The Ohio State University at Mansfield

Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this commentary is to discuss many of those issues in a single location. In terms of "Pros," for example, phages can be bactericidal, can increase in number over the course of treatment, tend to only minimally disrupt normal flora, are equally effective against antibiotic-sensitive and antibiotic-resistant bacteria, often are easily discovered, seem to be capable of disrupting bacterial biofilms, and can have low inherent toxicities. In addition to these assets, we consider aspects of phage therapy that can contribute to its safety, economics, or convenience, but in ways that are perhaps less essential to the phage potential to combat bacteria. For example, autonomous phage transfer between animals during veterinary application could provide convenience or economic advantages by decreasing the need for repeated phage application, but is not necessarily crucial to therapeutic success. We also consider possible disadvantages to phage use as antibacterial agents. These "Cons," however, tend to be relatively minor.

Phages as bactericidal agents have been employed for 90 years as a means of treating bacterial infections in humans as well as other species, a process known as phage therapy. In this review we explore both the early historical and more modern use of phages to treat human infections. We discuss in particular the little-reviewed French early work, along with the Polish, US, Georgian and Russian historical experiences. We also cover other, more modern examples of phage therapy of humans as differentiated in terms of disease. In addition, we provide discussions of phage safety, other aspects of phage therapy pharmacology, and the idea of phage use as probiotics.

Viruses of bacteria, known as bacteriophages or phages, were discovered nearly 100 years ago. Their potential as antibacterial agents was appreciated almost immediately, with the first 'phage therapy' trials predating Fleming's discovery of penicillin by approximately a decade. In this review, we consider phage therapy that can be used for treating bacterial infections in humans, domestic animals and even biocontrol in foods. Following an overview of the topic, we explore the common practice - both experimental and, in certain regions of the world, clinical - of mixing therapeutic phages into cocktails consisting of multiple virus types. We conclude with a discussion of the commercial and medical context of phage cocktails as therapeutic agents. In comparing off-the-shelf versus custom approaches, we consider the merits of a middle ground, which we deem 'modifiable'. Finally, we explore a regulatory framework for such an approach based on an influenza vaccine model.

ABSTRACT Firms in more concentrated industries earn lower returns, even after controlling for size, book‐to‐market, momentum, and other return determinants. Explanations based on chance, measurement error, capital structure, and persistent in‐sample cash flow shocks do not explain this finding. Drawing on work in industrial organization, we posit that either barriers to entry in highly concentrated industries insulate firms from undiversifiable distress risk, or firms in highly concentrated industries are less risky because they engage in less innovation, and thereby command lower expected returns. Additional time‐series tests support these risk‐based interpretations.

A distinction between ruminative and reflective types of private self-attentiveness is introduced and evaluated with respect to L. R. Goldberg's (1982) list of 1,710 English trait adjectives (Study 1), the five-factor model of personality (FFM) and A. Fenigstein, M. F. Scheier, and A. Buss's (1975) Self-Consciousness Scales (Study 2), and previously reported correlates and effects of private self-consciousness (PrSC; Studies 3 and 4). Results suggest that the PrSC scale confounds two unrelated, motivationally distinct dispositions--rumination and reflection--and that this confounding may account for the "self-absorption paradox" implicit in PrSC research findings: Higher PrSC scores are associated with more accurate and extensive self-knowledge yet higher levels of psychological distress. The potential of the FFM to provide a comprehensive framework for conceptualizing self-attentive dispositions, and to order and integrate research findings within this domain, is discussed.

In this commentary I consider use of the term "lysis from without" (LO) along with the phenomenon's biological relevance. LO originally described an early bacterial lysis induced by high-multiplicity virion adsorption and that occurs without phage production (here indicated as LO(V)). Notably, this is more than just high phage multiplicities of adsorption leading to bacterial killing. The action on bacteria of exogenously supplied phage lysin, too, has been described as a form of LO (here, LO(L)). LO(V) has been somewhat worked out mechanistically for T4 phages, has been used to elucidate various phage-associated phenomena including discovery of the phage eclipse, may be relevant to phage ecology, and, with resistance to LO (LO(R)), is blocked by certain phage gene products. Speculation as to the impact of LO(V) on phage therapy also is fairly common. Since LO(V) assays are relatively easily performed and not all phages are able to induce LO(V), a phage's potential to lyse bacteria without first infecting should be subject to at least in vitro experimental confirmation before the LO(V) label is applied. The term "abortive infection" may be used more generally to describe non-productive phage infections that kill bacteria.

