Development of the International Severe Asthma Registry (ISAR) : A Modified Delphi Study

This study is cofunded by Optimum Patient Care Global and AstraZeneca.Peer reviewedPostprin

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Gen SPTBN2; Neurodegeneració; Atàxia congènita no progressivaGen SPTBN2; Neurodegeneración; Ataxia congénita no progresivaSPTBN2 gene; Neurodegeneration; Non-progressive congenital ataxia(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by β-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R+D+I Plan co-funded with ERDF funds [Grant PI18/00147], and by the Generalitat Valenciana [Grant PROMETEO/2018/135]. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014−2020). P.S. had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. A.S.-M. has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)

Estudio de usabilidad y Validación piloto de un test del reconocimiento de emociones por ordenador para adultos mayores con enfermedad de Alzheimer y deterioro cognitivo leve de tipo amnésico

[EN] This study aimed to carry out a pilot validation of Affect-GRADIOR, a computer-based emotion recognition test, with older adults. The study evaluated its usability, reliability and validity for the screening of people with Alzheimer´s disease (AD) and amnestic mild cognitive impairment (aMCI). The test was administered to 212 participants (76.37 ± 6.20 years) classified into three groups (healthy controls, n = 69; AD, n = 84; and aMCI, n = 59) on the basis of detailed neurological, neuropsychological, laboratory and neuro-imaging evidence. Data on usability were collected by means of a questionnaire and automated evaluation. The validated test comprised 53 stimuli and 7 practice items (one per emotion). Participants reported that Affect-GRADIOR was accessible and user-friendly. It had high internal consistency (ordinal Cronbach's α = 0.96). Test-retest reliability correlations were significant and robust (r = 0.840, p < 0.001). Exploratory factor analysis supported a seven-factor model of the emotions assessed (neutral expression, happiness, surprise, disgust, sadness, anger and fear). Receiver operating characteristic curve analyses suggested that the test discriminated healthy older adults from AD and aMCI cases. Correct answer score improved MMSE predictive power from 0.547 to 0.560 (Cox & Snell R2, p = 0.012), and Affect-GRADIOR speed of processing score improved MMSE predictive power from 0.547 to 0.563 (Cox & Snell R2, p = 0.010). Affect-GRADIOR is a valid instrument for the assessment of the facial recognition of emotions in older adults with and without cognitive impairment

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by β-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2 -associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2 -associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanis