bluuebunny/crossref_metadata_2025 huggingface dataset:
Adhesins of Enterohemorrhagic
Escherichia coli
Authors: Stevens Mark P. , Wallis Timothy S.
Published: May 2014

Enterohemorrhagic
Escherichia coli
(EHEC) was first recognized as a cause of human disease in 1983 and is associated with diarrhea and hemorrhagic colitis, which may be complicated by life-threatening renal and neurological sequelae. EHEC are defined by their ability to produce one or more Shiga-like toxins (Stx), which mediate the systemic complications of EHEC infections, and to induce characteristic attaching and effacing lesions on intestinal epithelia, a phenotype that depends on the locus of enterocyte effacement. Acquisition of Stx-encoding bacteriophages by enteropathogenic
E. coli
is believed to have contributed to the evolution of EHEC, and consequently some virulence factors are conserved in both pathotypes. A key requirement for
E. coli
to colonize the intestines and produce disease is the ability to adhere to epithelial cells lining the gastrointestinal tract. Here, we review knowledge of the adhesins produced by EHEC and other Stx-producing
E. coli
, with emphasis on genetic, structural, and mechanistic aspects and their contribution to pathogenesis.
Uropathogenic
Escherichia coli
Authors: Mobley Harry L. T. , Donnenberg Michael S. , Hagan Erin C.
Published: May 2014

The urinary tract is among the most common sites of bacterial infection, and
Escherichia coli
is by far the most common species infecting this site. Individuals at high risk for symptomatic urinary tract infection (UTI) include neonates, preschool girls, sexually active women, and elderly women and men.
E. coli
that cause the majority of UTIs are thought to represent only a subset of the strains that colonize the colon.
E. coli
strains that cause UTIs are termed uropathogenic
E. coli
(UPEC). In general, UPEC strains differ from commensal
E. coli
strains in that the former possess extragenetic material, often on pathogenicity-associated islands (PAIs), which code for gene products that may contribute to bacterial pathogenesis. Some of these genes allow UPEC to express determinants that are proposed to play roles in disease. These factors include hemolysins, secreted proteins, specific lipopolysaccharide and capsule types, iron acquisition systems, and fimbrial adhesions. The current dogma of bacterial pathogenesis identifies adherence, colonization, avoidance of host defenses, and damage to host tissues as events vital for achieving bacterial virulence. These considerations, along with analysis of the
E. coli
CFT073, UTI89, and 536 genomes and efforts to identify novel virulence genes should advance the field significantly and allow for the development of a comprehensive model of pathogenesis for uropathogenic
E. coli
.Further study of the adaptive immune response to UTI will be especially critical to refine our understanding and treatment of recurrent infections and to develop vaccines.
Cytokines and
Escherichia coli
Sepsis
Authors: Kaech Chloé , Bochud Pierre-Yves , Calandra Thierry
Published: May 2014

This review reviews the critical role played by cytokines in the pathogenesis of
Escherichia coli
sepsis. It focuses on prototypic pro-inflammatory and anti-inflammatory cytokines and their influence on mortality in experimental animal models of
E. coli
endotoxemia and of live
E. coli
sepsis. The review reviews the results of clinical trials on anticytokine therapy in patients with severe sepsis or septic shock. The recognition of the critical role played by tumor necrosis factor (TNF), a secreted 17kDa cytokine, in endotoxic and gram-negative shock has been a major step forward in our understanding of the pathogenesis of sepsis. The review describes the role of TNF, IL1, and IL6 in animal models of
E. coli
endotoxemia and sepsis. Given the pivotal role played by TNF in experimental sepsis and the fact that elevated concentrations of TNF were detected in the circulation of patients with sepsis, anti-TNF treatment strategies were investigated as adjunctive therapy for severe sepsis and septic shock. Several studies demonstrated that high levels of interleukin-6 (IL-6) are associated with an increased risk for fatal outcome. Gamma interferon (IFN-γ), IL-12, and IL-18 are functionally related cytokines. A recent study has indicated that transgenic mice overexpressing IL-15 are resistant to an otherwise lethal intraperitoneal
E. coli
challenge. IL4, IL10, and IL13are prototypic anti-inflammatory cytokines. Their classification as anti-inflammatory cytokines is based on the observation that these molecules inhibit the production of proinflammatory cytokines (primarily TNF and IL1) and toxic oxygen and reactive nitrogen species by myeloid cells.
NLRs: Nucleotide-Binding Domain and Leucine-Rich-Repeat-Containing Proteins
Authors: Carneiro Leticia A. M. , Fritz JÖrg H. , Kufer Thomas A. , Travassos Leonardo H. , Benko Szilvia , Philpott Dana J.
Published: May 2014

