Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds.

Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular

Kano-based mapping of innovation strategies for renewable energy alternatives using hybrid interval type-2 fuzzy decision-making approach

In this study, it is aimed to identify innovative strategies for different renewable energy alternatives. In this context, the criteria that affect the effectiveness of renewable energy investments are first analyzed with the IT2 fuzzy DEMATEL. Then, 16 different strategies based on the Kano model are created. Also, appropriate innovative strategies have been determined for 5 different renewable energy types with IT2 fuzzy TOPSIS. Additionally, these alternatives are also ranked by using IT2 fuzzy VIKOR to make a comparative evaluation. Moreover, Monte Carlo simulation technique has been implemented to check and understand the objectiveness of the evaluation results. It is concluded that all results are quite coherent. The findings indicate that for the technical requirement dimension, the most important criteria are the availability of equipment and technological infrastructure. Regarding the customer satisfaction, it is identified that the possibility of sustainable consumption and competitive price play a key role. It is also determined that wind and solar energy alternatives are quite appropriate for all kinds of market conditions to create innovative strategies. For the biomass energy investments, new products should be developed by making radical innovations. In addition, it is seen that the hydroelectric energy alternative is not very suitable for its current form due to the low efficiency. Therefore, a detailed financial analysis should be carried out to solve this problem. Finally, as for geothermal energy investments, technical requirements should be satisfied to make more effective investments.Shanxi Philosophy and Social Science Foundation; Shanxi Research Foundation for Returned Overseas Student