In-Person and Remote Workshops for People With Neurocognitive Disorders: Recommendations From a Delphi Panel

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders

Evidence for natural antisense transcript-mediated inhibition of microRNA function

MicroRNAs (miRNAs) have the potential to regulate diverse sets of mRNA targets. In addition, mammalian genomes contain numerous natural antisense transcripts, most of which appear to be non-protein-coding RNAs (ncRNAs). We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 (BACE1), a critical enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript. We report here that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1-antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1-antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1-antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer's disease subjects compared to control individuals. Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover, bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter

Pathologies infiltratives et inflammatoires de l'hypophyse

C’est le traité de référence dans la discipline : livre unique, sans concurrent de cette envergure. Il couvre toute l’endocrinologie moderne, qui s’appuie sur l’apport de la biologie moléculaire, de la biochimie, de l’immunocytochimie, de l’imagerie moderne avec, en particulier la T.E.P. La physiopathologie, les symptômes, les éléments du diagnostic, les orientations pronostiques, les choix thérapeutiques sont exposés de façon exhaustive pour les affections touchant toutes les glandes endocrines : thyroïde, parathyroïde, surrénales, testicules, ovaires, hypophyse. Au total, il s’agit d’un ouvrage complet, moderne et pratique ; la richesse des illustrations, des arbres décisionnels, l’abondante bibliographie contribuent à en faire un outil indispensable au quotidien. Ce Traité d'endocrinologie conçu par et maintenant publié sous la direction de Philippe Chanson et Jacques Young est remarquable, par son contenu, d'abord, ensuite, par le fait qu'il est écrit en français, ce qui en fait un ouvrage unique. En effet, les grands traités d'endocrinologie de ces dernières années sont en anglais. La liste des 154 chapitres couvre la totalité de l'endocrinologie d'aujourd'hui dans tous ses aspects, depuis la biologie moléculaire à la pratique du clinicien, interniste ou chirurgien. Et le texte, les textes, sont d'enseignement fondamental pour l'étudiant autant que de présentations et discussions diagnostiques pour le clinicien averti comme pour celui qui cherche à s'instruire. Comme la nostalgie, pour reprendre le cliché bien connu, l'endocrinologie n'est plus ce qu'elle était. Le concept de glandes endocrines, s'il reste vrai dans son ensemble, est cependant dépassé par ces nouvelles découvertes qui montrent sécrétion et utilisation in loto de ces mêmes substances (hormones ?) par des organes aussi variés que le cerveau ou le tissu adipeux. Et le Traité d'endocrinologie présente et discute, nombreuses références à l'appui, les nouveaux concepts des mécanismes d'action des différentes classes d'hormones tant au niveau du soma que du psyché. Les implications pour la thérapeutique sont considérables et ce sera le malade qui finalement, bénéficiera de toutes ces connaissances présentées ici à son médecin. L'endocrinologie et son ouverture sur la neuro-endocrinologie constituent plus que jamais la science de nous-mêmes, dans la santé comme dans la maladie. Ce Traité d'endocrinologie est une magnifique présentation de l'état des choses

Absence of hypogonadism in a male patient with a giant prolactinoma: a clinical paradox.

peer reviewedBackground Impotence and decreased libido are the cardinal features of prolactinomas in males. We describe the unusual clinical, pathological and biochemical features in a male patient with a giant prolactinoma and normal gonadal function. Case Report A 57 year-old man presented with visual symptoms related to a 30 × 25 × 60 mm tumor of the sella and skull base. Biopsy revealed a pituitary adenoma and subsequent hormone profiles demonstrated grossly elevated serum prolactin (131,412 ng/ml), LH at the upper limit of normal and normal testosterone. The patient had no symptoms of decreased libido or impotence related to this giant prolactinoma. Immunohistochemistry revealed a tumor that was positive for prolactin, alpha-subunit and LH. Cabergoline greatly reduced prolactin levels but these remained above normal. LH, testosterone and alpha-subunit levels were decreased in parallel. Loss of libido and impotence became apparent when testosterone fell below normal, a situation that resolved with further cabergoline treatment and prolactin inhibition and testosterone therapy. Conclusions Sexual dysfunction is a hallmark of prolactinomas in males. Tumors that co-secrete prolactin and LH are extremely rare and this is the first such case reported in an adult male. In this case, normal testosterone was maintained by intact LH levels even in the face of the highest prolactin level reported to date.Introduction L’impuissance sexuelle et la diminution de libido sont les symptômes principaux du prolactinome chez l’homme. Nous décrivons un cas inhabituel sur les plans clinique, anatomopathologique et biologique chez un homme souffrant d’un prolactinome géant mais gardant une fonction gonadique normale. Cas clinique Un homme de 57 ans s’est présenté à la consultation avec des symptômes visuels en relation avec une tumeur de la selle turcique et de la base du crâne de 30 × 25 × 60 mm. La biopsie a révélé un adénome hypophysaire et les dosages hormonaux qui ont suivi ont révélé un taux de prolactine de 131 412 ng/ml. La LH était à la limite supérieure de la normale et la testostérone était normale. Le patient n’avait pas de diminution de libido, ni d’impuissance sexuelle en relation avec ce prolactinome géant. L’immunohistochimie a révélé une tumeur positive pour la prolactine, la sous-unité alpha et la LH. Un traitement par cabergoline a permis de réduire fortement le taux de prolactine sans toutefois le normaliser. Les taux de LH, testostérone et sous-unité alpha ont été diminués en parallèle. Le patient a alors observé une diminution de libido et une impuissance sexuelle qui sont devenues importantes lorsque la testostérone est tombée sous la barre inférieure de la normale. Conclusion La dysfonction sexuelle est un signe évident des prolactinomes chez l’homme. Une tumeur qui cosécrète prolactine et LH est extrêmement rare et le cas que nous rapportons est le premier rapporté chez un homme adulte. Dans ce cas, la valeur de testostérone normale était maintenue par la LH intacte qui était sécrétée par la tumeur malgré les valeurs les plus élevées de prolactine rapportées jusqu’à ce jour

Experimental gamma coincidence spectra recorded in prompt gamma neutron activation analysis

International audienceA feasibility study of gamma-gamma coincidence measurements in prompt gamma neutron activation analysis is carried out experimentally with a pulsed DT neutron generator, a polyethylene graphite cell and eight large NaI(Tl) scintillators. Detection limits are measured with multidimensional energy spectra created in gamma-gamma coincidence and compared to HPGe detector spectra. With a neutron emisison of 2.5 x 108 n.s-1, the detection limit for sulfur is about 15 g in 20 min, while the detection limit is larger than 200 g when using the HPGe detector spectra. Processing the summ of up to three coincident gamma-ray energies highlights useful signal for a dysprosium sample, and allows for detecting permanent magnets containing 4% mass dysprosium within a rotor mock-up composed of stainless steel

Prolactinomas Resistant to Standard Doses of Cabergoline : A multicenter study of 92 patients

Background: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB 652.0 mg weekly. Results: Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB max/w) was 3.5 mg (2.0-10.5). Despite a higher CABmax/w in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB max/w (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CABmax/w or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%). Conclusion: CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome