Comite De Research Articles

Protocol for a prospective quasi-experimental study on SARS-CoV-2 transmission during outdoor sports events in France: the COVID-ESO project

IntroductionThe spread of SARS-CoV-2 and its variants in the community remains a major concern despite the application of control measures including the banning of mass sporting events. The circulation of...

FROM ALEXANDRIA TO ASWAN: ROLE OF THE COMITÉ DE CONSERVATION DES MONUMENTS DE L’ART ARABE IN THE PROVINCES

Due to the massive scale of urbanization in the provinces of Egypt , the protection of architectural heritage is becoming more and more difficult and challenging , most restoration and conservation projects funded by international and governmental bodies consider cairo as their main priority while architectural heritage in several provinces of Egypt remains undocumented, unprotected or in the verge of being destroyed.Throughout seventy years of operation , the Comite de Conservation des Monuments de I'Art Arabe had unprecedented impact on the architectural heritage of Egypt .Despite being halted in 1954 ,the comite interventions are still visible on Cairo's urban fabric , however little is known about the comite interventions in the other provinces of Egypt . This research paper aims to shed lights on the formation and evolution of the comite, approaches of interventions and their impact on the built environment particularly in the provinces .The paper will discuss the formation and the evolution of the comite and its interventions in the provinces. Through the analysis and the re-interpretation of their own annual published bulletins,In order to take advantage from these approaches in future conservation projects .

High Plasma Concentration of Non-Esterified Polyunsaturated Fatty Acids Is a Specific Feature of Severe COVID-19 Pneumonia

Background: The pathogenesis of severe COVID-19 is frequently associated with an uncontrolled inflammatory response. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status.Methods: Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological features were assessed.Findings: Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response with higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients, suggesting an increase in phospholipase A2 activity. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels.Trial Registration: NCT04435223Funding Statement: This study was supported by grant (MN) from the COVIDOLIP – AOIc2020 (Institutional grant), by the INSERM (Centre de Recherche UMR 1231) and the ANR Investissements d’Avenir Grant (ANR-11 LABX-0021-01, Labex Lipstic).Declaration of Interest: The authors declare no existing conflict of interest.Ethics Approval Statement: The study fulfilled legal and ethics requirements: Approval was obtained from the CPP (Comité de Protection des Personnes SUD MEDITERRANEE V; 2017-A03404-49) for the original study and an amendment was obtained to include supplementary patients with severe COVID-19. All subjects (or their legal representatives) received written information and provided their consent to participate.

Isolation and Characterization of Nocardiae Associated with Foaming Coastal Marine Waters.

Nocardiosis is an infectious disease caused by Nocardia species that occurs worldwide, albeit more prevalently in tropical/subtropical regions. It can appear as either acute, subacute or as a chronic infection mostly with those with a compromised/weakened immune system. Inhalation of spores and or mycelium fragments is the main transmission route for developing pulmonary nocardiosis. In contrast, cutaneous nocardiosis usually occurs via direct contact. In the subtropical region of the Sunshine Coast in Australia foaming events with thick and persistent and orange-brown color foam have been observed during summer seasons in the near shore marine environments. This study reports the existence of nocardiae in these near shore marine environments by the use of a novel isolation method which used the gas requirements of nocardiae as a selective battery. A total of 32 nocardiae were isolated with the use of this novel method and subsequently conducted molecular identification methods confirmed that the isolates belonged to the genus Nocardia. Twenty-one isolates out of the 32 were closely related to N. nova strains MGA115 and one was related to CBU 09/875, in addition when compared with human pathogenic nocardiae twenty of the isolates were found to be related to N. nova strain JCM 6044. Isolates displayed varied resistance against some of the antibiotics tested when interpretation threshold recommended the Comite de L’Antibiogramme de la Societe Francaise de Microbiologie were used. The highest level of resistance against cefotaxime (n = 27) and ceftriaxone (n = 24). Some of the isolates (n = 6) that displayed resistance to selected antibiotics also possessed potential human pathogenic characteristics such as adherence and translocation through human long epithelial cells as well as displaying phage resistance (n = 26). They might thus present a potential public health risk if frequently encountered through exposure to aerosols generated by the foam as well as direct contact through a wound. Preventative measures to control the growth of nocardiae in such environments such as the control of pollutants, might prevent potential infections that might be caused by these bacteria in humans as well as in marine animals.

