Factors for a broad technology assessment of comprehensive genomic profiling in advanced cancer, a systematic review.

Comprehensive Genomic Profiling (CGP) allows for the identification of many targets. Reimbursement decision-making is, however, challenging because besides the health benefits of on-label treatments and costs, other factors related to diagnostic and treatment pathways may also play a role. The aim of this study was to identify which other factors are relevant for the technology assessment of CGP and to summarize the available evidence for these factors. After a scoping search and two expert sessions, five factors were identified: feasibility, test journey, wider implications of diagnostic results, organisation of laboratories, and "scientific spillover". Subsequently, a systematic search identified 83 studies collecting mainly evidence for the factors "test journey" and "wider implications of diagnostic results". Its nature was, however, of limited value for decision-making. We recommend the use of comparative strategies, uniformity in outcome definitions, and the inclusion of a comprehensive set of factors in future evidence generation.

Accumulation of airborne microplastics on leaves of different tree species in the urban environment.

Microplastics (MPs) are omnipresent in the environment and they are linked to ecosystem and human health problems. The atmospheric transport of MPs and the role of tree leaves in MP atmospheric deposition has not been adequately studied. MP concentrations on the leaves of different tree species in urban regions of the Netherlands and Portugal, along with related MP deposition, were investigated in this study. We collected leaves from cedar, eucalyptus, oak, pine and willow trees, together with monthly deposition of particles under the trees and in the open space in Coimbra (Portugal). In Wageningen (the Netherlands), we collected leaves from a fir and a holly tree at different heights above the ground and with dry and wet weather conditions. MPs were extracted through density separation and quantified under a microscope. Polymer types were identified using µ-FTIR. The results showed a higher number of MP particles on the needle-shaped leaves from fir (2.52 ± 2.14 particles·cm-2) and pine (0.5 ± 0.13 particles·cm-2) and significantly lower numbers of MPs per cm2 of leaf area on the bigger leaves from eucalyptus (0.038 ± 0.003 particles·cm-2) and cedar (0.037 ± 0.002 particles·cm-2). All tree leaves seemed to filter airborne MPs, especially the smallest particles. A non-significantly higher number of particles on leaves was detected on lower tree branches and after dry periods. The deposition of MPs under trees was generally higher than in the open space. Our results indicated that part of the MPs retained by the tree leaves floats down to lower branches and to the soil surface. We also saw that different tree species had different capacities to retain particles on their leaves over time. To control the transport of MPs through the atmosphere, it is essential to consider the role of different vegetation types in filtering small particles, especially in cities.

Specialization of anterior and posterior hippocampal functional connectivity differs in autism.

Structural and functional differences in the hippocampus have been related to the episodic memory and social impairments observed in autism spectrum disorder (ASD). In neurotypical individuals, hippocampal-cortical functional connectivity systematically varies between anterior and posterior hippocampus, with changes observed during typical development. It remains unknown whether this specialization of anterior-posterior hippocampal connectivity is disrupted in ASD, and whether age-related differences in this specialization exist in ASD. We examined connectivity of the anterior and posterior hippocampus in an ASD (N = 139) and non-autistic comparison group (N = 133) aged 5-21 using resting-state functional magnetic resonance imaging (MRI) data from the Healthy Brain Network (HBN). Consistent with previous results, we observed lower connectivity between the whole hippocampus and medial prefrontal cortex in ASD. Moreover, preferential connectivity of the posterior relative to the anterior hippocampus for memory-sensitive regions in posterior parietal cortex was reduced in ASD, demonstrating a weaker anterior-posterior specialization of hippocampal-cortical connectivity. Finally, connectivity between the posterior hippocampus and precuneus negatively correlated with age in the ASD group but remained stable in the comparison group, suggesting an altered developmental specialization. Together, these differences in hippocampal-cortical connectivity may help us understand the neurobiological basis of the memory and social impairments found in ASD.

The spatial distribution of microplastics in topsoils of an urban environment - Coimbra city case-study.

Due to their seemingly ubiquitous nature and links to environmental and human health problems, microplastics are quickly becoming a major concern worldwide. Artificial environments, such as those found in urban environments, represent some of the main sources of microplastic. However, very few studies have focused on the occurrence of microplastics in urban soils. The aim of the current research was to evaluate the microplastic contamination in urban soils from artificial and natural land uses throughout Coimbra city, Portugal. Sixty-seven spaces and ten land use areas were evaluated. The artificial land use areas were dumps, landfills, parking lots, industries and construction areas, and the natural land use areas were forests, urban parks, moors (wetlands), pastures and urban agricultural areas. Microplastic extraction was done by density separation. Quantification and size measurements of microplastics was carried out using a microscope. Polymer types were identified by µ-FTIR for 25% of the samples. The microplastic content ranged from 5 × 103 to 571 × 103 particles·kg-1, with a mean of 106 × 103 particle·kg-1. The green park was the land use with the highest concentration of microplastics (158 × 103 particle·kg-1) and the forest was the one with the lowest concentration (55 × 103 particle·kg-1). The landfill (150 × 103 particle·kg-1), industry (127 × 103 particle·kg-1) and dump (126 × 103 particle·kg-1) were the artificial spaces with the highest levels of microplastics. The main polymers detected were polypropylene and polyethylene, followed by polyvinyl chloride and rubber, and the main sizes measured between 50 and 250 µm. Our results indicate that natural spaces can contain higher amounts of microplastics as compared to artificial spaces in the urban environment. This suggests that microplastics are easily transported through the urban landscape and that urban green spaces can retain microplastics in their soils. Land use planning may present an opportunity to better control the levels of microplastics in urban environments.

The effect of estrogen on brown adipose tissue activity in male rats.

OBJECTIVE: Centrally administered estrogen can increase sympathetic nerve activity to brown adipose tissue, resulting in thermogenesis. The central thermogenic effects of estrogen have not been investigated in males. Therefore, this study sought to investigate the effects of peripherally and centrally administered estrogen on thermogenesis, heart rate and mean arterial pressure in male rats. Thermogenesis was assessed by monitoring brown adipose tissue temperature. RESULTS: Peripherally administered estrogen elicited no significant effect on brown adipose tissue temperature, heart rate or mean arterial pressure. Centrally administered estrogen elicited a coincident increase in both brown adipose tissue and core temperature. Centrally administered estrogen also resulted in a decrease in mean arterial pressure but had no effect on heart rate. With the present data it is not possible to elucidate whether changes in temperature were the result of thermogenic or thermoregulatory mechanisms.

Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats.

The role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5-10 µg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.

Democratizing the world health organization.

A progressive erosion of the democratic space appears as one of the emerging challenges in global health today. Such delimitation of the political interplay has a particularly evident impact on the unique public interest function of the World Health Organization (WHO). This paper aims to identify some obstacles for a truly democratic functioning of the UN specialized agency for health. The development of civil society's engagement with the WHO, including in the current reform proposals, is described. The paper also analyses how today's financing of the WHO--primarily through multi-bi financing mechanisms--risks to choke the agency's role in global health. Democratizing the public debate on global health, and therefore the role of the WHO, requires a debate on its future role and engagement at the country level. This desirable process can only be linked to national debates on public health, and the re-definition of health as a primary political and societal concern.