Background: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies.Objectives: The objective was to measure the psychological impact... Show moreBackground: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies.Objectives: The objective was to measure the psychological impact of facial skin cancer surgery on patients over a 1-year period. Secondary objective was to meas-ure the difference between Mohs micrographic surgery (MMS) and conventional excision (CE) on these parameters.Methods: This observational survey study was conducted between March 2019 and July 2020. Patients who had facial skin surgery using MMS or CE were selected. Five surveys were conducted on four timepoints (preoperative, 1 week, 3 months and 1 year post-operative) measuring the quality of life, perceived stigmatization, body image, satisfaction with facial appearance and psychosocial distress.Results: A total of 228 patients (MMS 154 patients, CE 74 patients) were included for the analysis. Scores for quality of life did not significantly change, in the year after surgery (PCS-12 mean 50.5, SD 9.3 and MCS-12 50.6, SD 9.4); however, stigmatiza-tion (F (3, 235,39) 7,26, p < 0.01, d = −0.07), body image concerns (F (3, 198,28) = 3.75, p < 0.01, d = −0.14), satisfaction with facial appearance (F (3, 205,18) = 10.74, p < 0.01, d = 0.43) and psychosocial distress (F (3, 208,69) = 9.26, p < 0.01, d = −0.15) did change over time. The use of MMS or CE did not significantly affect outcome scores after 1 year.Conclusion: Patients receiving facial skin cancer surgery exhibited low scores for perceived stigmatization and body image concerns. Their quality of life was not statistically inf luenced by facial surgery, and their satisfaction with their facial appearance and psychosocial distress even improved after 1 year. The results suggest that the surgical treatment type (MMS or CE) does not inf luence the outcome. The overall results can help in counselling strategies to improve expectations for patients receiving facial surgery. Show less
Until the 17th century, the Dutch coastal region of Zeeland ranked among Europe's most urbanized areas, driven by thriving international trade networks. People living in this time of flourishing... Show moreUntil the 17th century, the Dutch coastal region of Zeeland ranked among Europe's most urbanized areas, driven by thriving international trade networks. People living in this time of flourishing economy benefitted enormously from it in terms of employment opportunities and working conditions, which were reportedly better than in the rest of the Low Countries. However, the rapid growth of Zeeland's urban centers likely presented increasing challenges for the population in terms of accessing essential resources, including food, clean water, and housing. In the 19th century, Zeeland's economy ultimately faced a significant downturn due to the decline in the maritime trade, leading to a substantial reduction in its urban population. Examining patterns of urbanization and economic histories that differ from the commonly studied thriving industrial contexts in bioarcheological research, as exemplified by Zeeland, is a crucial yet relatively underexplored facet in our efforts to understanding the human past. To address this gap, this study investigates the impact of urbanization on the health of Zeeland's inhabitants over time by analyzing nonspecific stress markers (i.e., cribra orbitalia, porotic hyperostosis, and linear enamel hypoplasia) and chronic maxillary sinusitis in a sample of 246 individuals from three urban sites dating from 1030 to 1800 CE. Our analysis of skeletal remains reveals significant differences in the prevalence of porotic hyperostosis, linear enamel hypoplasia, and sinusitis between the medieval and post-medieval periods. These findings suggest that de-urbanization and economic decline adversely affected the health and well-being of the populations under study, influenced by factors such as working conditions and food availability. This study provides a new perspective on bioarcheological approaches to urbanization, shedding light on the intricate realities of urbanization in Zeeland and offering important insights into its complexities. Show less
ObjectiveTo assess the differences between endoscopic and radiological methods of analysis for diagnosing chronic maxillary sinusitis (CMS) in archaeological skeletal remains.Materials32 crania... Show moreObjectiveTo assess the differences between endoscopic and radiological methods of analysis for diagnosing chronic maxillary sinusitis (CMS) in archaeological skeletal remains.Materials32 crania from a Dutch post-medieval rural population.MethodsWe assessed the presence of bone changes indicative of CMS (i.e., bone growth and bone resorption) both endoscopically and through computed tomography (CT), and then compared results.ResultsWe observed moderate agreement between bone growth scores obtained through endoscopy and CT, and fair agreement when assessing bone resorption.ConclusionsCMS prevalence rates observed through CT may be comparable to rates assessed endoscopically, although caution is needed when making direct comparisons.SignificanceThis is the first study comparing data obtained through endoscopy and radiological methods in the study of CMS, informing paleopathologists about potential biases in data comparison.LimitationsOur small sample size likely impacted results.Suggestions for further researchFurther research is advised to fully explore the comparability of endoscopic and radiological method of analysis in the study of sinusitis.Data AvailabilityThe datasets generated and analyzed during the current study are available upon request. Show less