Eukaryotes have evolved strategies to detect microbial intrusion and instruct immune responses to limit damage from infection. Recognition of microbes and cellular damage relies on the detection of microbe-associated molecular patterns (MAMPs, also called PAMPS, or pathogen-associated molecular patterns) and so-called "danger signals" by various families of host pattern recognition receptors (PRRs). Members of the recently identified protein family of nucleotide-binding domain andleucine-rich-repeat-containing proteins (NLR), including Nod1, Nod2, NLRP3, and NLRC4, have been shown to detect specific microbial motifs and danger signals for regulating host inflammatory responses. Moreover, with the discovery that polymorphisms in
NOD1
,
NOD2
,
NLRP1
, and
NLRP3
are associated with susceptibility to chronic inflammatory disorders, the view has emerged that NLRs act not only as sensors butalso can serve as signaling platforms for instructing and balancing host immune responses. In this chapter, we explore the functions of these intracellular innate immune receptors and examine their implication in inflammatory diseases.
Salmonella
and Enteropathogenic
Escherichia coli
Interactions with Host Cells: Signaling Pathways
Authors: Goosney Danika L. , Kujat Choy Sonya L. , Finlay B. Brett
Published: May 2014

The host-pathogen interaction involves a myriad of initiations and responses from both sides. Bacterial pathogens such as enteropathogenic
Escherichia coli
(EPEC) and
Salmonella enterica
have numerous virulence factors that interact with and alter signaling components of the host cell to initiate responses that are beneficial to pathogen survival and persistence. The study of
Salmonella
and EPEC infection reveals intricate connections between host signal transduction, cytoskeletal architecture, membrane trafficking, and cytokine gene expression. The emerging picture includes elements of molecular mimicry by bacterial effectors and bacterial subversion of typical host events, with the result that EPEC is able to survive and persist in an extracellular milieu, while
Salmonella
establishes an intracellular niche and is able to spread systemically throughout the host. This review focuses on recent advances in our understanding of the signaling events stemming from the host-pathogen interactions specific to
Salmonella
and EPEC.
Genome Sequences of Three Frequently Used Listeria monocytogenes and Listeria ivanovii Strains
Authors: Klumpp Jochen , Staubli Titu , Schmitter Sibylle , Hupfeld Mario , Fouts Derrick E. , Loessner Martin J.
Published: May 2014

We present the complete
de novo
assembled genome sequences of
Listeria monocytogenes
strains WSLC 1001 (ATCC 19112) and WSLC 1042 (ATCC 23074) and
Listeria ivanovii
WSLC 3009, three strains frequently used for the propagation and study of bacteriophages because they are presumed to be free of inducible prophages.
Genome Sequence of the Nonpathogenic Pseudomonas aeruginosa Strain ATCC 15442
Authors: Wang Yujiao , Li Chao , Gao Chao , Ma Cuiqing , Xu Ping
Published: May 2014

Pseudomonas aeruginosa
ATCC 15442 is an environmental strain of the
Pseudomonas
genus. Here, we present a 6.77-Mb assembly of its genome sequence. Besides giving insights into characteristics associated with the pathogenicity of
P. aeruginosa
, such as virulence, drug resistance, and biofilm formation, the genome sequence may provide some information related to biotechnological utilization of the strain.
Integrative Conjugative Element ICE-βox Confers Oxidative Stress Resistance to Legionella pneumophila
In Vitro
and in Macrophages
Authors: Flynn Kaitlin J. , Swanson Michele S.
Published: April 2014

Integrative conjugative elements (ICEs) are mobile blocks of DNA that can contribute to bacterial evolution by self-directed transmission of advantageous traits. Here, we analyze the activity of a putative 65-kb ICE harbored by
Legionella pneumophila
using molecular genetics, conjugation assays, a phenotype microarray screen, and macrophage infections. The element transferred to a naive
L. pneumophila
strain, integrated site-specifically, and conferred increased resistance to oxacillin, penicillin, hydrogen peroxide, and bleach. Furthermore, the element increased survival of
L. pneumophila
within restrictive mouse macrophages. In particular, this ICE protects
L. pneumophila
from phagocyte oxidase activity, since mutation of the macrophage NADPH oxidase eliminated the fitness difference between strains that carried and those that lacked the mobile element. Renamed ICE-βox (for
β
-lactam antibiotics and
o
x
idative stress), this transposable element is predicted to contribute to the emergence of
L. pneumophila
strains that are more fit in natural and engineered water systems and in macrophages.

IMPORTANCE
Bacteria evolve rapidly by acquiring new traits via horizontal gene transfer. Integrative conjugative elements (ICEs) are mobile blocks of DNA that encode the machinery necessary to spread among bacterial populations. ICEs transfer antibiotic resistance and other bacterial survival factors as cargo genes carried within the element. Here, we show that
Legionella pneumophila
, the causative agent of Legionnaires’ disease, carries ICE-βox, which enhances the resistance of this opportunistic pathogen to bleach and β-lactam antibiotics. Moreover,
L. pneumophila
strains encoding ICE-βox are more resistant to macrophages that carry phagocyte oxidase. Accordingly, ICE-βox is predicted to increase the fitness of
L. pneumophila
in natural and engineered waters and in humans. To our knowledge, this is the first description of an ICE that confers oxidative stress resistance to a nosocomial pathogen.
Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia
Authors: Briese Thomas , Mishra Nischay , Jain Komal , Zalmout Iyad S. , Jabado Omar J. , Karesh William B. , Daszak Peter , Mohammed Osama B. , Alagaili Abdulaziz N. , Lipkin W. Ian
Published: April 2014

Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection.

