Glucocorticoid-Induced Impairment of Macrophage Antimicrobial Activity: Mechanisms and Dependence on the State of Activation

Experimental observations indicate that tissue macrophages deployed in great numbers at critical anatomic sites such as the liver, spleen, and lung are major targets for glucocorticoids compromising natural resistanceof the host. Therapeutic concentrations ofglucocorticoids appear to prevent destruction of microorganisms ingested by macrophages without interfering with phagocytosis, phagolysosomal fusion, and/or secretion of reactive oxygen intermediates. These findings indicate that at the cellular level the glucocorticoid target should be sought for in the nonoxidative armature of the phagocyte and that nonoxidative killing systems of resident tissue macrophages play an important role in natural resistance to opportunistic pathogens. Glucocorticoids do not prevent lymphokine-induced activation of oxidative killing systems. Thus, lymphokines such as interferon-γ can restore the microbicidal activity of macrophages functionally impaired by glucocorticoids. Counterbalance of the suppressive effect of glucocorticoids by lymphokines might only be possible, however, for pathogens susceptible to oxidative killing and not for microorganisms that are more resistant to reactive oxygen intermediates such as Aspergillus spores and Nocardia, opportunists that appear to be particularly associated with hypercortisolis

Effect of Prophylactic Fluconazole on the Frequency of Fungal Infections, Amphotericin B Use, and Health Care Costs in Patients Undergoing Intensive Chemotherapy for Hematologic Neoplasias

Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count >0.5 × 109/L, toxicity precluding further fluconazole use, and death. By KaplanMeier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01

Semantic Security and Indistinguishability in the Quantum World

At CRYPTO 2013, Boneh and Zhandry initiated the study of quantum-secure encryption. They proposed first indistinguishability definitions for the quantum world where the actual indistinguishability only holds for classical messages, and they provide arguments why it might be hard to achieve a stronger notion. In this work, we show that stronger notions are achievable, where the indistinguishability holds for quantum superpositions of messages. We investigate exhaustively the possibilities and subtle differences in defining such a quantum indistinguishability notion for symmetric-key encryption schemes. We justify our stronger definition by showing its equivalence to novel quantum semantic-security notions that we introduce. Furthermore, we show that our new security definitions cannot be achieved by a large class of ciphers -- those which are quasi-preserving the message length. On the other hand, we provide a secure construction based on quantum-resistant pseudorandom permutations; this construction can be used as a generic transformation for turning a large class of encryption schemes into quantum indistinguishable and hence quantum semantically secure ones. Moreover, our construction is the first completely classical encryption scheme shown to be secure against an even stronger notion of indistinguishability, which was previously known to be achievable only by using quantum messages and arbitrary quantum encryption circuits.Comment: 37 pages, 2 figure

Pretransplant Evaluation for Infections in Donors and Recipients of Solid Organs

The risk of infectious disease reactivation in recipients of and transmission by solid-organ transplants remains, and thorough screening and testing of recipient and donor is especially important. In conceiving screening strategies, it is crucial to consider the sensitivity and specificity of individual diagnostic tests in the context of their use. Furthermore, recognition of special risks for infectious complications of transplantation will help to guide preventive, diagnostic, and therapeutic steps in the control of infectious complications in individual patients. The acceptability of risks for infectious complications after transplantation depends also on the urgency of transplantation of a vital organ as well as the availability of organs. Although these principals are well accepted, standards for the extent of screening and criteria for inappropriate donors and exclusion of unfit recipients remain controversial to some exten

Classifications of Twin Star Solutions for a Constant Speed of Sound Parameterized Equation of State

We explore the possible mass radius relation of compact stars for the equation of states with a first order phase transition. The low density matter is described by a nuclear matter equation of state resulting from fits to nuclear properties. A constant speed of sound parametrization is used to describe the high density matter phase with the speed of sound $c_s^2=1$. A classification scheme of four distinct categories including twin star solutions, i. e. solutions with the same mass but differing radii, is found which are compatible with the $M \ge 2M_\odot$ pulsar mass constraint. We show the dependence of the mass and radius differences on the transition parameters and delineate that higher twin star masses are more likely to be accompanied by large radius differences. These massive twin stars are generated by high values of the discontinuity in the energy density and the lowest possible values of the transition pressure that still result in masses of $M \geq 2M_\odot$ at the maximum of the hadronic branch.Comment: 8 pages, 9 figure