Perceived empowerment and the impact of negative effects of the COVID-19 pandemic on the quality of life of persons with severe mental illness.

PURPOSE: Beyond its direct effects on physical health the COVID-19 pandemic has been shown to have negative effects on the living situation of people with severe mental illness (SMI). To date, there has been little research on resilience factors preventing people with SMI from experiencing negative effects of the COVID-19 pandemic. The objective of this study was to investigate the role of perceived empowerment (PE) as a resilience factor, preventing people with SMI from experiencing negative effects of the COVID-19 pandemic on daily living. METHODS: We investigated negative effects of the COVID-19 pandemic on daily living in 931 persons with SMI at two times within six month between June 2020 and Mai 2021. To take into account the longitudinal structure of the data we applied mixed effects regression analyses and longitudinal path models. RESULTS: A majority of participants experienced negative effects of the COVID-19 pandemic on several dimensions of daily living. Negative effects increased with rising levels of illness-related impairment but decreased as the level of PE rose. While negative effects of the COVID-19 pandemic at follow-up were negatively associated with overall subjective quality of life baseline, PE was negatively associated with the negative impact of the pandemic and positively with quality of life. CONCLUSION: Patients with SMI need support to reduce negative effects of the COVID-19 pandemic on their quality of life. The promotion of PE could help strengthen resilience in this target group. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00019086, registered on 3 January 2020. (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00019086).

Genomic basis for drought resistance in European beech forests threatened by climate change.

In the course of global climate change, Central Europe is experiencing more frequent and prolonged periods of drought. The drought years 2018 and 2019 affected European beeches (Fagus sylvatica L.) differently: even in the same stand, drought-damaged trees neighboured healthy trees, suggesting that the genotype rather than the environment was responsible for this conspicuous pattern. We used this natural experiment to study the genomic basis of drought resistance with Pool-GWAS. Contrasting the extreme phenotypes identified 106 significantly associated single-nucleotide polymorphisms (SNPs) throughout the genome. Most annotated genes with associated SNPs (>70%) were previously implicated in the drought reaction of plants. Non-synonymous substitutions led either to a functional amino acid exchange or premature termination. An SNP assay with 70 loci allowed predicting drought phenotype in 98.6% of a validation sample of 92 trees. Drought resistance in European beech is a moderately polygenic trait that should respond well to natural selection, selective management, and breeding.

Climate change is having a serious impact on many ecosystems. In the summer of 2018 and 2019, around two thirds of European beech trees were damaged or killed by extreme drought. It is critical to keep these beech woods healthy, as they are central to the survival of over 6,000 other species of animals and plants. The level of damage caused by the drought varied between forests. However, not all the trees in each forest responded in the same way, with severely damaged trees often sitting next to fully healthy ones. This suggests that the genetic make-up of each tree determines how well it can adapt to drought rather than its local environment. To investigate this further, Pfenninger et al. studied the genome of over 400 European beech trees from the Hesse region in Germany. The samples came from pairs of neighbouring trees that had responded differently to the droughts. The analysis found more than 80 parts of the genome that differed between healthy and damaged trees. Pfenninger et al. then used this information to create a genetic test which can quickly and inexpensively predict how well an individual beech tree might survive in a drought. Applying this test to another 92 trees revealed that it can reliably detect which ones were healthy and which ones were damaged. Beech forests are typically managed by private owners, agencies or breeders that could use this genetic test to select and reproduce trees that are better adapted to drought. The goal now is to develop the test so that it can be used more widely to manage European beech trees and potentially other species.

Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy.

Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with IL21, IL4, anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigen-specific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NY-ESO-1-specific B cells were detected in tumor-draining lymph nodes and were able to induce antigen-specific T-cell responses in vitro, indicating that this approach could be translated into clinical applications. Our results describe a technique for the exploitation of B-cell effector functions and provide the rationale for their use in combinatorial cancer immunotherapy. Cancer Immunol Res; 5(9); 730-43. ©2017 AACR.

Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma.

The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA-/CCR7-). Naïve T cells (CD45RA+/CCR7+) were decreased in the microenvironment compared to PBMC of patients, while regulatory T cells (CD4+/CD25+/CD127low and CD4+/CD39+) were elevated. Furthermore, we performed digital image analyses of entire cross sections of HNSCC to define the 'Immunoscore' (CD3+ and CD8+ cell infiltration in tumor core and invasive margin) and quantified MHC class I expression on tumor cells by immunohistochemistry. Immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were increased in TILs compared to peripheral T cells in flow-cytometric analysis. Human papillomavirus (HPV) positive tumors showed higher numbers of TILs, but a similar composition of T-cell subsets and checkpoint molecule expression compared to HPV negative tumors. Taken together, the tumor microenvironment of HNSCC is characterized by a strong infiltration of regulatory T cells and high checkpoint molecule expression on T-cell subsets. In view of increasingly used immunotherapies, a detailed knowledge of TILs and checkpoint molecule expression on TILs is of high translational relevance.