Summary
The human body is colonized by a diverse collective of microorganisms, including bacteria, fungi, protozoa and viruses. The smallest entity of this microbial conglomerate are the bacterial ...viruses. Bacteriophages, or phages for short, exert significant selective pressure on their bacterial hosts, undoubtedly influencing the human microbiome and its impact on our health and well‐being. Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. As such our bodies are frequently and continuously exposed to diverse collections of phages. Despite the prevalence of phages throughout our bodies, the extent of their interactions with human cells, organs, and immune system is still largely unknown. Phages physically interact with our mucosal surfaces, are capable of bypassing epithelial cell layers, disseminate throughout the body and may manipulate our immune system. Here, I establish the novel concept of an “intra‐body phageome,” which encompasses the collection of phages residing within the classically “sterile” regions of the body. This review will take a phage‐centric view of the microbiota, human body, and immune system with the ultimate goal of inspiring a greater appreciation for both the indirect and direct interactions between bacteriophages and their mammalian hosts.
A
bstract
A rather general method for determining the spin density matrix of a multi-particle system from angular decay data is presented. The method is based on a Bloch parameterisation of the
d
...-dimensional generalised Gell-Mann representation of
ρ
and exploits the associated Wigner- and Weyl-transforms on the sphere. Each parameter of a (possibly multipartite) spin density matrix can be measured from a simple average over an appropriate set of experimental angular decay distributions. The general procedures for both projective and non-projective decays are described, and the Wigner
P
and
Q
symbols calculated for the cases of spin-half, spin-one, and spin-3/2 systems. The methods are used to examine Monte Carlo simulations of
pp
collisions for bipartite systems:
pp → W
+
W
−
,
pp → ZZ
,
pp → ZW
+
,
pp →
W
+
t
¯
,
t
t
¯
, and those from the Higgs boson decays
H → WW
*
and
H
→
ZZ
*
. Measurements are proposed for entanglement detection, exchange symmetry detection and Bell inequality violation in bipartite systems.
Phage Therapy in the Postantibiotic Era Gordillo Altamirano, Fernando L; Barr, Jeremy J
Clinical microbiology reviews,
04/2019, Letnik:
32, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Antibiotic resistance is arguably the biggest current threat to global health. An increasing number of infections are becoming harder or almost impossible to treat, carrying high morbidity, ...mortality, and financial cost. The therapeutic use of bacteriophages, viruses that infect and kill bacteria, is well suited to be part of the multidimensional strategies to combat antibiotic resistance. Although phage therapy was first implemented almost a century ago, it was brought to a standstill after the successful introduction of antibiotics. Now, with the rise of antibiotic resistance, phage therapy is experiencing a well-deserved rebirth. Among the admittedly vast literature recently published on this topic, this review aims to provide a forward-looking perspective on phage therapy and its role in modern society. We cover the key points of the antibiotic resistance crisis and then explain the biological and evolutionary principles that support the use of phages, their interaction with the immune system, and a comparison with antibiotic therapy. By going through up-to-date reports and, whenever possible, human clinical trials, we examine the versatility of phage therapy. We discuss conventional approaches as well as novel strategies, including the use of phage-antibiotic combinations, phage-derived enzymes, exploitation of phage resistance mechanisms, and phage bioengineering. Finally, we discuss the benefits of phage therapy beyond the clinical perspective, including opportunities for scientific outreach and effective education, interdisciplinary collaboration, cultural and economic growth, and even innovative use of social media, making the case that phage therapy is more than just an alternative to antibiotics.
Patient empowerment has gained considerable importance but uncertainty remains about the best way to define and measure it. The validity of empirical findings depends on the quality of measures used. ...This systematic review aims to provide an overview of studies assessing psychometric properties of questionnaires purporting to capture patient empowerment, evaluate the methodological quality of these studies and assess the psychometric properties of measures identified.
Electronic searches in five databases were combined with reference tracking of included articles. Peer-reviewed articles reporting psychometric testing of empowerment measures for adult patients in French, German, English, Portuguese and Spanish were included. Study characteristics, constructs operationalised and psychometric properties were extracted. The quality of study design, methods and reporting was assessed using the COSMIN checklist. The quality of psychometric properties was assessed using Terwee's 2007 criteria.
30 studies on 19 measures were included. Six measures are generic, while 13 were developed for a specific condition (N=4) or specialty (N=9). Most studies tested measures in English (N=17) or Swedish (N=6). Sample sizes of included studies varied from N=35 to N=8261. A range of patient empowerment constructs was operationalised in included measures. These were classified into four domains: patient states, experiences and capacities; patient actions and behaviours; patient self-determination within the healthcare relationship and patient skills development. Quality assessment revealed several flaws in methodological study quality with COSMIN scores mainly fair or poor. The overall quality of psychometric properties of included measures was intermediate to positive. Certain psychometric properties were not tested for most measures.
Findings provide a basis from which to develop consensus on a core set of patient empowerment constructs and for further work to develop a (set of) appropriately validated measure(s) to capture this. The methodological quality of psychometric studies could be improved by adhering to published quality criteria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Phages need to attach to a receptor on the bacterial surface to initiate infection.•It is not common practice to identify these receptors before phage therapy use.•Identifying phage ...receptors could expand the applications of phage therapy.•Modern platforms facilitate the high-throughput screening of phage receptors.
