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1.
Clin Transl Sci ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664778

RESUMO

Zanamivir is a potent and highly selective inhibitor of influenza neuraminidase in which the inhibition of this enzyme prevents the virus from infecting other cells and specifically prevents release of the new virion from the host cell membrane. It is available as an oral powder for inhalation and intravenous formulations. The current population pharmacokinetic model based on data from eight studies of subjects treated with the intravenous formulation (125 healthy adults and 533 hospitalized adult and pediatric subjects with suspected or confirmed influenza) suggested a decreased zanamivir clearance in pediatric and renal impairment adult subjects. It also indicates that b.i.d. dosing is necessary to keep the exposure in influenza infected subjects above the 90% inhibitory concentration values of recently circulating viruses over the dosing interval. In the exposure-response analysis (phases II and III studies), no apparent relationship was found between zanamivir exposure and clinically relevant pharmacodynamic end points.

2.
J Environ Qual ; 48(2): 362-375, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30951130

RESUMO

Integrated buffer zones (IBZs) have recently been introduced in the Northwestern Europe temperate zone to improve delivery of ecosystem services compared with the services associated with long-established vegetated buffer zones. A common feature of all the studied IBZ sites is that tile drainage, which previously discharged directly into the streams, is now intercepted within the IBZ. Specifically, the design of IBZs combines a pond, where soil particles present in drain water or surface runoff can be deposited, and a planted subsurface flow infiltration zone. Together, these two components should provide an optimum environment for microbial processes and plant uptake of nutrients. Nutrient reduction capacities, biodiversity enhancement, and biomass production functions were assessed with different emphasis across 11 IBZ sites located in Denmark, Great Britain, and Sweden. Despite the small size of the buffer zones (250-800 m) and thus the small proportion of the drained catchment (mostly <1%), these studies cumulatively suggest that IBZs are effective enhancements to traditional buffer zones, as they (i) reduce total N and P loads to small streams and rivers, (ii) act as valuable improved habitats for aquatic and amphibian species, and (iii) offer economic benefits by producing fast-growing wetland plant biomass. Based on our assessment of the pilot sites, guidance is provided on the implementation and management of IBZs within agricultural landscapes.


Assuntos
Biodegradação Ambiental , Conservação dos Recursos Naturais , Monitoramento Ambiental , Poluição Difusa/prevenção & controle , Agricultura , Biomassa , Ecossistema , Europa (Continente) , Fósforo/análise , Plantas , Rios , Solo , Suécia , Movimentos da Água , Áreas Alagadas
3.
Artigo em Inglês | MEDLINE | ID: mdl-30941899

RESUMO

REASON FOR THE STUDY: To standardize the use of flow cytometry for classifying hematological malignancies and make the results reliable and reproducible across laboratories, the EuroFlow™ Consortium published a comprehensive specification of antibody-fluorochrome conjugates, standard protocols, and algorithms for analysis. The BD OneFlow™ system builds on, and further standardizes, the EuroFlow protocols. We aimed to assess the effects on safety, efficiency, and costs for laboratories of adopting the BD OneFlow reagent tubes (LST and B-CLPD T1) for diagnosing chronic lymphocytic leukemia. METHODS: We compared in-house laboratory processes and results with those using the LST and B-CLPD T1 reagent tubes with, and without, blood film morphology. Outcome measures included concordance in classification results, and efficiency within the laboratory, that is, resource usage, staff time, unwanted events, and cost-consequences. RESULTS: There was 100% concordance between the classifications made with in-house flow cytometry and those with the BD OneFlow reagent tubes. Using BD OneFlow tubes required 13 hours less staff time per month (i.e. for 100 samples) than the in-house process. Sensitivity analyses explored the effects of uncertainties in the price of the BD OneFlow tubes and the prevalence of CLL and identified the thresholds at which laboratories might expect cost-savings from adopting the BD OneFlow system. Laboratory and clinical staff considered the BD OneFlow system to be safe and effective. CONCLUSIONS: Laboratories adopting the BD OneFlow system for classifying patients with suspected CLL can expect safe, efficient processes that can be cost saving if the discount on the list price, and prevalence of CLL (which will both vary between sites and countries), is within the thresholds suggested by the health economics sensitivity analysis. © 2019 International Clinical Cytometry Society.

