Interprofessional Education in U.S. and Canadian Dental Schools: An ADEA Team Study Group Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153755/1/jddj002203372012769tb05381x.pd

Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. METHODS: We conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis. RESULTS: Fifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects. CONCLUSIONS: Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

Increased Avian Diversity Is Associated with Lower Incidence of Human West Nile Infection: Observation of the Dilution Effect

Recent infectious disease models illustrate a suite of mechanisms that can result in lower incidence of disease in areas of higher disease host diversity–the ‘dilution effect’. These models are particularly applicable to human zoonoses, which are infectious diseases of wildlife that spill over into human populations. As many recent emerging infectious diseases are zoonoses, the mechanisms that underlie the ‘dilution effect’ are potentially widely applicable and could contribute greatly to our understanding of a suite of diseases. The dilution effect has largely been observed in the context of Lyme disease and the predictions of the underlying models have rarely been examined for other infectious diseases on a broad geographic scale. Here, we explored whether the dilution effect can be observed in the relationship between the incidence of human West Nile virus (WNV) infection and bird (host) diversity in the eastern US. We constructed a novel geospatial contrasts analysis that compares the small differences in avian diversity of neighboring US counties (where one county reported human cases of WNV and the other reported no cases) with associated between-county differences in human disease. We also controlled for confounding factors of climate, regional variation in mosquito vector type, urbanization, and human socioeconomic factors that are all likely to affect human disease incidence. We found there is lower incidence of human WNV in eastern US counties that have greater avian (viral host) diversity. This pattern exists when examining diversity-disease relationships both before WNV reached the US (in 1998) and once the epidemic was underway (in 2002). The robust disease-diversity relationships confirm that the dilution effect can be observed in another emerging infectious disease and illustrate an important ecosystem service provided by biodiversity, further supporting the growing view that protecting biodiversity should be considered in public health and safety plans

Conducting longitudinal research with older widows : Exploring personal communities through multiple methods

This article reports on the process of undertaking a longitudinal multiple methods study with older women experiencing the transition of later life widowhood. A series of three qualitative in depth interviews were conducted with twenty-six older widows in North Staffordshire, United Kingdom. Interviews included the use of personal community diagrams to identify the structure of personal communities, and Christmas and Christmas cards to further explore social relationships and practices during transition. Examples of cases are given to illustrate the findings derived from the methods employed. The cases demonstrate the diverse and often paradoxical nature of social relationships within similar networks

Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses

Dendritic cells located at the body surfaces, e.g. skin, respiratory and gastrointestinal tract, play an essential role in the induction of adaptive immune responses to pathogens and inert antigens present at these surfaces. In the respiratory tract, multiple subsets of dendritic cells (RDC) have been identified in both the normal and inflamed lungs. While the importance of RDC in antigen transport from the inflamed or infected respiratory tract to the lymph nodes draining this site is well recognized, the contribution of individual RDC subsets to this process and the precise role of migrant RDC within the lymph nodes in antigen presentation to T cells is not clear. In this report, we demonstrate that two distinct subsets of migrant RDC - exhibiting the CD103+ and CD11bhi phenotype, respectively - are the primary DC presenting antigen to naïve CD4+ and CD8+ T lymphocytes in the draining nodes in response to respiratory influenza virus infection. Furthermore, the migrant CD103+ RDC subset preferentially drives efficient proliferation and differentiation of naive CD8+ T cells responding to infection into effector cells, and only the CD103+ RDC subset can present to naïve CD8+ T cells non-infectious viral vaccine introduced into the respiratory tract. These results identify CD103+ and CD11bhi RDC as critical regulators of the adaptive immune response to respiratory tract infection and potential targets in the design of mucosal vaccines

Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen

Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells

CCR5-binding chemokines produced in the draining lymph node after vaccinia virus infection guide naive CD8+ T cells toward DCs and away from the macrophage-rich zone, thereby facilitating optimal CD8+ T cell activation and cytokine production