Comparative study of imiquimod 3.75% vs. photodynamic therapy for actinic keratosis of the scalp

Background/purpose: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK). Methods: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months. Results: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent. Conclusion: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field

KAOS: A new automated computational method for the identification of overexpressed genes

Background: Kinase over-expression and activation as a consequence of gene amplification or gene fusion events is a well-known mechanism of tumorigenesis. The search for novel rearrangements of kinases or other druggable genes may contribute to understanding the biology of cancerogenesis, as well as lead to the identification of new candidate targets for drug discovery. However this requires the ability to query large datasets to identify rare events occurring in very small fractions (1-3 %) of different tumor subtypes. This task is different from what is normally done by conventional tools that are able to find genes differentially expressed between two experimental conditions. Results: We propose a computational method aimed at the automatic identification of genes which are selectively over-expressed in a very small fraction of samples within a specific tissue. The method does not require a healthy counterpart or a reference sample for the analysis and can be therefore applied also to transcriptional data generated from cell lines. In our implementation the tool can use gene-expression data from microarray experiments, as well as data generated by RNASeq technologies. Conclusions: The method was implemented as a publicly available, user-friendly tool called KAOS (Kinase Automatic Outliers Search). The tool enables the automatic execution of iterative searches for the identification of extreme outliers and for the graphical visualization of the results. Filters can be applied to select the most significant outliers. The performance of the tool was evaluated using a synthetic dataset and compared to state-of-the-art tools. KAOS performs particularly well in detecting genes that are overexpressed in few samples or when an extreme outlier stands out on a high variable expression background. To validate the method on real case studies, we used publicly available tumor cell line microarray data, and we were able to identify genes which are known to be overexpressed in specific samples, as well as novel ones

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

It is estimated that one-third of the world’s population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food – Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health

Enhanced photogeneration of polaron pairs in neat semicrystalline donor-acceptor copolymer films via direct excitation of interchain aggregates

We investigate the photogeneration of polaron pairs (PPs) in neat films of the semicrystalline donor–acceptor semiconducting copolymer PCPDTBT. Carefully selecting the solution-processing procedures, we obtain films with different amounts of crystallinity and interchain aggregation. We compare the photogeneration of PPs between the films by monitoring their photoinduced absorption in ultrafast pump–probe experiments, selectively exciting nonaggregated or aggregated polymer chains. The direct photoexcitation of interchain π-aggregates results in prompt (<100 fs) charge generation. Compared to the case where nonaggregated chains are excited, we find an 8-fold increase in the prompt PP to singlet-exciton ratio. We also show that highly crystalline lamellar nanostructures not containing π-stacked or any light-absorbing aggregates do not improve the efficiency of PP photogeneration. Our results show that light absorption from interchain aggregates is highly beneficial for charge photogeneration in semiconducting polymers and should be taken into account when optimizing film morphologies for photovoltaic devices

NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet

Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT1R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance

How to improve educational behaviors for caregivers and patients having Central Venous Access Device (CVAD). a scoping review

Objective: Central venous access devices (CVADs) are essential to the modern management of patients with hematological malignancies and solid tumors. Educational programs play a crucial role in promoting appropriate patient actions to support patient safety during hospitalization and homecare. This review aimed to identify literature concerning educational interventions to promote patients’ actions to overcome CVAD-related problems and improve self-monitoring and self-management. Materials and Methods: Documentary evaluation of international databases, such as PubMed, CINAHL, Scopus and Cochrane. Searching for data on population, context and concept regarding CVAD self-management. The extracted data was subject to thematic analysis. The following scoping reviews were developed using the five-stage framework outlined by Arksey and O’Malley, and advanced by Levac and colleagues. Results: Of the 2802 articles identified, 19 research articles were selected in this review. Educational programs have been shown to improve CVAD self management, to decrease stress and anxiety related to their use, and to reduce the onset of complications. In addition, nurses have proven to be the professional reference figure for educational interventions. Conclusions: The results of the study lead to the conclusion that programs aimed at improving selfcare and reducing the onset of complications in patients living with chronic and debilitating diseases should be made available to a larger portion of individuals. Both generic and specific programs are needed, in the different contexts of home and hospital, for the short and long term, in order to ameliorate participants’ abilities. The results of this study should, therefore, encourage health professionals to plan, carry out, and evaluate the establishment of educational programs with patient participation

