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A variety of neuropsychiatric complications has been described in association with Covid-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with Covid-19 seen in a multidisciplinary hospital center over six months. We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris -Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 Covid-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., Graphical Abstract Graphical Abstract

It has been claimed that Nigella sativa seeds (NSS), also known as black cumin, have antidiabetic and lipid-lowering properties. Our pilot study investigated the effects of powdered NSS on insulin secretion and lipid profile in healthy male volunteers. We conducted a double-blind, randomized, placebo-controlled 4-week trial in 30 subjects, receiving NSS powder (1 g/day) or placebo orally (15 subjects/group). Insulin secretion as determined by the hyperglycaemic clamp technique, insulin sensitivity as well as cholesterol and triglycerides serum concentrations, were measured before and after treatment. NSS powder administration was clinically well tolerated. It did not modify fasting glycaemia and insulinaemia, and was ineffective on glucose-induced insulin secretion and insulin sensitivity. No significant changes on serum lipids were observed after treatment in any treatment groups, nor between the two treatment groups. However, in the treated group only, there was a significant correlation between total cholesterol change after treatment and its baseline level (r = -0.71, P = 0.006, n = 13), and between low-density lipoprotein (LDL) cholesterol change after treatment and its baseline level (r = -0.74, P = 0.004, n = 13). No such correlations were found for high-density lipoprotein (HDL) cholesterol, and for triglycerides. These results do not confirm any NSS effect on glucose regulation; however, they suggest that NSS powder may be of interest in lowering lipid concentrations in hyperlipidaemic subjects.

The aim of this study was to assess the prevalence of long-term antipsychotic (AP) use in community-dwelling patients with dementia considering hospitalization periods as AP exposure or not. A retrospective study was carried out from 2009 to 2012 on a PACA-Alzheimer cohort (which included 31 963 patients in 2009 and 36 442 in 2012 from 5 million inhabitants). Three groups of patients were identified according to the longest exposure to APs without interruption: nonusers, short-term users (≤3 successive months without discontinuation), and long-term users. Sensitivity analyses on hospitalization periods were carried out. The percentage of patients with at least one AP dispensing was stable over the study period (25.6% in 2009 vs. 26.5% in 2012). In 2012, 27.6% were AP long-term users. This increased to 46.7% when hospitalization periods were counted as AP exposure. In comparison with nonusers, AP users took more benzodiazepines and antidepressants. Short-term users were men [odds ratio (OR)=1.2, 95% confidence interval (CI) (1.1-1.3)] older than 85 years old [OR=1.2, 95% CI (1.1-1.2)]. Long-term users were more exposed to benzodiazepines [OR=1.2, 95% CI (1.1-1.4)]. This study showed that long-term use of AP remained frequent in community-dwelling patients with dementia. It also showed that the prevalence of long-term users almost doubled when hospitalization periods were counted as AP exposure. This underlines the need to consider hospitalization periods when assessing medication exposure in populations with frequent periods of hospitalization.

The reactivation of artefact mechanisms is always a challenge for conservators. Non-invasive diagnostic techniques, applicable directly on the artifacts, allows for performing early-stage diagnostics and avoiding damage. The Acoustic Emission Monitoring of Historical Vehicles (ACUME_HV) project represents the first use of acoustic emission (AE) as a non-invasive technique for the diagnostics of historical vehicles. The aim of this project is to develop an objective, human-independent method. This will help museum personnel to make decisions regarding the reactivation of historical vehicle engines using measurements and data analysis rather than merely personal experience. Herein, we present the results of the first phase of the ACUME_HV project, which was focused on the development of a protocol for the use of AE during cold tests.

