Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features... Show moreChronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features. CNO pathophysiology, including the key drivers of inflammation, remains largely unknown. For pediatric CNO, a role for pro-inflammatory cytokine dysregulation has been proposed, but studies in adults are scarce. We therefore provide immunological characterization of adult CNO. Cross-sectional study in our referral center including adult CNO patients (n = 172) and healthy controls (n = 65). Inflammation parameters and systemic inflammatory based scores(SIBS, including neutrophil/lymphocyte ratio [NLR] and systemic immune inflammation index [SII]) were compared between groups. Cytokine expression was explored with electrochemiluminescent immunoassays in 33 patients, eight healthy controls and 21 osteoporosis patients. Routine inflammation markers were higher in patients than in controls, but generally remained within reference range. Systemic inflammation was more pronounced in patients with additional vertebral involvement as compared to those osteitis in the anterior chest wall alone, in patients with comorbid pustulosis palmoplantaris or psoriasis, and in patients with strongly rather than moderately increased lesional uptake on nuclear imaging. SII was elevated in CNO patients too, but NLR was not. Cytokine expression was generally nondifferential between patients and both control groups, and patients displayed low absolute concentrations of pro-inflammatory cytokines. In this adult CNO cohort, systemic inflammation was generally subtle, but more pronounced in patients with vertebral lesions, associated skin disease, and strongly increased uptake on nuclear imaging. SII was increased in patients compared to healthy controls. Contrasting pediatric studies, we found no increased expression of the pro-inflammatory cytokines that have been proposed to drive the inflammatory cascade, like interleukin-6, -8, and -17 (IL-6, IL-8, and IL-17), and tumor necrosis a (TNF-a). Further studies are needed to evaluate the use of SII in diagnosis and monitoring of CNO, and elucidate the role of cytokine dysregulation in adult disease.(C) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. Show less
Cunha, P.; Petit, E.; Coutelier, M.; Coarelli, G.; Mariotti, C.; Faber, J.; ... ; Durr, A. 2023
Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it... Show moreAlthough the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes—CACNA1A, ITPR1, SPTBN2, and KCNC3—were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist. Show less
Rieffe, C.; Broekhof, E.; Kouwenberg, M.; Faber, J.; Tsutsui, M.M.; Güroğlu, B. 2016
The distinction between proactive and reactive functions of aggression is one of the most common divisions when investigating aggression among children and adolescents. To date, self-report is the... Show moreThe distinction between proactive and reactive functions of aggression is one of the most common divisions when investigating aggression among children and adolescents. To date, self-report is the least used measurement, despite existing literature supporting the view that the best informant regarding internal processes and motives are children themselves. The main aim of this study was to examine the construct and concurrent validity of a new self-report questionnaire, which aims to disentangle acts of reactive vs. proactive aggression that are most common within the daily lives of children. We examined the self-report measure among 578 children (313 girls, 265 boys, mean age 11 years, range 9-13 years). Most children (90% boys; 85% girls) reported at least one act of aggression over the last four weeks. Furthermore, the outcomes support the two-factor structure (reactive and proactive aggression) and the questionnaire showed good concurrent and discriminant validity with measures for emotional and social functioning. This study validates the use of the self-report instrument for reactive and proactive aggression and demonstrates that children can successfully distinguish between their own motives for reactive and proactive forms of aggressive behaviours. Show less
Bastiaansen, T.; Ewing, M.; Boer, H. de; Kraan, T.V.; Vries, M. de; Peters, E.; ... ; Nossent, A.Y. 2012
