Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

Constraints on the structure and seasonal variations of Triton's atmosphere from the 5 October 2017 stellar occultation and previous observations

Context. A stellar occultation by Neptune's main satellite, Triton, was observed on 5 October 2017 from Europe, North Africa, and the USA. We derived 90 light curves from this event, 42 of which yielded a central flash detection. Aims. We aimed at constraining Triton's atmospheric structure and the seasonal variations of its atmospheric pressure since the Voyager 2 epoch (1989). We also derived the shape of the lower atmosphere from central flash analysis. Methods. We used Abel inversions and direct ray-tracing code to provide the density, pressure, and temperature profiles in the altitude range similar to 8 km to similar to 190 km, corresponding to pressure levels from 9 mu bar down to a few nanobars. Results. (i) A pressure of 1.18 +/- 0.03 mu bar is found at a reference radius of 1400 km (47 km altitude). (ii) A new analysis of the Voyager 2 radio science occultation shows that this is consistent with an extrapolation of pressure down to the surface pressure obtained in 1989. (iii) A survey of occultations obtained between 1989 and 2017 suggests that an enhancement in surface pressure as reported during the 1990s might be real, but debatable, due to very few high S/N light curves and data accessible for reanalysis. The volatile transport model analysed supports a moderate increase in surface pressure, with a maximum value around 2005-2015 no higher than 23 mu bar. The pressures observed in 1995-1997 and 2017 appear mutually inconsistent with the volatile transport model presented here. (iv) The central flash structure does not show evidence of an atmospheric distortion. We find an upper limit of 0.0011 for the apparent oblateness of the atmosphere near the 8 km altitude.J.M.O. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) and the European Social Fund (ESF) through the PhD grant SFRH/BD/131700/2017. The work leading to these results has received funding from the European Research Council under the European Community's H2020 2014-2021 ERC grant Agreement nffi 669416 "Lucky Star". We thank S. Para who supported some travels to observe the 5 October 2017 occultation. T.B. was supported for this research by an appointment to the National Aeronautics and Space Administration (NASA) Post-Doctoral Program at the Ames Research Center administered by Universities Space Research Association (USRA) through a contract with NASA. We acknowledge useful exchanges with Mark Gurwell on the ALMA CO observations. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. J.L.O., P.S.-S., N.M. and R.D. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709), they also acknowledge the financial support by the Spanish grant AYA-2017-84637-R and the Proyecto de Excelencia de la Junta de Andalucia J.A. 2012-FQM1776. The research leading to these results has received funding from the European Union's Horizon 2020 Research and Innovation Programme, under Grant Agreement no. 687378, as part of the project "Small Bodies Near and Far" (SBNAF). P.S.-S. acknowledges financial support by the Spanish grant AYA-RTI2018-098657-J-I00 "LEO-SBNAF". The work was partially based on observations made at the Laboratorio Nacional de Astrofisica (LNA), Itajuba-MG, Brazil. The following authors acknowledge the respective CNPq grants: F.B.-R. 309578/2017-5; R.V.-M. 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3 and 305917/2019-6; M.A. 427700/20183, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) -Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). G.B.R. acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016 and CAPES-PRINT/UNESP grant 88887.571156/2020-00, M.A. FAPERJ grant E26/111.488/2013 and A.R.G.Jr. FAPESP grant 2018/11239-8. B.E.M. thanks CNPq 150612/2020-6 and CAPES/Cofecub-394/2016-05 grants. Part of the photometric data used in this study were collected in the frame of the photometric observations with the robotic and remotely controlled telescope at the University of Athens Observatory (UOAO; Gazeas 2016). The 2.3 m Aristarchos telescope is operated on Helmos Observatory by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. Observations with the 2.3 m Aristarchos telescope were carried out under OPTICON programme. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 730890. This material reflects only the authors views and the Commission is not liable for any use that may be made of the information contained therein. The 1. 2m Kryoneri telescope is operated by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the "Unite des Communes valdotaines Mont-Emilius". The 0.81 m Main Telescope at the OAVdA was upgraded thanks to a Shoemaker NEO Grant 2013 from The Planetary Society. D.C. and J.M.C. acknowledge funds from a 2017 'Research and Education' grant from Fondazione CRT-Cassa di Risparmio di Torino. P.M. acknowledges support from the Portuguese Fundacao para a Ciencia e a Tecnologia ref. PTDC/FISAST/29942/2017 through national funds and by FEDER through COMPETE 2020 (ref. POCI010145 FEDER007672). F.J. acknowledges Jean Luc Plouvier for his help. S.J.F. and C.A. would like to thank the UCL student support observers: Helen Dai, Elise Darragh-Ford, Ross Dobson, Max Hipperson, Edward Kerr-Dineen, Isaac Langley, Emese Meder, Roman Gerasimov, Javier Sanjuan, and Manasvee Saraf. We are grateful to the CAHA, OSN and La Hita Observatory staffs. This research is partially based on observations collected at Centro Astronomico HispanoAleman (CAHA) at Calar Alto, operated jointly by Junta de Andalucia and Consejo Superior de Investigaciones Cientificas (IAA-CSIC). This research was also partially based on observation carried out at the Observatorio de Sierra Nevada (OSN) operated by Instituto de Astrofisica de Andalucia (CSIC). This article is also based on observations made with the Liverpool Telescope operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. Partially based on observations made with the Tx40 and Excalibur telescopes at the Observatorio Astrofisico de Javalambre in Teruel, a Spanish Infraestructura Cientifico-Tecnica Singular (ICTS) owned, managed and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). Tx40 and Excalibur are funded with the Fondos de Inversiones de Teruel (FITE). A.R.R. would like to thank Gustavo Roman for the mechanical adaptation of the camera to the telescope to allow for the observation to be recorded. R.H., J.F.R., S.P.H. and A.S.L. have been supported by the Spanish projects AYA2015-65041P and PID2019-109467GB-100 (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT1366-19. Our great thanks to Omar Hila and their collaborators in Atlas Golf Marrakech Observatory for providing access to the T60cm telescope. TRAPPIST is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant PDR T.0120.21. TRAPPIST-North is a project funded by the University of Liege, and performed in collaboration with Cadi Ayyad University of Marrakesh. E.J. is a FNRS Senior Research Associate

