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1. Growth Hormone and Growth Retardation in Autoimmune Type-1 Diabetes. Insulin an Important Endocrine Growth Factor

Author

Kamran Mahmood Ahmed Aziz

Subjects
General Medicine
Abstract

Growth hormone (GH) secretory alterations and dysregulations with insulin-like growth factor-I (IGF-1) axis among type-1 diabetic children and adolescents is well established. In this poorly controlled abnormal metabolic state, GH hypersecretion is observed with decreased levels of Insulin-like Growth Factors (IGFs), IGF binding proteins-3 (IGFBP-3), and growth hormone binding protein (GHBP). These all factors results in decreased growth velocity and growth retardation in type-1 diabetic children and adolescents. Insulin is the most important metabolic regulator of this system. Absolute insulin deficiency, as observed in type-1 diabetics, is the primary cause of this dysregulation and alterations. Several published studies have shown that elevated HbA1c and poor glycaemic control are the main factors of this abnormal metabolic state. Conversely, studies have also demonstrated that good glycaemic control with basal bolus insulin regimens or insulin pump can improve diabetic state with restoration of normal growth. Hence this perspective review focuses on these important aspects of growth abnormalities in type-1 diabetic patients and concludes that health care policy makers should develop a close monitoring program and system with multi-disciplinary team approach to prevent further diabetes related growth complications.

Published
2023

4. Expression patterns of LncRNA-GAS5 and its target APOBEC3C gene through miR-103 in breast cancer patients

Author

Rozhgar A. Khailany, Sherwan Ahmed Aziz, Belan O. Kanabe, Mehmet Ozaslan, İbrahim Kiliç, and Mustafa S. Al-Attar

Subjects
APOBEC, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Breast Neoplasms, General Medicine, Biology, Prognosis, medicine.disease_cause, medicine.disease, Gene Expression Regulation, Neoplastic, MicroRNAs, Breast cancer, Cytidine Deaminase, microRNA, Gene expression, medicine, Cancer research, Humans, Female, RNA, Long Noncoding, GAS5, Carcinogenesis, Gene
Abstract

Early diagnosis of breast cancer can increase the survivability of the patients and the patient’s quality of life. There is growing evidence demonstrating the active role of LncRNA-GAS5 and miR-103 in cancer biology. APOBEC enzymes are important players in immunity and may contribute to carcinogenesis. Mutation and expression alteration in the APOBEC gene family was found to have a strong correlation with breast cancer risk. This study aimed to evaluate the expression level of lncRNA-GAS5 and its target APOBEC3C in women with breast cancer through expression evaluation of miR-103. Moreover, the interaction between lncRNA-GAS5 and miR-103 was studied. In the present study, forty paired tumor and normal samples classified based on breast cancer subtypes and clinical features of patients were analyzed using gene expression studies. Immunohistochemical analysis of the gene products was performed to classify tumors. The RNA samples were extracted from breast tissue. Real-time PCR was conducted for APOBEC3C and Lnc-RNA GAS5 expression. In addition, miR-103a miScript Primer Assay was utilized for the expression of miR-103-5p. It was revealed that the expression level of APOBEC3C and lncRNA-GAS5 were significantly down-regulated; however, the miRNA-103 expression level was significantly up-regulated. GAS5 expression was positively correlated with APOBEC3C expression and negatively correlated with miR-103 expression. In conclusion, we observed down-regulation of APOBEC3C and LncRNA-GAS5 and up-regulation of miRNA 103 in breast cancer patients. The expression of GAS5 may provide a new potential treatment target for breast cancer. To clarify the role of these molecules in the cellular signaling pathways, further studies are required.

Published
2021

5. Genetic basis of common variable immunodeficiency: from common to variable

Author

H. Elkabli, Hind Dehbi, Khaoula Mokhantar, Ahmed Aziz Bousfiha, M.M. Moudatir, A. Allaoui, Leila Jeddane, and Fatima Ailal

Subjects
business.industry, Genetic heterogeneity, Common variable immunodeficiency, High-Throughput Nucleotide Sequencing, Genomics, General Medicine, Disease, Computational biology, medicine.disease, Hypogammaglobulinemia, Clinical Practice, Common Variable Immunodeficiency, medicine, Humans, Genetic Predisposition to Disease, Personalized medicine, Epigenetics, Precision Medicine, business
Abstract

Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiencies. It is characterized by hypogammaglobulinaemia, increased susceptibility to infections and impaired vaccine responses. CVID has an important, clinical, immunological and genetic heterogeneity. A minority of patients present with monogenic forms in CVID, unlike other primary immunodeficiencies. With the development of new technologies in genetics, including next generation sequencing, the number of identified genes in CVID is increasing. Therefore, CVID is now considered as an umbrella disease, gathering distinct pathological entities. It is currently recognized that CVID is a complex polygenic rather than a monogenic syndrome. A multi-omic approach combining genomics, epigenetics and proteomics will shed light on CVID complex pathophysiology, which still enigmatic. This integrative approach will also offer more targeted therapies, and therefore a personalized medicine. This review aims to discuss current knowledge concerning the genetic and molecular bases of CVID as well as their application in clinical practice.

Published
2021

6. Successful use of venous graft from native liver with hepatocellular carcinoma during living donor liver transplantation with no impact on recurrence rate: A retrospective cohort study

Author

Hazem Mohamed Zakaria, Emad Hamdy Gad, Nahal Kamel Gaballa, Ahmed Nabil Sallam, Islam Ismail Ayoub, Mohamed Eltabbakh, Shimaa Saad Elkholy, Sameh Abokoura, Taha Yassein, Osama Hegazy, Hany Abdelmeguid Shoreem, Hossam Eldeen Mohamed Soliman, Amr Ahmed Aziz, and Mohammad Taha

Subjects
Surgery, General Medicine
Abstract

There are still debates regarding using portal vein (PV) from liver with hepatocellular carcinoma (HCC) for vascular reconstruction. This study aimed to assess the feasibility and patency of PV venous graft from an explanted liver with HCC for the reconstruction of the hepatic veins tributaries or PV in living donor liver transplantation (LDLT) and to see if it has any risk on recurrence of HCC.We conducted a retrospective study on 81 patients with HCC who underwent LDLT from April 2004 to July 2022.Venous graft from native liver PV was used for vascular reconstruction in 31 patients as follows; reconstruction of V5 in 7 patients, V8 in 4 patients, V6 in 3 patients, combined V5 and V8 in 4 patients, V6 with V5/V8 in 5 patients, and as Y shape venous graft for 2 PV reconstruction in 8 patients. The implantation of the new conduit PV graft after reconstruction of the anterior sector tributaries was direct to the IVC in 8 patients, and to the common orifice of the left and middle hepatic veins in 12 patients. The 1 month, 3 months, and 1-year overall patency of the venous graft was 93.5%, 90.3%, and 84%, respectively. Nine patients had recurrent HCC. In multivariate analysis, the independent risk factors for HCC recurrence were AFP400 ng/mL (HR = 1.47, 95% CI: 1.69-2.31, P = 0.01), moderate/poor differentiated tumor (HR = 3.06, 95% CI: 2.58-6.29, P = 0.02), and microvascular invasion (HR = 2.51, 95% CI: 1.05-1.93, P = 0.01). Using a PV venous graft had no risk factor for HCC recurrence (P = 0.9).The use of PV venous graft of native liver with HCC for venous reconstruction is a feasible and valuable option in LDLT with good patency rates and no risk of HCC recurrence.

Published
2022

7. Molecular Characterization of Methicillin Resistant and Extended Spectrum ?-Lactamase Staphylococcus aureus Isolated from Burn Patients

Author

Shawnm Ahmed Aziz

Subjects
Penicillin binding proteins, Teicoplanin, business.industry, medicine.drug_class, medicine.medical_treatment, Antibiotics, General Medicine, biochemical phenomena, metabolism, and nutrition, Glycopeptide antibiotic, medicine.disease_cause, Microbiology, Antibiotic resistance, Staphylococcus aureus, medicine, Beta-lactamase, Vancomycin, business, medicine.drug
Abstract

Antibiotic resistance has become a major world health challenge and has limited the ability of physician's treatment. Staphylococcus aureus the most notorious pathogens causes morbidity and mortality especially in burn patients. However, Staphylococcus aureus rapidly acquired resistance to multiple antibiotics. Vancomycin, a glycopeptide antibiotic remains a drug of choice for treatment of severe Methicillin Resistance S. aureus infections. This study aimed to detect the emergence of beta-lactam and glycopeptide resistance genes. 50 clinical specimens of S. aureus collected from burn patients in burn and plastic surgery units in Sulaimani-Iraq city. All specimens were confirmed to be positive for S. aureus. All the isolates were assessed for their susceptibility to different antibiotics depending on NCCL standards, followed by Extended Spectrum Beta Lactamase detection by double disk diffusion synergy test. The production of ?- lactamases was evaluated in the isolated strains by several routine methods and polymerase chain reaction. Among the isolates 94% were Methicillin resistance and 34.28% were Extended Spectrum Beta Lactamase producer. PCR based molecular technique was done for the bla genes related to ?- lactamase enzymes by the specific primers, as well as genes which related to reduced sensitivity to Vancomycin were detected. The results indicated that all isolated showed the PBP1, PBP2, PBP3, PBP4, trfA and trfB, graSR, vraS except the vraR gene and the prolonged therapy of Methicillin resistance infection with teicoplanin have been associated with progress of resistance and the rise of tecoplanin resistance may be a prologue to evolving Vancomycin resistance. In conclusion, beta-lactam over taking can rise Vancomycin- Intermediate S. aureus strains leading to appearance of Vancomycin resistance although the treatment of Vancomycin resistant infections is challenging.

Published
2020

8. Inhibition of PI3K/C/EBPβ axis in tolerogenic bone marrow-derived dendritic cells of NOD mice promotes Th17 differentiation and diabetes development

Author

Chantal Guindi, Farhan Ullah Khan, Alexandre Cloutier, Puregmaa Khongorzul, Ahmed Aziz Raki, Simon Gaudreau, Patrick P. McDonald, Denis Gris, and Abdelaziz Amrani

Subjects
Physiology (medical), Biochemistry (medical), Public Health, Environmental and Occupational Health, General Medicine
Abstract

Dendritic cells (DCs) are key regulators of the adaptive immune response. Tolerogenic dendritic cells play a crucial role in inducing and maintaining immune tolerance in autoimmune diseases such as type 1 diabetes in humans as well as in the NOD mouse model. We previously reported that bone marrow-derived DCs (BM.DCs) from NOD mice, generated with a low dose of GM-CSF (GM/DCs), induce Treg differentiation and are able to protect NOD mice from diabetes. We had also found that the p38 MAPK/C/EBPβ axis is involved in regulating the phenotype, as well as the production of IL-10 and IL-12p70, by tolerogenic GM/DCs. Here, we report that the inhibition of the PI3K signaling switched the cytokine profile of GM/DCs toward Th17-promoting cytokines without affecting their phenotype. PI3K inhibition abrogated the production of IL-10 by GM/DCs, whereas it enhanced their production of IL-23 and TGFβ. Inhibition of PI3K signaling in tolerogenic GM/DCs also induced naive CD4

Published
2022

9. WARM VERSUS COLD INTERMITTENT BLOOD CARDIOPLEGIA FOR MYOCARDIAL PROTECTION DURING ON-PUMP CORONARY ARTERY BYPASS GRAFTING

Author

Waleed Ismail Kamel, Ayman Mahmoud Amin Amar, Ahmed Hassouna, Ahmed Aziz, and Hosam Ahmed Mohamed Ahmed

Subjects
Mechanical ventilation, Inotrope, medicine.medical_specialty, Randomization, business.industry, Defibrillation, medicine.medical_treatment, General Medicine, 030204 cardiovascular system & hematology, law.invention, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, law, Anesthesia, Cardiopulmonary bypass, Medicine, business, Prospective cohort study, Artery
Abstract

Background: Obtaining an optimal surgical result depends on performing a technically proficient operation while protecting the heart from potential damage. Cardioplegia is an essential component in myocardial protection during aortic cross-clamping and cardiopulmonary bypass. The development of cardioplegia solutions is one of the major advances in cardiac surgery that allowed surgeons to extend the period of ischemic arrest to well over 3 hours to perform complex surgical procedures without adversely affecting myocardial functio).Aim of the work: We sought to compare between two specific modalities of myocardial protection using either intermittent ante-grade cold blood cardioplegia or warm blood cardioplegia.Patients and Methods: This prospective study included 200 successive adult patients who have undergone elective on-pump coronary artery bypass grafting (CABG) operations. Randomization was done immediately before the beginning of the operation so that group allocation was blinded to the patient. Participants were recruited between 14 January 2017 and 10 July 2019 at Mahalla Cardiac Center. All patients were thoroughly evaluated preoperatively, intraoperatively, and postoperatively.Results: There was no statistically significant difference between the two groups as regards bypass and cross clamp times. However, there was a statistically significant difference between the two groups as regards spontaneous defibrillation. There were no significant differences in both groups regarding the needed either inotropic support, or an IABP to achieve weaning. The total period of mechanical ventilation was statistically shorter in the warm group compared to the cold group.Conclusion: We found that there was no difference in the clinical effect of warm or cold blood cardioplegia despite the relative increase in postoperative serum cTnI in the warm cardioplegia group. Both strategies appear to allow a comparable and satisfactory method for myocardial protection during the period of cardiac arrest.

