Intentional and unintentional medication nonadherence in psoriasis: the role of patients’ medication beliefs and habit strength [abstract only]

The accurate diagnosis of psoriasis has remained a challenge, as no disease-specific biomarkers have yet been identified. Currently, the diagnosis of chronic inflammatory diseases relies mainly on the assessment of visible symptoms or the histological features of the biopsy. This approach is heavily reliant on the experience of the clinician and, therefore, may lead to misdiagnosis as there are numerous different chronic inflammatory skin diseases that may present similar clinical features. Hence, the need for diagnostic biomarkers is clear. Although different investigations have reported the discovery of potential psoriasis biomarkers, still no accurate and reliable biomarker is available. Rather than searching for a single valid biomarker, we propose that applying a multicomponent bio-marker-based approach would result in a higher degree of success and translation into clinical practice. An extensive review of published studies to identify the most relevant psoriasis-specific biomarker candidates was conducted. This led us to conclude that the expression levels of specific genes in the skin hold the most promise as discriminatory biomarkers, resulting in the selection of five genes, the expression levels of which have been demonstrated to be exclusive for psoriasis vulgaris. We first conducted a preliminary validation study applying support vector machine-based classification and principle component analysis on the skin-derived expression data of 12 patients with psoriasis vulgaris and 12 healthy controls, previously produced in our departments. We then confirmed that the expression levels of the five genes in psoriatic lesions indeed present a unique pattern. Encouraged by these results, we continued to develop a quantitative polymerase chain reaction panel to allow the accurate measurement of expression levels for the five genes to be used in the studies to follow. Although we have yet to confirm these results in the context of other chronic inflammatory skin diseases, the results of previously published studies regarding these five genes are promising. Therefore, we are in the process of collecting additional skin samples from patients with chronic inflammatory disease (including different papulosquamous disorders and atopic dermatitis) to validate the discriminatory power of our panel. These results may further be translated to viable clinical diagnostic tests in the near future. This work was supported by the ERA Chair for Translational Genomics and Personalized Medicine at the University of Tartu

Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study

Background APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians’ perspective on overall success of apremilast in meeting expectations correlated with patients’ perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation

Enhancing CO2 plasma conversion using metal grid catalysts

The synergy between catalysis and plasma chemistry often enhances the yield of chemical reactions in plasma-driven reactors. In the case of CO2 splitting into CO and O2, no positive synergistic effect was observed in earlier studies with plasma reactors, except for dielectric barrier discharges, that do not have a high yield and a high efficiency. Here, we demonstrate that introducing metal meshes into radio frequency-driven plasma reactors increases the relative reaction yield by 20%–50%, while supported metal oxide catalysts in the same setups have no effect. We attribute this to the double role of the metal mesh, which acts both as a catalyst for direct CO2 dissociation as well as for oxygen recombination.</p

Dehydroalanine and Lysinoalanine in Thermolyzed Casein do not Promote Colon Cancer in the Rat

Thermolysis of proteins produces xenobiotic amino-acids such as the potentially toxic lysinoalanine, and the alkylating agent, dehydro¬alanine, which have been considered possible health hazards. We observed that thermolysed casein promoted aberrant crypt foci (ACF) and colon cancer growth in rats initiated with azoxymethane and speculated that promotion might be due to the formation of these compounds. To test this notion we first measured the concentration of the modified amino acids as a function of thermolysis time. The concentration of dehydroalanine in the casein paralleled the degree of promotion, that of lysinoalanine did not. We then tested diets containing foods with high levels of dehydroalanine (thermolysed sodium-caseinate, cooked Swiss cheese) for their effect on ACF promotion. They decreased the number and/or size of ACF significantly, indicating that dehydroalanine did not promote, but protected rats against colon carcinogenesis. These results do not support the notion that lysinoalanine or dehydroalanine are a hazard with respect to colon carcinogenicity

Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility

Food deprivation is known to affect physiology and behavior. Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability. In C. elegans, male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to their well-fed counterparts, suggesting that the mating circuit is repressed in low-food environments. This behavioral response could be mediated by sensory neurons exposed to the environment or by internal metabolic cues. We demonstrated that food-deprivation negatively regulates sex-muscle excitability through the activity of chemosensory neurons and insulin-like signaling. Specifically, we found that the repressive effects of food deprivation on the mating circuit can be partially blocked by placing males on inedible food, E. coli that can be sensed but not eaten. We determined that the olfactory AWC neurons actively suppress sex-muscle excitability in response to food deprivation. In addition, we demonstrated that loss of insulin-like receptor (DAF-2) signaling in the sex muscles blocks the ability of food deprivation to suppress the mating circuit. During low-food conditions, we propose that increased activity by specific olfactory neurons (AWCs) leads to the release of neuroendocrine signals, including insulin-like ligands. Insulin-like receptor signaling in the sex muscles then reduces cell excitability via activation of downstream molecules, including PLC-γ and CaMKII

Role of TNFα in pulmonary pathophysiology

Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death