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Depression is a common and highly disabling condition in older adults. It is a heterogenous disorder and there is emerging evidence of a link between inflammation and depression in older patients, with a possible inflammatory subtype of depression. Persistent low-level inflammation, from several sources including psychological distress and chronic disease, can disrupt monoaminergic and glutaminergic systems to create dysfunctional brain networks. Despite the evidence for the role of inflammation in depression, there is insufficient evidence to recommend use of any putative anti-inflammatory agent in the treatment of depression in older adults at this stage. Further characterisation of markers of inflammation and stratification of participants with elevated rates of inflammatory markers in treatment trials is needed.

This systematic review aimed to synthesise the results from studies investigating the effects of prebiotics and probiotics on kynurenine pathway metabolism. Thirteen studies were identified for inclusion, comprising 12 probiotic and two prebiotic arms. Participants included healthy individuals and individuals with various clinical conditions. Twelve metabolites were examined across the studies, using a range of biological samples. Across all interventions, 11 reported an effect on ≤ metabolite. Although limited by clinical and methodological heterogeneity, pooled analysis (n = 253) found probiotics to significantly affect serum kynurenine (g = 0.315, CI = 0.070 to 0.560, p = 0.012, 4 studies, I2 = 0%) and the kynurenine:tryptophan ratio (g = 0.442, CI = 0.074 to 0.810, p = 0.018, 4 studies, I2 = 42 %). Risk of bias across the studies was generally low. The results provide preliminary evidence that probiotics can modulate kynurenine pathway metabolism, with less evidence available regarding prebiotics. Future studies which further consider methodological confounds and sample characteristics are required, to establish intervention efficacy. PROSPERO registration #CRD42019154677.

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

This article rejects the claim made by other scholars that Plato in the Statesman, by employing the so-called ‘architect’ (ὁ ἀρχιτέκτων) in one of the early divisions leading to the definition of political expertise, prefigured and anticipated the architectonic conception of political expertise advanced by Aristotle. It argues for an alternative reading in which Plato in the Statesman, and in the only other of his works (Gorgias) in which the word appears, closely tracks the existing social role of the architektōn, who was designated as such only in virtue of appointment by a city to a role that was crucially defined as epitactic, involving overseeing the workers on site engaged in constructing some civic building works. It is this epitactic dimension of the role on which Plato relies in the Statesman, as opposed to the kind of claim to overarching integrative expertise that Aristotle would use the figure of architectonic political knowledge to make.

This systematic review investigated the effects of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity. MEDLINE complete, EMBASE, Scopus, Cochrane and CINAHL were searched between date of inception and October 2019. Seven trials were reviewed (a total of 130 participants, with 10 to 44 participants in each trial). Of these, five were single-arm interventions and included very low-energy diets adjunctive to comprehensive lifestyle interventions such as nutritional counselling, behavioural therapy and exercise programmes. Changes to taxa within the Firmicutes phylum were found, including reduced abundance of potentially beneficial butyrogenic microbes (Roseburia, Faecalbacterium prausnitzii, Lactobacillus, Bifidobacterium and Lachnospiraeceae). Conversely, increased abundance of potentially pathogenic or opportunistic microbes from the Bacteroidetes phylum was reported, including increases in Alistipes and Bacteroides taxa. However, outcomes were inconsistent, with some trials also showing decreases in Bacteroides taxa and increases in commensal microbiota, such as Lachnospiraceae and Bifidobacteriaceae. The changes in metabolic parameters observed from baseline to after the ultra-processed very low-energy diets were mostly beneficial or were not significantly altered. Although the selected articles were deemed to have satisfactory methodological quality, to understand the possible direct effects of these regimens on gut microbiota, further rigorously designed trials, with more standardised microbiological sequencing techniques and detailed reporting, are required. Study registration: Prospero ID: CRD42019124436.

While leaders in many times and places from ancient Greece to today have been called to account, it has been claimed that leaders in ancient Athens were called to account more than any other group in history. This paper surveys the distinctive ways in which Athenian accountability procedures gave the democratic people as a whole a meaningful voice in defining, revealing, and judging the misuse of office, and in holding every single official regularly and personally accountable for their use of their powers. By then assessing a drastic case of unaccountability in a certain moment of Athenian history – the rule of the Thirty in 404–403 BCE – and how accountability was ultimately imposed on them, the paper concludes with thoughts about what might deepen and restore trust in the accountability of public officials today.

Context Saffron (Crocus sativus L.) has gained interest as a potential treatment in psychiatry. Objective This systematic review and meta-analysis sought to investigate the effect of saffron supplementation, as both an adjunctive therapy and monotherapy, on symptoms of depression and anxiety in clinical and general populations compared with pharmacotherapy or placebo. Data sources Using the PRISMA guidelines, a systematic literature review of randomized controlled trials was conducted. Data extraction A meta-analysis was conducted to determine treatment effect. Risk of bias was assessed using the Jadad scale. Results Twenty-three studies were included. Saffron had a large positive effect size when compared with placebo for depressive symptoms (g = 0.99, P < 0.001) and anxiety symptoms (g = 0.95, P < 0.006). Saffron also had a large positive effect size when used as an adjunct to antidepressants for depressive symptoms (g = 1.23, P = 0.028). Egger’s regression test found evidence of publication bias. Conclusions Saffron could be an effective intervention for symptoms of depression and anxiety; however, due to evidence of publication bias and lack of regional diversity, further trials are required. PROSPERO registration CRD42017070060.

Gavin Lawrence (Chapter 2) opens the volume’s explorations by considering the dialogue’s overall ‘non-elenchtic method’, including collection and division but also the central roles of paradigm (paradeigma, translated also in this volume as ‘model’) and in particular of weaving as model of not only politics but also method and ontology, the latter a role that it plays in other related Platonic dialogues. Lawrence surveys the early divisions (257a1-259d6, ...

The Introduction is in three parts: a discussion of ‘politikos’ by Panos Dimas; an outline of the structure and methods in the Statesman by Susan Sauvé Meyer; and an overview of the volume by Melissa Lane. The first part addresses the meaning of the term ‘politikos’ that serves as the dialogue’s title, and the Eleatic Visitor’s claim that each part of the sprawling conversation is necessary for its dialectical purposes. It is argued that the expert politikos of the present dialogue is the philosopher-king of the Republic. It is contended that there is insufficient evidence for dating the Statesman in relation to the Sophist and Theaetetus, and good reason to be sceptical that Plato planned to write a further dialogue, Philosophos. The second part surveys the structure of the dialogue and the range of methods (dialectic, division, myth, paradeigma) it deploys. It is argued that the recurring task of distinguishing the politikos from rival claimants to that title does not count as a ‘division’ in the technical sense. The third part gives an overview of the arguments in the individual chapters.

Chapter 10 focusses on Statesman 303d4-305e7 and considers the Visitor’s seemingly three definitions of statecraft in the dialogue: 305c10-d5, 305e2-6, and 311b7-c7. By focusing on the role of the dunamis of given forms of expertise, and the metaphorical method of smelting metals at work in this section of the dialogue, it argues that a definition of statecraft (hē politikē) as ruling, caring, and weaving is reached in 305e2-6 and then fleshed out in 311b7-c7 by the explication of the ergon (task) which it is the role of that dunamis to accomplish. This is broadly consonant with a passage in Republic 5 identifying any given dunamis in terms of that over which it is set and what it accomplishes (apergazetai), a schema filled out in the Statesman by explicit reference to the ergon of a dunamis (305c4-5). Political expertise is not a passive body of knowledge but rather actively and precisely organized toward the realization of its distinctive task.