Cluster of COVID-19 in Northern France: A Retrospective Closed Cohort Study

Background: The Oise department in France has been heavily affected by COVID-19 in early 2020. Methods: Between 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies. Findings: Of the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P <0.001). The proportion of infected individuals who had no symptoms during the study period was 17.0% (95% CI = 11.2 – 23.4). The proportion of donors with anti-SARS-CoV-2 antibodies in two nearby blood banks of the Oise department was 3.0% (95% CI = 1.1 - 6.4). Interpretation: The relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex. Trial Registration: This study was registered with ClinicalTrials.gov (NCT04325646). Funding Statement: OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-ViroImmuno” ANR-14-CE14-0015-01 and the Gilead HIV cure program. LG is supported by the French Ministry of Higher Education, Research and Innovation.ME lab is funded by Institut Pasteur, Labex IBEID (ANR-10-LABX-62-IBEID), Reacting, EU grant Recover, ANR Oh’ticks. HM received core grants from the G5 Institut Pasteur Program, the Milieu Interieur Program (ANR-10-LABX-69-01) and INSERM. C.P. is supported by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS). SVDW lab is funded by Institut Pasteur, CNRS, Universite de Paris, Sante publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Ethical approval by the Comite de Protection des Personnes Ile de France III. Informed consent was obtained from all participants.

Robotic Surgery in Pediatric Oncology: Lessons Learned from the First 100 Tumours. A Nationwide Experience

Background: The use of robotics has become commonplace in adult oncology but remains rare in paediatric oncologic surgery. We present the results of a large nationwide experience with robotic surgery in children with benign and malignant tumours. Methods: Prospective analysis (ClinicalTrials.gov NCT03274050) of robotic procedures performed between 2008 and 2019. Children received treatment according to the ongoing SIOP/SIOPEN protocols. Indications were approved by a certified tumour board. Findings: A total of 100 tumours were resected during 92 procedures in 87 children (56 girls). The median age at surgery was 7·4 years (3·5-12); 20% of children harboured germinal genetic alterations predisposing to cancer. Procedures were performed by laparoscopy for abdominal (71%) or pelvic tumours (10%) and by retroperitoneoscopy (5%) or thoracoscopy (14%). No intraoperative tumour rupture occurred during robotic-assisted dissection. Eight conversions (9%) to an open approach occurred. Neuroblastic tumour (n=29) was the main group (19 neuroblastomas, three ganglioneuroblastomas, seven ganglioneuromas). Renal tumour was the second largest group (n=24, including 20 Wilms’ tumours). The other 47 tumours were neuroendocrine (n=13), adrenal (n=11), pancreatic (n=3), germ-cell (n=7), thymic (n=4), inflammatory myofibroblastic (n=4) and five different rare tumours. Overall, 50 tumours were malignant, 2 were borderline and 48 were benign. The median hospital stay was 3 days (2-4). Five post-operative surgical complications occurred within the first 30 days in four patients. During a follow-up of 1 to 28 months, one child (Wilms’ tumour) presented pleural recurrence. One girl with Wilms’ tumour died of central nervous system metastasis. Interpretation: Robotic surgery for paediatric tumours is feasible and may be an option in highly selected cases. Indications should be discussed by tumour boards to avoid widespread and uncontrolled application of the approach. Children with genetic predisposition to cancer seem good candidates for the robotic approach. Trial Registration: ClinicalTrials.gov NCT03274050 Funding: The sponsor was Assistance Publique–Hopitaux de Paris (APHP, Clinical Research and Innovation Delegation) and this project was funded by a grant from Necker Hospital. Declaration of Interests: None to declare. Ethics Approval Statement: This prospective analysis received approval from institutional review boards and an independent ethics committee (Comite de Protection des Personnes, CPP Ile de France VII). The sponsor was Assistance Publique–Hopitaux de Paris (APHP, Clinical Research and Innovation Delegation).

