AGO1 and AGO2 Act Redundantly in miR408-Mediated Plantacyanin Regulation

Background: In Arabidopsis, AGO1 and AGO2 associate with small RNAs that exhibit a Uridine and an Adenosine at their 59 end, respectively. Because most plant miRNAs have a 59U, AGO1 plays many essential roles in miRNA-mediated regulation of development and stress responses. In contrast, AGO2 has only been implicated in antibacterial defense in association with miR393*, which has a 59A. AGO2 also participates in antiviral defense in association with viral siRNAs. Principal Findings: This study reveals that miR408, which has a 59A, regulates its target Plantacyanin through either AGO1 or AGO2. Indeed, neither ago1 nor ago2 single mutations abolish miR408-mediated regulation of Plantacyanin. Only an ago1 ago2 double mutant appears compromised in miR408-mediated regulation of Plantacyanin, suggesting that AGO1 and AGO2 have redundant roles in this regulation. Moreover, the nature of the 59 nucleotide of miR408 does not appear essential for its regulatory role because both a wildtype 59A-MIR408 and a mutant 59U-MIR408 gene complement a mir408 mutant. Conclusions/Significance: These results suggest that miR408 associates with both AGO1 and AGO2 based on criteria that differ from the 59 end rule, reminiscent of miR390-AGO7 and miR165/166-AGO10 associations, which are not based on the nature of the 59 nucleotide

Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) μg/L, or ≤100 μg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age—31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31–5.31), age < 30 years (OR 2.30, CI95% 1.16–4.56), and P. aeruginosa (OR 2.09, CI95% 1.04–4.19)

Computed and subjective blue scleral color analysis as a diagnostic tool for iron deficiency

Computed and subjective blue scleral color analysis as a diagnostic tool for iron deficiency.Introduction : Iron deficiency (ID) is common in primary care and its diagnosis requires measurement using ferritin due to its non-specific clinical presentation. Blue sclera is described as a specific and sensitive sign of ID but there are few reports of this in the literature. We aimed to determine the diagnostic value of blue sclera for the diagnosis of ID.Methods : We enrolled a total of 74 patients suspected of having ID in a tertiary medical center. Pictures of their eyes were taken using a smartphone under similar daylight. Three independent physicians who were blinded from iron stores, graded the scleral color in anonymized pictures. A computer analysis of the picture yielded the blue percentile (BP) of the sclera. ID was defined where ferritin ≤ 30 μg/L (100 μg/L in case of inflammatory syndrome).Results : Final analysis included 67 patients (mean age 59.9 ± 20.1-year) with a male:female ratio of 0.8. Fifty-one patients had ID. Subjective blue scleral color was associated with ID for physician 1 (p = 0.03) with low sensitivity 60.8% [CI95: 46.1;74.2], specificity 68.8% [CI95: 41.3;89%] and high positive predictive value 86.1% [CI95: 70.5;95.3]. A non-significant trend was observed for other physicians (p = 0.05). Inter-rater reliability was poor (Fleiss’s κ 0.02-0.23). Computer analysis of the pictures showed higher BP in the ID group (p = 0.04). The area-under-the-curve of receiver-operating-characteristics curve was 0.7 [CI95: 0.54;0.85]. Sensitivity was 78.4% [CI95: 63.7;88.7], specificity was 50% [CI95: 24.7;75.3] with a threshold of 29.1. Assessment of blue sclera was not influenced by iris color, sex or anemia.Conclusion : Clinical assessment of blue sclera has good positive-predictive value for ID diagnosis. Computer analysis showed encouraging results correlated to clinical assessment. Improvement of this innovative method could provide simple diagnostic tool for ID diagnosis in primary care.Étude de la couleur bleue de la sclère pour le diagnostic de carence martiale : analyse clinique et informatisée.Introduction : la carence martiale (CM) est fréquente en soins primaires. Les signes cliniques sont pauvres : le diagnostic repose sur le dosage de la ferritine sérique. La présence d’une sclère bleue serait un signe sensible et spécifique de CM. Notre objectif était d’évaluer la valeur diagnostique de ce signe pour le diagnostic de CM.Méthodes : une photographie par smartphone des yeux de 74 patients suspects de CM était réalisée de façon standardisée. Trois médecins indépendants évaluaient en aveugle la couleur de la sclère sur les images anonymisées. Une analyse informatisée déterminait le percentile de bleue dans les pixels de la sclère. La CM était définie par une ferritine ≤ 30 μg/L (100 μg/L en cas de syndrome inflammatoire).Résultats : 67 patients (56% de femmes) étaient inclus dans l’analyse finale (âge moyen 59.9 ± 20.1 ans). 51 patients présentaient une CM. La présence d’une sclère bleue était significativement associée à la CM pour l’évaluateur 1 (p = 0.03) avec une sensibilité de 60.8% [IC95: 46.1;74.2], une spécificité de 68.8% [IC95: 41.3;89%] et une valeur prédictive positive de 86.1% [IC95: 70.5;95.3]. Une tendance non significative (p = 0.05) était observée pour les autres évaluateurs. L’analyse informatisée montrait un percentile de bleu plus élevé chez les patients avec CM (p = 0.04). L’aire sous la courbe de la courbe ROC était de 0.7 [IC95: 0.54;0.85], donnant une sensibilité de 78.4% [IC95: 63.7;88.7] et une spécificité de 50% [IC95: 24.7;75.3]. L’évaluation clinique et informatisée n’étaient influencées ni par le sexe, la couleur de l’iris ou la présence d’une anémie.Conclusion : la présence d’une sclère bleue a une forte valeur prédictive positive pour le diagnostic de CM. L’analyse informatisée est bien corrélée à l’évaluation clinique. L’amélioration de cette méthode permettrait de proposer un outil intéressant pour le diagnostic de la CM

