Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood-brain barrier endothelium

Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood-brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1-deficient, ICAM-2-deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium.

Beta-D-glucoside utilization by Mycoplasma mycoides subsp. mycoides SC: possible involvement in the control of cytotoxicity towards bovine lung cells

BACKGROUND: Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides small-colony type (SC) is among the most serious threats for livestock producers in Africa. Glycerol metabolism-associated H2O2 production seems to play a crucial role in virulence of this mycoplasma. A wide number of attenuated strains of M. mycoides subsp. mycoides SC are currently used in Africa as live vaccines. Glycerol metabolism is not affected in these vaccine strains and therefore it does not seem to be the determinant of their attenuation. A non-synonymous single nucleotide polymorphism (SNP) in the bgl gene coding for the 6-phospho-beta-glucosidase (Bgl) has been described recently. The SNP differentiates virulent African strains isolated from outbreaks with severe CBPP, which express the Bgl isoform Val204, from strains to be considered less virulent isolated from CBPP outbreaks with low mortality and vaccine strains, which express the Bgl isoform Ala204. RESULTS: Strains of M. mycoides subsp. mycoides SC considered virulent and possessing the Bgl isoform Val204, but not strains with the Bgl isoform Ala204, do trigger elevated levels of damage to embryonic bovine lung (EBL) cells upon incubation with the disaccharides (i.e., beta-D-glucosides) sucrose and lactose. However, strains expressing the Bgl isoform Val204 show a lower hydrolysing activity on the chromogenic substrate p-nitrophenyl-beta-D-glucopyranoside (pNPbG) when compared to strains that possess the Bgl isoform Ala204. Defective activity of Bgl in M. mycoides subsp. mycoides SC does not lead to H2O2 production. Rather, the viability during addition of beta-D-glucosides in medium-free buffers is higher for strains harbouring the Bgl isoform Val204 than for those with the isoform Ala204. CONCLUSION: Our results indicate that the studied SNP in the bgl gene is one possible cause of the difference in bacterial virulence among strains of M. mycoides subsp. mycoides SC. Bgl does not act as a direct virulence factor, but strains possessing the Bgl isoform Val204 with low hydrolysing activity are more prone to survive in environments that contain high levels of beta-D-glucosides, thus contributing in some extent to mycoplasmaemia.

The loss of trust in the European Union during the great recession since 2007: The role of heuristics from the national political system

How can we explain the decline in support for the European Union (EU) and the idea of European integration after the onset of the great recession in the fall of 2007? Did the economic crisis and the austerity policies that the EU imposed—in tandem with the IMF—on several member countries help cause this drop? While there is some evidence for this direct effect of EU policies, we find that the most significant determinant of trust and support for the EU remains the level of trust in national governments. Based on cue theory and using concepts of diffuse and specific support, we find that support for the EU is derived from evaluations of national politics and policy, which Europeans know far better than the remote political system of the EU. This effect, however, is somewhat muted for those sophisticated Europeans that are more knowledgeable about the EU and are able to form opinions about it independently of the national contexts in which they live. We also find that the recent economic crisis has led to a discernible increase in the number of those who are disillusioned with politics both at the national and the supranational level. We analyze 133 national surveys from 27 EU countries by estimating a series of cross-classified multilevel logistic regression models.

Dermatology in the immunosuppressed patient

This anniversary book gives an animated description of the first one hundred years of the Swiss Society of Dermatology and Venereology (SSDV – SGDV). The approximately 60 authors write from the subjective perspective of the contemporary witness and thus create a vibrant picture of their field and the times in which we live. “Spirit and Soul of Swiss Dermatology and Venereology 1913 – 2013” is therefore an ideal companion to the medical history book “Dermatologie und Venerologie in der Schweiz – ein historischer Rückblick” (2002 Editions Alphil, ISBN 2-940235-08-2), published in 2003 by the SSDV – SGDV for its 90th anniversary. The anniversary edition for the centennial is written in English in order to make the history of the SSDV – SGDV accessible to a larger international public. The introductory chapter is written in all four national languages (German, French, Italian, and Romansh) and also translated into English. It is followed by chapters about the university and non-university public dermatology and venereology departments, the memoirs of those presidents still living, and the depiction of the numerous sub-disciplines of dermatology. Further important chapters include a large contribution on the beginnings of dermatological research in Switzerland, a series of pieces on medical education and continuing education, and finally an overview of healthcare politics in Switzerland. Our friends in Germany, Austria, France, Italy and the USA have provided the outside perspective on Swiss dermatology and venereology in their essays. All in all an informative and entertaining overview of a very diverse medical specialty has been created, which combines historical facts with dynamic insights into this topical field and the current political healthcare framework.

The immune response of bovine mammary epithelial cells to live or heat-inactivated Mycoplasma bovis

Mycoplasma bovis is an emerging bacterial agent causing bovine mastitis. Although these cell wall-free bacteria lack classical virulence factors, they are able to activate the immune system of the host. However, effects on the bovine mammary immune system are not yet well characterized and detailed knowledge would improve the prevention and therapy of mycoplasmal mastitis. The aim of this study was to investigate the immunogenic effects of M. bovis on the mammary gland in an established primary bovine mammary epithelial cell (bMEC) culture system. Primary bMEC of four different cows were challenged with live and heat-inactivated M. bovis strain JF4278 isolated from acute bovine mastitis, as well as with the type strain PG45. The immune response was evaluated 6 and 24h after mycoplasmal challenge by measuring the relative mRNA expression of selected immune factors by quantitative PCR. M. bovis triggered an immune response in bMEC, reflected by the upregulation of tumor necrosis factor-α, interleukin(IL)-1β, IL-6, IL-8, lactoferrin, Toll-like receptor-2, RANTES, and serum amyloid A mRNA. Interestingly, this cellular reaction was only observed in response to live, but not to heat-inactivated M. bovis, in contrast to other bacterial pathogens of mastitis such as Staphylococcus aureus. This study provides evidence that bMEC exhibit a strong inflammatory reaction in response to live M. bovis. The lack of a cellular response to heat-inactivated M. bovis supports the current hypothesis that mycoplasmas activate the immune system through secreted secondary metabolites.

