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Dexamethasone is a synthetic glucocorticoid commonly used for the prevention and management of side effects in cancer patients undergoing chemotherapy. While it is effective as an anti-emetic and in preventing hypersensitivity reactions, dexamethasone depletes peripheral blood lymphocytes and impacts immune responses. The effect of dexamethasone on the number and quality of tumour-infiltrating leukocytes has not been reported. To address this, we calibrated the dose in two different strains of mice to achieve the same extent of peripheral blood lymphocyte depletion observed in patients with cancer. Doses that caused analogous depletion of T and B lymphocytes and NK cells from the peripheral blood, elicited no change in these populations within the tumour. The expression of immune checkpoint molecules PD-1, OX40, GITR and TIM3 on tumour-infiltrating lymphocytes was not altered. We found that dexamethasone had a small but significant deleterious impact on weakly efficacious chemoimmunotherapy but had no effect when the protocol was highly efficacious. Based on these results, we predict that dexamethasone will have a modest negative influence on the overall effectiveness of chemoimmunotherapy treatment.

IntroductionThere is clinical evidence of neurological manifestations in coronavirus disease-19 (COVID-19). However, it is unclear whether differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/spike protein (SP) uptake by cells of the cerebrovasculature contribute to significant viral uptake to cause these symptoms.MethodsSince the initial step in viral invasion is binding/uptake, we used fluorescently labeled wild type and mutant SARS-CoV-2/SP to study this process. Three cerebrovascular cell types were used (endothelial cells, pericytes, and vascular smooth muscle cells), in vitro.ResultsThere was differential SARS-CoV-2/SP uptake by these cell types. Endothelial cells had the least uptake, which may limit SARS-CoV-2 uptake into brain from blood. Uptake was time and concentration dependent, and mediated by angiotensin converting enzyme 2 receptor (ACE2), and ganglioside (mono-sialotetrahexasylganglioside, GM1) that is predominantly expressed in the central nervous system and the cerebrovasculature. SARS-CoV-2/SPs with mutation sites, N501Y, E484K, and D614G, as seen in variants of interest, were also differentially taken up by these cell types. There was greater uptake compared to that of the wild type SARS-CoV-2/SP, but neutralization with anti-ACE2 or anti-GM1 antibodies was less effective.ConclusionThe data suggested that in addition to ACE2, gangliosides are also an important entry point of SARS-CoV-2/SP into these cells. Since SARS-CoV-2/SP binding/uptake is the initial step in the viral penetration into cells, a longer exposure and higher titer are required for significant uptake into the normal brain. Gangliosides, including GM1, could be an additional potential SARS-CoV-2 and therapeutic target at the cerebrovasculature.

IntroductionSore throat is a common reason for overuse of antibiotics. The value of inflammatory or biomarkers in throat swab or saliva samples in predicting benefit from antibiotics is unknown.MethodsWe used the ‘person-based approach’ to develop an online tool to support self-swabbing and recruited adults and children with sore throats through participating general practices and social media. Participants took bacterial and viral swabs and a saliva sponge swab and passive drool sample. Bacterial swabs were cultured for streptococcus (Group A, B, C, F and G). The viral swab and saliva samples were tested using a routine respiratory panel PCR and Covid-19 PCR testing. We used remaining viral swab and saliva sample volume for biomarker analysis using a panel of 13 biomarkers.ResultsWe recruited 11 asymptomatic participants and 45 symptomatic participants. From 45 symptomatic participants, bacterial throat swab, viral throat swab, saliva sponge and saliva drool samples were returned by 41/45 (91.1%), 43/45 (95.6%), 43/45 (95.6%) and 43/45 (95.6%) participants respectively. Three saliva sponge and 6 saliva drool samples were of insufficient quantity. Two adult participants had positive bacterial swabs. Six participants had a virus detected from at least one sample (swab or saliva). All of the biomarkers assessed were detectable from all samples where there was sufficient volume for testing. For most biomarkers we found higher concentrations in the saliva samples. Due to low numbers, we were not able to compare biomarker concentrations in those who did and did not have a bacterial pathogen detected. We found no evidence of a difference between biomarker concentrations between the symptomatic and asymptomatic participants but the distributions were wide.ConclusionsWe have demonstrated that it is feasible for patients with sore throat to self-swab and provide saliva samples for pathogen and biomarker analysis. Typical bacterial and viral pathogens were detected but at low prevalence rates. Further work is needed to determine if measuring biomarkers using oropharyngeal samples can help to differentiate between viral and bacterial pathogens in patients classified as medium or high risk using clinical scores, in order to better guide antibiotic prescribing and reduce inappropriate prescriptions.