5.
PLoS One ; 14(1): e0210587, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30695019

RESUMO

BACKGROUND: Women from ethnic minority groups are at greater risk of developing mental health problems. Poor perinatal mental health impacts on maternal morbidity and mortality and can have a devastating impact on child and family wellbeing. It is important to ensure that services are designed to meet the unique needs of women from diverse backgrounds. AIM: The aim of the review was to explore ethnic minority women's experiences of perinatal mental ill health, help-seeking and perinatal mental health services in Europe. DATA SOURCES: Searches included CINAHL, Maternity and Infant Care, MEDLINE and PsycINFO with no language or date restrictions. Additional literature was identified by searching reference lists of relevant studies. DESIGN: This was a mixed method systematic review. Study selection, appraisal and data extraction were conducted by two researchers independently. A convergent approach was adopted for the analysis and the data were synthesised thematically. RESULTS: The 15 eligible studies included women from a range of minority ethnic backgrounds and were all undertaken in the United Kingdom (UK). Seven overarching themes were identified; awareness and beliefs about mental health, isolation and seeking support, influence of culture, symptoms and coping strategies, accessing mental health services, experiences of mental health services and what women want. CONCLUSION: Lack of awareness about mental ill health, cultural expectations, ongoing stigma, culturally insensitive and fragmented health services and interactions with culturally incompetent and dismissive health providers all impact on ethnic minority women's ability to receive adequate perinatal mental health support in the UK. Future research should focus on in-depth exploration of the experiences of these women across multiple European settings and interventions to reduce health inequalities among vulnerable mothers and families affected by perinatal mental ill health.


Assuntos
Grupos Étnicos/psicologia , Serviços de Saúde Mental , Saúde Mental , Grupos Minoritários/psicologia , Assistência Perinatal , Adaptação Psicológica , Cultura , Europa (Continente) , Feminino , Acesso aos Serviços de Saúde , Humanos , Apoio Social
6.
Syst Rev ; 7(1): 188, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424823

RESUMO

BACKGROUND: Women want to give birth in a safe and supportive environment where they are free to move and adopt different positions. Moving freely and using different positions in labour results in a range of physical and psychological benefits for women. However, many women report that they are restricted from moving freely during labour and birth and it is important to understand the factors that are influencing this. METHODS: A mixed-methods systematic review will be undertaken. Qualitative, quantitative and mixed-methods primary empirical studies will be identified by systematically searching seven electronic databases using a search strategy that includes medical subject headings (MeSH) and keywords to cover synonyms and related terms. In addition, reference-tracking will be undertaken, and expert researchers will be contacted to locate relevant studies. Two reviewers will be involved in the assessment of the studies against eligibility criteria, formal quality appraisal and data extraction. A results-based convergent synthesis will be undertaken, using narrative synthesis if the quantitative data are too heterogeneous for meta-analysis, meta-ethnography for the synthesis of the qualitative data and the production of a line of argument synthesis. Finally, confidence in the findings will be formally assessed and conclusions drawn. DISCUSSION: The findings of this review will allow researchers, practitioners and policy makers to better understand the factors influencing women's movement and the use of different positions during labour and birth. This will inform future research and the development of maternity services designed to implement best-evidence concerning movement and positioning during labour and birth into clinical practice. SYSTEMATIC REVIEW REGISTRATION: In accordance with the PRISMA-P guidelines (Moher et al. Syst Rev 4:1, 2015), the systematic review protocol was registered with the International Prospective Register of Systematic reviews (PROSPERO) on July 17, 2018 (CRD42018103354).

