Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud’s phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review

BACKGROUND: Systemic sclerosis is a rare autoimmune disease characterized by skin and organ fibrosis, and vasculopathy. Raynaud’s phenomenon is almost universally present in systemic sclerosis and can be the most debilitating symptom. Raynaud’s phenomenon may lead to the development of digital ulcers, potentially complicated by infection, tissue necrosis, and auto-amputation. Recommended treatments have variable efficacy. METHODS: We report the case of a 30-year-old woman with diffuse systemic sclerosis suffering from severe Raynaud’s phenomenon and digital ulcers with digital tissue necrosis who was treated with combination therapy of an endothelin receptor antagonist and phosphodiesterase 5 inhibitor. In addition, we reviewed the literature on the topic. RESULTS: Previous therapy with calcium-channel blockers, intravenous iloprost, and bosentan had all failed to control symptoms. We added sildenafil in combination with bosentan and observed a rapid and sustained treatment effect. Raynaud’s phenomenon severity, number of attacks, and attack duration decreased within 2 weeks of initiating treatment. Furthermore, this resulted in the healing of established digital ulcers. CONCLUSION: Our case report suggests that combination therapy may be a feasible treatment for the most severely affected and refractory patients. In our literature review, we found one retrospective study and three additional cases with similarly encouraging results

Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial):study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial

INTRODUCTION: Achieving gross total resection and endocrine remission in pituitary neuroendocrine tumours (PitNET) can be challenging, especially in PitNETs with cavernous sinus (CS) invasion, defined as a Knosp grade of 3 or 4. A potential target to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A), which expression is known to be significantly higher in PitNETs with CS invasion.METHODS AND ANALYSIS: The aim of this non-randomised, non-blinded, single centre, feasibility and dose-finding phase 1 trial is to determine the feasibility of intraoperative fluorescence imaging detection of PitNET tissue during endoscopic transsphenoidal surgery using the VEGF-A targeting optical agent bevacizumab-800CW (4, 5, 10 or 25 mg). Nine to fifteen patients with a PitNET with a Knosp grade of 3 or 4 will be included. Secondary objectives are: (1) To identify the optimal tracer dose for imaging of PitNET tissue during transsphenoidal surgery for further development in a phase 2 fluorescence molecular endoscopy trial. (2) To quantify fluorescence intensity in vivo and ex vivo with multidiameter single-fibre reflectance, single-fibre fluorescence (MDSFR/SFF) spectroscopy. (3) To correlate and validate both the in vivo and ex vivo measured fluorescence signals with histopathological analysis and immunohistochemical staining. (4) To assess the (sub)cellular location of bevacizumab-800CW by ex vivo fluorescence microscopy. Intraoperative, three imaging moments are defined to detect the fluorescent signal. The tumour-to-background ratios are defined by intraoperative fluorescence in vivo measurements including MDSFR/SFF spectroscopy data and by ex vivo back-table fluorescence imaging. After inclusion of three patients in each dose group, an interim analysis will be performed to define the optimal dose.ETHICS AND DISSEMINATION: Approval was obtained from the Medical Ethics Review Board of the University Medical Centre Groningen. Results will be disseminated through national and international journals. The participants and relevant patient support groups will be informed about the results.TRIAL REGISTRATION NUMBER: NCT04212793.</p

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Connecting the data landscape of long-term ecological studies: The SPI-Birds data hub

The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database (www.spibirds.org)\u2014a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration

No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes

Fusarium and allied fusarioid taxa (FUSA). 1

Seven Fusarium species complexes are treated, namely F. aywerte species complex (FASC) (two species), F. buharicum species complex (FBSC) (five species), F. burgessii species complex (FBURSC) (three species), F. camptoceras species complex (FCAMSC) (three species), F. chlamydosporum species complex (FCSC) (eight species), F. citricola species complex (FCCSC) (five species) and the F. concolor species complex (FCOSC) (four species). New species include Fusicolla elongata from soil (Zimbabwe), and Neocosmospora geoasparagicola from soil associated with Asparagus officinalis (Netherlands). New combinations include Neocosmospora akasia, N. awan, N. drepaniformis, N. duplosperma, N. geoasparagicola, N. mekan, N. papillata, N. variasi and N. warna. Newly validated taxa include Longinectria gen. nov., L. lagenoides, L. verticilliforme, Fusicolla gigas and Fusicolla guangxiensis. Furthermore, Fusarium rosicola is reduced to synonymy under N. brevis. Finally, the genome assemblies of Fusarium secorum (CBS 175.32), Microcera coccophila (CBS 310.34), Rectifusarium robinianum (CBS 430.91), Rugonectria rugulosa (CBS 126565), and Thelonectria blattea (CBS 952.68) are also announced her

Seasonal Changes in Colour: A Comparison of Structural, Melanin- and Carotenoid-Based Plumage Colours

Plumage coloration is important for bird communication, most notably in sexual signalling. Colour is often considered a good quality indicator, and the expression of exaggerated colours may depend on individual condition during moult. After moult, plumage coloration has been deemed fixed due to the fact that feathers are dead structures. Still, many plumage colours change after moult, although whether this affects signalling has not been sufficiently assessed.) displaying various coloration types (melanin-, carotenoid-based and structural). Birds were caught regularly during three years to measure plumage reflectance. We used models of avian colour vision to derive two variables, one describing chromatic and the other achromatic variation over the year that can be compared in magnitude among different colour types. All studied plumage patches but one (yellow breast of the blue tit) showed significant chromatic changes over the year, although these were smaller than for a typical dynamic trait (bill colour). Overall, structural colours showed a reduction in relative reflectance at shorter wavelengths, carotenoid-based colours the opposite pattern, while no general pattern was found for melanin-based colours. Achromatic changes were also common, but there were no consistent patterns of change for the different types of colours.Changes of plumage coloration independent of moult are probably widespread; they should be perceivable by birds and have the potential to affect colour signalling