Published
2020

10. Potential effect of pharmaceutical care to improve outcomes in patients with chronic kidney disease-mineral bone disorder in Sulaimani dialysis centers

Author

Hawkar Qadir Baiz, Tavga Ahmed Aziz, and Dana Ahmed Sharif

Subjects
General Medicine
Abstract

Objective: the present study was aimed to evaluate the role of pharmaceutical services in improving the outcome of mineral bone disorder in patients with advanced chronic kidney disease. Methodology: One hundred and twenty patients with chronic kidney disease-mineral bone disorder (CKD-MBD) screened for eligibility, seventy-six patients enrolled in the study and randomly allocated into two groups: pharmaceutical care and usual care, both groups interviewed by the pharmacist using specific questionnaire for assessing the quality of life (QoL). All the drug related problems (DRPs) including drug-drug interactions (DDIs) were recorded by the pharmacist. Blood samples were collected and utilized for analyzing the levels of vitamin D, phosphorous, calcium, albumin and parathyroid hormone at baseline and three months after. The pharmaceutical care group received all the educations about their medications and how to minimize DRPs; improve the QoL. Additionally, the pharmaceutical intervention included correcting the biochemical parameters. Results: Pharmaceutical care significantly improved patients QoL and minimized DRPs and DDIs. It was also effective in improving the biochemical parameters. Conclusion: Pharmaceutical care has a positive impact on improving the outcome of patients with CKD-MBD through attenuating DRPs, improving the biochemical parameters and the QoL.

Published
2020

11. Research of anti-GAD and anti-IA2 autoantibodies by ELISA test in a series of Moroccan pediatric patients with diabetes type 1

Author

Zahra Aadam, Leila Jeddane, Ahmed Aziz Bousfiha, O Belhiba, H. Salih Alj, Rachid Saile, and F Jennane

Subjects
Male, medicine.medical_specialty, endocrine system diseases, Adolescent, autoantibodies, 030231 tropical medicine, anti-IA2, Enzyme-Linked Immunosorbent Assay, medicine.disease_cause, Asymptomatic, Gastroenterology, Autoimmunity, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antigen, Internal medicine, Diabetes mellitus, medicine, Humans, Child, Autoimmune disease, Glycated Hemoglobin, Type 1 diabetes, biology, business.industry, Glutamate Decarboxylase, autoimmunity, Autoantibody, General Medicine, Articles, medicine.disease, Diabetes Mellitus, Type 1, classification, Child, Preschool, biology.protein, anti-GAD, ELISA, Female, medicine.symptom, Antibody, Protein Tyrosine Phosphatases, business
Abstract

Introduction: Type I diabetes (T1D) is an autoimmune disease with a prediabetic, asymptomatic period characterized by the selective destruction of insulin-producing β cells. During the pre-clinical phase, various auto-antibodies are generated against several beta cell antigens such as anti glutamate acid decarboxylase (Anti-GAD), anti tyrosine phosphatase (Anti-IA2). Today, the coupled detection of Anti-IA2 with that of Anti-GAD proves its great importance in the diagnosis and prediction of type 1 diabetes. The combined positivity for both antibodies has a specificity and a positive predictive value of 100%. Objectives: In this work, we evaluate the diagnostic value of anti-GAD and anti-IA2 antibodies in a series based on 78 Moroccan subjects initially under 16, suspected T1D. Results and Discussion: Our series consists mainly of 74% of newly diagnosed patients for T1D and 26% of confirmed diagnostic patients, of whom 52% are females. The mean age of diagnosis is 7 ± 4 years, the mean of HbA1c at the time of diagnosis is 11.63 ± 2.16%, and the percentage of family history in our series is 69%. The proportion of positive results for anti-IA2 antibodies and anti-GAD antibodies are, respectively, 76.92% and 62.82%, and 52.56% of patients are positive for both auto-antibodies. This study confirms that anti-GAD and anti-IA2 auto-antibodies assays can detect patients early and the autoantibodies can persist several years after diagnosis of type 1 diabetes. Conclusion: This study confirmed the diagnosis and classification of T1D (type 1A) in 87.18% of patients, and we reported that the prevalence of anti-GAD and anti-IA2 is higher in girls than in boys. Keywords: Type 1 diabetes; autoimmunity; autoantibodies; anti-GAD; anti-IA2; ELISA; classification.

Published
2020

12. Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents

Author

Rui Yang, Rubén Martínez-Barricarte, Janet Markle, Franck Rapaport, Stuart G. Tangye, Mathieu Bourgey, David Langlais, Anne Puel, Aziz Belkadi, Masato Ogishi, Simon J. Pelham, Jean-Laurent Casanova, Bertrand Boisson, Cindy S. Ma, Vivien Béziat, Eman Abou Moussa, Jérémie Rosain, Laurent Abel, Tomi Lazarov, Serkan Belkaya, Fatima Ailal, Ibtihal Benhsaien, Coralie Briand, Alessandro Plebani, Romain Lévy, Frederic Geissmann, Caroline Deswarte, Andrea Guennoun, Luis R. Saraiva, Tanwir Habib, Mehdi Emam, Vassilios Lougaris, Philippe Gros, Yu Jerry Zhou, Ahmed Aziz Bousfiha, Geetha Rao, Kathryn Payne, Sylvain Breton, Ai Ing Lim, Kang Liu, Kunihiko Moriya, Danielle T. Avery, Bénédicte Neven, Nico Marr, Jacinta Bustamante, Mélanie Migaud, and James P. Di Santo

Subjects
Myeloid, Primary Immunodeficiency Diseases, Naive B cell, Adaptive Immunity, Biology, Lymphocyte Activation, Consanguinity, Immunity, medicine, Humans, Protein Isoforms, Myeloid Cells, Lymphocytes, Child, B cell, CD86, Host Microbial Interactions, Homozygote, Hematopoietic Stem Cell Transplantation, General Medicine, Acquired immune system, Immunity, Innate, Proto-Oncogene Proteins c-rel, medicine.anatomical_structure, Mutation, Immunology, Female, Genes, rel, REL, CD8, Research Article
Abstract

We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for a loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid and myeloid cells. The patient had low frequencies of NK, effector memory cells reexpressing CD45RA (Temra) CD8(+) T cells, memory CD4(+) T cells, including Th1 and Th1*, Tregs, and memory B cells, whereas the counts and proportions of other leukocyte subsets were normal. Functional deficits of myeloid cells included the abolition of IL-12 and IL-23 production by conventional DC1s (cDC1s) and monocytes, but not cDC2s. c-Rel was also required for induction of CD86 expression on, and thus antigen-presenting cell function of, cDCs. Functional deficits of lymphoid cells included reduced IL-2 production by naive T cells, correlating with low proliferation and survival rates and poor production of Th1, Th2, and Th17 cytokines by memory CD4(+) T cells. In naive CD4(+) T cells, c-Rel is dispensable for early IL2 induction but contributes to later phases of IL2 expression. The patient’s naive B cells displayed impaired MYC and BCL2L1 induction, compromising B cell survival and proliferation and preventing their differentiation into Ig-secreting plasmablasts. Inherited c-Rel deficiency disrupts the development and function of multiple myeloid and lymphoid cells, compromising innate and adaptive immunity to multiple infectious agents.

Published
2021

13. Sepsis chez l’enfant: protocole d’orientation rapide vers la réanimation pédiatrique

Author

Ouissal Aissaoui, Meryem El-bouz, Abdelaziz Chlilek, Ahmed Aziz Bousfiha, and Widad Gueddari

Subjects
medicine.medical_specialty, Pediatric sepsis, Sepsis, enfant, réanimation pédiatrique, business.industry, Public health, High mortality, Global health, medicine, Developing country, General Medicine, Intensive care medicine, business, Open access journal
Abstract

Pediatric sepsis is associated with high mortality rates. The mortality is even higher in low income countries, therefor, implementation of simplified protocols of recognition, evaluation and management is crucial. These protocols must be tailored to local resources. We suggest in this letter a practical protocol allowing rapid transfer of pediatric sepsis patients to the PICU.

Published
2021

14. Dendritic Cells and Their Immunotherapeutic Potential for Treating Type 1 Diabetes

Author

Farhan Ullah Khan, Puregmaa Khongorzul, Ahmed Aziz Raki, Ashwini Rajasekaran, Denis Gris, and Abdelaziz Amrani

Subjects
Organic Chemistry, Dendritic Cells, General Medicine, T-Lymphocytes, Regulatory, Catalysis, Computer Science Applications, Inorganic Chemistry, Diabetes Mellitus, Type 1, Immune Tolerance, Humans, Immunotherapy, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract

Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells through a process that is primarily mediated by T cells. Emerging evidence suggests that dendritic cells (DCs) play a crucial role in initiating and developing this debilitating disease. DCs are professional antigen-presenting cells with the ability to integrate signals arising from tissue infection or injury that present processed antigens from these sites to naïve T cells in secondary lymphoid organs, thereby triggering naïve T cells to differentiate and modulate adaptive immune responses. Recent advancements in our knowledge of the various subsets of DCs and their cellular structures and methods of orchestration over time have resulted in a better understanding of how the T cell response is shaped. DCs employ various arsenal to maintain their tolerance, including the induction of effector T cell deletion or unresponsiveness and the generation and expansion of regulatory T cell populations. Therapies that suppress the immunogenic effects of dendritic cells by blocking T cell costimulatory pathways and proinflammatory cytokine production are currently being sought. Moreover, new strategies are being developed that can regulate DC differentiation and development and harness the tolerogenic capacity of these cells. Here, in this report, we focus on recent advances in the field of DC immunology and evaluate the prospects of DC-based therapeutic strategies to treat T1D.

Published
2022

16. Elucidating the Role of Ezh2 in Tolerogenic Function of NOD Bone Marrow-Derived Dendritic Cells Expressing Constitutively Active Stat5b

Author

Abdelaziz Amrani, Farhan Ullah Khan, Ahmed Aziz Raki, Gilles Dupuis, Echarki Zerif, Véronique Lullier, and Denis Gris

Subjects
Male, type 1 diabetes, Autoimmunity, Nod, T-Lymphocytes, Regulatory, lcsh:Chemistry, Mice, Bone Marrow, Mice, Inbred NOD, STAT5 Transcription Factor, lcsh:QH301-705.5, Spectroscopy, NOD mice, biology, Chemistry, histone methyltransferase, food and beverages, Cell Differentiation, General Medicine, nonobese diabetic mice, Adoptive Transfer, Computer Science Applications, Cell biology, medicine.anatomical_structure, Interferon Regulatory Factors, hormones, hormone substitutes, and hormone antagonists, animal structures, T cell, CD11c, Mice, Transgenic, Article, Catalysis, Inorganic Chemistry, Immune Tolerance, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Physical and Theoretical Chemistry, Interferon Regulatory Factor 4 and 8, Molecular Biology, CD86, MHC class II, Organic Chemistry, Stat5b transcription factor, tolerogenic dendritic cells, Granulocyte-Macrophage Colony-Stimulating Factor, Mesenchymal Stem Cells, Dendritic Cells, CD11c Antigen, Diabetes Mellitus, Type 1, lcsh:Biology (General), lcsh:QD1-999, biology.protein, IRF8, CD80
Abstract

Tolerogenic dendritic cells (toDCs) are crucial to controlling the development of autoreactive T cell responses and the prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active (CA) form of Stat5b under the control of a CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function are not fully understood. Here, we used bone marrow-derived DCs (BMDCs) from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDCs) and found that Stat5b-CA.BMDCs displayed high levels of MHC class II, CD80, CD86, PD-L1, and PD-L2 and produced elevated amounts of TGF&beta, but low amounts of TNF&alpha, and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 and Stat5b-CA bound gamma-interferon activated site (GAS) sequences in the Irf8 enhancer IRF8 transcription, whereas Stat5b but not Ezh2 bound GAS sequences in the Irf4 promoter to enhance IRF4 transcription. Injection of Stat5b-CA.BMDCs into prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DC function.