Two Intravenous Injections of Ketamine at 24h-Interval for the Acute Treatment of Severe Suicidal Ideas: A Randomised Double-Blind Placebo-Controlled Superiority Trial

Background: Ketamine is suggested to have rapid-onset anti-suicidal benefits. This must be confirmed in a large sample, alongside a potential moderating effect of comorbid mental disorders. Methods: Double-blind superiority trial comparing ketamine (0•5mg/kg) to placebo, conducted in seven teaching hospitals in France (KETIS). Participants aged 18 and older with current suicidal ideation were electronically randomised and stratified by centre and main diagnosis: bipolar, depressive, or other (non-psychotic) disorders. Two 40-min intravenous injections were administered at baseline and after 24 hours in addition to usual treatment. The primary outcome was the rate of patients in full suicidal remission at Day 3, according to clinician-rated Scale for Suicidal Ideation total score < 3. Analyses were conducted on an intention-to-treat basis. Registered on ClinicalTrials.gov (NCT02299440)(trial closed). Findings: 156 participants were recruited between April 13, 2015 and March 12, 2019 and randomised to placebo (n=83) or ketamine (n=73). More patients reached full remission of suicidal ideas at Day 3 in the ketamine than placebo arm (63•0 vs. 31•6%). However, this effect differed according to diagnoses (treatment: p<0•001; interaction: p=0•02): bipolar (Odds Ratio (OR 95% confidence interval)=14•1 (3•0 – 92•2), p=0•0005), depressive (OR=1•3 (0•3 – 5•2), p=0•6), or other disorders (OR=3•7 (0•9 – 17•3, p=0•07)). Side effects were limited. No manic or psychotic symptom was observed. Moreover, a mediating effect of mental pain was found. At Week 6, the ketamine arm remained superior to placebo for full suicidal remission (69•5 vs. 56•3%). Interpretation: This study confirmed the rapid, safe and persistent benefits of ketamine for acute care in suicidal patients. However, comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain could explain ketamine’s anti-suicidal effects. Clinical Trial Registration Details: This study is listed on www.ClinicalTrials.gov (NCT02299440), and EudraCT: 2014-001324-30 (trial closed). Funding Information: The study was funded by a national public grant (PHRC-N 2013). Declaration of Interests: FJ has no declaration of interests for the last 5 years. PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Alcediag-Alcen, Angelini, GSK, Janssen, Lundbeck, Otsuka, SAGE and Servier. Wissam El-Hage reports personal fees from EISAI, Janssen, Lundbeck, Otsuka, UCB and Chugai. PC received speaker and consultation fees from Exeltis, Janssen and Pfizer. GV is part of a scientific board for Janssen. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, SOBI, Takeda. He has served as consultant and/or speaker for Astra Zeneca, Boehringer-Ingelheim, Pierre Fabre, Lilly, Lundbeck, MAPREG, Otsuka, Pileje, SANOFI, Servier, LVMH and received compensation, and he has received research support from Servier. Co-founder and stock shareholder: Regstem. PM has received compensation as consultant and member of a scientific advisory board for Janssen. LS declares fees for advisory board, travel support activities of consultant and lecturer in the last 5 years received from Janssen, Lundbeck and Otsuka. PML declares fees for Advisory board, travel support activities of consultant, lecturer and faculty member in the last 5 years received from Eisai, Janssen, Lundbeck, Otsuka, Sanofi, Teva. MA declares fees from Astra Zeneca and Lundbeck, and has been invited to congresses by Janssen-Cilag, Otsuka, Lundbeck, Servier and Astra Zeneca. CD and PF have no conflicts of interests to declare Ethics Approval Statement: Ethics approval was obtained on July 18, 2014 from the Research Ethics Board “Comite de Protection des Personnes (CPP) Sud Mediterranee III”.All patients gave their informed, written and signed consent before inclusion.

Social Inequalities and Dynamics of the COVID-19 Epidemic: Evidence from France

Background: Our main objective was to study the early social dynamics of the COVID-19 epidemic in France, taking into account gender, class, and ethnicity inequalities in living conditions.Methods: A random population-based survey was conducted in France in May 2020, during and post COVID-19 lockdown, in which 77,588 participants aged 18-64 were included in this study. We used multinomial regressions to identify changes in social position and exposure factors associated with symptoms of anosmia/ageusia during the first epidemic peak in late March and thereafter.Findings: In all, 2,045 (1.53% (95%CI 1.46%-1.61%)) participants reported anosmia/ageusia (1.13% during the epidemic peak and 0.40% after), with strong variations according to regions. Women and ethno-racial minorities remained at higher risk of anosmia/ageusia during and after the peak. Whereas senior executive professionals were more affected than lower social classes at the peak of the epidemic, this effect disappeared afterwards. Adjusting on key exposure factors substantially attenuated these associations, except for gender differences. While high density of the place of residence was associated with anosmia/ageusia during the peak, but no longer after, the opposite trend was observed for living in overcrowded housing. Having worked outside the home during lockdown was the most strongly associated exposure factor, and even more so after the peak.Interpretation: The shift in the social profile of the epidemic was related to a shift in exposure factors under the implementation of stringent collective prevention measures. Our results notably stress the importance of working outside the home, all the more so in essential occupations.Funding Statement: Inserm (Institut National de la Santé et de la Recherche Médicale).French Ministry for Research. Drees. Dr. Bajos has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. [856478])Declaration of Interests: None.Ethics Approval Statement: The survey was approved by the CNIL (French independent administrative authority responsible for data protection) on April 25th 2020 (ref: MLD/MFI/AR205138) and by the “Comité de protection des personnes” (French equivalent of the Research Ethics Committee) on April 24th. The survey also obtained an agreement from the “Comité du Label de la statistique publique”, proving its adequacy to statistical quality standards.

Human NLRP1 Is a Sensor of 3CL Proteases from Pathogenic Coronaviruses in Lung Epithelial Cells

Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly, cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also cleave and inactivate the pyroptosis executioner Gasdermin (GSDM)-D. Consequently, Caspase-3 and GSDM-E promote alternative cell pyroptosis, a process exacerbated in cells exhibiting imparied type I interferon production. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to Interferon alterations identify GSDM-E/Caspase-3 as biological markers of disease severity. Overall, our findings identify NLRP1 as a key sensor of SARS-CoV-2 infection in lung epithelia.Funding Information: This project has been funded on lab own funds from unrelated grants from the Fondation pour la Recherche Médicale (FRM) and ERC StG (INFLAME) to EM, from ERC StG (ANTIViR) to CG, by the French Ministry of Health with the participation of the Groupement Interrégional de Recherche Clinique et d’Innovation Sud-Ouest Outre-Mer (PHRCI 2020 IMMUNOMARK-COV) to G-M.B. The ASB3 structure is supported by LABEX, Investissement d’Avenir and foundation Bettencourt grants to ON. MP and RP were respectively funded by a CIFRE PhD fellowship and a research grant from Invivogen. SB is supported by a PhD fellowship from Mali ministry of education and from the FRM (FDT 12794). SALC is supported by a Vaincre La Mucoviscidose (VLM) PhD fellowship.Declaration of Interests: Authors declare no conflict of interest. Ethics Approval Statement: All donors had given written informed consent and the study was approved by the ethical review board “Comité de Protection des Personnes Est-III” (ID-RCB 2020-A01292-37).

Deficient Thyroid Hormone Transport to the Brain Leads to Impairments in Axonal Caliber and Oligodendroglial Differentiation

Background: Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to profound brain alterations, including myelination impairments, in humans. We aimed to further explore the pathophysiological mechanisms underlying the MCT8 deficiency-associated myelination impairments to unravel new biomarkers and therapeutic targets. Methods: We have performed brain histological analysis on an MCT8-deficient subject and histological, ultrastructural, and MRI analysis in the brain of a mouse model of the syndrome, lacking MCT8 and enzyme deiodinase type 2 (DIO2, Mct8/Dio2 KO). Findings: We have found that the MCT8-deficient subject presents severely reduced myelin lipid and protein staining and increased proportion of small-calibre myelinated axons in detriment of large-calibre ones. Mct8/Dio2 KO mice present myelination impairments and abnormal oligodendroglial development, both in proliferation and maturation. Interpretation: We conclude that the greater proportion of small-calibre axons and differentiation impairments in oligodendrocyte precursor cells arise as potential mechanisms underlying the permanent myelination defects in MCT8-deficiency. Moreover, we present the Mct8/Dio2 KO mouse model, and magnetic resonance imaging (MRI) as a non-invasive biomarker, as highly valuable tools for preclinical studies involving MCT8 deficiency. These findings contribute to the understanding of the pathological mechanisms in MCT8 deficiency and suggest new biomarkers and therapeutic targets to consider therapeutic options for the neurological defects of patients. Funding Statement: This study was supported by grants from the Spanish Plan Nacional de I+D+i (Grant No. SAF2017-86342-R), Consejo Superior de Investigaciones Cientificas (Grant No. 2020AEP044), the Sherman Foundation (Grant No. OTR02211) and the Asociacion Corriendo con el Corazon por Hugo (Grant No OTR06190). Declaration of Interests: The authors declare no competing financial interest exist. Ethics Approval Statement: Human studies: Tissue samples were collected and processed following the guidelines and approval by the ethics committee of our Institution (Consejo Superior de Investigaciones Cientificas, CSIC, permit number SAF2011-25608) and with written informed consent from the parents of all subjects, in agreement with the Declaration of Helsinki. The smallest possible number of samples was used to perform these studies and all personal data were treated anonymously. Animal studies: All experimental procedures involving animals were performed following the European Union Council guidelines (directive 2010/63/UE) and Spanish regulations (R.D. 53/2013) and were approved by the ethics committee Comite de Etica y Experimentacion Humana y Animal (CEEHA) at Consejo Superior de Investigaciones Cientificas (CSIC) and by the Comunidad Autonoma de Madrid Review Board (proex 162/17) for the use of animals for scientific purposes.