IMPORTANCE
In most cases of Middle East respiratory syndrome (MERS), the route for human infection with the causative agent, MERS coronavirus (MERS-CoV), is unknown. Antibodies to and viral nucleic acids of MERS-CoV have been found in dromedaries, suggesting the possibility that they may serve as a reservoir or vector for human infection. However, neither whole viral genomic sequence nor infectious virus has been isolated from dromedaries or other animals in Saudi Arabia. Here, we report recovery of MERS-CoV from nasal swabs of dromedaries, demonstrate that MERS-CoV whole-genome consensus sequences from dromedaries and humans are indistinguishable, and show that dromedaries can be simultaneously infected with more than one MERS-CoV. Together with data indicating widespread dromedary infection in the Kingdom of Saudi Arabia, these findings support the plausibility of a role for dromedaries in human infection.
Humanized Mice for Studying Human Immune Responses and Generating Human Monoclonal Antibodies
Authors: Akkina Ramesh
Published: April 2014

The new-generation humanized (Hu) mouse models permit multilineage human hematopoiesis and generate T cells, B cells, macrophages, and dendritic cells required for a coordinated human immune response. Therefore, any desired antigen or human-specific pathogens that can infect humanized mice can be used to generate human antibody responses. Two leading humanized mouse models are currently being used. The Hu-HSC model uses the transplantation of human hematopoietic stem cells (HSCs), whereas the BLT mouse model is created by transplantation of human fetal liver, thymus, and HSC. A number of human pathogens such as HIV-1, dengue, Epstein-Barr virus, and hepatitis C virus have been studied in these systems. Responder antigen-specific B cells from these animals can be collected and used to generate human monoclonals by B-cell immortalization or by single-cell PCR methods to “rescue” antibody-producing genes for ectopic expression. Both models generate cellular and humoral immune responses. However, the antibodies generated are primarily of the IgM type because of the inefficient immunoglobulin class switch resulting in the suboptimal production of antigen-specific affinity-matured IgG. The current Hu mouse models thus far have permitted the analysis of human “antibodyome,” and recent reports demonstrated their utility in generating human monoclonal antibodies. Ongoing efforts at further refinements are expected to make these systems more efficient in the near future.
Antibody Engineering
Authors: Lo Kin-Ming , Leger Olivier , Hock Björn
Published: April 2014

Advanced molecular biology techniques developed during the past few decades have allowed the industry to exploit and commercialize the natural defense mechanisms that antibodies provide. This review discusses the latest advances in antibody-engineering technologies to enhance clinical efficacy and outcomes. For the constant regions, the choice of the antibody class and isotype has to be made carefully to suit the therapeutic applications. Engineering of the Fc region, either by direct targeted mutagenesis or by modifying the nature of itsN-glycan, has played an important role in recent years in increasing half-life or controlling effector functions. The variable regions of the antibody are responsible for binding affinity and exquisite specificity to the target molecule, which together with the Fc determine the drug's efficacy and influence the drug dose required to obtain the desired effectiveness. A key requirement during antibody development is therefore to affinity mature the variable regions when necessary, so that they bind the therapeutic target with sufficiently high affinity to guarantee effective occupancy over prolonged periods. If the antibody was obtained from a non-human source, such as rodents, a humanization process has to be applied to minimize immunogenicity while maintaining the desired binding affinity and selectivity. Finally, we discuss the next next-generation antibodies, such as antibody-drug conjugates, bispecific antibodies, and immunocytokines, which are being developed to meet future challenges.
The Role of Complement in Antibody Therapy for Infectious Diseases
Authors: Wibroe Peter P. , Helvig Shen Y. , Moein Moghimi S.
Published: April 2014

The complement system is part of the innate immune system, eliciting central immunoregulatory functions. Detection of foreign surfaces is either achieved through complement-specific patternrecognition molecules or mediated by antigen recognition of antibodies. Immunoglobulin A (IgA), IgG, and IgM all have the potential to initiate a complement response, with the efficiency and response development closely related to the antibody isotype, multimeric state, and degree of glycosylation. A group of serum proteins constitutes the central effector functions of complement, thus allowing direct cell lysis, opsonization, and inflammation. These effector functions can be used in antibody therapies, especially against infectious diseases, as the target membranes lack complement regulatory proteins. The relative contribution of each function and the interplay with direct antibody-mediated clearance is not fully exploited, thus suggesting an option for further rational optimization of antibody therapies.
Cheese Classification, Characterization, and Categorization: A Global Perspective
Authors: Almena-Aliste Montserrat , Mietton Bernard
Published: April 2014

Cheese is one of the most fascinating, complex, and diverse foods enjoyed today. Three elements constitute the cheese ecosystem: ripening agents, consisting of enzymes and microorganisms; the composition of the fresh cheese; and the environmental conditions during aging. These factors determine and define not only the sensory quality of the final cheese product but also the vast diversity of cheeses produced worldwide. How we define and categorize cheese is a complicated matter. There are various approaches to cheese classification, and a global approach for classification and characterization is needed. We review current cheese classification schemes and the limitations inherent in each of the schemes described. While some classification schemes are based on microbiological criteria, others rely on descriptions of the technologies used for cheese production. The goal of this review is to present an overview of comprehensive and practical integrative classification models in order to better describe cheese diversity and the fundamental differences within cheeses, as well as to connect fundamental technological, microbiological, chemical, and sensory characteristics to contribute to an overall characterization of the main families of cheese, including the expanding world of American artisanal cheeses.
The Microfloras and Sensory Profiles of Selected Protected Designation of Origin Italian Cheeses
Authors: Licitra Giuseppe , Carpino Stefania
Published: April 2014

Approximately 39 Italian cheeses carry protected designation of origin (PDO) status. These cheeses differ in their manufacturing technology and the microbial flora which comprise the finished products. The evolution of lactic microflora in cheeses with PDO status is of particular interest because the biochemical activities of these organisms participate in cheesemaking and may play an acknowledged role in the development of organoleptic characteristics during ripening. Nonstarter lactic acid bacteria (NSLAB) constitute complex microbial associations that are characterized by the occurrence of various species and many biotypes as a result of a number of selective conditions persisting during the manufacturing process and different ecological niches. The evolution of different species during ripening of Fiore Sardo showed that, when present,
Lactobacillus paracasei
persists and dominates the microflora of the cheese in the last period of ripening, suggesting that this species, more resistant to the constraints of the mature cheese, could be involved in proteolysis and in other enzymatic processes occurring during cheese ripening. In contrast, the stretching step typical of pasta filata cheese, such as Ragusano, induced a simplification of the raw milk profiles, allowing the persistence only of some predominant species, such as
Streptococcus thermophilus
,
Lactobacillus delbrueckii
subsp.
lactis
,
Lactococcus lactis
, and
Streptococcus macedonicus
, after the stretching step.
Lactobacillus plantarum
and
L. paracasei
were isolated from ripened Castelmagno PDO cheese samples with the highest frequencies. These species, generally absent in the milk, occur in dairy ecosystems and dominate the bacterial flora of many ripened semihard cheeses. In PDO long-ripened Italian cheese such as Parmigiano Reggiano, the NSLAB population is mainly formed by
L. paracasei
,
Lactobacillus rhamnosus
, and
Pediococcus acidilactici
.
Lactobacillus helveticus
,
L. delbrueckii
subsp.
lactis
, and
L. delbrueckii
subsp.
bulgaricus
were also detected. Continued insight into the microbial populations of traditional Italian cheeses will allow continued production of characteristic, high-quality cheeses which have been enjoyed for many centuries.
Towards an Ecosystem Approach to Cheese Microbiology
Authors: Wolfe Benjamin E. , Dutton Rachel J.
Published: April 2014

Cheese is an ideal environment to serve as a model for the behavior of microbes in complex communities and at the same time allow detailed genetic analysis. Linking organisms, and their genes, to their role in the environment becomes possible in the case of cheese since cheese microbial communities have been “in culture” for thousands of years, with the knowledge of how to grow these organisms passed down by generations of cheesemakers. Recent reviews have described several emerging approaches to link molecular systems biology to ecosystem-scale processes, known as ecosystems biology. These approaches integrate massive datasets now available through high-throughput sequencing technologies with measurements of ecosystem properties. High-throughput datasets uncover the “parts list” (e.g., the species and all the genes within each species) of an ecosystem as well as the molecular basis of interactions within this parts list. Novel computational frameworks make it possible to link species and their interactions to ecosystem properties. Applying these approaches across multiple temporal and spatial scales makes it possible to understand how changes in the parts lists over space and time lead to changes in ecosystems processes. By manipulating the species present within model systems, we can test hypotheses related to the role of microbes in ecosystem function. Due to the tractability of cheese microbial communities, we have the opportunity to use an ecosystems biology approach from the scale of individual microbial cells within a cheese to replicated cheese microbial communities across continents. Using cheese as a model microbial ecosystem can provide a way to answer important questions concerning the form, function, and evolution of microbial communities.
Cyclic AMP Signaling in Mycobacteria
Authors: Knapp Gwendowlyn S. , McDonough Kathleen A.
Published: April 2014

All cells must adapt to changing conditions, and many use cyclic AMP (cAMP) as a second messenger to sense and respond to fluctuations in their environment. cAMP is made by adenylyl cyclases (ACs), and mycobacteria have an unusually large number of biochemically distinct ACs. cAMP is important for gene regulation in mycobacteria, and the ability to secrete cAMP into host macrophages during infection contributes to
Mycobacterium tuberculosis
pathogenesis. This article discusses the many roles of cAMP in mycobacteria and reviews what is known about the factors that contribute to production, destruction, and utilization of this important signal molecule. Special emphasis is placed on cAMP signaling in
M. tuberculosis
complex bacteria and its importance to
M. tuberculosis
during host infection.
Genetics of Phage Lysis
Authors: Pimentel Madalena
Published: April 2014

