Opioid-environment interaction: Contrasting effects of morphine administered in a novel versus familiar environment on acute and repeated morphine induced behavioral effects and on acute morphine ERK activation in reward associated brain areas.

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction.

Cerium-Organic Framework UiO-66(Ce) as a Support for Nanoparticulate Gold for Use in Oxidation Catalysis.

An optimised synthesis of the metal-organic framework (MOF) UiO-66(Ce) is reported using a modulator-free route, yielding ~5 g of material with high crystallinity and 22% ligand defect. Two methods developed for loading gold nanoparticles onto the MOF. The first uses a double-solvent method to introduce HAuCl4 onto UiO-66(Ce), followed by reduction under 5% H2 in N2, while the second is a novel one-pot method where HAuCl4 is added to the synthesis mixture, forming Au nanoparticles within the pores of the UiO-66(Ce) during crystallisation. Analysis using powder X-ray diffraction (PXRD), nitrogen adsorption isotherms, transmission electron microscopy and small-angle X-ray scattering (SAXS) reveals that the two-step double-solvent method yields gold crystallites on the external surface of the MOF particles that are visible by PXRD. In contrast, the one-pot method forms smaller gold crystallites, with a distribution of sizes centred on ~4 nm diameter as seen by SAXS, with evidence from PXRD for the smallest particles being present within the MOF structure. The Au-loaded UiO-66(Ce) materials are evaluated for the catalytic oxidation of vanillyl alcohol to vanillin at 60 °C. Our findings indicate that incorporating Au nanoparticles via the one-pot synthesis method, enhances redox activity, achieving 43% conversion and 90% selectivity towards vanillin.

Determining Factors and Economic Injury Levels for Sphenophorus levis for Chemical and Biological Control in Irrigated and Non-irrigated Sugarcane Crops.

Globally, people use sugarcane (Saccharum officinarum) to produce sugar and ethanol. Rainfed or irrigated sugarcane agricultural systems are available. Among the pests affecting this crop, the weevil Sphenophorus levis, Vaurie 1978 (Coleoptera: Curculionidae), is increasingly becoming a significant threat in southern South America. Sphenophorus levis populations are controlled using chemical or biological measures. Control decisions hinge upon the economic injury level (EIL). The EIL delineates the pest density that results in financial losses for producers. This study aims to determine the EIL for S. levis, considering the factors favoring this insect pest and chemical and biological control methods in rainfed and irrigated systems. The intensity of S. levis attacks was monitored in commercial sugarcane plantations over four years in João Pinheiro, Minas Gerais, Brazil. Sampling occurred in a 50 × 50 × 30-cm-deep trench dug in the soil surrounding the sugarcane clump. The total number of stumps in the clump, including those attacked by S. levis, was tallied. The EILs for this pest were 5.93% and 4.85% of targeted stumps for chemical control in rainfed and irrigated crops, respectively. Biological control in sugarcane plots resulted in an EIL of 4.15% and 3.40% for stumps attacked in rainfed and irrigated crops, respectively. Pest attacks were more severe during rainy years and in older sugarcane crops. The EIL values determined in this study could inform integrated pest management programs for sugarcane crops.

A partial habituation method to test for anterograde and retrograde amnestic treatment effects: Evidence that antagonism of the NMDA receptor can induce anterograde but not retrograde amnestic effects.

BACKGROUND: A progressive decrease in spontaneous locomotion with repeated exposure to a novel environment has been assessed using both within and between-session measures. While both are well-established and reliable measurements, neither are useful alone as methods to concurrently assess treatment effects on acquisition and retention of habituation. NEW METHOD: We report a behavioral method that measures habituation by combining the within and between measurements of locomotion. We used a 30 min session divided into 6 five min blocks. In the first novel environment session activity was maximal in the first 5 min block but was reduced to a low level by the sixth block, indicative of within-session habituation. Using 8 daily sessions, we showed that this terminal block low level of activity progressed incrementally to the first block to achieve complete habituation. RESULTS/COMPARISON WITH EXISTING METHODS: Within-session activity across sessions was used to identify different stages of between session habituation. It was then possible to assess drug treatment effects from partial to complete habituation, so that treatment effects on retention of the previously acquired partial habituation, expressed as a reversion to an earlier within session habituation pattern (retrograde amnesia assessment), as well as the effects on new learning by the failure in subsequent sessions to acquire complete between-session habituation (anterograde amnesia assessment). CONCLUSIONS: The use of spontaneous motor activity to assess learning and memory effects provides the opportunity to assess direct treatment effects on behavior and motor activity in contrast to many learning and memory models.