Rakers, M.; Hattem, N. van; Simic, I.; Chavannes, N.; Peet, P. van; Bonten, T.; ... ; Os, H. van 2024
Background While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among... Show moreBackground While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among different patient subgroups. Panel management, which involves proactive care for specific patient risk groups, could offer a promising approach to tailor RPM to these groups. This study aims to (i) assess the perception of healthcare professionals and other stakeholders regarding the adoption and (ii) identify the barriers and facilitators for successfully implementing such a panel management approach. Methods In total, nineteen semi-structured interviews and two focus groups were conducted in the Netherlands. Three authors reviewed the audited transcripts. The Consolidated Framework for Implementation Strategies (CFIR) domains were used for the thematic analysis. Results A total of 24 participants (GPs, nurses, health insurers, project managers, and IT consultants) participated. Overall, a panel management approach to RPM in primary care was considered valuable by various stakeholders. Implementation barriers encompassed concerns about missing necessary risk factors for patient stratification, additional clinical and technical tasks for nurses, and reimbursement agreements. Facilitators included tailoring consultation frequency and early detection of at-risk patients, an implementation manager accountable for supervising project procedures and establishing agreements on assessing implementation metrics, and ambassador roles. Conclusion Panel management could enhance proactive care and accurately identify which patients could benefit most from RPM to mitigate CVD risk. For successful implementation, we recommend having clear agreements on technical support, financial infrastructure and the criteria for measuring evaluation outcomes. Show less
Chemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued,... Show moreChemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued, most prospective drugs failed in the follow-up studies due to clinical inefficacy, and hence there is a clear need for alternative approaches. Allosteric modulators of receptor function represent an excellent opportunity for novel drugs, as they modulate receptor activation in a controlled manner and display increased selectivity, and their pharmacological profile can be insurmountable. Here, we discuss allosteric ligands and their pharmacological characterization for modulation of chemokine receptors. Ligands are included if (1) they show clear signs of allosteric modulation in vitro and (2) display evidence of binding in a topologically distinct manner compared to endogenous chemokines. We discuss how allosteric ligands affect binding of orthosteric (endogenous) ligands in terms of affinity as well as binding kinetics in radioligand binding assays. Moreover, their effects on signaling events in functional assays and how their binding site can be elucidated are specified. We substantiate this with examples of published allosteric ligands targeting chemokine receptors and hypothetical graphs of pharmacological behavior. This review should serve as an effective starting point for setting up assays for characterizing allosteric ligands to develop safer and more efficacious drugs for chemokine receptors and, ultimately, other G protein-coupled receptors. Show less
Masquerades form an important part of indigenous African religions, and headpieces of masks are found all over the world as an iconic African art form. Contrary to expectation, however, the... Show moreMasquerades form an important part of indigenous African religions, and headpieces of masks are found all over the world as an iconic African art form. Contrary to expectation, however, the geographical distribution of masking is very restricted, occurring only in three areas of the continent, mainly situated in the forested zones. I explain this peculiar distribution by tracing the ecological and historical parameters of the societies that harbor mask rituals. The main ecological factors are the absence of cattle and the type of horticulture, while a crucial historical element is the long history of slave raiding and trading to which the continent has been subjected. These factors have led to societies in which both gender and local power arrangements show a marked indeterminacy, operating as internal arenas between men and women, and between different groups of men. Crucial in the explanation of masquerades is the fact that masking is completely absent from societies that practice cattle husbandry with the Bos indicus species (zebu). Since sleeping sickness prohibits cattle husbandry, wherever the tsetse fly thrives, masks appear. Show less
