Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Holistic processing of impossible objects: Evidence from Garner’s speeded-classification task

Holistic processing, the decoding of the global structure of a stimulus while the local parts are not explicitly represented, is a basic characteristic of object perception. The current study was aimed to test whether such a representation could be created even for objects that violate fundamental principles of spatial organization, namely impossible objects. Previous studies argued that these objects cannot be represented holistically in long-term memory because they lack coherent 3D structure. Here, we utilized Garner’s speeded classification task to test whether the perception of possible and impossible objects is mediated by similar holistic processing mechanisms. To this end, participants were asked to make speeded classifications of one object dimension while an irrelevant dimension was kept constant (baseline condition) or when this dimension varied (filtering condition). It is well accepted that ignoring the irrelevant dimension is impossible when holistic perception is mandatory, thus the extent of Garner interference in performance between the baseline and filtering conditions serves as an index of holistic processing. Critically, in Experiment 1, similar levels of Garner interference were found for possible and impossible objects implying holistic perception of both object types. Experiment 2 extended these results and demonstrated that even when depth information was explicitly processed, participants were still unable to process one dimension (width/depth) while ignoring the irrelevant dimension (depth/width, respectively). The results of Experiment 3 replicated the basic pattern found in Experiments 1 and 2 using a novel set of object exemplars. In Experiment 4, we used possible and impossible versions of the Penrose triangles in which information about impossibility is embedded in the internal elements of the objects which participant were explicitly asked to judge. As in Experiments 1–3, similar Garner interference was found for possible and impossible objects. Taken together, these findings emphasize the centrality of holistic processing style in object perception and suggest that it applies even for atypical stimuli such as impossible objects.     

Gaining and maintaining recognition as a paediatric postgraduate trainer

Consultants who act as Educational or Clinical Supervisors to postgraduate doctors must now be recognised as trainers by the GMC. This is a formal process conducted at employer level using supporting information against domains formulated by the Academy of Medical Educators. Recognition is recommended to Health Education England and reported to the GMC. This article addresses how paediatricians in the UK can gain recognition as a trainer of foundation doctors and specialty trainees in paediatrics and how to maintain that recognition over the 5-year cycle.     

Preserved Knowledge of Maps of Countries: Implications for the Organization of Semantic Memory

We describe two patients with selectively preserved knowledge of the category of countries. Following a series of cerebral infarcts, patient DB presented with severe perceptual impairment, including dense apperceptive agnosia, prosopagnosia, and topographical agnosia. Despite these deficits, he could effortlessly name countries from their outline maps. Patient WH, who suffered from semantic dementia, had severe naming and comprehension difficulties, with extremely sparse residual semantic knowledge. Remarkably, the category of countries was preserved. First, we argue that, for both patients, this category preservation occurs at a semantic level. Second, we discuss our findings in the context of three current models of category-specific effects (perceptual, ontogenetic, and evolutionary models). We argue that the perceptual model (Humphreys and colleagues) cannot easily accommodate our findings. By contrast, the ontogenetic (Warrington and colleagues) and evolutionary models (Caramazza and colleagues) can explain our findings. However, some modifications to both models are required. The ontogenetic model needs to envisage a spatial channel for the development of map knowledge, which is anatomically separate from channels of other categories of knowledge. The evolutionary model needs to envisage the possibility that some categories of knowledge, such as countries, may not be prewired, but learned during ontogenetic development.     

