ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. Results: We found the heterozygous missense variant in the ɑkinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder

Body mass index and progressive hand osteoarthritis: data from the Oslo hand osteoarthritis cohort

Pathophysiology and treatment of rheumatic disease

Cardiorespiratory Fitness and Cardiovascular Risk in Patients With Ankylosing Spondylitis: A Cross-Sectional Comparative Study

Pathophysiology and treatment of rheumatic disease

Responsiveness and Interpretability of 2 Measures of Physical Function in Patients With Spondyloarthritis

Background. Maintenance or improvement of physical function is an important treatment target in the management of patients with axial spondyloarthritis (axSpA); measurement tools that can detect changes in physical function are therefore important.Objectives. The objective of this study was to compare responsiveness and interpretability of the patient-reported Bath Ankylosing Spondylitis Functional Index (BASFI) and the Ankylosing Spondylitis Performed-Based Improvement (ASPI) in measuring change in physical function after exercise in patients with axSpA.Design. This was a sub-study of 58 patients nested within a randomized controlled trial comparing the effect of 12 weeks of exercise with usual care.Methods. Responsiveness and interpretability were assessed according to the Consensus-based Standards for the selection of health status Measurement Instrument. Responsiveness was assessed by testing 8 predefined hypotheses for ASPI and BASFI. Interpretability was assessed by: (1) using patients' reported change as an anchor ("a little better" = minimal important change) and (2) by categorizing patients with a 20% improvement as responders.Results. For ASPI and BASFI, 5 of 8 (63%) versus 2 of 8 (25%) of the predefined hypotheses for responsiveness were confirmed. The minimal important change values for improvement in physical function were 3.7 seconds in ASPI and 0.8 points (on a scale from 0 to 10) for BASFI. In the intervention group, 21 of 30 (70%) and 13 of 30 (43%) of the patients were categorized as responders measured with ASPI and BASFI, respectively. There was a tendency towards a floor effect in BASFI, as 8 of 58 (14%) patients scored the lowest value at baseline.Limitations. This study was limited by its moderate sample size.Conclusions. Our findings suggest that ASPI is preferable over BASFI when evaluating physical function after exercise interventions in patients with axSpA.Orthopaedics, Trauma Surgery and Rehabilitatio

Development of a Framework Identifying Domains and Elements of Importance for Arthritis Rehabilitation

Background: Rehabilitation is effective and beneficial for patients with arthritis. The lack of a common structure for describing the content of rehabilitation makes it difficult to compare, transfer and implement research evidence into clinical practice. Objective: To develop a framework comprising domains and elements of importance when describing arthritis rehabilitation. Methods: On the basis of a systematic literature search and review, the framework was developed through a 9-step development process, including 5 Delphi consensus rounds within the Scandinavian Team Arthritis Register - European Team Initiative for Care Research (STAR-ETIC) collaboration, a group of clinicians, researchers and patients from northern Europe. Results: Based on Donabedian's healthcare model, the International Classification of Function, Disability and Health, and a rehabilitation model by D. T. Wade, 4 domains (context, structure, process and outcome) were defined. Within each domain, the most important and relevant key elements for describing rehabilitation were selected. This framework contains 1 key element under context, 9 under structure, 3 under process, and 9 under outcome. Conclusion: The STAR-ETIC framework can be used to describe arthritis rehabilitation, by emphasizing key elements in 4 main domains. A common framework may facilitate comparisons of rehabilitation programmes across countries and different levels of care, and may improve the implementation of rehabilitation research in clinical practice

Review: Comparative methane production in mammalian herbivores

Methane (CH4) production is a ubiquitous, apparently unavoidable side effect of fermentative fibre digestion by symbiotic microbiota in mammalian herbivores. Here, a data compilation is presented of in vivo CH4 measurements in individuals of 37 mammalian herbivore species fed forage-only diets, from the literature and from hitherto unpublished measurements. In contrast to previous claims, absolute CH4 emissions scaled linearly to DM intake, and CH4 yields (per DM or gross energy intake) did not vary significantly with body mass. CH4 physiology hence cannot be construed to represent an intrinsic ruminant or herbivore body size limitation. The dataset does not support traditional dichotomies of CH4 emission intensity between ruminants and nonruminants, or between foregut and hindgut fermenters. Several rodent hindgut fermenters and nonruminant foregut fermenters emit CH4 of a magnitude as high as ruminants of similar size, intake level, digesta retention or gut capacity. By contrast, equids, macropods (kangaroos) and rabbits produce few CH4 and have low CH4 : CO2 ratios for their size, intake level, digesta retention or gut capacity, ruling out these factors as explanation for interspecific variation. These findings lead to the conclusion that still unidentified host-specific factors other than digesta retention characteristics, or the presence of rumination or a foregut, influence CH4 production. Measurements of CH4 yield per digested fibre indicate that the amount of CH4 produced during fibre digestion varies not only across but also within species, possibly pointing towards variation in microbiota functionality. Recent findings on the genetic control of microbiome composition, including methanogens, raise the question about the benefits methanogens provide for many (but apparently not to the same extent for all) species, which possibly prevented the evolution of the hosting of low-methanogenic microbiota across mammals