Aging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While... Show moreAging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While chronological age serves as a strong risk factor for age-related health conditions, considerable heterogeneity exists in the aging trajectories of individuals, suggesting that biological age may provide a more nuanced understanding of the aging process. However, the concept of biological age lacks a clear operationalization, leading to the development of various biological age predictors without a solid statistical foundation. This paper addresses these limitations by proposing a comprehensive operationalization of biological age, introducing the “AccelerAge” framework for predicting biological age, and introducing previously underutilized evaluation measures for assessing the performance of biological age predictors. The AccelerAge framework, based on Accelerated Failure Time (AFT) models, directly models the effect of candidate predictors of aging on an individual’s survival time, aligning with the prevalent metaphor of aging as a clock. We compare predictors based on the AccelerAge framework to a predictor based on the GrimAge predictor, which is considered one of the best-performing biological age predictors, using simulated data as well as data from the UK Biobank and the Leiden Longevity Study. Our approach seeks to establish a robust statistical foundation for biological age clocks, enabling a more accurate and interpretable assessment of an individual’s aging status. Show less
Observations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are... Show moreObservations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are necessary for providing novel insights into the nature and function of dark states, especially since these are not directly accessible in spectroscopy experiments. Here, we will focus on signatures of dark-type states in chlorosomes, a light-harvesting complex from green sulfur bacteria well-known for uniting a broad absorption band with very efficient energy transfer. In agreement with experiments, our simulations of two-dimensional electronic spectra capture the ultrafast exciton transfer occurring in 100s of femtoseconds within a single chlorosome cylinder. The sub-100 fs process corresponds to relaxation within the single-excitation manifold in a single chlorosome tube, where all initially created populations in the bright exciton states are quickly transferred to dark-type exciton states. Structural inhomogeneities on the local scale cause a redistribution of the oscillator strength, leading to the emergence of these dark-type exciton states, which dominate ultrafast energy transfer. The presence of the dark-type exciton states suppresses energy loss from an isolated chlorosome via fluorescence quenching, as observed experimentally. Our results further question whether relaxation to dark-exciton states is a leading process or merely competes with transfer to the baseplate within the photosynthetic apparatus of green sulfur bacteria. Show less
Paus, L.V. de; Yu, A.; Janssen, A.P.A.; Berg, R.J.B.H.N. van den; Heitman, L.H.; Stelt, M. van der 2024
The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor... Show moreThe cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI-121 that stabilized the inactive conformation of the CB2R. Here, we report the structure-based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click-chemistry with fluorophore-azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function. Show less
Fluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore,... Show moreFluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore, the presentstudy was set up to investigate the effect of fluency training on speechfluency, comprehensibility, and accentedness of interpreter trainees. Twogroups of interpreter trainees at a university in Iran took part in the study,receiving the same amount of instruction and practice (12 hours over 4weeks). The experimental group (N=30) spent 33% of the time (i.e., 4 of the12 hours in the training program) on dedicated fluency strategy training,encouraging the memorization, repetition, and retelling of audio and videomaterials. The remaining 67% was spent on training general speaking skills.The control group (N=30) were only taught general speaking skills in thetraining program but received no dedicated fluency training. Systematicinterviews were run to assess the interpreter trainees’ speech fluency,comprehensibility and accentedness, which were judged independently bythree expert raters at three moments of testing, i.e., pretest, immediateposttest, and delayed posttest (one month later). The findings revealed thatthe fluency training significantly enhanced the interpreter trainees’ fluency,and to a lesser extent the students’ comprehensibility but had only amarginal effect on accentedness. The pedagogical implication would be thatawareness training on speech fluency Show less
The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality... Show moreThe clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers. Show less
Mulholland, M.; Depuydt, M.A.C.; Jakobsson, G.; Ljungcrantz, I.; Grentzmann, A.; To, F.; ... ; Engelbertsen, D. 2024
The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we... Show moreThe interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade.Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production. Show less
