scholarly journals General Anesthetic-Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ailin Luo ◽  
Xiaole Tang ◽  
Yilin Zhao ◽  
Zhiqiang Zhou ◽  
Jing Yan ◽  
...  

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.

Author(s):  
Philippe Menasché

• Experimental studies suggest that bone marrow-derived stem cells can improve function of infarcted myocardium• This benefit seems to involve paracrine signalling and limitation of left ventricular remodelling rather than true regeneration of cardiomyocytes from donor cells• These experimental findings have been translated in the clinical setting into significant, although moderate, improvements in cardiac function and LV remodelling but the extent to which these benefits impact on event-free long term survival remains to be determined• Optimisation of this therapeutic strategy will require a more comprehensive characterisation of cell functionality and an improvement in the methods used in cell transfer, engraftment, survival and integration.


2007 ◽  
Vol 66 (3) ◽  
pp. 435-441 ◽  
Author(s):  
M. S. Fewtrell ◽  

Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming – long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.


2021 ◽  
Author(s):  
Philipp Porada ◽  
Selina Baldauf ◽  
Jose Raggio ◽  
Fernando Maestre ◽  
Britta Tietjen

<p>Manipulative experiments typically show a decrease in dryland biocrust cover and altered species composition under climate change. Biocrust-forming lichens, such as the globally distributed <em>Diploschistes diacapsis</em>, are particularly affected and show a decrease in cover with simulated climate change. However, the underlying mechanisms are not fully understood, and long-term interacting effects of different drivers are largely unknown due to the short-term nature of the experimental studies conducted so far. We addressed this gap and successfully parameterised a process-based model for <em>D. diacapsis</em> to quantify how changing atmospheric CO<sub>2</sub> , temperature, rainfall amount and relative humidity affect its photosynthetic activity and cover. We also mimicked a long-term manipulative climate change experiment to understand the mechanisms underlying observed patterns in the field. The model reproduced observed experimental findings: warming reduced lichen cover, whereas less rainfall had no effect on lichen performance. This warming effect was caused by the associated decrease in relative humidity and non-rainfall water inputs, which are major water sources for biocrust-forming lichens. Warming alone, however, increased cover because higher temperatures promoted photosynthesis during early morning hours with high lichen activity. When combined, climate variables showed non-additive effects on lichen cover, and effects of increased CO<sub>2</sub> levelled off with decreasing levels of relative humidity. Our results show that a decrease in relative humidity, rather than an increase in temperature, may be the key factor for the survival of the lichen <em>D. diacapsis</em> under climate change and that effects of increased CO<sub>2</sub> levels might be offset by a reduction in non-rainfall water inputs in the future. Because of a global trend towards warmer and drier air and the widespread global distribution of <em>D. diacapsis</em>, this will affect lichen-dominated dryland biocrust communities and their role in regulating ecosystem functions worldwide.</p>


1975 ◽  
Vol 126 (2) ◽  
pp. 127-145 ◽  
Author(s):  
Lawrence Bartak ◽  
Michael Rutter ◽  
Antony Cox

There is now extensive evidence that autistic children manifest a specific cognitive defect involving language impairment (Rutter, 1974). The presence of such a deficit is demonstrated by the pattern of clinical findings (Rutter, 1968; Rutter, Bartak and Newman, 1971), the long term course of the disorder (Rutter, 1970), and the results of systematic experimental studies (Hermelin and O'Connor, 1970). Nevertheless, basic questions remain concerning the meaning of this deficit for theories on the nature and causation of infantile autism. First, what are the boundaries of the cognitive deficit and in particular does it extend outside language? Second, does it constitute the primary handicap which gives rise to other symptoms? Thirdly, if it does, does the cognitive deficit lead directly to the behavioural syndrome or must there be an interaction with a particular set of environmental or other circumstances for the syndrome to develop?


2018 ◽  
Vol 32 (8) ◽  
pp. 850-854 ◽  
Author(s):  
Jack E James

Background: There is a large corpus of observational evidence claiming that coffee is health protective and a similarly large corpus of experimental psychopharmacological evidence to suggest that habitual caffeine consumption may be harmful to health. Aim: The purpose of this study was to examine the disjunction between observational and experimental findings with specific reference to the implications of coffee/caffeine consumption for elevated blood pressure, cardiovascular disease, type 2 diabetes and neurodegenerative disease. Method: Illustrative recent major reviews alleging health protective effects from coffee consumption were examined in light of findings from relevant experimental studies of caffeine. Findings: Decades-long coffee consumption is but one of countless lifestyle variables that may benefit or harm health. Contradictions concerning the implications of coffee/caffeine consumption for health between observational and experimental research are attributable mostly to poor control over potential confounders in observational studies. Conclusion: When considered in the context of experimental evidence concerning caffeine’s known pharmacological actions, there is reason to be sceptical about observational findings alleging health-protective effects from coffee consumption. Long-term randomised trials are needed to end the enduring interpretative disjunction between observational and experimental evidence concerning coffee/caffeine consumption and health.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Shuhua Gao ◽  
Cheng Xiang ◽  
Kairong Qin ◽  
Changkai Sun

