Patterned Surface Activation of Cyclo-Olefin Polymers for Biochip Applications

Two different surface activation methods (UV/ozone and oxygen plasma treatment) were applied for patterned surface activation of cyclo-olefin polymer (COP) surfaces combined with different masking techniques (metal shadow mask and protective tape). Surface properties were characterized by various methods such as contact angle measurement, ATR-IR, XPS and Surface enhanced ellipsometric contrast (SEEC) microscopy. UV/ozone and oxygen plasma allowed for patterned surface modification of COP leading to the formation of carboxylic and hydroxyl groups on the activated part of the surface. Stability against organic solvents was determined by rinsing the activated substrates with 2-propanol. For UV/ozone treatment it was found that a thin film of degradation products remains on the COP surface and is at least partly removed in the following washing or rinsing steps

Dynamics within the CD95 death-inducing signaling complex decide life and death of cells

CD95-mediated apoptotic and NF-κB signaling were described by a simple kinetic model. We used a model reduction technique to reduce the number of reactions from 92 to 23 while maintaining a good model fit.p43-FLIP, which is generated at the CD95 DISC by procaspase-8 cleavage, was found to be the link between the CD95 DISC and the NF-κB pathway. P43-FLIP interacts with the IKK complex and leads to its activation.The CD95 DISC complex acts as a signal processor that diverges signals into the apoptotic and NF-κB pathways depending on the amounts of specific DISC proteins.Life/death decisions in CD95 signaling are determined by c-FLIPL and procaspase-8 in a non-linear way

Lateglacial and Holocene climate and environmental change in the northeastern Mediterranean region: Diatom evidence from Lake Dojran (Republic of Macedonia/Greece)

The juncture between the west-east and north-south contrasting Holocene climatic domains across the Mediterranean is complex and poorly understood. Diatom analysis of Lake Dojran (Republic of Macedonia/Greece) provides a new insight into lake levels and trophic status during the Lateglacial and Holocene periods in the northeastern Mediterranean. Following a very shallow or even desiccated state at the core base at ca. 12,500 cal yr BP, indicated by sedimentological and hydro-acoustic data, diatoms indicate lake infilling, from a shallow state with abundant benthos to a plankton-dominated relatively high lake level and eutrophic state thereafter. Diatom-inferred shallowing between ca. 12,400 - 12,000 cal yr BP and a very low lake level and eutrophic, oligosaline state between ca. 12,000 - 11,500 cal yr BP provide strong evidence for Younger Dryas aridity. The earliest Holocene (ca. 11,500 - 10,700 cal yr BP) was characterised by a high lake level, followed by a lake-level reduction and increased trophic level between ca. 10,700-8,500 cal yr BP. The lake was relatively deep and exhibited peak Holocene trophic level between ca. 8,500-3,000 cal yr BP, becoming shallow thereafter. The diatom data provide more robust evidence and strengthen previous lake-level interpretation based on sedimentological and geochemical data during the earliest, mid and late Holocene, and also clarify previous uncertainty in interpretation of Lateglacial and early-Holocene lake-level change. Our results are also important in disentangling regional climate effects from local catchment dynamics during the Holocene, and to this end we exploit extant regional palynological evidence for vegetation change in the highlands and lowlands. The importance of seasonality in driving Holocene climate change is assessed by reference to the summer and winter latitudinal temperature gradient (LTG) model of Davis and Brewer (2009). We suggest that increased precipitation drove the high lake level during the earliest Holocene. The early- Holocene low lake level and relatively high trophic state may result climatically from high seasonality of precipitation and locally from limited, nutrient-rich catchment runoff. We argue that the mid- Holocene relatively deep and eutrophic state was driven mainly by local vegetation succession and associated changes in catchment processes, rather than showing a close relationship to climate change. The late-Holocene shallow state may have been influenced by a temperature-induced increase in evaporative concentration, but was coupled with clear evidence for intensified human impact. This study improves understanding of Lateglacial and Holocene climate change in the northeastern Mediterranean, suggests the important role of the LTG on moisture availability during the Holocene, and clarifies the influence of catchment processes on palaeohydrology

Epigenetic Aspects of a New Probiotic Concept—A Pilot Study

Several studies report the important role of an altered gut microbiota in the development of obesity, highlighting the potential use of probiotics in the treatment of obesity. The aim of this study is to investigate the effect of a novel probiotic approach on the expression of specific miRNAs and mRNAs associated with obesity in combination with the hypocholesterolemic octacosanol. Twenty overweight/obese women participated in a randomized, placebo-controlled, double-blind study and were randomly divided into two groups: the intervention group (daily one capsule containing Lactobacillus plantarum 299v (DSM9843), Saccharomyces cerevisiae var. boulardii, and 40 mg octacosanol; N = 12) and the placebo group (N = 8). Changes in lipid parameters and expression of miRNAs and mRNAs were assessed before (T0) and after the 12-week intervention (T1). After the intervention, the expression of miR-155-5p (9.38 ± 0.85 vs. 8.38 ± 1.06, p = 0.05) and miR-24-3p (3.42 ± 0.38 vs. 2.71 ± 0.97, p = 0.031) showed significant decreases in the intervention group when compared to the control group. At T1, the expression of miR-155-5p (8.69 ± 1.31 vs. 9.3 ± 0.85, p = 0.04), miR-125b-5p (5.41 ± 1.18 vs. 5.99 ± 1.36, p = 0.049), and TNF-α (10.24 ± 1.66 vs. 11.36 ± 1.12, p = 0.009) were significantly decreased in the intervention group. No changes in lipids and anthropometric parameters were observed. The novel probiotic approach had a positive effect on regulating the expression of certain miRNAs and mRNAs important for regulating inflammation and adipogenesis, which are essential for obesity onset and control

Increased efficacy of influenza virus vaccine candidate through display of recombinant neuraminidase on virus like particles

Vaccination against influenza virus can reduce the risk of influenza by 40% to 60%, they rely on the production of neutralizing antibodies specific to influenza hemagglutinin (HA) ignoring the neuraminidase (NA) as an important surface target. Vaccination with standardized NA concentration may offer broader and longer-lasting protection against influenza infection. In this regard, we aimed to compare the potency of a NA displayed on the surface of a VLP with a soluble NA. The baculovirus expression system (BEVS) and the novel virus-free Tnms42 insect cell line were used to express N2 NA on gag-based VLPs. To produce VLP immunogens with high levels of purity and concentration, a two-step chromatography purification process combined with ultracentrifugation was used. In a prime/boost vaccination scheme, mice vaccinated with 1 µg of the N2-VLPs were protected from mortality, while mice receiving the same dose of unadjuvanted NA in soluble form succumbed to the lethal infection. Moreover, NA inhibition assays and NA-ELISAs of pre-boost and pre-challenge sera confirm that the VLP preparation induced higher levels of NA-specific antibodies outperforming the soluble unadjuvanted NA

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1 beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4 x 4-weekly doses of canakinumab (50 + 50 + 25 + 25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses >= 50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p <= 0.0083), and the percentage of patients experiencing >= 1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing >= 1 flare for canakinumab doses >= 50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p <= 0.05). The incidence of adverse events was similar across treatment groups.Conclusions Single canakinumab doses >= 50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg

Immunological imprinting of the antibody response in COVID-19 patients

In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection

Metabolic and crystal arthropathies: 112. Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Canakinumab, a fully human anti-IL-1β antibody has been shown to control inflammation in gouty arthritis. This study evaluated changes in health-related quality of life (HRQoL) in patients treated with canakinumab or triamcinolone acetonide (TA). Methods: An 8-wk, dose-ranging, active controlled, single-blind study in patients (≥18 to ≤80 years) with acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150 mg sc or TA 40 mg im. HRQoL was assessed using patient reported outcomes evaluating PCS and MCS, and subscale scores of SF-36® [acute version 2]) and functional disability (HAQ-DI©). Results: In canakinumab 150 mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved in 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) and at 8 wks improved to 86.1 and 86.6 (mean increases of 44.6 and 50.6); these were higher than levels seen in the general US population. TA group, showed less improvement in 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain). Functional disability scores, measured by the HAQ-DI© decreased in both treatment groups (Table 1). Conclusions: Gouty arthritis patients treated with canakinumab showed a rapid improvement in physical and mental well-being based on SF-36® scores. In contrast to the TA group, patients treated with canakinumab showed improvement in 7 days in physical function and bodily pain approaching levels of the general population. Disclosure statement: U.A., A.F., V.M., D.R., P.S. and K.S. are employees and shareholders of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support and consultancy fees from Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and EnzymeRx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultation fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interes

Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial

Patient-centered motives and expectations of the treatment of actinic keratoses (AK) have received little attention until now. Hence, we aimed to profile and cluster treatment motivations and expectations among patients with AK in a nationwide multicenter, cross-sectional study including patients from 14 German skin cancer centers. Patients were asked to complete a self-administered questionnaire. Treatment motives and expectations towards AK management were measured on a visual analogue scale from 1–10. Specific patient profiles were investigated with subgroup and correlation analysis. Overall, 403 patients were included. The highest motivation values were obtained for the items “avoid transition to invasive squamous cell carcinoma” (mean ± standard deviation; 8.98 ± 1.46), “AK are considered precancerous lesions” (8.72 ± 1.34) and “treating physician recommends treatment” (8.10 ± 2.37; p < 0.0001). The highest expectation values were observed for the items “effective lesion clearance” (8.36 ± 1.99), “safety” (8.20 ± 2.03) and “treatment-related costs are covered by health insurance” (8.00 ± 2.41; p < 0.0001). Patients aged ≥77 years and those with ≥7 lesions were identified at high risk of not undergoing any treatment due to intrinsic and extrinsic motivation deficits. Heat mapping of correlation analysis revealed four clusters with distinct motivation and expectation profiles. This study provides a patient-based heuristic tool for a personalized treatment decision in patients with AK