The present paper argues that, despite appearance to the contrary, Kierkegaard’s writings offer promising argumentational resources for addressing the problem of evil. According to Kierkegaard, ...however, in order to make use of these resources at all, one must necessarily be willing to shift the battleground, so to speak: from a third- to a genuine first-person perspective, namely the perspective of what Climacus dubs Religiousness A. All (yet also only) those who seek deliberate self-annihilation before God—a God in relation to whom they perceive themselves always in the wrong—shall discover the ideal that an unwavering and in fact unconditional thankfulness (namely, for being forgiven) is to be considered the only appropriate attitude towards God and as such both necessary and sufficient for coming to terms with evil and suffering, at least in the life of someone making that discovery. I will argue that Kierkegaard’s (non-)pseudonymous writings provide reasons, at times unwittingly, for adopting the perspective of Religiousness A; however, I will also and ultimately argue that the principle of infinite thankfulness as a corollary of that perspective flounders when it comes to making sense of (the eschatological implications of) the suffering of others.
Abstract
The article critically engages Menachem Fisch’s account of normative frameworks, in particular of (rational) transitions between them. I argue, first, that exposure to the normative ...criticism leveled at us by other human beings is indeed “capable of destabilizing normative commitment” to one’s own underlying framework beliefs and standards, as Fisch holds; however, closer scrutiny reveals that such exposure is neither sufficient nor necessary but rather accidental in this respect. Second, I will try to show that Søren Kierkegaard’s account of how people fundamentally change their mind provides resources for both a substantial critique of Fisch and a more adequate understanding of the transitions in question. The article argues, third, that Fisch’s framework model – though meaningful, in fact heuristically indispensable in and as of itself – has robust
transcendental
implications which as such are being ignored, if not directly denied by Fisch and, precisely
by
being ignored or denied, unnecessarily weaken the overall plausibility of his account. Finally, and
ex post
, I will address an important objection raised by some commentators.
The article aims to uncover a deep ambivalence in the figure of Job, as it is presented in the book of the same title, especially in the latter’s “poetry” or dialogue section. This ambivalence ...corresponds to and in fact emerges from what appears to be a pragmatic paradox: Job is in the wrong (i.e., guilty) in relation to God, precisely by claiming to be right (i.e., innocent); conversely, he can be and must be considered right, if and to the extent that he honestly renounces the latter claim. Accordingly, he cannot both be right (or wrong) and claim to be right or (or wrong)—a special case of what is observed, within epistemology, as an incompatibility of truth and assertibility conditions. In the present text, this core thesis is developed in four steps: the first introduces and briefly contextualizes the claim; the second tries to demonstrate that it provides at least sufficient means for making narrative sense of the book as a whole and, in particular, the controversy between Job and his friends; a third paragraph tackles the (philosophical and/or theological) presuppositions and implications of the thesis from a Christian standpoint, whereas the conclusion addresses the question of if and how the previous findings bear upon the rationality issue. Here, a final paradox emerges: that which would appear to be most rational from a Christian perspective (the task of sin consciousness) must be deemed humanly impossible to fulfill; considering the latter possible renders the task futile, hence irrational.
Occupational health researchers and practitioners have mainly focused on the individual and organizational levels, whereas the team level has been largely neglected. In this study, we define
as ...employees' shared perceptions of the extent to which their team is concerned, cares, and communicates about health issues. Based on climate, signaling, and social exchange theories, we examined a multilevel model of team health climate and its relationships with five well-established health-related outcomes (i.e., subjective general health, psychosomatic complaints, mental health, work ability, and presenteeism). Results of multilevel analyses of data provided by 6,449 employees in 621 teams of a large organization showed that team health climate is positively related to subjective general health, mental health, and work ability, and negatively related to presenteeism, above and beyond the effects of team size, age, job tenure, job demands, job control, and employees' individual perceptions of health climate. Moreover, additional analyses showed that a positive team health climate buffered the negative relationship between employee age and work ability. Implications for future research on team health climate and suggestions for occupational health interventions in teams are discussed.
Purpose
– In many countries, both the number of older people in need of care and the number of employed caregivers of elderly relatives will increase over the next decades. The purpose of this paper ...is to examine the extent to which perceived organizational, supervisor, and coworker support for eldercare reduce employed caregivers’ strain and weaken the relationship between eldercare demands and strain.
Design/methodology/approach
– Survey data were collected from 100 employed caregivers from one organization.
Findings
– Results showed that eldercare demands were positively related to strain, and perceived organizational eldercare support (POES) was negatively related to strain. In addition, high POES weakened the relationship between eldercare demands and strain.
Research limitations/implications
– The cross-sectional design and use of self-report scales constitute limitations of the study.
Practical implications
– POES is a resource for employed caregivers, especially when their eldercare demands are high.
Originality/value
– This research highlights the relative importance of different forms of perceived support for reducing employed caregivers’ strain and weakening the relationship between eldercare demands and strain.
