Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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

Dosage quantitatif de K, Ca, Ti, et Fe dans les minéraux argileux par fluorescence des rayons X. Méthode des poudres. Problème posé par le dosage de Si et Al

Rapid determination of K, Ca, Ti, Fe, Si, and A1 in clay mineral specimens is possible, using X -ray fluorescence on the powder, without melting or pelletizing, or on the powder diluted with silica. It can be shown that the mutual replacement of the different oxides of the clay mineral has little effect on the total mass absorption coefficient for the radiation considered. As a result the inter-element effect is weak. Moreover its effect is considerably reduced by diluting the sample in silica, which has a linear coefficient of absorption near to that of clay minerals. On the other hand particle size and mineralogical effects are negligible because of the very small size of the clay minerals. These methods give very rapid results of comparable value to classical chemical methods for K, Ca, Ti, and Fe. Si and A1 can often be determined rapidly in a semi -quantitative way.Il est possible de doser rapidement, par fluorescence des rayons X, sur poudre sans fusion ni pastillage, ou sur poudre diluée dans, la silice, le potassium, le calcium, le titane, le fer, la silice et l'alumine dans des échantillons de minéraux argileux. On montre que les remplacements mutuels des différents oxydes composant les minéraux argileux modifient peu le coefficient d'absorption massique total pour les rayonnements envisagés. En conséquence, l'effet inter-élément est faible. De plus, son rôle est considérablement amoindri en diluant l'échantillon dans la silice qui a un coefficient d'absorption linéaire voisin de celui des minéraux argileux. D'autre part les effets granulométriques et minéralogiques sont négligeables en raison de la très faible taille des minéraux argileux. Ces méthodes donnent des résultats très rapides, dont la valeur est comparable à ceux obtenus par voie chimique classique pour K, Ca, Ti et Fe. Pour ce qui concerne Si et Al, ils peuvent toutefois être dosés rapidement, d'une façon semi-quantitative.Nicolas Jean, Douillet Philippe, Quintin M. Dosage quantitatif de K, Ca, Ti, et Fe dans les minéraux argileux par fluorescence des rayons X. Méthode des poudres. Problème posé par le dosage de Si et Al. In: Bulletin du Groupe français des argiles. Tome 19, fascicule 1, 1967. pp. 5-21

Utilisation de la méthode des poudres, sans fusion ni pastillage, pour le dosage rapide de K, Ca, Ti, Mn et Fe dans les roches silicatées à l'aide de la fluorescence des rayons X

A l'aide de la fluorescence des rayons X, compte tenu de la composition chimique moyenne des roches de l'écorce terrestre, du coefficient total d'absorption et en choisissant une granulométrie convenable, il est possible de doser rapidement, sans fusion ni pastillage, K, Ca, Ti, Mn, Fe dans des poudres de matériaux silico˗alumineux. Cette méthode peut être encore améliorée en diluant les échantillons dans la silice.Nicolas Jean, Quintin M., Douillet Philippe. Utilisation de la méthode des poudres, sans fusion ni pastillage, pour le dosage rapide de K, Ca, Ti, Mn et Fe dans les roches silicatées à l'aide de la fluorescence des rayons X. In: Bulletin de la Société française de Minéralogie et de Cristallographie, volume 89, 4, 1966. pp. 469-476

Variabilité spatiale des conditions climatiques locales au niveau du bassin versant de la Rivière d'Auray

Rapport d'étude LETG UMR 6554 - SML