Long‐term effects of neonatal hippocampal lesions on novelty preference in monkeys

In a recent longitudinal study to assess the development of incidental recognition memory processes in monkeys, we showed that the effects of neonatal hippocampal lesions did alter incidental recognition memory only when the animals reached the juvenile period (Zeamer et al., 2010 ). The current follow‐up study tested whether this incidental memory loss was long‐lasting, i.e., present in adulthood, or only transitory, due to functional compensation with further brain maturation. The same animals with neonatal hippocampal lesions and their sham‐operated controls were re‐tested in the visual paired‐comparison task when they reached adulthood (48 months). The results demonstrated that, at least for easily discriminable color pictures of objects, the involvement of the hippocampus was only transitory, given that when re‐tested as adults, animals with neonatal hippocampal lesions performed as well as sham‐operated controls at all delays. Yet, significant recognition memory impairment was re‐instated when the discriminability of the stimuli was made more difficult (black/white pictures of similar objects). The data demonstrate profound functional remodeling within the hippocampus and its interactions with different medial temporal lobe structures from the juvenile period to adulthood, which is substantiated by a parallel morphological maturation of hippocampal intrinsic circuits (Lavenex et al., 2007a ; Jabès et al., 2011 ). © 2013 Wiley Periodicals, Inc.     

Recognition of lysozyme using surface imprinted bacterial cellulose nanofibers

Here, we developed the lysozyme imprinted bacterial cellulose (Lyz-MIP/BC) nanofibers via the surface imprinting strategy that was designed to recognize lysozyme. This study includes the molecular imprinting method onto the surface of bacterial cellulose nanofibers in the presence of lysozyme by metal ion coordination, as well as further characterizations methods FTIR, SEM and contact angle measurements. The maximum lysozyme adsorption capacity of Lyz-MIP/BC nanofibers was found to be 71 mg/g. The Lyz-MIP/BC nanofibers showed high selectivity for lysozyme towards bovine serum albumin and cytochrome c. Overall, the Lyz-MIP/BC nanofibers hold great potential for lysozyme recognition due to the high binding capacity, significant selectivity and excellent reusability.     

Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis

The acute phase protein pentraxin 3 (PTX3) is a pattern recognition receptor involved in regulation of the host immune response. This relatively newly discovered member of the pentraxin superfamily elicits both immunostimulatory and immunoregulatory functions preventing autoimmune pathology and orchestrated clearance of pathogens through opsonization of damage- and pathogen-associated molecular patterns (DAMP/PAMP). Thus, PTX3 has been described as a possible evolutionary precursor to immunoglobulins. While shown to provide protection against specific bacterial and fungal pathogens, persistent elevation of PTX3 levels following initial onset of infection appear to predict poor patient outcome and may contribute to disease sequelae such as tissue damage and coagulopathy. Measurement of PTX3 following onset of sepsis may improve patient risk assessment and thus be useful in guiding subsequent therapeutic interventions including steroidal anti-inflammatory and altered antibiotic therapies. In this review, we summarize the role of PTX3 in inflammatory syndromes and its utility as a marker of sepsis disease severity.     

Self-assembly of short peptides to form hydrogels: Design of building blocks,physical properties and technological applications

Hydrogels are unique supramolecular solid-like assemblies composed mainly of water molecules that are held by molecular networks. Physical hydrogels that are formed by a set of non-covalent interactions to establish a well-ordered scaffold devoid of any chemical cross-linking are especially intriguing for various biotechnological and medical applications. Peptides are particularly interesting building blocks of physical gels because of the role of polypeptides as structural elements in biological systems, the extensive ability for their chemical and biological decoration and functionalization, and the facile synthesis of natural and modified peptides. This review describes the assembly and properties of physical hydrogels that have been formed by the self-association of very simple peptide building blocks. Natural short peptides, as short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N-terminal protection, even a protected amino acid can serve as an efficient hydrogelator. Further elucidation of hydrogelators’ assembly, as well as the characterization of their physical properties, can guide the rational design of building blocks for a desired application. The possible mechanism of self-assembly is discussed in line with the chemical nature of the short peptides. Different methods have been used to induce hydrogel assembly, which may significantly affect the mechanical characteristics of the resulting gels. Here, special emphasis is given to methods that allow either spatial control of hydrogel formation or modulation of physical properties of the gel. Finally, the parameters that influence hydrogelation are described, and insights for their design are provided.