Resume Introduction La technique de mesure de la composition corporelle par impedancemetrie bioelectrique (BIA) perd en precision en cas de maigreur ou de forte obesite, du fait des limites du modele mathematique cylindrique employe. La BIA segmentaire minimise cette cause d’erreur en modelisant le corps comme un assemblage de cinq cylindres. De nouveaux outils, dont l’utilisation est facilitee, permettraient de realiser les mesures de la composition des differents segments du corps afin d’etablir des correlations avec certains parametres metaboliques de facon plus aisee en pratique clinique en comparaison avec la DEXA. Synthese des faits Chez 36 sujets de 15 a 69 ans couvrant une plage d’Indice de Masse Corporelle (IMC) de 13 a 41 kg/m2 chez qui la composition corporelle est mesuree grâce a la DEXA en comparaison avec la BIA conventionnelle. La composition de chaque segment est precisement predite (r = 0,726 a 0,987), de meme que la masse grasse tronculaire (r = 0,9575 ; erreur moyenne 2,25 [95 %IC : 1,41–3,09]). Pour la masse grasse du corps entier la prediction est excellente (r2 = 0,9755 ; erreur moyenne 0,532[IC : –0,495–1,56]) et elle reste excellente chez les sujets maigres (r = 0,925 ; pente : 0,953, ordonnee 0,46 ; erreur moyenne 0,015 [IC : –1,1-1,13]). Chez 20 personnes explorees par petit dejeuner standardise avec modelisation mathematique, l’insulino-sensibilite determinee par l’oral minimal model (OMM-SI) s’avere davantage correlee a la MG tronculaire (r = –0,686) qu’a la MG totale ou a celle des membres. Conclusion L’approche segmentaire augmente la precision de la BIA conventionnelle y compris chez les sujets maigres.

Resume L’amyotrophie spinale distale de type 1 (DSMA1), egalement appelee atrophie musculaire spinale avec atteinte respiratoire de type 1 (SMARD1) est une maladie neuromusculaire rare, liee a des mutations du gene IGHMBP2, de transmission autosomique recessive. Nous rapportons l’observation d’une petite fille d’1 an admise pour une insuffisance respiratoire aigue sur pneumopathie. L’association a une surelevation de la coupole diaphragmatique droite sur la radiographie thoracique et des retractions articulaires distales avait permis de suspecter le diagnostic de DSMA1. Celui-ci avait ete confirme par la biopsie musculaire et l’analyse moleculaire. Encore meconnu, ce diagnostic devrait etre evoque devant toute insuffisance respiratoire associee a une paralysie phrenique et une atrophie musculaire distale survenant dans la premiere annee de vie. L’electromyogramme avec etude des vitesses de conduction nerveuse et la biopsie musculaire evoquent le diagnostic qui doit etre confirme par l’analyse genetique. L’identification des mutations permet de proposer un diagnostic prenatal.

This study investigated the prevalence and consequences of heterozygous CYP21A2 mutations in premature pubarche (PP) girls.We investigated 36 French Mediterranean girls with isolated PP. We performed synacthen testing with 17OHP and 21-deoxycortisol evaluation, along with molecular analysis of the CYP21A2 gene in girls with abnormal elevation of one of these two adrenal steroids. Three girls (8.3%) had nonclassical adrenal hyperplasia, secondary to compound heterozygosity that associated at least one severe mutation for the three girls. A heterozygous mutation of the CYP21A2 gene was confirmed by molecular biology in eight girls (22%); a deletion of the CYP21A2 gene was found in one of them. Biological hyperandrogenism was found in the prepubertal CYP21A2 mutation carriers, whereas the four heterozygous girls who were followed long enough to have reached pubertal age presented biological and clinical hyperandrogenism.We underline the high prevalence of heterozygous CYP21A2 mutations in girls with PP and demonstrate the usefulness of systematic screening by synacthen testing, both to improve their future clinical management and to prevent the transmission of classical adrenal hyperplasia to future offspring. Because of the severe metabolic and cardiovascular consequences of hyperandrogenism, long-term follow-up of these heterozygous patients is mandatory.

