Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses.

MOTIVATION: In vitro and in vivo selection of vaccines is time consuming, expensive and the selected vaccines may not be able to provide protection against broad-spectrum viruses because of emerging antigenically novel disease strains. A powerful computational model that incorporates these protein/DNA or RNA level fluctuations can effectively predict antigenically variant strains, and can minimize the amount of resources spent on exclusive serological testing of vaccines and make wide spectrum vaccines possible for many diseases. However, in silico vaccine prediction remains a grand challenge. To address the challenge, we investigate the use of linear and non-linear regression models to predict the antigenic similarity in foot-and-mouth disease virus strains and in influenza strains, where the structure and parameters of the non-linear model are optimized using an evolutionary algorithm (EA). In addition, we examine two different scoring methods for weighting the type of amino acid substitutions in the linear and non-linear models. We also test our models with some unseen data. RESULTS: We achieved the best prediction results on three datasets of SAT2 (Foot-and-Mouth disease), two datasets of serotype A (Foot-and-Mouth disease) and two datasets of influenza when the scoring method based on biochemical properties of amino acids is employed in combination with a non-linear regression model. Models based on substitutions in the antigenic areas performed better than those that took the entire exposed viral capsid proteins. A majority of the non-linear regression models optimi Z: ed with the EA: performed better than the linear and non-linear models whose parameters are estimated using the least-squares method. In addition, for the best models, optimi Z: ed non-linear regression models consist of more terms than their linear counterparts, implying a non-linear nature of influences of amino acid substitutions. Our models were also tested on five recently generated FMDV datasets and the best model was able to achieve an 80% agreement rate.

Correction: King et al. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus. Viruses 2022, 14, 1820.

In the original publication [...].

Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus.

Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP266, VP280 and VP1155, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (Lpro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses.

Psychosocial impact of hypodontia in children.

INTRODUCTION: The purpose of this cross-sectional study was to determine the psychosocial impact of hypodontia (multiple dental agenesis) in children and the influence of factors such as severity of hypodontia, number of retained deciduous teeth, age, and sex. The implications of hypodontia for affected patients have been poorly investigated; this, in part, relates to the lack of appropriate measurements to assess the impact of oral conditions on quality of life, particularly among children and adolescents. METHODS: A total of 123 children (49.6% boys, 50.4% girls; mean age, 13.6 years; SD, 1.6 years) were recruited on the basis of predetermined inclusion criteria to either a hypodontia group or a routine orthodontic group of similar treatment need (index of orthodontic treatment need, dental health component 4 or 5) but without hypodontia. Each patient completed the child perceptions questionnaire and 2 visual analog scales to determine the global effects of hypodontia on esthetics and function. RESULTS: The mean number of missing teeth in the hypodontia group was 4.52 (SD, 3.33). There were no statistically significant differences in child perceptions questionnaire scores (overall or at domain level) or visual analog scores between the hypodontia and the routine orthodontic groups (P >0.05). Univariable linear regression analyses provided some evidence that difficulty with chewing was associated with the severity of hypodontia (P = 0.030). CONCLUSIONS: In this sample, hypodontia did not appear to affect the psychosocial status of patients any more than other features of a malocclusion measured with the index of orthodontic treatment need, dental health component 4 or 5. Patients with hypodontia did, however, have more difficulty in chewing when the deciduous teeth associated with the missing permanent teeth had been exfoliated. This highlights the possible importance of retaining deciduous teeth in patients with severe hypodontia.

Space maintenance.

OBJECTIVE: The use of a space maintainer appliance, or restoration of a carious primary tooth that can then act as a natural space maintainer, may potentially obviate the consequences of loss of arch length and the need for complex orthodontic treatment at a later stage. Nevertheless, all space maintainer appliances are plaque retentive and may predispose to dental caries and gingival inflammation. Space maintainer appliances may also impinge on the soft tissues, interfere with eruption of adjacent teeth, fracture, and become dislodged or lost. This review article provides a summary of the available evidence, and considers the indications for space maintenance. METHODS: Medline and Ovid Medline were scanned, and additionally a hand-search of non-listed peer-reviewed papers written in English was performed. A total of 16 pertinent papers published between 1987 and 2007 that satisfied the inclusion criteria were selected for discussion. CONCLUSIONS: There is limited evidence to recommend either for or against the use of space maintainers to prevent or reduce the severity of malocclusion in the permanent dentition. Decisions regarding the use of space maintainers should be guided by balancing the occlusal disturbance that may result if one is not used against the potential plaque accumulation and caries that the appliance may cause.

An update on oral hygiene products and techniques.

UNLABELLED: The aim of this article is to update the reader on oral hygiene products and techniques. The evidence relating to the range of toothbrushing, interdental cleaning products and chemotherapeutic agents currently on the market will be discussed. It will be seen that choice of many of the oral hygiene products currently on the market is still largely a matter of personal preference. CLINICAL RELEVANCE: An inadequate oral hygiene regime may lead to caries and periodontal disease. It is important for clinicians to be able to recommend a preventive programme for dental and periodontal health that is supported by high quality, evidence-based clinical research.