EVALUATION OF THE COUPLING BETWEEN ELECTROENCEPHALOGRAM (EEG) AND GALVANIC SKIN RESPONSE (GSR) SIGNALS VERSUS THE COMPLEX STRUCTURE OF MUSIC

Since skin activity, like other organs, is controlled by the brain, we decoded the correlation among the brain and skin responses in auditory stimulation by complexity-based analysis of EEG and GSR signals. Three pieces of music were selected according to the difference in the fractal exponent and sample entropy of embedded noises in them. We calculated the fractal dimension and sample entropy of EEG and GSR signals for 11 subjects in rest and response to these music pieces. The correlation coefficients of 0.9525 and 0.9822 in the case of fractal dimension and sample entropy demonstrated a strong correlation between the complexities of the GSR and EEG signals. Therefore, we can state that the skin and brain responses are coupled. This method can be applied to evaluate the relationship between the human brain and other organs.

The impact of chronic co-exposure to different heavy metals on small fibers of peripheral nerves. A study of metal industry workers

Background Chronic exposure to heavy metals affects various organs, among them the brain and peripheral nerves. Polyneuropathy is mainly length-dependent with predominantly sensory symptoms. There have been few studies on small fiber neuropathy due to heavy metal intoxication. Methods We investigated 41 metal industry workers, mean age 51.3 ± 10.5 years, with at least 5 years’ professional exposure to heavy metals, and 36 age- and sex-matched healthy controls. We performed neurological examinations, and assessed blood levels of cadmium, lead, and zinc protoporphyrin, urine levels of arsenic, standard, sensory and motor electrophysiological tests in the ulnar and peroneal nerves, sympathetic skin responses from the palm and foot, and quantitative sensation testing from dermatomes C8 and S1. Discussion The results of standard conduction tests of all nerves significantly differed between groups. The latency of sympathetic skin responses achieved from the foot was also statistically significantly prolonged in the study group. Significant differences were seen in both C8 and S1 regions for temperature and pain thresholds, and for vibratory threshold only in the S1 region, while the dispersions of low and high temperatures were important exclusively in the C8 region. Conclusions We can conclude that co-exposure to many heavy metals results in explicit impairment of peripheral nerves. The lesion is more pronounced within small fibers and is predominantly connected with greater impairment of temperature-dependent pain thresholds. The evaluation of small fiber function should be considered in the early diagnosis of toxic polyneuropathy or in low-dose exposure to heavy metals.

A molecularly defined skin test reagent for the diagnosis of bovine tuberculosis compatible with vaccination against Johne’s Disease

Tuberculin Purified Protein Derivatives (PPDs) exhibit multiple limitations: they are crude extracts from mycobacterial cultures with largely unknown active components; their production depends on culture of mycobacteria requiring expensive BCL3 production facilities; and their potency depends on the technically demanding guinea pig assay. To overcome these limitations, we developed a molecularly defined tuberculin (MDT) by adding further antigens to our prototype reagent composed of ESAT-6, CFP-10 and Rv3615c (DIVA skin test, DST). In vitro screening using PBMC from infected and uninfected cattle shortlisted four antigens from a literature-based list of 18 to formulate the MDT. These four antigens plus the previously identified Rv3020c protein, produced as recombinant proteins or overlapping synthetic peptides, were formulated together with the three DST antigens into the MDT to test cattle experimentally and naturally infected with M. bovis, uninfected cattle and MAP vaccinated calves. We demonstrated significant increases in MDT-induced skin responses compared to DST in infected animals, whilst maintaining high specificity in unvaccinated or MAP vaccinated calves. Further, MDT can also be applied in in vitro blood-based interferon-gamma release assays. Thus, MDT promises to be a robust diagnostic skin and blood test reagent overcoming some of the limitations of PPDs and warrants full validation.

Topically applied methyl nicotinate evokes a temporary inflammation on human skin

Some challengers such as methylnicotinate (MN) have been used in human models to study the anti-inflammatory effect of topical formulations. However, MN skin responses are still poorly understood and widely varied. In the present study we aim to contribute to better characterise those responses. Eight healthy participants were selected. All procedures were approved by the institutional Ethics Committee. Two aqueous MN dilutions (0.5% and 1.0%) were left in contact for 1 minute in the anterior forearm skin. Following exposure, skin reactions were clinically and biometrically assessed at 30, 60 and 120 minutes and compared with baseline. Measurements involved the ICDRG clinical score scale and select analytical technologies - laser Doppler flowmetry, Polarised Spectroscopy, Transepidermal Water Loss Meter, and High Resolution Sonography. Results have shown that MN application evoked a maximal response at 30 minutes with an increase in the ICDRG score between 1-2. Significant changes in TEWL and microcirculation were observed, as was an increased dermal hypoecogenicity (edema), detected by HRS. These effects are compatible with a localised short-duration inflammation and reinforce the interest of MN to be used as a safe and controllable challenger in human models.

IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors

ObjectivesTo determine the relationship between synovial versus skin transcriptional/histological profiles in patients with active psoriatic arthritis (PsA) and explore mechanistic links between diseased tissue pathology and clinical outcomes.MethodsTwenty-seven active PsA patients were enrolled in an observational/open-label study and underwent biopsies of synovium and paired lesional/non-lesional skin before starting anti-tumour necrosis factor (TNF) (if biologic-naïve) or ustekinumab (if anti-TNF inadequate responders). Molecular analysis of 80-inflammation-related genes and protein levels for interleukin (IL)-23p40/IL-23p19/IL-23R were assessed by real-time-PCR and immunohistochemistry, respectively.ResultsAt baseline, all patients had persistent active disease as per inclusion criteria. At primary end-point (16-weeks post-treatment), skin responses favoured ustekinumab, while joint responses favoured anti-TNF therapies. Principal component analysis revealed distinct clustering of synovial tissue gene expression away from the matched skin. While IL12B, IL23A and IL23R were homogeneously expressed in lesional skin, their expression was extremely heterogeneous in paired synovial tissues. Here, IL-23 transcriptomic/protein expression was strongly linked to patients with high-grade synovitis who, however, were not distinguishable by conventional clinimetric measures.ConclusionsPsA synovial tissue shows a heterogeneous IL-23 axis profile when compared with matched skin. Synovial molecular pathology may help to identify among clinically indistinguishable patients those with a greater probability of responding to IL-23 inhibitors.