Many experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%–7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to investigate the hypoxic effects on MSC expansion quantitatively through mathematical modeling to elucidate the corresponding biological mechanism. A two-compartment model based on ordinary differential equations (ODEs), which incorporate cellular division and senescence via state transition, was developed to describe the MSC expansion process. Parameters of this model were fitted to experimental data and used to interpret the different proliferative capacities of MSCs under hypoxia and normoxia along with model sensitivity analysis. The proposed model was tested on data from two separate experimental studies, and it could reproduce the observed growth characteristics in both conditions. Overall, this compartmental model with a logistic state transition rate was sufficient to explain the experimental findings and highlighted the promotive role of hypoxia in MSC proliferation. This in silico study suggests that hypoxia can enhance MSC long-term expansion mainly by delaying replicative senescence, which is indicated by the slowdown of the state transition rate in our model. Therefore, this explanatory model may provide theoretical proof for the experimentally observed MSC growth superiority under hypoxia and has the potential to further optimize MSC culture protocols for regenerative medicine applications.


The results of experimental studies of masonry on the action of dynamic and static (short-term and long-term) loads are presented. The possibility of plastic deformations in the masonry is analyzed for different types of force effects. The falsity of the proposed approach to the estimation of the coefficient of plasticity of masonry, taking into account the ratio of elastic and total deformations of the masonry is noted. The study of the works of Soviet scientists revealed that the masonry under the action of seismic loads refers to brittle materials in the complete absence of plastic properties in it in the process of instantaneous application of forces. For the cases of uniaxial and plane stress states of the masonry, data on the coefficient of plasticity obtained from the experiment are presented. On the basis of experimental studies the influence of the strength of the so-called base materials (brick, mortar) on the bearing capacity of the masonry, regardless of the nature of the application of forces and the type of its stress state, is noted. The analysis of works of prof. S. V. Polyakov makes it possible to draw a conclusion that at the long application of the load, characteristic for the masonry are not plastic deformations, but creep deformations. It is shown that the proposals of some authors on the need to reduce the level of adhesion of the mortar to the brick for the masonry erected in earthquake-prone regions in order to improve its plastic properties are erroneous both from the structural point of view and from the point of view of ensuring the seismic resistance of structures. It is noted that the proposal to assess the plasticity of the masonry of ceramic brick walls and large-format ceramic stone with a voidness of more than 20% is incorrect, and does not meet the work of the masonry of hollow material. On the basis of the analysis of a large number of research works it is concluded about the fragile work of masonry.


Problems when calculating reinforced concrete structures based on the concrete deformation under compression diagram, which is presented both in Russian and foreign regulatory documents on the design of concrete and reinforced concrete structures are considered. The correctness of their compliance for all classes of concrete remains very approximate, especially a significant difference occurs when using Euronorm due to the different shape and sizes of the samples. At present, there are no methodical recommendations for determining the ultimate relative deformations of concrete under axial compression and the construction of curvilinear deformation diagrams, which leads to limited experimental data and, as a result, does not make it possible to enter more detailed ultimate strain values into domestic standards. The results of experimental studies to determine the ultimate relative deformations of concrete under compression for different classes of concrete, which allowed to make analytical dependences for the evaluation of the ultimate relative deformations and description of curvilinear deformation diagrams, are presented. The article discusses various options for using the deformation model to assess the stress-strain state of the structure, it is concluded that it is necessary to use not only the finite values of the ultimate deformations, but also their intermediate values. This requires reliable diagrams "s–e” for all classes of concrete. The difficulties of measuring deformations in concrete subjected to peak load, corresponding to the prismatic strength, as well as main cracks that appeared under conditions of long-term step loading are highlighted. Variants of more accurate measurements are proposed. Development and implementation of the new standard GOST "Concretes. Methods for determination of complete diagrams" on the basis of the developed method for obtaining complete diagrams of concrete deformation under compression for the evaluation of ultimate deformability of concrete under compression are necessary.


2012 ◽  
Vol 163 (10) ◽  
pp. 417-421
Author(s):  
Urs Fischbacher

Experiments and forest economic questions During the last decades experiments have gained great importance in economics. These experiments deal with questions that are of significance for forest economic research, too. Timber production, for example, is characterised by long-term decisions and, in addition, forestry produces important public goods. In this article the experimental method is introduced. Furthermore, experimental findings are presented, e.g., concerning time preferences and externalities, and possible applications for the study of forest product markets and institutions are outlined.


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