Fracture hospitalizations between years 2000 and 2007 in Switzerland: a trend analysis

Summary: In Switzerland, the total number and incidence of hospitalizations for major osteoporotic fractures increased between years 2000 and 2007, while hospitalizations due to hip fracture decreased. The cost impact of shorter hospital stays was offset by the increasing cost per day of hospitalization. Introduction: The aim of the study was to establish the trends and epidemiological characteristics of hospitalizations for major osteoporotic fractures (MOF) between years 2000 and 2007 in Switzerland. Methods: Sex- and age-specific trends in the number and crude and age-standardized incidences of hospitalized MOF (hip, clinical spine, distal radius, and proximal humerus) in women and men aged ≥45years were analyzed, together with the number of hospital days and cost of hospitalization, based on data from the Swiss Federal Statistical Office hospital database and population statistics. Results: Between 2000 and 2007, the absolute number of hospitalizations for MOF increased by 15.9% in women and 20.0% in men, mainly due to an increased number of non-hip fractures (+37.7% in women and +39.7% in men). Hospitalizations for hip fractures were comparatively stable (−1.8% in women and +3.3% in men). In a rapidly aging population, in which the number of individuals aged ≥45years grew by 11.1% (women) and 14.6% (men) over the study period, the crude and age-standardized incidences of hospitalizations decreased for hip fractures and increased for non-hip MOF, both in women and men. The length of hospital stay decreased for all MOF in women and men, the cost impact of which was offset by an increase in the daily costs of hospitalization. Conclusions: Between years 2000 and 2007, hospitalizations for MOF continued to increase in Switzerland, driven by an increasing number and incidence of hospitalizations for non-hip fractures, although the incidence of hip fractures has decline

Conditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesis

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 7 (2012): e43039, doi:10.1371/journal.pone.0043039.The transition metal, copper (Cu), is an enzymatic cofactor required for a wide range of biochemical processes. Its essentiality is demonstrated by Menkes disease, an X-linked copper deficiency disorder characterized by defects in nervous-, cardiovascular- and skeletal systems, and is caused by mutations in the ATP7A copper transporter. Certain ATP7A mutations also cause X-linked Spinal Muscular Atrophy type 3 (SMAX3), which is characterized by neuromuscular defects absent an underlying systemic copper deficiency. While an understanding of these ATP7A-related disorders would clearly benefit from an animal model that permits tissue-specific deletion of the ATP7A gene, no such model currently exists. In this study, we generated a floxed mouse model allowing the conditional deletion of the Atp7a gene using Cre recombinase. Global deletion of Atp7a resulted in morphological and vascular defects in hemizygous male embryos and death in utero. Heterozygous deletion in females resulted in a 50% reduction in live births and a high postnatal lethality. These studies demonstrate the essential role of the Atp7a gene in mouse embryonic development and establish a powerful model for understanding the tissue-specific roles of ATP7A in copper metabolism and disease.This work was supported by National Institutes of Health Grants DK59893 and DK093386 to M.J.P., and DK44464 to J.D.G

Comparing international coverage of 9/11 : towards an interdisciplinary explanation of the construction of news

This article presents an interdisciplinary model attempting to explain how news is constructed by relying on the contributions of different fields of study: News Sociology, Political Communications, International Communications, International Relations. It is a first step towards developing a holistic theoretical approach to what shapes the news, which bridges current micro to macro approaches. More precisely the model explains news variation across different media organization and countries by focusing on the different way the sense of newsworthiness of journalists is affected by three main variables: national interest, national journalistic culture, and editorial policy of each media organization. The model is developed on the basis of an investigation into what shaped the media coverage of 9/11 in eight elite newspapers across the US, France, Italy and Pakistan

Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites

Autoantibodies to insulin are a harbinger of autoimmunity in type 1 diabetes in humans and in non-obese diabetic mice. To understand the genesis of these autoantibodies, we investigated the interactions of insulin-specific T and B lymphocytes using T cell and B cell receptor transgenic mice. We found spontaneous anti-insulin germinal center (GC) formation throughout lymphoid tissues with GC B cells binding insulin. Moreover, because of the nature of the insulin epitope recognized by the T cells, it was evident that GC B cells presented a broader repertoire of insulin epitopes. Such broader recognition was reproduced by activating naive B cells ex vivo with a combination of CD40 ligand and interleukin 4. Thus, insulin immunoreactivity extends beyond the pancreatic lymph node–islets of Langerhans axis and indicates that circulating insulin, despite its very low levels, can have an influence on diabetogenesis

Desperately constructing ethnic audiences: Anti-immigration discourses and minority audience research in the Netherlands

This article examines how minority ethnic audiences are measured, and thus constructed, in the Netherlands today. The analysis shows that this process is tightly woven into the dominant assimilationist and neoliberal discourse. This discourse portrays specific minority groups as deviant in relation to an essentialized notion of Dutchness. Furthermore, it presents social inclusion as an opportunity that is limited to well-adjusted, profitable consumers. Different attempts to represent minority audiences – including efforts to promote a more just minority representation in Dutch media – are compelled to accommodate to this dominant discourse. The article underscores the limited scope for contesting current hegemonic representations of minority groups and national belonging in the Netherlands

Structural variation of centromeric endogenous retroviruses in human populations and their impact on cutaneous T-cell lymphoma, Sézary syndrome, and HIV infection

© 2019 The Author(s). Background: Human Endogenous Retroviruses type K HML-2 (HK2) are integrated into 117 or more areas of human chromosomal arms while two newly discovered HK2 proviruses, K111 and K222, spread extensively in pericentromeric regions, are the first retroviruses discovered in these areas of our genome. Methods: We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. Results: We found that the 5′ LTR-gag region of K111 proviruses is missing in certain individuals, creating pericentromeric instability. K111 deletion (-/- K111) is seen in about 15% of Caucasian, Asian, and Middle Eastern populations; it is missing in 2.36% of African individuals, suggesting that the -/- K111 genotype originated out of Africa. As we identified the -/-K111 genotype in Cutaneous T-cell lymphoma (CTCL) cell lines, we studied whether the -/-K111 genotype is associated with CTCL. We found a significant increase in the frequency of detection of the -/-K111 genotype in Caucasian patients with severe CTCL and/or Sézary syndrome (n = 35, 37.14%), compared to healthy controls (n = 160, 15.6%) [p = 0.011]. The -/-K111 genotype was also found to vary in HIV-1 infection. Although Caucasian healthy individuals have a similar frequency of detection of the -/- K111 genotype, Caucasian HIV Long-Term Non-Progressors (LTNPs) and/or elite controllers, have significantly higher detection of the -/-K111 genotype (30.55%; n = 36) than patients who rapidly progress to AIDS (8.5%; n = 47) [p = 0.0097]. Conclusion: Our data indicate that pericentromeric instability is associated with more severe CTCL and/or Sézary syndrome in Caucasians, and appears to allow T-cells to survive lysis by HIV infection. These findings also provide new understanding of human evolution, as the -/-K111 genotype appears to have arisen out of Africa and is distributed unevenly throughout the world, possibly affecting the severity of HIV in different geographic areas

The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy