Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis—Insights From Other Diseases

Regulatory T cells (Tregs) are believed to be dysfunctional in autoimmunity. Juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) result from a loss of normal immune regulation in specific tissues such as joints or muscle and skin, respectively. Here, we discuss recent findings in regard to Treg biology in oligo-/polyarticular JIA and JDM, as well as what we can learn about Treg-related disease mechanism, treatment and biomarkers in JIA/JDM from studies of other diseases. We explore the potential use of Treg immunoregulatory markers and gene signatures as biomarkers for disease course and/or treatment success. Further, we discuss how Tregs are affected by several treatment strategies already employed in the therapy of JIA and JDM and by alternative immunotherapies such as anti-cytokine or co-receptor targeting. Finally, we review recent successes in using Tregs as a treatment target with low-dose IL-2 or cellular immunotherapy. Thus, this mini review will highlight our current understanding and identify open questions in regard to Treg biology, and how recent findings may advance biomarkers and new therapies for JIA and JDM

Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus

Introduction: One-dimensional rating scales are widely used in research and in the clinic to assess individuals’ perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli. Methods: To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors. Results: Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales. Discussion: These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli

Denoising task-related fMRI:Balancing noise reduction against signal loss

Preprocessing fMRI data requires striking a fine balance between conserving signals of interest and removing noise. Typical steps of preprocessing include motion correction, slice timing correction, spatial smoothing, and high-pass filtering. However, these standard steps do not remove many sources of noise. Thus, noise-reduction techniques, for example, CompCor, FIX, and ICA-AROMA have been developed to further improve the ability to draw meaningful conclusions from the data. The ability of these techniques to minimize noise while conserving signals of interest has been tested almost exclusively in resting-state fMRI and, only rarely, in task-related fMRI. Application of noise-reduction techniques to task-related fMRI is particularly important given that such procedures have been shown to reduce false positive rates. Little remains known about the impact of these techniques on the retention of signal in tasks that may be associated with systemic physiological changes. In this paper, we compared two ICA-based, that is FIX and ICA-AROMA, two CompCor-based noise-reduction techniques, that is aCompCor, and tCompCor, and standard preprocessing using a large (n = 101) fMRI dataset including noxious heat and non-noxious auditory stimulation. Results show that preprocessing using FIX performs optimally for data obtained using noxious heat, conserving more signals than CompCor-based techniques and ICA-AROMA, while removing only slightly less noise. Similarly, for data obtained during non-noxious auditory stimulation, FIX noise-reduction technique before analysis with a covariate of interest outperforms the other techniques. These results indicate that FIX might be the most appropriate technique to achieve the balance between conserving signals of interest and removing noise during task-related fMRI.</p

Dissociation between individual differences in self-reported pain intensity and underlying fMRI brain activation

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related to interindividual differences in pain was not detected, despite clear sensitivity of the Blood Oxygenation Level-Dependent (BOLD) signal to small differences in noxious stimulus intensities within individuals. These findings suggest fMRI may not be a useful objective measure to infer reported pain intensity

Tungiasis: high prevalence, parasite load, and morbidity in a rural community in Lagos State, Nigeria

Background: Tungiasis is common in resource-poor populations throughout Latin America, the Caribbean, and sub-Saharan Africa, but epidemiologic data from Africa on this ectoparasitosis are scarce.\ud \ud Methods: A cross-sectional study was carried out in a representative sample of a rural community in Lagos State, 54 km west of Lagos (Nigeria). In the dry season, 142 households of the community were randomly selected and visited. Family members were examined for the presence of tungiasis. The localization, number, and stage of penetrated fleas, as well as the associated morbidity, were documented.\ud \ud Results: Five hundred and fifty-seven individuals were examined, 299 (53.7%) males and 258 (46.3%) females. In total, 252 (45.2%; 95% confidence interval, 41.1–49.5) were infested with Tunga penetrans. The prevalence was highest between the ages of 5 and 14 years, decreased in adults, and increased again in the elderly. There was no statistically significant difference between the prevalence in males and females (47.2% vs. 43.0%; P = 0.3). Almost 95% of lesions were localized on the feet. Ten per cent of individuals presented with sand fleas on the hands and elbows. The median parasite load was six (interquartile range, 3–16). Individuals aged 60 years or over had significantly more lesions (median of 41 lesions; P < 0.01). About one-third of the study participants found it difficult to walk; in 10% of cases, fissures were present. Superinfection was common.\ud \ud Conclusions: The prevalence of tungiasis and the parasite load were high, and the severity of the disease was considerable. The prevalence and parasite burden showed a characteristic distribution. In western Nigeria, tungiasis needs to be regarded as an important public health problem