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Plants of the Asteraceae family have been used in traditional medicine for centuries due to their main antimicrobial and analgesic activities. A liniment from Artemisia californica has recently been tested on patients affected by either acute pain or chronic pain conditions with great success.The aim of this study was to evaluate the anti-inflammatory activity of sesquiterpene lactones (SLs), representing the majority in the Asteraceae family. Leucodin, α-santonin and sclareolide (three SLs) were chosen to undergo chemical modifications. This pool of molecules underwent molecular modeling experiments using an in-house program, WATGEN, predicting the water network and its contribution to the overall affinity of the enzyme-ligand complex. The anti-inflammatory activity and the ability of compounds to modulate COX-2 expression have been evaluated in LPS-stimulated RAW 264.7 cells and in RIF-1 cells treated according to the Photodynamic Therapy (PDT) protocols using Photoprin (PH) as photosensitizer. Furthermore, commercially available assay kits were used to evaluate the concentration of PGE-2 and the direct inhibition of COX-2. All the tested molecules fit well in the enzyme binding pocket, but to get a substantial inhibition of the expression and activity of the enzyme as well as a reduction in the PGE2 concentration, high concentrations of the compounds are needed. The only exceptions being leucodin itself and FP6, one of the α-santonin derivatives, presenting a CF3 functional group. We believe that this class of compounds has some interesting potential in the treatment of pain and inflammation. Although, the activity seems to be due to a mechanism related to the expression of the COX enzymes rather than on a direct inhibition.

Treatments for retinoblastoma (Rb) vary depending on the size and location of the intraocular lesions and include chemotherapy and radiation therapy. We examined whether agents used to treat Rb induce a pro-survival phenotype associated with increased expression of survivin, a member of the inhibitor of apoptosis family of proteins. We document that exposure to carboplatin, topotecan or radiation resulted in elevated expression of survivin in two human Rb cell lines but not in normal retinal pigmented epithelial (RPE) cells. Cellular levels of survivin were attenuated in Rb cells exposed to an imidazolium-based survivin suppressant, Sepantronium bromide (YM155). Protein expression patterns of survivin in RPE cells were not altered following treatment protocols involving exposure to YM155. Including YM155 with chemotherapy or radiation increased levels of apoptosis in Rb cells but not in RPE cells. Intraocular luciferase expressing Rb tumors were generated from the Rb cell lines and used to evaluate the effects of carboplatin and YM155 on in-vivo survivin expression and tumor growth. Carboplatin induced expression of survivin while carboplatin combined with YM155 reduced survivin expression in tumor bearing eyes. The combination protocol was also most effective in reducing the rate of tumor regrowth. These results indicate that targeted inhibition of the anti-apoptotic protein survivin provides a therapeutic advantage for Rb cells and tumors treated with chemotherapy.

BackgroundWhen caring for patients with chronic conditions such as chronic obstructive pulmonary disease (COPD), health care professionals (HCPs) rely on multiple data sources to make decisions. Collating and visualizing these data, for example, on clinical dashboards, holds the potential to support timely and informed decision-making. Most studies on data-supported decision-making (DSDM) technologies for health care have focused on their technical feasibility or quantitative effectiveness. Although these studies are an important contribution to the literature, they do not further our limited understanding of how HCPs engage with these technologies and how they can be designed to support specific contexts of use. To advance our knowledge in this area, we must work with HCPs to explore this space and the real-world complexities of health care work and service structures. ObjectiveThis study aimed to qualitatively explore how DSDM technologies could support HCPs in their decision-making regarding COPD care. We created a scenario-based research tool called Respire, which visualizes HCPs’ data needs about their patients with COPD and services. We used Respire with HCPs to uncover rich and nuanced findings about human-data interaction in this context, focusing on the real-world challenges that HCPs face when carrying out their work and making decisions. MethodsWe engaged 9 respiratory HCPs from 2 collaborating health care organizations to design Respire. We then used Respire as a tool to investigate human-data interaction in the context of decision-making about COPD care. The study followed a co-design approach that had 3 stages and spanned 2 years. The first stage involved 5 workshops with HCPs to identify data interaction scenarios that would support their work. The second stage involved creating Respire, an interactive scenario-based web app that visualizes HCPs’ data needs, incorporating feedback from HCPs. The final stage involved 11 one-to-one sessions with HCPs to use Respire, focusing on how they envisaged that it could support their work and decisions about care. ResultsWe found that HCPs trust data differently depending on where it came from and who recorded it, sporadic and subjective data generated by patients have value but create challenges for decision-making, and HCPs require support in interpreting and responding to new data and its use cases. ConclusionsOur study uncovered important lessons for the design of DSDM technologies to support health care contexts. We show that although DSDM technologies have the potential to support patient care and health care delivery, important sociotechnical and human-data interaction challenges influence the design and deployment of these technologies. Exploring these considerations during the design process can ensure that DSDM technologies are designed with a holistic view of how decision-making and engagement with data occur in health care contexts.

Summary: Digital technology is having a major impact on many areas of society, and there is equal opportunity for impact on science. This is particularly true in the environmental sciences as we seek to understand the complexities of the natural environment under climate change. This perspective presents the outcomes of a summit in this area, a unique cross-disciplinary gathering bringing together environmental scientists, data scientists, computer scientists, social scientists, and representatives of the creative arts. The key output of this workshop is an agreed vision in the form of a framework and associated roadmap, captured in the Windermere Accord. This accord envisions a new kind of environmental science underpinned by unprecedented amounts of data, with technological advances leading to breakthroughs in taming uncertainty and complexity, and also supporting openness, transparency, and reproducibility in science. The perspective also includes a call to build an international community working in this important area. The Bigger Picture: Digital technology is having a major impact on many areas of society, and there is equal opportunity for impact on science in addressing grand scientific challenges. This is particularly true in the environmental sciences as we seek to understand the complexities of the natural environment under climate change. This perspective reports on the outcomes from a summit in this area, attended by 42 researchers selected as leading experts operating at the interface between digital technology and the environmental sciences. The key output of this workshop was the Windermere Accord, a collective statement around what is required to achieve a transformative effect through digital technology based around four key pillars of investigation, namely using technology to tame uncertainty; growing advocates and champions to enable, empower, and influence; embracing a new open and transparent style of science; and enabling integration and sophisticated treatment of feedbacks in complex environmental systems. These pillars all feed into the decision-making processes and are supported by a growing community. Looking forward, the accord also identified a pathway with particular emphasis on building an international, cross-disciplinary community to address the key challenges and achieve the real opportunities around digital technology and the environment.

Digital citizen science platforms are prominent examples of modern volunteerism that provide people with opportunities to observe natural phenomena and to engage in scientific processes. In this study, we explore the values and motivations underlying sustained participation in digital citizen science projects through the lenses of two social psychology theories (Schwartz’s Human Values Theory and Self-Determination Theory). We present in-depth analyses of interviews with 15 long-term volunteers in two digital citizen science initiatives (Järviwiki and Safecast) that have been collecting environmental data for a decade in Finland and Japan. Our results advance the understanding of the values underpinning motivations. Our analyses show that openness-to-change values, such as self-direction, are important for initial participation, yet a diverse range of values, except for power, play a role in sustaining participation. Our study also shows that the values related to sustained participation are linked with extrinsic motivations, suggesting that when extrinsic motivators are self-directed, people will not only perform tasks willingly and enthusiastically but also in a sustained manner. Conceptualizing the behavioral continuum that drives volunteering actions provides practical insights that can assist the design, development, and evaluation of digital citizen science platforms.