9,432 research outputs found

    Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data

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    Lista completa dos Autores: Holmes MV, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, Prieto-Merino D, Dehghan A, Trompet S, Wong A, Cavadino A, Drogan D, Padmanabhan S, Li S, Yesupriya A, Leusink M, Sundstrom J, Hubacek JA, Pikhart H, Swerdlow DI, Panayiotou AG, Borinskaya SA, Finan C, Shah S, Kuchenbaecker KB, Shah T, Engmann J, Folkersen L, Eriksson P, Ricceri F, Melander O, Sacerdote C, Gamble DM, Rayaprolu S, Ross OA, McLachlan S, Vikhireva O, Sluijs I, Scott RA, Adamkova V, Flicker L, Bockxmeer FM, Power C, Marques-Vidal P, Meade T, Marmot MG, Ferro JM, Paulos-Pinheiro S, Humphries SE, Talmud PJ, Mateo Leach I, Verweij N, Linneberg A, Skaaby T, Doevendans PA, Cramer MJ, van der Harst P, Klungel OH, Dowling NF, Dominiczak AF, Kumari M, Nicolaides AN, Weikert C, Boeing H, Ebrahim S, Gaunt TR, Price JF, Lannfelt L, Peasey A, Kubinova R, Pajak A, Malyutina S, Voevoda MI, Tamosiunas A, Maitland-van der Zee AH, Norman PE, Hankey GJ, Bergmann MM, Hofman A, Franco OH, Cooper J, Palmen J, Spiering W, de Jong PA, Kuh D, Hardy R, Uitterlinden AG, Ikram MA, Ford I, Hyppönen E, Almeida OP, Wareham NJ, Khaw KT, Hamsten A, Husemoen LL, Tjønneland A, Tolstrup JS, Rimm E, Beulens JW, Verschuren WM, Onland-Moret NC, Hofker MH, Wannamethee SG, Whincup PH, Morris R, Vicente AM, Watkins H, Farrall M, Jukema JW, Meschia J, Cupples LA, Sharp SJ, Fornage M, Kooperberg C, LaCroix AZ, Dai JY, Lanktree MB, Siscovick DS, Jorgenson E, Spring B, Coresh J, Li YR, Buxbaum SG, Schreiner PJ, Ellison RC, Tsai MY, Patel SR, Redline S, Johnson AD, Hoogeveen RC, Hakonarson H, Rotter JI, Boerwinkle E, de Bakker PI, Kivimaki M, Asselbergs FW, Sattar N, Lawlor DA, Whittaker J, Davey Smith G, Mukamal K, Psaty BM, Wilson JG, Lange LA, Hamidovic A, Hingorani AD, Nordestgaard BG, Bobak M, Leon DA, Langenberg C, Palmer TM, Reiner AP, Keating BJ, Dudbridge F, Casas JP; InterAct Consortium.To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies

    Impact of introducing electronic acute kidney injury alerts in primary care

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    Background: Acute kidney injury (AKI) is associated with decreased survival, future risk of chronic kidney disease and longer hospital stays. Electronic alerts (e-alerts) for AKI have been introduced in the UK in order to facilitate earlier detection and improve management. The aim of this study was to establish if e-alerts in primary care were acted on by examining timing of repeat creatinine testing.Methods: The National Health Service England Acute Kidney Injury electronic alert algorithm was introduced in April 2015 across both primary and secondary care in NHS Tayside accompanied by a programme of education. Data from a 12-month period (2012) predating introduction of the e-alerts were compared with a 12-month period following implementation of ealerts for AKI. Biochemistry testing following the AKI episode, timing of repeat tests and numbers of patients hospitalized within 7 days of episode were compared between the two time periods.Results: During the 12 months after e-alert introduction, 9781 AKI e-alerts were generated. Of these, 1460 (14.9%) alerts were generated in primary care. Median duration to repeat blood testing for these primary care alerts was 5 days for AKI Stage 1 [interquartile range (IQR) 2-10], 2 days for Stage 2 (IQR 1-5) and 1 day (IQR 0-2) for Stage 3. During 2012 (prior to e-alert implementation) 8812 AKI episodes were identified. Of these, 2650 tests (30.1%) were requested by primary care staff. Median duration to repeat creatinine testing was longer: 55 days (IQR 20-142) for Stage 1, 38 days (IQR 15-128) for Stage 2 was and 53 days (IQR 20-137) for Stage 3. More patients had biochemistry tests repeated within 7 days of AKI onset, pre-alert implementation; 252 (9.5%) versus 857 (58.7%) (P&lt;0.001). Rates of hospitalization within 7 days of AKI increased from 342 (12.9%) pre-implementation to 372 (25.5%) post-implementation (P&lt;0.001).Conclusions: Within primary care, e-alert implementation was associated with higher rates of creatinine monitoring, but also higher rates of hospitalization.</p

    Role of human milk oligosaccharides in Group B Streptococcus colonisation.

