L\'amylose Laryngée À Propos D\'un Cas

L\'amylose localisée est caractérisée par un dépôt de protéines fibrillaires dans un site de l\'organisme sans atteinte systémique. La localisation laryngée est très rare. Ce diagnostic doit être évoqué devant toute lésion d\'allure bénigne du larynx. Les auteurs rapportent un cas d\'amylose laryngée colligé sur une période de 10 ans.Localized amyloidosis is characterized by the deposition of amyloid fibres in a particular site or organ system in the absence of systemic involvement. The laryngeal location of amylosis is rare. The diagnosis must be suspected in front of any tumor of benign speed of the larynx. Authors report a case of laryngeal amyloidosis brought during a period of 10 years. Journal Tunisien d\'ORL et de chirurgie cervico-faciale Vol. 16 2006: pp. 30-3

Le Carcinome Mucoépidermoïde De La Parotide : Apropos De 5 Cas

Les tumeurs des glandes salivaires représentent moins de 5% de toutes les tumeurs de la tête et du cou. Parmi eux, le carcinome mucoépidermoïde est la tumeur la plus fréquente. Quarante cinq pour cent des carcinomes mucoépidermoïdes se développent au niveau de la glande parotide. Cette lésion se voit surtout chez l\'adulte vers la 5ème décade. Le diagnostic est confirmé seulement à l\'examen anatomopathologique. Son pronostic est fonction des critères histologiques.Salivary gland tumors account for less than 5% of the head and neck neoplasms. Among them, mucoepidermoid carcinoma is the most common malignant salivary gland tumor. About 45% of mucoepidermoid carcinomas occur in the parotid gland, and appear around the fifth decade of life. A certain diagnostic can be obtained only after post-operative histological examination. Histological examination indicates the patient prognosis. Journal Tunisien d\'ORL et de chirurgie cervico-faciale Vol. 16 2006: pp. 39-4

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV-2 RBD and ACE2 PD might be prone to small molecule modulation, due to the hydrophilic nature of the bi-molecular recognition process and the presence of druggable hot spots. The fundamental objective is to identify, and provide to the international scientific community, hit molecules potentially suitable to enter the drug discovery process, preclinical validation and development. © 2020 Wiley-VCH Gmb

New microwave assisted radiolabelling method and rat brain biodistribution study of two new 99mTc-tricarbonyl complexes as potential brain imaging agents

Two new cyclopentadienyl piperidine derivatives, namely ferrocene carboxylic acid 1-ethyl-3-hydroxypiperidinyl ester and ferrocene carboxylic acid 4-hydroxypiperidinyl ester, were synthesized. The ligands were then radiolabelled with 99mTc using two different approaches. The first method consisted of reacting the ligand precursor with Mn(CO)5Br in pertechnetate 99mTcO4 - in normal saline and dimethyl formamide (DMF) at 150°C for 1 h. The yields were 70% and 90%, respectively. For the second method, the reactions mixtures were placed in a microwave oven for 2 min at 650 watt. The yields were higher than 90% for both 99mTc complexes. Biodistribution studies showed that tricarbonyl{eta5- [carboxy-3-hydroxy(N-ethyl)piperidine]cyclopentadienyl}technetium(I) had the highest brain uptake. The regional distribution in the brain also demonstrated relatively higher uptake of tricarbonyl{eta5-[carboxy-3-hydroxy(N-ethyl) piperidine]cyclopentadienyl}technetium(I) in the colliculus (1.97% ID/g tissue,) with the colliculus to cerebellum ratio of 1.99. We conclude that the radiolabelling can be achieved by microwave activation, and tricarbonyl{eta5-[carboxy-3- hydroxy(N-ethyl)piperidine]cyclopentadienyl}technetium(I) has the potential for use as central nervous system (CNS) imaging agent