We have been witnessing an increased interest in bacteriophage studies focused on their use as antibacterial agents to fight pathogenic bacteria. This interest is a consequence of the phages' ability to lyse a bacterial host. Until recently, little was known about the mechanisms used by mycobacteriophages to induce lysis of their complex hosts. However, studies on Ms6-induced lysis have changed this scenario and provided new insights into the mechanisms of bacteriophage-induced lysis. Specific lysis protein genes have been identified in mycobacteriophage genomes, reflecting the particular mycobacterial cell envelope composition. These include enzymes that target mycolic acid–containing lipids and proteins that participate in the secretion of the phage endolysin, functioning as chaperone-like proteins. This chapter focuses on the current knowledge of mycobacteriophage-induced lysis, starting with an overview of phage lysis and basic features of the lysis players.
Noncoding RNA in Mycobacteria
Authors: Arnvig Kristine B. , Cortes Teresa , Young Douglas B.
Published: April 2014

Efforts to understand the molecular basis of mycobacterial gene regulation are dominated by a protein-centric view. However, there is a growing appreciation that noncoding RNA, i.e., RNA that is not translated, plays a role in a wide variety of molecular mechanisms. Noncoding RNA comprises rRNA, tRNA, 4.5S RNA, RnpB, and transfer-messenger RNA, as well as a vast population of regulatory RNA, often dubbed “the dark matter of gene regulation.” The regulatory RNA species comprise 5′ and 3′ untranslated regions and a rapidly expanding category of transcripts with the ability to base-pair with mRNAs or to interact with proteins. Regulatory RNA plays a central role in the bacterium's response to changes in the environment, and in this article we review emerging information on the presence and abundance of different types of noncoding RNA in mycobacteria.
Gene Transfer in
Mycobacterium tuberculosis
: Shuttle Phasmids to Enlightenment
Authors: Jacobs, Jr. William R.
Published: April 2014

Infectious diseases have plagued humankind throughout history and have posed serious public health problems. Yet vaccines have eradicated smallpox and antibiotics have drastically decreased the mortality rate of many infectious agents. These remarkable successes in the control of infections came from knowing the causative agents of the diseases, followed by serendipitous discoveries of attenuated viruses and antibiotics. The discovery of DNA as genetic material and the understanding of how this information translates into specific phenotypes have changed the paradigm for developing new vaccines, drugs, and diagnostic tests. Knowledge of the mechanisms of immunity and mechanisms of action of drugs has led to new vaccines and new antimicrobial agents. The key to the acquisition of the knowledge of these mechanisms has been identifying the elemental causes (i.e., genes and their products) that mediate immunity and drug resistance. The identification of these genes is made possible by being able to transfer the genes or mutated forms of the genes into causative agents or surrogate hosts. Such an approach was limited in
Mycobacterium tuberculosis
by the difficulty of transferring genes or alleles into
M. tuberculosis
or a suitable surrogate mycobacterial host. The construction of shuttle phasmids—chimeric molecules that replicate in
Escherichia coli
as plasmids and in mycobacteria as mycobacteriophages—was instrumental in developing gene transfer systems for
M. tuberculosis.
This review will discuss
M. tuberculosis
genetic systems and their impact on tuberculosis research.
RNA Viruses: A Case Study of the Biology of Emerging Infectious Diseases
Authors: J. Woolhouse Mark E. , Adair Kyle , Brierley Liam
Published: April 2014

There are 180 currently recognized species of RNA virus that can infect humans, and on average, 2 new species are added every year. RNA viruses are routinely exchanged between humans and other hosts (particularly other mammals and sometimes birds) over both epidemiological and evolutionary time: 89% of human-infective species are considered zoonotic and many of the remainder have zoonotic origins. Some viruses that have crossed the species barrier into humans have persisted and become human-adapted viruses, as exemplified by the emergence of HIV-1. Most, however, have remained as zoonoses, and a substantial number have apparently disappeared again. We still know relatively little about what determines whether a virus is able to infect, transmit from, and cause disease in humans, but there is evidence that factors such as host range, cell receptor usage, tissue tropisms, and transmission route all play a role. Although systematic surveillance for potential new human viruses in nonhuman hosts would be enormously challenging, we can reasonably aspire to much better knowledge of the diversity of mammalian and avian RNA viruses than exists at present.
Antibiotic Resistance in and from Nature
Authors: Davies Julian
Published: April 2014

Recent studies have shown that antibiotic resistance genes are omnipresent in nature. Human use of antimicrobial compounds as therapeutics, growth-promoting agents, pesticides, etc., over the past half century have contributed to this situation.
Factors Impacting the Control of Rabies
Authors: Nel Louis H.
Published: April 2014

Rabies is a classical zoonosis that has been known to man for ages. The disease can be caused by several viral species in the
Lyssavirus
genus, but the type species, rabies virus (RABV), is by far the most important from a zoonosis perspective. The extreme neurotropism of RABV and the evolutionarily conserved elements and structures of the mammalian brain suggest that this virus evolved an ultimate niche for replication, simultaneously exploiting classical social behavior of a wide diversity of hosts among the chiropters and carnivores. There is substantial evidence that RABV originated in bats and later switched hosts to yield globally disseminated canine rabies. Following the revolutionary work of Louis Pasteur, control and elimination of dog rabies was achieved in Europe, but widespread colonial introduction of European strains of dog RABV to other parts of the world occurred. Thus, dog rabies spread rapidly in the 1900s, and today the vast majority of the tens of thousands of annual human rabies cases stem from dog rabies, which has become endemic in the entire developing world. The fact that human rabies is preventable, through control in the dog reservoir on one hand and through effective prophylaxis in cases of exposure on the other hand, is an indictment of public health strategies and practices. This article discusses some of the drivers that have contributed to the recurrent neglect of rabies in the modern world, as well as evolving One Health-based rabies control partnerships and initiatives that have been progressive, productive, and promising of true global benefits.
Defining the Future of One Health
Authors: Jeggo Martyn , Mackenzie John S.
Published: April 2014