7.
Reprod Health ; 15(1): 58, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618359

RESUMO

BACKGROUND: The practice of antenatal breast expression (ABE) has been proposed as a strategy to promote successful breastfeeding. Although there has been some focus on the evaluation of the effects of ABE in promotion of breastfeeding, little or no evidence exists on women's experiences of ABE or opinions on ABE, particularly amongst overweight or obese women. METHODS: This study aimed to explore women's knowledge, practices and opinions of ABE, and any differences within the overweight and obese subgroups. A cross-sectional survey was undertaken using an online questionnaire distributed by a maternity user group representative via social media. Quantitative data were analysed using Chi-square and Fisher's exact tests in SPSS. Simple thematic analysis was used for the qualitative data. RESULTS: A total of 688 responses were analysed; the sample represented a group of breastfeeding mothers, of whom 64.5% had heard of ABE, 8.2% had been advised to do ABE, and 14.2% had undertaken ABE. Of the women who had been advised to do ABE, 67.9% had complied. Most participants (58.6%) were unsure if ABE was a good idea; however 80.9% would consider doing ABE if it was found to be helpful to prepare for breastfeeding. Women in the overweight or obese subgroups were significantly more likely to have heard of ABE (p < 0.001), and positive opinion of ABE also increased with higher BMI groups. The qualitative data demonstrated participants felt ABE may be beneficial when mother or baby have medical problems, and in preparation for breastfeeding, but highlighted their concerns that it may interfere with nature and be harmful, and that they wanted more information and knowledge about ABE. CONCLUSIONS: Amongst women who have breastfed, many have heard of ABE, compliance with advice to undertake ABE is relatively high, and ABE is considered an acceptable practice. Further investigation into the benefits and safety of ABE is warranted, to address the needs of childbearing women for evidence-based information about this practice. If the evidence base is established, overweight and obese pregnant women could be an important target group for this intervention.


Assuntos
Aleitamento Materno/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Cuidado Pré-Natal/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Gravidez , Cuidado Pré-Natal/métodos , Pesquisa Qualitativa , Inquéritos e Questionários , Adulto Jovem
8.
Sci Total Environ ; 612: 840-852, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28881307

RESUMO

An 11year dataset of concentrations of E. coli at 10 spatially-distributed sites in a mixed land-use catchment in NE Scotland (52km2) revealed that concentrations were not clearly associated with flow or season. The lack of a clear flow-concentration relationship may have been due to greater water fluxes from less-contaminated headwaters during high flows diluting downstream concentrations, the importance of persistent point sources of E. coli both anthropogenic and agricultural, and possibly the temporal resolution of the dataset. Point sources and year-round grazing of livestock probably obscured clear seasonality in concentrations. Multiple linear regression models identified potential for contamination by anthropogenic point sources as a significant predictor of long-term spatial patterns of low, average and high concentrations of E. coli. Neither arable nor pasture land was significant, even when accounting for hydrological connectivity with a topographic-index method. However, this may have reflected coarse-scale land-cover data inadequately representing "point sources" of agricultural contamination (e.g. direct defecation of livestock into the stream) and temporal changes in availability of E. coli from diffuse sources. Spatial-stream-network models (SSNMs) were applied in a novel context, and had value in making more robust catchment-scale predictions of concentrations of E. coli with estimates of uncertainty, and in enabling identification of potential "hot spots" of faecal contamination. Successfully managing faecal contamination of surface waters is vital for safeguarding public health. Our finding that concentrations of E. coli could not clearly be associated with flow or season may suggest that management strategies should not necessarily target only high flow events or summer when faecal contamination risk is often assumed to be greatest. Furthermore, we identified SSNMs as valuable tools for identifying possible "hot spots" of contamination which could be targeted for management, and for highlighting areas where additional monitoring could help better constrain predictions relating to faecal contamination.


Assuntos
Monitoramento Ambiental , Escherichia coli/isolamento & purificação , Fezes , Microbiologia da Água , Agroquímicos , Animais , Hidrologia , Gado , Escócia , Estações do Ano , Análise Espacial
9.
Sci Total Environ ; 607-608: 391-402, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28700972

RESUMO

Accurate quantification of suspended sediments (SS) and particulate phosphorus (PP) concentrations and loads is complex due to episodic delivery associated with storms and management activities often missed by infrequent sampling. Surrogate measurements such as turbidity can improve understanding of pollutant behaviour, providing calibrations can be made cost-effectively and with quantified uncertainties. Here, we compared fortnightly and storm intensive water quality sampling with semi-continuous turbidity monitoring calibrated against spot samples as three potential methods for determining SS and PP concentrations and loads in an agricultural catchment over two-years. In the second year of sampling we evaluated the transferability of turbidity calibration relationships to an adjacent catchment with similar soils and land cover. When data from nine storm events were pooled, both SS and PP concentrations (all in log space) were better related to turbidity than they were to discharge. Developing separate calibration relationship for the rising and falling limbs of the hydrograph provided further improvement. However, the ability to transfer calibrations between adjacent catchments was not evident as the relationships of both SS and PP with turbidity differed both in gradient and intercept on the rising limb of the hydrograph between the two catchments. We conclude that the reduced uncertainty in load estimation derived from the use of turbidity as a proxy for specific water quality parameters in long-term regulatory monitoring programmes, must be considered alongside the increased capital and maintenance costs of turbidity equipment, potentially noisy turbidity data and the need for site-specific prolonged storm calibration periods.

