An Alternative Pathway of Imiquimod-Induced Psoriasis-Like Skin Inflammation in the Absence of Interleukin-17 Receptor A Signaling

Topical application of imiquimod (IMQ) on the skin of mice induces inflammation with common features found in psoriatic skin. Recently, it was postulated that IL-17 has an important role both in psoriasis and in the IMQ model. To further investigate the impact of IL-17RA signaling in psoriasis, we generated IL-17 receptor A (IL-17RA)–deficient mice (IL-17RAdel) and challenged these mice with IMQ. Interestingly, the disease was only partially reduced and delayed but not abolished when compared with controls. In the absence of IL-17RA, we found persisting signs of inflammation such as neutrophil and macrophage infiltration within the skin. Surprisingly, already in the naive state, the skin of IL-17RAdel mice contained significantly elevated numbers of Th17- and IL-17-producing γδ T cells, assuming that IL-17RA signaling regulates the population size of Th17 and γδ T cells. Upon IMQ treatment of IL-17RAdel mice, these cells secreted elevated amounts of tumor necrosis factor-α, IL-6, and IL-22, accompanied by increased levels of the chemokine CXCL2, suggesting an alternative pathway of neutrophil and macrophage skin infiltration. Hence, our findings have major implications in the potential long-term treatment of psoriasis by IL-17-targeting drugs

Exercise reduces systemic immune inflammation index (SII) in childhood cancer patients

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a randomized-controlled trial. Results show associations between inflammation markers and patient-reported outcomes. Compared to the control group, SII was significantly reduced following exercise (p=0.036). Anti-inflammatory effects of exercise are also present in CCPs and may underlie exercise-induced benefits on symptoms. Clinical Trial Registration Number: NCT02612025

Ionospheric and thermospheric response to the 27–28 February 2014 geomagnetic storm over north Africa

International audienc

Adherence to the Qatar dietary guidelines: a cross-sectional study of the gaps, determinants and association with cardiometabolic risk amongst adults

Abstract Background The Qatar Dietary Guidelines (QDGs) were developed as part of the national strategy to prevent chronic diseases. This study aims at characterizing gaps between the QDGs and usual dietary and lifestyle patterns in Qatar, identifying demographic and socioeconomic determinants of adherence to the QDGs and investigating the association between adherence and cardiometabolic risk. Methods This study is based on the Qatar National STEPwise cross-sectional survey which was conducted on a nationally representative sample of Qatari adults, aged 18 to 64 years (n = 1109). Data collection included socio-demographic characteristics, lifestyle factors, anthropometric (weight, height and waist circumference (WC)), and blood pressure measurements. The dietary intake of participants was evaluated using a non-quantitative food frequency questionnaire (FFQ). Biochemical assessment was performed to measure the fasting levels of blood sugar, triglycerides (TG) and HDL cholesterol. The metabolic syndrome (MetS) was defined as the presence of three or more cardiometabolic risk factors. To examine adherence to the guidelines, each specifc recommendation was matched to corresponding data drawn from the survey. To investigate the association of sociodemographic, lifestyle and cardiometabolic characteristics with adherence to the QDGs, an adherence score was calculated. Results More than 83% of adults did not meet the recommendations for vegetables, fruits, whole grains, legumes and high fibre intakes, 70% were overweight or obese, 50–72% reported frequent consumption of sweetened beverages and sweets, and 47% reported frequent consumption of fast foods. Younger adults, the unemployed, the least educated and those not married had lower adherence to the QDGs. Adherence was inversely associated with elevated WC (OR: 0.88, 95% CI:0.82–0.95) and the MetS (OR:0.84,95% CI:0.74–0.96). Conclusions Building on the identified gaps and vulnerable population groups, the study findings should provide a road map for the prioritization of interventions and the development of culture- specific programs aiming at promoting adherence to dietary guidelines in Qatar, while serving as a model to other countries in the region

A ‘High Risk’ Lifestyle Pattern Is Associated with Metabolic Syndrome among Qatari Women of Reproductive Age: A Cross-Sectional National Study

This study investigated the effect of lifestyle patterns, as a combination of diet, physical activity and smoking, on Metabolic Syndrome (MetS) among Qatari women of childbearing age (n = 418), a population group particularly vulnerable to the health sequela of this syndrome. Using data from the National WHO STEPwise survey conducted in Qatar in 2012, Principal Component Factor Analysis was performed to derive lifestyle patterns with survey variables related to the frequency of consumption of 13 foods/food groups, physical activity levels, and smoking status. MetS was diagnosed using ATPIII criteria. Three lifestyle patterns were identified: ‘High Risk’ pattern, characterized by intakes of fast foods, sweets and sugar sweetened beverages, in addition to lower levels of physical activity and higher smoking prevalence; ‘Prudent’ pattern, driven mainly by higher intakes of fruits, vegetables, fish, and whole grains; and ‘Traditional’ pattern which included beans, meat, dairy products, and a low prevalence of smoking. Among these three lifestyle patterns, only the ‘High Risk’ was associated with MetS, whereby subjects belonging to the third tertile of this pattern’s score had 2.5 times the odds of MetS compared to those belonging to the first tertile. The findings of this study demonstrated the synergy among high risk behaviors among Qatari women in increasing the odds of MetS; the latter being a major risk factor for cardiovascular diseases

Evidence of K+ homeostasis disruption in cellular dysfunction triggered by 7-ketocholesterol, 24S-hydroxycholesterol, and tetracosanoic acid (C24:0) in 158N murine oligodendrocytes

International audienceImbalance in the homeostasis of K+ ions has been reported to contribute to the pathogenesis of neurodegenerative diseases. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC), and tetracosanoic acid (C24:0), often found at increased levels in patients with Alzheimer's disease, Multiple Sclerosis and X-ALD, are able to trigger numerous nerve cell dysfunctions. We therefore studied the impact of 7KC, 24S-OHC, and C24:0 on 158N murine oligodendrocytes, and determined their impact on K+ homeostasis. The effects of 7KC, 24S-OHC and C24:0 on lipid membrane organization and membrane potential were examined with merocyanine 540 (MC540) and bis-(1,3-diethylthiobarbituric acid) trimethine oxonol (DiSBAC2(3)), respectively. The intracellular concentration of K+ ([K+]i) was measured by flame photometry and the ratiometric approach using the PBFI-AM fluorescence indicator. To determine the relationships between [K+]i and lipotoxicity, 158N cells were pre-treated with a universal Kv channels blocker, 4-aminopyridine (4-AP), without or with 7KC, 24S-OHC or C24:0. Cell adhesion, cell growth, mitochondrial depolarization, cytoplasmic membrane integrity, the presence of SubG1 and the morphological aspect of the nuclei were determined with various microscopy, flow cytometry and biochemistry methods. 7KC, 24S-OHC and C24:0 induced changes in lipid content and polarization of the cytoplasmic membrane. These events were associated with increased [K+]i. Blocking Kv channels with 4-AP exacerbated 7KC-, 24S-OHC- and C24:0-induced cell dysfunction. 4-AP exacerbated loss of cell adhesion and cell growth inhibition, amplified mitochondrial depolarization and cytoplasmic membrane damage, and increased the percentage of SubG1 cells. The positive correlation between [K+]i and cell death supports the potential involvement of K+ in 7KC-, 24S-OHC-, and C24:0-induced cytotoxicity