This paper recounts the history of One Health; the philosophy behind the initiative; and the current situation at the international, national, and regional level. It cites examples of where a One Health approach has successfully delivered.
Combating the Triple Threat: The Need for a One Health Approach
Authors: King Lonnie J.
Published: April 2014

We live in a world that is rapidly changing, complex, and progressively interconnected. The convergence of people, animals, and their products embedded in an ever-changing environment has created a new dynamic. This dynamic is characterized by new threats to the health of humans, animals, and the environment. In addition, the health of each of these three domains is profoundly and inextricably linked and elaborately connected. Our interconnectedness strongly suggests that our future success in improving health will be based on a new integrative, holistic, and collaborative approach termed One Health. One Health demands that we work across professions, disciplines, and old boundaries. The challenges to our health are unique and profound, and old solutions to our new “wicked” problems are no longer as relevant or effective as in the past. The concept of One Health is not new but has reemerged as a concept to both better understand the triple threats to health and to better address these contemporary challenges using new approaches. This article discusses the health threats to each domain and calls for a new model to confront these challenges by shifting strategies and interventions upstream, closer to the origins of the threats. One Health is a new paradigm that can be used to improve the health of people, animals, and our environment as a collective rather than restricting our actions to any single domain.
Medial opening wedge distal femoral osteotomy for post-traumatic secondary knee osteoarthritis
Authors: Matsui Gen , Akiyama Takenori , Ikemura Satoshi , Mawatari Taro
Published: April 2014

Osteoarthritis of the knee secondary to femoral fracture is difficult to treat. There are some surgical options, such as total knee arthroplasty or correction osteotomy. Opening wedge high tibial osteotomy is an established treatment of gonarthrosis. However, few reports are available on the effectiveness of a medial opening wedge distal femoral osteotomy. We present a case of a medial opening wedge distal femoral osteotomy on gonarthrosis secondary to a malunited femoral fracture with varus deformity and leg length discrepancy. This osteotomy was performed at the deformed femur, with locking plate fixation and autologous bone graft. Six months after the surgery, the osteotomy site was filled with bridging callus. Two years later, the Knee Society Score improved from 45 to 90 points. Medial opening wedge distal femoral osteotomy can be a useful method to treat knee osteoarthritis associated with distal femoral deformity.
Trichobezoar: a diagnosis which is hard to swallow and harder to digest
Authors: Sanneerappa Phani Bhushan Jeerigehalli , Hayes Hannah Marie , Daly Edwina , Moodley Visalatchee n/a
Published: April 2014

An 11-year-old girl with normal development and good academic progress at school presented with an abdominal mass. She lived with her aunt as her mother suffered from severe bipolar disorder and was unable to raise her. There were also multiple bereavements in the family. She had a history of alopecia and admitted to have eaten her hair to relieve stress. Examination was normal apart from a solid mass in the left hypogastrium. CT abdomen revealed a huge intra-abdominal mass covering most of the lumen. Open laparotomy was performed to remove the mass which was confirmed to be a trichobezoar. She made a good postoperative recovery and was discharged after 7 days. She has been referred to psychology services. Bereavement alone without psychiatric, physical disability or autism can be associated with trichobezoar. More studies are needed to study the association of trichotillomania, trichophagia and trichobezoar.
Curious case of calciphylaxis leading to acute mitral regurgitation
Authors: Gallimore Grant Gardner , Curtis Blair , Smith Andria , Benca Michael
Published: April 2014

Calciphylaxis is uncommon and typically seen in patients with end-stage renal disease. It has been defined as a vasculopathic disorder characterised by cutaneous ischaemia and necrosis due to calcification, intimal fibroplasia and thrombosis of pannicular arterioles. We present the case of a 74-year-old woman with chronic kidney disease stage III who developed calciphylaxis leading to mitral valve calcification, chordae tendineae rupture and acute mitral regurgitation. Although an alternative explanation can typically be found for non-uraemic calciphylaxis, her evaluation did not reveal any usual non-uraemic causes including elevated calcium–phosphorus product, hyperparathyroidism, or evidence of connective tissue disease. Her wounds improved with sodium thiosulfate, pamidronate, penicillin and hyperbaric oxygen therapies but she ultimately decompensated with the onset of acute mitral regurgitation attributed to rupture of a previously calcified chordae tendineae. This case highlights an unusual case of calciphylaxis without clear precipitant as well as a novel manifestation of the disease.
Necrotising fasciitis due to an infected sebaceous cyst
Authors: Bosman W M P F , Brekelmans W , Verduijn P S , Borger van der Burg B L S , Ritchie E D
Published: April 2014

The current case presents a patient who was admitted to our hospital with the diagnosis of cellulitis of the right groin. In the following days, the patient's condition deteriorated and developed a septic shock. Exploration in the operating room showed a necrotising fasciitis of the adductor muscles, with an infected sebaceous cyst in the inguinal crest as port d'entrée. After extensive surgical debridement, antibiotic therapy, haemodynamic and respiratory support, the patient recovered. Necrotising fasciitis is a rare but very lethal condition, which necessitates aggressive surgical therapy and antibiotic support. The current case report is the first report to show a necrotising fasciitis due to an infected sebaceous cyst.
Acute alveolar sarcoidosis presenting with hypoxaemic respiratory failure
Authors: Gera Kamal , Gupta Nitesh , Ahuja Anuradha , Shah Ashok
Published: April 2014

Alveolar sarcoidosis is a less commonly seen pulmonary manifestation of the disease. An acute presentation of this radiological pattern with hypoxaemic respiratory failure has been documented only once, four decades ago. A 30-year-old man presented with acute onset of progressive and persistent dyspnoea over 20 days ago with hypoxaemic respiratory failure. Imaging demonstrated mediastinal lymphadenopathy and coalescent parenchymal alveolar opacities having ill-defined margins along with air bronchograms in the mid and lower zones bilaterally, suggestive of alveolar sarcoidosis. A restrictive pattern with a diffusion defect was seen on pulmonary function testing. Bronchoscopic evaluation revealed non-caseating granulomas on histopathology confirming pulmonary sarcoidosis. This was further supported by an elevated serum ACE level and negative Mantoux test. Oral prednisolone elicited a rapid clinical and radiological response. Alveolar sarcoidosis can rarely present acutely with hypoxaemic respiratory failure, which can respond remarkably and expeditiously to appropriate therapy.
A late presentation of isolated lymph node tuberculosis postintravesical BCG therapy for superficial bladder cancer: a novel case
Authors: Tasleem Ali Moostapha , Varga Branislav , Mahmalji Wasim , Madaan Sanjeev
Published: May 2014

Intravesical BCG immunotherapy is commonly used in the treatment of superficial bladder cancer. We recount the case of an 82-year-old British man who completed a course of BCG immunotherapy in 2011 for superficial bladder cancer, and presented in January 2013 with a loss of appetite, loss of weight and severe back pain. CT scanning, followed by MRI displayed a 5.7cm×5 cm conglomerated necrotic, haemorrhagic mass of lymph nodes in the para-aortic region. A CT-guided biopsy revealed granulomatous inflammation, focal fibrosis and acid-fast bacilli consistent withMycobacterium tuberculosis(TB). The patient was treated with combination antituberculous medication, and is recovering. To our knowledge, this is the only reported case of lymph node TB secondary to intravesical BCG immunotherapy. We suggest that in patients treated with postintravesical BCG with enlarged lymph nodes, a diagnosis of secondary TB should be considered.
Malignant renal angiomyolipoma without tuberous sclerosis
Authors: Cusano Antonio , Abarzua-Cabezas Fernando , Meraney Anoop
Published: April 2014

A 68-year-old woman presented with abdominal pain, fatigue, anorexia and night sweats. Imaging studies identified a vascular mass extending from the upper pole of the right kidney with anterior displacement to the abdominal midline, consistent with renal cell carcinoma. A radical nephrectomy and right pelvic lymph node dissection was performed. Pathology determined a grade 4 malignant epithelioid angiomyolipoma that invaded hilar and perinephric adipose tissue. Gross tumour was also present within the renal vein, sinus, pelvis, capsule and perinephric fat. The tumour was HMB-45 positive, supporting the diagnosis of a typical angiomyolipoma in association with the high-grade epithelioid tumour.
The spatiotemporal association of non-prescription retail sales with cases during the 2009 influenza pandemic in Great Britain
Authors: Todd Stacy , Diggle Peter J , White Peter J , Fearne Andrew , Read Jonathan M
Published: April 2014

Objective

To assess whether retail sales of non-prescription products can be used for syndromic surveillance and whether it can detect influenza activity at different spatial scales. A secondary objective was to assess whether changes in purchasing behaviour were related to public health advice or levels of media or public interest.

Setting

The UK.

Participants

National and regional influenza case estimates and retail sales from a major British supermarket.

Outcome measures

Weekly, seasonally adjusted sales of over-the-counter symptom remedies and non-pharmaceutical products; recommended as part of the advice offered by public health agencies; were compared with weekly influenza case estimates. Comparisons were made at national and regional spatial resolutions. We also compared sales to national measures of contemporaneous media output and public interest (Internet search volume) related to the pandemic.

Results

At a national scale there was no significant correlation between retail sales of symptom remedies and cases for the whole pandemic period in 2009. At the regional scale, a minority of regions showed statistically significant positive correlations between cases and sales of adult ‘cold and flu’ remedies and cough remedies (3.2%, 5/156, 3.8%, 6/156), but a greater number of regions showed a significant positive correlation between cases and symptomatic remedies for children (35.6%, 55/156). Significant positive correlations between cases and sales of thermometers and antiviral hand gels/wash were seen at both spatial scales (Cor 0.477 (95% CI 0.171 to 0.699); 0.711 (95% CI 0.495 to 0.844)). We found no significant association between retail sales and media reporting or Internet search volume.

