The Normative Implications of the Doctrine of Creatio Ex Nihilo and Nikolai Berdyaev. Towards a Renewed Christian Orthodox Understanding of Human Freedom for the Postmodern Twenty-First Century

This is the final version. Available on open access from the International Journal of Orthodox Theology via the link in this recordThis paper examines the relationship between the doctrine of ‘creation out of nothing’ and the traditional Eastern Orthodox theological understanding of human freedom as submission to the Church’s teachings, regulations, and laws. Further, it explains that the established Christian Orthodox view of human freedom as submission to the Church is frequently at odds with the postmodern understanding of human freedom. Lastly, it focuses on Nikolai Berdyaev - a late 19th and early 20th century Russian religious thinker - and by analysing his philosophical interpretation of the doctrine of creatio ex nihilo, it develops a more attuned to postmodernism Christian Orthodox theological understanding of freedom which views human freedom as an absolute and unlimited choice

Using Therapeutic Sin-Talk in a (Post)Modern Environment: a Theologically Acceptable Choice or a Contemporary Eastern Orthodox Problem?

This is the final version. Available on open access from the International Journal of Orthodox Theology via the link in this recordA glimpse at Christian Orthodox writings published over the last twenty years illustrates that numerous Eastern Orthodox scholars acknowledge that, to a large extent, our present era is postmodern. Given that, one would expect that in its contact with broader society, the Orthodox Church would communicate in a contemporary language compatible with the basic tenets of postmodernism that would allow it to effectively carry out its mission in today’s allegedly postmodern age. Yet this is hardly the case. Greatly motivated by the neopatristic movement and its call to return to the Church Fathers and renew Eastern Orthodoxy by grounding it on patristic sources, the Orthodox Church frequently uses pre-modern patristic language in the present day. That is particularly true for the therapeutic language various Orthodox clerics and hierarchs use to describe human sin. For them, just like for many prominent late antique patristic authors, sin is a sickness of the soul, and the Orthodox Church is the only institution capable of adequately curing this sickness. But is such a pre-modern patristic therapeutic sin-talk compatible with postmodernism and, hence, able to effectively communicate with the present era, which many Orthodox scholars consider postmodern? In this paper, I answer this question negatively, arguing that the Eastern Orthodox therapeutic language of human sin has difficulties effectively communicating with postmodernism because it clashes with pluralism, a fundamental characteristic of postmodernism

Principles for integrating reactive species into in vivo biological processes:examples from exercise physiology

The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question

Potential applications of NRF2 modulators in cancer therapy

The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2

Using the MitoB method to assess levels of reactive oxygen species in ecological studies of oxidative stress

In recent years evolutionary ecologists have become increasingly interested in the effects of reactive oxygen species (ROS) on the life-histories of animals. ROS levels have mostly been inferred indirectly due to the limitations of estimating ROS from in vitro methods. However, measuring ROS (hydrogen peroxide, H2O2) content in vivo is now possible using the MitoB probe. Here, we extend and refine the MitoB method to make it suitable for ecological studies of oxidative stress using the brown trout Salmo trutta as model. The MitoB method allows an evaluation of H2O2 levels in living organisms over a timescale from hours to days. The method is flexible with regard to the duration of exposure and initial concentration of the MitoB probe, and there is no transfer of the MitoB probe between fish. H2O2 levels were consistent across subsamples of the same liver but differed between muscle subsamples and between tissues of the same animal. The MitoB method provides a convenient method for measuring ROS levels in living animals over a significant period of time. Given its wide range of possible applications, it opens the opportunity to study the role of ROS in mediating life history trade-offs in ecological settings

The development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders

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Montmorency cherry juice reduces muscle damage caused by intensive strength exercise.

addresses: Sports and Exercise Science Research Centre, London South Bank University, London, United Kingdom. [email protected]: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov'tThis is a non-final version of an article published in final form in Medicine and Science in Sports and Exercise, 2011, Vol. 43, Issue 8, pp. 1544 – 1551. © 2011 American College of Sports Medicine (ACSM)Montmorency cherries contain high levels of polyphenolic compounds including flavonoids and anthocyanins possessing antioxidant and anti-inflammatory effects. We investigated whether the effects of intensive unilateral leg exercise on oxidative damage and muscle function were attenuated by consumption of a Montmorency cherry juice concentrate using a crossover experimental design

Quercetin and Epigallocatechin Gallate Induce in Vitro a Dose-Dependent Stiffening and Hyperpolarizing Effect on the Cell Membrane of Human Mononuclear Blood Cells

