Anomalous monism and mental causality : on the debate of Donald Davidson’s philosophy of the mental

The English version of the first chapter of Erwin Rogler and Gerhard Preyer: Materialismus, anomaler Monismus und mentale Kausalität. Zur gegenwärtigen Philosophie des Mentalen bei Donald Davidson und David Lewis (2001) "Anomaler Monismus und Mentale Kausalität. Ein Beitrag zur Debatte über Donald Davidsons Philosophie des Mentalen" is a contribution to the current debates on the philosophy of the mental and mental causality initiated from Donald Davidson's philosophy with his article "Mental Events" (1970). It is the intent of the English version to give a response to the controversy among American, British and Australian philosophers in the context of a global exchange of ideas on problems understanding the mental. Contents 1. Preliminary Remarks 2. The Critique of Property-Epiphenomenalism and Counterarguments (a) The Enlargement of Nomological Reasoning (b) The Counterfactual Analysis (c) Supervenient Causality 3. Are Mental Properties real or unreal (fictive)? Abstract Things and events are fundamental entities in Davidson's ontology. Less distinct is the ontological status of properties, especially of mental types. Despite of some eliminative allusions there are weighty reasons to understand Davidson's philosophy of mind as including intentional realism. With it, the question of mental causality arises. There are two striking solutions to this problem: the epiphenomenalism of mental properties and the downward causation of mental events. Davidson cannot accept either. He claims to justify the mental as supervenient causality in order to thus integrate it into physicalism (his version of monism). But his argument at best proves the explanatory, not the causal relevance of mental properties. For this and for other reasons, Davidson fails the aspired synthesis of a sufficiently strong physicalism and the autonomy of the mental; a project whose realization is anyhow hard to achieve

JAK efficacy in Crohn’s disease

Inhibition of Janus kinases in Crohn’s disease (CD) patients has shown conflicting results in clinical trials. Tofacitinib, a pan-JAK inhibitor showed efficacy in ulcerative colitis (UC) and has been approved for the treatment of patients with moderate to severe UC. In contrast, studies in patients suffering from CD were disappointing and the primary endpoint of clinical remission could not be met in the respective phase II induction and maintenance trials. Subsequently, the clinical development of tofacitinib was discontinued in CD. In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. Subsequently phase III programs in CD have been initiated for both substances, which are still ongoing. Several newer molecules of this class of orally administrated immunosuppressants are tested in clinical programs. The concern of side effects of systemic JAK inhibition is addressed by either exclusively intestinal action or higher selectivity (Tyk2 inhibitors). In general, JAK inhibitors constitute a new promising class of drugs for the treatment of CD

Microbial Sensing by the Intestinal Epithelium in the Pathogenesis of Inflammatory Bowel Disease

Recent years have raised evidence that the intestinal microbiota plays a crucial role in the pathogenesis of chronic inflammatory bowels diseases. This evidence comes from several observations. First, animals raised under germ-free conditions do not develop intestinal inflammation in several different model systems. Second, antibiotics are able to modulate the course of experimental colitis. Third, genetic polymorphisms in a variety of genes of the innate immune system have been associated with chronic intestinal inflammatory diseases. Dysfunction of these molecules results in an inappropriate response to bacterial and antigenic stimulation of the innate immune system in the gastrointestinal tract. Variants of pattern recognition receptors such as NOD2 or TLRs by which commensal and pathogenic bacteria can be detected have been shown to be involved in the pathogenesis of IBD. But not only pathways of microbial detection but also intracellular ways of bacterial processing such as autophagosome function are associated with the risk to develop Crohn's disease. Thus, the “environment concept” and the “genetic concept” of inflammatory bowel disease pathophysiology are converging via the intestinal microbiota and the recognition mechanisms for an invasion of members of the microbiota into the mucosa

The heart and the gut

The heart and the gut seem to be two organs that do not have much in common. However, there is an obvious and clinically relevant impact of gut functions on the absorption of drugs and oral therapies on the one hand. On the other hand, the gut determines the quantity of nutrient uptake and plays a central role in metabolic diseases. Patients with inflammatory bowel diseases appear to have a higher risk for coronary heart disease despite a lower prevalence of ‘classical' risk factors, indicating additional links between the gut and the heart. However, they certainly have a ‘leaky' intestinal barrier associated with increased permeability for bacterial wall products. An impaired intestinal barrier function will be followed by bacterial translocation and presence of bacterial products in the circulation, which can contribute to atherosclerosis and chronic heart failure (CHF) as recent data indicate. Impaired cardiac function in CHF vice versa impacts intestinal microcirculation leading to a barrier defect of the intestinal mucosa and increased bacterial translocation. These pathways and the most recent insights into the impact of the gut on acute and chronic heart disease will be discussed in this revie

The Intestinal Barrier-Shielding the Body from Nano- and Microparticles in Our Diet

Nano- and microparticles are an implicit part of the human diet. They are unknowingly ingested with our food that contains them as additives or pollutants. However, their impact on human health is not yet understood and controversially discussed. The intestinal epithelial barrier shields our body against exogenous influences, such as commensal bacteria, pathogens, and body-foreign particles and, therefore, protects our body integrity. Breakdown of the intestinal epithelial barrier and aberrant immune responses are key events in the pathogenesis of inflammatory bowel disease (IBD). Epithelial lesions might enable systemic translocation of nano- and microparticles into the system, eventually triggering an excessive immune response. Thus, IBD patients could be particularly vulnerable to adverse health effects caused by the ingestion of synthetic particles with food. The food-additive titanium dioxide (TiO$_{2}$) serves as a coloring agent in food products and is omnipresent in the Western diet. TiO$_{2}$ nanoparticles exacerbate intestinal inflammation by activation of innate and adaptive immune response. Because of serious safety concerns, the use of TiO$_{2}$ as a food additive was recently banned from food production within the European Union. Due to environmental pollution, plastic has entered the human food chain, and plastic microparticles have been evidenced in the drinking water and comestible goods. The impact of plastic ingestion and its resulting consequences on human health is currently the subject of intense research. Focusing on TiO$_{2}$ and plastic particles in the human diet and their impact on epithelial integrity, gut homeostasis, and intestinal inflammation, this review is addressing contemporary hot topics which are currently attracting a lot of public attention

New insights into the pathogenesis of Crohn's disease: are they relevant for therapeutic options?

During the last few years significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A genetic susceptibility to Crohn's disease has been proven by identification of variations as risk factor NOD2/CARD15. Functional data on NOD2/CARD15 and NF-kappaB activation indicate that an inflammatory reaction of the intestinal mucosa, as an immediate response of the innate immune system, may be necessary for the maintenance of gut homeostasis. Crohn's disease is now also discussed as an impaired and inadequate immune reaction and no longer only as a hyper-responsiveness of the mucosal immune system. Data on NOD2/CARD15 expression suggest that macrophages and epithelial cells could be the locus of the primary pathophysiological defect and that T-cell activation might just be a secondary effect inducing chronification of the inflammation, perhaps as backup mechanism to insufficient innate immunity. In addition to NOD2/CARD15 there are more "innate" pathways by which commensal and pathogenic bacteria can directly be hindered to invade the human body (such as interaction with Toll like receptors, TLRs and defensins). The "germ-concept" and the "genetic concept" of IBD pathophysiology are converging. However, more time is needed until these important insights in IBD pathogenesis will make their way into routine diagnostic procedures and treatment of patients with IBD

Schwerer Verlauf einer Miliartuberkulose bei einem 34-jährigen Patienten mit Colitis ulcerosa und HIV-Infektion unter einer TNF-α-Antikörper-Therapie

Zusammenfassung : Ein 34-jähriger HIV-positiver Patient mit Colitis ulcerosa unter Anti- Tumor-Nekrose-Faktor-(TNF-)α-Therapie mit Infliximab wurde bei zunehmender Verschlechterung des Allgemeinzustands mit intermittierend febrilen Temperaturen, progredienter Lymphopenie, Anämie, Thrombopenie und Neutropenie in die Klinik der Autoren überwiesen. Trotz negativer Screeninguntersuchungen vor Beginn und während der Therapie mit Infliximab wurde schließlich eine Miliartuberkulose diagnostiziert und eine tuberkulostatische Therapie begonnen. Im Verlauf kam es bei dem Patienten zu einer progredienten Verschlechterung des klinischen Zustandsbilds mit Entwicklung einer schweren exsudativ-nekrotisierenden Form der Pankreatitis. Im weiteren Verlauf verstarb der Patient unter zunehmender respiratorischer Erschöpfung nach Entwicklung von progredienten pulmonalen Infiltraten und Pleuraergüsse

Fäkale Mikrobiota-Transplantation : Bereit für die Klinik?

