Expression sites of the collectin SP-D suggest its importance in first line host defence: power of combining in situ hybridisation, RT-PCR and immunohistochemistry

Surfactant proteins A and D are pattern recognition molecules that play a role in pulmonary host defence. In this paper, we describe for the first time the expression and localisation of both collectins in various porcine tissues using a combination of in situ hybridisation (ISH), RT-PCR and immunohistochemistry (IHC). SP-D was expressed in several tissues including lung, tongue, intestinal tract, thymus, skin, gall bladder and lacrimal gland. Focal SP-D expression was detected in oesophagus, stomach, kidney, liver, prostate and spleen with both histological techniques. These tissues tested negative with RT-PCR. In contrast, SP-A expression was limited to the lung as measured by ISH and IHC. Interestingly, analysis by RT-PCR showed that thymus, trachea, jejunum and duodenum are positive for the presence of SP-A mRNA. We conclude that the combination of different methods can be advantageous if tissue-specific expression is studied. The importance of SP-D in innate immune defence of the pig is underlined by its expression at the potential ports of entry of pathogens.     

Assessing Lung Cancer Screening Programs under Uncertainty in a Heterogeneous Population

Background

Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population.

Demand-oriented and demand-driven health care: the development of a typology

In most European countries, there is an increasing demand for demand-oriented and demand-driven approaches in the development of health care policy and the organization of health care services. Both approaches, in which the main focus is on 'the demand', are seen as counterparts of the supply-oriented approach, that has 'the supply' as point of departure. However, there is much confusion about the definition of the concepts. To identify the different views, and to examine to what extent there is consensus in the Netherlands about the concepts of demand-orientation and demand-driven care, a Delphi study was done among 26 experts; scientists, health care insurance companies, health care suppliers, the government, independent advisory bodies and client interest groups. The study resulted in a typology. The similarities and differences between the two concepts were demonstrated in five dimensions; responsibility, control, need-determination, formal embedment of vision in organization and choice. Furthermore, the typology was used to identify existing types of services as being either demand-oriented or demand-driven services. The typology provides an understanding of the similarities and differences between the two concepts, and appears to be a useful tool in identifying services to the extent that they are demand oriented or demand driven.     

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.     

Anchoring molecular mechanisms to the adverse outcome pathway for skin sensitization: Analysis of existing data

Allergic contact dermatitis (ACD) is a hypersensitivity immune response induced by small protein-reactive chemicals. Currently, the murine local lymph node assay (LLNA) provides hazard identification and quantitative estimation of sensitizing potency. Given the complexity of ACD, a single alternative method cannot replace the LLNA, but it is necessary to combine methods through an integrated testing strategy (ITS). In the development of an ITS, information regarding mechanisms and molecular processes involved in skin sensitization is crucial. The recently published adverse outcome pathway (AOP) for skin sensitization captures mechanistic knowledge into key events that lead to ACD. To understand the molecular processes in ACD, a systematic review of murine in vivo studies was performed and an ACD molecular map was constructed. In addition, comparing the molecular map to the limited human in vivo toxicogenomic data available suggests that certain processes are similarly triggered in mice and humans, but additional human data will be needed to confirm these findings and identify differences. To gain insight in the molecular mechanisms represented by various human in vitro systems, the map was compared to in vitro toxicogenomic data. This analysis allows for comparison of emerging in vitro methods on a molecular basis, in addition to mathematical predictive value. Finally, a survey of the current in silico, in chemico, and in vitro methods was used to indicate which AOP key event is modeled by each method. By anchoring emerging classification methods to the AOP and the ACD molecular map, complementing methods can be identified, which provides a cornerstone for the development of a testing strategy that accurately reflects the key events in skin sensitization.