Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure

The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node

Now the wars are over: The past, present and future of Scottish battlefields

Battlefield archaeology has provided a new way of appreciating historic battlefields. This paper provides a summary of the long history of warfare and conflict in Scotland which has given rise to a large number of battlefield sites. Recent moves to highlight the archaeological importance of these sites, in the form of Historic Scotland’s Battlefields Inventory are discussed, along with some of the problems associated with the preservation and management of these important cultural sites

Indymedia and the long story of rebellion against neoliberal capitalism

Indymedia was born of the anti-globalisation movement of the late 1990s and quickly spread to become a social movement in its own right. This article reflects on how prescient the claims of the anti-globalisation movement have proven to be and how 20 years ago Indymedia and the anti-globalisation movement predicted there was trouble ahead and that neoliberalism was a central part of the problem. It notes how a history of struggle and protest emanating from the days of Indymedia has developed over time building a counter-politics that is becoming ever wiser about the multiple intersectional harms of capitalism and ever more sophisticated in its political response. The challenge is what comes next

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later.</p> <p>Case presentation</p> <p>We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease.</p> <p>Conclusions</p> <p>This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease) of a common disease (lyme infection) is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.</p

Examining the validity and utility of two secondary sources of food environment data against street audits in England

Background: Secondary data containing the locations of food outlets is increasingly used in nutrition and obesity research and policy. However, evidence evaluating these data is limited. This study validates two sources of secondary food environment data: Ordnance Survey Points of Interest data (POI) and food hygiene data from the Food Standards Agency (FSA), against street audits in England and appraises the utility of these data. Methods: Audits were conducted across 52 Lower Super Output Areas in England. All streets within each Lower Super Output Area were covered to identify the name and street address of all food outlets therein. Audit-identified outlets were matched to outlets in the POI and FSA data to identify true positives (TP: outlets in both the audits and the POI/FSA data), false positives (FP: outlets in the POI/FSA data only) and false negatives (FN: outlets in the audits only). Agreement was assessed using positive predictive values (PPV: TP/(TP+FP)) and sensitivities (TP/(TP+FN)). Variations in sensitivities and PPVs across environment and outlet types were assessed using multi-level logistic regression. Proprietary classifications within the POI data were additionally used to classify outlets, and agreement between audit-derived and POI-derived classifications was assessed. Results: Street audits identified 1172 outlets, compared to 1100 and 1082 for POI and FSA respectively. PPVs were statistically significantly higher for FSA (0.91, CI: 0.89-0.93) than for POI (0.86, CI: 0.84-0.88). However, sensitivity values were not different between the two datasets. Sensitivity and PPVs varied across outlet types for both datasets. Without accounting for this, POI had statistically significantly better PPVs in rural and affluent areas. After accounting for variability across outlet types, FSA had statistically significantly better sensitivity in rural areas and worse sensitivity in rural middle affluence areas (relative to deprived). Audit-derived and POI-derived classifications exhibited substantial agreement (p < 0.001; Kappa = 0.66, CI: 0.63 - 0.70). Conclusions: POI and FSA data have good agreement with street audits; although both datasets had geographic biases which may need to be accounted for in analyses. Use of POI proprietary classifications is an accurate method for classifying outlets, providing time savings compared to manual classification of outlets

Acute traumatic abdominal wall hernia

Although blunt abdominal trauma is frequent, traumatic abdominal wall hernias (TAWH) are rare. We describe a large TAWH with associated intra-abdominal lesions that were caused by high-energy trauma. The diagnosis was missed by clinical examination but was subsequently revealed by a computed tomography (CT) scan. Repair consisted of an open anatomical reconstruction of the abdominal wall layers with reinforcement by an intraperitoneal composite mesh. The patient recovered well and the results of a post-operative CT scan are presented

Blood pressure and site-specific cancer mortality: evidence from the original Whitehall study

Studies relating blood pressure to cancer risk have some shortcomings and have revealed inconsistent findings. In 17498 middle-aged London-based government employees we related systolic and diastolic blood pressure recorded at baseline examination (1967-1970) to the risk of cancer mortality risk at 13 anatomical sites 25 years later. Following adjustment for potential confounding and mediating factors, inverse associations between blood pressure and mortality due to leukaemia and cancer of the pancreas (diastolic only) were seen. Blood pressure was also positively related to cancer of the liver and rectum (diastolic only). The statistically significant blood pressure-cancer associations seen in this large-scale prospective investigation offering high power were scarce and of sufficiently small magnitude as to be attributable to chance or confounding

HIV Treatment as Prevention: Debate and Commentary-Will Early Infection Compromise Treatment-as-Prevention Strategies?

Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection—before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy—will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser