Causal Genes in Multiple Sclerosis a direct positive causal effect for CCL2. Since in general we observed a different magnitude for the gene specific causal effect we hypothesize that in cerebellum and medulla the effect of each gene expression is direct but also mediated by the others. These results confirm the importance of the involvement of NF-κB signaling pathway in brain tissue for the development of the disease and improve our understanding in the pathogenesis of MS.

Here we investigate protein levels in 69 multiple sclerosis (MS) cases and 143 healthy controls (HC) from twenty Sardinian families to search for promising biomarkers in plasma. Using antibody suspension bead array technology, the plasma levels of 56 MS-related proteins were obtained. Differences between MS cases and HC were estimated using Linear Mixed Models or Linear Quantile Mixed Models. The proportion of proteins level variability, explained by a set of 119 MS-risk SNPs as to the literature, was also quantified. Higher plasma C9 and CYP24A1 levels were found in MS cases compared to HC (p < 0.05 after Holm multiple testing correction), with protein level differences estimated as, respectively, 0.53 (95% CI: 0.25, 0.81) and 0.42 (95% CI: 0.19, 0.65) times plasma level standard deviation measured in HC. Furthermore, C9 resulted in both statistically significantly higher relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS) compared to HC, with SPMS showing the highest differences. Instead, CYP24A1 was statistically significantly higher only in RRMS as compared to HC. Respectively, 26% (95% CI: 10%, 44%) and 16% (95% CI: 9%, 39%) of CYP24A1 and C9 plasma level variability was explained by known MS-risk SNPs. Our results highlight C9 and CYP24A1 as potential biomarkers in plasma for MS and allow us to gain insight into molecular disease mechanisms.

Background Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-c (PPARc) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process. Objectives To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris. Methods This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland. Patients aged 12-30 years with facial acne, an Investigator Global Assessment (IGA) score of 3-4, and an inflammatory and noninflammatory lesion count of 20-100 were randomized to topical application of the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The co-primary efficacy endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse events (AEs) and serious AEs. This study was registered with EudraCT (2018-003307-19). Results Between Q1 in 2019 and Q1 in 2020 450 patients [n = 418 (92Á9%) IGA 3; n = 32 (7Á1%) IGA 4] were randomly assigned to NAC-GED 5% (n = 150), NAC-GED 2% (n = 150) or vehicle (n = 150). The percentage change in TLC reduction was statistically significantly higher in both the NAC-GED 5% [-57Á1%, 95% confidence interval (CI) -60Á8 to -53Á4; P < 0Á001] and NAC-GED 2% (-44Á7%, 95% CI -49Á1 to -40Á1; P < 0Á001) groups compared with vehicle (-33Á9%, 95% CI -37Á6 to -30Á2). A higher proportion of patients treated with

To limit the first spread of COVID-19 in March 2020, the Italian government imposed strict lockdown measures to the population. Despite necessary to reduce the virus transmission and the burden to the hospitals, social isolation has caused detrimental effects on psychological wellbeing and mental health. Moreover, during this period, it was also difficult to deliver psychological treatments and psychiatric assistance. A short (a weekly session for 9 weeks) mindfulness-based meditation program, named Integral Meditation (IM), was administered entirely online to healthy adults from Italy. This is a two-groups pre–post-quasi-experimental study in which the two groups, treated and control, were not randomized. Through matching procedures aimed at overcoming the absence of randomization, we analyzed a sample of 84 subjects (42 for each group). By applying linear mixed effect models, we tested the hypothesis of a beneficial effect of IM on wellbeing, perceived stress, and state anxiety, as measured by three self-reported questionnaires (WEMWBS, PSS, and STAI-X1, respectively), assuming that this effect could be different according to the level of baseline trait anxiety, as measured by STAI-X2. The results showed a statistically significant effect of STAI-X1 (β = −8.24 [95%CI −15.39; −1.09], p = 0.02) and WEMWBS (β = 4.61 [95%CI 0.94; 8.29], p = 0.01) in the higher trait anxiety subgroup only. No statistically significant effect of IM was observed for PSS. These results suggest that our IM, delivered online, may increase mental wellbeing and decrease anxiety specifically in subjects with higher trait anxiety.

Sleep of inadequate quantity and quality is increasing in the present 24 h society, with a negative impact on physical and mental health. Mindfulness-based interventions (MBIs) generate a state of calm behavior that can reduce hyperactivity and improve sleep. We hypothesized that our specific MBI, administered online, may improve sleep quality and foster emotion regulation and mindfulness. The Pittsburgh Sleep Quality Index (PSQI), Sleep Condition Indicator (SCI), Arousal Predisposition Scale (APS), Ford Insomnia Response to Stress Test (FIRST), Sleep Hygiene Index (SHI) and Insomnia Severity Index (ISI) were used to measure sleep quality and stability. Emotion regulation and mindfulness were measured via the Emotion Regulation Questionnaire (ERQ) and Five Facet Mindfulness Questionnaire (FFMQ). Our MBI included 12 biweekly integral meditation (IM) classes, recorded IM training for individual practice, and dietary advice to promote sleep regulation. Fifty-six voluntary poor sleepers with a PSQI score of >5 were randomly allocated to treated (n = 28) and control (n = 28) groups. Linear mixed models were used to estimate the effectiveness of the intervention. Statistically significant results were observed in the FFMQ sub-domain non-reactivity to inner experience (β = 0.29 [0.06; −0.52], p = 0.01), PSQI (β = −1.93 [−3.43; −0.43], p = 0.01), SCI (β = 3.39 [0.66; 6.13], p = 0.02) and ISI (β = −3.50 [−5.86; −1.14], p = 0.004). These results confirm our hypothesis regarding the beneficial effects of our intervention on sleep quality.