Loss-of-function mutations in CARD14 are associated with a severe variant of atopic dermatitis.
J Allergy Clin Immunol. 2018 Sep 21;:
Authors: Peled A, Sarig O, Sun G, Samuelov L, Ma CA, Zhang Y, Dimaggio T, Nelson CG, Stone KD, Freeman AF, Malki L, Vidal LS, Chamarthy LM, Briskin V, Mohamad J, Pavlovski M, Walter JE, Milner JD, Sprecher E
BACKGROUND: Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease which is known to be, at least in part, genetically determined. Mutations in CARD14 have been shown to result in various forms of psoriasis and related disorders.
OBJECTIVE: We aimed to identify rare DNA variants conferring a significant risk for AD through genetic and functional studies in a cohort of patients affected with severe atopic dermatitis.
METHODS: Whole exome and direct gene sequencing, immunohistochemistry, real-time PCR, ELISA and functional assays in human keratinocytes were used.
RESULTS: In a cohort of individuals referred with severe atopic dermatitis, DNA sequencing revealed in 4 patients two rare heterozygous missense mutations in CARD14 encoding the Caspase Recruitment Domain-Containing Protein 14, a major regulator of NF-κB. A dual luciferase reporter assay demonstrated that both mutations exert a dominant loss-of-function effect and result in decreased NF-κB signaling. Accordingly, immunohistochemistry staining showed decreased expression of CARD14 in patient skin as well as decreased levels of activated p65, a surrogate marker for NF-κB activity. CARD14-deficient or mutant-expressing keratinocytes displayed abnormal secretion of key mediators of innate immunity.
CONCLUSIONS: While dominant gain-of-function mutations in CARD14 are associated with psoriasis and related diseases, loss-of-function mutations in the same gene are associated with a severe variant of atopic dermatitis.
PMID: 30248356 [PubMed - as supplied by publisher]
19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.
J Magn Reson Imaging. 2018 Sep 24;:
Authors: Couch MJ, Ball IK, Li T, Fox MS, Biman B, Albert MS
Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic.
LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.
PMID: 30248212 [PubMed - as supplied by publisher]
A comparative evaluation of dental caries status and salivary properties of children aged 5-14 years undergoing treatment for acute lymphoblastic leukemia, type I diabetes mellitus, and asthma - In vivo.
J Indian Soc Pedod Prev Dent. 2018 Jul-Sep;36(3):283-289
Authors: Dubey S, Saha S, Tripathi AM, Bhattacharya P, Dhinsa K, Arora D
Background: The subjective sensation of dry mouth, xerostomia, is a well-recognized problem in adults, however, relatively little attention has been paid to this issue in children. Xerostomia commonly occurs as an adverse effect of drugs in asthma and leukemia, which alter the composition and flow of saliva and systemic diseases, including diabetes. It decreases the oral pH and significantly increases the development of plaque and dental caries.
Aim: This study aims to evaluate and compare the dental caries status and salivary properties of children aged 5-14 years undergoing treatment for acute lymphoblastic leukemia, type 1 diabetes mellitus, and asthma - in vivo.
Materials and Methods: The study was divided into two parts: Part I: Oral examination was performed and dental caries status Decayed, Missing, Filled Teeth/ decayed, extraction, filled teeth (DMFT/deft) was noted and Part II: Salivary analysis was performed by GC Saliva-Check BUFFER kit to check for hydration, viscosity, pH of saliva, salivary flow, and buffering capacity.
Statistical Analysis: All statistical analysis was performed using the SPSS 21 statistical software version. Inferential statistics were performed using Chi-square test and ANOVA. Post hoc pairwise comparison was done using Post hoc Tukey's test.
Results: The prevalence of mean DMFT/deft with regard to salivary properties was highest in leukemic patients followed in descending order by diabetic and asthmatic patients.
Conclusions: Leukemic patients had significantly higher caries and decreased salivary properties while asthmatic patients showed the least caries prevalence and best salivary properties.
PMID: 30246751 [PubMed - in process]
[Evaluation of asthma awareness among teachers in Bursa].
Tuberk Toraks. 2018 Jun;66(2):150-155
Authors: Aydın Güçlü Ö, Karadağ M, Macunluoğlu AC, Demirdöğen Çetinoğlu E, Ediger D
Introduction: The purpose of this study was to elucidate the asthma knowledge level of primary-secondary school teachers in Bursa, and factors associated with this subject.
Materials and Methods: In our study 1812 teachers from 64 randomly selected primary schools in Bursa were included.
Result: It was known by the vast majority of participants that asthma symptoms, asthma is not a contagious disease and may be familial, medications taken by inhalation. It was known by 64.1% of the teachers that asthmatic children do not mind doing sports. Approximately one of the two teachers knew that the medication were not addictive.
Conclusions: The knowledge level of the teachers was related to female gender and age. We think that an asthma education program is needed for Turkish teachers to increase their understanding about what asthma is, its impact and how to meet the needs of a child with asthma to achieve improved wellbeing and school attendance.
PMID: 30246659 [PubMed - in process]
Direct health-care costs for children diagnosed with genetic diseases are significantly higher than for children with other chronic diseases.
Genet Med. 2018 Sep 24;:
Authors: Marshall DA, Benchimol EI, MacKenzie A, Duque DR, MacDonald KV, Hartley T, Howley H, Hamilton A, Gillespie M, Malam F, Boycott KM
PURPOSE: We aimed to estimate direct health-care costs and physician utilization for a cohort of children diagnosed with genetic diseases.
METHODS: Retrospective cohort study using population-based provincial health administrative data for children with genetic diseases (n = 255) compared with three matched cohorts (asthma n = 1275, diabetes n = 255, general population n = 1275). We estimated direct health-care costs and resource use 5 years after diagnosis in five categories: physician billing, same day surgery, emergency, inpatient hospitalizations, and home care.
RESULTS: During the postdiagnostic period, annual mean total costs for the genetic disease cohort were significantly higher than all other cohorts. Annual mean total costs for all cohorts were highest in the year after diagnosis with costs for the genetic disease cohort between 4.54 and 19.76 times higher during the 5 years. Inpatient hospitalizations and physician billing accounted for the majority of costs. The genetic disease cohort received more care from specialists, whereas the chronic disease cohorts received more care from general practitioners.
CONCLUSION: Direct health-care costs for children with genetic diseases are significantly higher than children with/without a chronic disease, particularly in the year after diagnosis. These findings are important when considering resource allocation and funding prioritization for children with genetic diseases.
PMID: 30245512 [PubMed - as supplied by publisher]