Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EV were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–a T cell receptor (pre-TCRa) expression. Low circulating naive ab T cell counts at birth persisted over time, with normal memory ab and high gd T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue ab T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive ab T cell counts but high gd T cell counts. Although residual pre-TCRa expression drove the differentiation of more ab T cells, autoimmune conditions were more frequent in these patients compared with the general population

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

U - Z

UBRABUM          voir UPRAPUM UGAR-APIM          zone : B, E, F Nom(s) OB : Ugar-apim Attestations A.GÀR-a-pí-im     LH 9 : 1 Commentaire général Terroir documenté par un texte provenant de Terqa (1) (= Tall al‑Ashara, n° HIGEOMES 16). UGAR-DAGAN          zone : B Nom(s) OB : Ugar-Dagan Attestations ú-ga-ar-dda-ganki     ARM 1 56 : 12 Commentaire général Terroir proche de Mari attesté par ARM 1 56. Bibliographie sélective par ordre chronologique ▸ J.‑M. Durand, LAPO 17, 1998, p. 525, 548 : p...

A - E

ABA          zone : D, E Nom(s) OB : Aba ; Habum Attestations a-ba-a     DCS 97 : 8 ; YBC 4499 (Hallo JCS 18, p. 57-87) : 30 ha-bi-im     ARM 13 143 : 2′ Commentaire général Montagne mentionnée en relation avec la ville de Talhayum (1). Les « itinéraires paléo-babyloniens » contiennent une étape entre les montagnes Hasam (= Tektek) et Aba – donc probablement en rase campagne. Cette étape suit celle de Mammagira (à l’est) et intervient avant celle de Samum (à l’ouest). Une identification avec ..

L - P

LA'UŠ          zone : B Nom(s) OB : La'uš Attestations la-úš?ki     ARM 7 180 : ii′ ⸢35′⸣ Commentaire général Localité du royaume de Mari selon le texte ARM 7 180 : ii′ 35′. Bibliographie sélective par ordre chronologique ▸ B. Groneberg, RGTC 3, 1980, p. 152 : s.v. La'uš LADA          zone : E Nom(s) OB : Lada Attestations la-a-da     UIOM 2134 (Goetze JCS 7, p. 51-55) : iii 28 la-a-da-a     UIOM 2370 (Goetze JCS 7, p. 54) : 6 Commentaire général Localité attestée par les « itinéraires paléo-..

G - K

GADAŠŠUM          zone : E, F, G Nom(s) OB : Gadaššum Attestations ga-da-ši-imki     Inédit [TH 72-2] : 34 Commentaire général Ville située à l’ouest du Tigre, non loin de Ninet (= Tall Kuyunjik, n° HIGEOMES 94). Bibliographie sélective par ordre chronologique ▸ M. Birot, Syria 50, 1973, p. 4 : route qui passe par Gadaššum puis rejoint le Tigre à Adum ▸ B. Groneberg, RGTC 3, 1980, p. 77 : s.v. Gadašum ▸ P. Marello, MARI 7, 1993, p. 279 n. 22 : sur le Tigre ▸ F. Joannès, Amurru 1, 1996, p. 340..