Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions

The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ induced AIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that can trigger AIM2 inflammasome and IL-1β activation in psoriasis. Furthermore, cathelicidin LL-37 interfered with DNA-sensing inflammasomes, which thereby suggests an anti-inflammatory function for this peptide. Thus, our data reveal a link between the AIM2 inflammasome, cathelicidin LL-37, and autoinflammation in psoriasis, providing new potential targets for the treatment of this chronic skin disease.

Aspergillus infection in pulmonary cavitating lesions with right atrial myxoma

Cardiac myxomas are rare primary tumors with varied clinical presentations that may pose a diagnostic challenge. Here, we describe the case of a 21-year-old man with multiple cavitating lung lesions with aspergillosis and underlying right atrial myxoma, who presented with hemoptysis and weight loss. He was successfully treated with right atrial myxoma resection and antifungal agents, with no recurrence or complications after one year of follow-up.

Commissioned Research on HPV Frequency in Cervical Cancers and Premalignant lesions of the Cervix

This report documents an investigation of the frequency of human papillomavirus (HPV) genotypes across cervical disease states in Northern Ireland ranging from koilocytosis to cervical cancer. It builds upon earlier work by the Northern Ireland HPV Working Group which reported a HPV prevalence of 17.1% overall in women aged 20-65 years irrespective of pathology and 13.2% among women in the screening age group (20-60 years) with normal cytology (Anderson et al. 2012, Anderson et al. 2013).

A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol

Aim
To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance.

Background
Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy.

Design
A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods.

Methods
Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012).

Discussion
Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.

Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens

Cationic amphipathic α-helical peptides are intensively studied classes of host defence peptides (HDPs). Three peptides, peptide glycine-leucine-amide (PGLa-AM1), caerulein-precursor fragment (CPF-AM1) and magainin-AM1, originally isolated from norepinephrine-stimulated skin secretions of the African volcano frog Xenopus amieti (Pipidae), were studied for their antimicrobial and immunomodulatory activities against oral and respiratory pathogens. Minimal effective concentrations (MECs), determined by radial diffusion assay, were generally lower than minimal inhibitory concentrations (MICs) determined by microbroth dilution. PGLa-AM1 and CPF-AM1 were particularly active against Streptococcus mutans and all three peptides were effective against Fusobacterium nucleatum, whereas Enterococcus faecalis and Candida albicans proved to be relatively resistant micro-organisms. A type strain of Pseudomonas aeruginosa was shown to be more susceptible than the clinical isolate studied. PGLa-AM1 displayed the greatest propensity to bind lipopolysaccharide (LPS) from Escherichia coli, P. aeruginosa and Porphyromonas gingivalis. All three peptides showed less binding to P. gingivalis LPS than to LPS from the other species studied. Oral fibroblast viability was unaffected by 50. μM peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with 1 or 10. μM magainin-AM1 but not following treatment with PGLa-AM1 or CPF-AM1. In conclusion, as well as possessing potent antimicrobial actions, the X. amieti peptides bound to LPS from three human pathogens and had no effect on oral fibroblast viability. CPF-AM1 and PGLa-AM1 show promise as templates for the design of novel analogues for the treatment of oral and dental diseases associated with bacteria or fungi.

The impact of rehabilitation using removable partial dentures and functionally orientated treatment on oral health-related quality of life: a randomised controlled clinical trial

OBJECTIVES: This study aimed to compare two different tooth replacement strategies for partially dentate older patients; namely functionally orientated treatment according to the principles of the shortened dental arch (SDA) and conventional treatment using removable partial dentures (RPDs) using a randomised controlled clinical trial. The primary outcome measure for this study was impact on oral health-related quality of life (OHRQoL) measured using the short form of the oral health impact profile (OHIP-14).

METHODS: Patients aged 65 years and older were randomly allocated to two different treatment groups: the RPD group and the SDA group. For the RPD group each patient was restored to complete arches with cobalt-chromium RPDs used to replace missing teeth. For the SDA group, patients were restored to a premolar occlusion of 10 occluding pairs of natural and replacement teeth using resin bonded bridgework (RBB). OHRQoL was measured using the OHIP-14 questionnaire administered at baseline, 1 month, 6 months and 12 months after treatment intervention.

RESULTS: In total, 89 patients completed the RCT: 44 from the RPD group and 45 from the SDA group. Analysis using a mixed model of covariance (ANCOVA) illustrated that treatment according to the SDA concept resulted in significantly better mean OHIP-14 scores compared with RPD treatment (p<0.05). This result was replicated in both treatment centres used in the study.

CONCLUSIONS: In terms of impact on OHRQoL, treatment based on the SDA concept achieved significantly better results than that based on RPDs 12 months after treatment intervention (trial registration no. ISRCTN26302774).