Bayesian hybrid index and genomic cline estimation with the R package gghybrid.

Admixture, the interbreeding of individuals from differentiated source populations, is now known to be a widespread phenomenon. Genomic studies of natural hybridisation can help to answer many questions on the impacts of admixture on adaptive evolution, reproductive isolation, and speciation. When a large variety of admixture proportions between two source populations exist, both geographic and genomic cline analysis are suitable methods for inferring biased, restricted or excessive gene flow at individual loci into the foreign genomic background, providing evidence for reproductive isolation, selection across an environmental transition, balancing selection, and adaptive introgression. Genomic cline analysis replaces geographic location with genome-wide hybrid index and is therefore useable in circumstances that violate geographic cline assumptions. Here, I introduce gghybrid, an R package for simple and flexible Bayesian estimation of Buerkle's hybrid index and Fitzpatrick's logit-logistic genomic clines using bi-allelic data, suitable for both small and large datasets. gghybrid allows any ploidy and uses Structure input file format. It has separate functions for hybrid index and cline estimation, treating each individual and locus respectively as an independent analysis, making it highly parallelisable. Admixture proportions from other software can alternatively be used in cline analysis, alongside parental allele frequencies. Parameters can be fixed and samples pooled for statistical model comparison with AIC or waic. Here, I describe the functions, pipeline, and statistical properties of gghybrid. Simulations reveal that model comparison with waic is preferred, and use of Bayesian posterior distributions and p values to select candidate non-null loci is problematic and should be avoided.

The stingless bee Trigona spinipes (Hymenoptera: Apidae) is at risk from a range of insecticides via direct ingestion and trophallactic exchanges.

BACKGROUND: The stingless bee, Trigona spinipes, is an important pollinator of numerous native and cultivated plants. Trigona spinipes populations can be negatively impacted by insecticides commonly used for pest control in crops. However, this species has been neglected in toxicological studies. Here we observed the effects of seven insecticides on the survival of bees that had fed directly on insecticide-contaminated food sources or received insecticides via trophallactic exchanges between nestmates. The effects of insecticides on flight behavior were also determined for the compounds considered to be of low toxicity. RESULTS: Imidacloprid, spinosad and malathion were categorized as highly toxic to T. spinipes, whereas lambda-cyhalothrin, methomyl and chlorfenapyr were of medium to low toxicity and interfered with two aspects of flight behavior evaluated here. Chlorantraniliprole was the only insecticide tested here that had no significant effect on T. spinipes survival, although it did interfere with one aspect of flight capacity. A single bee that had ingested malathion, spinosad or imidacloprid, could contaminate three, four and nineteen other bees, respectively via trophallaxis, resulting in the death of the recipients. CONCLUSION: This is the first study to evaluate the ecotoxicology of a range of insecticides that not only negatively affected T. spinipes survival, but also interfered with flight capacity, a very important aspect of pollination behavior. The toxicity of the insecticides was observed following direct ingestion and also via trophallactic exchanges between nestmates, highlighting the possibility of lethal effects of these insecticides spreading throughout the colony, reducing the survival of non-foraging individuals. © 2023 Society of Chemical Industry.

The Potential of Metarhizium anisopliae Blastospores to Control Aedes aegypti Larvae in the Field.

Entomopathogenic fungi are promising as an environmentally benign alternative to chemical pesticides for mosquito control. The current study investigated the virulence of Metarhizium anisopliae blastospores against Aedes aegypti under both laboratory and field conditions. Virulence bioassays of conidia and blastospores were conducted in the laboratory, while field simulation bioassays were conducted under two conditions: totally shaded (TS) or partially shaded (PS). In the first bioassay (zero h), the larvae were added to the cups shortly after the preparation of the blastospores, and in the subsequent assays, larvae were added to the cups 3, 6, 9, and 12 days later. The survival of the larvae exposed to blastospores in the laboratory was zero on day two, as was the case for the larvae exposed to conidia on the sixth day. Under TS conditions, zero survival was seen on the third day of the bioassay. Under PS conditions, low survival rates were recorded on day 7. For the persistence bioassay under PS conditions, low survival rates were also observed. Metarhizium anisopliae blastospores were more virulent to Ae. aegypti larvae than conidia in the laboratory. Blastospores remained virulent under field simulation conditions. However, virulence rapidly declined from the third day of field bioassays. Formulating blastospores in vegetable oil could protect these propagules when applied under adverse conditions. This is the first time that blastospores have been tested against mosquito larvae under simulated field conditions, and the current study could be the basis for the development of a new biological control agent.

Morphine and dopamine: Low dose apomorphine can prevent both the induction and expression of morphine locomotor sensitization and conditioning.

The disinhibition of dopamine neurons in the VTA by morphine is considered an important contributor to the reward potency of morphine. In this report, three experiments were conducted in which a low dose of apomorphine (0.05 mg/kg) was used as a pretreatment to reduce dopamine activity. Locomotor hyperactivity was used as the behavioral response to morphine (10.0 mg/kg). In the first experiment, five treatments with morphine induced the development of locomotor and conditioned hyperactivity that were prevented by apomorphine given 10 min prior to morphine. Apomorphine before either vehicle or morphine induced equivalent reductions in locomotion. In the second experiment, the apomorphine pretreatment was initiated after induction of a conditioned hyperactivity and apomorphine prevented the expression of the conditioning. To assess the effects of apomorphine on VTA and the nucleus accumbens, ERK measurements were carried out after the induction of locomotor and conditioned hyperactivity. Increased ERK activation was found and these effects were prevented by the apomorphine in both experiments. A third experiment was conducted to assess the effects of acute morphine on ERK before locomotor stimulation was induced by morphine. Acute morphine did not increase locomotion, but a robust ERK response was produced indicating that the morphine-induced ERK activation was not secondary to locomotor stimulation. ERK activation was again prevented by the apomorphine pretreatment. We suggest that contiguity between the ongoing behavioral activity and the morphine activation of the dopamine reward system incentivizes and potentiates the ongoing behavior generating equivalent behavioral sensitization and conditioned effects.

Production of Escovopsis weberi (Ascomycota: Hypocreales) Mycelial Pellets and Their Effects on Leaf-Cutting Ant Fungal Gardens.

The maintenance of the symbiosis between leaf-cutting ants and their mutualistic fungus Leucoagaricus gongylophorus Singer (Moller) is vital for the survival of both species. The specialist fungal parasite Escovopsis weberi Muchovej & Della Lucia is a threat to this symbiosis, causing severe damage to the fungal garden. Mycelial pellets are resistant fungal structures that can be produced under laboratory conditions. These structures were studied for use in biological pest control, but the production of mycelial pellets has not previously been documented in Escovopsis. One of the aims of this study was to induce Escovopsis weberi to produce mycelial pellets and investigate the potential of these pellets for the control of leaf-cutting ants. We compared the pathogenicity of Escovopsis weberi mycelial pellets and conidia against mini-colonies of Acromyrmex subterraneus subterraneus Forel when applied in the form of baits. Worker ants were able to distinguish mycelial pellets from conidia, as baits with mycelial pellets were more attractive to workers than those with conidia, causing a greater negative impact on colony health. All types of baits containing Escovopsis weberi influenced the foraging activity but only treatments with viable fungal propagules resulted in an increase in the quantity of waste material, with a significant negative impact on the fungal garden biomass. The results provided novel information regarding Escovopsis recognition by worker ants and differences between conidia and mycelial pellet dynamics in leaf-cutting ant colonies, with new perspectives for the biological control of these important pests.

The spatial and temporal reconstruction of a medieval moat ecosystem.

Moats and other historical water features had great importance for past societies. The functioning of these ecosystems can now only be retrieved through palaeoecological studies. Here we aimed to reconstruct the history of a stronghold's moat during its period of operation. Our spatio-temporal approach allowed mapping of the habitat changes within a medieval moat for the first time. Using data from four cores of organic deposits taken within the moat system, we describe ecological states of the moat based on subfossil Chironomidae and Ceratopogonidae assemblages. We found that over half (57%) of the identified dipteran taxa were indicative of one of the following ecological states: limnetic conditions with or without periodic water inflow, or marshy conditions. Samples representing conditions unfavourable for aquatic insects were grouped in a separate cluster. Analyses revealed that the spatio-temporal distribution of midge assemblages depended mostly on depth differences and freshwater supply from an artificial channel. Paludification and terrestrialization did not happen simultaneously across the moat system, being greatly influenced by human activity. The results presented here demonstrate the importance of a multi-aspect approach in environmental archaeology, focusing not only on the human environment, but also on the complex ecology of the past ecosystems.

Genomic insights into the genotype-environment mismatch and conservation units of a Qinghai-Tibet Plateau endemic cypress under climate change.

