Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

Activities related with electricity consumption in the Spanish residential sector: variations between days of the week, Autonomous Communities and size of towns

Nowadays the electricity consumption in the residential sector attracts policy and research efforts, in order to propose saving strategies and to attain a better balance between production and consumption, by integrating renewable energy production and proposing suitable demand side management methods. To achieve these objectives it is essential to have real information about household electricity demand profiles in dwellings, highly correlated, among other aspects, with the active occupancy of the homes and to the personal activities carried out in homes by their occupants. Due to the limited information related to these aspects, in this paper, behavioral factors of the Spanish household residents, related to the electricity consumption, have been determined and analyzed, based on data from the Spanish Time Use Surveys, differentiating among the Autonomous Communities and the size of municipalities, or the type of days, weekdays or weekends. Activities involving a larger number of houses are those related to Personal Care, Food Preparation and Washing Dishes. The activity of greater realization at homes is Watching TV, which together with Using PC, results in a high energy demand in an aggregate level. Results obtained enable identify prospective targets for load control and for efficiency energy reduction recommendations to residential consumers.

Assessment of the anthelmintic activity of medicinal plant extracts and purified condensed tannins against free-living and parasitic stages of Oesophagostomum dentatum

Background: Plant-derived condensed tannins (CT) show promise as a complementary option to treat gastrointestinal helminth infections, thus reducing reliance on synthetic anthelmintic drugs. Most studies on the anthelmintic effects of CT have been conducted on parasites of ruminant livestock. Oesophagostomum dentatum is an economically important parasite of pigs, as well as serving as a useful laboratory model of helminth parasites due to the ability to culture it in vitro for long periods through several life-cycle stages. Here, we investigated the anthelmintic effects of CT on multiple life-cycles stages of O. dentatum. Methods: Extracts and purified fractions were prepared from five plants containing CT and analysed by HPLC-MS. Anthelmintic activity was assessed at five different stages of the O. dentatum life cycle; the development of eggs to infective third-stage larvae (L3), the parasitic L3 stage, the moult from L3 to fourth-stage larvae (L4), the L4 stage and the adult stage. Results: Free-living larvae of O. dentatum were highly susceptible to all five plant extracts. In contrast, only two of the five extracts had activity against L3, as evidenced by migration inhibition assays, whilst three of the five extracts inhibited the moulting of L3 to L4. All five extracts reduced the motility of L4, and the motility of adult worms exposed to a CT-rich extract derived from hazelnut skins was strongly inhibited, with electron microscopy demonstrating direct damage to the worm cuticle and hypodermis. Purified CT fractions retained anthelmintic activity, and depletion of CT from extracts by pre-incubation in polyvinylpolypyrrolidone removed anthelmintic effects, strongly suggesting CT as the active molecules. Conclusions: These results suggest that CT may have promise as an alternative parasite control option for O. dentatum in pigs, particularly against adult stages. Moreover, our results demonstrate a varied susceptibility of different life-cycle stages of the same parasite to CT, which may offer an insight into the anthelmintic mechanisms of these commonly found plant compounds.

Remarkable dynamics of nanoparticles in the urban atmosphere

Nanoparticles emitted from road traffic are the largest source of respiratory exposure for the general public living in urban areas. It has been suggested that adverse health effects of airborne particles may scale with airborne particle number, which if correct, focuses attention on the nanoparticle (less than 100 nm) size range which dominates the number count in urban areas. Urban measurements of particle size distributions have tended to show a broadly similar pattern dominated by a mode centred on 20–30 nm diameter emitted by diesel engine exhaust. In this paper we report the results of measurements of particle number concentration and size distribution made in a major London park as well as on the BT Tower, 160 m aloft. These measurements taken during the REPARTEE project (Regents Park and BT Tower experiment) show a remarkable shift in particle size distributions with major losses of the smallest particle class as particles are advected away from the traffic source. In the Park, the traffic related mode at 20–30 nm diameter is much reduced with a new mode at <10 nm. Size distribution measurements also revealed higher number concentrations of sub-50 nm particles at the BT Tower during days affected by higher turbulence as determined by Doppler Lidar measurements and are indicative of loss of nanoparticles from air aged during less turbulent conditions. These results are suggestive of nanoparticle loss by evaporation, rather than coagulation processes. The results have major implications for understanding the impacts of traffic-generated particulate matter on human health.

TNF-α influences the lateral dynamics of TNF receptor I in living cells

In mammalian cells, inflammation is mainly mediated by the binding of tumor necrosis factor alpha to tumor necrosis factor receptor 1. In this study, we investigated lateral dynamics of TNF-R1 before and after ligand binding using high-density single-particle tracking in combination with photoactivated localization microscopy. Our single-molecule data indicates the presence of tumor necrosis factor receptor 1 with different mobilities in the plasma membrane, suggesting different molecular organizations. Cholesterol depletion led to a decrease of slow receptor species and a strong increase in the average diffusion coefficient. Moreover, as a consequence of tumor necrosis factor-alpha treatment, the mean diffusion coefficient moderately increased while its distribution narrowed. Based on our observation, we propose a refined mechanism on the structural arrangement and activation of tumor necrosis factor receptor 1 in the plasma membrane.

