In NSCLC, reduction of metabolic activity after one cycle of chemotherapy is closely correlated with final outcome of therapy. Using metabolic response as an end point may shorten the duration of phase II studies evaluating new cytotoxic drugs and may decrease the morbidity and costs of therapy in nonresponding patients.

Recently developed major histocompatibility complex (MHC) multimer technologies allow visualization and isolation of antigen-specific T cells. However, functional analysis and in vivo transfer of MHC multimer-stained cells is hampered by the persistence of T-cell receptor (TCR) MHC interactions and subsequently induced signaling events. As MHC monomers do not stably bind to TCRs, we postulated that targeted disassembly of multimers into MHC monomers would result in dissociation of surface-bound TCR ligands. We generated a new type of MHC multimers, which can be monomerized in the presence of a competitor, resulting in rapid loss of the staining reagent. Following dissociation, the T cells are phenotypically and functionally indistinguishable from untreated cells. This 'reversible' T-cell staining procedure, which maintains the specificity and sensitivity of MHC multimer staining while preserving the functional status of T lymphocytes, may be of broad benefit for ex vivo investigation of T-cell functions and clinical applications.

Despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. New, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8 ؉ T cells and conserved among Orthopoxvirus species including variola virus. This finding has permitted analysis and monitoring of epitope-specific T cell responses after immunization and demonstration of the identified T cell specificity in an A*0201-positive human donor. Vaccination of transgenic mice allowed us to compare the immunogenicity of several vaccinia viruses including highly attenuated, replication-deficient modified vaccinia virus Ankara (MVA). MVA vaccines elicited levels of CD8 ؉ T cell responses that were comparable to those induced by the replication-competent vaccinia virus strains. Finally, we demonstrate that MVA vaccination is fully protective against a lethal respiratory challenge with virulent vaccinia virus strain Western Reserve. Our data provide a basis to rationally estimate immunogenicity of safe, second-generation poxvirus vaccines and suggest that MVA may be a suitable candidate.

The Allostatic Load Index (ALI) has been used to establish associations between stress and health-related outcomes. This review summarizes the measurement and methodological challenges of allostatic load in occupational settings. Databases of Medline, PubPsych, and Cochrane were searched to systematically explore studies measuring ALI in working adults following the PRISMA statement. Study characteristics, biomarkers and methods were tabulated. Methodological quality was evaluated using a standardized checklist. Sixteen articles (2003–2013) met the inclusion criteria, with a total of 39 (range 6–17) different variables used to calculate ALI. Substantial heterogeneity was observed in the number and type of biomarkers used, the analytic techniques applied and study quality. Particularly, primary mediators were not regularly included in ALI calculation. Consensus on methods to measure ALI in working populations is limited. Research should include longitudinal studies using multi-systemic variables to measure employees at risk for biological wear and tear.

Deregulated apoptosis is an identifying feature of myelodysplastic syndromes (MDS). Whereas apoptosis is increased in the bone marrow (BM) of low-risk MDS patients, progression to high-risk MDS correlates with an acquired resistance to apoptosis and an aberrant expression of BCL-2 proteins. To overcome the acquired apoptotic resistance in high-risk MDS, we investigated the induction of apoptosis by inhibition of pro-survival BCL-2 proteins using the BCL-2/-XL/-W inhibitor ABT-737 or the BCL-2-selective inhibitor ABT-199. We characterized a cohort of 124 primary human BM samples from MDS/secondary acute myeloid leukemia (sAML) patients and 57 healthy, age-matched controls. Inhibition of anti-apoptotic BCL-2 proteins was specifically toxic for BM cells from high-risk MDS and sAML patients, whereas low-risk MDS or healthy controls remained unaffected. Notably, ABT-737 or ABT-199 treatment was capable of targeting the MDS stem/progenitor compartment in high-risk MDS/sAML samples as shown by the reduction in CD34(+) cells and the decreased colony-forming capacity. Elevated expression of MCL-1 conveyed resistance against both compounds. Protection by stromal cells only partially inhibited induction of apoptosis. Collectively, our data show that the apoptotic resistance observed in high-risk MDS/sAML cells can be overcome by the ABT-737 or ABT-199 treatment and implies that BH3 mimetics might delay disease progression in higher-risk MDS or sAML patients.

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An increased consumption of energy-dense, nutrient-poor food and beverages as a result of a changing obesogenic environment contributes substantially to the increasing prevalence of childhood overweight and obesity. This paper reviews the nature and extent of food industry influences which expose children to commercial influences and thus might affect unhealthy dietary behaviour and finally contributes to obesity. A systematic search of nine electronic databases (including PubMed, PsycINFO, EconLit) and reference lists of original studies and reviews using key search terms identified 1900 articles. Of these only thirty-six articles met the inclusion and quality criteria. A narrative synthesis of the reviewed studies revealed six key obesogenic environments by which the food industry possibly influences obesity-related dietary behaviours in young children. These were schools, retailers, mass media “television”, mass media “internet”, home and promotional campaigns. Identifying these obesogenic environments is critical for monitoring and controlling the food industry, the development of effective environmental-level interventions to prevent childhood overweight and obesity and to identify knowledge gaps to be addressed in future research to support informed decisions of policy makers.