Neonatal Listeriosis Presentation and Outcome: A Prospective Study of 189 Cases

Background: Listeriosis is caused by the foodborne pathogen Listeria monocytogenes. It can present as a maternal-neonatal infection. We implemented the nationwide prospective cohort MONALISA and analyzed the features of neonatal listeriosis. Methods: We studied all neonates born alive from mothers with microbiologically-proven maternal-neonatal listeriosis enrolled from November 2009 to December 2017. We analyzed presentation, neonatal outcome at discharge and predictors of severe presentation and outcome. Findings: We studied 189 infants. 133/189 (70%) had abnormal clinical status at birth, including acute respiratory distress in 106/189 (56%). 132/189 (70%) infants developed early-onset listeriosis and 12/189 (6%) late onset listeriosis who all presented with acute meningitis. 17/189 (9%) had major adverse outcomes: 3% death (5/189), 6% (12/189) severe brain injury, 2% (3/189) severe bronchopulmonary dysplasia, 15/17 in infants born < 34 weeks of gestation (p < 0·0001 versus infants born ≥ 34 weeks of gestation). Maternal antimicrobial treatment ≥1 day before delivery was associated with a significant decrease of infants’ severity (resulting in significantly less inotropic drugs, fluid resuscitation, or mechanical ventilation requirement), OR 0·23 [95% confidence interval CI 0·09-0·51], p < 0·0001). Interpretation: Antenatal maternal antimicrobial treatment is associated with reduced neonatal listeriosis severity, justifying the prescription of preemptive maternal antimicrobial therapy when maternal-fetal listeriosis is suspected. Neonatal outcome is better than reported earlier, and its major determinant is gestational age at birth. Trial Registration: The study is registered at clinicaltrials.gov (NCT01520597). Funding Statement: Institut Pasteur, Inserm, French Public Health Agency, Programme Hospitalier de Recherche Clinique. Declaration of Interests: None to declare Ethics Approval Statement: All mothers provided written informed consent. In accordance with French legislation, the MONALISA Study received institutional review board approval by a local ethics committee (Comite de protection des personnes, Ile de France -3, Nov 6 2009).

A Monocyte/Dendritic Cell Molecular Signature of SARS-CoV-2 Related Multisystem Inflammatory Syndrome in Children (MIS-C) with Severe Myocarditis

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κ B activity, TNF-α signaling, associated with decreased gene expression of NF-κ B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.Funding: The study was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by the “URGENCE COVID-19” fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the “Investment for the Future” program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Intérieur”, grant ANR-10-LABX-69-01), the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL and “CoVarImm” to DD and JDS), and by the FASTFoundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single-Cell@Imagine is supported by the Paris Region and the “Investissements d’avenir” program through the 2019 ATF funding – Sésame Filières PIA (Grant N°3877871).CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its“Investments for the Future” program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Médicale (FRMN°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship.Conflict of Interest: DD, FRL, JT and MMM are listed as inventors on a patent application related to this technology (European Patent Application no. EP21305197, entitled “Methods of predicting multisystem inflammatory syndrome (MIS-C) with severe myocarditis in subjects suffering from a SARS-CoV-2 infection”).Ethical Approval: The study was approved by the Ethics Committee (Comité de Protection des Personnes Ouest IV, n° DC-2017-2987).

