Viral Induced Effects on a Vulnerable Epithelium; Lessons Learned From Paediatric Asthma and Eosinophilic Oesophagitis.

The epithelium is integral to the protection of many different biological systems and for the maintenance of biochemical homeostasis. Emerging evidence suggests that particular children have epithelial vulnerabilities leading to dysregulated barrier function and integrity, that resultantly contributes to disease pathogenesis. These epithelial vulnerabilities likely develop in utero or in early life due to various genetic, epigenetic and environmental factors. Although various epithelia are uniquely structured with specific function, prevalent allergic-type epithelial diseases in children potentially have common or parallel disease processes. These include inflammation and immune response dysregulation stemming from atypical epithelial barrier function and integrity. Two diseases where aetiology and pathogenesis are potentially linked to epithelial vulnerabilities include Paediatric Asthma and Eosinophilic Oesophagitis (EoE). For example, rhinovirus C (RV-C) is a known risk factor for paediatric asthma development and is known to disrupt respiratory epithelial barrier function causing acute inflammation. In addition, EoE, a prevalent atopic condition of the oesophageal epithelium, is characterised by similar innate immune and epithelial responses to viral injury. This review examines the current literature and identifies the gaps in the field defining viral-induced effects on a vulnerable respiratory epithelium and resulting chronic inflammation, drawing from knowledge generated in acute wheezing illness, paediatric asthma and EoE. Besides highlighting the importance of epithelial structure and barrier function in allergic disease pathogenesis regardless of specific epithelial sub-types, this review focuses on the importance of examining other parallel allergic-type disease processes that may uncover commonalities driving disease pathogenesis. This in turn may be beneficial in the development of common therapeutics for current clinical management and disease prevention in the future.

Efficacy of antimicrobial polymer coatings in an animal model of bacterial infection associated with foreign body implants.

OBJECTIVES: To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS: Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS: In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS: Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.

Perceived continuity and pitch shifts for complex tones with unresolved harmonics.

Brief complex tone bursts with fundamental frequencies (F0s) of 100, 125, 166.7, and 250 Hz were bandpass filtered between the 22nd and 30th harmonics, to produce waveforms with five regularly occurring envelope peaks ("pitch pulses") that evoked pitches associated with their repetition period. Two such tone bursts were presented sequentially and separated by a silent interval of two periods (2/F0). When the relative phases of the two bursts were varied, such that the interpulse interval (IPI) between the last pulse of the first burst and the first pulse of the second burst was varied, the pitch of the whole sequence was little affected. This is consistent with previous results suggesting that the pitch integration window may be "reset" by a discontinuity. However, when the interval between the two bursts was filled with a noise with the same spectral envelope as the complex, variations in IPI had substantial effects on the pitch of the sequence. It is suggested that the presence of the noise causes the two tones bursts to appear continuous, hence, resetting does not occur, and the pitch mechanism is sensitive to the phase discontinuity across the silent interval.

Pitch shifts for complex tones with unresolved harmonics and the implications for models of pitch perception.

Complex tone bursts were bandpass filtered, 22nd-30th harmonic, to produce waveforms with five regularly occurring envelope peaks ("pitch pulses") that evoked pitches associated with their repetition period. Two such tone bursts were presented sequentially and separated by an interpulse interval (IPI). When the IPI was varied, the pitch of the whole sequence was shifted by between +2% and -5%. When the IPI was greater than one period, little effect was seen. This is consistent with a pitch mechanism employing a long integration time for continuous stimuli that resets in response to temporal discontinuities of greater than about one period of the waveform. Similar pitch shifts were observed for fundamental frequencies from 100 to 250 Hz. The pitch shifts depended on the IPI duration relative to the period of the complex, not on the absolute IPI duration. The pitch shifts are inconsistent with the autocorrelation model of Meddis and O'Mard [J. Acoust. Soc. Am. 102, 1811-1820 (1997)], although a modified version of the weighted mean-interval model of Carlyon et al. [J. Acoust. Soc. Am. 112, 621-633 (2002)] was successful. The pitch shifts suggest that, when two pulses occur close together, one of the pulses is ignored on a probabilistic basis.