Optofluidic Microreactors for Advanced Photocatalysis

This PhD project explores the application of hollow-core photonic crystal fibres (HC- PCFs) as a novel and advanced characterization technique to monitor photocatalysis. The use of HC-PCFs as the core element of a newly developed characterisation platform has many benefits: HC-PCF’s light-guiding abilities and low-loss properties make absorp- tion spectroscopy based screening of reaction intermediates at low sample concentrations possible. The photoreduction of methyl viologen by carbon nanodots (CNDs) was studied and compared to theory by modelling reaction pathways. Oxidation states of cobaloximes, that are currently employed as molecular catalysts for solar hydrogen generation, could be studied and analysed in different pH environments. Furthermore, a novel enzyme based photocatalyst was characterized and its application in photocatalysis explored. With the resulting new insight and understanding of the reaction kinetics and reaction pathways, these nanoscale photocatalytic systems can be improved further to increase conversion efficiency. A functionalisation of HC-PCFs by depositing gold nanoparticles on the core wall lays the foundation towards surface-enhanced Raman sensing of reaction interme- diates. Spatial light modulation (SLM) techniques are applied to excite a wide variety of higher-order modes with well-defined cross-sectional intensity distributions inside the HC-PCF’s core. An automated fast-switching between inverted higher-order modes can in the future be exploited to enable pump-probe and diffusion/ adhesion measurements.EPSRC, NanoDT

Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

B-cell chronic lymphocytic leukaemia (B-CLL) remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR) which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells

How the Direction of Screws Affects the Primary Stability of a Posterior Malleolus Osteosynthesis under Torsional Loading: A Biomechanical Study

Insufficient fixation of a posterior malleolus fracture (PM) can lead to posttraumatic complications such as osteoarthritis and chronic pain. The purpose of this biomechanical study was to test the hypothesis of whether the direction of PM screw fixation has an impact on the primary stability of osteosynthesis of a PM under torsional loading. PM fractures of 7 pairs human cadaveric lower leg specimens were stabilized with posterior to anterior (p.a.) or anterior to posterior (a.p.) screw fixation. Stability of the osteosynthesis was biomechanically tested using cyclic external torsional loading levels, in 2 Nm steps from 2 Nm up to 12 Nm, under constant monitoring with 3D ultrasonic marker (Zebris). The primary stability does not differ between both stabilizations ( p = 0.378) with a medium effect size (η 2 p = 0.065). The movement of the PM tends to be marginally greater for the osteosynthesis with a.p. screws than with p.a. screws. Whether a.p. screws or the alternative p.a. screw fixation is performed does not seem to have an influence on the primary stability of the osteosynthesis of the PM fixation under torsional loading. Although osteosynthesis from posterior seems to be more stable, the biomechanical results in the torsional test show quite equivalent stabilities. If there is no significant dislocation of the PM, a.p. screw fixation could be a minimally invasive but stable surgical strategy

Candida-Reactive T Cells for the Diagnosis of Invasive Candida Infection—A Prospective Pilot Study

Background: Blood or tissue culture or histology prove invasive Candida infection, but long time to result, limited feasibility and sensitivity call for new approaches. In this pilot project, we describe the diagnostic potential of quantitating Candida-reactive, CD4/CD69/CD154 positive lymphocytes in blood of patients with invasive Candida infection.Methods: We used flow cytometry quantitating Candida-reactive, CD4/CD69/CD154 positive lymphocytes from peripheral blood of patients with invasive Candida infection, from patients at risk and healthy volunteers as controls.Results: Elevated levels of Candida-reactive lymphocytes were measured in 13 patients with proven invasive Candida infection and in one patient with probable hepatosplenic candidiasis. Results of three candidemia patients were uninterpretable due to autofluorescence of samples. Twelve of 13 patients had Candida identified to species level by conventional methods, and T cell reactivity correctly identified Candida species in 10 of 12 patients. Nine hematological high-risk patients and 14 healthy donors had no elevated Candida-reactive T cell counts.Conclusions: This Candida-reactive lymphocyte assay correctly identified the majority of patients with invasive Candida infection and the respective species. Our assay has the potential to support diagnosis of invasive Candida infection to species level and to facilitate tailored treatment even when biopsies are contraindicated or cultures remain negative

COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From immunology to treatment

Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.AC was supported by the Fundação para a Ciência e a Tecnologia (FCT) (CEECIND/03628/2017, UIDB/50026/2020 and UIDP/50026/2020), and the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023). This research received no other external funding

Drought and Waterlogging Stress Regimes in Northern Peatlands Detected Through Satellite Retrieved Solar-Induced Chlorophyll Fluorescence

The water table depth (WTD) in peatlands determines the soil carbon decomposition rate and influences vegetation growth, hence the above-ground carbon assimilation. Here, we used satellite-observed Solar-Induced chlorophyll Fluorescence (SIF) as a proxy of Gross Primary Production (GPP) to investigate water-related vegetation stress over northern peatlands. A linear model with interaction effects was used to relate short- and long-term anomalies in SIF with WTD anomalies and the absolute WTD. Most locations showed the occurrence of drought and waterlogging stress though regions with exclusively waterlogging or drought stress were also detected. As a spatial median, minimal water-related vegetation stress was found for a WTD of -0.22 m (short-term) and -0.20 m (long-term) (+/- 0.01 m, 95% confidence interval of statistical uncertainty). The stress response observed with SIF is supported by an analysis of in situ GPP data. Our findings provide insight into how changes in WTD of northern peatlands could affect GPP under climate change.Water table depth is an important variable influencing the carbon cycle and vegetation growth in northern peatlands. In this paper, the impact of changing wetness conditions on vegetation growth over peatlands was studied through satellite measurements of solar-induced fluorescence (SIF), which is a radiation signal emitted by vegetation during photosynthesis. Previous studies over ecosystems on mineral soil, that is, not over peatland, suggested a response of SIF to drought conditions. In our study, it was shown that peatland vegetation experiences moisture-related growth stress under both very wet and very dry conditions, which might reduce the photosynthesis efficiency and the ability to capture and store CO2. Stress due to drought conditions was detected for peatlands in the south of the Western Siberian Lowlands and the Boreal Plains. Stress due to prolonged wet conditions occurred for example, in the north of the Western Siberian Lowlands and the north of the Hudson Bay Lowlands.Spaceborne Solar-Induced Fluorescence (SIF) data was used to analyze soil moisture-related vegetation stress regimes in northern peatlandsFor most locations, waterlogging as well as drought stress regimes occurred and alternated depending on peatland water level dynamicsThe SIF-based stress response observations are supported by in situ data of Gross Primary Productio

Altered Serum IgG Levels to a-Synuclein in Dementia with Lewy Bodies and Alzheimer’s Disease.

Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against asynuclein is not well known. We explored serum IgG levels to monomeric a-synuclein in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-asynuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against a-synuclein in DLB and AD, which may relate to a disturbed a-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target a-synuclein in neurodegenerative disease.Fil: Koehler, Niklas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Stransky, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Shing, Mona. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Gaertner, Susanne. Department of Psychiatry and Psychotherapy, EBERHARD-KARLS-UNIVERSITY;Fil: Meyer, Mirjam. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schreitmueller, Brigitte. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Leyhe, Thomas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Laske, Cristoph. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Maetzler, Walter. Department of Neurodegeneration. HERTIE INSTITUTE FOR CLINICAL BRAIN RESEARCH;Fil: Kahle, Philipp. FUNCTIONAL NEUROGENETICS. HERTIE INSTITUTE FOR CLINICAL;Fil: Celej, Maria Soleda. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY; Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);Fil: Jovin, Thomas M.. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY;Fil: Fallgatter, Andreas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Batra, Anil. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Buchkremer, Gherard. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schott, Klauss. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Richartz-Salzburger, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY

Universitäre Notaufnahmen in der Coronapandemie – Ergebnisse des ReCovERRegisters / University emergency departments in the corona pandemic—Results from the ReCovER registry

Background: The current COVID-19 pandemic, despite the availability of rapid tests and the start of the vaccination campaign, continues to pose major challenges to emergency departments (ED). Structured collection of demographic, clinical, as well as treatment-related data provides the basis for establishing evidence-based processes and treatment concepts. Aim of the work: To present the systematic collection of clinical parameters in patients with suspected COVID-19 in the Registry for COVID-19 in the Emergency Room (ReCovER) and descriptive presentation of the first 1000 patients. Materials and methods: Data from patients with suspected COVID-19, regardless of evidence of SARS-CoV‑2 infection, are continuously entered into a web-based, anonymized registry in ED at six university hospitals. Results: Between 19 May 2020 and 13 January 2021, 1000 patients were entered into the registry, of whom 594 patients (59.4%) were in the SARS-CoV‑2 positive group (PG) and 406 patients (40.6%) were in the negative group (NG). Patients of the PG had significantly fewer pre-existing conditions and a significantly longer latency between symptom onset and presentation to the ED (median 5 vs. 3 days), were more likely to suffer from cough, myalgia, fatigue, and loss of smell/taste and had significantly higher oxygen requirements than NG patients. The rate of severe disease progression was significantly higher in the PG, and persistent symptoms were more common after discharge (11.1 vs. 4.6%). Conclusions: The multicenter collection of comprehensive clinical data on COVID-19 suspected cases in the ED allows analysis of aspects specific to the situation in Germany in particular. This is essential for a targeted review and adaptation of internationally published strategies