There is a tremendous need for developing new useful prognostic factors in ovarian cancer. Galectins are a family of carbohydrate binding proteins which have been suggested to serve as prognostic ...factors for various cancer types. In this study, the presence of Galectin-1, -3, and -7 was investigated in 156 ovarian cancer specimens by immunochemical staining. Staining was evaluated in the cytoplasm and nucleus of cancer cells as well as the peritumoral stroma using a semi quantitative score (Remmele (IR) score). Patients' overall survival was compared between different groups of Galectin expression. Galectin (Gal)-1 and -3 staining was observed in the peritumoral stroma as well as the nucleus and cytoplasm of tumor cells, while Gal-7 was only present in the cytoplasm of tumor cells. Patients with Gal-1 expression in the cytoplasm or high Gal-1 expression in the peritumoral stroma showed reduced overall survival. Nuclear Gal-3 staining correlated with a better outcome. We observed a significantly reduced overall survival for cases with high Gal-7 expression and a better survival for Gal-7 negative cases, when compared to cases with low expression of Gal-7. We were able to show that both tumor and stroma staining of Gal-1 could serve as negative prognostic factors for ovarian cancer. We were able to confirm cytoplasmic Gal-7 as a negative prognostic factor. Gal-3 staining in the nucleus could be a new positive prognosticator for ovarian cancer.
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various ...implications in cancer biology. In this study, the presence of galectin (Gal)-8 and -9 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining was evaluated using semi-quantitative immunoreactivity (IR) scores and correlated to clinical and pathological data. Different types of galectin expression were compared with respect to disease-free survival (DFS) and overall survival (OS). Gal-8 served as a new positive prognostic factor for the OS and DFS of ovarian cancer patients. Gal-9 expression determined the DFS and OS of ovarian cancer patients in two opposing ways-moderate Gal-9 expression was correlated with a reduced outcome as compared to Gal-9 negative cases, while patients with high Gal-9 expression showed the best outcome.
Progressive respiratory failure and hyperinflammatory response is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. Despite mounting evidence of disruption of the ...hypothalamus-pituitary-adrenal axis in COVID-19, relatively little is known about the tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adrenal glands and associated changes. Here we demonstrate adrenal viral tropism and replication in COVID-19 patients. Adrenal glands showed inflammation accompanied by inflammatory cell death. Histopathologic analysis revealed widespread microthrombosis and severe adrenal injury. In addition, activation of the glycerophospholipid metabolism and reduction of cortisone intensities were characteristic for COVID-19 specimens. In conclusion, our autopsy series suggests that SARS-CoV-2 facilitates the induction of adrenalitis. Given the central role of adrenal glands in immunoregulation and taking into account the significant adrenal injury observed, monitoring of developing adrenal insufficiency might be essential in acute SARS-CoV-2 infection and during recovery.
The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage ...disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC).
Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining,
Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization.
IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.
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•Immunomodulatory imide drugs (IMiDs) inhibit bladder smooth muscle contraction.•IMiDs reduce bladder detrusor cell growth and actin formation.•IMiDs exhibit vasoregulatory functions in organ baths.•Novel drug class effect for IMiDs.•Molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.
Lower urinary tract symptoms (LUTS) involve benign prostatic hyperplasia (BPH) and overactive bladder (OAB). Standard-of-care medical treatment includes α
-blockers and antimuscarinics for reduction ...of prostate and detrusor smooth muscle tone, respectively, and 5α-reductase inhibitors (5-ARI) to prevent prostate growth. Current medications are marked by high discontinuation rates due to unfavourable balance between efficacy and treatment-limiting side effects, ranging from dry mouth for antimuscarinics to cardiovascular dysregulation and a tendency to fall for α
-blockers, which results from hypotension, due to vasorelaxation. Agonist-induced smooth muscle contractions are caused by activation of receptor-coupled G-proteins. However, little is known about receptor- and organ-specific differences in coupling to G-proteins. With YM-254890, a small molecule inhibitor with presumed specificity for Gα
became recently available. Here, we investigated effects of YM-254890 on prostate, bladder and vascular smooth muscle contraction, and on growth-related functions in prostate stromal cells.
Contractions of human prostate and detrusor tissues, porcine renal and coronary arteries were induced in an organ bath. Proliferation (EdU assay), growth (colony formation), apoptosis and cell death (flow cytometry), viability (CCK-8) and actin organization (phalloidin staining) were studied in cultured human prostate stromal cells (WPMY-1).
Contractions by α
-adrenergic agonists, U46619, endothelin-1, and neurogenic contractions were nearly completely inhibited by YM-254890 (30 nM) in prostate tissues. Contractions by cholinergic agonists, U46619, endothelin-1, and neurogenic contractions were only partly inhibited in detrusor tissues. Contractions by α
-adrenergic agonists, U46619, endothelin-1, and neurogenic contractions were strongly, but not fully inhibited in renal arteries. Contractions by cholinergic agonists were completely, but by U46619 and endothelin-1 only strongly inhibited, and neurogenic contractions reduced by half in coronary arteries. YM-254890 had no effect on agonist-independent contractions induced by highmolar (80 mM) potassium chloride (KCl). Neurogenic detrusor contractions were fully sensitive to tetrodotoxin. In WPMY-1 cells, YM-254890 caused breakdown of actin polymerization and organization, and obvious, but clearly limited decreases of proliferation rate, colony formation and viability, and slightly increased apoptosis.
Intracellular post-receptor signaling pathways are shared by Gα
-coupled contractile receptors in multiple smooth muscle-rich organs, but to different extent. While inhibition of Gα
causes actin breakdown, anti-proliferative effects were detectable but clearly limited. Together this may aid in developing future pharmaceutical targets for LUTS and antihypertensive medication.
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