Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either i.p. saline, mephedrone (10mg/kg), caffeine (10mg/kg) or combined caffeine and mephedrone twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day two), elevated plus maze (EPM, day eight) exploration, rectal temperature changes (day nine) and prepulse inhibition of acoustic startle (PPI, day 15) response were assessed. Seven days after the final injection, brain regions were collected for measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Time to go global: a consultation on global health competencies for postgraduate doctors

BACKGROUND: Globalisation is having profound impacts on health and healthcare. We solicited the views of a wide range of stakeholders in order to develop core global health competencies for postgraduate doctors. METHODS: Published literature and existing curricula informed writing of seven global health competencies for consultation. A modified policy Delphi involved an online survey and face-to-face and telephone interviews over three rounds. RESULTS: Over 250 stakeholders participated, including doctors, other health professionals, policymakers and members of the public from all continents of the world. Participants indicated that global health competence is essential for postgraduate doctors and other health professionals. Concerns were expressed about overburdening curricula and identifying what is 'essential' for whom. Conflicting perspectives emerged about the importance and relevance of different global health topics. Five core competencies were developed: (1) diversity, human rights and ethics; (2) environmental, social and economic determinants of health; (3) global epidemiology; (4) global health governance; and (5) health systems and health professionals. CONCLUSIONS: Global health can bring important perspectives to postgraduate curricula, enhancing the ability of doctors to provide quality care. These global health competencies require tailoring to meet different trainees' needs and facilitate their incorporation into curricula. Healthcare and global health are ever-changing; therefore, the competencies will need to be regularly reviewed and updated

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Pregnant and seeking asylum; exploring experiences ‘from booking to baby’

YesPregnant women seeking asylum in the UK may be particularly vulnerable with poor underlying health, more complex pregnancies and an increased risk of maternal and perinatal mortality. Studies have shown that some women seeking asylum have poor experiences of maternity care. This is despite the implementation of NICE guidelines to improve care for women with complex social factors. This article reports on a phenomenological study undertaken in West Yorkshire, aiming to explore the maternity care experiences of local pregnant asylum seeking women, to inform service development. Six women were interviewed over a three-month period. The findings focused more broadly on their experiences of living in the UK whilst being an asylum seeker and pregnant rather than focusing on maternity care, although this was included. Five key themes emerged: ‘pre-booking challenges’, ‘inappropriate accommodation’, ‘being pregnant and dispersed’, ‘being alone and pregnant’ and ‘not being asked or listened to’. These findings could be used as the basis for training midwives to understand how the difficulties women experience can impact on their health and social needs

Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship

The power of light – From dental materials processing to diagnostics and therapeutics

Harnessing the power of light and its photonic energy is a powerful tool in biomedical applications. Its use ranges from biomaterials processing and fabrication of polymers to diagnostics and therapeutics. Dental light curable materials have evolved over several decades and now offer very fast (≤ 10 s) and reliable polymerization through depth (4–6 mm thick). This has been achieved by developments on two fronts: (1) chemistries with more efficient light absorption characteristics (camphorquinone [CQ], ~30 L mol-1 cm1[ʎmax 470 nm]; monoacylphosphine oxides [MAPO], ~800 L mol-1 cm-1 [ʎmax 385 nm]; bisacylphosphine oxide [BAPO], ~1,000 L mol-1 cm-1 [ʎmax 385 nm]) as well mechanistically efficient and prolonged radical generation processes during and after light irradiation, and; (2) introducing light curing technologies (light emitting diodes [LEDs] and less common lasers) with higher powers (≤ 2 W), better spectral range using multiple diodes (short: 390–405 nm; intermediate: 410–450 nm; and long: 450–480 nm), and better spatial power distribution (i.e. homogenous irradiance). However, adequate cure of materials falls short for several reasons, including improper selection of materials and lights, limitations in the chemistry of the materials, and limitations in delivering light through depth. Photonic energy has further applications in dentistry which include transillumination for diagnostics, and therapeutic applications that include photodynamic therapy, photobiomodulation, and photodisinfection. Light interactions with materials and biological tis-sues are complex and it is important to understand the advantages and limitations of these interactions for successful treatment outcomes. This article highlights the advent of photonic technologies in dentistry, its applications, the advantages and limitations, and possible future developments

Long‐term trends in migrating Brassicogethes aeneus in the UK

BACKGROUND The pollen beetle (Brassicogethes aeneus) causes significant yield loss in oilseed rape (Brassica napus). Predicting population changes remains a scientific challenge, especially since its phenology and abundance varies dramatically over space and time. We used generalized additive models to investigate the long-term trends in pollen beetle annual, seasonal and monthly counts from Rothamsted 12.2 m suction-traps. We hypothesised that the beetle's abundance is positively related to the area of oilseed rape at a national and regional level. We used random forest models to investigate the inter-generational relationship within years. RESULTS Although B. aeneus annual counts and area of oilseed rape grown in the UK both increased by 162% and 113%, respectively, over the time period, they were not significantly related. The size of the immigrating pollen beetle population (up to June 1st) can be explained both by the size of the population in the previous summer and prevailing winter temperatures, indicating a positive feedback mechanism. CONCLUSION Currently, pollen beetle numbers continue to increase in the UK, meaning that control issues may persist, however the relationship between counts in spring, during the susceptible phase of the crop, and counts in the previous summer indicates that it may be possible to forecast the counts of the spring migration of B. aeneus a few months in advance using suction-trap samples, which could aid decisions on control options