11.
Lancet Respir Med ; 5(2): 135-146, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28094141

RESUMO

BACKGROUND: Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting. METHODS: In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5-6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5-10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKline's RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response-a composite of vital sign stabilisation and hospital discharge-in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620. FINDINGS: Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the oseltamivir group. Four patients with influenza A/H1N1pdm09 in the oseltamivir group developed H275Y resistance mutations. Adverse events were reported in 373 (61%) of treated patients and were similar across treatment groups; the most common adverse events (300 mg intravenous zanamivir, 600 mg intravenous zanamivir, oseltamivir) were diarrhoea (10 [5%], 15 [7%], 14 [7%]), respiratory failure (11 [5%], 14 [7%], 11 [5%]), and constipation (7 [3%], 13 [6%], 10 [5%]). 41 (7%) treated patients died during the study (15 [7%], 15 [7%], 11 [5%]); the most common causes of death were respiratory failure and septic shock. INTERPRETATION: Time to clinical response to intravenous zanamivir dosed at 600 mg was not superior to oseltamivir or 300 mg intravenous zanamivir. All treatments had a similar safety profile in hospitalised patients with severe influenza. FUNDING: GlaxoSmithKline.


Assuntos
Antivirais/administração & dosagem , Hospitalização , Influenza Humana/tratamento farmacológico , Oseltamivir/administração & dosagem , Zanamivir/administração & dosagem , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
Reprod Health ; 14(1): 1, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28057003

RESUMO

BACKGROUND: Freedom from discrimination is one of the key principles in a human rights-based approach to maternal and newborn health. OBJECTIVE: To review the published evidence on discrimination against Romani women in maternity care in Europe, and on interventions to address this. SEARCH STRATEGY: A systematic search of eight electronic databases was undertaken in 2015 using the terms "Roma" and "maternity care". A broad search for grey literature included the websites of relevant agencies. DATA EXTRACTION AND SYNTHESIS: Standardised data extraction tables were utilised, quality was formally assessed and a line of argument synthesis was developed and tested against the data from the grey literature. RESULTS: Nine hundred papers were identified; three qualitative studies and seven sources of grey literature met the review criteria. These revealed that many Romani women encounter barriers to accessing maternity care. Even when they are able to access care, they can experience discriminatory mistreatment on the basis of their ethnicity, economic status, place of residence or language. The grey literature revealed some health professionals held underlying negative beliefs about Romani women. There were no published research studies examining the effectiveness of interventions to address discrimination against Romani women and their infants in Europe. The Roma Health Mediation Programme is a promising intervention identified in the grey literature. CONCLUSIONS: There is evidence of discrimination against Romani women in maternity care in Europe. Interventions to address discrimination against childbearing Romani women and underlying health provider prejudice are urgently needed, alongside analysis of factors predicting the success or failure of such initiatives.


Assuntos
Serviços de Saúde Materna/normas , Obstetrícia/normas , Discriminação Social/prevenção & controle , Feminino , Promoção da Saúde , Direitos Humanos , Humanos , Gravidez , Romênia
13.
Cochrane Database Syst Rev ; (1): CD002201, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26730723

RESUMO

BACKGROUND: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review. OBJECTIVES: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Date of last search: 13 August 2013. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. MAIN RESULTS: The searches identified 15 studies; four studies with 91 participants (children and adults) were included; duration of studies ranged from six weeks to six months. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another study (43 participants) demonstrated a significant increase in serum phospholipid essential fatty acid content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3 fatty acid supplementation compared to control. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes and a significant decrease in the leukotriene B4 to leukotriene B5 ratio in participants taking omega-3 supplements compared to placebo. AUTHORS' CONCLUSIONS: This review found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. This review has highlighted the lack of data for many outcomes meaningful to people with or making treatment decisions about cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.