AB0578 SUBCLINICAL ENTHESITIS IN PSORIASIS patiEntS AS prediCtor OF ARTHRITIS (EPESCA STUDY): PRELIMINARY RESULTS

Background:Enthesitis is one of the typical pathological signs of spondyloarthritis such as psoriatic arthritis (PsA) and it seems to be the Primum movens of the disease. Clinical assessment of enthesitis showed to be less sensitive, compared to ultrasound (US) evaluation, in identifying enthesitis in patients with PsA [1].OMERACT defined US enthesitis as: "hypoechoic and/or thickened insertion of the tendon close to the bone (within 2 mm from the bony cortex), which exhibits Doppler signal if active and that may show erosions, enthesophytes/calcifications as a sign of structural damage" [3]The reported prevalence of subclinical enthesitis in psoriasis (PsO) patients in different countries ranges between 7% and 20% [2].Objectives:The main objective of this study was to estimate, by US evaluation, the prevalence of subclinical enthesitis in PsO patients without any clinical signs of enthesitis. Secondary objectives were to analyze differences, in terms of age, sex, BMI, PsO onset and diagnosis, among patients with enthesitis (active or not active), enthesopathy and without any alteration of enthesis.According to the OMERACT definition of ultrasound enthesitis, patients were divided into 4 groups: patients with active enthesitis (AE) defined as the presence of power-Doppler signal in a hypoechoic and/or thickened insertion of the tendon close to the bone; patient with enthesitis (En) defined as hypoechoic and/or thickened insertion of the tendon close to the bone without PD signal; patients with enthesopathy (Ep) defined as the presence of structural damage (erosions, enthesophytes/calcifications); patients without any alteration of enthesis (WE).Methods:Patients with at least 18 years and a diagnosis of PsO made by a Dermatologist were included. Exclusion criteria were the presence of clinical symptoms or signs of articular or entheseal involvement, diagnosis of arthritis and therapy with bDMARDs or tsDMARDs.All patients underwent US examination on grey scale and Power Doppler (PD) ultrasonography of 6 sites (Achilles, quadriceps, distal and proximal patellar, plantar fascia and triceps enthesis) bilaterally. Ultrasound was performed by an experienced sonographer, using a Logiq P9 equipped with 6-12 MHz broad band linear transducer. Data were reported as frequencies and median with interquartile range. To check differences among these four groups, we used chi-square test or Kruskall-Wallis test. P-value ≤ 0.05 is considered statistically significant.Results:We enrolled 124 consecutive psoriasis patients (47 [37.9%] female) with median age 57.7 (45.3-66.5) years, median disease duration 20.4 (10.1-30.8) years, median BMI 27 [24-29]. Patients with AE, En, Ep were 20.2% (25/124), 49.2% (61/124) and 18.5% (23/124), respectively.Patients WE (12.1%, 15/124) showed significantly lower BMI, younger age and shorter diagnostic delay compared to the other patients.All signs of enthesopathy/enthesitis were more frequently observed at Achilles (33.1%, 41/124), triceps (23.4%, 29/124), quadriceps (20.2%, 25/124), distal patellar (18.5%, 23/124) and proximal patellar (4.8%, 6/124) enthesis.Conclusion:Subclinical enthesitis is quite common in PsO patients, and about 20% showed active enthesitis. The enthesopathy seems to be more frequent in patients with increased delay in PsO diagnosis, older age and higher BMI.References:[1]Bandinelli F. et al. Ultrasound detects occult entheseal involvement in early psoriatic arthritis independently of clinical features and psoriasis severity. Clin Exp Rheumatology. Mar-Apr 2013;31(2):219-24.[2]Zuliani F. et al. Ultrasonographic detection of subclinical enthesitis and synovitis: a possible stratification of psoriatic patients without clinical musculoskeletal involvement. Clin Exp Rheumatol Jul-Aug 2019;37(4):593-599.[3]Balint P. V. et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis 2018 Dec;77(12):1730-1735.Disclosure of Interests:None declared

Graphene-passivated nickel as an efficient hole-injecting electrode for large area organic semiconductor devices

Efficient injection of charge from metal electrodes into semiconductors is of paramount importance to obtain high performance optoelectronic devices. The quality of the interface between the electrode and the semiconductor must, therefore, be carefully controlled. The case of organic semiconductors presents specific problems: ambient deposition techniques, such as solution processing, restrict the choice of electrodes to those not prone to oxidation, limiting potential applications. Additionally, damage to the semiconductor in sputter coating or high temperature thermal evaporation poses an obstacle to the use of many device-relevant metals as top electrodes in vertical metal–semiconductor–metal structures, making it preferable to use them as bottom electrodes. Here, we propose a possible solution to these problems by implementing graphene-passivated nickel as an air stable bottom electrode in vertical devices comprising organic semiconductors. We use these passivated layers as hole-injecting bottom electrodes, and we show that efficient charge injection can be achieved into standard organic semiconducting polymers, owing to an oxide free nickel/graphene/polymer interface. Crucially, we fabricate our electrodes with low roughness, which, in turn, allows us to produce large area devices (of the order of millimeter squares) without electrical shorts occurring. Our results make these graphene-passivated ferromagnetic electrodes a promising approach for large area organic optoelectronic and spintronic devices.We acknowledge funding from EPSRC (EP/P005152/1, EP/M005143/1). R.M. and K.N. acknowledges funding from the EPSRC Cambridge NanoDTC (Grant No. EP/G037221/1). J.A.-W. acknowledges the support of his Research Fellowship from the Royal Commission for the Exhibition of 1851, and Royal Society Dorothy Hodgkin Research Fellowship. R. S. W. acknowledges support from a CAMS-UK fellowship

Outcome following a short period of adalimumab dose escalation as rescue therapy in psoriatic patients

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI&lt; 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy