Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Attentional deficits in Alzheimer’s: investigating the role of acetylcholine with computational modelling

Attention is a very important cognitive process that is employed for many actions in our everydaylife (e.g. watching television, reading a paper, washing our face, eatingand so on). It is therefore essential to investigate further the underlying mechanisms inneuro-degenerativeconditions, like Alzheimer’s disease, in which ourattentional abilities are reduced(Festa, Heindel, & Ott, 2010; Foster, Behrmann, & Stuss, 1999; Hao et al., 2005; Porter, Tales, et al., 2010; Redel et al., 2012; A. Tales et al., 2002a; Vallejo et al., 2016).Alzheimer’s disease is a condition that can take severalyears if not decades from the time it starts to the time the full symptoms are shown (Tijms & Visser, 2018).In those years of disease progression,there are a number of pathological processes that are taking place, however one of the starting point of the pathologyis believed to be the aggregation of βamyloids into plaques(Gordon et al., 2018; Tijms & Visser, 2018). Irrespective ofthe amount of research that has taken place,manyquestionsremain on how the disease unfolds and how to identify individual’s position in the disease’s trajectory(Gordon et al., 2018; Ryman et al., 2014)