Conclusions

This study provides evidence that the British public responded appropriately to health messaging about hygiene. Non-prescription retail sales at a national level are not useful for the detection of cases. However, at finer spatial scales, in particular age-groups, retail sales may help augment existing surveillance and merit further study.
Secondary triage in prehospital emergency ambulance services: a systematic review
Authors: Eastwood Kathryn , Morgans Amee , Smith Karen , Stoelwinder Johannes
Published: May 2014

Objective

Secondary telephone triage to divert low-acuity patients to alternative non-ambulance services before ambulance arrival has been trialled in the UK and USA as a management strategy to cope with the increase in ambulance demand. The objective of this systematic review was to examine the literature on the structure, safety and success of secondary triage systems.

Methods

For inclusion in the study, the telephone triage system had to be a secondary process, receiving referred patients who had already been categorised as low priority by a primary triage process. Two independent reviewers conducted the search to identify relevant studies. Six articles and one report were identified.

Results

The major theme of the papers was the safety and accuracy of secondary telephone triage in identifying low-acuity patients. Two studies also discussed patient satisfaction. There was a low incidence of adverse events, as expected as these patients had already been subjected to primary telephone triage. In the studies identifying ambulance dispatch as a potential final disposition, at least half of the patients were diverted away from ambulance dispatch. In the studies that identified self/home care as a final disposition, a maximum of 31% of patients were categorised to this outcome. Otherwise all patients were recommended for assessment by a healthcare professional other than ambulance clinicians. Patients appeared to be satisfied with secondary telephone triage on follow-up.

Conclusions

These results suggest that, while secondary triage of these patients is safe, further research is required to determine its most appropriate structure and its effect on ambulance demand.
Systemic reactions and anaphylaxis with an acute serum tryptase ≥14 μg/L: retrospective characterisation of aetiology, severity and adherence to National Institute of Health and Care Excellence (NICE) guidelines for serial tryptase measurements and specialist referral
Authors: Srivastava Sapna , Huissoon Aarnoud P , Barrett Victoria , Hackett Scott , Dorrian Susan , Cooke Matthew W , Krishna Mamidipudi T
Published: April 2014

Aims

To characterise patients with systemic reactions and anaphylaxis with an acute serum tryptase of ≥14 μg/L against recently published World Allergy Organisation (WAO) diagnostic criteria. To also perform a clinical audit to assess adherence to National Institute of Health and Care Excellence (NICE) guideline recommendations regarding serial tryptase measurements and specialist referral.

Methods

A systematic retrospective survey (2006–2010) was carried out (n=171; males=86; mean age±SD 48±20 years) and data were extracted from emergency department and specialist allergy clinic records.

Results

34 patients (20%) had a grade 1 reaction, 61 (36%) grade 2, 46 (27%) grade 3 and 6 patients (4%) grade 4 (24 patients (13%) could not be graded due to lack of adequate clinical details) and 6% developed a biphasic response. Serial tryptase measurements were not available in 117 (69%) of the cohort. 97 (57%) patients were referred for specialist assessment, and 72 (74%) attended. 50% of cases were diagnosed with idiopathic systemic reactions/anaphylaxis and 28%, 14% and 8% triggered by drugs, foods and other allergies including disorders of mast cell overload, respectively. A weak positive correlation was detected between acute serum tryptase and severity.

Conclusions

The correlation between acute serum tryptase and severity of anaphylaxis/systemic reactions is weak. A significant proportion of patients with raised acute serum tryptase had mild reactions which did not meet WAO criteria for anaphylaxis and this may reduce the specificity of the test. The commonest aetiology in this cohort was idiopathic followed by drug and food allergies. NICE guidelines relating to serial tryptase measurements and specialist referral were not followed, and there is an urgent need to raise the awareness among clinicians involved in the management of anaphylaxis.
Improved estimation of size-transition matrices using tag–recapture data
Authors: Lloyd-Jones Luke R. , Nguyen Hien D. , Wang You-Gan , O’Neill Michael F.
Published: April 2014

We derive a new method for determining size-transition matrices (STMs) that eliminates probabilities of negative growth and accounts for individual variability. STMs are an important part of size-structured models, which are used in the stock assessment of aquatic species. The elements of STMs represent the probability of growth from one size class to another, given a time step. The growth increment over this time step can be modelled with a variety of methods, but when a population construct is assumed for the underlying growth model, the resulting STM may contain entries that predict negative growth. To solve this problem, we use a maximum likelihood method that incorporates individual variability in the asymptotic length, relative age at tagging, and measurement error to obtain von Bertalanffy growth model parameter estimates. The statistical moments for the future length given an individual’s previous length measurement and time at liberty are then derived. We moment match the true conditional distributions with skewed-normal distributions and use these to accurately estimate the elements of the STMs. The method is investigated with simulated tag–recapture data and tag–recapture data gathered from the Australian eastern king prawn (Melicertus plebejus).