The Zollinger-Ellison syndrome is due to an endocrine gastrin-secreting tumor, the gastrinoma. This tumor is often malignant and patients develop metastases in 25% of cases. The usual localizations of gastrinomas are at the head of the pancreas, the duodenal wall and the peripancreatic lymph nodes. Ectopic localizations, such as stomach, small bowel, gallbladder, liver or ovaries, are rare. We report the case of an intrahepatic gastrinoma, surgically treated by left hepatectomy. Upon review of scientific literature, we found 19 cases of intrahepatic gastrinoma. This diagnosis is always difficult to establish, even after a complete preoperative imaging and an extensive operative search for a possible primary tumor. The best evidence for diagnosis is the gastrinemia decreasing to a normal range after liver resection, and the absence of recurrence in long-term follow-up.

Distal spinal-muscular atrophy 1 (DSMA1) or spinal-muscular atrophy with respiratory distress type 1 (SMARD1) is a rare neuromuscular disorder resulting from IGHMBP2 mutations. It is an autosomal recessive disease. We present the case of a 1-year-old girl admitted for respiratory failure associated with pneumonia. Right hemidiaphragmic elevation on the chest radiograph and distal retractions suggested the diagnosis of DSMA1. It was confirmed by muscle biopsy and molecular analysis. This unrecognized diagnosis should be considered when respiratory failure develops in the first year of life and is associated with diaphragmatic paralysis and distal muscle atrophy. Electromyography with measurement of nerve conduction velocity and muscle biopsy suggest the diagnosis, which must be confirmed by genetic analysis. After identifying the mutations, it is possible to perform prenatal diagnosis.

The TSH receptor is a key element of thyroid homeostasis and many gain or loss of function mutations have been described since its cloning in 1989. Behind classical and severe forms like toxic adenomas, non-autoimmune familial or sporadic hyperthyroidism or inversely complete TSH resistance syndromes, new methodological approaches allow now the functional characterization of milder clinical situations : linear regression analysis of activating mutations can differentiate mutations with moderate constitutive activity and non functional receptor's variants ; the early oligomerization of wild-type and mutated receptors in intracellular compartments explain the dominant inheritance of mild form of TSH resistance. However many aspects of TSH receptor signalization remain to be explored, for example its persistent activity after internalization, and their clinical implications to be determined. Finally, new modulators of TSH receptor with attractive therapeutic potential are being developed.

Pancreatic beta cell hyperactivity is known to occur in obesity, particularly in insulin-resistant states. Our aim was to investigate whether changes in neuronal nitric oxide synthase (nNOS) function affect beta cell compensation in two relevant models: the Zucker fa/fa rats and pancreatic islets from obese humans.Glucose-induced insulin response was evaluated in the isolated perfused rat pancreas and in human pancreatic islets from obese individuals. Expression of nNOS (also known as NOS1) and subcellular localisation of nNOS were studied by quantitative RT-PCR, immunoblotting, immunofluorescence and electron microscopy.Pancreatic beta cells from Zucker fa/fa rats and obese individuals were found to be hyper-responsive to glucose. Pharmacological blockade of nNOS was unable to modify beta cell response to glucose in fa/fa rats and in islets from obese individuals, suggesting an abnormal control of insulin secretion by the enzyme. In both cases, nNOS activity in islet cell extracts remained unchanged, despite a drastic increase in nNOS protein and an enhancement in the dimer/monomer ratio, pointing to the presence of high amounts of catalytically inactive enzyme. This relative decrease in activity could be mainly related to increases in islet asymmetric dimethyl-arginine content, an endogenous inhibitor of nNOS activity. In addition, mitochondrial nNOS level was decreased, which contrasts with a strongly increased association with insulin granules.Increased nNOS production and dimerisation, together with a relative decrease in catalytic activity and relocalisation, are involved in beta cell hyperactivity in insulin-resistant rats but also in human islets isolated from obese individuals.