Assuntos
Fibrose Cística/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Adulto , Criança , Ácidos Graxos Ômega-6/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Essays Biochem ; 59: 43-69, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26504250

RESUMO

Biological membranes allow life as we know it to exist. They form cells and enable separation between the inside and outside of an organism, controlling by means of their selective permeability which substances enter and leave. By allowing gradients of ions to be created across them, membranes also enable living organisms to generate energy. In addition, they control the flow of messages between cells by sending, receiving and processing information in the form of chemical and electrical signals. This essay summarizes the structure and function of membranes and the proteins within them, and describes their role in trafficking and transport, and their involvement in health and disease. Techniques for studying membranes are also discussed.


Assuntos
Proteínas de Membrana/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Animais , Transporte Biológico , Humanos , Proteínas de Membrana/química , Dados de Sequência Molecular
15.
J Appl Anim Welf Sci ; 17(1): 1-17, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23927074

RESUMO

Lethal control is used extensively in New Zealand to control nonnative nonhuman mammals. Respondents were surveyed about 8 mammal groups considered pests and their attitudes toward their control and pest status. They also identified the most appropriate method of control for the 8 different mammals. Information was gathered from 3 groups of respondents: nonhuman animal protectionists, conservationists, and the general public. Conservationists routinely rated all animal groups as more severe pests than the general public or animal protectionists, who provided the lowest scores. Rats, stoats, brushtail possums, and rabbits were identified as the 4 most serious pests by all 3 groups. Conservationists were 5.7 and 2.6 times more likely to prefer a lethal method of control than protectionists and the general public, respectively. For all 3 groups an increase in pest score for a given animal saw a decline in importance placed upon the animal's welfare. This relationship was strong for the general public but weak for conservationists and animal protectionists. Understanding aspects of potentially opposing viewpoints may be invaluable in supporting the development of new welfare-focused control methods.


Assuntos
Animais Selvagens , Atitude , Controle de Pragas , Opinião Pública , Bem-Estar do Animal , Animais , Conservação dos Recursos Naturais , Coleta de Dados , Feminino , Humanos , Masculino , Mustelidae , Nova Zelândia , Coelhos , Ratos , Trichosurus
16.
Cochrane Database Syst Rev ; (11): CD002201, 2013 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-24282091

RESUMO

BACKGROUND: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. OBJECTIVES: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Date of last search: 08 July 2013. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. MAIN RESULTS: The searches identified 14 studies; four studies with 91 participants were included. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another study (43 participants) demonstrated a significant increase in serum phospholipid essential fatty acid content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3 fatty acid supplementation compared to control. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes and a significant decrease in the leukotriene B4 to leukotriene B5 ratio in participants taking omega-3 supplements compared to placebo. AUTHORS' CONCLUSIONS: This review found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. This review has highlighted the lack of data for many outcomes meaningful to people with or making treatment decisions about cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.


Assuntos
Fibrose Cística/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Biochem J ; 456(2): 297-309, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24015703

RESUMO

The majority of the polytopic proteins that are synthesized at the ER (endoplasmic reticulum) are integrated co-translationally via the Sec61 translocon, which provides lateral access for their hydrophobic TMs (transmembrane regions) to the phospholipid bilayer. A prolonged association between TMs of the potassium channel subunit, TASK-1 [TWIK (tandem-pore weak inwardly rectifying potassium channel)-related acid-sensitive potassium channel 1], and the Sec61 complex suggests that the ER translocon co-ordinates the folding/assembly of the TMs present in the nascent chain. The N-terminus of both TASK-1 and Kcv (potassium channel protein of chlorella virus), another potassium channel subunit of viral origin, has access to the N-glycosylation machinery located in the ER lumen, indicating that the Sec61 complex can accommodate multiple arrangements/orientations of TMs within the nascent chain, both in vitro and in vivo. Hence the ER translocon can provide the ribosome-bound nascent chain with a dynamic environment in which it can explore a range of different conformations en route to its correct transmembrane topology and final native structure.


Assuntos
Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Canais de Potássio de Domínios Poros em Tandem/biossíntese , Retículo Endoplasmático/metabolismo , Células HeLa , Humanos , Membranas Intracelulares/metabolismo , Proteínas de Membrana/química , Proteínas do Tecido Nervoso/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Canais de Potássio de Domínios Poros em Tandem/química , Sinais Direcionadores de Proteínas , Estrutura Secundária de Proteína , Canais de Translocação SEC
18.
J Cell Sci ; 126(Pt 2): 464-72, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23230148

RESUMO

The integration of transmembrane (TM)-spanning regions of many channels and ion transporters is potentially compromised by the presence of polar and charged residues required for biological function. Although the two TMs of the ATP-gated ion channel subunit P2X2 each contain charged/polar amino acids, we found that each TM is efficiently membrane inserted when it is analysed in isolation, and uncovered no evidence for cooperativity between these two TMs during P2X2 integration. However, using minimal N-glycosylation distance mapping, we find that the positioning of TM2 in newly synthesized P2X2 monomers is distinct from that seen in subunits of the high-resolution structures of assembled homologous trimers. We conclude that P2X2 monomers are initially synthesised at the endoplasmic reticulum in a distinct conformation, where the extent of the TM-spanning regions is primarily defined by the thermodynamic cost of their membrane integration at the Sec61 translocon. In this model, TM2 of P2X2 subsequently undergoes a process of positional editing within the membrane that correlates with trimerisation of the monomer, a process requiring specific polar/charged residues in both TM1 and TM2. We postulate that the assembly process offsets any energetic cost of relocating TM2, and find evidence that positional editing of TM2 in the acid-sensing ion channel (ASIC1a) is even more pronounced than that observed for P2X2. Taken together, these data further underline the potential complexities involved in accurately predicting TM domains. We propose that the orchestrated repositioning of TM segments during subunit oligomerisation plays an important role in generating the functional architecture of active ion channels, and suggest that the regulation of this underappreciated biosynthetic step may provide an elegant mechanism for maintaining ER homeostasis.


Assuntos
Retículo Endoplasmático/metabolismo , Canais Iônicos/metabolismo , Canais Iônicos Sensíveis a Ácido/química , Canais Iônicos Sensíveis a Ácido/metabolismo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Membrana Celular/metabolismo , Células Cultivadas , Células HeLa , Humanos , Canais Iônicos/química , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Subunidades Proteicas , Ratos , Receptores Purinérgicos P2X2/química , Receptores Purinérgicos P2X2/metabolismo , Transdução de Sinais , Termodinâmica
20.
Sci Total Environ ; 434: 123-9, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22425175

RESUMO

Analysis of water samples and accompanying flow data collected (on ~100 occasions) from well defined land drain outlets located in a small catchment in NE Scotland were made over a five year period. The complex relationship between individual sources that can exist even within a small (200 ha) agriculturally managed headwater catchment was clearly evident. On average ~60% of the measured flow from the catchment outlet was accounted for, with ~50% originating from field drains and 10% from the farmyard. Certain field drains stopped flowing during the summer. Flow from the farmyard was continuous, and because livestock were present all year round also represented a renewable source of potential contaminants. The majority of nitrate and suspended sediment originated directly from field drainage. The variability in nitrate concentration between individual field drains was large and probably reflected differences in soil drainage properties. Farmyard drainage contributed a large proportion of the ammonium, phosphate and Faecal Indicator Organisms (FIO) measured as a flux from the catchment. On numerous sampling occasions the combined flux from individual sources was greater than the corresponding loss measured at the catchment outlet. This was attributed to result from the temporary storage/retention mechanisms (sedimentation, transformation or biological uptake/exchange) that can operate within the stream channel. Despite many fields being grazed and/or receiving regular applications of slurry/manure, the majority ~60% of the total flux of FIO still originated from the 'farmyard', with significant contributions from the field drains only occurring during the autumn. The presence of field drinkers and secure well maintained fencing denying cattle access to the open drainage channel (often a recommended best management practice) may well have contributed to this observation. Benefits to water quality that might arise from riparian management, such as buffer strips in this particular situation may be limited due to the dominant contribution originating from land drains and farmyard.

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