Single-mode waveguides with SU-8 polymer core and cladding for MOEMS applications

Fabrication and optical characterization of single-mode polymeric embedded waveguides are performed. A specific material combination (SU-8 2005 as core and the modified SU-8 mr-L 6050XP as cladding) is chosen in order to obtain a small refractive index difference for single-mode propagation combined with the conventional fabrication method UV lithography to facilitate the integration of different types of optical detection methods on lab-on-a-chip systems. We analyze the behavior of the refractive index and carefully observe how the value of the refractive index can be tailored during processing. We show that we can fabricate waveguides with an index difference in the order of 10-3 , where both the core material and the cladding material are based on SU-8. The refractive index measurements are performed on thin polymeric films, while further optical characterizations are performed on waveguides with a height of 4.5 mum. We study the mode profiles of these waveguides and confirm that only the fundamental mode is excited. We also study the absorption spectra of the material in the wavelength range 800-1600 nm combined with cut-back measurements. We find that the waveguides have a propagation loss of 0.2-3 dB/cm in this wavelength range

Integrated optical readout for miniaturization of cantilever-based sensor system

We present the fabrication and characterisation of an integrated optical read-out scheme based on single-mode waveguides for cantilever-based sensors. The cantilever bending is read out by monitoring changes in the optical intensity of light transmitted through the cantilever that also acts as a waveguide. The complete system is fabricated in the photo-sensitive polymer SU-8. We show theoretical calculations on the expected sensitivity both when operated in air and liquid and compare these with experimental characterisation of the system in air where the cantilever is deflected mechanically. The experimental results compare well with the results obtained from the theoretical calculations.Peer reviewe

Milloin selkäkivun taustalla on tulehduksellinen sairaus?

Noin 40 % suomalaista on kärsinyt selkäkivusta edellisen kuukauden aikana. Pienellä osalla heistä on ¬tulehduksellinen rankasairaus, aksiaalinen spondylartriitti. Jos sairaus diagnosoidaan, potilasta voidaan auttaa omaehtoiseen harjoitteluun ohjaavalla fysioterapialla ja modernilla ¬antireumaattisella lääkehoidolla. Reumatologin arviosta hyötyvät potilaat on kuitenkin haastavaa löytää, koska oirekuva on moninainen. Kansainväliset suositukset pyrkivät nopeuttamaan diagnoosiin pääsyä ja hoidon aloitusta. Hoitamaton aksiaalinen spondylartriitti voi johtaa nikamia luuduttavaan selkärankareumaan ja perifeeristen nivelten muutoksiin

Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus

Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-α (TNF-α), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP

Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus

Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-α (TNF-α), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP

Active conventional treatment and three different biological treatments in early rheumatoid arthritis : phase IV investigator initiated, randomised, observer blinded clinical trial

OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.Peer reviewe

Effectiveness and drug survival of TNF-inhibitors in the treatment of psoriatic arthritis : A prospective cohort study

Background and objectives: Tumor necrosis factor (TNF)-inhibitors are used to treat psoriatic arthritis (PsA), but only a limited number of observational studies on this subject have been published thus far. The aim of this research was to analyze the effectiveness and drug survival of TNF-inhibitors in the treatment of PsA. Methods: PsA patients identified from the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first, second, or third TNF-inhibitor treatment between 2004 and 2014 were included. Effectiveness was measured using ACR and EULAR response criteria and modeled using ordinal logistic regression. Treatment persistence was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards model. Results: The study comprised 765 patients and 990 TNF-inhibitor treatment courses. EULAR moderate treatment responses at 6 months were achieved by 68% and 37% of the users of the first and the second or the third biologic, respectively. The probabilities of discontinuing the treatment within 12 and 24 months were 20% and 28%, respectively. Adjusted treatment responses to all TNF-inhibitors were similar; however, co-therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was not associated with better effectiveness. Adalimumab [hazard ratio (HR) = 0.62; 95% confidence interval (CD: 0.44-0.88] was superior to infliximab in drug survival while etanercept (HR = 0.77, 95% CI: 0.55-1.1) and golimumab (HR = 0.75, 95% CI: 0.46-1.2) did not differ from it. Co-medication with csDMARDs did not statistically improve drug survival. Conclusion: All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis

Background and Objectives: Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT). Methods: A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias. Results: Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo. Conclusions No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.Peer reviewe

Do patient-reported measures of disease activity in rheumatoid arthritis vary between countries? Results from a Nordic collaboration

Objectives To investigate whether patient-reported outcomes vary across countries and are influenced by cultural/contextual factors. Specifically, we aimed to assess inter-country differences in tender joint count (TJC), pain and patient's global health assessment (PGA), and their impact on disease activity (DAS28-CRP) in RA patients from five Nordic countries. Methods We collected data (baseline, 3- and 12-months) from rheumatology registers in the five countries comprising RA patients starting a first ever MTX or a first ever TNF inhibitor (TNFi). In order to assess the role of context (=country), we separately modelled TJC, pain and PGA as functions of objective variables (CRP, swollen joint count, age, sex, calendar period and disease duration) with linear models. Analyses were performed at each time point and for both treatments. We further assessed the impact of inter-country differences on DAS28-CRP. Results A total of 27 645 RA patients started MTX and 19 733 started a TNFi. Crude inter-country differences at MTX start amounted to up to 4 points (28 points scale) for TJC, 10 and 27 points (0-100 scale) for pain and PGA, respectively. Corresponding numbers at TNFi start were 3 (TJC), 27 (pain) and 24 (PGA) points. All differences were reduced at 3- and 12-months, and attenuated when adjusting for the objective variables. The variation in predicted DAS28-CRP across countries amounted to Conclusions Inter-country differences in TJC, pain and PGA are greater than expected based on differences in objective measures, but have a small clinical impact on DAS28-CRP across countries.Peer reviewe