Men report more permissive sexual attitudes and behavior than do women. This experiment tested whether these differences might result from false accommodation to gender norms (distorted reporting consistent with gender stereotypes). Participants completed questionnaires under three conditions. Sex differences in self-reported sexual behavior were negligible in a bogus pipeline condition in which participants believed lying could be detected, moderate in an anonymous condition, and greatest in an exposure threat condition in which the experimenter could potentially view participants responses. This pattern was clearest for behaviors considered less acceptable for women than men (e.g., masturbation, exposure to hardcore & softcore erotica). Results suggest that some sex differences in self-reported sexual behavior reflect responses influenced by normative expectations for men and women.

Bacteriophage growth may be differentiated into sequential steps: (i) phage collision with an adsorption-susceptible bacterium, (ii) virion attachment, (iii) virion nucleic acid uptake, (iv) an eclipse period during which infections synthesize phage proteins and nucleic acid, (v) a "post-eclipse" period during which virions mature, (vi) a virion release step, and (vii) a diffusion-delimited period of virion extracellular search for bacteria to adsorb (1). The latent period begins at the point of virion attachment (ii) and/or nucleic acid uptake (iii) and ends with infection termination, spanning both the eclipse (iv) and the post-eclipse maturation (v) periods. For lytic phages, latent-period termination occurs at lysis, i.e., at the point of phage-progeny release (vi). A second compound step is phage adsorption, which, depending upon one's perspective, can begin with virion release (vi), may include the virion extracellular search (vii), certainly involves virion collision with (i) and then attachment to (ii) a bacterium, and ends either with irreversible virion attachment to bacteria (ii) or with phage nucleic acid uptake into cytoplasm (iii). Thus, the phage life cycle, particularly for virulent phages, consists of an adsorption period, virion attachment/nucleic acid uptake, a latent period, and virion release ((2), p. 13, citing d'Herelle). The duration of these steps together define the phage generation time and help to define rates of phage population growth. Also controlling rates of phage population growth is the number of phage progeny produced per infection: the phage burst size. In this chapter we present protocols for determining phage growth parameters, particularly phage rate of adsorption, latent period, eclipse period, and burst size.

This paper is intended to make explicit some aspects of the interactions which have recently come to light between the theory of classical knots and links, the theory of monoidal categories, Hopf-algebra theory, quantum integrable systems, the theory of exactly solvable models in statistical mechanics, and quantum field theories. The main results herein show an intimate relation between representations of certain monoidal categories arising from the study of new knot invariants or from physical considerations and quantum groups (that is, Hopf algebras). In particular categories of modules and comodules over Hopf algebras would seem to be much more fundamental examples of monoidal categories than might at first be apparent. This fundamental role of Hopf algebras in monoidal categories theory is also manifest in the Tannaka duality theory of Deligne and Mime [ 8a ], although the relationship of that result and the present work is less clear than might be hoped.

Bacteriophages (phages) modify microbial communities by lysing hosts, transferring genetic material, and effecting lysogenic conversion. To understand how natural communities are affected it is important to develop predictive models. Here we consider how variation between models--in eclipse period, latent period, adsorption constant, burst size, the handling of differences in host quantity and host quality, and in modeling strategy--can affect predictions. First we compare two published models of phage growth, which differ primarily in terms of how they model the kinetics of phage adsorption; one is a computer simulation and the other is an explicit calculation. At higher host quantities (approximately 10(8) cells/ml), both models closely predict experimentally determined phage population growth rates. At lower host quantities (10(7) cells/ml), the computer simulation continues to closely predict phage growth rates, but the explicit model does not. Next we concentrate on predictions of latent-period optima. A latent-period optimum is the latent period that maximizes the population growth of a specific phage growing in the presence of a specific quantity and quality of host cells. Both models predict similar latent-period optima at higher host densities (e.g., 17 min at 10(8) cells/ml). At lower host densities, however, the computer simulation predicts latent-period optima that are much shorter than those suggested by explicit calculations (e.g., 90 versus 1,250 min at 10(5) cells/ml). Finally, we consider the impact of host quality on phage latent-period evolution. By taking care to differentiate latent-period phenotypic plasticity from latent-period evolution, we argue that the impact of host quality on phage latent-period evolution may be relatively small.