Modelling the impact of deferring HCV treatment on liver-related complications in HIV coinfected men who have sex with men

BACKGROUND AND AIMS Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression. METHODS We developed an individual-based model of liver disease progression in HIV/HCV coinfected men who have sex with men. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale. RESULTS The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5 years if treatment was initiated in F2 to almost 15 years if it was deferred until F4. CONCLUSIONS Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with replicating HCV infection.

Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health

BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.

Health literacy builds resilience among individuals and communities

Health is created in the context of everyday life, and health literacy originates in and helps shape the sociocultural context in which people live. Empowerment, equity, co-production and cultural capital have been shown to be positively associated with people’s health.

Cross-Layer Optimizations for Multimedia Distribution over Wireless Multimedia Sensor Networks and Flying Ad-Hoc Networks with Quality of Experience Support

The proliferation of multimedia content and the demand for new audio or video services have fostered the development of a new era based on multimedia information, which allowed the evolution of Wireless Multimedia Sensor Networks (WMSNs) and also Flying Ad-Hoc Networks (FANETs). In this way, live multimedia services require real-time video transmissions with a low frame loss rate, tolerable end-to-end delay, and jitter to support video dissemination with Quality of Experience (QoE) support. Hence, a key principle in a QoE-aware approach is the transmission of high priority frames (protect them) with a minimum packet loss ratio, as well as network overhead. Moreover, multimedia content must be transmitted from a given source to the destination via intermediate nodes with high reliability in a large scale scenario. The routing service must cope with dynamic topologies caused by node failure or mobility, as well as wireless channel changes, in order to continue to operate despite dynamic topologies during multimedia transmission. Finally, understanding user satisfaction on watching a video sequence is becoming a key requirement for delivery of multimedia content with QoE support. With this goal in mind, solutions involving multimedia transmissions must take into account the video characteristics to improve video quality delivery. The main research contributions of this thesis are driven by the research question how to provide multimedia distribution with high energy-efficiency, reliability, robustness, scalability, and QoE support over wireless ad hoc networks. The thesis addresses several problem domains with contributions on different layers of the communication stack. At the application layer, we introduce a QoE-aware packet redundancy mechanism to reduce the impact of the unreliable and lossy nature of wireless environment to disseminate live multimedia content. At the network layer, we introduce two routing protocols, namely video-aware Multi-hop and multi-path hierarchical routing protocol for Efficient VIdeo transmission for static WMSN scenarios (MEVI), and cross-layer link quality and geographical-aware beaconless OR protocol for multimedia FANET scenarios (XLinGO). Both protocols enable multimedia dissemination with energy-efficiency, reliability and QoE support. This is achieved by combining multiple cross-layer metrics for routing decision in order to establish reliable routes.

An investigation into the factors that encourage learner participation in a large group medical classroom

BACKGROUND: Effective lectures often incorporate activities that encourage learner participation. A challenge for educators is how to facilitate this in the large group lecture setting. This study investigates the individual student characteristics involved in encouraging (or dissuading) learners to interact, ask questions, and make comments in class. METHODS: Students enrolled in a Doctor of Veterinary Medicine program at Ross University School of Veterinary Medicine, St Kitts, were invited to complete a questionnaire canvassing their participation in the large group classroom. Data from the questionnaire were analyzed using Excel (Microsoft, Redmond, WA, USA) and the R software environment (http://www.r-project.org/). RESULTS: One hundred and ninety-two students completed the questionnaire (response rate, 85.7%). The results showed statistically significant differences between male and female students when asked to self-report their level of participation (P=0.011) and their confidence to participate (P<0.001) in class. No statistically significant difference was identified between different age groups of students (P=0.594). Student responses reflected that an "aversion to public speaking" acted as the main deterrent to participating during a lecture. Female participants were 3.56 times more likely to report a fear of public speaking than male participants (odds ratio 3.56, 95% confidence interval 1.28-12.33, P=0.01). Students also reported "smaller sizes of class and small group activities" and "other students participating" as factors that made it easier for them to participate during a lecture. CONCLUSION: In this study, sex likely played a role in learner participation in the large group veterinary classroom. Male students were more likely to participate in class and reported feeling more confident to participate than female students. Female students in this study commonly identified aversion to public speaking as a factor which held them back from participating in the large group lecture setting. These are important findings for veterinary and medical educators aiming to improve learner participation in the classroom. Potential ways of addressing this challenge include addition of small group activities and audience response systems during lectures, and inclusion of training interventions in public speaking at an early stage of veterinary and medical curricula.

Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS).

Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG (n=26), IgM (n=25) and leptospiral antigens (n=26). Three general staining patterns for IgG/IgM were observed in lungs of dogs with LPHS with most tissues showing more than one staining pattern: (1) alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3) staining of intra-alveolar fluid. Healthy control lung showed no staining, whereas haemorrhagic lung from dogs not infected with Leptospira showed staining of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens were not detected. We conclude that deposition of IgG/IgM is demonstrable in the majority of canine lungs with naturally occurring LPHS, similar to what has been described in other species. Our findings suggest involvement of the host humoral immunity in the pathogenesis of LPHS and provide further evidence to support the dog as a natural disease model for human LPHS.