Clinical and Microbiological Assessments of COVID-19 in Healthcare Workers: A Prospective Longitudinal Study

Background: A comprehensive assessment of COVID-19 in healthcare workers (HCWs) including the investigation of viral shedding duration is critical.Methods: A longitudinal study including 319 HCWs was conducted. After SARS-CoV-2 screening with RT-PCR assay, other respiratory pathogens were tested with a multiplex molecular panel. For SARS-CoV-2 positive HCWs, the normalized viral load was determined weekly; viral culture and virus neutralization assay were also performed. For 190 HCWs tested negative for SARS-CoV-2, serological testing was performed one month after the inclusion.Findings: Of the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; two of them developed severe COVID-19. The proportion of smell and taste dysfunction was significantly higher in SARS-CoV-2 positive HCWs than in negative ones (38.8% vs 9.5% and 37.3% vs 10.7%, respectively, p 5.0 log 10 cp/ml (Ct value 37). More than 90% of samples with cultivable virus had a viral load > 4.5 log 10 cp/ml (Ct Interpretation: Our data suggest that the monitoring of normalized viral load (or its estimation through Ct values) can be useful for discontinuing isolation of HCWs and facilitating their safe return to work. HCWs presenting mild COVID-19 are unlikely infectious 10 days after symptom onset.Trial Registration: The clinical study registered on ClinicalTrial.gov (NCT04341142) has been fully detailed.Funding: Fondation des Hospices Civils de Lyon. bioMérieux provided diagnostic kits.Declaration of Interests: Several authors (KBP, FAF, GO, VC) are bioMérieux employees. AB has received a grant from bioMérieux and has served as consultant for bioMérieux. KBP, FAF, GO VC and AB were involved in data analysis, interpretation and wrote the article.Ethics Approval Statement: Written informed consent was obtained from all participants and approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37).

المعماري أنطونيو لاشياك (1856-1946) في سياق إعادة إحياء العمارة المملوكية

Antonio Lasciac was one of the most active of European architects working in Egypt in the late nineteenth and early twentieth century. His output was as eclectic as it was prolific, comprising buildings and decoration in neo‑Renaissance, neo‑Gothic and neo‑Mamluk styles. This paper focuses on of the origins of the motifs on his buildings decorated in Mamluk revival style, and particularly on his villa at Rafut, in Slovenia, beside the modern border of Gorizia in Italy. The paper first gives a background to the rise of the neo‑Mamluk style in Egypt before analyzing Lasciac’s contributions to it. In one of his early buildings, the neo‑Renaissance palace of Yūsuf Kamāl at Matariyya, a newly‑discovered neo‑Mamluk room is discussed. The detailed analysis of his villa at Rafut and later buildings show the unusual extent to which the decorative motifs he used were accurately based on earlier Mamluk designs, reflecting his long‑standing involvement as a board member of the Comite de conservation des monuments de l’art arabe.

The Need to Develop New Antimicrobial Molecules, as Revealed by in vitro Assessment of Drug Resistance in Staphylococcal Skin Infections Treated with Autologous Bacterial Vaccine

Staphylococcus spp. is a facultative pathogen, which can be found in the commensal microbiota of humans, most often in moist skinfolds and mucous membranes. This microorganism has the ability to cause various infections, in almost every organ of the body, with an increased frequency in the skin and soft tissues, being involved in pathologies like acne, folliculitis, furunculosis, hidradenitis suppurativa, cellulitis, abscesses, but also in secondary infections in diseases with an altered cutaneous barrier. The prolonged evolution of these diseases and severe outcome can be influenced by various factors, most importantly being the antimicrobial resistance. We have evaluated the antimicrobial susceptibility profiles, according to the Comite de l` Antibiogramme de la Societe Francaise de Microbiologie recommendations, for strains of Staphylococcus spp. isolated from acne or different types of skin and soft tissue infections in patients recommended to receive autologous bacterial vaccine. Most frequent identified species was Staphylococcus epidermidis, followed by Staphylococcus aureus. The antimicrobial resistance was higher for antibiotics usually used in the treatment of skin and soft tissue infections, with interesting differences of the resistance profile for the strains isolated from patients before receiving autologous bacterial vaccine compared with the ones from individuals already treated. Another important finding was represented by the differences in the resistance profile according to the age group of the patients. The results of this study underline the importance of antimicrobial resistance surveillance in finding new molecules and alternative therapies, the necessity of a personalized approach in medical acts and of a continuous connection between clinic and laboratory research.

