Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

Background: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. Results: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor’s association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. Conclusion: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. Trial registration: Clinical trial registration number: ClinicalTrials.govNCT01776021

Draft Genome Sequences of Two Extensively Drug-Resistant Strains of Mycobacterium tuberculosis Belonging to the Euro-American S Lineage

We report the whole-genome sequencing of two extensively drug-resistant tuberculosis strains belonging to the Euro-American S lineage. The RSA 114 strain showed single-nucleotide polymorphisms predicted to have drug efflux activity

Estimating the Economic Value of Automated Virtual Reality Cognitive Therapy for Treating Agoraphobic Avoidance in Patients With Psychosis: Findings From the gameChange Randomized Controlled Clinical Trial

Background:An automated virtual reality cognitive therapy (gameChange) has demonstrated its effectiveness to treat agoraphobia in patients with psychosis, especially for high or severe anxious avoidance. Its economic value to the health care system is not yet established.Objective:In this study, we aimed to estimate the potential economic value of gameChange for the UK National Health Service (NHS) and establish the maximum cost-effective price per patient.Methods:Using data from a randomized controlled trial with 346 patients with psychosis (ISRCTN17308399), we estimated differences in health-related quality of life, health and social care costs, and wider societal costs for patients receiving virtual reality therapy in addition to treatment as usual compared with treatment as usual alone. The maximum cost-effective prices of gameChange were calculated based on UK cost-effectiveness thresholds. The sensitivity of the results to analytical assumptions was tested.Results:Patients allocated to gameChange reported higher quality-adjusted life years (0.008 QALYs, 95% CI –0.010 to 0.026) and lower NHS and social care costs (–£105, 95% CI –£1135 to £924) compared with treatment as usual (£1=US $1.28); however, these differences were not statistically significant. gameChange was estimated to be worth up to £341 per patient from an NHS and social care (NHS and personal social services) perspective or £1967 per patient from a wider societal perspective. In patients with high or severe anxious avoidance, maximum cost-effective prices rose to £877 and £3073 per patient from an NHS and personal social services perspective and societal perspective, respectively.Conclusions:gameChange is a promising, cost-effective intervention for the UK NHS and is particularly valuable for patients with high or severe anxious avoidance. This presents an opportunity to expand cost-effective psychological treatment coverage for a population with significant health needs.Trial Registration:ISRCTN Registry ISRCTN17308399; https://www.isrctn.com/ISRCTN1730839

Phylogenomic classification and the evolution of Clonal complex 5 methicillin-resistant Staphylococcus aureus in the Western Hemisphere

Clonal complex 5 methicillin-resistant Staphylococcus aureus (CC5-MRSA) includes multiple prevalent clones that cause hospital-associated infections in the Western Hemisphere. Here, we present a phylogenomic study of these MRSA to reveal their phylogeny, spatial and temporal population structure, and the evolution of selected traits. We studied 598 genome sequences, including 409 newly generated sequences, from 11 countries in Central, North, and South America, and references from Asia and Europe. An early-branching CC5-Basal clade is well-dispersed geographically, is methicillin-susceptible and MRSA predominantly of ST5-IV such as the USA800 clone, and includes separate subclades for avian and porcine strains. In the early 1970s and early 1960s, respectively, two clades appeared that subsequently underwent major expansions in the Western Hemisphere: a CC5-I clade in South America and a CC5-II clade largely in Central and North America. The CC5-I clade includes the ST5-I Chilean/Cordobes clone, and the ST228-I South German clone as an early offshoot, but is distinct from other ST5-I clones from Europe that nest within CC5-Basal. The CC5-II clade includes divergent strains of the ST5-II USA100 clone, various other clones, and most known vancomycin-resistant strains of S. aureus, but is distinct from ST5-II strain N315 from Japan that nests within CC5-Basal. The recombination rate of CC5 was much lower than has been reported for other S. aureus genetic backgrounds, which indicates that recurrence of vancomycin resistance in CC5 is not likely due to an enhanced promiscuity. An increased number of antibiotic resistances and decreased number of toxins with distance from the CC5 tree root were observed. Of note, the expansions of the CC5-I and CC5-II clades in the Western Hemisphere were preceded by convergent gains of resistance to fluoroquinolone, macrolide, and lincosamide antibiotics, and convergent losses of the staphylococcal enterotoxin p (sep) gene from the immune evasion gene cluster of phage ΦSa3. Unique losses of surface proteins were also noted for these two clades. In summary, our study has determined the relationships of different clades and clones of CC5 and has revealed genomic changes for increased antibiotic resistance and decreased virulence associated with the expansions of these MRSA in the Western Hemisphere.Fil: Challagundla, Lavanya. University of Mississippi; Estados UnidosFil: Reyes, Jinnethe. Universidad El Bosque; ColombiaFil: Rafiqullah, Iftekhar. University of Mississippi; Estados UnidosFil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Echaniz-Aviles, Gabriela. Instituto Nacional de Salud Pùblica; MéxicoFil: Velazquez-Meza, Maria E.. Instituto Nacional de Salud Pública; MéxicoFil: Castillo-Ramírez, Santiago. Universidad Nacional Autónoma de México; MéxicoFil: Fittipaldi, Nahuel. University of Toronto; Canadá. Public Health Ontario Laboratory; CanadáFil: Feldgarden, Michael. National Institutes of Health; Estados UnidosFil: Chapman, Sinéad B.. Broad Institute of MIT and Harvard; Estados UnidosFil: Calderwood, Michael S.. Dartmouth–Hitchcock Medical Center; Estados UnidosFil: Carvajal, Lina P.. Universidad El Bosque; ColombiaFil: Rincon, Sandra. Universidad El Bosque; ColombiaFil: Blake, Hanson. University of Texas; Estados UnidosFil: Planet, Paul J.. University of Pennsylvania; Estados UnidosFil: Arias, Cesar A.. Universidad El Bosque; Colombia. University of Texas; Estados UnidosFil: Diaz, Lorena. Universidad El Bosque; ColombiaFil: Robinson, D. Ashley. University of Mississippi; Estados Unido