Published
2020

17. Clinical outcomes of lithium disilicate glass-ceramic crowns fabricated with CAD/CAM technology: A systematic review

Author

Omar El-Mowafy, Saira Paredes, and Ahmed Aziz

Subjects
Ceramics, medicine.medical_treatment, MEDLINE, Dentistry, 02 engineering and technology, Cochrane Library, Esthetics, Dental, 01 natural sciences, Dental porcelain, 0103 physical sciences, Medicine, Humans, General Dentistry, Survival rate, 010302 applied physics, Crowns, business.industry, General Medicine, 021001 nanoscience & nanotechnology, Dental Porcelain, Clinical trial, Systematic review, Data extraction, Dental Prosthesis Design, Computer-Aided Design, 0210 nano-technology, business, Prosthodontics
Abstract

The use of ceramic materials and the computer-aided design/computer-aided manufacturing (CAD/CAM) technology for the fabrication of complete-coverage restorations has significantly increased in the last decade. The aim of this study was to evaluate the survival rate of anterior and posterior monolithic and bilayered lithium disilicate glass-ceramic (LDGC) CAD/CAM crowns, and to identify the types of complications associated with the main clinical outcomes reported in clinical trials. MEDLINE/PubMed, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched by 2 independent reviewers for clinical studies published between 2006 and 2019, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The electronic search was supplemented by a hand search. Quality assessment for the included studies was performed. Qualitative and quantitative data was extracted from each study. Out of 219 studies, 6 studies that evaluated LDGC CAD/CAM crowns were identified and used for data extraction. The included studies had 154 participants, who received 204 crowns. The shortto medium-term survival and success rates were high. Biological complications occurred more frequently than technical complications. No esthetic complications were reported. This review indicated that the medium-term survival rate of LDGC CAD/CAM crowns was high. Further multicenter studies with longer follow-ups and larger sample sizes are needed in order to augment the data already in existence.

Published
2020

18. Genetic biomarkers: Potential roles in cancer diagnosis

Author

Suhel Mawlood Najjar, Mehmet Ozaslan, Rozhgar A. Khailany, Muhammad Safdar, and Sherwan Ahmed Aziz

Subjects
Genetic Markers, medicine.medical_specialty, business.industry, Disease progression, Cancer, General Medicine, Bioinformatics, medicine.disease, Epigenesis, Genetic, Molecular genetics, Neoplasms, Epidemiology, medicine, Biomarkers, Tumor, Biomarker (medicine), Humans, Epigenetics, RNA, Neoplasm, Differential diagnosis, Risk assessment, business
Abstract

Biomarkers are indicators of pathogenic processes, typical biological processes, or pharmacological reactions to a therapy. It has several potential usages in cancer; differential diagnosis, prognosis, risk assessment, therapeutic response, and monitoring of disease progression. Recently, advances in oncomarkers raised significant opportunities for enhancing management of cancer. Chromosomal aberration, molecular impairment and epigenetic alteration might be applied to diagnose and prognose cancer and its epidemiology. Some oncomarkers are specific and highly sensitive for detection. An oncomarker might be used to see how the body reacts to an intervention or a situation. The present study represents a short review about various genetic oncomarkers with diagnostic and prognostic values.

Published
2020

19. Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

Author

Zobaida Alsum, Soraya Boucherit, Lluis Quintana-Murci, Peng Zhang, Luigi D. Notarangelo, Joseph A. Church, Daxing Gao, Rabih Halwani, Lazaro Lorenzo, Thomas M. Carlile, Maria F. Rojas-Duran, Ahmed Aziz Bousfiha, Yuval Itan, Laurent Abel, Flore Rozenberg, Fabien G. Lafaille, Wendy V. Gilbert, Jean-Laurent Casanova, Vimel Rattina, Marc Tessier-Lavigne, Lorenz Studer, Trine H. Mogensen, Bastian Zimmer, Benoit Henry, Søren R. Paludan, Shen-Ying Zhang, Franck Rapaport, Gregory A. Smith, Saleh Al-Muhsen, Michael J. Ciancanelli, Gaspard Kerner, Jessica L. McAlpine, Kerry Dobbs, Madalina E. Carter-Timofte, Laura Marques, Oliver Harschnitz, Osefame Ewaleifoh, Mary Hasek, Dominik Paquet, Marc Tardieu, Naima Amenzoui, Yoon Seung Lee, Dylan Kwart, Rockefeller University [New York], Memorial Sloane Kettering Cancer Center [New York], Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Northwestern University Feinberg School of Medicine, Aarhus University Hospital, National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Sharjah, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ibn Rochd University Hospital of Casablanca, University Hassan II of Casablanca, Morocco., King Saud University [Riyadh] (KSU), Centro Hospitalar do Porto, University of Southern California (USC), Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Stanford University, This work was funded in part by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Clinical and Translational Science Award program (grant nos. UL1TR000043 and UL1TR001866), NIH grants (nos. R01AI088364 to J.L.C. and S.Y.Z., R01NS072381 to J.-L.C. and S.-Y.Z. and R01GM101316 to W.G.), a grant from the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (no. ANR-10-LABX-62-IBEID to L.A.) and the French National Research Agency (ANR) under the ‘Investments for the future’ program (no. ANR-10-IAHU-01 to L.A.), the ANR grant IEIHSEER (no. ANR-14-CE14-0008-01 to S.-Y.Z.), the Lundbeck Foundation (grant no. R268-2016-3927 to S.R.P.), the Rockefeller University, INSERM, Paris Descartes University and the St Giles Foundation., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0008,IEIHSEER,L'encéphalite Herpétique de l'enfant résulte de déficits héréditaires d'immunité contre l'HSV-1: une exception ou une règle?(2014), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Hôpital Cochin [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Southern California [Los Angeles, CA, USA], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Central Nervous System, Male, 0301 basic medicine, Intrinsic immunity, viruses, Central nervous system, Herpesvirus 1, Human, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, RNA, Small Nucleolar, Genetic Predisposition to Disease, Small nucleolar RNA, Neurons, Immunity, Infant, RNA, General Medicine, Middle Aged, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, 030220 oncology & carcinogenesis, Forebrain, Metagenome, Female, Encephalitis, Herpes Simplex, Small nuclear RNA, medicine.drug
Abstract

International audience; Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31 deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31 thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism.

Published
2019

20. Efficacy and safety of Ginkgo biloba extract as an “add-on” treatment to metformin for patients with metabolic syndrome: a pilot clinical study

Author

Tavga Ahmed Aziz, Saad Abdulrahman Hussain, Taha Othman Mahwi, and Zheen Aorahman Ahmed

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Placebo, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Chemical Health and Safety, medicine.diagnostic_test, business.industry, Insulin, General Medicine, medicine.disease, Metformin, 030104 developmental biology, chemistry, 030221 ophthalmology & optometry, Glycated hemoglobin, Metabolic syndrome, Lipid profile, business, Safety Research, medicine.drug
Abstract

Background and aim Ginkgo biloba (GKB) extract has shown to be beneficial in experimental models of metabolic and inflammatory disorders such as diabetes and metabolic syndrome (MTS). The objective of this pilot clinical study was to evaluate the effects of GKB extract as an "add-on" treatment with metformin (Met) in MTS patients. Patients and methods We performed a randomized, placebo-controlled, double-blinded clinical study in subjects with MTS. Forty patients completed the 90-day clinical trial and were randomly allocated to administer either GKB extract (120 mg capsule/day) or placebo (120 mg starch/day) as an add-on treatment with their currently used doses of Met for 90 days. During the study, body mass index (BMI), waist circumference (WC), serum leptin, glycated hemoglobin (HbA1c), fasting serum glucose (FSG), insulin, insulin resistance (IR), visceral adiposity index (VAI), lipid profile, and the inflammatory markers high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were evaluated. Results GKB extract significantly decreases HbA1c, FSG and insulin levels, IR, BMI, WC, VAI, serum leptin, and the inflammatory markers compared to baseline values. Simultaneously, GKB did not negatively affect the functions of the liver, kidney, and hematopoietic system. Conclusion The use of GKB extract as an adjuvant with Met was effective in improving the outcome of patients with MTS.

Published
2018

21. Patient Preference for the Boarding at Emergency Department of Aseer Central Hospital when Emergency is Working with Its Maximum Capacity and Inpatient Admission is Full

Author

Hassan Abdulrahman Ogran, Kamran Mahmood Ahmed Aziz, Abdulrahim Mushabbab Hamhom, Amal Ali Alahmari, Ali Mousa Alahmari, and Osamah Mohammed Alqahtani

Subjects
Arabic, business.industry, language, medicine, General Medicine, Overcrowding, Emergency department, Medical emergency, medicine.disease, business, Patient preference, language.human_language, Cardiovascular mortality
Abstract

Overcrowding in Emergency Department usually results in serious consequences such as delay in facilities, medical errors and medical complications as well. This occurs because delay in transfer of the patients from ED to inpatient departments. We conducted this study to know patients’ and their attendants preferences to stay in ED or to be shifted to in-patient units. Data was collected via Arabic translated questioner. A total of 316 applicants included in the study (after inclusion / exclusion criteria), 144 patients with 157 patient attendants. 75 (52.1%) were male, while 69 (47.9%) were females. The preferred area for boarding was ED curtained space for 77.8% of patients and 79% of patient watcher as compared to 11.8% patients and 15.3% attendants who accepted the admission to inpatient hallway (p- value 0.253). Regarding the comparison of boarding time (8 hours and 24 hours), 55.5% of patients preferred in ED with 8 hours scenario versus 29.9% who preferred inpatient hallway (p=0.0897). When 24 hours scenario was compared, it was found that 59% patients preferred ED while 49.7% preferred inpatient hallway (p= 0.252). Current study proves that collectively patients prefer to stay in ED (either curtained space or hallway); this is because the patients received quick facilities and attention from the staff. However, with 24 hours scenario, more patients now preferred to stay in in-patient hallway; this is because of delay in transfer of the patients from ED, and delay or lack in facilities which usually occur during overcrowding. We concluded that patient and their preferences differ in different settings. However, overcrowding in ED should be dealt seriously with transfer of patients to in-patient departments / wards as soon as possible to avoid medical errors and complications.

