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Abstract Background International travel could facilitate the spread of antimicrobial-resistant bacteria including extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). Previous studies, which attempted to understand the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels, are limited to western travellers. Methods We established a prospective cohort of 90 Hong Kong travellers to investigate gut microbiota determinants and associated risk factors for the acquisition of ESBL-E. Baseline characteristics and travel-associated risk factors were gathered through questionnaires. Faecal samples were collected in 3-4 days before and after travel. Antimicrobial susceptibility of ESBL-E isolates was tested, and gut microbiota were profiled by 16S rDNA amplicon sequencing. Non-parametric tests were used to detect potential associations, and logistic regression models were used to quantify the associations. Random forest models were constructed to identify microbial predictors for ESBL-E acquisition. Results In total, 49 (54.4%) participants were tested negative for ESBL-E colonization before travel and were followed up after travel. A total of 60 ESBL-E isolates were cultured from 20 (40.8%) participants. Having low Actinobacteria richness and low abundance of short-chain fatty acid-producing bacteria in the gut microbiota before travel increased the risk of acquiring ESBL-E and the risk can be further exacerbated by eating raw seafood during travel. Besides, post-travel ESBL-E positive participants had increased abundances of several opportunistic pathogens such as Staphylococcus, Enterococcus, Escherichia/Shigella and Klebsiella. The random forest model integrating pre-travel microbiota and the identified travel-related risk factor could predict ESBL-E acquisition with an area under the curve of 75.4% (95% confidence interval: 57.9–93.0%). Conclusions In this study, we identified both travel-related risk factors and microbiota predictors for the risk of ESBL-E acquisition. Our results provide foundational knowledge for future developments of microbiota-based interventions to prevent ESBL-E acquisition during international travels.

This world premiere brings together the vital forces of the Capitole: the Ballet, the Chorus and the Orchestra under the direction of Maxime Pascal. An exceptional evening at the Halle aux grains. In 1912, with Daphnis and Chloe, Ravel offered Diaghilev's Ballets Russes a veritable choreographic symphony with choir, a masterpiece of French music that was taken up by the choreographer Fokine and the dancer Nijinsky. A century later, the great choreographer Thierry Malandain reinvents, for the Ballet du Capitole, this pastoral myth of innocence in love and unfolds a vast and fascinating impressionist fresco. Preceded by his rereading of Debussy's famous Après-midi d'un faune, this world premiere brings together the vital forces of the Capitole: the Ballet, the Chorus and the Orchestra under the direction of Maxime Pascal. An exceptional evening at the Halle aux grains.

This world premiere brings together the vital forces of the Capitole: the Ballet, the Chorus and the Orchestra under the direction of Maxime Pascal. An exceptional evening at the Halle aux grains. In 1912, with Daphnis and Chloe, Ravel offered Diaghilev's Ballets Russes a veritable choreographic symphony with choir, a masterpiece of French music that was taken up by the choreographer Fokine and the dancer Nijinsky. A century later, the great choreographer Thierry Malandain reinvents, for the Ballet du Capitole, this pastoral myth of innocence in love and unfolds a vast and fascinating impressionist fresco. Preceded by his rereading of Debussy's famous Après-midi d'un faune, this world premiere brings together the vital forces of the Capitole: the Ballet, the Chorus and the Orchestra under the direction of Maxime Pascal. An exceptional evening at the Halle aux grains.

Plasmodione is a potent early antiplasmodial compound. A metabolic study on mice treated with plasmodione revealed that 6-hydroxy–plasmodione was the main metabolite eliminated in the urine of treated mice. To block the metabolic pathway in the host, the introduction of fluorine at C-6 of the 3-benzylmenadione core was applied and showed potent antiplasmodial activity similar to that of the plasmodione analogue in vitro. In this work, a library of 38 6-fluoro-3-benzylmenadione analogues (a series) was constructed by incorporating structurally diverse groups in place of the 4-(trifluoromethyl) substituent present in the antiplasmodial plasmodione, via three synthetic routes. All new compounds were tested against the P. falciparum NF54 strain and for cytotoxicity with the rat L6 line. With a fluorine atom at C-6, A-a-21 was revealed to be the only compound from the a series, superior to the 6-H- analogue from the b series, with an IC50 value of 70 nM versus 200 nM. Then, five other fluorine-based 3-benzylmenadiones, in which the fluorine was introduced in various positions of the 3-benzylmenadione core, were synthetized to assist our understanding of the impact of fluorine on antiplasmodial potencies in vitro; in particular, the aim here was to compare the effects of human serum and P. berghei species in these drug screens. This was also conducted in vivo with the P. berghei-infected mouse model. In the P. berghei species assay, PD and the 4′-fluoro-3′-trifluoromethyl-benzylmenadione A-b-9 exhibited a similar antiplasmodial behavior toward P. falciparum versus P. berghei. In the human serum versus Albumax assays, only the 6-fluoro–plasmodione showed a lower shift factor between Albumax assays and human serum conditions, suggesting a lower protein binding for the 6-F-PD compared to plasmodione or A-b-9. In vivo, 6-fluoro–plasmodione proved to be the most potent 3-benzylmenadione, reducing parasitemia by 50% after oral administration at 50 mg/kg.

Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8 + T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8 + T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B -deficient CD8 + T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8 + T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8 + T lymphocytes in the setting of acute myocardial infarction. Immune cells contribute to adverse remodeling following myocardial infarction. Here the authors show in mice and pigs that CD8 + lymphocytes release Granzyme B in the infarcted heart leading to cardiomyocyte death, enhanced inflammation and deterioration of cardiac function.

Carotenoid-containing oil droplets in the avian retina act as cut-off filters to enhance colour discrimination. We report a confocal resonance Raman investigation of the oil droplets of the domestic chicken, Gallus gallus domesticus. We show that all carotenoids present are in a constrained conformation, implying a locus in specific lipid binding sites. In addition, we provide proof of a recent conclusion that all carotenoid-containing droplets contain a mixture of all carotenoids present, rather than only a subset of them-a conclusion that diverges from the previously-held view. Our results have implications for the mechanism(s) giving rise to these carotenoid mixtures in the differently-coloured droplets.

Central nervous system (CNS) disorders such as neurodegenerative diseases, multiple sclerosis, or even brain ischemia represent major therapeutic challenges with limited effective treatments. The sigma-1 receptor (S1R), a unique ligand-operated molecular chaperone enriched at mitochondria-associated membranes, has emerged as a promising drug target due to its role in neuroprotection and neuroinflammation. Building upon our previously identified S1R ligand (compound 1), we designed and synthesized six novel benzamide derivatives through pharmacomodulation to optimize affinity, selectivity, and safety profiles. Among these, compound 2 demonstrated superior S1R affinity, improved selectivity over the sigma-2 receptor (S2R), and favorable ADME properties, including enhanced permeability and markedly reduced in vitro cardiac toxicity compared to the lead compound. Functional assays confirmed the agonist activity of key derivatives, while safety evaluations revealed low cytotoxicity and minimal off-target receptor interactions. Collectively, these findings support compound 2 as a promising candidate for further preclinical development in S1R-related CNS disorders.

Magnetic skyrmions are nanoscale spin configurations that are efficiently created and manipulated. They hold great promises for next-generation spintronics applications. In parallel, the interplay of magnetism, superconductivity and spin-orbit coupling has proved to be a versatile platform for engineering topological superconductivity predicted to host non-abelian excitations, Majorana zero modes. We show that topological superconductivity can be induced by proximitizing skyrmions and conventional superconductors, without need for additional ingredients. Apart from a previously reported Majorana zero mode in the core of the skyrmion, we find a more universal chiral band of Majorana modes on the edge of the skyrmion. We show that the chiral Majorana band is effectively flat in the physically relevant parameter regime, leading to interesting robustness and scaling properties. In particular, the number of Majorana modes in the (nearly-)flat band scales with the perimeter length of the system, while being robust to local disorder. Skyrmions, Majorana fermions and topological superconductivity are active areas of research within the condensed matter physics community and each offer the promise of new physics and potential applications. Here, the authors theoretically demonstrate that by bringing skyrmions into close proximity with a superconductor topological superconductivity can be induced, as well as Majorana states localized at the edges of the skyrmions.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype–phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first ‘European Forum on Visceral Myopathy’. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy.

ObjectivesTo compare the clinical manifestations, disease activity and disease burden between patients with radiographic (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) over a 5-year follow-up period in the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort.MethodsPatients from the DESIR cohort who had X-ray images of the sacroiliac joints available at baseline and did not leave the study during the 5-year follow-up period because of a diagnosis other than axSpA were included. A unilateral rating of ‘obvious sacroiliitis’ by the local reader was considered sufficient for classification as r-axSpA. The incidence of first episodes of peripheral and extra-rheumatic manifestations was compared between the two groups using the incidence rate ratio and Cox regressions adjusted for sex, age and tumour necrosis factor blocker (TNFb) intake. Mean values of patient-reported outcomes (PROs) and days of sick leave over 5 years of follow-up were compared using mixed models adjusted for sex, age, TNFb intake and baseline values.ResultsIn total, 669 patients were included, of whom 185 (27.7%) and 484 (72.3%) were classified as r-axSpA and nr-axSpA, respectively. At baseline, the r-axSpA patients showed a significantly higher prevalence of males. After adjusting for age, sex and TNFb intake, Cox regressions for peripheral and extra-rheumatic manifestations did not show any significant differences between groups. Mixed models also showed similar mean levels in PROs and days of sick leave between groups over time.ConclusionThe incidence of peripheral and extra-rheumatic manifestations as well as the disease burden over time remained similar between r-axSpA and nr-axSpA groups after adjusting for intermediate variables.Trial registration number NCT01648907