Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with “health”, “gingivitis” and “periodontitis”. These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14+ monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by “gingivitis-associated” biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface

Impact of External Cue Validity on Driving Performance in Parkinson's Disease

This study sought to investigate the impact of external cue validity on simulated driving performance in 19 Parkinson's disease (PD) patients and 19 healthy age-matched controls. Braking points and distance between deceleration point and braking point were analysed for red traffic signals preceded either by Valid Cues (correctly predicting signal), Invalid Cues (incorrectly predicting signal), and No Cues. Results showed that PD drivers braked significantly later and travelled significantly further between deceleration and braking points compared with controls for Invalid and No-Cue conditions. No significant group differences were observed for driving performance in response to Valid Cues. The benefit of Valid Cues relative to Invalid Cues and No Cues was significantly greater for PD drivers compared with controls. Trail Making Test (B-A) scores correlated with driving performance for PDs only. These results highlight the importance of external cues and higher cognitive functioning for driving performance in mild to moderate PD

Factors associated with dog ownership and contact with dogs in a UK community

BACKGROUND: Dogs are popular pets in many countries. Identifying differences between those who own dogs or have contact with dogs, and those who do not, is useful to those interested in the human-animal bond, human health and for provision of veterinary services. This census-based, epidemiological study aimed to investigate factors associated with dog ownership and contact with dogs, in a semi-rural community of 1278 households in Cheshire, UK. RESULTS: Twenty-four percent of households were identified as dog-owning and 52% owned a pet of some type. Multivariable logistic regression suggested that households were more likely to own a dog if they had more occupants (five or more); if they had an adult female household member; or if they owned a horse. The age structure of the households was also associated with dog ownership, with households containing older children (between six and 19 years of age) and young adults (between 20 and 29 years of age), more likely to own dogs. We also found that dog owning households were more likely to be multi-dog households than single-dog if they also owned a cat or a bird, or if the household contained a person of 20–29 years old. Dog owners reported increased contact with dogs, other than their own, compared to those that did not own dogs and this contact appeared to be mainly through walking. CONCLUSION: Some household types are more likely to own a dog than others. This study supports the suggestion that dogs are more common in families who have older children (6–19 years), as has been generally observed in other countries. Dog owners are also more likely to have contact with dogs other than their own, compared with those not owning a dog

Polymicrobial oral biofilm models: simplifying the complex

Over the past century, numerous studies have used oral biofilm models to investigate growth kinetics, biofilm formation, structure and composition, antimicrobial susceptibility and host–pathogen interactions. In vivo animal models provide useful models of some oral diseases; however, these are expensive and carry vast ethical implications. Oral biofilms grown or maintained in vitro offer a useful platform for certain studies and have the advantages of being inexpensive to establish and easy to reproduce and manipulate. In addition, a wide range of variables can be monitored and adjusted to mimic the dynamic environmental changes at different sites in the oral cavity, such as pH, temperature, salivary and gingival crevicular fluid flow rates, or microbial composition. This review provides a detailed insight for early-career oral science researchers into how the biofilm models used in oral research have progressed and improved over the years, their advantages and disadvantages, and how such systems have contributed to our current understanding of oral disease pathogenesis and aetiology

Joint toxicity of cadmium and ionizing radiation on zooplankton carbon incorporation, growth and mobility

The risk of exposure to radioactive elements is seldom assessed considering mixture toxicity, potentially over- or underestimating biological and ecological effects on ecosystems. This study investigated how three end points, carbon transfer between phytoplankton and Daphnia magna, D. magna mobility and growth, responded to exposure to γ-radiation in combination with the heavy metal cadmium (Cd), using the MIXTOX approach. Observed effects were compared with mixture effects predicted by concentration addition (CA) and independent action (IA) models and with deviations for synergistic/antagonistic (S/A), dose-level (DL), and dose-ratio (DR) dependency interactions. Several patterns of response were observed depending on the end point tested. DL-dependent deviation from the IA model was observed for carbon incorporation with antagonism switching to synergism at higher doses, while the CA model indicated synergism, mainly driven by effects at high doses of γ-radiation. CA detected antagonism regarding acute immobilization, while IA predicted DR-dependency. Both CA and IA also identified antagonism for daphnid growth. In general, effects of combinations of γ-radiation and Cd seem to be antagonistic at lower doses, but synergistic at the higher range of the doses tested. Our results highlight the importance of investigating the effects of exposure to γ-radiation in a multistressor context

Self-reported impulsivity and inhibitory control in problem gamblers

Impulsivity is considered a core feature of problem gambling, however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports-betting) and non-strategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and non-strategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers

Lateralized deficit of response inhibition in early-onset schizophrenia

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence of executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS). Methods. Twenty-one adolescents with the onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized as paranoid (n=10) and undifferentiated subtypes (n=11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response. Results. The undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT. Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients with undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Interpreting viral deep sequencing data with GLUE

Using deep sequencing technologies such as Illumina’s platform, it is possible to obtain reads from the viral RNA population revealing the viral genome diversity within a single host. A range of software tools and pipelines can transform raw deep sequencing reads into Sequence Alignment Mapping (SAM) files. We propose that interpretation tools should process these SAM files, directly translating individual reads to amino acids in order to extract statistics of interest such as the proportion of different amino acid residues at specific sites. This preserves per-read linkage between nucleotide variants at different positions within a codon location. The samReporter is a subsystem of the GLUE software toolkit which follows this direct read translation approach in its processing of SAM files. We test samReporter on a deep sequencing dataset obtained from a cohort of 241 UK HCV patients for whom prior treatment with direct-acting antivirals has failed; deep sequencing and resistance testing have been suggested to be of clinical use in this context. We compared the polymorphism interpretation results of the samReporter against an approach that does not preserve per-read linkage. We found that the samReporter was able to properly interpret the sequence data at resistance-associated locations in nine patients where the alternative approach was equivocal. In three cases, the samReporter confirmed that resistance or an atypical substitution was present at NS5A position 30. In three further cases, it confirmed that the sofosbuvir-resistant NS5B substitution S282T was absent. This suggests the direct read translation approach implemented is of value for interpreting viral deep sequencing data