The Zollinger-Ellison syndrome is due to an endocrine gastrin-secreting tumor, the gastrinoma. This tumor is often malignant and patients develop metastases in 25% of cases. The usual localizations of gastrinomas are at the head of the pancreas, the duodenal wall and the peripancreatic lymph nodes. Ectopic localizations, such as stomach, small bowel, gallbladder, liver or ovaries, are rare. We report the case of an intrahepatic gastrinoma, surgically treated by left hepatectomy. Upon review of scientific literature, we found 19 cases of intrahepatic gastrinoma. This diagnosis is always difficult to establish, even after a complete preoperative imaging and an extensive operative search for a possible primary tumor. The best evidence for diagnosis is the gastrinemia decreasing to a normal range after liver resection, and the absence of recurrence in long-term follow-up.

Introduction L’insulinotherapie dans le diabete de type 2, souvent necessaire en cas d’echec des antidiabetiques oraux, voit parfois son efficacite limitee par les effets secondaires, notamment la prise de poids. Nous avons evalue la securite et l’efficacite d’un traitement par exenatide apres arret d’une insulinotherapie chez des diabetiques de type 2. Patients et Methodes Depuis le 15/04/2008, la substitution de l’insuline par de l’exenatide a ete proposee a 23 patients (12 hommes et 11 femmes) sous association insuline (dose moyenne 62 ± 42 U/j) et ADO, et ayant du mal a controler leur poids. Leurs caracteristiques etaient les suivantes : âge 63,4 ± 9,9 ans, anciennete du diabete 14,5 ± 11,3 ans, duree de l’insulinotherapie 2,9 ± 2,0 ans, IMC initial 34,9 ± 7,9 kg/m 2 , HbA1c 7,9 ± 2,2 %. Les comparaisons ont ete realisees par test de Student (apparie ou non), test de Wicoxon ou test exact de Fisher. Resultats Une insulinotherapie a du etre reprise chez 10 sujets, dont 8 au cours du 1 er mois (6 pour mauvais controle glycemique, 2 pour intolerance digestive). Les groupes « sevrage reussi » et « reprise de l’insuline » etaient similaires concerant l’âge, l’anciennete du diabete, la duree de l’insulinotherapie, l’IMC et l’HbA1c, mais les doses d’insuline etaient plus faibles dans le groupe « sevrage reussi » (40,7 ± 24,9 vs 95,0 ± 41,7, P = 0,002). Chez les 13 sujets (56,5 %) toujours sous exenatide et sevres en insuline, le recul moyen est de 10,4 mois (extremes 4,2–17,6). Au suivi, la variation de poids est de – 4,6 ± 5,2 kg (P = 0,008), la variation d’HbA1c moyenne de – 1,18 ± 0,76 % (P Conclusion Le remplacement de l’insuline par de l’exenatide peut etre propose dans le diabete de type 2 lorsque le controle ponderal est insuffisant. Ce traitement a permis une amelioration simultanee du poids et de l’HbA1c chez pres de 50 % des patients traites. La majorite des echecs est detectable au cours du premier mois, et le risque d’echec est plus important pour les patients traites par de fortes doses d’insuline. Il serait souhaitable de confirmer ces resultats chez un plus grand nombre de sujets.

Introduction Nous avons precedemment demontre que la NO synthase neuronale (nNOS) est impliquee dans le controle de la secretion d’insuline chez le rat. Chez l’homme, nous avons retrouve l’expression de la nNOS dans les cellules b pancreatiques. Notre objectif est donc rechercher si la nNOS, comme chez le rat, est capable de moduler la secretion d’insuline dans les ilots pancreatiques humains. Materiels et methodes La secretion insuline a ete evaluee sur 10 ilots pendant 90 minutes, en presence de de glucose et de differents modulateurs pharmacologiques. Resultats L’inhibition de la nNOS par 10 mm de L-NAME amplifie la secretion d’insuline induite par 8,3 et 16,7 mm de glucose (+ 35 % et + 33 % respectivement, P Conclusion Dans les ilots pancreatiques humains, de faibles niveaux de NO modulent negativement la secretion d’insuline (S-nitrosylation de proteines du metabolisme), tandis qu’a plus fortes concentrations, le NO amplifie la secretion d’insuline, probablement via la nitration de proteines de l’exocytose.