Published
2018

22. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI):a single-blind randomised controlled trial

Author

Derek J Hausenloy, Rajesh K Kharbanda, Ulla Kristine Møller, Manish Ramlall, Jens Aarøe, Robert Butler, Heerajnarain Bulluck, Tim Clayton, Ali Dana, Matthew Dodd, Thomas Engstrom, Richard Evans, Jens Flensted Lassen, Erika Frischknecht Christensen, José Manuel Garcia-Ruiz, Diana A Gorog, Jakob Hjort, Richard F Houghton, Borja Ibanez, Rosemary Knight, Freddy K Lippert, Jacob T Lønborg, Michael Maeng, Dejan Milasinovic, Ranjit More, Jennifer M Nicholas, Lisette Okkels Jensen, Alexander Perkins, Nebojsa Radovanovic, Roby D Rakhit, Jan Ravkilde, Alisdair D Ryding, Michael R Schmidt, Ingunn Skogstad Riddervold, Henrik Toft Sørensen, Goran Stankovic, Madhusudhan Varma, Ian Webb, Christian Juhl Terkelsen, John P Greenwood, Derek M Yellon, Hans Erik Bøtker, Anders Junker, Anne Kaltoft, Morten Madsen, Evald Høj Christiansen, Lars Jakobsen, Steen Carstensen, Steen Dalby Kristensen, Troels Thim, Karin Møller Pedersen, Mette Tidemand Korsgaard, Allan Iversen, Erik Jørgensen, Francis Joshi, Frants Pedersen, Hans Henrik Tilsted, Karam Alzuhairi, Kari Saunamäki, Lene Holmvang, Ole Ahlehof, Rikke Sørensen, Steffen Helqvist, Bettina Løjmand Mark, Anton Boel Villadsen, Bent Raungaard, Leif Thuesen, Martin Kirk Christiansen, Philip Freeman, Svend Eggert Jensen, Charlotte Schmidt Skov, Ahmed Aziz, Henrik Steen Hansen, Julia Ellert, Karsten Veien, Knud Erik Pedersen, Knud Nørregård Hansen, Ole Ahlehoff, Helle Cappelen, Daniel Wittrock, Poul Anders Hansen, Jens Peter Ankersen, Kim Witting Hedegaard, John Kempel, Henning Kaus, Dennis Erntgaard, Danny Mejsner Pedersen, Matthias Giebner, Troels Martin Hansen Hansen, Mina Radosavljevic-Radovanovic, Maja Prodanovic, Lidija Savic, Marijana Pejic, Dragan Matic, Ana Uscumlic, Ida Subotic, Ratko Lasica, Vladan Vukcevic, Alfonso Suárez, Beatriz Samaniego, César Morís, Eduardo Segovia, Ernesto Hernández, Iñigo Lozano, Isaac Pascual, Jose M. Vegas-Valle, José Rozado, Juan Rondán, Pablo Avanzas, Raquel del Valle, Remigio Padrón, Alfonso García-Castro, Amalia Arango, Ana B. Medina-Cameán, Ana I. Fente, Ana Muriel-Velasco, Ángeles Pomar-Amillo, César L. Roza, César M. Martínez-Fernández, Covadonga Buelga-Díaz, David Fernández-Gonzalo, Elena Fernández, Eloy Díaz-González, Eugenio Martinez-González, Fernando Iglesias-Llaca, Fernando M. Viribay, Francisco J. Fernández-Mallo, Francisco J. Hermosa, Ginés Martínez-Bastida, Javier Goitia-Martín, José L. Vega-Fernández, Jose M. Tresguerres, Juan A. Rodil-Díaz, Lara Villar-Fernández, Lucía Alberdi, Luis Abella-Ovalle, Manuel de la Roz, Marcos Fernández-Carral Fernández-Carral, María C. Naves, María C. Peláez, María D. Fuentes, María García-Alonso, María J. Villanueva, María S. Vinagrero, María Vázquez-Suárez, Marta Martínez-Valle, Marta Nonide, Mónica Pozo-López, Pablo Bernardo-Alba, Pablo Galván-Núñez, Polácido J. Martínez-Pérez, Rafael Castro, Raquel Suárez-Coto, Raquel Suárez-Noriega, Rocío Guinea, Rosa B. Quintana, Sara de Cima, Segundo A. Hedrera, Sonia I. Laca, Susana Llorente-Álvarez, Susana Pascual, Teodorna Cimas, Anthony Mathur, Eleanor McFarlane-Henry, Gerry Leonard, Jessry Veerapen, Mark Westwood, Martina Colicchia, Mary Prossora, Mervyn Andiapen, Saidi Mohiddin, Valentina Lenzi, Jun Chong, Rohin Francis, Amy Pine, Caroline Jamieson-Leadbitter, Debbie Neal, J. Din, Jane McLeod, Josh Roberts, Karin Polokova, Kristel Longman, Lucy Penney, Nicki Lakeman, Nicki Wells, Oliver Hopper, Paul Coward, Peter O'Kane, Ruth Harkins, Samantha Guyatt, Sarah Kennard, Sarah Orr, Stephanie Horler, Steve Morris, Tom Walvin, Tom Snow, Michael Cunnington, Amanda Burd, Anne Gowing, Arvindra Krishnamurthy, Charlotte Harland, Derek Norfolk, Donna Johnstone, Hannah Newman, Helen Reed, James O'Neill, John Greenwood, Josephine Cuxton, Julie Corrigan, Kathryn Somers, Michelle Anderson, Natalie Burtonwood, Petra Bijsterveld, Richard Brogan, Tony Ryan, Vivek Kodoth, Arif Khan, Deepti Sebastian, Diana Gorog, Georgina Boyle, Lucy Shepherd, Mahmood Hamid, Mohamed Farag, Nicholas Spinthakis, Paulina Waitrak, Phillipa De Sousa, Rishma Bhatti, Victoria Oliver, Siobhan Walshe, Toral Odedra, Ying Gue, Rahim Kanji, Alisdair Ryding, Amanda Ratcliffe, Angela Merrick, Carol Horwood, Charlotte Sarti, Clint Maart, Donna Moore, Francesca Dockerty, Karen Baucutt, Louise Pitcher, Mary Ilsley, Millie Clarke, Rachel Germon, Sara Gomes, Thomas Clare, Sunil Nair, Jocasta Staines, Susan Nicholson, Oliver Watkinson, Ian Gallagher, Faye Nelthorpe, Janine Musselwhite, Konrad Grosser, Leah Stimson, Michelle Eaton, Richard Heppell, Sharon Turney, Victoria Horner, Natasha Schumacher, Angela Moon, Paula Mota, Joshua O'Donnell, Abeesh Sadasiva Panicker, Anntoniette Musa, Luke Tapp, Suresh Krishnamoorthy, Valerie Ansell, Danish Ali, Samantha Hyndman, Prithwish Banerjee, Martin Been, Ailie Mackenzie, Andrew McGregor, David Hildick-Smith, Felicity Champney, Fiona Ingoldby, Kirstie Keate, Lorraine Bennett, Nicola Skipper, Sally Gregory, Scott Harfield, Alexandra Mudd, Christopher Wragg, David Barmby, Ever Grech, Ian Hall, Janet Middle, Joann Barker, Joyce Fofie, Julian Gunn, Kay Housley, Laura Cockayne, Louise Weatherlley, Nana Theodorou, Nigel Wheeldon, Pene Fati, Robert F. Storey, James Richardson, Javid Iqbal, Zul Adam, Sarah Brett, Michael Agyemang, Cecilia Tawiah, Kai Hogrefe, Prashanth Raju, Christine Braybrook, Jay Gracey, Molly Waldron, Rachael Holloway, Senem Burunsuzoglu, Sian Sidgwick, Simon Hetherington, Charmaine Beirnes, Olga Fernandez, Nicoleta Lazar, Abigail Knighton, Amrit Rai, Amy Hoare, Jonathan Breeze, Katherine Martin, Michelle Andrews, Sheetal Patale, Amy Bennett, Andrew Smallwood, Elizabeth Radford, James Cotton, Joe Martins, Lauren Wallace, Sarah Milgate, Shahzad Munir, Stella Metherell, Victoria Cottam, Ian Massey, Jane Copestick, Jane Delaney, Jill Wain, Kully Sandhu, Lisa Emery, Charlotte Hall, Chiara Bucciarelli-Ducci, Rissa Besana, Jodie Hussein, Sheila Bell, Abby Gill, Emily Bales, Gary Polwarth, Clare East, Ian Smith, Joana Oliveira, Saji Victor, Sarah Woods, Stephen Hoole, Angelo Ramos, Annaliza Sevillano, Anne Nicholson, Ashley Solieri, Emily Redman, Jean Byrne, Joan Joyce, Joanne Riches, John Davies, Kezia Allen, Louie Saclot, Madelaine Ocampo, Mark Vertue, Natasha Christmas, Raiji Koothoor, Reto Gamma, Wilson Alvares, Stacey Pepper, Barbara Kobson, Christy Reeve, Iqbal Malik, Emma Chester, Heidi Saunders, Idah Mojela, Joanna Smee, Justin Davies, Nina Davies, Piers Clifford, Priyanthi Dias, Ramandeep Kaur, Silvia Moreira, Yousif Ahmad, Lucy Tomlinson, Clare Pengelley, Amanda Bidle, Sharon Spence, Rasha Al-Lamee, Urmila Phuyal, Hakam Abbass, Tuhina Bose, Rebecca Elliott, Aboo Foundun, Alan Chung, Beth Freestone, Dr Kaeng Lee, Dr Mohamed Elshiekh, George Pulikal, Gurbir Bhatre, James Douglas, Lee Kaeng, Mike Pitt, Richard Watkins, Simrat Gill, Amy Hartley, Andrew Lucking, Berni Moreby, Damaris Darby, Ellie Corps, Georgina Parsons, Gianluigi De Mance, Gregor Fahrai, Jenny Turner, Jeremy Langrish, Lisa Gaughran, Mathias Wolyrum, Mohammed Azkhalil, Rachel Bates, Rachel Given, Rajesh Kharbanda, Rebecca Douthwaite, Steph Lloyd, Stephen Neubauer, Deborah Barker, Anne Suttling, Charlotte Turner, Clare Smith, Colin Longbottom, David Ross, Denise Cunliffe, Emily Cox, Helena Whitehead, Karen Hudson, Leslie Jones, Martin Drew, Nicholas Chant, Peter Haworth, Robert Capel, Rosalynn Austin, Serena Howe, Trevor Smith, Alex Hobson, Philip Strike, Huw Griffiths, Brijesh Anantharam, Pearse Jack, Emma Thornton, Adrian Hodgson, Alan Jennison, Anna McSkeane, Bethany Smith, Caroline Shaw, Chris Leathers, Elissa Armstrong, Gayle Carruthers, Holly Simpson, Jan Smith, Jeremy Hodierne, Julie Kelly, Justin Barclay, Kerry Scott, Lisa Gregson, Louise Buchanan, Louise McCormick, Nicci Kelsall, Rachel Mcarthy, Rebecca Taylor, Rebecca Thompson, Rhidian Shelton, Roger Moore, Sharon Tomlinson, Sunil Thambi, Theresa Cooper, Trevor Oakes, Zakhira Deen, Chris Relph, Scott prentice, Lorna Hall, Angela Dillon, Deborah Meadows, Emma Frank, Helene Markham-Jones, Isobel Thomas, Joanne Gale, Joanne Denman, John O'Connor, Julia Hindle, Karen Jackson-Lawrence, Karen Warner, Kelvin Lee, Robert Upton, Ruth Elston, Sandra Lee, Vinod Venugopal, Amanda Finch, Catherine Fleming, Charlene Whiteside, Chris Pemberton, Conor Wilkinson, Deepa Sebastian, Ella Riedel, Gaia Giuffrida, Gillian Burnett, Helen Spickett, James Glen, Janette Brown, Lauren Thornborough, Lauren Pedley, Maureen Morgan, Natalia Waddington, Oliver Brennan, Rebecca Brady, Stephen Preston, Chris Loder, Ionela Vlad, Julia Laurence, Angelique Smit, Kirsty Dimond, Michelle Hayes, Loveth Paddy, Jacolene Crause, Nadifa Amed, Priya Kaur-Babooa, Roby Rakhit, Tushar Kotecha, Hossam Fayed, Antonis Pavlidis, Bernard Prendergast, Brian Clapp, Divaka Perara, Emma Atkinson, Howard Ellis, Karen Wilson, Kirsty Gibson, Megan Smith, Muhammed Zeeshan Khawaja, Ruth Sanchez-Vidal, Simon Redwood, Sophie Jones, Aoife Tipping, Anu Oommen, Cara Hendry, DR Fazin Fath-Orboubadi, Hannah Phillips, Laurel Kolakaluri, Martin Sherwood, Sarah Mackie, Shilpa Aleti, Thabitha Charles, Liby Roy, Rob Henderson, Rod Stables, Michael Marber, Alan Berry, Andrew Redington, Kristian Thygesen, Henning Rud Andersen, Colin Berry, Andrew Copas, Tom Meade, Henning Kelbæk, Hector Bueno, Paul von Weitzel-Mudersbach, Grethe Andersen, Andrew Ludman, Nick Cruden, Dragan Topic, Zlatko Mehmedbegovic, Jesus Maria de la Hera Galarza, Steven Robertson, Laura Van Dyck, Rebecca Chu, Josenir Astarci, Zahra Jamal, Daniel Hetherington, Lucy Collier, British Heart Foundation, University College London Hospitals NHS Foundation Trust, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden, National Institute for Health Research (Reino Unido), Singapore Ministry of Health, Ministry of Education (Singapur), and Unión Europea. European Cooperation in Science and Technology (COST)

Subjects
Male, Death, Sudden, Cardiac/prevention & control, medicine.medical_treatment, Myocardial Infarction, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Medicine, ST-SEGMENT ELEVATION, Single-Blind Method, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Prospective cohort study, Heart Failure/etiology, 11 Medical and Health Sciences, Myocardial Infarction/complications, General Medicine, Middle Aged, RC666, Combined Modality Therapy, LIMB, 3. Good health, Intention to Treat Analysis, Hospitalization, Treatment Outcome, Ischemic Preconditioning, Myocardial, Female, Life Sciences & Biomedicine, Ischemic Preconditioning, Myocardial/methods, medicine.medical_specialty, CONDI-2/ERIC-PPCI Investigators, ISCHEMIA/REPERFUSION INJURY, 03 medical and health sciences, CARDIOPROTECTION, Medicine, General & Internal, Percutaneous Coronary Intervention, General & Internal Medicine, Humans, In patient, Aged, Heart Failure, Intention-to-treat analysis, Science & Technology, ADJUNCT, business.industry, Percutaneous coronary intervention, medicine.disease, United Kingdom, SIZE, Death, Sudden, Cardiac, Emergency medicine, Myocardial infarction complications, Single blind, business, TASK-FORCE
Abstract

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Published
2019

23. Convergence Angle of Preparations for Lithium Disilicate Glass-Ceramic Crowns by Dental Students and Its Effect on Crown Retention

Author

Ahmed Aziz and Omar El-Mowafy

Subjects
Male, Ceramics, 020205 medical informatics, RelyX Unicem, medicine.medical_treatment, Students, Dental, 02 engineering and technology, Crown (dentistry), 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Materials Testing, 0202 electrical engineering, electronic engineering, information engineering, medicine, Lithium disilicate, Humans, Orthodontics, Crowns, business.industry, Significant difference, 030206 dentistry, General Medicine, Dental Porcelain, stomatognathic diseases, Dental Prosthesis Design, Posterior teeth, Computer-Aided Design, Female, Clinical education, business, Prosthodontics, Mandibular molar
Abstract

The aims of this study were to determine the convergence angles of posterior teeth prepared by dental students at the University of Toronto for lithium disilicate glass-ceramic (LDGC) CAD/CAM crowns and to investigate their effect on loss of retention rate. A total of 280 preparations for posterior monolithic LDGC CAD/CAM crowns were performed on 270 patients (169 women and 101 men). Crowns were cemented with RelyX Unicem and Calibra Universal resin cements. Mesial, distal, and angle of convergence were measured on the bitewing radiographs. Cemented crowns were followed for up to six years. Data were analyzed for tooth type and location and for operator experience. The results showed the majority of convergence angles were greater than the recommended guidelines but fell within a clinically acceptable range (20 to 24 degrees). However, angles of convergence for mandibular molar preparations were highest (28.06±5.50 degrees), while maxillary premolars exhibited the lowest values (24.72±6.59 degrees). No significant difference was found between the results of dental students and foreign-trained dentists. Over a six-year observation period, only two crowns lost retention. The findings of this study indicated that ideal taper angles were impractical and difficult to achieve in clinical education settings.

Published
2019

24. Le profil clinique et immunologique de 15 patients Marocains atteints de syndrome hyper IgM

Author

J. Najib, Naima Elhafidi, Leila Jeddane, Hanane Salih Alj, Ibtihal Benhsaien, Fatima Ailal, Jalila El Bakkouri, Ahmed Aziz Bousfiha, Noureddine Rada, and Hind Ouair

Subjects
Male, 0301 basic medicine, Hyper IgM syndrome, T-Lymphocytes, Hyper-IgM Immunodeficiency Syndrome, Lymphocyte, Opportunistic Infections, Immunoglobulin E, immunology, 03 medical and health sciences, 0302 clinical medicine, medicine, immunologie, Humans, Case Series, clinic, Child, clinique, 030203 arthritis & rheumatology, therapy, B-Lymphocytes, biology, business.industry, Infant, Cryptosporidium, General Medicine, medicine.disease, biology.organism_classification, Syndrome hyper IgM, Pathophysiology, Morocco, 030104 developmental biology, medicine.anatomical_structure, Immunoglobulin M, Child, Preschool, Immunology, biology.protein, Female, business, Intracellular, thérapie
Abstract

Le Syndrome hyper IgM est un déficit immunitaire héréditaire bien connu, décrit pour la première fois en 1961. Il est causé par un défaut au niveau des lymphocytes B, caractérisé par un taux sérique normal ou élevé des IgM et un taux bas ou nul des IgG, IgA, IgE résultant d'une déficience de la commutation isotypique. Ses manifestations cliniques sont dominées par les infections à répétition, surtout du tube digestif, de la sphère ORL et des poumons. Le syndrome est causé par un défaut de commutation de classe d'immunoglobuline dans les cellules B, et une diminution de la capacité des monocytes à induire la prolifération des lymphocytes T. Le résultat net de tous ces défauts est la susceptibilité accrue aux infections opportunistes à Pneumocystis jiroveci, Cryptosporidium spp et d'autres organismes intracellulaires, ainsi qu'une fréquence élevée d'infections bactériennes et virales. L'intérêt de ce projet est d'illustrer l'importance de la compréhension des mécanismes physiopathologiques associés à cette susceptibilité accrue aux infections, ce qui permettra une meilleure prise en charge diagnostique et thérapeutique des patients atteint du Syndrome hyper IgM (SHIM).

Published
2017

25. Syndrome d’activation macrophagique compliquant une lymphohistiocytose familiale

Author

Yousra El Boussaadni, Noufissa Benajiba, Ahmed Aziz Bousfiha, and Fatima Ailal

Subjects
medicine.medical_specialty, syndrome d´activation macrophagique, Case Report, 030204 cardiovascular system & hematology, genetic study, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, 0302 clinical medicine, fièvre, Humans, Medicine, fever, Gynecology, lcsh:R5-920, business.industry, Macrophage Activation Syndrome, lcsh:Public aspects of medicine, lcsh:RA1-1270, General Medicine, Prognosis, familial lymphohistiocytosis, lymphohistiocytose familiale, Child, Preschool, 030220 oncology & carcinogenesis, étude génétique, Female, lcsh:Medicine (General), business
Abstract

Le syndrome d'activation macrophagique (SAM) est une entité anatomoclinique due à une stimulation inappropriée des macrophages. Il demeure une pathologie rare, caractérisée par des signes cliniques peu spécifiques et des éléments biologiques dont l'association doit faire évoquer le diagnostic. Il peut être d'origine primaire ou secondaire, son pronostic reste encore sombre. Nous rapportons une observation d'un nourrisson de 3 ans et 4 mois ayant été admis dans notre service pour prise en charge d'une SAM primitif afin de rappeler aux praticiens la nécessité de penser à une cause primitive devant des situations particulières.

Published
2017

26. Anti-Inflammatory Activity of Silibinin in Animal Models of Chronic Inflammation

Author

Saad Abdulrahman Hussain, Bushra Hasan Marouf, Zheen Aorahman Ahmed, and Tavga Ahmed Aziz

Subjects
business.industry, medicine.drug_class, Silibinin, Granulation tissue, Inflammation, General Medicine, medicine.disease, Anti-inflammatory, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Granuloma, Edema, Immunology, Chronic inflammatory response, Medicine, medicine.symptom, business, Dexamethasone, medicine.drug
Abstract

Attenuation of the chronic inflammatory response is a beneficial strategy to combat several human diseases. Traditional medicine offers many plant extracts and pure natural compounds as treatment options of a wide variety of disorders including acute and chronic inflammation. The present study was designed to evaluate the anti-inflammatory effect of silibinin in experimental animal models of chronic and granulomatous inflammations. Forty-eight rats were used to induce chronic inflammation in the hind paw with formalin and granulomatous inflammation with sterile cotton pellets. The anti-inflammatory activity of silibinin (300 mg/kg, P.O) was evaluated in the two models, and compared with that produced by dexamethasone (1 mg/kg, P.O). Silibinin decreased significantly the formation of exudate and granulation tissue compared with the vehicle, but still significantly lower than that produced by dexamethasone. In conclusion, our data suggest that silibinin inhibits the production of edema and granulation tissue in experimental animal models of chronic inflammation, and could be a potential choice for the treatment of chronic inflammatory disorders.

Published
2014

27. The value of serum FGF-23 as a cardiovascular marker in HD patients

Author

Ahmed Aziz, Yasser Elshahawy, Hayam Aref, Abd Elbasat Elsawy, Hayam Ahmed, Dawlat Sany, and Mohamed Abd El Rahman

Subjects
Fibroblast growth factor 23, Adult, Male, medicine.medical_specialty, Time Factors, Heart Ventricles, Serum albumin, chemistry.chemical_element, lcsh:Medicine, Calcium, Gastroenterology, chemistry.chemical_compound, Predictive Value of Tests, Renal Dialysis, Risk Factors, Internal medicine, Medicine, Humans, Mass index, Creatinine, Univariate analysis, Chi-Square Distribution, biology, business.industry, lcsh:R, General Medicine, Middle Aged, Prognosis, Confidence interval, Echocardiography, Doppler, Fibroblast Growth Factors, Fibroblast Growth Factor-23, Endocrinology, chemistry, Cardiovascular Diseases, biology.protein, Linear Models, Kidney Failure, Chronic, Female, business, Cardiac symptoms, Biomarkers
Abstract

Fibroblast growth factor 23 (FGF-23) is a recently discovered regulator of phos­phate and mineral metabolism and has been associated with both progression of CKD and mortality in dialysis patients. To evaluate the association between serum FGF-23 levels and echocardiographic measurements in long-term HD (HD) patients without cardiac symptoms, we studied 90 consecutive patients treated in a single HD center (51 males, 39 females; mean age 41.5 ± 14.2 years, mean HD duration 71.2 ± 14.2 months). Comprehensive echocardiography was performed after HD and blood samples were obtained before HD. The serum FGF-23 level in dialysis patients was 95.7 ± 88.4 pg/mL. In univariate analysis, serum calcium levels (r = 0.33, P

Published
2014

28. Effects 0f Aliskiren on the Absorption of Monosaccharides in Animal Model of Fructose-induced Metabolic Syndrome

Author

Tavga Ahmed Aziz, Zheen Orahman Ahmed, Rbab Mohammed Utba, and Saad Abdulrahman Hussain

Subjects
General Medicine
Abstract

The renin angiotensin system (RAS) was involved in various metabolic processes including insulin secretion, carbohydrate absorption and proliferation of adipose tissue. This study aims to evaluate the effects of aliskiren on the absorption of glucose in rats with fructose-induced metabolic syndrome. The results showed that treatment with aliskiren attenuates the increase in body weight and improves fasting serum glucose, insulin, triglycerides and cholesterol levels. Moreover, absorption of glucose was significantly decreased after oral glucose load in high-fructose diet fed rats. In conclusion, aliskiren significantly reduces body weight, fasting serum glucose, insulin, triglyceride and total cholesterol levels, and the rate of glucose absorption after oral glucose load in high fructose-fed rats.

Published
2018

29. Structural and Functional Coronary Artery Abnormalities in Patients With Vasospastic Angina Pectoris

Author

Peter Ong, Ahmed Aziz, Henrik Steen Hansen, Anastasios Athanasiadis, Eva Prescott, and Udo Sechtem

Subjects
Angina Pectoris, Variant, Male, medicine.medical_specialty, Acute coronary syndrome, Coronary Vessel Anomalies, Cardiomyopathy, Coronary Vasospasm, Coronary Artery Disease, Autonomic Nervous System, Coronary artery disease, Muscle, Smooth, Vascular, Sudden cardiac death, Internal medicine, Intravascular ultrasound, medicine, Humans, cardiovascular diseases, Coronary atherosclerosis, Inflammation, medicine.diagnostic_test, business.industry, Vasospasm, General Medicine, Atherosclerosis, medicine.disease, Oxidative Stress, Coronary vasospasm, Cardiology, Female, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business
Abstract

Coronary spasm is involved in many clinical scenarios, such as stable angina, acute coronary syndrome, sudden cardiac death, non-ischemic cardiomyopathy, arrhythmia and syncope. In recent years, imaging tools such as computerized tomographic angiography, intravascular ultrasound or optical coherence tomography have been applied to study the coronary pathology in patients with vasospastic angina. Patients with vasospastic angina represent a heterogeneous cohort of patients with regard to the extent of concomitant coronary atherosclerosis. They share the common pathophysiological phenomenon of vascular smooth muscle hyperreactivity leading to spasm caused by various factors that may also overlap. Focal coronary spasm is related to epicardial atherosclerosis and in the presence of obstructive coronary artery disease it may be useful to treat the lesion to prevent further spasm. The aim of this article is to review structural and functional coronary artery abnormalities in patients with vasospastic angina.

Published
2015

30. Correlation of Urine Biomarkers: Microalbuminuria and Spot Urine Protein among Diabetic Patients. Application of Spot Urine Protein in Diabetic Kidney Disease, Nephropathy, Proteinuria Estimation, Diagnosing and Monitoring

Author

Kamran Mahmood Ahmed Aziz

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Urology, Urine, urologic and male genital diseases, Nephropathy, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, Drug Discovery, medicine, Immunology and Allergy, Albuminuria, Humans, Diabetic Nephropathies, Aged, Creatinine, Proteinuria, business.industry, Biochemistry (medical), General Medicine, Dipstick, Middle Aged, medicine.disease, Endocrinology, chemistry, ROC Curve, Microalbuminuria, Female, medicine.symptom, business, Biomarkers
Abstract

Current study has invented a new method for utilizing spot urine protein among diabetic patients. There have been various efforts and strategies in research internationally to detect, diagnose and monitor nephropathy/DKD. Although 24-hour urine studies are gold standard, however, there exist some controversies about microalbuminuria and spot urine protein. The current study was designed to utilize spot urine protein among diabetic patients and to find its association with routine dipstick urine test for albumin, and microalbuminuria. The study demonstrated significant association of spot urine protein with urine dipstick albumin, and has demonstrated increasing spot urine protein with increasing albumin in urine (p-value < 0.0001). This study also demonstrated significantly higher levels of spot urine protein between the groups with nephropathy/DKD as compared to those without nephropathy/DKD (p-value < 0.0001). Similarly, spot urine protein and spot urine protein/creatinine were also significantly associated with microalbumin and microalbumin/creatinine in urine. Significant regression models for spot urine protein and microalbuminuria were also developed and proposed to detect and estimate microalbumin in urine while utilizing spot urine protein (< 0.0001). Synthesized regression equations and models can be used confidently to detect, rule out and monitor proteinuria and DKD. ROC curves were utilized to detect spot urine protein cutoff points for nephropathy and DKD with high specificity and sensitivity. Some important patents were also discussed in the paper regarding albuminuria/proteinuria detection and management. Current study has demonstrated and concluded, for the first time, that there exists a significant association of spot urine protein with routine dipstick albumin in urine and microalbuminuria. It is also essential to detect early, monitor and manage proteinuria, hypertension and dyslipidemia with good glycemic control to prevent diabetes complications.

Published
2015

31. Variation of hepatic enzymes with Vitamin B12 and D3 levels in cirrhotic patients

Author

Syeda Sara Fatima, Syed Mohammad Ali Abidi, Mir Ali Raza Talpur, Kiran Fatima, Tufail Raza, Hasnain Abbas Dharamshi, Ahmed Aziz Siddiqui, Tahira Naqvi, Ahmad Faraz, Amber Batool, and Farwa Fatima

Subjects
chemistry.chemical_classification, Vitamin, medicine.medical_specialty, Cirrhosis, business.industry, Hepatocellular damage, General Medicine, Plasma levels, medicine.disease, digestive system diseases, Elevated alt, chemistry.chemical_compound, Enzyme, Endocrinology, chemistry, Internal medicine, medicine, Alkaline phosphatase, Vitamin B12, business
Abstract

OBJECTIVE: To determine variation of hepatic enzymes Vitamin B12 and D3 levels in cirrhotic patients. DESIGN: Cross sectional study. SETTING: Cirrhotic patients in Abbasi Shaheed Hospital. PARTICIPANTS: 250 patients in Abbasi Shaheed Hospital with diagnosis of cirrhosis including 141 males and 109 females. VARIABLE PARAMETERS: They include mean ALT, GGT, Alkaline phosphatase levels along with Vitamin B12 and D3 levels in blood. RESULTS: Vitamin B12 levels were 1249.59±487.01pg/ml and 1422.28±627.75pg/ml in males and females respectively while Vitamin D3 levels were found to be 17.15±10.45 nmol/L in males and 14.80±14.24 nmol/L in females. Vitamin B12 levels were found to be positively correlated with the elevation of ALT and were negatively correlated with elevation of ALT, GGT and Alkaline Phosphatase. The ALT levels were 50.0±21.88 in males and 14.80±14.24 in females, Alkaline phosphatase to be 311.46±107.98 in males while female Alkaline phosphatase were 346.47±101.60. GGT levels to be 41.70±10.62 in males and 45.01±13.74 in females. CONCLUSION: Cirrhotic patients suffering from severe hepatocellular damage have their elevated levels of Vitamin B12 and depressed Vitamin D3 levels in plasma accompanied by a positive association with elevated ALT and GGT plasma levels

Published
2015

32. Amplatzer left atrial appendage occlusion through a patent foramen ovale

Author

Wenaweser, Peter Martin, Shakir, Samera, Meier, Bernhard, Körmendy, Dezsö, Glökler, Steffen, Khattab, Ahmed Aziz, Windecker, Stephan, Nietlispach, Fabian, University of Zurich, and Meier, Bernhard

Subjects
Radiology Nuclear Medicine and imaging, 10209 Clinic for Cardiology, 2741 Radiology, Nuclear Medicine and Imaging, 610 Medicine & health, General Medicine, Cardiology and Cardiovascular Medicine, 2705 Cardiology and Cardiovascular Medicine
Abstract

OBJECTIVES: To assess feasibility and outcomes of left atrial appendage (LAA) closure when using a patent foramen ovale (PFO) for left atrial access. Background: Because of the fear of entering the left atrium too high, using a PFO for left atrial access during LAA occlusion (LAAO) is generally discouraged. We report our single-center experience using a concomitant PFO for LAAO, thereby avoiding transseptal puncture. METHODS: LAAO was performed with local anesthesia and fluoroscopic guidance only (no echocardiography). The Amplatzer Cardiac Plug (ACP) was used in all patients. After LAAO, the PFO was closed at the same sitting, using an Amplatzer occluder through the ACP delivery sheath. Patients were discharged the same or the following day on dual antiplatelet therapy for 1-6 months, at which time a follow-up transesophageal echocardiogram (TEE) was performed. RESULTS: In 49 (96%) of 51 patients (35 males, age 70.9 ± 11.9 years), LAAO was successful using the PFO for left atrial access. In one patient, a long tunnel PFO precluded LAAO, which was performed via a more caudal transseptal puncture. In a second patient, a previously inserted ASD occluder precluded LAAO, which was abandoned because of pericardial bleeding. PFO closure was successful in all patients. Follow-up TEE was performed in 43 patients 138 ± 34 days after the procedure. It showed proper sitting of both devices in all patients. CONCLUSIONS: Using a PFO for LAAO had a high success rate and could be the default access in all patients with a PFO, potentially reducing procedural complications arising from transseptal puncture.

Published
2014

34. Érythrodermie néonatale: ne pas méconnaitre un déficit immunitaire

Author

Fatima Ailal, Yousra El Boussaadni, Noufissa Benajiba, Sihame Dikhaye, Aziza El Ouali, and Ahmed Aziz Bousfiha

Subjects
Gynecology, medicine.medical_specialty, lcsh:R5-920, business.industry, lcsh:Public aspects of medicine, Erythroderma, nouveau né, lcsh:RA1-1270, General Medicine, medicine.disease, Immunologic Deficiency Syndromes, syndrome d´omenn, medicine, erythrodermie, business, lcsh:Medicine (General)
Abstract

Les érythrodermies du nouveau-né sont des tableaux rares, d'évolutions chroniques et potentiellement mortelles. Leurs étiologies sont diverses et variées dominées par les ichtyoses, le déficit immunitaire primaire, ou plus exceptionnellement le psoriasis sévère, les maladies métaboliques, la dermatite atopique ou une cause infectieuse. La détermination rapide de la cause sous-jacente est cruciale pour une meilleure prise en charge. Cependant, le diagnostic constitue un défi pour le clinicien et est souvent retardé en raison de la nature non spécifique des signes cliniques et histopathologiques. L'objectif de notre travail est de rappeler aux praticiens une étiologie grave de l'érythrodermie néonatale: le déficit immunitaire ceci à travers l'observation d'un nourrisson suivi pour une érythrodermie évoluant depuis la naissance, hospitalisé pour une fièvre prolongée, et chez qui un interrogatoire minutieux, un examen clinique soigneux, ainsi que l'évolution ont pu redresser le diagnostic vers un déficit immunitaire.

Published
2014

35. Le déficit immunitaire humoral: mieux le connaître pour mieux le prendre en charge

Author

Hanane Salih Alj, Ahmed Aziz Bousfiha, Jalila El Bakkouri, Zahra Aadam, and Fatima Ailal

Subjects
medicine.medical_specialty, Agammaglobulinemia, Humoral immune deficiency, medicine, Humans, IgA deficiency, IgG Deficiency, déficit immunitaire commun variable, Gynecology, lcsh:R5-920, business.industry, lcsh:Public aspects of medicine, déficit en IgA, Common variable immunodeficiency, common variable immunodeficiency, IgA Deficiency, Immunologic Deficiency Syndromes, lcsh:RA1-1270, Seminar, General Medicine, Déficit immunitaire humoral, agammaglobulinémie, medicine.disease, Immunity, Humoral, lcsh:Medicine (General), business
Abstract

Les déficits immunitaires humoraux (DIH) sont des maladies hétérogènes allant des formes asymptomatiques rencontrés lors des déficits sélectifs en immunoglobulines A (IgA) et en sous-classes d'IgG aux formes graves des agammaglobulinémies congénitales. Les patients atteints de DIH présentent souvent des infections ORL ou des voies respiratoires récidivantes ou sévères. Ces patients peuvent présenter un certain nombre de complications non infectieuses, telles que des manifestations auto-immunes et des entéropathies, qui pourraient être le seul symptôme clinique révélateur. Les formes sévères des DIH sont facilement diagnostiquées grâce au dosage des IgG totaux, des IgA et des IgM. La thérapie substitutive par les immunoglobulines reste le traitement de choix chez ces patients.

