The CB1R system within the nucleus accumbens of vervet monkeys

La libération de dopamine (DA) dans le noyau accumbens (NAc) est centrale dans le circuit de récompense, et un déséquilibre de la concentration de la DA joue un rôle majeur dans la dépendance. Anatomiquement, le NAc peut être divisé en 2 parties, le cœur (« core ») et la capsule (« shell »), ces 2 régions reçoivent des projections dopaminergiques de l’aire tegmentale ventrale (ATV). La libération de DA dans la capsule est impliquée dans les sensations de récompenses associées à la dépendance, alors que le cœur fait partie du circuit moteur avec la substance noire et encode les patrons moteurs des mouvements des yeux et la locomotion. Chez les rongeurs, le système endocannabinoïde (eCB) est présent dans le NAc, est impliqué dans la neuromodulation, et semble jouer un rôle dans la libération de la DA. La plante de cannabis, contient entre autre le delta-9-tetrahydrocannabinol qui produit ses effets psychotropes en activant le récepteur cannabinoïde 1 (CB1R), en partie en altérant la libération de DA. En tant que tel, il est supposé que le système CB1R joue un rôle crucial dans la médiation des propriétés gratifiantes de la cannabis et d'autres drogues d'abus, et peut-être la valeur des récompenses naturelles. Cette étude vise à caractériser l’expression et la localisation de CB1R, et des enzymes métaboliques des eCBs, la NAPE-PLD et la FAAH dans le NAc du singe vervet (Chlorocebus sabaeus) à l’aide des méthodes d’immunobuvardage et d’immunohistochimie. Nous avons trouvé que CB1R, NAPE-PLD et FAAH sont exprimés dans le cœur et la capsule du NAc. Ces 3 protéines sont présentes dans les cellules medium spiny neurons et les fast-spiking interneurons GABAergiques. Ces protéines n’ont pas été toutefois retrouvées dans les projections dopaminergiques ou les astrocytes. Ces données démontrent que le système CB1R est présent dans le NAc du singe et est donc parfaitement positionné pour jouer un rôle dans le circuit de récompense en désinhibant la libération de DA. De façon beaucoup plus large, le système eCB du singe pourrait également jouer un rôle dans la perception, la motivation et la sélection d’action.Dopamine (DA) release onto the nucleus accumbens (NAc) is central to the reward circuit, the dysregulation of which plays a role in addiction. The NAc can be anatomically divided into a core and shell. Both regions receive DA projections from the ventral tegmental area (VTA). VTA DA release onto the shell mediates feelings of reward associated with addiction, while the core is part of a motor circuit with the substantia nigra (SN) that encodes relevant motor patterns for eye movements and locomotion. In rodents, the endocannabinoid (eCB) system, which modulates neurotransmission, is present in the NAc, and plays a role in the modulation of DA release. Marijuana, which contains among others the active phytocannabinoid delta-9-tetrahydrocannabinol, produces its psychoactive effects by activating the cannabinoid receptor type 1 (CB1R), which may cause these effects by altering DA release. As such, it is hypothesized that the CB1R system plays a crucial role in mediating the rewarding properties of marijuana and other drugs of abuse, and possibly the value of natural rewards. Expression patterns of CB1R, the eCB synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), and the eCB degradation enzyme fatty acid amide hydrolase (FAAH) in the NAc have not been described in monkeys and humans. It is therefore the goal of the present study to characterize the expression and localization of these components of the eCB system within the NAc of vervet monkeys (Chlorocebus sabaeus) using Western Blots and immunohistochemistry. We found that CB1R, NAPE-PLD, and FAAH are expressed across the NAc, both in the core and shell. CB1R, NAPE-PLD, and FAAH are localized in GABAergic medium spiny projection neurons (MSNs), and in fast-spiking GABAergic interneurons (FSIs). CB1R, NAPE-PLD, and FAAH did not co-localize with dopaminergic projections, or astrocytes. These data indicate that the CB1R system is also present in the monkey NAc and suggests that it may play an important role in the brain reward circuit through a disinhibitory action on DA release. Thus, the primate eCB system may play a considerable role in reward perception, motivation, and action selection

Prospects of Detecting Non-thermal Protons in Solar Flares via Lyman Line Spectroscopy: Revisiting the Orrall-Zirker Effect

Solar flares are efficient particle accelerators, with a substantial fraction of the energy released manifesting as non-thermal particles. While the role that non-thermal electrons play in transporting flare energy is well studied, the properties and importance of non-thermal protons is rather less well understood. This is in large part due to the paucity of diagnostics, particularly at the lower-energy (deka-keV) range of non-thermal proton distributions in flares. One means to identify the presence of deka-keV protons is by an effect originally described by \cite{1976ApJ...208..618O}. In the Orrall-Zirker effect, non-thermal protons interact with ambient neutral hydrogen, and via charge exchange produce a population of energetic neutral atoms (ENAs) in the chromosphere. These ENAs subsequently produce an extremely redshifted photon in the red wings of hydrogen spectral lines. We revisit predictions of the strength of this effect using modern interaction cross-sections, and numerical models capable of self-consistently simulating the flaring non-equilibrium ionization stratification, and the non-thermal proton distribution (and, crucially, their feedback on each other). We synthesize both the thermal and non-thermal emission from \lya\ and \lyb, the most promising lines that may exhibit a detectable signal. These new predictions are are weaker and more transient than prior estimates, but the effects should be detectable in fortuitous circumstances. We degrade the \lyb\ emission to the resolution of the Spectral Imaging of the Coronal Environment (SPICE) instrument on board Solar Orbiter, demonstrating that though likely difficult, it should be possible to detect the presence of non-thermal protons in flares observed by SPICE.Comment: Accepted for publication in The Astrophysical Journa