The bioactivity of polyphenols is closely linked to their ability to interact with biological membranes. The study evaluates the in vitro effect of quercetin and epigallocatechin on the membrane anisotropy and transmembrane potential of peripheral blood mononuclear cells (PBMCs) isolated from 26 type 2 diabetes mellitus patients compared to 25 age matched controls. The in vitro assays were analyzed in correlation with the biochemical and inflammatory profile of the subjects and with insulin resistance parameters (HOMA-IR, plasma resistin) as well. For type 2 diabetes patients, the increase of HOMA-IR and resistin concentration was associated with a significant decrease of the PBMCs membrane anisotropy. The two tested polyphenols induced a dose-dependent hyperpolarizing effect and stiffening of the cell membranes for all tested subjects. Physiological levels of quercetin and epigallocatechin gallate had the tendency to normalize the PBMCs membrane anisotropy of the cells isolated from diabetes patients, bringing it to the level of cells isolated from normoglycemic ones. Epigallocatechin gallate induced higher effects compared to quercetin on the membranes isolated from subjects with higher cardiovascular risk. The decrease of membrane fluidity and the hyperpolarizing effect could explain the cardiovascular protective action of the tested compounds

Olive oil with high polyphenolic content induces both beneficial and harmful alterations on rat redox status depending on the tissue

Olive oil (OO) possesses a predominant role in the diet of Mediterranean countries. According to a health claim approved by the European Food Safety Authority, OO protects against oxidative stress‑induced lipid peroxidation in human blood, when it contains at least 5 mg of hydroxytyrosol and its derivatives per 20 g. However, studies regarding the effects of a total OO biophenols on redox status in vivo are scarce and either observational and do not provide a holistic picture of their action in tissues. Following a series of in vitro screening tests an OO containing biophenols at 800 mg/kg of OO was administered for 14 days to male Wistar rats at a dose corresponding to 20 g OO/per day to humans. Our results showed that OO reinforced the antioxidant profile of blood, brain, muscle and small intestine, it induced oxidative stress in spleen, pancreas, liver and heart, whereas no distinct effects were observed in lung, colon and kidney. The seemingly negative effects of OO follow the recently formulated idea in toxicology, namely the real life exposure scenario. This study reports that OO, although considered a nutritional source rich in antioxidants, it exerts a tissues specific action when administered in vivo

Plasma markers of oxidative stress are uncorrelated in a wild mammal.

This is the final version of the article. Available from Wiley via the DOI in this record.Oxidative stress, which results from an imbalance between the production of potentially damaging reactive oxygen species versus antioxidant defenses and repair mechanisms, has been proposed as an important mediator of life-history trade-offs. A plethora of biomarkers associated with oxidative stress exist, but few ecological studies have examined the relationships among different markers in organisms experiencing natural conditions or tested whether those relationships are stable across different environments and demographic groups. It is therefore not clear to what extent studies of different markers can be compared, or whether studies that focus on a single marker can draw general conclusions regarding oxidative stress. We measured widely used markers of oxidative damage (protein carbonyls and malondialdehyde) and antioxidant defense (superoxide dismutase and total antioxidant capacity) from 706 plasma samples collected over a 4-year period in a wild population of Soay sheep on St Kilda. We quantified the correlation structure among these four markers across the entire sample set and also within separate years, age groups (lambs and adults), and sexes. We found some moderately strong correlations between some pairs of markers when data from all 4 years were pooled. However, these correlations were caused by considerable among-year variation in mean marker values; correlation coefficients were small and not significantly different from zero after accounting for among-year variation. Furthermore, within each year, age, and sex subgroup, the pairwise correlation coefficients among the four markers were weak, nonsignificant, and distributed around zero. In addition, principal component analysis confirmed that the four markers represented four independent axes of variation. Our results suggest that plasma markers of oxidative stress may vary dramatically among years, presumably due to environmental conditions, and that this variation can induce population-level correlations among markers even in the absence of any correlations within contemporaneous subgroups. The absence of any consistent correlations within years or demographic subgroups implies that care must be taken when generalizing from observed relationships with oxidative stress markers, as each marker may reflect different and potentially uncoupled biochemical processes.We would like to thank Melissa M. Page, Ruth Banks, Christopher Mitchell and Sharon Mitchell for technical assistance and the St Kilda summer field teams of 2010-2013. In addition, we are very grateful to the National Trust for Scotland for permission to carry out fieldwork on St Kilda, and QinetiQ, Angus Campbell and Kilda Cruises for logistic support. LLC was supported by a BBSRC EASTBIO Doctoral Training Partnership Studentship and DHN by a BBSRC David Phillips Fellowship. The Soay sheep project was supported by a NERC responsive mode grant to JMP over the course of our four-year study