Das Mikrobiom oder die intestinale Mikrobiota ist in den letzten Jahren zunehmend ins wissenschaftliche wie öffentliche Interesse gerückt. Es ist Inhalt einer Vielzahl von Medienberichten und Publikationen. Insbesondere die Rolle des Mikrobioms in der Entstehung verschiedenster Erkrankungen sowie die Möglichkeiten, die intestinale Mikrobiota in ihrer Zusammensetzung in therapeutischer Absicht zu beeinflussen, ist von grossem Interesse. Hier rückte in den letzten Jahren zunehmend die fäkale Mikrobiota-Transplantation (FMT) in den Fokus, in deren Rahmen der Spenderstuhl einem anderen Patienten verabreicht wird. Die FMT ist inzwischen die Therapie der Wahl für die Behandlung der rezidivierenden C.-difficile-Kolitis. Einmalig via Koloskopie verabreicht, stellt sie eine sichere und hocheffiziente Therapieform dar. Da das Mikrobiom auch mit zahlreichen anderen Erkrankungen assoziiert ist, wird die FMT auch zur Therapie verschiedenster anderer gastroenterologischer, chronisch-entzündlicher, metabolischer, maligner oder neuropsychiatrischer Erkrankungen erwogen. Hier ist die Datenlage allerdings noch dünn und weitere Forschung ist dringend nötig. = Ces dernières années, le microbiome ou microbiote intestinal attire de plus en plus l’intérêt des scientifiques et du public. Il fait l’objet d’une multitude de publications et de rapports dans les médias. En particulier le rôle du microbiome dans le développement de diverses maladies ainsi que les possibilités d’influencer la composition du microbiote intestinal à des fins thérapeutiques sont de grand intérêt. Dans ce domaine, une attention croissante est accordée ces dernières années à la bactériothérapie fécale (en anglais fecal microbiota transplantation, FMT), dans le cadre de laquelle la matière fécale d’un donneur est greffée à un autre patient. La FMT est désormais le traitement de première intention de la colite récidivante à C. difficile. Appliquée une unique fois par coloscopie, elle est un traitement sûr et hautement efficace. Le microbiome étant aussi associé à de nombreuses autres maladies, la FMT est également envisagée pour le traitement de toutes sortes d’autres maladies gastro-entérologiques, inflammatoires chroniques, métaboliques, malignes ou neuropsychiatriques. Mais là, les données disponibles sont encore maigres et des recherches plus avancées sont urgemment nécessaires. = Negli ultimi anni il microbioma, o microbiota intestinale, è stato oggetto di un crescente interesse scientifico e pubblico ed è argomento di un gran numero di relazioni e pubblicazioni dei media. In particolare, il ruolo del microbioma nello sviluppo di varie malattie e alla possibilità di influenzare la composizione del microbiota intestinale con intento terapeutico è di grande rilevanza. A questo riguardo, negli ultimi anni, l’attenzione si è sempre più concentrata sul trapianto di microbiota fecale (FMT/”fecal microbiota transplant”) in cui le feci del donatore vengono somministrate ad un altro paziente. La FMT è diventata la terapia di scelta per il trattamento della colite da C. difficile ricorrente. Somministrata una volta tramite colonscopia, è una forma di terapia sicura e molto efficace. Dato che il microbioma è associato anche a numerose altre malattie, la FMT è presa in considerazione pure per la terapia di un’ampia varietà di altre malattie gastroenterologiche, cronico-infiammatorie, metaboliche, maligne o neuropsichiatriche. Qui, tuttavia, i dati disponibili sono ancora scarsi e occorre urgentemente proseguire la ricerca

The impact of cold spells on the incidence of infectious gastroenteritis and relapse rates of inflammatory bowel disease: a retrospective controlled observational study

Goals: We aimed to assess the impact of very cold days on inflammatory bowel disease (IBD) flares and infectious gastroenteritis (IG). We defined a cold day using the World Meteorological definition of an ice day, which is a day with a maximum temperature below 0°C. Background: Recently, we have shown that heat waves increase the risk for IG and IBD flares. Study: We retrospectively collected data from 738 IBD and 786 IG patients admitted to the University Hospital of Zurich between 2001 and 2005 and from 506 patients with other noninfectious chronic intestinal inflammations as controls. Climate data were received by the Swiss Federal Office for Meteorology and Climatology. Results: There was no evidence for an increased risk of IBD flares (relative risk, RR = 0.99, 95% confidence interval, CI: 0.72-1.33, = 0.94) or IG flares (RR = 1.16, 95% CI: 087-1.52, = 0.30) on very cold days. This negative finding was confirmed in alternative formulations with lagged or cumulative (possibly lagged) effects. Conclusion: In this retrospective controlled observational study, no evidence for an increase in hospital admissions due to flares of IBD and IG during cold days was observed. This may be attributed to not relevantly altered bacterial growth conditions during cold days compared to heat waves