Overestimation of moderate carotid stenosis assessed by both Doppler US and contrast enhanced 3D-MR angiography in the CARMEDAS study.

International audiencePURPOSE: To evaluate the agreement and diagnostic accuracy of Contrast enhanced magnetic resonance angiography (CE-MRA), Doppler ultrasound (DUS) and Digital subtraction angiography (DSA) in the assessment of carotid stenosis. METHODS: DUS, CE-MRA and DSA were performed in 56 patients included in the Carotide-angiographie par résonance magnétique-échographie-doppler-angioscanner (CARMEDAS) multicenter study with a carotid stenosis ≥ 50%. Three readers evaluated stenoses on CE-MRA and DSA (NASCET criteria). Velocities criteria were used for stenosis estimation on DUS. RESULTS: CE-MRA had a sensitivity and specificity of 96-98% and 66-83% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 94% and 76-84% respectively for carotid stenoses ≥ 70%. The interobserver agreement of CE-MRA was excellent, except for moderate stenoses (50-69%). DUS had a sensitivity and specificity of 88 and 75% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 83 and 86% respectively for carotid stenoses ≥ 70%. Combined concordant CE-MRA and DUS had a sensitivity and specificity of 100 and 85-90% respectively for carotid stenoses ≥ 50% and a sensitivity and specificity of 96-100% and 80-87% respectively for carotid stenoses ≥ 70%. The positive predictive value of the association CE-MRA and DUS for carotid stenoses ≥ 70% is calculated between 77 and 82% while the negative predictive value is calculated between 97 and 100%. CE-MRA and DUS have concordant findings in 63-72%, and the overestimations cases were recorded only for carotid stenosis ≤ 69%. CONCLUSION: Combined DUS-CE-MRA is excellent for evaluation of severe stenosis but remains debatable in moderate stenosis (50-69%) due to the risk of overestimations

Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry

From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.À partir des 198 premiers dossiers enregistrés dans le Registre Français de l'Acromégalie, 68 patients porteurs de macroadénomes somatotropes avec extension extrasellaire ont été analysés, après exclusion des cas ayant bénéficié d'une radiothérapie conventionnelle ou stéréotaxique. Chez ces sujets (dont 37 femmes), âgés de 21 à 77 ans (45,7 ± 13,3 ans), les concentrations de GH variaient de 2 à 260 pg/L (38,6 ± 44,3). L'IGF I variait de 86 à 967 % de la limite supérieure pour l'âge (303 ± 164). Le diamètre maximal de l'adénome sur l'IRM variait de 11 à 36,5 mm (20,4 ± 6,5), avec atteinte d'au moins un sinus caverneux dans 68 % des cas. Trois sous-groupes ont été définis: 20 patients traités exclusivement par analogues retard de la somatostatine (groupe M), pendant une durée moyenne de 3 ans (extrêmes 1-7 ans), 48 patients traités initialement par chirurgie transphénoïdale (groupe C), dont 21 traités, en seconde intention, par les analogues retard de la somatostatine (groupe CM) pendant une durée moyenne de 1,2 ans (extrêmes 0,2-2 ans). Les 3 groupes étaient comparables en termes de masse tumorale et de niveau initial de GH et d'IGF-I. Les patients du groupe M étaient significativement plus âgés que les patients des 2 autres groupes (p < 0,05). Résultats: 46 % des patients du groupe C après chirurgie et 45 % des patients du groupe M présentaient une valeur moyenne de GH inférieure à 2,5 μg/L. La rémission biologique (GH < 2,5 μg/L et IGF1 normal) était obtenue dans 31 % des cas dans le groupe C, contre 25 % dans le groupe M. Dans ce groupe, une diminution du plus grand diamètre tumoral était observée chez 10 patients (71,5 %), comprise entre 10 % et 25 % pour 7 d'entre eux (50 %) et supérieure à 50 % pour trois des patients (21,5 %). Dans le groupe CM, le taux de rémission biologique (42 %) et les valeurs finales de GH et IGF1 n'étaient pas significativement différentes de ceux du groupe M. En conclusion, ces données suggèrent une efficacité comparable, en termes de pourcentage de rémission, du traitement chirurgical et du traitement par analogues de la somatostatine dans les macroadénomes somatotropes avec extension extrasellaire