Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options

Genotype-specific responses in Atlantic salmon (Salmo salar) subject to dietary fish oil replacement by vegetable oil: a liver transcriptomic analysis

<p>Abstract</p> <p>Background</p> <p>Expansion of aquaculture is seriously limited by reductions in fish oil (FO) supply for aquafeeds. Terrestrial alternatives such as vegetable oils (VO) have been investigated and recently a strategy combining genetic selection with changes in diet formulations has been proposed to meet growing demands for aquaculture products. This study investigates the influence of genotype on transcriptomic responses to sustainable feeds in Atlantic salmon.</p> <p>Results</p> <p>A microarray analysis was performed to investigate the liver transcriptome of two family groups selected according to their estimated breeding values (EBVs) for flesh lipid content, 'Lean' or 'Fat', fed diets containing either FO or a VO blend. Diet principally affected metabolism genes, mainly of lipid and carbohydrate, followed by immune response genes. Genotype had a much lower impact on metabolism-related genes and affected mostly signalling pathways. Replacement of dietary FO by VO caused an up-regulation of long-chain polyunsaturated fatty acid biosynthesis, but there was a clear genotype effect as fatty acyl elongase (elovl2) was only up-regulated and desaturases (Δ5 fad and Δ6 fad) showed a higher magnitude of response in Lean fish, which was reflected in liver fatty acid composition. Fatty acid synthase (FAS) was also up-regulated by VO and the effect was independent of genotype. Genetic background of the fish clearly affected regulation of lipid metabolism, as PPARα and PPARβ were down-regulated by the VO diet only in Lean fish, while in Fat salmon SREBP-1 expression was up-regulated by VO. In addition, all three genes had a lower expression in the Lean family group than in the Fat, when fed VO. Differences in muscle adiposity between family groups may have been caused by higher levels of hepatic fatty acid and glycerophospholipid synthesis in the Fat fish, as indicated by the expression of FAS, 1-acyl-sn-glycerol-3-phosphate acyltransferase and lipid phosphate phosphohydrolase 2.</p> <p>Conclusions</p> <p>This study has identified metabolic pathways and key regulators that may respond differently to alternative plant-based feeds depending on genotype. Further studies are required but data suggest that it will be possible to identify families better adapted to alternative diet formulations that might be appropriate for future genetic selection programmes.</p

Sustainability Mining: Water for Mining, and Mining Water

This chapter examines the multifaceted nature of the relationship between water and mining. Several perspectives are offered. Mines are located to gain access to the mineral, but this is always in the context of water. The conditions under which the water has carved a catchment are strongly influenced by the climatic regime and the geological foundations under which the soil has been formed and vegetation has evolved. Mining is an embedded activity, located unambiguously in a landscape shaped by water. Mining as an activity must have a strategy for accessing, disposing of and using water. Mining relies on water for its operation, often using it intensively to achieve its production quota. This chapter also explores the relationship between mining and the use of water in the urban setting. Engineering feats, technological developments and regulatory frameworks facilitated by a history of mining in Western Australia (WA) have led to accessibility and exploitation of water for other purposes. How water is extracted can be likened to ‘mining water’ and how the treatment of water for human consumption uses mining by-products is considered. These perspectives highlight societal vulnerabilities to the environmental, psychological, sociocultural and political impacts of mining, that go beyond traditional perspectives of the advantages or disadvantages and cost benefit analysis of mining in society. The consequence of this traditional perspective is that water can be treated solely as a commodity, while other values of water are overlooked. Reconsidering the fundamental value and importance of water to society together with the embedded nature of mines in the landscape enables an insightful perspective on the contribution that mining and water make to society. Secondly, recognising the influence that mining has on patterns of water use, regulation and distribution may enable further consideration of sustainable water use in other settings

Adjusting wastewater treatment effluent standards to protect the receiving waters: the case of low flow rivers in central Spain

[EN] Freshwater quality is deteriorating worldwide. In populated areas, urban pollution is the main pressure on surface continental waters, but intensive wastewater treatment is costly. Setting standards for treatment of wastewater before discharge is a major policy instrument for water authorities, balancing environmental gains and operational costs. Discharge permits usually define concentration limits at the discharge point of the plant effluent. This approach, however, may not guarantee the good status of the receiving waters. Discharge permits should be directly linked to pollutant concentration in the river. Our paper develops an approach to adaptively adjust discharge permits and applies it to Madrid and the Manzanares river, a city of more than 3 million inhabitants discharging its treated wastewater to a stream having less than 2 m(3) s(-1) average flow. Stricter limits to 5-day biological oxygen demand (11 mg O-2 L-1), ammonium (0.5 mg N-NH4 L-1), nitrate (5.9 mg N-NO3 L-1), and phosphate (0.17 mg P-PO4 L-1) at plant effluent are required to meet the river environmental objectives. The results can be generalized to assess wastewater management decisions in other geographical areas.The authors wish to thank the Tagus River Basin Authority (Confederacion Hidrografica del Tajo) for their availability and readiness to share information, and the anonymous reviewers for their valuable and constructive comments. This research was funded by the Botin Foundation, Spain.Bolinches, A.; De Stefano, L.; Paredes Arquiola, J. (2020). Adjusting wastewater treatment effluent standards to protect the receiving waters: the case of low flow rivers in central Spain. 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Testosterone is inversely related to brain activity during emotional inhibition in schizophrenia

Sex steroids affect cognitive function as well as emotion processing and regulation. They may also play a role in the pathophysiology of schizophrenia. However, the effects of sex steroids on cognition and emotion-related brain activation in schizophrenia are poorly understood. Our aim was to determine the extent to which circulating testosterone relates to brain activation in men with schizophrenia compared to healthy men during cognitive-emotional processing. We assessed brain activation in 18 men with schizophrenia and 22 age-matched healthy men during an emotional go/no-go task using fMRI and measured total serum testosterone levels on the same morning. We performed an ROI analysis to assess the relationship between serum testosterone and brain activation, focusing on cortical regions involved the emotional go/no-go task. Slower RT and reduced accuracy was observed when participants responded to neutral stimuli, while inhibiting responses to negative stimuli. Healthy men showed a robust increase in activation of the middle frontal gyrus when inhibiting responses to negative stimuli, but there was no significant association between activation and serum testosterone level in healthy men. Men with schizophrenia showed a less pronounced increase in activation when inhibiting responses to negative stimuli; however, they did show a strong inverse association between serum testosterone level and activation of the bilateral middle frontal gyrus and left insula. Additionally, increased accuracy during inhibition of response to negative words was associated with both higher serum testosterone levels and decreased activation of the middle frontal gyrus in men with schizophrenia only. We conclude that endogenous hormone levels, even within the normal range, may play an enhanced modulatory role in determining the neural and behavioural response during cognitive-emotional processing in schizophrenia