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- Lévy, Romain, et al.
(author)
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
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Journal article (peer-reviewed)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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- Naranjo, A., et al.
(author)
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Smokers and non-smokers with rheumatoid arthritis have similar clinical status : data from the multinational QUEST-RA database
- 2010
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In: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 28:6, s. 820-827
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Journal article (peer-reviewed)abstract
- Objectives To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. Methods The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RE), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as "never smoked", "currently smoking" and "former smokers". Patient groups with different smoking status were compared for demographic and RA measures. Results Among the 7,307 patients with smoking data available, status as "never smoked," "current smoker" and "former smoker" were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32; 1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41; 1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). Conclusion RA patients who had ever smoked were more likely to have RF and nodules, hut values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
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- Sabbagh, H. J., et al.
(author)
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A multi-country study on the impact of sex and age on oral features of COVID-19 infection in adolescents and young adults
- 2022
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In: Bmc Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Oral diseases are features of COVID-19 infection. There is, however, little known about oral diseases associated with COVID-19 in adolescents and young adults (AYA). Therefore, the aim of this study was to assess oral lesions' association with COVID-19 infection in AYA; and to identify if sex and age will modify these associations. Methodology Data was collected for this cross-sectional study between August 2020 and January 2021 from 11-to-23 years old participants in 43-countries using an electronic validated questionnaire developed in five languages. Data collected included information on the dependent variables (the presence of oral conditions- gingival inflammation, dry mouth, change in taste and oral ulcers), independent variable (COVID-19 infection) and confounders (age, sex, history of medical problems and parents' educational level). Multilevel binary logistic regression was used for analysis. Results Complete data were available for 7164 AYA, with 7.5% reporting a history of COVID-19 infection. A significantly higher percentage of participants with a history of COVID-19 infection than those without COVID-19 infection reported having dry mouth (10.6% vs 7.3%, AOR = 1.31) and taste changes (11.1% vs 2.7%, AOR = 4.11). There was a significant effect modification in the association between COVID-19 infection and the presence of dry mouth and change in taste by age and sex (P = 0.02 and < 0.001). Conclusion COVID-19 infection was associated with dry mouth and change in taste among AYA and the strength of this association differed by age and sex. These oral conditions may help serve as an index for suspicion of COVID-19 infection in AYA.
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- Sabbagh, H. J., et al.
(author)
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Anxiety among Adolescents and Young Adults during COVID-19 Pandemic: A Multi-Country Survey
- 2022
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:17
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Journal article (peer-reviewed)abstract
- (1) Background: Adolescents-and-young-adults (AYA) are prone to anxiety. This study assessed AYA’s level of anxiety during the COVID-19 pandemic; and determined if anxiety levels were associated with country-income and region, socio-demographic profile and medical history of individuals. (2) Methods: A survey collected data from participants in 25 countries. Dependent-variables included general-anxiety level, and independent-variables included medical problems, COVID-19 infection, age, sex, education, and country-income-level and region. A multilevel-multinomial-logistic regression analysis was conducted to determine the association between dependent, and independent-variables. (3) Results: Of the 6989 respondents, 2964 (42.4%) had normal-anxiety, and 2621 (37.5%), 900 (12.9%) and 504 (7.2%) had mild, moderate and severe-anxiety, respectively. Participants from the African region (AFR) had lower odds of mild, moderate and severe than normal-anxiety compared to those from the Eastern-Mediterranean-region (EMR). Also, participants from lower-middle-income-countries (LMICs) had higher odds of mild and moderate than normal-anxiety compared to those from low-income-countries (LICs). Females, older-adolescents, with medical-problems, suspected-but-not-tested-for-COVID-19, and those with friends/family-infected with COVID-19 had significantly greater odds of different anxiety-levels. (4) Conclusions: One-in-five AYA had moderate to severe-anxiety during the COVID-19-pandemic. There were differences in anxiety-levels among AYAs by region and income-level, emphasizing the need for targeted public health interventions based on nationally-identified priorities. © 2022 by the authors.
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- Sabbagh, H. J., et al.
(author)
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Cigarettes' use and capabilities-opportunities-motivation-for-behavior model: a multi-country survey of adolescents and young adults
- 2022
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In: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 10
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Journal article (peer-reviewed)abstract
- The use of cigarettes among adolescents and young adults (AYA) is an important issue. This study assessed the association between regular and electronic-cigarettes use among AYA and factors of the Capability-Motivation-Opportunity-for-Behavior-change (COM-B) model. A multi-country survey was conducted between August-2020 and January-2021, Data was collected using the Global-Youth-Tobacco-Survey and Generalized-Anxiety-Disorder-7-item-scale. Multi-level logistic-regression-models were used. Use of regular and electronic-cigarettes were dependent variables. The explanatory variables were capability-factors (COVID-19 status, general anxiety), motivation-factors (attitude score) and opportunity-factors (country-level affordability scores, tobacco promotion-bans, and smoke free-zones) controlling for age and sex. Responses of 6,989-participants from 25-countries were used. Those who reported that they were infected with COVID-19 had significantly higher odds of electronic-cigarettes use (AOR = 1.81, P = 0.02). Normal or mild levels of general anxiety and negative attitudes toward smoking were associated with significantly lower odds of using regular-cigarettes (AOR = 0.34, 0.52, and 0.75, P < 0.001) and electronic-cigarettes (AOR = 0.28, 0.45, and 0.78, P < 0.001). Higher affordability-score was associated with lower odds of using electronic-cigarettes (AOR = 0.90, P = 0.004). Country-level-smoking-control policies and regulations need to focus on reducing cigarette affordability. Capability, motivation and opportunity factors of the COM-B model were associated with using regular or electronic cigarettes.
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