CLINICAL SIGNIFICANCE: Functionally orientated treatment delivery resulted in significantly better outcomes compared to removable dentures in terms of impact on OHRQoL.

Cost-effectiveness of ART restorations in elderly adults: a randomized clinical trial

BACKGROUND: As the world population ages, the requirement for cost-effective methods of treating chronic disease conditions increases. In terms of oral health, there is a rapidly increasing number of dentate elderly with a high burden of maintenance. Population surveys indicate that older individuals are keeping their teeth for longer and are a higher caries risk group. Atraumatic Restorative Treatment (ART) could be suitable for patients in nursing homes or house-bound elderly, but very little research has been done on its use in adults.

OBJECTIVES: To compare the cost-effectiveness of ART and a conventional technique (CT) for restoring carious lesions as part of a preventive and restorative programme for older adults.

METHODS: In this randomized clinical trial, 82 patients with carious lesions were randomly allocated to receive either ART or conventional restorations. Treatment costs were measured based on treatment time, materials and labour. For the ART group, the cost of care provided by a dentist was also compared to the cost of having a hygienist to provide treatment. Effectiveness was measured using percentage of restorations that survived after a year.

RESULTS: Eighty-two patients received 260 restorations, that is, 128 ART and 132 conventional restorations. 91.1% of the restorations were on one surface only. After a year, 252 restorations were assessed in 80 patients. The average cost for ART and conventional restorations was €16.86 and €28.71 respectively; the restoration survival percentages were 91.1% and 97.7%, respectively. This resulted in a cost-effectiveness ratio of 0.18 (ART) and 0.29 (CT). When the cost of a hygienist to provide ART was inserted in the analysis, the resulting ratio was 0.14.

CONCLUSIONS: Atraumatic restorative treatment was found to be a more cost-effective alternative to treat older adults after 1 year, compared to conventional restorations, especially in out of surgery facilities and using alternative workforce such as hygienists. Atraumatic restorative treatment can be a useful tool to provide dental care for frail and fearful individuals who might not access dental treatment routinely.

Caries and the older patient

Ageing of the population, together with prolonged retention of teeth, has brought new challenges to dentistry. Whereas in the past oral care for the elderly was restricted to provision of dentures, older patients are now presenting with dental caries and failed restorations. These problems may have an impact on their general health and quality of life. Poor oral hygiene, xerostomia and diet are among the risk factors for caries in older patients and need to be addressed in order to achieve control of the disease. Carious lesions can be treated conservatively in many cases or may need surgical management.

CLINICAL RELEVANCE: Caries is an oral health issue among older patients and can result in tooth loss. Oral health has a great impact on general health and quality of life of elderly people.

Age-related oral changes

Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects.

CLINICAL RELEVANCE: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

The importance of oral health for the systemic well being of an ageing population

The proportion of adults over the age of 60 years is expanding rapidly across European Union countries, including the Republic of Ireland. As the older population has grown faster than the total population, the proportion of older persons relative to the rest of the population has increased considerably (Figure 1). This trend mirrors the arrival of the “baby boomer� generation into early old age and will have wide ranging effects on social, political and economic spheres as well as presenting significant challenges for healthcare delivery and public healthcare policy.

Survey of oral health behaviours of patients receiving methadone therapy at a drug rehabilitation centre

Background: This survey aimed to record the dietary habits and oral health behaviours of patients undergoing methadone maintenance therapy at a Scottish drug rehabilitation centre.The objectives were to obtain descriptive data for each of the participants on items including dietary habits, oral hygiene practices and dental health. The study also aimed to explore explanatory relationships between dietary habits, oral hygiene practices and dental health (DMFT) in methadone users.
Methods: A cross – sectional descriptive study using survey methodology was conducted of consecutive adult patients undergoing methadone maintenance therapy at a non-residential drug rehabilitation centre in Dundee, Scotland. A self-completion retrospective questionnaire was distributed to 66 consecutive patients.
Results: A response rate of 74.2% was achieved. Participants reported low daily intakes of fresh fruit and vegetables with diets high in fatty foods. Respondents reported regular snacking between meals and consumption of large amounts of sugared carbonated drinks. Oral hygiene practices were poorly adhered to and a high level of dental disease was observed amongst participants. Poisson regression analysis revealed that the amount of alcohol consumed per day (p=0.02), the length of time taking methadone (p=0.002) the amount of sugar added to hot drinks (p<0.0001) and regular dental attendance (p=0.0001) were all independently associated with poor dental health.
Conclusions: Dietary habits and adherence to oral hygiene practices amongst this group of patients were very poor. This study suggests that these behaviours were contributing to the high levels of dental disease observed in this group.