Evidenciação dos ativos intangíveis pelas empresas de Tecnologia da Informação da B3

Este estudo teve como objetivo analisar o nível de evidenciação dos ativos intangíveis no setor de Tecnologia da Informação listadas na B3, durante o período de 2010 a 2017. Para isso, elaborou-se um checklist a partir dos critérios de divulgação exigidos pelo Comitê de Pronunciamentos Contábeis 04 (CPC, 2010). Analisaram-se as Demonstrações Contábeis das empresas do setor de Tecnologia da Informação listadas na Brasil, Bolsa, Balcão (B3), identificando os itens do cheklist a fim de mensurar o nível de evidenciação dessas empresas, com base nos itens atendidos ou não por elas. Os resultados demonstraram que a Empresa Senior Solution S.A. apresentou o maior nível de evidenciação. Porém, cabe ressaltar que nenhuma das empresas analisadas cumpriu totalmente com o que é determinado pelo CPC 04 (CPC, 2010). O item de divulgação menos observado pelas empresas foi a evidenciação da rubrica da demonstração do resultado em que qualquer amortização tenha sido incluída. O nível de evidenciação apresentado pelas empresas foi em média de 81,72%, considerando o total de itens ao longo do período analisado. Este estudo contribui ao apresentar aspectos da evidenciação dos ativos intangíveis que não têm sido atendidos pelas empresas, permitindo que estas atuem para melhorar qualitativamente a evidenciação desses ativos, a fim de obterem reações positivas do mercado.

Participación política de víctimas: sujetos de reparación colectiva en Colombia

El artículo expone una investigación de tipo narrativo desarrollada con el Comité de Coordinación de Sujetos Nacionales de Reparación Colectiva, el cual, conformado por diversas organizaciones sociales, en el marco del conflicto armado colombiano, ha posicionado el papel de las víctimas en el proceso de paz y en la reconstrucción del país a través del diálogo y la participación en escenarios políticos. La investigación involucró a Afromupaz, la redepaz, el ipc, la ctc y el colectivo de periodistas, y visibiliza las apuestas y logros de las iniciativas colectivas de las víctimas en el contexto de la Ley 1448.

Hospital Admissions for Acute Myocardial Infarction Before and After Lockdown According to Regional Prevalence of COVID-19 and Patient Profile