Cities are recognised as key enablers for the world’s sustainable future. Urban sprawl and inefficient use of land are important issues significantly impacting the provision and use of open green spaces. The United Nations Sustainable Development Goal (SDG) indicator 11.7.1 aims at globally monitoring the amount of land that is dedicated by cities for public space. In Europe, the indicator “Share of urban population without green urban areas in their neighbourhood” is supposed to correspond to the SDG11.7.1 but is currently on-hold due to methodological issues and lack of data. Moreover, to efficiently assess public space conditions, timely and spatially disaggregated information is essential but not yet widely adopted by urban practitioners. Hereafter, we use a combination of satellite and crowdsourced Earth Observations (EO) to model physical accessibility to urban green spaces in four European cities. Findings suggest that it is technically feasible to derive information on the share of urban population without green urban areas in their neighbourhood. Results demonstrate that the proposed methodology represents a consistent, valid, reliable, low-cost, timely and continuous source of information for sustainable urban development. Open and free EO data can be a good complement to enhance official and traditional statistics on urban areas facilitating EU reporting against the SDG indicator for better comparison between EU countries.

This analysis briefly compares the economic impacts of three potential future management scenarios for Šumava National Park (NP) in the Czech Republic: (1) continuation of current management, (2) the adoption of draft Bills that would declassify protected areas and enable developments (e.g. ski lift development) within some of the Park ’ s most valuable habitats for wildlife, and (3) the adoption of proposals to expand the wilderness area in the Park ’ s core with associated tourism opportunities. The proposals in the draft Bills have the potential to generate employment through ski lift development, but much of this activity will use imported labour and/or be short-term (e.g. associated with construction work). The financial viability of this development is uncertain for a number of reasons, including: likely requirements to compensate for damage to protected habitats, reduced future snow cover due to climate change, and competition to attract sufficient visitors to use the ski lift. The economic impacts of the adoption of the draft Bills (and, to a lesser extent, of continuing with current management) would also include negative effects on current nature tourism activity and on its long-term potential to expand. Currently, and certainly if the proposed plans in the draft Bill are adopted, the value of the NP as an area of wilderness and high-quality ecosystems will be reduced. This would weaken one of its key selling points as a tourism and recreation destination. The opportunity for international branding of the national park based on these ecosystems would be diminished. This damage to ecosystems would go against the views of the 75% of the Czech population who agree that it is important to halt the loss of biodiversity because we have a moral obligation to look after nature. Pro-wilderness development offers an alternative scenario. It would allow economic opportunities to be pursued to promote nature-based tourism at new locations and activities around an expanded non-intervention zone, while not undermining the ecological integrity of the NP. The Šumava NP is a unique area which supports a wide variety of habitats and species and has the potential to form one of the largest areas of natural forest and wetland habitat in Central Europe. This tourism offer is in keeping with visitor ’ s preferences (identified in a 2010 survey), and can exploit global growth in ecotourism activity. The best access points to the Šumava NP ’ s wilderness are currently regarded as being “full” in that further increases in visitors would damage the wilderness experience which draws visitors. Therefore, there is perceived to be demand for a larger number of carefully managed access points to a larger wilderness area. To maximise the local economic benefits of this tourism development around the park, appropriate training for the local workforce is required. Local benefits could be enhanced through nature-based tourism development that is spread throughout the communities in and around the park. This would not conflict with the park ’ s wild image that attracts visitors, and this visitor market could grow with support from expanded marketing activity. The potential local economic benefits from the pro-wilderness development option include: maintaining and expanding employment in management of the National Park ’ s habitats, visitor facilities and access points; increased nature-based tourism trade in the villages within and surrounding the Park; increased opportunities to attract financing for local economic development (e.g. training and SME support for nature-based tourism), and for the Park ’ s management, both internationally (e.g. from EU funding sources), and locally (e.g. through fees for visitors using specific facilities); a greater proportion of value-added in the tourism offer being generated within the local community, meaning more income can be retained locally and support greater indirect economic activity, and maintaining forestry employment. Key aspects of this analysis are the way in which tourism potential at the Park is developed, and the extent of logging as a measure to manage bark beetle. Šumava NP borders the Bayerischer Wald NP in Germany, which has developed a successful nature-based tourism industry. This offers a proven model to pursue sustainable economic development under the pro-wilderness development scenario, and a unique opportunity for complementary promotion of the two parks branded as the “Wild Heart of Europe”. More specific predictions of economic and employment impacts will require a full economic study. However, this initial analysis indicates that the pro-wilderness scenario offers a more economically and environmentally sustainable development plan for Šumava NP than either the current situation or the plans proposed in draft Bills. It is recommended that proposals in draft Bills should not be pursued at least until a fuller economic evaluation of options has been undertaken.