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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Ruifrok, Anneloes E, et al.
(författare)
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Study protocol : Differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: Individual patient data (IPD) meta-analysis and health economic evaluation
- 2014
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Ingår i: Systematic Reviews. - : Springer Science and Business Media LLC. - 2046-4053. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/designRandomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.
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- Skrastad, Ragnhild B., et al.
(författare)
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A prospective study of screening for hypertensive disorders of pregnancy at 11-13 weeks in a Scandinavian population
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 93:12, s. 1238-1247
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the prediction of preeclampsia and gestational hypertension using maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at gestational weeks 11-13 in a Scandinavian population with a medium to high prior risk for developing hypertensive disorders of pregnancy. DesignProspective screening study. SettingNational Center for Fetal Medicine, Trondheim, Norway. Population579 women who were nulliparous or had a previous history of preeclampsia or gestational hypertension. MethodsWomen were examined between 11(+0) and 13(+6)weeks, with interviews for maternal characteristics and measurements of MAP, UtAPI, PAPP-A and PlGF. The tests were evaluated separately and in combined models with receiver operating characteristics (ROC) curves. Main outcome measuresPrediction of preeclampsia, severe preeclampsia and gestational hypertension. ResultsThe best model for severe preeclampsia (MAP+UtAPI+PlGF+PAPP-A) achieved an area under the ROC curve of 0.866 [95% confidence interval (95% CI) 0.756-0.976]. The best models for preeclampsia (MAP+UtAPI+age) achieved 0.738 (0.634-0.841), gestational hypertension (MAP) 0.820 (0.727-0.913) and hypertensive disorders in pregnancy overall (MAP+PlGF+age) 0.783 (0.709-0.856). Using the best model we could identify 61.5% (95% CI 31.6-86.1) of severe preeclampsia, 38.5% (95% CI 20.2-59.4) of preeclampsia and 42.9% (95% CI 21.8-66) of gestational hypertension at a fixed 10% false-positive rate. ConclusionsMaternal characteristics, MAP, UtAPI, PAPP-A and PlGF showed limited value as screening tests. Further research on biochemical and biophysical tests and algorithms combining these parameters is needed before first trimester screening for hypertensive disorders of pregnancy is included in antenatal care in Scandinavia.
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