Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations

Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

<p>Abstract</p> <p>Background</p> <p>The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters.</p> <p>Methods</p> <p>For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD.</p> <p>Results</p> <p>Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity criteria were reported in French or English. Overall, the mean number of items on the modified version of STARD was 12.4 (range: 2 to 18).</p> <p>Conclusion</p> <p>This systematic review provides a critical appraisal and repository of instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. More research is needed to pursue the validation of the existing instruments and the development of patient versions. This will help researchers capture the complexity of the decision-making process within specific clinical encounters.</p

Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

<p>Abstract</p> <p>Background</p> <p>Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for <it>Clostridium difficile </it>infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use.</p> <p>Methods</p> <p>We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy.</p> <p>Results</p> <p>Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens).</p> <p>Conclusions</p> <p>In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could significantly reduce overuse of fluoroquinolones.</p

Expression of auxin-binding protein1 during plum fruit ontogeny supports the potential role of auxin in initiating and enhancing climacteric ripening

Auxin-binding protein1 (ABP1) is an active element involved in auxin signaling and plays critical roles in auxin-mediated plant development. Here, we report the isolation and characterization of a putative sequence from Prunus salicina L., designated PslABP1. The expected protein exhibits a similar molecular structure to that of well-characterized maize-ABP1; however, PslABP1 displays more sequence polarity in the active-binding site due to substitution of some crucial amino-acid residues predicted to be involved in auxin-binding. Further, PslABP1 expression was assessed throughout fruit ontogeny to determine its role in fruit development. Comparing the expression data with the physiological aspects that characterize fruit-development stages indicates that PslABP1 up-regulation is usually associated with the signature events that are triggered in an auxin-dependent manner such as floral induction, fruit initiation, embryogenesis, and cell division and elongation. However, the diversity in PslABP1 expression profile during the ripening process of early and late plum cultivars seems to be due to the variability of endogenous auxin levels among the two cultivars, which consequently can change the levels of autocatalytic ethylene available for the fruit to co-ordinate ripening. The effect of auxin on stimulating ethylene production and in regulating PslABP1 was investigated. Our data suggest that auxin is involved in the transition of the mature green fruit into the ripening phase and in enhancing the ripening process in both auxin- and ethylene-dependent manners thereafter

Implementing shared decision-making in nutrition clinical practice: A theory-based approach and feasibility study

<p>Abstract</p> <p>Background</p> <p>There are a growing number of dietary treatment options to choose from for the management of many chronic diseases. Shared decision making represents a promising approach to improve the quality of the decision making process needed for dietary choices that are informed by the best evidence and value-based. However, there are no studies reporting on theory-based approaches that foster the implementation of shared decision making in health professions allied to medicine. The objectives of this study are to explore the integration of shared decision making within real nutritional consultations, and to design questionnaires to assess dieticians' intention to adopt two specific behaviors related to shared decision making using the Theory of Planned Behavior.</p> <p>Methods</p> <p>Forty dieticians will audiotape one clinical encounter to explore the presence of shared decision making within the consultation. They will also participate to one of five to six focus groups that aim to identify the salient beliefs underlying the determinants of their intention to present evidence-based dietary treatment options to their patients, and clarify the values related to dietary choices that are important to their patients. These salient beliefs will be used to elaborate the items of two questionnaires. The internal consistency of theoretical constructs and the temporal stability of their measurement will be checked using the test-retest method by asking 35 dieticians to complete the questionnaire twice within a two-week interval.</p> <p>Discussion</p> <p>The proposed research project will be the first study to: provide preliminary data about the adoption of shared decision making by dieticians and theirs patients; elicit dieticians' salient beliefs regarding the intention to adopt shared decision making behaviors, report on the development of a specific questionnaire; explore dieticians' views on the implementation of shared decision making; and compare their views regarding the implementation of shared decision making in different clinical settings.</p> <p>It is anticipated that the results generated by the proposed research project will significantly contribute to the emergence of shared decision making in nutrition through a theory-based approach.</p

Breast cancer risk and drinking water contaminated by wastewater: a case control study