Published
2014

36. Revisiting Human IL-12R beta 1 Deficiency A Survey of 141 Patients From 30 Countries

Author

Chris Nieuwhof, Yu-Lung Lau, Klara Frecerova, Suzanne T. Anderson, Vas Novelli, Dinakantha S. Kumararatne, Figen Dogu, Matías Oleastro, Barbara Pietrucha, Melike Keser, Xi-qiang Yang, Anete Sevciovic Grumach, Renate Blüetters-Sawatzki, Necil Kutukculer, Lucile Janniere, Sigifredo Pedraza, María Isabel Gaillard, Isabel Caragol, Ruth Aldana, Parisa Adimi, Orchidée Filipe-Santos, Liliane Schandené, Ludovic de Beaucoudrey, Alejandra King, Rainer Doffinger, Sergio D. Rosenzweig, Dewton Moraes-Vasconcelos, Guzide Aksu, Pamela Pui Wah Lee, Abdulaziz Al-Ghonaium, Aurélie Cobat, David Tuerlinckx, Michael Levin, Mohammed Bejaoui, Nevin Hatipoğlu, Kinda Schepers, Francisco J. Espinosa-Rosales, Andrea Bernasconi, Aydan Ikinciogullari, Jacob Levy, Mohammad S. Ehlayel, Małgorzata Pac, Darko Richter, David A. Lammas, David B. Lewis, Janine Reichenbach, Gonul Tanir, Joachim Freihorst, Tuba Turul Ozgur, Sulaiman Al-Ajaji, Masao Matsuoka, Jacqueline Feinberg, Smita Y. Patel, Abdullah A. Alangari, Judith Yancoski, Andrew Exley, Saleh Al-Muhsen, Ridha Barbouche, Tatsunori Sakai, Ana Codoceo, Xiao-Fei Kong, Claire-Anne Siegrist, Jamila El Baghdadi, Bernhard Fleckenstein, Xiaochuan Wang, Sami Al-Hajjar, Ingrid Müller-Fleckenstein, Capucine Picard, Gabriela Castro, Jean-Laurent Casanova, Tong-Xin Chen, Frans De Baets, Namik Ozbek, Alain Fischer, Liliana Bezrodnik, Aileen C. Cohen, Ariane Chapgier, Olle Jeppsson, Imen Ben-Mustapha, Saniye Gülle, Revathi Raj, Françoise Mascart, Arina Samarina, Davood Mansouri, Nima Parvaneh, Yoann Rose, Koon Wing Chan, Yuanyuan Xie, Alberto José da Silva Duarte, Ahmed Aziz Bousfiha, Claire Fieschi, Steven M. Holland, Meteran Ozen, Walther H. Haas, Stéphanie Boisson-Dupuis, Carlos Rodríguez-Gallego, Li-Ping Jiang, Ayper Somer, Suna Asilsoy, André Efira, Yaryna Boyko, Laurent Abel, Setareh Mamishi, Xiaohong Wang, Ulrich Baumann, Filomeen Haerynck, Zobaida Alsum, Kuender D Yang, Jacinta Bustamante, Daniela Di Giovani, Ozden Sanal, Maylis de Suremain, Yildiz Camcioglu, Christiane Vermylen, Ben-Zion Garty, Jutta Bernhöft, Ivelisse Natera, Suliman Al-Jumaah, Chaomin Zhu, David Nadal, Husn H. Frayha, Cigdem Aydogmus, Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, Department of Pediatrics, King Faysal Hospital and Research center, Coll Med, Prince Naif Ctr Immunol Res, King Saud University [Riyadh] (KSU), Coll Med, Dept Pediat, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Sami Ulus Children Hlth & Dis Training & Res Ctr, Ankara, Dept Pediat, King Fahad Natl Guard Hosp, Shahid Beheshti University of Medical Sciences, Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Dept Immunol, Juan Pedro Garrahan Natl Hosp Pediat, Schneider Childrens Med Ctr Israel, Hospital Universitario de Gran Canaria Dr Negrin, Immunol Lab, Vall d'Hebron University Hospital [Barcelona], Ege University, Dept Clin Biochem & Immunol, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Inflammat & Immunol Unit, Dept Pathol, Papworth Hosp NHS Fdn Trust, Inflammat & Immunol Unit, Dept Thorac Med, Karolinska University Hospital [Stockholm], Univ Childrens Hosp Zurich, Dept Infect Dis, Lviv Reg Specialized Childrens Hosp, St Marys Hosp, Imperial Coll Sch Med, Childrens Mem Hlth Inst, Immunobiol Clin, Hop Erasme, Université Libre de Bruxelles [Bruxelles] (ULB), Immunodeficiency Dept, Hop Erasme, Lab Vaccinol & Mucosal Immun, Dept Internal Med, Natl Hosp Org Kumamoto Med Ctr, Laboratory of Virus Control, Kyoto University [Kyoto], University of Geneva [Switzerland], Dept Int Relat, Minist Hlth Slovaquie, Dept Pediat Hematol & Oncol, Dept Pediat Pulmonol & Neonatol, Hannover Medical School [Hannover] (MHH), Univ Hosp Ctr Rebro, Dept Pediat Pulmonol & Immunol, Ghent University Hospital, Infect Dis Unit, Great Ormond St Hosp Sick Children, Ctr Immune Regulat, Univ Birmingham, Sch Med, MRC, Cliniques Universitaires Saint-Luc [Bruxelles], Dept Pediat, Mt Godinne Clin, Catholic University Louvain, Dept Internal Med, Div Clin & Expt Immunol, Maastricht University [Maastricht], Dept Infect Dis Epidemiol, Unit Resp Infect, Robert Koch Institute [Berlin] (RKI), Univ Erlangen Nurnberg, Pediatric Department, Ben-Gurion University of the Negev (BGU), Stanford University [Stanford], Lab Clin Infect Dis, NIAID, TMRC, NIH, Bethesda, Dept Pediat Allergy, Chang Gung Childrens Hosp, Dept Clin Immunol, Fudan University [Shanghai], Clin Immunol Lab, Chongqing Medical University, Dept Paediat & Adolescent Med, The University of Hong Kong (HKU), Universidade Federal da Bahia (UFBA), Dept Pediat,Sch Med, Shanghai Jiao Tong University [Shanghai], Univ Hosp Caracas, Hosp Ninos Luis Calvo Mackenna, Childrens Hosp Ricardo Gutierrez Buenos Aires, Dept Dermatol, Lab Invest Dermatol & Immunodeficiencies, Universidade de São Paulo (USP), Dept Pulmonol, Childrens Hosp Federico Gomez, Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Natl Ctr Bone Marrow Graft, Tunis, Clinical Immunology Unit, Ibn Rochd Hospital King Hassan II University-Aïn Chok, Genetics Unit, Military Hospital Mohamed V, Baskent universitesi, Dept Pediat Infect Dis & Clin Immunol, Istanbul Univ, Dept Pediat Infect Dis & Immunol, Bakirkoy Matern & Childrens State Hosp, Dr Behcet Uz Children Res & Training Hosp, Department of Pediatrics, Infectious Diseases, Cerrahpacsa Medical School, Hacettepe University = Hacettepe Üniversitesi, Fac Med Malatya, Tehran University of Medical Sciences (TUMS), Dept Biochem, Minist Hlth Mexico, Department of Pediatric and Adolescent Medicine, Hamad medical corporation, Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Çocuk Sağlığı ve Hastalıkları, Ege Üniversitesi, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rockefeller University [New York], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, Université libre de Bruxelles (ULB), Université Catholique de Louvain = Catholic University of Louvain (UCL), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Stanford University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Siegrist, Claire-Anne, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), King Saud University [Riyadh] ( KSU ), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Hannover Medical School [Hannover] ( MHH ), Robert Koch Institute [Berlin] ( RKI ), Ben-Gurion University of the Negev ( BGU ), The University of Hong Kong ( HKU ), Universidade Federal da Bahia ( UFBA ), Universidade de São Paulo ( USP ), Tehran University of Medical Sciences, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Interne Geneeskunde, RS: CARIM School for Cardiovascular Diseases, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, and UCL - (MGD) Service de pédiatrie

Subjects
Male, Proband, [SDV]Life Sciences [q-bio], Mycobacterium tuberculosis/isolation & purification, Mycobacterium bovis/isolation & purification, Disease, Interleukin-12 Receptor beta 1 Subunit - deficiency, genetics, Cytokines - blood, 0302 clinical medicine, Mycobacterium bovis - isolation & purification, Child, 0303 health sciences, ddc:618, Interleukin-12 Receptor beta 1 Subunit/*deficiency/genetics, Nontuberculous Mycobacteria/isolation & purification, biology, Age Factors, Nontuberculous Mycobacteria, Mycobacterium Infections, Nontuberculous/epidemiology/genetics, General Medicine, Middle Aged, Mycobacterium bovis, Penetrance, Mycobacteria, Atypical - isolation & purification, 3. Good health, Child, Preschool, Cytokines, Female, medicine.symptom, Adult, medicine.medical_specialty, Tuberculosis, Adolescent, Genotype, Mycobacterium Infections, Nontuberculous, Mycobacterium tuberculosis - isolation & purification, Cytokines/blood, Asymptomatic, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Internal medicine, General & Internal Medicine, Interleukin-12 Receptor beta 1 Subunit, medicine, Humans, Survival analysis, 030304 developmental biology, Mycobacterium Infections, Atypical - epidemiology, genetics, [ SDV ] Life Sciences [q-bio], business.industry, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, Survival Analysis, Immunology, Nontuberculous mycobacteria, business, 030215 immunology
Abstract

WOS: 000283840300002, PubMed ID: 21057261, Interleukin-12 receptor beta 1 (IL-12R beta 1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guerin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years +/- 9.8 years (range, 0.5-46.4 yr). IL-12R beta 1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought., Rockefeller University Center for Clinical and Translational Science [5UL1RR024143-03]; Rockefeller University; ANRFrench National Research Agency (ANR); PHRC; EUEuropean Union (EU) [LHSP-CT-2005-018736]; BNP Paribas Foundation; Dana Foundation; March of DimesMarch of Dimes; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale; Howard Hughes Medical InstituteHoward Hughes Medical Institute, The St. Giles Laboratory of Human Genetics of Infectious Diseases is supported by grants from The Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143-03, and The Rockefeller University, ANR, PHRC, EU (LHSP-CT-2005-018736), BNP Paribas Foundation, the Dana Foundation, and the March of Dimes. LDB is supported by the Fondation pour la Recherche Medicale as part of the PhD program of Pierre et Marie Curie University (Paris, France). JLC was an International Scholar of the Howard Hughes Medical Institute.

Published
2010

37. Determination of cytosolic citrulline and nitrate as indicators of nitric oxide in bladder cancer: possible association with basic fibroblast growth factor

Author

Ahmed Aziz, Ali Khalifa, and Sanaa Eissa

Subjects
medicine.medical_specialty, Angiogenesis, Clinical Biochemistry, Basic fibroblast growth factor, Urinary Bladder, Schistosomiasis, Biology, urologic and male genital diseases, medicine.disease_cause, Nitric Oxide, Nitric oxide, Immunoenzyme Techniques, chemistry.chemical_compound, Cytosol, Reference Values, Internal medicine, medicine, Citrulline, Biomarkers, Tumor, Humans, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Bladder cancer, Nitrates, General Medicine, medicine.disease, Amino acid, Endocrinology, chemistry, Urinary Bladder Neoplasms, Fibroblast Growth Factor 2, Carcinogenesis
Abstract

Background: Nitric Oxide (NO) and nitrosamines have been implicated in bladder carcinogenesis. Apart from its implication in carcinogenesis, NO contributes to the regulation of tumor angiogenesis via angiogenic peptides exemplified by basic fibroblast growth factor (bFGF). Objectives and methods: In order to examine NO pattern in normal, schistosomal, and malignant bladder cytosols, we have used a combined approach by measuring nitrate and the amino acid citrulline. The results were correlated to bFGF, which were measured in bladder cytosols by an EIA method. Results: Comparison between normal, schistosomal, and malignant bladder groups showed that patients with schistosomiasis and bladder cancer had significantly higher cytosolic nitrate, citrulline, and bFGF levels. There were no apparent correlations between these investigated parameters and tumor histologic features. The level of citrulline was strongly correlated to nitrate level and both were correlated to bFGF level in bladder cancer and schistosomiasis groups. Conclusions: Our findings indicate that NO and bFGF were significantly elevated in schistosomiasis and bladder cancer compared to normal bladders. Moreover, the consistent association of NO with bFGF found in the present work, support the hypothesis that the angiogenic peptide bFGF may be modulated by NO and suggest a useful target in antiangiogenic therapy in bladder cancer.

