Risk Factors for Alveolar Echinococcosis in Humans

A case-control study of alveolar echinococcosis cases in Germany identifies several risk factors for the disease

Altered Cytokine Expression and Barrier Properties after In Vitro Infection of Porcine Epithelial Cells with Enterotoxigenic Escherichia coli and Probiotic Enterococcus faecium

The aim of the present study was to elucidate the effects of the probiotic feed additive Enterococcus faecium NCIMB 10415 (E. faecium) on porcine jejunal epithelial cells (IPEC-J2) during an in vitro challenge with enterotoxigenic Escherichia coli (ETEC). Cells were incubated with E. faecium, ETEC, or both, and the effects on barrier function and structure and intra- and intercellular signaling were determined. Coincubation with E. faecium abolished the ETEC- induced decrease in transepithelial resistance (Rt). No differences were seen in the expression levels of the intercellular connecting tight junction proteins examined. However, for the first time, a reorganization of the monolayer was observed in ETEC-infected cells but not in coincubated cells. ETEC induced an increase in cytotoxicity that was prevented by coincubation, whereas apoptosis rates were not affected by bacterial treatment. ETEC increased the mRNA expression and release of proinflammatory cytokines TNF-α, IL-1α, and IL-6 which could be prevented by coincubation for TNF-α mRNA expression and IL-6 protein. Likewise, cAMP concentrations elevated by ETEC were reduced in coincubated cells. These findings indicate a protective effect of the probiotic E. faecium on inflammatory responses during infection with ETEC

New Topoisomerase Inhibitors:Evaluating the Potency of Gepotidacin and Zoliflodacin in Fluoroquinolone-Resistant Escherichia coli upon tolC Inactivation and Differentiating Their Efflux Pump Substrate Nature

Inactivating tolC in multidrug-resistant Escherichia coli with differing sequence types and quinolone resistance-determining mutations reveals remarkably potentiated activity of the first-in-class topoisomerase inhibitors gepotidacin and zoliflodacin. Differences between both structurally unrelated compounds in comparison to fluoroquinolones regarding the selectivity of E. coli RND (resistance-nodulation-cell division)-type transporters, efflux inhibitors, and AcrB porter domain mutations were demonstrated. The findings should reinforce efforts to develop efflux-bypassing drugs and provide AcrB targets with critical relevance for this purpose

Real-life long-term outcomes of upfront surgery in patients with resectable stage I-IIIA non-small cell lung cancer

Treatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I–IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010–2017. Data of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA). With a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OSbut only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS. The study showed favourable outcomes of resectable stage I–IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy

Exploring the Molecular Conformation Space by Soft Molecule–Surface Collision

Biomolecules function by adopting multiple conformations. Such dynamics are governed by the conformation landscape whose study requires characterization of the ground and excited conformation states. Here, the conformational landscape of a molecule is sampled by exciting an initial gas-phase molecular conformer into diverse conformation states, using soft molecule-surface collision (0.5-5.0 eV). The resulting ground and excited molecular conformations, adsorbed on the surface, are imaged at the single-molecule level. This technique permits the exploration of oligosaccharide conformations, until now, limited by the high flexibility of oligosaccharides and ensemble-averaged analytical methods. As a model for cellulose, cellohexaose chains are observed in two conformational extremes, the typical "extended" chain and the atypical "coiled" chain-the latter identified as the gas-phase conformer preserved on the surface. Observing conformations between these two extremes reveals the physical properties of cellohexaose, behaving as a rigid ribbon that becomes flexible when twisted. The conformation space of any molecule that can be electrosprayed can now be explored

Effect of feeding Alphitobius diaperinus meal on fattening performance and meat quality of growing-finishing pigs

A total of 48 piglets with an average weight of 26 kg were allocated to 4 experimental groups of 12 animals, balanced according to litter, sex and weight, and fattened on feed containing 0, 3, 6, or 9% of Alphitobius diaperinus meal (ADM) replacing soybean meal (SOY) as protein source. The control feed contained 10.7% SOY while in the 9% ADM feed SOY was completely replaced. Feed was accessible ad libitum in transponder-controlled feeders. Feed consumption and fattening performance records started when the animals reached 35 kg. The 3-way crossbred animals (Landrace x Large White sows mated to Duroc, Pietrain, or Large White sire line bores) were slaughtered at a target carcass weight of 86 kg. No linear effect of ADM on daily gain and feed consumption was found. No effect on lean meat content nor on any of the meat quality traits was observed. The content of polyunsaturated fatty acids (PUFA) in the backfat increased with increasing amount of ADM in the feed. It is concluded that ADM may replace SOY in pig feed without exerting detrimental effects on growth performance, carcass composition and meat quality except for a higher PUFA-content in the adipose tissue

Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131

Gram-negative bacteria partly rely on efflux pumps to facilitate growth under stressful conditions and to increase resistance to a wide variety of commonly used drugs. In recent years E. coli ST131 has emerged as a major cause of extraintestinal infection frequently exhibiting an MDR phenotype. The contribution of efflux to MDR in emerging E. coli MDR clones however, is not well studied. We characterized strains from an international collection of clinical MDR-E. coli isolates by MIC testing with and without the addition of the AcrAB-TolC efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). MIC data for 6 antimicrobial agents and their reversion by NMP were analyzed by Principal Component Analysis (PCA). PCA revealed a group of 17/34 MDR-E. coli exhibiting increased susceptibility to treatment with NMP suggesting an enhanced contribution of efflux pumps to antimicrobial resistance in these strains (termed "enhanced efflux phenotype" [EEP]). Only 1/17 EEP strains versus 12/17 non-EEP MDR strains belonged to the ST131 clonal group. Whole-genome sequencing revealed marked differences in efflux-related genes between EEP and control strains, with the majority of notable amino-acid substitutions occurring in AcrR, MarR and SoxR. qRT-PCR of multiple efflux-related genes showed significant overexpression of the AcrAB-TolC-system in EEP strains, whereas in the remaining strains we found enhanced expression of alternative efflux proteins. We conclude that a proportion of MDR E. coli exhibit an EEP, which is linked to an overexpression of the AcrAB-TolC-efflux-pump and a distinct array of genomic variations. Members of ST131, although highly successful, are less likely to exhibit the EEP