Gut Microbiome: Profound Implications For Diet And Disease

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease

Comparative, cross-sectional study of the format, content and timing of medication safety letters issued in Canada, the USA and the UK

Objectives To assess consistency in the format and content, and overlap of subject and timing, of medication safety letters issued by regulatory health authorities to healthcare providers in Canada, the USA and the UK. Design A cross-sectional study comparing medication safety letters issued for the purpose of alerting healthcare providers to newly identified medication problems associated with medications already on the market. Setting Online databases operated by Health Canada, the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency were searched to select medication safety letters issued between 1 January 2010 and 31 December 2014. Format, content and timing of each medication safety letter were assessed using an abstraction tool comprising 21 characteristics deemed relevant by consensus of the research team. Main outcome measures Main outcome measures included, first, characteristics (format and content) of medication safety letters and second, overlap of subject and release date across countries. Results Of 330 medication safety letters identified, 227 dealt with unique issues relating to medications available in all three countries. Of these 227 letters, 21 (9%) medication problems were the subject of letters released in all three countries; 40 (18%) in two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters issued in all three countries were released within 6 months of each other. Conclusions Significant discrepancies in both the subject and timing of medication safety letters issued by health authorities in three countries (Canada, the USA and the UK) where medical practice is otherwise comparable, raising questions about why, how and when medication problems are identified and communicated to healthcare providers by the authorities. More rapid communication of medication problems and better alignment between authorities could enhance patient safety

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Deep Carbon in Earth: Early Career Scientist Contributions to the Deep Carbon Observatory

Since its inception, the Deep Carbon Observatory (DCO) has coalesced a multidisciplinary and international group of researchers focused on understanding and quantifying Earth’s deep carbon budget. Carbon is the fourth most abundant element in the universe, and understanding carbon chemistry under a variety of environmental conditions impacts all aspects of planetary sciences, including planet formation, the form and function of planetary interiors, and the origin and diversity of life. DCO recognizes that is integrating and promoting the contributions of early career scientists are integral to the advancement of knowledge regarding the quantities, movements, origins, and forms of Earth’s deep carbon through field, experimental, analytical, and computational research. Early career scientists represent the future of deep carbon science and contribute substantially to ongoing research by implementing innovative ideas, challenging traditional working schemes, and bringing a globally interconnected perspective to the scientific community. This research topic highlights the contributions at the forefront of deep carbon research by DCO Early Career Scientist community. The manuscripts of this Frontiers e-volume bear evidence of the rapid advances in deep carbon science, and highlights the importance of approaching this field from a plethora of different angles integrating disciplines as diverse as mineralogy, geochemistry and microbiology. This integration is fundamental in understanding the movements and transformations of carbon across its deep cycle

Deep carbon in earth: Early career scientist contributions to the deep carbon observatory

Since its inception, the Deep Carbon Observatory (DCO) has coalesced a multidisciplinary and international group of researchers focused on understanding and quantifying Earth’s deep carbon budget. Carbon is the fourth most abundant element in the universe, and understanding carbon chemistry under a variety of environmental conditions impacts all aspects of planetary sciences, including planet formation, the form and function of planetary interiors, and the origin and diversity of life. DCO recognizes that is integrating and promoting the contributions of early career scientists are integral to the advancement of knowledge regarding the quantities, movements, origins, and forms of Earth’s deep carbon through field, experimental, analytical, and computational research. Early career scientists represent the future of deep carbon science and contribute substantially to ongoing research by implementing innovative ideas, challenging traditional working schemes, and bringing a globally interconnected perspective to the scientific community. This research topic highlights the contributions at the forefront of deep carbon research by DCO Early Career Scientist community. The manuscripts of this Frontiers e-volume bear evidence of the rapid advances in deep carbon science, and highlights the importance of approaching this field from a plethora of different angles integrating disciplines as diverse as mineralogy, geochemistry and microbiology. This integration is fundamental in understanding the movements and transformations of carbon across its deep cycle