BACKGROUND: Drinking water contaminated by wastewater is a potential source of exposure to mammary carcinogens and endocrine disrupting compounds from commercial products and excreted natural and pharmaceutical hormones. These contaminants are hypothesized to increase breast cancer risk. Cape Cod, Massachusetts, has a history of wastewater contamination in many, but not all, of its public water supplies; and the region has a history of higher breast cancer incidence that is unexplained by the population's age, in-migration, mammography use, or established breast cancer risk factors. We conducted a case-control study to investigate whether exposure to drinking water contaminated by wastewater increases the risk of breast cancer. METHODS: Participants were 824 Cape Cod women diagnosed with breast cancer in 1988–1995 and 745 controls who lived in homes served by public drinking water supplies and never lived in a home served by a Cape Cod private well. We assessed each woman's exposure yearly since 1972 at each of her Cape Cod addresses, using nitrate nitrogen (nitrate-N) levels measured in public wells and pumping volumes for the wells. Nitrate-N is an established wastewater indicator in the region. As an alternative drinking water quality indicator, we calculated the fraction of recharge zones in residential, commercial, and pesticide land use areas. RESULTS: After controlling for established breast cancer risk factors, mammography, and length of residence on Cape Cod, results showed no consistent association between breast cancer and average annual nitrate-N (OR = 1.8; 95% CI 0.6 – 5.0 for ≥ 1.2 vs. < .3 mg/L), the sum of annual nitrate-N concentrations (OR = 0.9; 95% CI 0.6 – 1.5 for ≥ 10 vs. 1 to < 10 mg/L), or the number of years exposed to nitrate-N over 1 mg/L (OR = 0.9; 95% CI 0.5 – 1.5 for ≥ 8 vs. 0 years). Variation in exposure levels was limited, with 99% of women receiving some of their water from supplies with nitrate-N levels in excess of background. The total fraction of residential, commercial, and pesticide use land in recharge zones of public supply wells was associated with a small statistically unstable higher breast cancer incidence (OR = 1.4; 95% CI 0.8–2.4 for highest compared with lowest land use), but risk did not increase for increasing land use fractions. CONCLUSION: Results did not provide evidence of an association between breast cancer and drinking water contaminated by wastewater. The computer mapping methods used in this study to link routine measurements required by the Safe Drinking Water Act with interview data can enhance individual-level epidemiologic studies of multiple health outcomes, including diseases with substantial latency

Population-Specific Responses to Interspecific Competition in the Gut Microbiota of Two Atlantic Salmon (Salmo salar) Populations

The gut microbial community in vertebrates plays a role in nutrient digestion and absorption, development of intestine and immune systems, resistance to infection, regulation of bone mass and even host behavior and can thus impact host fitness. Atlantic salmon (Salmo salar) reintroduction efforts into Lake Ontario, Canada, have been unsuccessful, likely due to competition with non-native salmonids. In this study, we explored interspecific competition effects on the gut microbiota of two Atlantic salmon populations (LaHave and Sebago) resulting from four non-native salmonids. After 10 months of rearing in semi-natural stream tanks under six interspecific competition treatments, we characterized the gut microbiota of 178 Atlantic salmon by parallel sequencing the 16S rRNA gene. We found 3978 bacterial OTUs across all samples. Microbiota alpha diversity and abundance of 27 OTUs significantly differed between the two populations. Interspecific competition reduced relative abundance of potential beneficial bacteria (six genera of lactic acid bacteria) as well as 13 OTUs, but only in the LaHave population, indicating population-specific competition effects. The pattern of gut microbiota response to interspecific competition may reflect local adaptation of the host-microbiota interactions and can be used to select candidate populations for improved species reintroduction success

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

MAPPIN'SDM – The Multifocal Approach to Sharing in Shared Decision Making

BACKGROUND: The wide scale permeation of health care by the shared decision making concept (SDM) reflects its relevance and advanced stage of development. An increasing number of studies evaluating the efficacy of SDM use instruments based on various sub-constructs administered from different viewpoints. However, as the concept has never been captured in operable core definition it is quite difficult to link these parts of evidence. This study aims at investigating interrelations of SDM indicators administered from different perspectives. METHOD: A comprehensive inventory was developed mapping judgements from different perspectives (observer, doctor, patient) and constructs (behavior, perception) referring to three units (doctor, patient, doctor-patient-dyad) and an identical set of SDM-indicators. The inventory adopted the existing approaches, but added additional observer foci (patient and doctor-patient-dyad) and relevant indicators hitherto neglected by existing instruments. The complete inventory comprising a doctor-patient-questionnaire and an observer-instrument was applied to 40 decision consultations from 10 physicians from different medical fields. Convergent validities were calculated on the basis of Pearson correlation coefficients. RESULTS: Reliabilities for all scales were high to excellent. No correlations were found between observer and patients or physicians neither for means nor for single items. Judgements of doctors and patients were moderately related. Correlations between the observer scales and within the subjective perspectives were high. Inter-perspective agreement was not related to SDM performance or patient activity. CONCLUSION: The study demonstrates the contribution to involvement made by each of the relevant perspectives and emphasizes the need for an inter-subjective approach regarding SDM measurement