Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of Vitamin D and other UVB-Induced molecules

Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome

Objective To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT). Methods sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes. Results Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7–161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2–212.2) than in HC (10.7 pg/ml [IQR] 4.9–21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT −10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall. Conclusions Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT

IgG 3 + B cells are associated with the development of multiple sclerosis

Objectives Disease‐modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised B‐cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically. Methods We designed a 31‐parameter B‐cell‐focused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the B‐cell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of non‐MS controls. Results Nine distinct CD20+IgD−IgG3+ B‐cell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27−CD38− and CD27+CD38hiCD71hi memory B‐cell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38− double‐negative B‐cell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38− subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched‐memory B‐cell subset. Conclusion We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression

Analysis of human performance as a measure of mental fatigue

In our day to day, we often experience a sense of being tired due to mental or physical workload. Along with that, there is also a feeling of degrading performance, even after the completion of simple tasks. These mental states however, are often not felt consciously or are ignored. This is an attitude that may result in human error, failure, and may lead to potential health problems together with a decrease in quality of life. States of acute mental fatigue may be detected with the close monitoring of certain indicators, such as productivity, performance and health indicators. In this paper, a model and prototype are proposed to detect and monitor acute acute fatigue, based on non-invasive Humancomputer Interaction (HCI). This approach will enable the development of better working environments, with an impact on the quality of life and the work produced.This work was developed in the context of the project CAMCoF - Contextaware Multimodal Communication Framework funded by ERDF - European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT - Funda ção para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within project FCOMP-01-0124-FEDER-028980

Habitable Zones and UV Habitable Zones around Host Stars

Ultraviolet radiation is a double-edged sword to life. If it is too strong, the terrestrial biological systems will be damaged. And if it is too weak, the synthesis of many biochemical compounds can not go along. We try to obtain the continuous ultraviolet habitable zones, and compare the ultraviolet habitable zones with the habitable zones of host stars. Using the boundary ultraviolet radiation of ultraviolet habitable zone, we calculate the ultraviolet habitable zones of host stars with masses from 0.08 to 4.00 \mo. For the host stars with effective temperatures lower than 4,600 K, the ultraviolet habitable zones are closer than the habitable zones. For the host stars with effective temperatures higher than 7,137 K, the ultraviolet habitable zones are farther than the habitable zones. For hot subdwarf as a host star, the distance of the ultraviolet habitable zone is about ten times more than that of the habitable zone, which is not suitable for life existence.Comment: 5 pages, 3 figure

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS

The BES f_0(1810): a new glueball candidate

We analyze the f_0(1810) state recently observed by the BES collaboration via radiative J/\psi decay to a resonant \phi\omega spectrum and confront it with DM2 data and glueball theory. The DM2 group only measured \omega\omega decays and reported a pseudoscalar but no scalar resonance in this mass region. A rescattering mechanism from the open flavored KKbar decay channel is considered to explain why the resonance is only seen in the flavor asymmetric \omega\phi branch along with a discussion of positive C parity charmonia decays to strengthen the case for preferred open flavor glueball decays. We also calculate the total glueball decay width to be roughly 100 MeV, in agreement with the narrow, newly found f_0, and smaller than the expected estimate of 200-400 MeV. We conclude that this discovered scalar hadron is a solid glueball candidate and deserves further experimental investigation, especially in the K-Kbar channel. Finally we comment on other, but less likely, possible assignments for this state.Comment: 11 pages, 4 figures. Major substantive additions, including an ab-initio, QCD-based computation of the glueball inclusive decay width, evaluation of final state effects, and enhanced discussion of several alternative possibilities. Our conclusions are unchanged: the BES f_0(1810) is a promising glueball candidat

Structure-affinity relationships (SARs) and structure-kinetics relationships (SKRs) of Kv11.1 blockers

Medicinal Chemistr

Confinement and Chiral Symmetry Breaking via Domain-Like Structures in the QCD Vacuum

A qualitative mechanism for the emergence of domain structured background gluon fields due to singularities in gauge field configurations is considered, and a model displaying a type of mean field approximation to the QCD partition function based on this mechanism is formulated. Estimation of the vacuum parameters (gluon condensate, topological susceptibility, string constant and quark condensate) indicates that domain-like structures lead to an area law for the Wilson loop, nonzero topological susceptibility and spontaneous breakdown of chiral symmetry. Gluon and ghost propagators in the presence of domains are calculated explicitly and their analytical properties are discussed. The Fourier transforms of the propagators are entire functions and thus describe confined dynamical fields.Comment: RevTeX, 48 pages (32 pages + Appendices A-E), new references added [1,2,4,5] and minor formulae corrected for typographical error

Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation

Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal