Repelling neoliberal world-making? How the ageing–dementia relation is reassembling the social

Growing old ‘badly’ is stigmatizing, a truism that is enrolled into contemporary agendas for the biomedicalization of ageing. Among the many discourses that emphasize ageing as the root cause of later life illnesses, dementia is currently promoted as an epidemic and such hyperbole serves to legitimate its increasing biomedicalization. The new stigma however is no longer contained to simply having dementia, it is failing to prevent it. Anti-ageing cultures of consumption, alongside a proliferation of cultural depictions of the ageing–dementia relation, seem to be refiguring dementia as a future to be worked on to eliminate it from our everyday life. The article unpacks this complexity for how the ageing–dementia relation is being reassembled in biopolitics in ways that enact it as something that can be transformed and managed. Bringing together Bauman’s theories of how cultural communities cope with the otherness of the other with theories of the rationale for the making of monsters – such as the figure of the abject older person with dementia – the article suggests that those older body-persons that personify the ageing–dementia relation, depicted in film and television for example, threaten the modes of ordering underpinning contemporary lives. This is not just because they intimate loss of mind, or because they are disruptive, but because they do not perform what it is to be ‘response-able’ and postpone frailty through managing self and risk

Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds

Polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls in fish from the Netherlands: concentrations, profiles and comparison with DR CALUX® bioassay results

Fish from Dutch markets were analysed for concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) and compared with the new European maximum residue levels (MRLs), set in 2006. In a first study on 11 different fish and shellfish from various locations, concentrations of PCDD/Fs were nearly all below the MRL for PCDD/Fs [4 pg toxic equivalents (TEQ) per gram wet weight (ww)] and nearly all below 8 pg total TEQ/g ww, the new MRL for the sum of PCDD/Fs and DL-PCBs. Some samples exceeded the total TEQ MRL, such as anchovy, tuna and sea bass. Furthermore, 20 (out of 39) wild eel samples exceeded the specific MRL for eel (12 pg total TEQ/g ww), as the study revealed PCDD/F TEQ levels of 0.2-7.9 pg TEQ/g ww and total TEQ values of 0.9 to 52 pg/g ww. TEQ levels in farmed and imported eel were lower and complied with the MRLs. Smoking eel, a popular tradition in the Netherlands, only had marginal effects on PCDD/F and DL-PCB concentrations. Owing to volatilization, concentrations of lower-chlorinated PCBs were reduced to below the limit of quantification after smoking. DL-PCBs contributed 61-97% to the total TEQ in all eel samples. This also holds for other fish and shellfish (except shrimps): DL-PCB contributed (on average) from 53 (herring) to 83% (tuna) to the total TEQ. Principal-component analysis revealed distinctive congener profiles for PCDD/Fs and non-ortho PCBs for mussels, pikeperch, herring and various Mediterranean fish. The application of new TCDD toxic equivalency factors (TEFs) set by the World Health Organization in 2006 (to replace the 1997 TEFs) resulted in lower TEQ values, mainly owing to a decreased mono-ortho PCB contribution. This decrease is most pronounced for eel, owing to the relative high mono-ortho PCB concentrations in eel. Consequently, a larger number of samples would comply with the MRLs when the new TEFs are applied. The DR CALUX (R) assay may be used for screening total TEQ levels in eel, in combination with gas chromatography-high resolution mass spectrometry confirmation of suspected samples. An almost 1:1 correlation was found when the 1997 TEFs were applied, but, surprisingly, a 1.4-fold overestimation occurred with application of the 2006 TEFs