Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates.

Dietary habits have been associated with alterations of the human gut resident microorganisms contributing to obesity, diabetes and cancer1. In Western diets, red meat is a frequently eaten food2, but long-term consumption has been associated with increased risk of disease3,4. Red meat is enriched in N-glycolylneuraminic acid (Neu5Gc) that cannot be synthesized by humans5. However, consumption can cause Neu5Gc incorporation into cell surface glycans6, especially in carcinomas4,7. As a consequence, an inflammatory response is triggered when Neu5Gc-containing glycans encounter circulating anti-Neu5Gc antibodies8,9. Although bacteria can use free sialic acids as a nutrient source10-12, it is currently unknown if gut microorganisms contribute to releasing Neu5Gc from food. We found that a Neu5Gc-rich diet induces changes in the gut microbiota, with Bacteroidales and Clostridiales responding the most. Genome assembling of mouse and human shotgun metagenomic sequencing identified bacterial sialidases with previously unobserved substrate preference for Neu5Gc-containing glycans. X-ray crystallography revealed key amino acids potentially contributing to substrate preference. Additionally, we verified that mouse and human sialidases were able to release Neu5Gc from red meat. The release of Neu5Gc from red meat using bacterial sialidases could reduce the risk of inflammatory diseases associated with red meat consumption, including colorectal cancer4 and atherosclerosis13

Elaboration and properties of plasticised chitosan-based exfoliated nano-biocomposites

A series of plasticised chitosan-based materials and nanocomposites were successfully prepared by thermomechanical kneading. During the processing, the montmorillonite (MMT) platelets were fully delaminated. The nanoclay type and content and the preparation method were seen to have an impact on the crystallinity, morphology, glass transition temperature, and mechanical properties of the samples. When higher content (5%) of MMT–Na+ or either content (2.5% or 5%) of chitosan-organomodified MMT (OMMT–Ch) was used, increases in crystallinity and glass transition temperature were observed. Compared to the neat chitosan, the plasticised chitosan-based nano-biocomposites showed drastically improved mechanical properties, which can be ascribed to the excellent dispersion and exfoliation of nanoclay and the strong affinity between the nanoclay and the chitosan matrix. The best mechanical properties obtained were Young's modulus of 164.3 MPa, tensile strength of 13.9 MPa, elongation at break of 62.1%, and energy at break of 0.671 MPa. While the degree of biodegradation was obviously increased by the presence of glycerol, a further increase might be observed especially by the addition of unmodified nanoclay. This could surprisingly contribute to full (100%) biodegradation after 160 days despite the well-known antimicrobial property of chitosan. The results in this study demonstrate the great potential of plasticised chitosan-based nano-biocomposites in applications such as e.g., biodegradable packaging materials

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

A Photometric and Spectroscopic Study of the Cataclysmic Variable ST LMi during 2005-2006

We present orbit-resolved spectroscopic and photometric observations of the polar ST LMi during its recent low and high states. In the low state spectra, we report the presence of blue and red satellites to the H-alpha emission line; the velocities and visibility of the satellites vary with phase. This behavior is similar to emission line profile variations recently reported in the low state of AM Her, which were interpreted as being due to magnetically-confined gas motions in large loops near the secondary. Our low-state spectroscopy of ST LMi is discussed in terms of extreme chromospheric activity on the secondary star. Concurrent photometry indicates that occasional low-level accretion may be present, as well as cool regions on the secondary near L1. Furthermore, we report a new ``extreme low-state'' of the system at V~18.5mag. Our orbital high-state spectroscopy reveals changes in the emission line profiles with orbital phases that are similar to those reported by earlier high-state studies. The complicated emission line profiles generally consist of two main components. The first has radial velocity variations identical to that of the major emission H-alpha component seen in the low state. The second is an additional red-shifted component appearing at the phases of maximum visibility of the accreting column of the white dwarf; it is interpreted as being due to infall velocities on the accreting magnetic pole of the white dwarf. At the opposite phases, an extended blue emission wing appears on the emission line profiles. We confirm the presence of a broad absorption feature near 6275Ang which has been previously identified as Zeeman sigma(-) absorption component to H-alpha. This feature appears at just those phases when the accretion pole region is mostly directly visible and most nearly face-on to the observer.Comment: 16 pages, 1 table, 17 figures. To appear in the Astronomical Journa

Screening adult patients with a tracheostomy tube for dysphagia: a mixed-methods study of practice in the UK

Background: Patients with tracheostomy tubes are at risk of aspiration and swallowing problems (dysphagia) and because of their medical acuity, complications in this patient population can be severe. It is well recognised that swallow screening in stroke significantly reduces potential complications by allowing early identification and appropriate management of patients at risk (by health professionals), thereby reducing delays in commencing oral intake and preventing unnecessary, costly interventions by speech and language therapists (SLTs). However, there is no standardised swallow screen for the tracheostomised population and there is a paucity of literature regarding either current or best practice in this area. Aims: The aim of this study was therefore to investigate current United Kingdom (UK) practice for swallow (dysphagia) screening for adult patients with tracheostomy tubes and to explore and describe health professionals’ perceptions of their current practice/current systems used. Methods and Procedures: A mixed methods approach was adopted, comprising a semi-structured online questionnaire and recorded follow-up telephone interviews. Participants were SLTs, nurses and physiotherapists working with patients with tracheostomies. Responses were analysed to determine current practice with regard to swallow screening. Thematic analysis of interviews allowed further exploration and clarification of the questionnaire findings. Outcomes and Results: Two-hundred and twenty one questionnaires were completed. Approximately half (45%) of the participants worked in trusts with formal swallow screens, whilst the remainder used a variety of other approaches to identify patients at risk, often relying on informal links with multidisciplinary teams (MDT). In line with current evidence, patients with neurological diagnoses and a tracheostomy were consistently referred directly to speech and language therapy. Only a quarter of questionnaire participants thought their current system was effective at identifying patients at risk of swallowing problems. Eleven questionnaire participants were interviewed. They highlighted the important role of MDT team working here, emphasising both its strengths and weaknesses when working with these patients. Conclusions and Implications: Current practice in the UK for screening patients with a tracheostomy for swallow problems is varied and often sub-optimal. Despite the evidence base for enhancing outcomes, MDT working is still perceived as problematic. A swallow screening tool for use with this population, to enhance MDT working and ensuring that practice fits in line with current evidence, may improve patient safety and care

Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17

Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patient

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole

MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen