Blowing Away Fatty Liver: Mission Impossible?
Ontology highlight
ABSTRACT:
SUBMITTER: McLean AEB
PROVIDER: S-EPMC7885836 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Blowing Away Fatty Liver: Mission Impossible?
McLean Anna E B AEB Gagnadoux Frédéric F Yee Brendon J BJ
American journal of respiratory and critical care medicine 20210201 4
Similar Datasets
Project description: Not available
| S-EPMC10955311 | biostudies-literature
Project description:BackgroundCardiovascular disease (CVD) risk prediction models are often used to identify individuals at high risk of CVD events. Providing preventive treatment to these individuals may then reduce the CVD burden at population level. However, different prediction models may predict different (sets of) CVD outcomes which may lead to variation in selection of high risk individuals. Here, it is investigated if the use of different prediction models may actually lead to different treatment recommendations in clinical practice.MethodThe exact definition of and the event types included in the predicted outcomes of four widely used CVD risk prediction models (ATP-III, Framingham (FRS), Pooled Cohort Equations (PCE) and SCORE) was determined according to ICD-10 codes. The models were applied to a Dutch population cohort (n = 18,137) to predict the 10-year CVD risks. Finally, treatment recommendations, based on predicted risks and the treatment threshold associated with each model, were investigated and compared across models.ResultsDue to the different definitions of predicted outcomes, the predicted risks varied widely, with an average 10-year CVD risk of 1.2% (ATP), 5.2% (FRS), 1.9% (PCE), and 0.7% (SCORE). Given the variation in predicted risks and recommended treatment thresholds, preventive drugs would be prescribed for 0.2%, 14.9%, 4.4%, and 2.0% of all individuals when using ATP, FRS, PCE and SCORE, respectively.ConclusionWidely used CVD prediction models vary substantially regarding their outcomes and associated absolute risk estimates. Consequently, absolute predicted 10-year risks from different prediction models cannot be compared directly. Furthermore, treatment decisions often depend on which prediction model is applied and its recommended risk threshold, introducing unwanted practice variation into risk-based preventive strategies for CVD.
| S-EPMC6326414 | biostudies-literature
Project description:ObjectiveIn children many antiepileptic drugs (AEDs) are prescribed off-label due to a lack of well-designed randomized controlled trials (RCTs). We conducted a multicenter RCT in the Netherlands to compare levetiracetam and valproic acid as monotherapy in children with newly diagnosed epilepsy. After 2 years, we had to stop this investigator-initiated trial prematurely because the inclusion rate was too low. We analyzed the reasons for this failure, assessed the various issues involved in performing RCTs in children, and now give recommendations for future studies.MethodsA questionnaire was completed by all investigators involved in the study. It included questions about the motivation to participate and the perceived reasons for recruitment failure. We also studied literature about financial, logistic, legal, and ethical aspects of RCTs in children.ResultsMain reasons for recruitment failure were overestimation of the number of eligible AED-naive children referred by general pediatricians; personal preferences of investigators for specific antiepileptic drugs; and the extensive administrative load due to extra regulations and guidelines for children. Fundraising for investigator-initiated trials is difficult and the majority of RCTs concerning AEDs are sponsored by pharmaceutical companies. Involving children requires balancing between protection and participation; the randomization procedure and obtaining informed consent are complex for both children and parents.SignificancePerforming RCTs with AEDs in children is important but complicated by logistic, regulatory, legal, and ethical restrictions. Based on our recent experience, our advice to colleagues who are planning a similar trial would be to perform a feasibility pilot study; to set up intensive collaboration with referring pediatricians; to arrange support of a clinical trials unit and a local research nurse during the complete trial period; and to incorporate the possibility of extending the recruitment period. Major investments, both financially from governmental organizations and in time, are imperative for independent RCTs in children.
| S-EPMC5939385 | biostudies-literature
Project description:Antisense oligonucleotides can regulate gene expression in living cells. As such, they regulate cell function and division, and can modulate cellular responses to internal and external stresses and stimuli. Although encouraging results from preclinical and clinical studies have been obtained and significant progress has been made in developing these agents as drugs, they are not yet recognized as effective therapeutics. Several major hurdles remain to be overcome, including problems with efficacy, off-target effects, delivery and side effects. The lessons learned from antisense drug development can help in the development of other oligonucleotide-based therapeutics such as CpG oligonucleotides, RNAi and miRNA.