Monitoring the EU protected Geomalacus maculosus (Kerry Slug): what are the factors affecting catch returns in open and forested habitats?

Geomalacus maculosus is a slug species protected under EU law with a distribution limited to the west of Ireland and north-west Iberia. The species, originally thought to be limited within Ireland to deciduous woodland and peatland, has been found in a number of commercial conifer plantations since 2010. While forest managers are now required to incorporate the protection of the species where it is present, no clear species monitoring protocols are currently available. This study examines the efficacy of De Sangosse refuge traps across three habitats frequently associated with commercial forest plantations in Ireland and compares them with hand searching, a commonly used method for slug monitoring. Catch data during different seasons and under different weather conditions are also presented. Results indicate that autumn is the optimal time for sampling G. maculosus but avoiding extremes of hot or cold weather. While refuge traps placed at 1.5 m on trees in mature conifer plantations and directly on exposed rock in blanket peatlands result in significantly greater catches, hand searching is the most successful approach for clear-fell areas. Hand searches in clear-fell preceded by rain are likely to result in greater numbers caught. The results of this study form, for the first time, the basis for G. maculosus monitoring guidelines for forestry managers. © 2016, The Ecological Society of Japa

Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology

Automated virtual reality (VR) cognitive therapy for patients with psychosis: study protocol for a single-blind parallel group randomised controlled trial (gameChange)

Introduction Many patients with psychosis experience everyday social situations as anxiety-provoking. The fears can arise, for example, from paranoia, hallucinations, social anxiety or negative-self beliefs. The fears lead patients to withdraw from activities, and this isolation leads to a cycle of worsening physical and mental health. Breaking this cycle requires highly active treatment directly in the troubling situations so that patients learn that they can safely and confidently enter them. However patients with psychosis seldom receive such life-changing interventions. To solve this problem we have developed an automated psychological treatment delivered in virtual reality (VR). It allows patients to experience computer simulations of the situations that they find anxiety-provoking. A virtual coach guides patients, using cognitive techniques, in how to overcome their fears. Patients are willing to enter VR simulations of anxiety-provoking situations because they know the simulations are not real, but the learning made transfers to the real world.Methods and analysis 432 patients with psychosis and anxious avoidance of social situations will be recruited from National Health Service (NHS) secondary care services. In the gameChange trial, they will be randomised (1:1) to the six-session VR cognitive treatment added to treatment as usual or treatment as usual alone. Assessments will be conducted at 0, 6 (post-treatment) and 26 weeks by a researcher blind to allocation. The primary outcome is avoidance and distress in real-life situations, using a behavioural assessment task, at 6 weeks. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention-to-treat. Moderation and mediation will be tested. An economic evaluation will be conducted.Ethics and dissemination The trial has received ethical approval from the NHS South Central - Oxford B Research Ethics Committee (19/SC/0075). A key output will be a high-quality automated VR treatment for patients to overcome anxious avoidance of social situations.Trial registration number ISRCTN17308399

Global Biobank Meta-analysis Initiative:Powering genetic discovery across human disease

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.</p

Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics

Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification