527 research outputs found

    Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

    Get PDF
    Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al

    How do we create, and improve, the evidence base? 

    Get PDF
    Providing best clinical care involves using the best available evidence of effectiveness to inform treatment decisions. Producing this evidence begins with trials and continues through synthesis of their findings towards evidence incorporation within comprehensible, usable guidelines, for clinicians and patients at the point of care. However, there is enormous wastage in this evidence production process, with less than 50% of the published biomedical literature considered sufficient in conduct and reporting to be fit for purpose. Over the last 30 years, independent collaborative initiatives have evolved to optimise the evidence to improve patient care. These collaborations each recommend how to improve research quality in a small way at many different stages of the evidence production and distillation process. When we consider these minimal improvements at each stage from an 'aggregation of marginal gains' perspective, the accumulation of small enhancements aggregates, thereby greatly improving the final product of 'best available evidence'. The myriad of tools to reduce research quality leakage and evidence loss should be routinely used by all those with responsibility for ensuring that research benefits patients, that is, those who pay for research (funders), produce it (researchers), take part in it (patients/participants) and use it (clinicians, policy makers and service commissioners)

    Coronary age as a risk factor in the modified Framingham risk score

    Get PDF
    BACKGROUND: Clinical guidelines emphasize risk assessment as vital to patient selection for medical primary intervention. However, risk assessment methods are restricted in their ability to predict further coronary events. The most widely accepted tool in the United States is the Framingham risk score. In these equations age is a powerful risk factor. Although the extent of coronary atherosclerosis increases with age, there is large inter-individual variability in the rate of development and progression of this disease. This fact limits the utility of Framingham scoring when applied to individuals. Electron beam tomography (EBT), which measures coronary calcium, provides a non-invasive method for assessing coronary plaque burden, thus offering the possibility of providing a more accurate estimate of an individual's "arterial age" than from chronological age alone. METHODS: In this paper we discuss a new and simple method for incorporating the coronary calcium score (CCS) to modify the Framingham Risk Assessment (FRA). Using this method, a coronary artery calcium (CAC) age equivalent is generated that replaces chronological age in Framingham scoring. RESULTS AND DISCUSSION: Using a percentile table of CCS scores by age group and sex, individuals are matched to the age group whose calcium score most closely approximates their own individual score. The original 10-year absolute risk score of a 65-year old man with a CCS of 6 based on chronological age is 10%, whereas the modified absolute risk score based on CAC age equivalents is 2%. CONCLUSION: Our approach of replacing chronological age with CAC age equivalents in the Framingham equations possesses simplicity of application combined with precision. Physicians can easily derive adjusted Framingham risk scores and prescribe intervention methods based on patients' ten-year risks. The adjusted ten-year risks are likely to be more accurate than unadjusted risks since they are based on coronary calcium score information. The modified FRA approach not only may increase the predicted risk for some patients, but also may decrease the predicted risk for others, making it a more precise adjustment than other methods

    Gender Differences in Carbohydrate Metabolism and Carbohydrate Loading

    Get PDF
    Prior to endurance competition, many endurance athletes participate in a carbohydrate loading regimen in order to help delay the onset of fatigue. The "classic" regimen generally includes an intense glycogen depleting training period of approximately two days followed by a glycogen loading period for 3–4 days, ingesting approximately 60–70% of total energy intake as carbohydrates, while the newer method does not consist of an intense glycogen depletion protocol. However, recent evidence has indicated that glycogen loading does not occur in the same manner for males and females, thus affecting performance. The scope of this literature review will include a brief description of the role of estradiol in relation to metabolism and gender differences seen in carbohydrate metabolism and loading

    “Excellence R Us”: university research and the fetishisation of excellence

    Get PDF
    The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship

    Detailed Mitochondrial Phenotyping by High Resolution Metabolomics

    Get PDF
    Mitochondrial phenotype is complex and difficult to define at the level of individual cell types. Newer metabolic profiling methods provide information on dozens of metabolic pathways from a relatively small sample. This pilot study used “top-down” metabolic profiling to determine the spectrum of metabolites present in liver mitochondria. High resolution mass spectral analyses and multivariate statistical tests provided global metabolic information about mitochondria and showed that liver mitochondria possess a significant phenotype based on gender and genotype. The data also show that mitochondria contain a large number of unidentified chemicals

    Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L

    Full text link
    [EN] Rhamnus ludovici-salvatoris, endemic to the Gymnesian Islands, coexists with the related and widespread R. alaternus in Mallorca and Menorca. In both species, the population genetic structure using RAPD, and flowering during a 3-year period to check for possible phenological barriers, were analyzed. Rhamnus ludovici-salvatoris showed lower genetic diversity and stronger population structure than R. alaternus, the Cabrera population being less diverse and the most differentiated. Rhamnus ludovici-salvatoris flowered one month later, although flowering of both species coincided sporadically. These congeners seem to have diverged through isolation by time and differentiation in habitat. The population genetic structure of R. ludovici-salvatoris could mainly be due to the existence of small populations on the one hand, and a gene flow caused by rare hybridization events on the other, which may also explain the presence of morphologically intermediate individuals in Menorca. The conservation of R. ludovici-salvatoris populations may include population reinforcements and other in situ interventions.Ferriol Molina, M.; Llorens García, L.; Gil, L.; Boira Tortajada, H. (2009). Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L. Plant Systematics and Evolution. 277(1-2):105-116. doi:10.1007/s00606-008-0110-3S1051162771-2Affre L, Thompson JD, Debussche M (1997) Genetic structure of continental and island populations of the Mediterranean endemic Cyclamen balearicum (Primulaceae). Amer J Bot 84(4): 437–451BOIB (2005) Decreto 75/2005. BOIB 106: 29–32Bolmgren K, Oxelman B (2004) Generic limits in Rhamnus L. s.l. (Rhamnaceae) inferred from nuclear and chloroplast DNA sequence phylogenies. Taxon 53(2):383–390Bolòs O, Molinier R (1958) Recherches phytosociologiques dans l’île de Majorque. Collectanea Botanica 34:699–865Cardona MA (1979) Consideracions sobre l’endemisme i l’origen de la flora de las Illes Balears. Butlletí del Institut Catalá de Historia Natural 44 (Sec. Bot. 3):7–15Cardona MA, Contandriopoulos J (1979) Endemism and evolution in the islands of the Western Mediterranean. In: Bramwell D (ed) Plants and islands. Academic Press, London, pp 133–169Chodat L (1924) Contributions à la Géo-Botanique de Majorque. PhD Thesis, Université de Genève—Institut de Botanique, SwitzerlandCollins D, Mill RR, Moller M (2003) Species separation of Taxus baccata, T. canadensis, and T. cuspidata (Taxaceae) and origins of their reputed hybrids inferred from RAPD and cpDNA data. Amer J Bot 90(2):175–182Cronk QCB (1997) Islands: stability, diversity, conservation. Biodivers Conserv 6(3):477–493Doyle JJ, Doyle JL (1990) Isolation of plant DNA from fresh tissue. Focus 12:13–15Ducarme V, Wesselingh RA (2005) Detecting hybridization in mixed populations of Rhinanthus minor and Rhinanthus angustifolius. Folia Geobot 40(2/3):151–161Englishloeb GM, Karban R (1992) Consequences of variation in flowering phenology for seed head herbivory and reproductive success in Erigeron glaucus (Compositae). Oecologia 89:588–595Gautier F, Caluzon G, Suk JP, Violanti D (1994) Age et durée de la crise de salinité Messinienne. Comptes Rendus de l’Académie des Sciences de Paris 318:1103–1109Gerard PR, Fernandez-Manjarres JF, Frascaria-Lacoste N (2006) Temporal cline in a hybrid zone population between Fraxinus excelsior L. and Fraxinus angustifolia Vahl. Molec Ecol 15:3655–3667Gil L, Llorens L, Tébar FJ, Costa M (1995) La vegetación de la isla de Cabrera. In: Guía de la excursión geobotánica de las XV Jornadas de Fitosociología. Datos sobre la vegetación de Cabrera. Palma de Mallorca: Universitat de les Illes Balears, pp 51–77Gulías J, Flexas J, Abadía A, Medrano H (2002) Photosynthetic responses to water deficit in six Mediterranean sclerophyll species: possible factors explaining the declining distribution of Rhamnus ludovici-salvatoris, and endemic Balearic species. Tree Physiol 22:687–697Gulías J, Traveset A, Riera N, Mus M (2004) Critical stages in the recruitment process of Rhamnus alaternus L. Ann Bot 93:723–731Gustafsson S, Sjögren-Gulve P (2002) Genetic diversity in the rare orchid, Gymnadenia odoratissima and a comparison with the more common congener, G. conopsea. Conserv Genet 3:225–234Gustafsson S (2003) Population genetic analyses in the orchid genus Gymnadenia—a conservation genetic perspective. PhD Thesis, Uppsala University, SwedenGustafsson S, Lönn M (2003) Genetic differentiation and habitat preference of flowering-time variants within Gymnadenia conopsea. Heredity 91:284–292Harris W (1996) Genecological aspects of flowering patterns of populations of Kunzea ericoides and K. sinclairii (Myrtaceae). New Zealand J Bot 34:333–354Hendry AP, Dray T (2005) Population structure attributable to reproductive time: isolation by time and adaptation by time. Molec Ecol 14:901–916Hosokawa K, Minami M, Kawahara K, Nakamura I, Shibata T (2000) Discrimination among three species of medicinal Scutellaria plants using RAPD markers. Pl Med 66:270–272Huang Z, Liu L, Zhou T, Ju B (2005) Effects of environmental factors on the population genetic structure in chukar partridge (Alectoris chukar). J Arid Environ 62:427–434Juan A, Crespo MB, Cowan RS, Lexer C, Fay F (2004) Patterns of variability and gene flow in Medicago citrina, an endangered endemic of islands in the western Mediterranean, as revealed by amplified fragment length polymorphism (AFLP). Molec Ecol 13:2679–2690Krijgsman W, Hilgen FJ, Raffi I, Sierro FJ, Wilson DS (1999) Chronology, causes and progression of the Messinian salinity crisis. Nature 400:652–655Lamont BB, He T, Enright NJ, Krauss SL, Miller BP (2003) Anthropogenic disturbance promotes hybridization between Banksia species by altering their biology. J Evol Biol 16:551–557Lennartsson T (1997) Seasonal differentiation—a conservative reproductive barrier in two grassland Gentianella (Gentianaceae) species. Pl Syst Evol 208:45–69Martinez-Solis I, Iranzo J, Estrelles E, Ibars AM (1993) Leaf domatia in the section Alaternus (Miller) DC. of the genus Rhamnus (Rhamnaceae). Bot J Linn Soc 112:311–318McIntosh ME (2002) Flowering phenology and reproductive output in two sister species of Ferocactus (Cactaceae). Pl Ecol 159:1–13Nei M (1973) Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci USA 70:3321–3323Nei M (1978) Estimation of average heterozigosity and genetic distance from a small number of individuals. Genetics 89:583–590Nei M, Li W (1979) Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci USA 79:5269–5273Nybom H, Bartish IV (2000) Effects of life history traits and sampling strategies on genetic diversity estimates obtained with RAPD markers in plants. Perspect Pl Ecol Evol Syst 3(2):93–114Oostermeijer JGB, Luijten SH, Ellis-Adam AC, den Nijs JCM (2002) Future prospects for the rare, late-flowering Gentianella germanica and Gentianopsis ciliata in Dutch nutrient-poor calcareous grasslands. Biol Conserv 104:339–350Pease CM, Lande R, Bull JJ (1989) A model of population growth, dispersal and evolution in a changing environment. Ecology 70(6):1657–1664Perron M, Gordon AG, Bousquet J (1995) Species-specific RAPD fingerprints for the closely related Picea mariana and P. rubens. Theor Appl Genet 91:142–149Pierce S, Ceriani RM, Villa M, Cerabolini B (2006) Quantifying relative extinction risks and targeting intervention for the orchid flora of a natural park in the European prealps. Conserv Biol 20(6):1804–1810Richardson JE, Fay MF, Cronk QCB, Bowman D, Chase MW (2000) A phylogenetic analysis of Rhamnaceae using rbcL and trnL-F plastid DNA sequences. Amer J Bot 87(9):1309–1324Roselló JA, Sáez L (2000) Index Balearicum: an annotated check-list of the vascular plants described from the Balearic Islands. Collect Bot 25(1):3–203Roselló JA, Cebrián MC, Mayol M (2002) Testing taxonomic and biogeographical relationships in a narrow mediterranean endemic complex (Hippocrepis balearica) using RAPD markers. Ann Bot 89:321–327Sales E, Nebauer SG, Mus M, Segura J (2001) Population genetic study in the Balearic plant species Digitalis minor (Scrophulariaceae) using RAPD markers. Amer J Bot 88(10):1750–1759Sherwin WB, Moritz C (2000) Managing and monitoring genetic erosion. In: Young AG, Clarke GM (eds) Genetics, demography and viability of fragmented populations. Cambridge University Press, Cambridge, pp 9–34Sneath PHA, Sokal RR (1973) Numerical taxonomy. Freeman and Co., San FranciscoTraveset A, Gulías J, Riera N, Mus M (2003) Transition probabilities from pollination to establishment in a rare dioecious shrub species (Rhamnus ludovici-salvatoris) in two habitats. J Ecol 91:427–437Tutin TG, Heywood VH, Burges NA, Valentine DH, Walters SM, Webb DA (eds) (2001) Flora Europaea, vol 2. Rosaceae to Umbelliferae. Cambridge University Press, CambridgeWright S (1931) Evolution in Mendelian populations. Genetics 16:97–159Zimmerman M (1980a) Reproduction in Polemonium: pre-dispersal seed predation. Ecology 61:502–506Zimmerman M (1980b) Reproduction in Polemonium: competition for pollinators. Ecology 61:497–50

    The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients

    Get PDF
    BACKGROUND: Among older cancer patients, there is uncertainty about the degree to which venous thromboembolism (VTE) and its treatment increase the risk of death or major hemorrhage. OBJECTIVE: To determine the prevalence of VTE in a cohort of older cancer patients, as well as the degree to which VTE increased the risk of death or major hemorrhage. METHODS: We conducted a retrospective cohort study of linked Surveillance, Epidemiology, and End Results cancer registry and Medicare administrative claims data. Patients with any of ten invasive cancers diagnosed during 1995 through 1999 were included; the independent variable was VTE diagnosed concomitantly with cancer diagnosis. Outcomes included major hemorrhage during the first year after cancer diagnosis and all-cause mortality; RESULTS: Overall, about 1% of patients who were diagnosed with cancer also had a VTE diagnosed concomitantly. After adjusting for sociodemographic factors and cancer stage and grade, concomitant VTE was associated with a relative increase in the risk of death for 8 of the 10 cancer types; the increase in risk tended to range 20–40% across most cancer types. Approximately 16.8% (95% confidence interval [CI] 14.9–18.8%) of patients with a concomitant VTE and 7.9% (95% CI 7.7–8.0%) of patients without a VTE experienced a major hemorrhage during the year after cancer diagnosis (P value <.001). The excess risk of hemorrhage associated with VTE varied substantially across cancer types, ranging from no significant excess (kidney and uterine cancer) to 11.5% (lymphoma). CONCLUSION: Concomitant VTE is not only a marker and potential mediator of increased risk of death among older cancer patients, but patients with a VTE have a marked increased risk of major hemorrhage
    corecore