Habitat loss induced by climate warming is a major threat to biodiversity, particularly to threatened species. Understanding the genetic diversity and distributional responses to climate change of threatened species is critical to facilitate their conservation and management. Cupressus gigantea, a rare conifer found in the eastern Qinghai-Tibet Plateau (QTP) at 3000-3600 m.a.s.l., is famous for its largest specimen, the King Cypress, which is >55 m tall. Here, we obtained transcriptome data from 96 samples of 10 populations covering its whole distribution and used these data to characterize genetic diversity, identify conservation units, and elucidate genomic vulnerability to future climate change. After filtering, we identified 145,336, 26,103, and 2833 single nucleotide polymorphisms in the whole, putatively neutral, and putatively adaptive datasets, respectively. Based on the whole and putatively neutral datasets, we found that populations from the Yalu Tsangpo River (YTR) and Nyang River (NR) catchments could be defined as separate management units (MUs), due to distinct genetic clusters and demographic histories. Results of gradient forest models suggest that all populations of C. gigantea may be at risk due to the high expected rate of climate change, and the NR MU had a higher risk than the YTR MU. This study deepens our understanding of the complex evolutionary history and population structure of threatened tree species in extreme environments, such as dry river valleys above 3000 m.a.s.l. in the QTP, and provides insights into their susceptibility to global climate change and potential for adaptive responses.

Lethal and sublethal effects of insecticides used in the management of Plutella xylostella (Lepidoptera: Plutellidae) on the predator Cycloneda sanguinea L. (Coleoptera: Coccinellidae).

BACKGROUND: The application of synthetic insecticides is the main strategy used to reduce the damage caused by the diamondback moth Plutella xylostella in commercial Brassica crops. However, incorrect insecticide use can cause biological and ecological disturbances in agroecosystems. Cycloneda sanguinea is a generalist voracious predator and is distributed widely in cultivated and noncultivated ecosystems. This study investigated the efficiency of four insecticides for the control of P. xylostella and the lethal and sublethal effects of these insecticides on C. sanguinea. RESULTS: Spinosad (92% mortality) and chlorfenapyr (76% mortality) were highly toxic to P. xylostela. However, chlorantraniliprole (10% mortality) and methomyl (no mortality) were ineffective against this pest. Chlorantraniliprole was the only insecticide that was highly toxic to C. sanguinea by contact (90% mortality), however, it was nontoxic following the ingestion of chlorantraniliprole-contaminated aphids. Interestingly, ingestion of prey contaminated with methomyl and chlorfenapyr was highly toxic (100% mortality) to C. sanguinea. Spinosad was nontoxic to C. sanguinea via exposure to contaminated surfaces and following ingestion of contaminated prey. However, direct contact of the insects with both methomyl and spinosad significantly affected C. sanguinea flight activity (vertical flight and free-fall flight), whereas chlorfenapyr impacted vertical flight only. CONCLUSION: These findings showed that chlorantraniliprole was not only ineffective for the control of P. xylostela, but was also highly toxic to C. sanguinea. The results indicated that spinosad was efficient against P. xylostela and was of low toxicity to C. sanguinea; however, the deleterious effects of this insecticide on flight behavior could result in reduced predatory efficiency. © 2022 Society of Chemical Industry.

Context evoked morphine conditioned effects can be equivalent to morphine induced drug effects in terms of behavioral response and ERK activation in reward associated subcortical brain structures.

Conditioned drug cues can evoke brief drug-like responses. In this report we show that using brief test sessions, contextual cues can induce conditioned hyperlocomotion and ERK responses equivalent to morphine induced responses. To assess acute unconditioned effects, rats that received morphine (MOR-1) or vehicle (VEH-1) were immediately placed onto an arena for a 5-min locomotion recording session after which ERK was measured in the ventral tegmental area (VTA) and nucleus accumbens (NAc). There were no differences in locomotion between the groups. However, the MOR-1 group had strong ERK activation in VTA and NAc. To assess MOR-conditioned effects, a chronic phase was carried out according to a Pavlovian conditioning protocol. There were two MOR paired groups (MORP), one MOR unpaired (MOR-UP) group and two VEH groups. The treatments were administered over 5 daily five minute test sessions. The final conditioning test was on day 6, in which one of the MOR-P groups and one of the VEH groups received VEH (MOR-P/VEH-6 and VEH/VEH-6, respectively). The other MOR-P group and VEH group received MOR (MOR-P/MOR; VEH/MOR-6, respectively). The MOR-UP group received VEH (MOR-UP/VEH-6). Rats received the treatments immediately prior to a 5-minute arena test, and after the session ERK was measured. No morphine induced locomotor stimulation was observed on day 1 but on days 2 to 5, hyperlocomotion in both MOR-P groups occurred. On test day 6, the MOR-P/VEH-6 and the MOR-P/MOR-6 groups had comparable locomotor stimulant responses and similar ERK activity in the VTA and NAc. The MOR-UP group did not differ from the VEH group. We suggest that ERK activation evoked by acute morphine served as a Pavlovian unconditioned stimulus to enable the contextual cues to acquire morphine conditioned stimulus properties and increase the incentive value of the contextual cues.

