Light stimulated healing of chronic wounds by use of optical waveguides and light management microstructures

Presentation at the EPIC Biophotonics Symposium in Berlin, on 27.11.2015

Gustatory responses in primates to the sweetener aspartame and their phylogenetic implications

Two-bottle preference tests have been applied to 70 (sub-) species of the order of Primates and, for comparison, to the tree shrew (Tupaia belangeri) to determine their responses to aspartame (APM), the first known sweet-tasting dipeptide which has to man a sweetness potency of about 200 times that of sucrose. It was found that only the Cercopithecidae, the Hylobatidae and the Pongidae respond like man to this dipeptide and prefer it to water. The other primates tested to date, show no response to this sweetener. From a phylogenetic point of view, we note that APM shows species specificity similar to thaumatin. Thus, a clear dichotomy exists within the order of Primates with respect to both thaumatin and APM. The results here illustrate once more the gustatory diversity among primates and are a compelling argument for the existence of different sweet taste receptors or recognition sites in primate specie

Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice

Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from selfhealing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drugresistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches

Association between clinic-level quality of care and patient-level outcomes in multiple sclerosis

Background: Multiple sclerosis (MS) quality of care guidelines are consensus-based. The effectiveness of the recommendations is unknown.// Objective: To determine whether clinic-level quality of care affects clinical and patient-reported outcomes.// Methods: This nationwide observational cohort study included patients with adult-onset MS in the Swedish MS registry with disease onset 2005–2015. Clinic-level quality of care was measured by four indicators: visit density, magnetic resonance imaging (MRI) density, mean time to commencement of disease-modifying therapy, and data completeness. Outcomes were Expanded Disability Status Scale (EDSS) and patient-reported symptoms measured by the Multiple Sclerosis Impact Scale (MSIS-29). Analyses were adjusted for individual patient characteristics and disease-modifying therapy exposure.// Results: In relapsing MS, all quality indicators benefitted EDSS and physical symptoms. Faster treatment, frequent visits, and higher data completeness benefitted psychological symptoms. After controlling for all indicators and individual treatment exposures, faster treatment remained independently associated with lower EDSS (−0.06, 95% confidence interval (CI): −0.01, −0.10) and more frequent visits were associated with milder physical symptoms (MSIS-29 physical score: −16.2%, 95% CI: −1.8%, −29.5%). Clinic-level quality of care did not affect any outcomes in progressive-onset disease.// Conclusion: Certain quality of care indicators correlated to disability and patient-reported outcomes in relapse-onset but not progressive-onset disease. Future guidelines should consider recommendations specific to disease course..

Microvascular and Morphologic Changes of the Macula over Lifetime.

In ocular, neurologic, and cardiovascular diseases, macular segmentation data from spectral-domain optical coherence tomography (SD-OCT) provide morphologic, and OCT-angiography (OCTA) results give microvascular information about the macula. Age was shown to influence both methods' measurements. To further characterize this association, macular SD-OCT and OCTA changes were investigated in a population of juvenile, adult, and older individuals. Macular segment thickness and superficial (SCP) and deep plexus (DCP) vascular density (VD) of 157 healthy individuals aged 10-79 years were analyzed retrospectively. One-way analysis of variance (ANOVA) was used to compare age groups. The association between macular segmentation and OCTA parameters and between these and age was evaluated using linear regression. ANOVA and linear regression analysis showed a thickness decrease in the whole macular and in the ganglion cell and inner plexiform layers with age. While the foveal avascular zone area remained constant between age groups, VD of the SCP and DCP also decreased with age. In multiple linear regression, SCP and DCP VD were associated with inner macular segment thickness in an age-independent way. To conclude, the age-related microvascular and morphological changes in the macula described in this study can contribute to improving the understanding of macular aging processes and better interpreting OCT(A) results in healthy individuals and patients suffering from various retinal diseases

Trajectories of disease-modifying therapies and associated sickness absence and disability pension among 1923 people with multiple sclerosis in Sweden