Hsc70 is a novel interactor of NF-kappaB p65 in living hippocampal neurons

Signaling via NF-κB in neurons depends on complex formation with interactors such as dynein/dynactin motor complex and can be triggered by synaptic activation. However, so far a detailed interaction map for the neuronal NF-κB is missing. In this study we used mass spectrometry to identify novel interactors of NF-κB p65 within the brain. Hsc70 was identified as a novel neuronal interactor of NF-κB p65. In HEK293 cells, a direct physical interaction was shown by co-immunoprecipitation and verified via in situ proximity ligation in healthy rat neurons. Pharmacological blockade of Hsc70 by deoxyspergualin (DSG) strongly decreased nuclear translocation of NF-κB p65 and transcriptional activity shown by reporter gene assays in neurons after stimulation with glutamate. In addition, knock down of Hsc70 via siRNA significantly reduced neuronal NF-κB activity. Taken together these data provide evidence for Hsc70 as a novel neuronal interactor of NF-κB p65.

Leveraging everyday technology for people living with dementia: a case study

– The purpose of this paper is to present the self-described “journey” of a person with dementia (Brian; author 3) in his re-learning of old technologies and learning of new ones and the impact this had on his life. Design/methodology/approach – This is a single case study detailing the participant's experiences collaborating with a researcher to co-create methods of facilitating this learning process, which he documented in the form of an online blog and diary entries. These were analysed using NVivo to reveal the key themes. Findings – Brian was able to relearn previously used technologies and learn two new ones. This lead to an overarching theme of positive outlook on life supported by person-centredness, identity and technology, which challenged negative perceptions about dementia. Research limitations/implications – The paper provides an example of how learning and technology improved the life of one person with dementia. By sharing the approach the authors hope to encourage others to embrace the challenge of designing and developing innovative solutions for people with a dementia diagnosis by leveraging both current mainstream technology and creating novel bespoke interventions for dementia. Originality/value – The personal perspective of a person with dementia and his experiences of (re-) learning provide a unique insight into the impact of technology on his life.

High prevalence of undernutrition and low dietary diversity in institutionalised elderly living in Sri Lanka

This research received no specific grant from any funding agency in the public, commercial and not-for-profit sectors. The authors wish to thank the participants, administrators and caregivers of the homes for elders for their enthusiastic cooperation and also the Nutrition Research Team of the Department of Applied Nutrition, Wayamba University of Sri Lanka, for their valuable assistance during the course of the study. The authors also wish to thank Mr. S. Rahanan for coordination and the assistance given in data collection especially in Tamil speaking participants. K.M.R designed and managed the study, interpreted the data and drafted the manuscript. M.P.P.M contributed to the data collection, data analysis and coordination of the study. M.W, K.G.J and J.A.L assisted in data interpretation and critical revision of the manuscript. The authors declare that there is no conflict of interest of any kind involved in this study or this publication. Ethical clearance for this study was obtained from the Ethical Review Committee of the Sri Lanka Medical Association (ERC/13-037).

Living to die and dying to live: the survival strategy behind leaf senescence

Senescence represents the final developmental act of the leaf, during which the leaf cell is dismantled in a coordinated manner to remobilize nutrients and to secure reproductive success. The process of senescence provides the plant with phenotypic plasticity to help it adapt to adverse environmental conditions. Here, we provide a comprehensive overview of the factors and mechanisms that control the onset of senescence. We explain how the competence to senesce is established during leaf development, as depicted by the senescence window model. We also discuss the mechanisms by which phytohormones and environmental stresses control senescence, as well as the impact of source-sink relationships on plant yield and stress tolerance. In addition, we discuss the role of senescence as a strategy for stress adaptation and how crop production and food quality could benefit from engineering or breeding crops with altered onset of senescence.

“Very sore nights and days”: the child’s experience of illness in early modern England, c. 1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.

Living the Revolution: urban communes & soviet socialism, 1917-1932

This book follows a revolutionary trend popular among young activists and would-be radicals after 1917, the formation of collective units of cohabitation and association known as 'urban communes'. In these spaces, activists tried to live what they understood as the 'socialist lifestyle', self-consciously putting Marxist and Bolshevik theories into practice. By telling the story of the urban communes, this book reveals how grand revolutionary ideals, such as collectivism, equality, proletarian ethics, and modern practice, were experienced, understood, and appropriated on a human level. This enables us to better understand the messy realities of the early Soviet state, showing how ideological beliefs and revolutionary contingencies actually came into being during this time.