Published
2000

38. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author

Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesus, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G., Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L., Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Mehlal Sedkaoui, Souad, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Bigio, Benedetta, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Seeleuthner, Yoann, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Alkhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Bustamante, Jacinta, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David C, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, THORN, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Troya, Jesús, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey J., Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton L., Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’Angio’, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, McElheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Erikstrup, Christian, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, Von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Townsend, Liam, Cheallaigh, Cliona Ni, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, Bourke, Nollaig, O'Farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouadma, Lila, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, De Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Alavoine, Loubna, Behillil, Sylvie, Burdet, Charles, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geijtenbeek, Suzanne Geerlings Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos, Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés A., Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein S., Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Milner, Joshua D., Mironska, Kristina, Ng, Lisa F.P., Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., von Bernuth, Horst, Zawadzki, Pawel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Le Got, Stéphane, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grand Hôpital de l'Est Francilien (GHEF), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Edouard Herriot [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, Howard Hughes Medical Institute, Rockefeller University, European Commission, Jeffrey Modell Foundation, Université de Bordeaux, Meath Foundation, National Human Genome Research Institute, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation du Souffle, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, St. Giles Foundation, Ministère des Solidarités et de la Santé, Sorbonne Université, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Meyer Foundation, Fondation de France, National Cancer Institute, European Regional Development Fund, Fundación DISA, Ministero della Salute, ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: IdEx Bordeaux (ANR-10-IDEX- 003-02), Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesu, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bonradenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Vandreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Members of the The Milieu Intérieur Consortium: Laurent Abel1 , Andres Alcover2 , Hugues Aschard2 , Philippe Bousso2 , Nollaig Bourke3 , Petter Brodin4 , Pierre Bruhns2 , Nadine Cerf-Bensussan5 , Ana Cumano2 , Christophe D’Enfert2 , Ludovic Deriano2 , Marie-Agnès Dillies2 , James Di Santo2 , Françoise Dromer2 , Gérard Eberl2 , Jost Enninga2 , Jacques Fellay6 , Ivo Gomperts-Boneca2 , Milena Hasan2 , Gunilla Karlsson Hedestam4 , Serge Hercberg7 , Molly A. Ingersoll2 , Olivier Lantz8 , Rose Anne Kenny3 , Mickaël Ménager5 , Frédérique Michel2 , Hugo Mouquet2 , Cliona O’Farrelly3 , Etienne Patin2 , Sandra Pellegrini2 , Antonio Rausell5 , Frédéric Rieux-Laucat5 , Lars Rogge2 , Magnus Fontes9 , Anavaj Sakuntabhai2 , Olivier Schwartz2 , Benno Schwikowski2 , Spencer Shorte2 , Frédéric Tangy2 , Antoine Toubert10 , Mathilde Touvier12 , Marie-Noëlle Ungeheuer2 , Christophe Zimmer2 , Matthew L. Albert11 , Darragh Duffy2 , Lluis Quintana-Murc, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Ministère des Solidarités et de la Santé (France), National Health and Medical Research Council (Australia), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Michailidis, Eleftherios, García-Prat, Marina, Paul, Stephanie, Metz, Christine N., Barreiros, Lucila, Domínguez-Garrido, Elena, Vidigal, Mateus, Beek, Diederik van der, Stepanovskyy, Yuriy, Tangye, Stuart G., Quintana-Murci, Lluis, Kan, Nelli, Nussenzweig, Michel C., Baris, Hagit N., Dyer, Adam, Bourke, Nollaig, Vinh, Donald C., Spaan, András N., Fellay, Jacques, Mane, Shrikant M., Anderson, MarK S., Andreakos, Evangelos, Haljasmägi, Liis, Mogensen, Trine, Lamballerie, Xavier de, Soler-Palacín, Pere, Martínez-Picado, Javier, Gregersen, Peter K., Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Prost, Nicolas de, Amador-Borrero, Blanco, Troya, Jesús, Rivière, Jacques G., Gentile, Stephanie, Rosen, Lindsey B., Tharaux, Pierre-Louis, Stépanian, Alain, Mégarbane, Bruno, Heath, James R., Franco, José Luis, Anaya, Juan Manuel, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Velez, Marcela, Planas, Anna M., Nussbaum, Robert, Bousfiha, Ahmed Aziz, Ramírez-Santana, Carolina, Intensive care medicine, Internal medicine, AII - Infectious diseases, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, Radiology and nuclear medicine, AMS - Rehabilitation & Development, VU University medical center, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anesthesiology, APH - Quality of Care, ACS - Heart failure & arrhythmias, Özçelik, Tayfun, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center, Admin, Oskar, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques 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Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Megarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Coulibaly, B, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Nussbaum, R, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de 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Marseglia, G.L., Batten, I., Reddy, C., McElheron, M., Noonan, C., Connolly, E., Fallon, A., Storgaard, M., Jørgensen, S., Erikstrup, C., Pedersen, O.B., Sørensen, E., Mikkelsen, S., Dinh, K.M., Larsen, MAH, Paulsen, I.W., Von Stemann, J.H., Hansen, M.B., Ostrowski, S.R., Townsend, L., Cheallaigh, C.N., Bergin, C., Martin-Loeches, I., Dunne, J., Conlon, N., Bourke, N., O'Farrelly, C., Abel, L., Allavena, C., Andrejak, C., Angoulvant, F., Azoulay, C., Bachelet, D., Bartoli, M., Basmaci, R., Behilill, S., Beluze, M., Benech, N., Benkerrou, D., Bhavsar, K., Bitker, L., Bouadma, L., Bouscambert-Duchamp, M., Paz, P.C., Cervantes-Gonzalez, M., Chair, A., Chirouze, C., Coelho, A., Cordel, H., Couffignal, C., Couffin-Cadiergues, S., d'Ortenzio, E., De Montmollin, E., Debard, A., Debray, M.P., Deplanque, D., Descamps, D., Desvallée, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V., Epaulard, O., Esperou, H., Esposito-Farese, M., Etienne, M., Garot, D., Gault, 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Briseño-Roa, L., Gribouval, O., Pelet, A., Alcover, A., Aschard, H., Bousso, P., Brodin, P., Bruhns, P., Cerf-Bensussan, N., Cumano, A., D'Enfert, C., Deriano, L., Dillies, M.A., Di Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hedestam, G.K., Hercberg, S., Ingersoll, M.A., Lantz, O., Kenny, R.A., Ménager, M., Michel, F., Patin, E., Rausell, A., Rieux-Laucat, F., Rogge, L., Fontes, M., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Zimmer, C., Albert, M.L., Duffy, D., Quintana-Murci, L., Alavoine, L., Behillil, S., Burdet, C., Charpentier, C., Dechanet, A., Ecobichon, J.L., Frezouls, W., Houhou, N., Lehacaut, J., Manchon, P., Nouroudine, M., Quintin, C., Thy, M., van der Werf, S., Vignali, V., Chahine, A., Waucquier, N., Migaud, M.C., Djossou, F., Mergeay-Fabre, M., Lucarelli, A., Demar, M., Bruneau, L., Gérardin, P., Maillot, A., Payet, C., Laviolle, B., Paris, C., Desille-Dugast, M., Fouchard, J., Pistone, T., Perreau, P., Gissot, V., Le Goas, C., Montagne, S., Richard, L., Bouiller, K., Desmarets, M., Meunier, A., Lefévre, B., Jeulin, H., Legrand, K., Lomazzi, S., Tardy, B., Gagneux-Brunon, A., Bertholon, F., Botelho-Nevers, E., Kouakam, C., Leturque, N., Roufai, L., Amat, K., Espérou, H., Hendou, S., van Agtmael, M., Algera, A.G., Appelman, B., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bonta, P., Bos, L., Botta, M., de Brabander, J., de Bree, G., de Bruin, S., Buis, DTP, Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Dijkstra, M., Dongelmans, D.A., Dujardin, RWG, Elbers, P., Fleuren, L., Geijtenbeek, SGT, Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., Lim, EHT, van Mourik, N., Nellen, J., Nossent, E.J., Paulus, F., Peters, E., Pina-Fuentes, DAI, van der Poll, T., Preckel, 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[0000-0002-5582-9110], Kisand, Kai [0000-0002-5426-4648], Okada, Satoshi [0000-0002-4622-5657], Puel, Anne [0000-0003-2603-0323], Jouanguy, Emmanuelle [0000-0002-7358-9157], Tiberghien, Pierre [0000-0002-9310-8322], Zhang, Qian [0000-0002-9040-3289], Särekannu, Karita [0000-0002-5984-668X], Cobat, Aurélie [0000-0001-7209-6257], Abel, Laurent [0000-0001-7016-6493], Casanova, Jean-Laurent [0000-0002-7782-4169], Prost, Nicolas de [0000-0002-4833-4320], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Luyt, Charles-Edouard [0000-0001-7424-2705], Amador-Borrero, Blanco [0000-0001-6170-8721], Poissy, Julien [0000-0001-6017-5353], Richard, Pascale [0000-0003-1864-3824], Cognasse, Fabrice [0000-0001-8041-928X], Troya, Jesús [0000-0001-7323-114X], Trouillet-Assant, Sophie [0000-0001-6439-4705], Belot, Alexandre [0000-0003-4902-5332], Saker, Kahina [0000-0001-8825-5400], Rivière, Jacques G. [0000-0003-1055-2063], Gentile, Stephanie [0000-0003-3858-9503], Rosen, Lindsey B. 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[0000-0002-6147-1880], Haerynck, Filomeen [0000-0001-9161-7361], Duvlis, Sotirija [0000-0001-8587-7386], Nussbaum, Robert [0000-0003-3445-8880], Bousfiha, Ahmed Aziz [0000-0002-5011-9873], El Bakkouri, Jalila [0000-0003-2303-3369], Ramírez-Santana, Carolina [0000-0003-2137-4899], Paul, Stephanie [0000-0002-8830-4273], Pan-Hammarström, Qiang [0000-0003-1990-8804], Hammarström, Lennart [0000-0002-8635-9609], Dupont, Annabelle [0000-0002-1554-9931], Kurolap, Alina [0000-0002-7005-3621], Metz, Christine N. [0000-0002-1013-1691], Aiuti, Alessandro [0000-0002-5398-1717], Casari, Giorgio [0000-0002-0115-8980], Lampasona, Vito [0000-0001-5162-8445], Ciceri, Fabio [0000-0003-0873-0123], Barreiros, Lucila [0000-0002-9818-2345], Domínguez-Garrido, Elena [0000-0002-2066-0511], Vidigal, Mateus [0000-0002-8895-652X], Zatz, Mayana [0000-0003-3970-8025], Beek, Diederik van der [0000-0002-4571-044X], Stepanovskyy, Yuriy [0000-0001-6339-5490], Boyarchuk, Oksana [0000-0002-1234-0040], Nukui, Yoko [0000-0002-6123-5212], Vidaur, Loreto [0000-0002-6720-4900], Tangye, Stuart G. [0000-0002-5360-5180], Burrel, Sonia [0000-0002-7783-2601], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Klocperk, Adam [0000-0002-1526-4557], Kan, Nelli [0000-0003-3564-6496], Shcherbina, Anna [0000-0002-3113-4939], Lau, Yu-Lung [0000-0002-4780-0289], Leung, Daniel [0000-0002-9360-6233], Coulongeat, Matthieu [0000-0003-1986-3546], Marlet, Julien [0000-0002-8645-8703], Koning, Rutger [0000-0003-3128-5072], Reyes, Luis Felipe [0000-0003-1172-6539], Venet, Fabienne [0000-0003-0462-4235], Monneret, Guillaume [0000-0002-9961-5739], Nussenzweig, Michel C. [0000-0003-0592-8564], Baris, Hagit N. [0000-0003-4065-7560], Hagin, David [0000-0003-2702-1031], Wauters, Joost [0000-0002-5983-3897], Meyts, Isabelle [0000-0003-1214-0302], Dyer, Adam [0000-0003-1356-510X], Bourke, Nollaig [0000-0003-4313-6859], Halwani, Rabih [0000-0002-6516-7771], and Sharif-Askari, Narjes Saheb [0000-0003-0482-6777]

Subjects
Interferon Type I/immunology, AUTOIMMUNITY, [SDV]Life Sciences [q-bio], Interferó, Gastroenterology, COVID-19 (Malaltia), Immunoglobulin G, Basic medicine, 0302 clinical medicine, Medicine and Health Sciences, 80 and over, Immunologia, Young adult, Child, Neutralizing, MYASTHENIA-GRAVIS PATIENTS, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, biology, General Medicine, Middle Aged, 3. Good health, COVID-19/immunology, Settore MED/03, 030220 oncology & carcinogenesis, Child, Preschool, Interferon Type I, Antibody, medicine.symptom, INTERFERON, Adult, medicine.medical_specialty, Adolescent, Critical Illness, Immunology, Population, Aged, Antibodies, Neutralizing, Autoantibodies, COVID-19, Case-Control Studies, Humans, Infant, Infant, Newborn, Interferon-alpha, Young Adult, Alpha interferon, Immunoglobulins, IMMUNITY, Asymptomatic, PATIENT, 03 medical and health sciences, Internal medicine, medicine, Preschool, education, Antibodies, Neutralizing/blood, HOMENS, 030304 developmental biology, ANTINUCLEAR, business.industry, Autoantibody, Case-control study, Antibodies, Neutralizing/immunology, Autoantibodies/blood, Autoantibodies/immunology, COVID-19/mortality, Immunoglobulin G/blood, Immunoglobulin G/immunology, Interferon-alpha/immunology, Newborn, DISTINCT FUNCTIONS, ALPHA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Immunoglobulines
Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University of Paris. P.B. was supported by the FRM (EA20170638020). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation

Published
2021

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