Risk Factors for Venous Thromboembolism in Severe COVID-19: A Study-Level Meta-Analysis of 21 Studies

Venous thromboembolism (VTE) in patients with COVID-19 in intensive care units (ICU) is frequent, but risk factors (RF) remain unidentified. In this meta-analysis (CRD42020188764) we searched for observational studies from ICUs reporting the association between VTE and RF in Medline/Embase up to 15 April 2021. Reviewers independently extracted data in duplicate and assessed the certainty of the evidence using the GRADE approach. Analyses were conducted using the random-effects model and produced a non-adjusted odds ratio (OR). We analysed 83 RF from 21 studies (5296 patients). We found moderate-certainty evidence for an association between VTE and the D-dimer peak (OR 5.83, 95%CI 3.18–10.70), and length of hospitalization (OR 7.09, 95%CI 3.41–14.73) and intubation (OR 2.61, 95%CI 1.94–3.51). We identified low-certainty evidence for an association between VTE and CRP (OR 1.83, 95% CI 1.32–2.53), D-dimer (OR 4.58, 95% CI 2.52–8.50), troponin T (OR 8.64, 95% CI 3.25–22.97), and the requirement for inotropic drugs (OR 1.67, 95% CI 1.15–2.43). Traditional VTE RF (i.e., history of cancer, previous VTE events, obesity) were not found to be associated to VTE in COVID-19. Anticoagulation was not associated with a decreased VTE risk. VTE RF in severe COVID-19 correspond to individual illness severity, and inflammatory and coagulation parameters

Computed and Subjective Blue Scleral Color Analysis as a Diagnostic Tool for Iron Deficiency: A Pilot Study

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Effect of procyanidin on dietary iron absorption in hereditary hemochromatosis and in dysmetabolic iron overload syndrome: A crossover double-blind randomized controlled trial

International audienceBackground & aims: Type I hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) are the two most prevalent iron overload diseases. Although many food components, particularly polyphenols, reduce iron bioavailability, there is no clinically validated nutritional strategy to reduce food-iron absorption in patients with these diseases. We aimed to determine whether supplementation with 100 mg of procyanidins during a meal reduces dietary iron absorption in patients with HH or DIOS.Methods: 20 HH and 20 DIOS patients were enrolled in a double-blind three-period crossover randomized study. Basal serum iron level was measured following an overnight fast. Each patient consumed a standardized test iron-rich meal containing 43 mg of iron with two capsules of placebo or procyanidin supplementation. Each period was separated by a 3-day wash-out period. The primary objective was a reduction of dietary iron absorption, assessed by a reduction of serum-iron area under the curve (AUC) corrected for baseline serum iron.Results: All patients completed the study. The meal and the procyanidin supplements were well tolerated. In both HH and DIOS patients, the iron-rich meal induced a significant increase of serum iron compared with baseline at 120, 180, 240 min, from 8 to 9.1%(p = 0.002, 0.001 and 0.003, respectively) in DIOS and from 15.8 to 25.7% (p < 0.001) in HH. Iron absorption was 3.5-fold higher in HH than in DIOS (p < 0.001). Procyanidin supplementation did not significantly modify iron absorption in DIOS (AUC of added iron 332.87 +/- 649.55 vs 312.61 +/- 678.61 mu mol.h/L, p = 0.916) or in HH (1168.62 +/- 652.87 vs 1148.54 mu mol.h/L +/- 1290.05, p = 0.917).Conclusions: An iron-rich test meal led to a marked increase in iron absorption in HH but a mild increase in DIOS. Procyanidin supplementation does not significantly reduce dietary iron absorption in either disease. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) μg/L, or ≤100 μg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age—31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31–5.31), age P. aeruginosa (OR 2.09, CI95% 1.04–4.19)

A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report

International audienceAceruloplasminemia is a rare autosomal recessive inherited disorder. Mutations in the ceruloplasmin gene cause depressed ferroxidase activity leading to iron accumulation. The clinical phenotype is highly variable: anemia, retinopathy, diabetes mellitus, psychiatric disorders, and neurological symptoms including parkinsonian disorders and dementia are the main features of this disease. Characterized by high serum ferritin with low transferrin saturation, aceruloplasminemia uniquely combines brain, liver and systemic iron overload. We report here four new cases of aceruloplasminemia in a consanguineous North-African family. Genetic sequencing revealed a homozygous missense variant c.656T&gt;A in exon 4 of the ceruloplasmin gene, which had been described previously as of &quot;unknown significance&quot; in the dbSNP database and never associated with ACP in the HGMD database. Ferroxidase activity was strongly depressed. Clinical manifestations varied among cases. The proband exhibited mild microcytic anemia, diabetes mellitus, psychosis and parkinsonism, whereas the other cases were asymptomatic or mildly anemic, although high serum ferritin and brain iron deposition were documented in all of them. Therapeutic management was complex. The proband started deferoxamine treatment when already symptomatic and he rapidly declined. In the asymptomatic cases, the treatment was associated with poor tolerance and was discontinued due to anemia requiring red blood cell transfusion. Our series illustrates the need for new therapeutic approaches to aceruloplasminemia

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis

International audienceBackground The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. Methods In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. Results We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I 2 =94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I 2 =94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I 2 =95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I 2 =92%, vs 9.0%, 95% CI 6.9% to 11.4%, I 2 =95%; p interaction <0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, p interaction =0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I 2 =96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I 2 =93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I 2 =84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates. Conclusions Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease

Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series

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