Phage therapy--application of bacteria-specific viruses to reduce densities of pathogenic or nuisance bacteria--is a two-step process involving phage penetration to target bacteria followed by bacteria killing. Any analysis of these steps is inherently ecological as they represent phage-environment interactions, i.e., between phages and bacteria as well as between phages and body tissues. In considering phages more generically, as selectively toxic antibacterial agents employed to treat bacterial infections, the term "ecology" may be fairly cleanly replaced with the term "pharmacology". Pharmacology, in turn, may be distinguished into two major components: pharmacokinetics and pharmacodynamics. Pharmacokinetics is explicitly a description of the body's impact on a drug (e.g., movement through and between body compartments) whereas pharmacodynamics is a description of a drug's impact on the body. "Body" includes both body tissues and microbial flora, so an important component of antibacterial pharmacodynamics is inhibition of the growth of target bacteria. Our guiding premise is that phage therapy may be rationally improved through a better understanding of phage pharmacokinetics and pharmacodynamics. Our primary conclusions are (i) that the principle advantages of phages, over antibiotics, are the former's relative safety and ease of discovery; (ii) that phage therapy efficacy is highly dependent on attaining relatively high phage "killing titers"; (iii) that attainment of sufficient titers solely via in situ phage replication should, in some or many circumstances, not be counted upon; and (iv) that phage replication nonetheless may provide a "margin of safety" toward attaining phage therapy efficacy.

Across two studies, the authors examined the role of individual differences in transportability, the tendency to become transported into narratives, in predicting the degree of attitude change resulting from persuasive narratives. In Study 1 ( N = 137), participants were persuaded by a story promoting tolerance toward homosexuals only to the extent that they self-rated as highly transportable. In Study 2 ( N = 298), this finding was replicated using the topic of affirmative action. Study 2 further showed that the effects of transportability were unique to narratives and did not extend to rhetorical communications. Across both studies, the link between transportability and attitudes was found to be mediated by emotional, empathic responses as opposed to rationalistic appraisals. The theoretical and applied implications of this work are discussed.

We assessed the impact of two distinct forms of socially desirable responding—self‐deceptive enhancement and impression management—on sexuality self‐reports (n = 504) under anonymous testing conditions. Results revealed significant positive relationships between self‐deceptive enhancement and sexual adjustment variables for both sexes. Impression management was significantly negatively related to a number of intrapersonal (e.g., unrestricted sexual fantasies, sexual drive) and interpersonal (e.g., sexual experience, virginity status) sexual behaviors for females, and to unrestricted sexual attitudes and fantasies for males. We calculated correlations were first calculated between self‐deceptive enhancement, impression management, and personality and conservatism scores. Self‐deceptive enhancement and impression management were significantly associated with personality for males and females, and with conservatism for females only. When personality and conservatism variance were partialed out, associations between self‐deceptive enhancement and sexuality variables were eliminated, but associations between impression management and sexuality measures remained significant. These findings highlight the importance of a two‐factor approach to assessing socially desirable responding, and provide modest support for the view that response bias may intrude in self‐report sex data, even under anonymous testing conditions.

We investigated birth order effects on personality and achievement in four studies (N = 1,022 families) including both student and adult samples. Control over a wide range of variables was effected by collecting within-family data: Participants compared their siblings (and themselves) on a variety of personality and achievement dimensions. Across four diverse data sets, first-borns were nominated as most achieving and most conscientious. Later-borns were nominated as most rebellious, liberal, and agreeable. The same results obtained whether or not birth order was made salient (to activate stereotypes) during the personality ratings. Overall, the results support predictions from Sulloway's niche model of personality development, as well as Zajonc's confluence model of intellectual achievement.

EDITORIAL article Front. Microbiol., 15 June 2017Sec. Antimicrobials, Resistance and Chemotherapy Volume 8 - 2017 | https://doi.org/10.3389/fmicb.2017.00981

Bacteriophages, or phages, are viruses of members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective, these especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections versus lysogeny, pseudolysogeny and/or the phage carrier state), (2) the means of virion release (lytic versus chronic release) and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate versus non-temperate phages). We address in particular the use or overuse of what can be a somewhat equivocal phrase, 'Lytic or lysogenic', especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between 'Lytic' versus 'Lysogenic' phage types.