Phage therapy, the clinical use of viruses that kill bacteria, is a promising strategy in the fight against antimicrobial resistance. Before administration, phages undergo a careful examination of their safety and interactions with target bacteria. This characterization seldom includes identifying the receptor on the bacterial surface involved in phage adsorption. In this perspective article, we propose that understanding the function and location of these phage receptors can open the door to improved and innovative ways to use phage therapy. With knowledge of phage receptors, we can design intelligent phage cocktails, discover new phage-derived antimicrobials, and steer the evolution of phage-resistance towards clinically exploitable phenotypes. In an effort to jump-start this initiative, we recommend priority groups of hosts and phages. Finally, we review modern approaches for the identification of phage receptors, including molecular platforms for high-throughput mutagenesis, synthetic biology, and machine learning.
The human body is host to large numbers of bacteriophages (phages)⁻a diverse group of bacterial viruses that infect bacteria. Phage were previously regarded as bystanders that only impacted immunity ...indirectly via effects on the mammalian microbiome. However, it has become clear that phages also impact immunity directly, in ways that are typically anti-inflammatory. Phages can modulate innate immunity via phagocytosis and cytokine responses, but also impact adaptive immunity via effects on antibody production and effector polarization. Phages may thereby have profound effects on the outcome of bacterial infections by modulating the immune response. In this review we highlight the diverse ways in which phages interact with human cells. We present a computational model for predicting these complex and dynamic interactions. These models predict that the phageome may play important roles in shaping mammalian-bacterial interactions.
Intraclass correlation coefficients (ICC) are recommended for the assessment of the reliability of measurement scales. However, the ICC is subject to a variety of statistical assumptions such as ...normality and stable variance, which are rarely considered in health applications.
A Bayesian approach using hierarchical regression and variance-function modeling is proposed to estimate the ICC with emphasis on accounting for heterogeneous variances across a measurement scale. As an application, we review the implementation of using an ICC to evaluate the reliability of Observer OPTION
, an instrument which used trained raters to evaluate the level of Shared Decision Making between clinicians and patients. The study used two raters to evaluate recordings of 311 clinical encounters across three studies to evaluate the impact of using a Personal Decision Aid over usual care. We particularly focus on deriving an estimate for the ICC when multiple studies are being considered as part of the data.
The results demonstrate that ICC varies substantially across studies and patient-physician encounters within studies. Using the new framework we developed, the study-specific ICCs were estimated to be 0.821, 0.295, and 0.644. If the within- and between-encounter variances were assumed to be the same across studies, the estimated within-study ICC was 0.609. If heteroscedasticity is not properly adjusted for, the within-study ICC estimate was inflated to be as high as 0.640. Finally, if the data were pooled across studies without accounting for the variability between studies then ICC estimates were further inflated by approximately 0.02 while formerly allowing for between study variation in the ICC inflated its estimated value by approximately 0.066 to 0.072 depending on the model.
We demonstrated that misuse of the ICC statistics under common assumption violations leads to misleading and likely inflated estimates of interrater reliability. A statistical analysis that overcomes these violations by expanding the standard statistical model to account for them leads to estimates that are a better reflection of a measurement scale's reliability while maintaining ease of interpretation. Bayesian methods are particularly well suited to estimating the expanded statistical model.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Self-monitoring of physical activity (PA) and diet are key components of behavioral weight loss programs. The purpose of this study was to assess the relationship between diet (mobile app, website, ...or paper journal) and PA (mobile app vs no mobile app) self-monitoring and dietary and PA behaviors.
This study is a post hoc analysis of a 6-month randomized weight loss trial among 96 overweight men and women (body mass index (BMI) 25-45 kg/m(2)) conducted from 2010 to 2011. Participants in both randomized groups were collapsed and categorized by their chosen self-monitoring method for diet and PA. All participants received a behavioral weight loss intervention delivered via podcast and were encouraged to self-monitor dietary intake and PA.
Adjusting for randomized group and demographics, PA app users self-monitored exercise more frequently over the 6-month study (2.6±0.5 days/week) and reported greater intentional PA (196.4±45.9 kcal/day) than non-app users (1.2±0.5 days/week PA self-monitoring, p<0.01; 100.9±45.1 kcal/day intentional PA, p=0.02). PA app users also had a significantly lower BMI at 6 months (31.5±0.5 kg/m(2)) than non-users (32.5±0.5 kg/m(2); p=0.02). Frequency of self-monitoring did not differ by diet self-monitoring method (p=0.63); however, app users consumed less energy (1437±188 kcal/day) than paper journal users (2049±175 kcal/day; p=0.01) at 6 months. BMI did not differ among the three diet monitoring methods (p=0.20).
These findings point to potential benefits of mobile monitoring methods during behavioral weight loss trials. Future studies should examine ways to predict which self-monitoring method works best for an individual to increase adherence.
Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phageto-bacteria ...ratios were increased, relative to the adjacent environment on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non-host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces.
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