Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope

The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of SLE that builds upon the existing treatment guideline for adults living with SLE published in 2017. This will incorporate advances in the assessment, diagnosis, monitoring, non-pharmacological and pharmacological management of SLE. General approaches to management as well as organ-specific treatment, including lupus nephritis and cutaneous lupus, will be covered. This will be the first guideline in SLE using a whole life course approach from childhood through adolescence and adulthood. The guideline will be developed with people with SLE as an important target audience in addition to healthcare professionals. It will include guidance related to emerging approved therapies and account for National Institute for Health and Care Excellence Technology Appraisals, National Health Service England clinical commissioning policies and national guidance relevant to SLE. The guideline will be developed using the methods and rigorous processes outlined in ‘Creating Clinical Guidelines: Our Protocol’ by the British Society for Rheumatology

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Composition of woody species in a dynamic forest-woodland-savannah mosaic in Uganda: implications for conservation and management

Forest¿woodland¿savannah mosaics are a common feature in the East African landscape. For the conservation of the woody species that occur in such landscapes, the species patterns and the factors that maintain it need to be understood. We studied the woody species distribution in a forest¿woodland¿savannah mosaic in Budongo Forest Reserve, Uganda. The existing vegetation gradients were analyzed using data from a total of 591 plots of 400 or 500 m2 each. Remotely sensed data was used to explore current vegetation cover and the gradients there in for the whole area. A clear species gradient exists in the study area ranging from forest, where there is least disturbance, to wooded grassland, where frequent fire disturbance occurs. Most species are not limited to a specific part of the gradient although many show a maximum abundance at some point along the gradient. Fire and accessibility to the protected area were closely related to variation in species composition along the ordination axis with species like Cynometra alexandri and Uvariopsis congensis occurring at one end of the gradient and Combretum guenzi and Lonchocarpus laxiflorus at the other. The vegetation cover classes identified in the area differed in diversity, density and, especially, basal area. All vegetation cover classes, except open woodland, had indicator species. Diospyros abyssinica, Uvariopsis congensis, Holoptelea grandis and all Celtis species were the indicator species for the forest class, Terminalia velutina and Albizia grandbracteata for closed woodland, Grewia mollis and Combretum mole for very open woodland and Lonchocarpus laxiflorus, Grewia bicolor and Combretum guenzi for the wooded grassland class. Eleven of the species occurred in all cover classes and most of the species that occurred in more than one vegetation cover class showed peak abundance in a specific cover class. Species composition in the study area changes gradually from forest to savannah. Along the gradient, the cover classes are distinguishable in terms of species composition and vegetation structure. These classes are, however, interrelated in species composition. For conservation of the full range of the species within this East African landscape, the mosaic has to be managed as an integrated whole. Burning should be varied over the area with the forest not being burnt at all and the wooded grassland burnt regularly. The different vegetation types that occur between these two extremes should be maintained using a varied fire regim

Differential effects of thyroid hormone manipulation and ß adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T(3)) in on the first day of life. T(3) and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective beta3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T(3) (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T(3) administration raised plasma T(3) concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T(3) administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets

Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD