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.

Objectives: The carbapenemase-encoding gene bla NDM-1 has been reported in Vietnam during the last 10 years, and bla NDM -producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of bla NDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of bla NDM-1 -encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study., Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the bla NDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients., Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding bla NDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding bla NDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same bla NDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques., Conclusions: The plasmids encoding the bla NDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis., Competing Interests: Competing Interests None to declare., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A carbapenem-resistant Citrobacter sedlakii strain AA2CS carrying bla NDM-5 was detected in outdoor aerosols of a wastewater treatment plant (WWTP) in China and the whole genome was sequenced subsequently. AA2CS was captured in an aerobic tank with aerosol particles of sizes ranging from 4.7 to 7.0 μm. Besides bla NDM-5 , AA2CS also harbored 21 other antibiotic resistance genes and displayed a high level of resistance to ampicillin, cefotaxime, ceftazidime, tetracycline, and meropenem. Bla NDM-5 was located on the IncX3 plasmid (pCSNDM-5) with an IS 3000 -IS5- bla NDM-5 - ble MBL - trpF - dsbD -IS 26 structure. pCSNDM-5 was highly homologous to other bla NDM-5 -carrying IncX3 plasmids in China and can be transferred to the Escherichia coli recipient J53. To our knowledge, this is the first report of carbapenem-resistant Enterobacteriaceae in outdoor aerosols in WWTPs.

Background: The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among patients at hospitals in LMICs, with increased risk of hospital-acquired infections., Methods: We isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from faecal samples collected in 2017 from patients at admission and discharge at a Vietnamese neonatal intensive care unit (NICU). 126 CRKP were whole-genome sequenced. The phylogenetic relationship between the isolates and between clinical CRKP isolates collected in 2012-2018 at the same hospital were investigated., Results: NDM-type carbapenemase-(61%) and KPC-2-encoding genes (41%) were the most common carbapenem resistance genes observed among the admission and discharge isolates. Most isolates (56%) belonged to three distinct clonal clusters of ST15, carrying bla KPC-2 , bla NDM-1 and bla NDM-4 , respectively. Each cluster also comprised clinical isolates from blood collected at the study hospital. The most dominant ST15 clone was shown to be related to isolates collected from the same hospital as far back as in 2012., Conclusions: Highly resistant CRKP were found colonising admission and discharge patients at a Vietnamese NICU, emphasising the importance of continued monitoring. Whole-genome sequencing revealed a population of CRKP consisting mostly of ST15 isolates in three clonally related clusters, each related to blood isolates collected from the same hospital. Furthermore, clinical isolates collected from previous years (dating back to 2012) were shown to likely be clonally descended from ST15 isolates in the largest cluster, suggesting a successful hospital strain which can colonise inpatients., (© 2021. The Author(s).)