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Bacterial meningitis (BM) is a global public health issue that affects patients of all ages. The two leading causes of BM worldwide are Streptococcus pneumoniae (the pneumococcus) and Neisseria meningitidis (the meningococcus). Despite the use of antibiotics and vaccines, both pneumococcal meningitis (PM) and meningococcal meningitis (MM) result in high case fatality rates and long-term neurological sequelae. Moreover, increasing resistance to first-line antibiotics, limited vaccine coverage, serotype replacement in vaccinated population, and lack of adjunctive therapies to control brain damage are all matters of concern in the management of PM and MM. The availability of animal models of PM and MM is crucial to characterize the pathogenetic and pathophysiologic mechanisms of disease as well as to identify novel antimicrobial agents, adjuvant therapies and vaccine candidates. Historically, animal models of BM employed large animals to mimic the disease in humans, such as monkeys for MM and rabbits for PM. However, since the introduction of rodents, both rats and mice have demonstrated to be robust, reliable, and suitable species for modeling both PM and MM. Depending on the route of infection, the dose of bacterial inoculum, the animal age and strain, different experimental readouts are obtained that permit to answer specific scientific questions. This chapter describes the main features of two models of PM and MM developed in the infant rat and adult mouse, respectively. Each model system presents unique characteristics that allow to study different aspects of the disease. The broad range of different forms of brain injury that can be observed in the PM infant rat model enables to study the entire spectrum of the pathophysiology of brain damage in PM and allows to evaluate novel therapeutic strategies and their impact on long-term neurological sequelae. The MM mouse model is suitable to investigate the role of meningococcal virulence factors in the disease, the host–parasite interactions in the central nervous system, and the efficacy of drugs to control the infection and limit brain damage in MM.

BackgroundThe interactions between tumor cells and the host immune system play a crucial role in lung cancer progression and resistance to treatment. The alterations of EGFR signaling have the potential to produce an ineffective tumor-associated immune microenvironment by upregulating a series of immune suppressors, including inhibitory immune checkpoints, immunosuppressive cells, and cytokines. Elevated Heparin-binding EGF-like growth factor (HB-EGF) expression, one EGFR ligand correlated with higher histology grading, worse patient prognosis, and lower overall survival rate, acts as a chemotactic factor. However, the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the accumulation of immune cells in the tumor microenvironment remains unclear.MethodsThe clinical association of HB-EGF expression in lung cancer was examined using the Gene Expression Omnibus (GEO) repository. HB-EGF expression in different cell types was determined using single-cell RNA sequencing (scRNA-seq) dataset. The correlation between HB-EGF expression and cancer-immune infiltrated cells was investigated by performing TIMER and ClueGo pathways analysis from TCGA database. The chemotaxis of HB-EGF and macrophage infiltration was investigated using migration and immunohistochemical staining.ResultsThe high HB-EGF expression was significantly correlated with poor overall survival in patients with lung adenocarcinoma (LUAD) but not lung squamous cell carcinoma (LUSC). Moreover, HB-EGF expression was correlated with the infiltration of monocytes, macrophages, neutrophils, and dendritic cells in LUAD but not in LUSC. Analysis of scRNA-seq data revealed high HB-EGF expression in lung cancer cells and myeloid cells. Results from the pathway analysis and cell-based experiment indicated that elevated HB-EGF expression was associated with the presence of macrophage and lung cancer cell migration. HB-EGF was highly expressed in tumors and correlated with M2 macrophage infiltration in LUAD.ConclusionsHB-EGF is a potential prognostic marker and therapeutic target for lung cancer progression, particularly in LUAD.

Additional file 2: Figure S2. IL-1β significantly correlated with MMP-9 at 18 hpi (p=0.04, r=0.5126; n=17) (A), but showed only a trend at 42 hpi (p=0.07, r=0.3940; n=22) (B).

Swidden cultivation practices have been seen as a major driver of deforestation and forest degradation in Southeast Asia. Using two case studies from Vietnam, this paper examines discourses around swidden practices at multiple levels of governance. Our findings show diverse interpretations of swidden resulting in different policy preferences and policy translations when addressing the issue. At national level, swidden is blamed as a principal driver of deforestation and forest degradation, and as such is a practice to be eliminated. As a result of this national stance, provincial level authorities see the existence of swidden as a failure by which their political performance will be judged. Conversely, swidden communities are seen at district level as an innovative solution to help resource-limited police forces ensure national security in border areas. Local commune and village leaders view swidden as a traditional practice to be respected, so as to maintain harmonious relationships amongst social groups, and avoid ethnic groups protesting against the government. Such differences in discourses and political interests have led to swidden becoming an ‘invisible’ issue, with government authorities failing to collect and report on data. Not recognizing swidden also means that swidden actors are practically ‘forgotten’ in the design and implementation of Reducing Emissions from Deforestation and Forest Degradation (REDD+) and Payments for Ecosystem Services (PES). Their omission from forest conservation and management incentive programmes could lead to further social marginalization, and potentially result in deforestation and forest degradation in the area. Our findings suggest that REDD+ policies should take into account diverging political interests on controversial land uses such as swidden cultivation.

Payments for Ecosystem Services schemes, or PES, offer a useful approach to account for the largely unrecognized value of ecosystem services provided by the forestry sector. However, the actual impacts of PES schemes, both in effectively protecting the environmental quality of an ecosystem, such as the water filtration capacity of a forest, and on improving local livelihoods, often remain unknown. Policy evaluation in general, and for newly established policies in particular, plays a critical role in providing essential feedback about what is actually happening on the ground. Thus, for PES to generate outcomes that are effective, efficient and equitable, policy makers must develop a functional evaluation system. As PES schemes around the world face similar problems in monitoring and evaluation, we draw on the case of Vietnam—the first country in Asia to introduce a nationwide PES scheme—and analyze the effectiveness of the monitoring and evaluation activities of the Payment for Forest Environmental Services program (PFES). We also offer practical policy recommendations for future PFES implementation. We find that monitoring and evaluation of PFES in Vietnam is still in its infancy. Although there is a strong accounting of revenues generated from ecosystem services buyers, there is a discernible lack of ability to assess the quantity and quality of ecosystem services being enhanced by the program; fulfillment of contractual obligations; the appropriateness of financial flows; or socio-economic impacts of the program. We argue that a functioning PES evaluation system must include an accessible grievance mechanism to ensure transparency and accountability in the distribution of PES revenues from central to local levels.

Additional file 1: Figure S1. At 18 hpi, inflammatory cytokines – TNF-α, IL-6 and IL-1β – correlated with each other (n=17).

Additional file 1: Figure S1. At 18 hpi, inflammatory cytokines – TNF-α, IL-6 and IL-1β – correlated with each other (n=17).