High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders.

See Rogawski (doi:) for a scientific commentary on this article. The MCT ketogenic diet, an established treatment for drug-resistant epilepsy, leads to an elevation of plasma decanoic acid and ketones. Chang et al. show that decanoic acid, rather than ketones, provides anti-seizure activity in several ex vivo rat models of epilepsy, likely through the direct inhibition of AMPA receptors.

Summary Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug‐resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure‐induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.

The role of eHealth in conflict settings is increasingly important to address geographic, epidemiologic and clinical disparities. This study categorizes various forms of eHealth usage in conflict and aims to identify gaps in evidence to make recommendations for further research and practice. The analysis was carried out via a narrative hermeneutic review methodology. Articles that fulfilled the following screening criteria were reviewed: (1) describing an eHealth intervention in active conflict or ongoing insurgency, (2) an eHealth intervention targeting a conflict-affected population, (3) an e-learning platform for delivery in conflict settings and (4) non-interventional descriptive reviews relating to eHealth in conflict. Of the 489 papers eligible for screening, 46 merited final inclusion. Conflict settings described include Somalia, Sudan, Afghanistan, Syria, Iraq, Pakistan, Chechnya, Gaza and the Democratic Republic of Congo. Thirty-six studies described specific eHealth initiatives, while the remainder were more generic review papers exploring general principles. Analysis resulted in the elucidation of three final categories of current eHealth activity in conflict-affected settings: (1) eHealth for clinical management, (2) e-learning for healthcare in conflict and (3) eHealth for information management in conflict. Obvious disparities in the distribution of technological dividends from eHealth in conflict are demonstrated by this review. Conflict-affected populations are predominantly subject to ad hoc and voluntary initiatives delivered by diaspora and civil society organizations. While the deployment of eHealth technologies in conflict settings is increasingly normalized, there is a need for further clarification of global norms relating to practice in this context.

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The financial crisis has put pressure on government budgets across Europe. The expectation is that this also has affected public transport budgets in metropolitan areas. This article looks at five cases of metropolitan public transport to see to what extent this is the case. Multi-level governance and fiscal federalism explain the rather surprising outcome. This article is aimed to be a first step into a better understanding of the effect of governance in public transport in a broad sense. It develops the understanding of how the organizational context influences those funding decisions and the related outcome in terms of public transport services provided and passengers transported. The article shows that the effect of budget pressure was varied over the five cases depending on governance in those cases and overall can be characterized as limited. Funding and supply generally kept growing, despite the pressure put on budgets by the financial crisis.

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