Prevalence of Moderate to Severe Periodontitis in an 18–19th Century Sample—St. Bride’s Lower Churchyard (London, UK)

The aim of the study was to determine the prevalence of moderate to severe periodontitis in 18–19th century skulls in the St Bride’s Lower Churchyard in London, UK. Materials and methods: A total of 105 adult skulls (66 M: F 39) from the Museum of London collection were examined for evidence of dental disease. The primary method was to measure the presence of moderate to severe periodontitis. Other dental pathologies were recorded such as tooth wear, calculus, and caries. Results: Overall, the prevalence of moderate to severe periodontitis in the sample was 21–24%. Males were observed to be more susceptible to periodontal disease than females. The severity of bone loss in the skull collection also increased with age. There was no significant difference in the amount of calculus deposition when comparing either age or sex. A total of 14% of the individuals in the sample showed signs of smoking. Conclusion: The results of the study indicated that the prevalence of moderate to severe periodontitis in an 18–19th century skull sample was 21–24%, which was higher than in previous studies. This may be due to the lack of basic personal mouth care and professional dental treatment as well as known risk factors such as smoking, stress, low socioeconomic status, and malnutrition

Response to Comment on "The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)".

This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Rosas, A., et al. (2018). "Response to Comment on “The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)”." Science 359(6380). on Science 09 Mar 2018: Vol. 359, Issue 6380, eaar3820, DOI: 10.1126/science.aar3820The comment by DeSilva challenges our suggestion that brain growth of the El Sidrón J1 Neandertal was still incomplete at 7.7 years of age. Evidence suggests that endocranial volume is likely to represent less than 90% adult size at El Sidrón as well as Neandertal male plus Krapina samples, in line with further evidence from endocranial surface histology and dural sinus groove size

Mechanisms of leukocyte migration across the blood–retina barrier

Immune-mediated inflammation in the retina is regulated by a combination of anatomical, physiological and immuno-regulatory mechanisms, referred to as the blood–retina barrier (BRB). The BRB is thought to be part of the specialised ocular microenvironment that confers protection or “immune privilege” by deviating or suppressing destructive inflammation. The barrier between the blood circulation and the retina is maintained at two separate anatomical sites. These are the endothelial cells of the inner retinal vasculature and the retinal pigment epithelial cells on Bruch’s membrane between the fenestrated choroidal vessels and the outer retina. The structure and regulation of the tight junctions forming the physical barrier are described. For leukocyte migration across the BRB to occur, changes are needed in both the leukocytes themselves and the cells forming the barrier. We review how the blood–retina barrier is compromised in various inflammatory diseases and discuss the mechanisms controlling leukocyte subset migration into the retina in uveoretinitis in more detail. In particular, we examine the relative roles of selectins and integrins in leukocyte interactions with the vascular endothelium and the pivotal role of chemokines in selective recruitment of leukocyte subsets, triggering adhesion, diapedesis and migration of inflammatory cells into the retinal tissue

Controlled Crystallization of the Lipophilic Drug Fenofibrate During Freeze-Drying: Elucidation of the Mechanism by In-Line Raman Spectroscopy

We developed a novel process, “controlled crystallization during freeze-drying” to produce drug nanocrystals of poorly water-soluble drugs. This process involves freeze-drying at a relatively high temperature of a drug and a matrix material from a mixture of tertiary butyl alcohol and water, resulting in drug nanocrystals incorporated in a matrix. The aim of this study was to elucidate the mechanisms that determine the size of the drug crystals. Fenofibrate was used as a model lipophilic drug. To monitor the crystallization during freeze-drying, a Raman probe was placed just above the sample in the freeze-dryer. These in-line Raman spectroscopy measurements clearly revealed when the different components crystallized during freeze-drying. The solvents crystallized only during the freezing step, while the solutes only crystallized after the temperature was increased, but before drying started. Although the solutes crystallized only after the freezing step, both the freezing rate and the shelf temperature were critical parameters that determined the final crystal size. At a higher freezing rate, smaller interstitial spaces containing the freeze-concentrated fraction were formed, resulting in smaller drug crystals (based on dissolution data). On the other hand, when the solutes crystallized at a lower shelf temperature, the degree of supersaturation is higher, resulting in a higher nucleation rate and consequently more and therefore smaller crystals. In conclusion, for the model drug fenofibrate, a high freezing rate and a relatively low crystallization temperature resulted in the smallest crystals and therefore the highest dissolution rate

Inflammation-Associated Nitrotyrosination Affects TCR Recognition through Reduced Stability and Alteration of the Molecular Surface of the MHC Complex

Nitrotyrosination of proteins, a hallmark of inflammation, may result in the production of MHC-restricted neoantigens that can be recognized by T cells and bypass the constraints of immunological self-tolerance. Here we biochemically and structurally assessed how nitrotyrosination of the lymphocytic choriomeningitis virus (LCMV)-associated immunodominant MHC class I-restricted epitopes gp33 and gp34 alters T cell recognition in the context of both H-2Db and H-2Kb. Comparative analysis of the crystal structures of H-2Kb/gp34 and H-2Kb/NY-gp34 demonstrated that nitrotyrosination of p3Y in gp34 abrogates a hydrogen bond interaction formed with the H-2Kb residue E152. As a consequence the conformation of the TCR-interacting E152 was profoundly altered in H-2Kb/NY-gp34 when compared to H-2Kb/gp34, thereby modifying the surface of the nitrotyrosinated MHC complex. Furthermore, nitrotyrosination of gp34 resulted in structural over-packing, straining the overall conformation and considerably reducing the stability of the H-2Kb/NY-gp34 MHC complex when compared to H-2Kb/gp34. Our structural analysis also indicates that nitrotyrosination of the main TCR-interacting residue p4Y in gp33 abrogates recognition of H-2Db/gp33-NY complexes by H-2Db/gp33-specific T cells through sterical hindrance. In conclusion, this study provides the first structural and biochemical evidence for how MHC class I-restricted nitrotyrosinated neoantigens may enable viral escape and break immune tolerance

Architectures of control in consumer product design

Copyright @ 2005 Social Services Research GroupThe idea of architectures of control is introduced through examples ranging from urban planning to digital rights management, and the intentions behind their use in consumer products are examined, with reference to case studies of printer cartridges and proposed 'optimum lifetime products.' The reactions of the technical community and consumers themselves are also explored, along with some wider implications for society