Oxygen Reduction Reaction in Alkaline Media Causes Iron Leaching from Fe-N-C Electrocatalysts.

The electrochemical activity of modern Fe-N-C electrocatalysts in alkaline media is on par with that of platinum. For successful application in fuel cells (FCs), however, also high durability and longevity must be demonstrated. Currently, a limited understanding of degradation pathways, especially under operando conditions, hinders the design and synthesis of simultaneously active and stable Fe-N-C electrocatalysts. In this work, using a gas diffusion electrode half-cell coupled with inductively coupled plasma mass spectrometry setup, Fe dissolution is studied under conditions close to those in FCs, that is, with a porous catalyst layer (CL) and at current densities up to -125 mA·cm-2. Varying the rate of the oxygen reduction reaction (ORR), we show a remarkable linear correlation between the Faradaic charge passed through the electrode and the amount of Fe dissolved from the electrode. This finding is rationalized assuming that oxygen reduction and Fe dissolution reactions are interlinked, likely through a common intermediate formed during the Fe redox transitions in Fe species involved in the ORR, such as FeNxCy and Fe3C@N-C. Moreover, such a linear correlation allows the application of a simple metric─S-number─to report the material's stability. Hence, in the current work, a powerful tool for a more applied stability screening of different electrocatalysts is introduced, which allows on the one hand fast performance investigations under more realistic conditions, and on the other hand a more advanced mechanistic understanding of Fe-N-C degradation in CLs.

Proposed Diagnostic Criteria and Classification of Canine Mast Cell Neoplasms: A Consensus Proposal.

Mast cell neoplasms are one of the most frequently diagnosed malignancies in dogs. The clinical picture, course, and prognosis vary substantially among patients, depending on the anatomic site, grade and stage of the disease. The most frequently involved organ is the skin, followed by hematopoietic organs (lymph nodes, spleen, liver, and bone marrow) and mucosal sites of the oral cavity and the gastrointestinal tract. In cutaneous mast cell tumors, several grading and staging systems have been introduced. However, no comprehensive classification and no widely accepted diagnostic criteria have been proposed to date. To address these open issues and points we organized a Working Conference on canine mast cell neoplasms in Vienna in 2019. The outcomes of this meeting are summarized in this article. The proposed classification includes cutaneous mast cell tumors and their sub-variants defined by grading- and staging results, mucosal mast cell tumors, extracutaneous/extramucosal mast cell tumors without skin involvement, and mast cell leukemia (MCL). For each of these entities, diagnostic criteria are proposed. Moreover, we have refined grading and staging criteria for mast cell neoplasms in dogs based on consensus discussion. The criteria and classification proposed in this article should greatly facilitate diagnostic evaluation and prognostication in dogs with mast cell neoplasms and should thereby support management of these patients in daily practice and the conduct of clinical trials.

Exaggerated hypoxic pulmonary vasoconstriction without susceptibility to high altitude pulmonary edema.

BACKGROUND: Abnormally high pulmonary artery pressure (PAP) in hypoxia due to exaggerated hypoxic pulmonary vasoconstriction (HPV) is a key factor for development of high-altitude pulmonary edema (HAPE). It was shown that about 10% of a healthy Caucasian population has an exaggerated HPV that is comparable to the response measured in HAPE-susceptible individuals. Therefore, we hypothesized that those with exaggerated HPV are HAPE-susceptible. METHODS AND RESULTS: We screened 421 healthy Caucasians naïve to high altitude for HPV using Doppler echocardiography for assessment of systolic PAP in normobaric hypoxia (PASPHx; Po2 corresponding to 4500 m). Subjects with exaggerated HPV and matched controls were exposed to 4559 m with an identical protocol that causes HAPE in 62% of HAPE-S. Screening revealed 39 subjects with exaggerated HPV, of whom 33 (PASPHx 51±6 mmHg) ascended within 24 hours to 4559 m. Four (13%) of them developed HAPE during the 48 h-stay. This incidence is significantly lower than the recurrence rate of 62% previously observed in HAPE-S in the same setting. None of the control subjects (PASPHx 33±5 mmHg) developed HAPE. CONCLUSION: An exaggerated HPV cannot be considered a surrogate maker for HAPE-susceptibility although excessively elevated PAP is a hallmark in HAPE, while a normal HPV appears to protect from HAPE in this study.

Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma.

BACKGROUND: Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. METHODS: Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. RESULTS: Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. CONCLUSION: We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients.

Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model.

BACKGROUND: B cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine. METHODS: In the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed. RESULTS: Feasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2±23.8 days vs. 41.8±1.6 days and 39.8±3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype. CONCLUSION: We present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.

Animal-based model to investigate the minimum tumor size detectable with an electrical impedance scanning technique.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the minimum tumor size detectable with electrical impedance scanning (EIS) in laboratory animals. MATERIALS AND METHODS: VX2 tumor cells (1 mm3) were implanted bilaterally into the upper leg musculature of five white New Zealand rabbits. EIS and ultrasound (US) were performed before, during, and immediately after implantation and on every 2nd day thereafter until tumors could be visualized with both modalities. This was followed by an extended follow-up regimen until a tumor size of 1 cm3 was reached. Rabbits were anesthetized subcutaneously. RESULTS: Tumors could not be implanted in one rabbit. Neither EIS nor US were performed in one rabbit due to severe skin alterations at the implantation site. No focal increase in conductance was visible before or immediately after tumor injection. The smallest tumor identified with EIS was determined with US to be approximately 8 mm3. The mean tumor size at initial detection was 52 mm3 (determined with EIS). In two cases, the tumor was first seen with US (EIS detection was delayed with a delay of 1 and 2 days, respectively). In all remaining cases, tumors were detected simultaneously with both EIS and US. All tumors were visible with EIS. CONCLUSION: The animal-based model is feasible. VX2 tumors are detectable with EIS. Tumors characterized by a focal spot at EIS could be detected starting at a tumor size of 7.5 mm3.