Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency

This study shows that mutations affecting the DNA binding domain of IKAROS can impair the interaction with the target DNA sequence thereby preventing heterochromatin and pericentromeric localization (HC-PC) of the protein. Our results also indicate an impairment of pericentromeric localization of IKAROS by overexpression of a truncated variant, caused by an immature stop codon in IKZF1. We also describe an additional variant in TNFSF10, encoding Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL), additionally presented in individuals of Family A. Our results indicate that this variant may impair the TRAIL-induced apoptosis in target cell lines and prohibit the NFκB activation by TRAIL and may act as a modifier in Family A. Introduction Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency with an estimated incidence of 1:50,000–1:25,000. The disease is characterized by recurrent infections, due to a marked decrease in serum IgG commonly in association with reduced IgM and/or IgA. Most CVID-affected individuals have reduced numbers of isotype-switched memory B cells but relative preservation of pre-germinal center B cells (1–3). As a clinically and genetically heterogeneous disorder, CVID has a variable age of onset. In a recent study, an early disease onset (T, c.427C>T, p.Arg143Trp NM_006060.6, rs757521297) in exon 4 of IKZF1, which segregated with the clinical phenotype (Figures 1A,B). The...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Authors: Rombauts A, Abelenda-Alonso G, Cuervo G, Gudiol C, Carratalà J Abstract INTRODUCTION: Despite adequate antibiotic coverage, community-acquired pneumonia (CAP) remains a leading cause of hospitalization and mortality worldwide. It induces both a local pulmonary and a systemic inflammatory response, particularly significant in severe cases. The intensity of the dysregulated host response varies from patient to patient and has a negative impact on survival and other outcomes. AREAS COVERED: This comprehensive review summarizes the pathophysiological aspects of the inflammatory response in CAP, brie...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Reissier S, Cattoir V Abstract INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview on structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely typ...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Publication date: Available online 9 October 2020Source: Journal of Genetics and GenomicsAuthor(s): Huiyun Liu, Ke Wang, Huali Tang, Qiang Gong, Lipu Du, Xinwu Pei, Xingguo Ye
Source: Journal of Genetics and Genomics - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 10 October 2020Source: Meta GeneAuthor(s): Mansour Zamanpoor, Hamid Ghaedi, Mir Davood Omrani
Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research
CONCLUSIONS: Immunohistochemistry seems to be a promising option not only in clinical recognition, but also in the selection and monitoring of treatment effects. However, these methods have not yet recommended for routine clinical use. PMID: 33032462 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
CONCLUSION: In this study, no influence of tear substitutes containing different viscosities of hyaluronic acid on the measurement results of optical coherence tomography could be determined. Therefore, 0.1%, 0.2% and 0.3% hyaluronic acid can be applied to the patient to improve the corneal surface before the examination with optical coherence tomography, without influencing the measurement results of optical coherence tomography. PMID: 33036058 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
CONCLUSIONS: Considering the low number of university students disclosing sexual assaults to health professionals or support services, the results of this survey suggest more work is needed to facilitate greater disclosures to health professionals enabling victims to access the services they need regardless of alcohol use. PMID: 33032303 [PubMed - in process]
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
CONCLUSION: This study found that childhood cancer survivors in New Zealand had a high prevalence of developmental dental abnormalities and it identified potential risk factors related to their cancer treatment. Inequitable access to oral rehabilitation for this patient group argues for a mechanism for consistent improved access to publicly funded dental care across district health boards in New Zealand. PMID: 33032302 [PubMed - in process]
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
Conclusions: (1) Data at our center suggests at least a regional implementation gap in GBS screening and IAP. (2) The decline in the resistance rate ofE. coli for all antimicrobial substances might indicate that the reduction of prenatal antibiotics use is beneficial and that neonatal antibiotic stewardship programs should include pregnant women as well.What is Known:• GBS screening and intrapartum antibiotic prophylaxis led to a 32%-reduction in GBS disease in Germany with a 0.75 (92:122) ratio of early-onset disease to late-onset disease in 2009–2010.• Prenatal antibiotic use might increase the risk of E....
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
Conclusion: By underlining the gaps of knowledge and attitude towards breastfeeding of nurses working in NICUs, this study provides an insight into what needs to be improved, with the aim of promoting higher rates of breastfeeding in the preterm population.What is Known:•Breastfeeding is particularly challenging in the preterm population, despite its universally recognized health benefits.•Improving healthcare professionals ’ knowledge and attitude towards breastfeeding has been shown to be crucial for promoting breastfeeding in NICUs.What is New:•Our results provide useful insight into nurses ’ ...
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
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