The Chemoenzymatic Synthesis of Glycan-Terminated Oligo(Leu)x

Synthesis with papain for peptides with an N-terminal glucose group indicated a preference for the grafters with a longer linker between the glucose moiety and the Phe. Computational modeling was performed to investigate further, and here are all the files used to generate the models as well as the resulting models

DataSheet1_The chemoenzymatic synthesis of glycan-terminated oligo(Leu)x.docx

Introduction: Glycopeptides contain carbohydrate moieties (glycans) covalently attached to the side chain and/or terminal peptide units. Since glycans are present on cell surfaces, these constructs can potentially address a wide array of therapeutic functions. To overcome the deficiencies associated with current synthetic routes to glycopeptides, such as costly processes and toxic reagents, this work aimed to develop versatile environmentally friendly protease-catalyzed peptide synthesis routes to peptides decorated with a glycan at their N-terminus.Methods: “Grafters” were first synthesized that consist of a glycan conjugated directly, or through a spacer, to the amine group of L-Phe-ethyl ester (Phe-OEt). The role of Phe-OEt is to increase the conjugate’s recognition by the protease (papain) catalytic active site. A series of grafters were synthesized with variation of the glycan structure, linkage-chemistry, and presence of an oligo (ethylene glycol) “spacer” of varied length between the glycan and Phe-OEt moiety. High grafter efficiency will result by the successful acceptance of the grafter at the enzymes S1/S2 subsites, formation of an acyl enzyme complex and subsequent conversion to glycan-terminated oligo(Leu)x (x ≥ 1), as opposed to construction of non-glycan N-terminated oligo(Leu)x.Results and discussion: While glycan-Phe-OEt grafters without a spacer between the glycan and Phe-OEt resulted in low grafter efficiency (8.3% ± 2.0%), insertion of a short oligo (ethylene glycol) spacer between the glycan and Phe-OEt moieties (glycan-PEGn-Phe-OEt, n ≥ 3) increased the grafter efficiency by 3-fold–24.5% ± 1.8%. In addition, computational modeling was performed using Rosetta software provided insights on a molecular level of how grafter efficiency is influenced by the PEG spacer length.</p

Potentially inappropriate prescribing (PIP) in long-term care (LTC) patients: validation of the 2014 STOPP-START and 2012 Beers criteria in a LTC population--a protocol for a cross-sectional comparison of clinical and health administrative data.

INTRODUCTION: Potentially inappropriate prescribing (PIP) is frequent and problematic in older patients. Identifying PIP is necessary to improve prescribing quality; ideally, this should be performed at the population level. Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Beers criteria were developed to identify PIP in clinical settings and are useful at the individual patient level; however, they are time-consuming and costly to apply. Only a subset of these criteria is applicable to routinely collected population-level health administrative data (HAD) because the clinical information necessary to implement these tools is often missing from databases. The performance of subsets of STOPP/START and Beers criteria in HAD compared with clinical data from the same patients is unknown; furthermore, the performance of the updated 2014 STOPP-START and 2012 Beers criteria compared with one another is also unknown. METHODS AND ANALYSIS: A cross-sectional study of linked HAD and clinical data will be conducted to validate the subsets of STOPP/START and Beers criteria applicable to HAD by comparing their performance when applied to clinical and HAD for the same patients. Eligible patients will be 66 years and over and recently admitted to 1 of 6 long-term care facilities in Ottawa, Ontario. The target sample size is 275, but may be less if statistical significance can be achieved sooner. Medication, diagnostic and clinical data will be collected by a consultant pharmacist. The main outcome measure is the proportion of PIP missed by the subset of STOPP/START and Beers criteria applied to HAD when compared with clinical data. ETHICS AND DISSEMINATION: The study was approved by the Ottawa Health Services Network Research Ethics Board, the Bruyère Continuing Care Research Ethics Board and the ethics board of the City of Ottawa Long Term Care Homes. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders. TRIAL REGISTRATION NUMBER: NCT02523482.</p