A new method to study learning and memory using spontaneous locomotor activity in an open-field arena.

BACKGROUND: Reduced locomotion with repeated exposure to a novel environment is often used as a measure of the basic adaptive learning process of habituation. While this is a well-established and reliable measure of habituation, it is not useful for the investigation of neurobiological changes before and after habituation because of the uncontrolled differential activity levels in a novel versus habituated environment. In this study we report a behavioral method that uses spontaneous locomotion to measure habituation, in which the total spontaneous locomotion in an initially novel environment does not change with repeated testing but, the ratio of central to peripheral activity does change and is indicative of habituation. The test sessions are brief (5 min) and the locomotion is measured in 2 separate zones. The peripheral zone comprises 8/9 of the test arena and the central zone 1/9 of the arena. RESULTS/COMPARISON WITH EXISTING METHODS: In contrast to methods that use between-session reductions in locomotion to assess habituation, this method employs brief test sessions in which overall activity between sessions does not change, but the distribution of locomotion in the periphery versus the central zone of the arena does change. The brevity of the test session also enables us to utilize post-trial drug treatment protocols to impact memory consolidation. CONCLUSIONS: The progressive change in the central/peripheral activity ratio with repeated testing can be determined independently of total activity and provides a habituation acquisition function that permits the measurement of neurobiological changes without the complication of effects related to changes in locomotor activity per se. The present report also presents evidence that this method can be used with post-trial drug treatment protocols to study the learning and memory effects of the post-trial treatments without the use of explicit rewards and punishments.

Seeing through the hedge: Phylogenomics of Thuja (Cupressaceae) reveals prominent incomplete lineage sorting and ancient introgression for Tertiary relict flora.

The Eastern Asia (EA) - North America (NA) disjunction is a well-known biogeographic pattern of the Tertiary relict flora; however, few studies have investigated the evolutionary history of this disjunction using a phylogenomic approach. Here, we used 2369 single copy nuclear genes and nearly full plastomes to reconstruct the evolutionary history of the small Tertiary relict genus Thuja, which consists of five disjunctly distributed species. The nuclear species tree strongly supported an EA clade Thuja standishii-Thuja sutchuenensis and a "disjunct clade", where western NA species T. plicata is sister to an EA-eastern NA disjunct Thuja occidentalis-Thuja koraiensis group. Our results suggested that the observed topological discordance among the gene trees as well as the cytonuclear discordance is mainly due to incomplete lineage sorting, probably facilitated by the fast diversification of Thuja around the Early Miocene and the large effective population sizes of ancestral lineages. Furthermore, approximately 20% of the T. sutchuenensis nuclear genome is derived from an unknown ancestral lineage of Thuja, which might explain the close resemblance of its cone morphology to that of an ancient fossil species. Overall, our study demonstrates that single genes may not resolve interspecific relationships for disjunct taxa, and that more reliable results will come from hundreds or thousands of loci, revealing a more complex evolutionary history. This will steadily improve our understanding of their origin and evolution.

Metarhizium anisopliae blastospores are highly virulent to adult Aedes aegypti, an important arbovirus vector.