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    Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBS disease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protect against GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed to investigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabs were collected at delivery, as well as colostrum/breast milk, infant nasopharyngeal and rectal swabs at birth, 6 days and days 60-89 postpartum from 183 Gambian mother/infant pairs. GBS colonisation and serotypes were determined using culture and PCR. (1)H nuclear magnetic resonance spectroscopy was used to characterise the mother's Lewis status and HMO profile in breast milk. Mothers who were Lewis-positive were significantly less likely to be colonised by GBS (X (2)=12.50, P<0.001). Infants of Lewis-positive mothers were less likely GBS colonised at birth (X (2)=4.88 P=0.03) and more likely to clear colonisation between birth and days 60-89 than infants born to Lewis-negative women (P=0.05). There was no association between Secretor status and GBS colonisation. In vitro work revealed that lacto-N-difucohexaose I (LNDFHI) correlated with a reduction in the growth of GBS. Our results suggest that HMO such as LNDFHI may be a useful adjunct in reducing maternal and infant colonisation and hence invasive GBS disease. Secretor status offers utility as a stratification variable in GBS clinical trials

    Amblyopia and quality of life: a systematic review

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    Background/Aims Amblyopia is a common condition which can affect up to 5% of the general population. The health-related quality of life (HRQoL) implications of amblyopia and/or its treatment have been explored in the literature. Methods A systematic literature search was undertaken (16th-30th January 2007) to identify the HRQoL implications of amblyopia and/or its treatment. Results A total of 25 papers were included in the literature review. The HRQoL implications of amblyopia related specifically to amblyopia treatment, rather than the condition itself. These included the impact upon family life; social interactions; difficulties undertaking daily activities; and feelings and behaviour. The identified studies adopted a number of methodologies. The study populations included; children with the condition; parents of children with amblyopia; and adults who had undertaken amblyopia treatment as a child. Some studies developed their own measures of HRQoL, and others determined HRQoL through proxy measures. Conclusions The reported findings of the HRQoL implications are of importance when considering the management of cases of amblyopia. Further research is required to assess the immediate and long-term effects of amblyopia and/or its treatment upon HRQoL using a more standardised approach

    ‘Framing the project’ of international human rights law: Reflections on the dysfunctional ‘family’ of the Universal Declaration

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    Full text embargoed until November 2013.The task of ‘framing the project’ of international human rights law is daunting to say the least. First, there is the sheer enormity and complexity of the international human rights law ‘project’: adequately mapping the subject and its key related issues is impossible in a whole book, let alone a short chapter. Secondly, it is daunting because of the sense of epistemic responsibility involved. Every framing inevitably involves selection – if not pre-selection – through the conscious (and/or unconscious) placing of focus upon features or factors considered to be significant and/or valuable. As Gitlin puts it, framing is a way of choosing, underlining and presenting ‘what exists, what happens and what matters’. In this sense, the founding document (or as Entman might put it, the inaugural ‘communicating text’) of international human rights law (the Universal Declaration of Human Rights, UDHR) functions as a particularly potent form of framing, for it selects aspects of perceived reality, making them not just salient but symbolically central to the entire philosophical, moral, juridical order designated by the term ‘international human rights law’

    Effects of gestational age at birth on cognitive performance : a function of cognitive workload demands

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    Objective: Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth. Methods: Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n = 1326 children (gestation range: 23–41 weeks) were assessed with the K-ABC and a Mathematics Test. Results: Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA2 (quadratic term) on low cognitive workload: R2 = .02, p<0.001; moderate cognitive workload: R2 = .09, p<0.001; and high cognitive workload tasks: R2 = .14, p<0.001. Specifically, disproportionally lower scores were found for very (<32 weeks gestation) and moderately (32–33 weeks gestation) preterm children the higher the cognitive workload of the tasks. Early biological factors such as gestation and neonatal complications explained more of the variance in high (12.5%) compared with moderate (8.1%) and low cognitive workload tasks (1.7%). Conclusions: The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth

    Targeting AMPK signaling in combating ovarian cancers: opportunities and challenges

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    The development and strategic application of effective anticancer therapies have turned out to be one of the most critical approaches of managing human cancers. Nevertheless, drug resistance is the major obstacle for clinical management of these diseases especially ovarian cancer. In the past years, substantial studies have been carried out with the aim of exploring alternative therapeutic approaches to enhance efficacy of current chemotherapeutic regimes and reduce the side effects caused in order to produce significant advantages in overall survival and to improve patients' quality of life. Targeting cancer cell metabolism by the application of AMP-activated protein kinase (AMPK)-activating agents is believed to be one of the most plausible attempts. AMPK activators such as 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside, A23187, metformin, and bitter melon extract not only prevent cancer progression and metastasis but can also be applied as a supplement to enhance the efficacy of cisplatin-based chemotherapy in human cancers such as ovarian cancer. However, because of the undesirable outcomes along with the frequent toxic side effects of most pharmaceutical AMPK activators that have been utilized in clinical trials, attentions of current studies have been aimed at the identification of replaceable reagents from nutraceuticals or traditional medicines. However, the underlying molecular mechanisms of many nutraceuticals in anticancer still remain obscure. Therefore, better understanding of the functional characterization and regulatory mechanism of natural AMPK activators would help pharmaceutical development in opening an area to intervene ovarian cancer and other human cancers.postprin
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