| S-EPMC2497463 | biostudies-literature
Project description:This paper demonstrates the fraction collection of the novel sugar trehalulose, using a modified ion chromatograph. The Ion Chromatography (IC) method, previously published for the analysis of trehalulose, was augmented with a suppressor and purpose-made switching valve unit. A sample of stingless bee honey was then run, following the three main steps:•Separation of trehalulose fraction•Lyophilization•Confirmation of trehalulose The method should be applicable to not only sugar analysis but to any bioactive compound separable by IC. The authors were not able to find a similar method within currently published literature.
| S-EPMC11919326 | biostudies-literature
Project description:The classical complement pathway is initiated by the large (~800 kDa) and flexible multimeric C1 complex. Its catalytic function is triggered by the proteases hetero-tetramer C1r2s2, which is associated to the C1q sensing unit, a complex assembly of 18 chains built as a hexamer of heterotrimers. Initial pioneering studies gained insights into the main architectural principles of the C1 complex. A dissection strategy then provided the high-resolution structures of its main functional and/or structural building blocks, as well as structural details on some key protein-protein interactions. These past and current discoveries will be briefly summed up in order to address the question of what is still ill-defined. On a functional point of view, the main molecular determinants of C1 activation and its tight control will be delineated. The current perspective remains to decipher how C1 really works and is controlled in vivo, both in normal and pathological settings.
| S-EPMC4222235 | biostudies-literature
Project description: Not available
| S-EPMC7158219 | biostudies-literature
Project description:The harm-benefit analysis (HBA) is a cornerstone of the European Directive 2010/63/EU (the Directive). The Directive regulates the care and handling of animals used for scientific purposes in the European Union (EU). Since its implementation, there has been ongoing debate around the practical applicability of the HBA for research project review processes. The objectives of this study are to analyze the operationalization of HBA in EU member states and investigate the consistency of HBA's implementation in terms of national legislation and available policy documents. To meet these objectives, we evaluated the transposition of the HBA requirement into national legislation. We also conducted a comprehensive comparative cross-national analysis of all guidance documents pertinent to HBA. The results of our study show that there are (1) deficits in the transposition of the HBA requirement into national laws, (2) significant discrepancies in available policy documents relating to HBA, and (3) insufficiently consistent implementations of HBA in European countries.
| S-EPMC10878508 | biostudies-literature
Project description:Early animal embryonic development requires maternal products that drive developmental processes prior to the activation of the zygotic genome at the mid-blastula transition. During and after this transition, maternal products may continue to act within incipient zygotic developmental programs. Mechanisms that control maternally-inherited products to spatially and temporally restrict developmental responses remain poorly understood, but necessarily depend on posttranscriptional regulation. We report the functional analysis and molecular identification of the zebrafish maternal-effect gene mission impossible (mis). Our studies suggest requirements for maternally-derived mis function in events that occur during gastrulation, including cell movement and the activation of some endodermal target genes. Cell transplantation experiments show that the cell movement defect is cell autonomous. Within the endoderm induction pathway, mis is not required for the activation of early zygotic genes, but is essential to implement nodal activity downstream of casanova/sox 32 but upstream of sox17 expression. Activation of nodal signaling in blastoderm explants shows that the requirement for mis function in endoderm gene induction is independent of the underlying yolk cell. Positional cloning of mis, including genetic rescue and complementation analysis, shows that it encodes the DEAH-box RNA helicase Dhx16, shown in other systems to act in RNA regulatory processes such as splicing and translational control. Analysis of a previously identified insertional dhx16 mutation shows that the zygotic component of this gene is also essential for embryonic viability. Our studies provide a striking example of the interweaving of maternal and zygotic genetic functions during the egg-to-embryo transition. Maternal RNA helicases have long been known to be involved in the development of the animal germ line, but our findings add to growing evidence that these factors may also control specific gene expression programs in somatic tissues.
| S-EPMC3088167 | biostudies-literature