BACKGROUND: There is limited information on the trajectories of disease-modifying therapy (DMT) use and their association with sickness absence and/or disability pension (SADP) among people with multiple sclerosis (PwMS). The objective of the study was to identify trajectories of DMT use over 10 years among PwMS, identify sociodemographic and clinical factors associated with the trajectories, and to assess the association between identified trajectories and SADP days. METHODS: A longitudinal register-based study was conducted, on a prospective data set linked across six nationwide registers, assessing treatment courses of PwMS with DMTs for the 10 years following multiple sclerosis (MS) onset. The study included 1923 PwMS with MS onset in 2007-2010, when aged 19-56 years. In each 6-month-period, their treatment was categorized as before treatment, high-efficacy, non-high-efficacy, or no DMT. Sequence analysis was performed to identify sequences of the treatment categories and cluster them into different DMT trajectories. Cluster belonging, in relation to demographic and clinical characteristics, was assessed through log-multinomial regression analysis. The association of trajectories/cluster-belonging with SADP net days was assessed using generalized estimating equation (GEE) models. RESULTS: Cluster analyses identified 4 trajectories of DMT use: long-term non-high-efficacy DMTs (38.6%), escalation to high-efficacy DMTs (31.2%), delayed start and escalation to high-efficacy DMTs (15.4%), and discontinued/ no DMT (14.2%). Age, MS type, expanded disability status scale (EDSS) score and the number of DMT switches were associated with cluster belonging. The youngest age group (18-25) were more likely to be in the escalation to high-efficacy cluster. People with primary progressive MS were more likely to be in the delayed start or discontinued/ no DMT cluster. Higher EDSS scores were associated to being in the other three clusters than in the long-term non-high-efficacy DMTs cluster. Higher number of DMT switches were associated with being in the escalation to high-efficacy DMTs cluster but less likely to be in the delayed start or discontinued/ no DMT clusters. Descriptive analyses showed a trend of fewer mean SADP days among PwMS using non-high-efficacy DMT than the other clusters about 9 years after onset. PwMS in the escalation to high-efficacy and discontinued/no DMT clusters had more SADP days. PwMS in the delayed start and escalation to high-efficacy DMTs cluster, started with fewer SADP days which increased over time. SADP days adjusted through GEE models showed trends comparable with the descriptive analysis. CONCLUSION: This study described the long-term real-world trajectories of DMT use among PwMS in Sweden using sequence analysis and showed the association of the trajectories with SADP days as well as sociodemographic and clinical characteristics

‘All the corridors are the same’: a qualitative study of the orientation experiences and design preferences of UK older adults living in a communal retirement development

Environments need to be designed such that they support successful orientation for older adults and those with dementia who often experience marked difficulties in their orientation abilities. To better understand how environments can compensate for decreasing orientation skills, voice should be given directly to those experiencing dementia to describe how they find their way and to understand their design preferences. This study explored the navigational experiences and design preferences of older adults with memory difficulties living in a retirement development. In-depth semi-structured interviews with 13 older adults experiencing memory difficulties were conducted. All participants were residents of one retirement development in the United Kingdom. Questions began broadly, for example, to describe their experiences of navigating in their living environment, before discussing any specific navigation difficulties in detail. Thematic analysis identified three main themes: highlighting environmental design that causes disorientation, strategies to overcome disorientation, and residents’ suggestions to improve the design. The design suggestions were particularly informative, heavily focusing on the importance of having memorable and meaningful spaces which were favoured more than signage as an orientation aid. The findings demonstrate the need to consider environmental design to support orientation for those with memory difficulties. Of particular importance is the use of meaningful and relevant landmarks as orientation aids which can additionally stimulate conversation and increase wellbeing. Given the range of suggestions in dementia-friendly design guidelines aimed to support orientation, it is crucial to speak directly to those living in different environments to learn how they find their way around and what design works in their environment