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Ruptured intracranial dermoid cyst manifesting as new onset seizure: a case report

Intracranial dermoid cysts are rare tumors derived from ectopic epithelial cells. They are slow-growing benign entities, but can cause significant morbidity through compression of neurovascular structures and, rarely, rupture into the subarachnoid space. We present a rare case of a spontaneously ruptured intracranial dermoid cyst presenting as new onset seizures due to chemical meningitis caused by dissemination of fat droplets

Water flux in boreal forest during two hydrologically contrasting years; species specific regulation of canopy conductance and transpiration

We estimated the reduction of transpiration from drought for tree species in a mixed boreal 60-year-old stand in central Sweden. Actual transpiration was estimated from direct measurements of sap flow rate in Pinus sylvestris and Picea abies trees during two consecutive years with contrasting precipitation. Drought-induced reduction of transpiration (transpiration deficit) was quantified as the difference between the measured sap flow and the transpiration calculated for non-limiting soil water conditions. The drought-free transpiration was estimated on an hourly basis from Penman-Monteith equation with the parameterized canopy conductance (gc) functions for individual species. The values of gc for fitting a two-parameter function of radiation and vapour pressure deficit were obtained for a 3-d period by inverting the Penman-Monteith equation. Canopy conductance of pine was similar relative to spruce on ground area basis. This made gc of pine larger relative to spruce per leaf area unit, since pine tree foliage mass was about one third that of spruce. Transpiration deficit was small in the growth season of 1995. It reached about 10 % for spruce during the summer months. In 1994, however, the transpiration deficit was large for both species and extended throughout most of the growth season. During summer 1994, the decreased canopy conductance caused a 20 and 22 % reduction in gross photosynthesis for pine and spruce, respectively, indicating a loss of production of at least that proportion. Pines were less sensitive to drought spells as compared to the more shallow-rooted spruces. On the other hand, spruce utilised the precipitation incoming in small quantities more effectively and responded faster. Species composition of boreal forest can affect stand scale fluxes and this should be recognised by process models. (© Inra/Elsevier, Paris.)Flux d'eau dans une forêt boréale pendant deux années à pluviométrie contrastée ; régulation spécifique de la conductance du couvert et de la transpiration. La réduction de la transpiration sous l'effet de la sécheresse a été estimée dans une forêt boréale mélangée de 60 ans dans le centre de la Suède. La transpiration réelle a été estimée à partir des mesures directes de flux de sève chez Pinus sylvestris et Picea abies pendant deux années successives marquées par des précipitations contrastées. La réduction de transpiration (ou déficit de transpiration) liée à la sécheresse a été quantifiée par la différence entre le flux de sève mesuré et la transpiration calculée en conditions non limitantes de disponibilité en eau. La transpiration maximale a été estimée au pas de temps horaire à partir de l'équation de Penman-Monteith avec des paramètres de la fonction de conductance du couvert (gc) calibrés pour chacune des deux espèces. Les valeurs de gc pour ajuster une fonction à deux paramètres du rayonnement et du déficit de saturation de l'air ont été obtenues sur une période de 3 j par inversion de l'équation de Penman-Monteith. La conductance du couvert ramenée à l'unité de surface au sol du pin était du même ordre de grandeur que celle de l'épicéa. Mais sachant que la biomasse foliaire des pins n'était environ que d'un tiers de celle des épicéas, gc était plus grande chez le pin par unité de surface foliaire. Le déficit de transpiration a été faible pendant la saison de végétation 1995, atteignant environ 10 % chez l'épicéa pendant les mois d'été. En 1994, le déficit de transpiration a été important pour les deux espèces étudiées, et a duré une grande partie de la saison de végétation. Pendant l'été 1994, la réduction de la conductance du couvert a causé 20 % de réduction de photosynthèse brute chez les pins, et 22 % chez les épicéas, ce qui correspond à une perte de production sensiblement du même ordre. Les pins se sont montrés moins sensibles à la sécheresse que les épicéas, en liaison avec un système racinaire plus superficiel chez ces derniers. Toutefois, les épicéas ont montré une plus forte aptitude et une plus grande rapidité à utiliser les faibles précipitations. Ainsi, la composition en espèces de la forêt boréale peut influencer les flux à l'échelle du peuplement, ce qui doit être pris en compte dans les modèles. (© Inra/Elsevier, Paris.