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

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

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

The Performance Effect of Scheduled Carbohydrate and Caffeine Intake during Simulated Team Sport Match-Play

The aim of the current investigation was to identify the effects of scheduled carbohydrate (CHO) and caffeine (CAF) supplementation on simulated team sport match-play performance. Ten male hurling players completed three hurling match-play simulation protocols (HSP) performed 7 days apart in a double-blind, randomized design. Supplementation included CHO, CHO + CAF, and placebo (PLA). In a randomized order, participants ingested either a 6% CHO solution, a PLA solution of similar taste, or a combined intake of 6% CHO solution + 200 mg CAF capsule. At specific time points (Pre-0 min; half time (HT)-30 min; full time (FT)-60 min), participants completed a repeated sprint protocol (RAST; 12 7 20 m). Physiological [% maximal oxygen uptake (%VO2max), % mean oxygen uptake (%VO2mean), % maximal heart rate (%HRmax), % mean heart rate (%HRmean), respiratory exchange ratio (RER), and blood lactate (BLa)] and performance [(best sprint time (RSAbest), mean sprint time (RSAmean), and rate of perceived exertion (RPE)] variables were monitored throughout each simulation. Non-significant differences were observed between supplement trials (CHO, CHO + CAF, and PLA) for BLa (\u3b72 = 0.001, small), %VO2max (\u3b72 = 0.001, small), %VO2mean (\u3b72 = 0.004, small), %HRmax (\u3b72 = 0.007, small), %HRmean (\u3b72 = 0.018, small), RER (\u3b72 = 0.007, small), RPE (\u3b72 = 0.007, small), and RSAbest (\u3b72 = 0.050, small). RSAmean performance significantly improved in CHO + CAF trials compared to PLA, with sprint times significantly improved from Pre to FT also (\u3b72 = 0.135, medium). A significant difference was observed in BLa between time points (Pre, HT, and FT) (\u3b72 = 0.884, large) in % HRmax (\u3b72 = 0.202, medium), %HRmean (\u3b72 = 0.477, large), and RER (\u3b72 = 0.554, large) across halves and in RPE across time points (\u3b72 = 0.670, large). Our data provide novel data regarding the effects of CHO and CAF supplementation on team sport performance, with co-ingestion of CHO + CAF reducing the decrement in repeated sprint performance compared to PLA

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

Obstacles to local payments for ecosystem services schemes for water management at the catchment scale: a case study from Eastern Scotland

Water catchment management negotiates a complex landscape of local and expert knowledge, cultural and historical norms, property rights, and the pressures of environmental change. Various schemes have developed in recent years that aim to provide an integrated, consultative approach to environmental management, among which payment for ecosystem services (PES) has emerged as a successful example. Yet, there are certain characteristics of catchment landscapes that problematise the implementation of PES schemes for water management. This paper explores these characteristics in a case study of the Lunan water catchment area in Angus, Scotland. We report on a scientific research project to develop and implement a tilting weir system in the catchment that aims to address wetland nutrient and sediment pollution, winter flooding in the upper catchment, and summer water shortages in the lower catchment. Socio-scientific methods investigate the potential use of a PES approach to support the local management of the tilting weir system for the provision of multiple benefits at the catchment scale. Research shows evidence of conflicting levels of support between farmers and residents for both the intervention itself and the PES approach, diverse perceptions of rights and responsibilities in relation to water, and the challenges of identifying an adequate PES intermediary in the current institutional framework

Where and why are species' range shifts hampered by unsuitable landscapes?

There is widespread concern that species will fail to track climate change if habitat is too scarce or insufficiently connected. Targeted restoration has been advocated to help species adapt, and a “conductance” metric has been proposed, based on simulation studies, to predict effective habitat configurations. However, until now there is very little empirical evidence on how the configuration of habitat is affecting expansion at species' cool range margins. We analysed the colonisation events that have occurred in continuously monitored trap locations for 54 species of southerly distributed moths in Britain between 1985 and 2011. We tested whether the time until colonisation was affected by attributes of each species, and of intervening landcover and climate between the trap and the baseline distribution (1965–1985). For woodland species, the time until colonisation of new locations was predicted by the “conductance” of woodland habitat, and this relationship was general, regardless of species' exact dispersal distances and habitat needs. This shows that contemporary range shifts are being influenced by habitat configuration as well as simple habitat extent. For species associated with farmland or suburban habitats, colonisation was significantly slower through landscapes with a high variance in elevation and/or temperature. Therefore, it is not safe to assume that such relatively tolerant species face no geographical barriers to range expansion. We thus elucidate how species' attributes interact with landscape characteristics to create highly heterogeneous patterns of shifting at cool range margins. Conductance, and other predictors of range shifts, can provide a foundation for developing coherent conservation strategies to manage range shifts for entire communities

Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids

RP2 mutations cause a severe form of X-linked retinitis pigmentosa (XLRP). The mechanism of RP2-associated retinal degeneration in humans is unclear, and animal models of RP2 XLRP do not recapitulate this severe phenotype. Here, we developed gene-edited isogenic RP2 knockout (RP2 KO) induced pluripotent stem cells (iPSCs) and RP2 patient-derived iPSC to produce 3D retinal organoids as a human retinal disease model. Strikingly, the RP2 KO and RP2 patient-derived organoids showed a peak in rod photoreceptor cell death at day 150 (D150) with subsequent thinning of the organoid outer nuclear layer (ONL) by D180 of culture. Adeno-associated virus-mediated gene augmentation with human RP2 rescued the degeneration phenotype of the RP2 KO organoids, to prevent ONL thinning and restore rhodopsin expression. Notably, these data show that 3D retinal organoids can be used to model photoreceptor degeneration and test potential therapies to prevent photoreceptor cell death