Aim: to evaluate the impact of a nationwide lockdown in France on acute myocardial infarction (AMI) admissions, by patient characteristics and regional prevalence of the pandemic. Methods and Results: We collected data from 21 centres participating in the on-going FRENCHIE registry (NCT04050956), which collects data from all patients admitted for STEMI or NSTEMI within 48 hours of symptom onset. We compared weekly admissions in the 4 weeks preceding and the 4 weeks following institution of the lockdown. We observed a brutal 30% decrease in AMI admissions (24% for STEMI and 36% for NSTEMI, P=0.14) following institution of the lockdown, with similar trends according to gender (30% decrease in both men and women), risk factors, and regional prevalence of COVID-19. The decrease was numerically greater in patients aged 80 years or more (44% vs 27%, P=0.10). Patient characteristics, including time to hospital admission in STEMI patients, did not differ between the 2 periods. In-hospital mortality was numerically higher following institution of the lockdown (5.2% vs 3.4%, P=0.12), with similar trends for STEMI and NSTEMI. Conclusion: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message in case of a second wave of the pandemic or future major epidemics.Funding Statement: The FRENCHIE registry is supported by Recherche Hospitalo-universitaire en santé (RHU) iVasc within the programme "Investissements d'avenir", and sponsored by Assistance Publique – Hôpitaux de Paris (Délégation à la Recherche Clinique et à l'Innovation).Declaration of Interests: YC reports research Grants to the Institution or Consulting/Lecture Fees from : Novartis , Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Coste reports having received fees from Amgen, AstraZeneca, Bayer and Servier, outside the submitted work G. Lemesle reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BristolMyers Squibb, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, and The Medicine Co, outside the submitted work. FS reports personal fees from Amgen, Astra Zeneca, Bayer, BMS, MSD, Pfizer, and Sanofi, outside the submitted work D. Angoulvant reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Sanofi, Amgen, Novartis, Novo-Nordisk, Servier and MSD, outside the submitted work C. Bouleti reports receiving consulting and lecture fees from Novartis and AstraZeneca, outside the submitted work. G. Cayla has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Goube reports receiving consulting and lecture fees from AMGEN, SANOFI, BMS, ABBOT, outside the submitted work. T. Lhermusier has received research grants/consultant fees/lectures fees from AstraZeneca, Boston scientifics and Abbott, outside the submitted work A. Saib reports lectures fees from Novartis, outside the submitted work JG Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, BoehringerIngelheim, Bristol-Myers Squibb/Pfizer, Sanofi, and Daiichi-Sankyo and grants from Bayer, BristolMyers Squibb/Pfizer and Biosensors, outside the submitted work. F. Boccara reports research grants from Amgen; lecture fees from Janssen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. And personal consultant or lecture fees from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Intercept, MSD, Novartis, Pfizer, Sanofi, and Servier, outside the submitted work. T. Simon reports grants from Astrazeneca, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi, and personal fees for board membership and/or consultancy and/or lectures from AstraZeneca, BMS, Sanofi, and Novartis, outside the submitted work. N. Danchin has received research grants, or speaking and consulting fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli-Lilly, Intercept, MSD, Novartis, Novo-Nordisk, Pfizer, Sanofi, Servier, outside the submitted work. The other authors have nothing to report.Ethics Approval Statement: FRENCHIE has been approved by the Comité de Protection des Personnes and by the French data regulatory authority (Commission Nationale de l'Informatique et des Libertés).

Clinical Outcomes of Patients with COVID-19 and Chronic Inflammatory and Autoimmune Rheumatic Diseases: A Multicentric Matched-Cohort Study

Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.

Análisis de la actividad laboral de los profesionales sanitarios en formación de la Región de Murcia ante la pandemia por COVID-19

El presente estudio pretende analizar, ante el estado de emergencia sanitaria española (BOE Orden SND/232/2020) decretado por la pandemia del nuevo coronavirus 2019-nCoV, la situación en la que se encuentran los profesionales en formación del Servicio Murciano de Salud (SMS). Para ello se ha realizado un estudio descriptivo llevado a cabo a través de la recogida de datos mediante formulario directo, canalizado a través de la red que conforma el Comité de Empresa, habiéndose obtenido respuesta por parte de al menos un residente de cada uno de los servicios que conforman el SMS y alcanzando un tamaño de muestra que permite la total representatividad del colectivo a estudio. Se trata de un estudio que destaca por la rapidez de reclutamiento de la muestra y la rapidez en su redacción, lo que sirve como una importante herramienta para condicionar futuras políticas y decisiones en el ámbito de los profesionales en formación. La falta de acceso a material de protección por más de la mitad de la población a estudio junto con dificultades para el acceso a información actualizada por parte de la administración, son algunos de los resultados obtenidos tras el análisis de las respuestas. En general, existe una mayoría de residentes que continúan con su labor asistencial, que mantienen el número de guardias mensuales, que piensa que recibe formación oficial adecuada y que se está realizando un plan de contingencia apropiado. The present study intends to analyze the situation of professionals in training in the Murcian Health Service (SMS) during the state of sanitary emergency in Spain (BOE Order SND/232/2020) due to the pandemic of the new coronavirus 2019-nCoV. To achieve this objective, a descriptive study has been carried out through the collection of data via direct form, channeled through the network that makes up the Comité de Empresa. A response from at least one resident of each of the services that make up the SMS has been obtained. This has allowed a sample size that represents a large amount of the group under study. This is a study that stands out for the rapid acquisition and analysis of the sample, which serves as an important tool to condition future policies and decisions in the field of professionals in training. The lack of access to protection material for more than half of the population under study, as well as difficulties in accessing updated information from the administration are some of the results obtained after analyzing the responses. Overall, there is a majority of residents that continue with their work assistance and which maintain the same number of 24-hour shifts. It is also a main opinion that there is an appropriate health training and contingency plan against COVID-19.