BACKGROUND: The use of entomopathogenic fungi (EPF) for the control of adult mosquitoes is a promising alternative to synthetic insecticides. Previous studies have only evaluated conidiospores against adult mosquitoes. However, blastospores, which are highly virulent against mosquito larvae and pupae, could also be effective against adults. METHODS: Metarhizium anisopliae (ESALQ 818 and LEF 2000) blastospores and conidia were first tested against adult Aedes aegypti by spraying insects with spore suspensions. Blastospores were then tested using an indirect contact bioassay, exposing mosquitoes to fungus-impregnated cloths. Virulence when using blastospores suspended in 20% sunflower oil was also investigated. RESULTS: Female mosquitoes sprayed with blastospores or conidia at a concentration of 108 propagules ml-1 were highly susceptible to both types of spores, resulting in 100% mortality within 7 days. However, significant differences in virulence of the isolates and propagules became apparent at 107 spores ml-1, with ESALQ 818 blastospores being more virulent than LEF 2000 blastospores. ESALQ 818 blastospores were highly virulent when mosquitoes were exposed to black cotton cloths impregnated with blastospores shortly after preparing the suspensions, but virulence declined rapidly 12 h post-application. The addition of vegetable oil to blastospores helped maintain virulence for up to 48 h. CONCLUSION: The results showed that blastospores were more virulent to adult female Ae. aegypti than conidia when sprayed onto the insects or applied to black cloths. Vegetable oil helped maintain blastospore virulence. The results show that blastospores have potential for use in integrated vector management, although new formulations and drying techniques need to be investigated.

Morphine reward effects and morphine behavioral sensitization: The adventitious association of morphine activation of brain reward effects with ongoing spontaneous activity.

The development of sensitization is one of the hallmarks of addictive drugs such as morphine. We administered morphine (10 mg/kg; MOR) to induce locomotor sensitization and ERK activation in the VTA and NAc. In the first experiment, four groups of rats received five daily 30 min sessions in an open-field, and locomotion was measured. For the first four sessions, one group received MOR pre-test (MOR-P); a second group received vehicle pre-test (MOR-UP) and MOR 30 min post-test; the remaining 2 groups received vehicle (VEH) pre-test. On the fifth session, the MOR-P, MOR-UP, and one VEH group received MOR pre-test and the remaining VEH group received VEH. Sensitization emerged in the first 5 min and progressed over to the second and third 5 min blocks only in the MOR-P group. For the second experiment, 4 groups received MOR and 4 groups VEH, and were then returned to their home cage and after 5, 15, 30 or 60 min post-injection, were euthanized for ERK measurements in VTA and NAc. ERK activation increased and peaked at 5 min post injection in the MOR group and then declined to VEH levels by 30 min. Another two groups received either MOR or VEH immediately before a 5 min arena test and ERK was measured immediately post-test. MOR had no effect on locomotion but increased ERK in the VTA and NAc. The peak ERK activation in VTA reflected activation of reward systems by morphine that reinforced locomotor behavior and with repeated treatments, induced a sensitization effect.

Lewy Body Dementia Association's Industry Advisory Council: proceedings of the second annual meeting.

In 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing and planned efforts toward the council's goals. The meeting also featured a discussion about the effects of the COVID-19 pandemic on Lewy body dementia clinical research, lessons learned from that experience, and how those lessons can be applied to the design and conduct of future clinical trials. This report provides a brief summary of the meeting proceedings with a focus on efforts to improve and adapt future Lewy body dementia clinical research.

The Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) randomised controlled trial to evaluate an outpatient pre-cardiac surgery diabetes management intervention: a study protocol.

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.

Reduced odds of diabetes associated with high plasma salivary α-amylase activity in Qatari women: a cross-sectional study.

The association of salivary α-amylase activity (SAA) activity or low copy number of its coding gene AMY1 with diabetes remains controversial. We aimed to reinvestigate the association of these factors with diabetes in Qatar, where diabetes prevalence is about 16%. We obtained cross-sectional data of 929 Qataris (age > 18 years) from the Qatar Biobank. We estimated AMY1 copy number variants (CNV) from whole-genome data, and quantified the SAA activity in plasma (pSAA). We used adjusted logistic regression to examine the association between pSAA activity or AMY1 CNV and diabetes odds. We found a significant association between high pSAA activity, but not AMY1 CNV, and reduced odds of diabetes in Qatari women. The OR per pSAA activity unit was 0.95 [95% CI 0.92, 0.98] (p = 0.002) (pSAA activity range: 4.7 U/L to 65 U/L) in women. The association is driven largely by the highest levels of pSAA activity. The probability of having diabetes was significantly lower in the fifth pSAA activity quintile relative to the first (0.21 ± 0.03 (Q1) versus 0.82 ± 0.02 (Q5)), resulting in significantly reduced diabetes prevalence in Q5 in women. Our study indicates a beneficial effect of high pSAA activity, but not AMY1 CN, on diabetes odds in Qatari women, and suggests pSAA activity levels as a potential marker to predict future diabetes in Qatari women.