Male prisoners (n = 450) estimated public reaction to the label “ex-con” and endorsed likely stigma management strategies. Although most anticipate significant rejection, they prefer preventative telling to withdrawal and secrecy as adjustments. OLS regression finds factors promoting exclusion (devaluation/discrimination beliefs and reduced job opportunities) related to withdrawal and secrecy, whereas factors favoring inclusion (“wise” family and friends and plans to attend church) increase preventative telling and reduce withdrawal and secrecy. To enhance public safety by increasing ex-convicts' openness and visibility, policies should promote social support and economic opportunities. Successful reentry may improve rule-following in general, whereas exclusionary practices may work against post-release control.

The use of viruses infecting bacteria (bacteriophages or phages) to treat bacterial infections has been ongoing clinically for approximately 100 years. Despite that long history, the growing international crisis of resistance to standard antibiotics, abundant anecdotal evidence of efficacy, and one successful modern clinical trial of efficacy, this phage therapy is not yet a mainstream approach in medicine. One explanation for why phage therapy has not been subject to more widespread implementation is that phage therapy research, both preclinical and clinical, can be insufficiently pharmacologically aware. Consequently, here we consider the pharmacological obstacles to phage therapy effectiveness, with phages in phage therapy explicitly being considered to serve as drug equivalents. The study of pharmacology has traditionally been differentiated into pharmacokinetic and pharmacodynamic aspects. We therefore separately consider the difficulties that phages as virions can have in traveling through body compartments toward reaching their target bacteria (pharmacokinetics) and the difficulties that phages can have in exerting antibacterial activity once they have reached those bacteria (pharmacodynamics). The latter difficulties, at least in part, are functions of phage host range and bacterial resistance to phages. Given the apparently low toxicity of phages and the minimal side effects of phage therapy as practiced, phage therapy should be successful so long as phages can reach the targeted bacteria in sufficiently high numbers, adsorb, and then kill those bacteria. Greater awareness of what obstacles to this success generally or specifically can exist, as documented in this review, should aid in the further development of phage therapy toward wider use.

Although free-swimming planktonic bacteria historically have been the typical focus of microbiological studies, the natural state of many or most bacteria is one where they instead are associated with surfaces and/or each other. For many pathogenic as well as nuisance bacteria, including biofouling bacteria, it consequently is within the context of this biofilm state that antibacterial strategies must be implemented. For reasons that are not fully understood, however, biofilm-associated bacteria tend to be less susceptible to treatments with standard chemical antibacterial agents than are planktonic bacteria, and this appears to be especially an issue with the use of less-harsh agents such as antibiotics. Within a variety of contexts the development of less- or selectively toxic antibacterial agents capable of clearing biofilms therefore would be welcome. In this review we consider the use of three categories of such agents as anti-biofilm antibacterials. These are lytic viruses of bacteria, that is, bacteriophages, effecting phage-mediated biocontrol of bacteria (a.k.a., phage therapy); purified phage-encoded enzymes that digest bacterial cell-wall material (endolysins or simply lysins); and a second category of phage-encoded enzymes that digest the extracellular polymeric substance (EPS) that are particularly notable components of bacterial biofilms (EPS depolymerases). These agents have been shown to reduce the bacterial density of a diversity of biofilms and, in many cases, tend to be lacking in inherent toxicity against the tissues of animals. Here we consider these phage-based anti-biofilm strategies with emphasis on ecological aspects of their action and with particular consideration of EPS depolymerases.

Abstract: We provide the first documented case of the extinction in the twentieth century of a widely recognized primate taxon. During surveys in Ghana and Côte d'Ivoire in 1993–1999, we were unable to find any surviving populations of Miss Waldron's red colobus monkey ( Procolobus badius waldroni ), a primate taxon endemic to the forests of this part of West Africa. We conclude that this monkey, which at least one authority considers worthy of species status, is probably extinct. Hunting by humans appears to be the ultimate cause of the extinction. Until our surveys began, little attention had been paid to the plight of this red colobus monkey, despite its listing as endangered by the World Conservation Union. The extinction of other large animals in the Upper Guinea rainforest region is likely to follow soon unless more attention is paid to the full range of endangered forms and more resources are devoted to their rigorous protection.