Epigenetic patterns in Atlantic herring (Clupea harengus): Temperature and photoperiod as environmental stressors during larval development.

Understanding the molecular mechanisms underlying individual responses to environmental changes is crucial for species conservation and management. Pelagic fishes including Atlantic herring (Clupea harengus) are of particular interest because of their key ecological and economic roles and their susceptibility to a changing ocean from global warming. Temperature and photoperiod have been linked with spawning time and location in adult herring, but no study has thus far investigated the role of environmental factors on gene regulation during the vulnerable early developmental stages. Here, we examine DNA methylation patterns of larval herring bred under two temperatures (11°C and 13°C) and photoperiod (6 and 12 h) regimes in a 2 × 2 factorial design. We found consistently high levels of global methylation across all individuals and a decline in global methylation with increased developmental stage that was more pronounced at 13°C (p ≤ 0.007) than at 11°C (p ≥ 0.21). Most of the differentially methylated sites were in exon and promoter regions for genes linked to metabolism and development, some of which were hypermethylated at higher temperature. These results demonstrate the important role of DNA methylation during larval development and suggest that this molecular mechanism might be key in regulating early-stage responses to environmental stressors in Atlantic herring.

The transition from dental school to postgraduate dental foundation training: strengthening the interaction between stakeholders.

This article demonstrates the benefits of collaboration between dental educators in undergraduate and postgraduate settings, to facilitate the transition of dental students into dental foundation training (DFT). The School of Dental Sciences at Newcastle University and Health Education England, working across north-east and north Cumbria, have strengthened links by forming a dental foundation programme undergraduate liaison group (FPUG) involving all stakeholders. The group has shared information between the organisations, enhanced stakeholder engagement, and developed several initiatives including workshops to help prepare final year students for the transition to DFT. A small investment in time has been highly effective, and the formation of a similar group merits consideration in other areas of the UK.

Learning outcomes: Exploring implications of adopting a different level of detail.

INTRODUCTION: Outcome-based programmes provide a framework to support educators and learners in understanding content and end points within taught courses. Management of these outcomes in the Dental Degree at Newcastle University has been a challenge in relation to quality assurance and enhancement, having over 1500 detailed student-level outcomes (SLO). This research aimed to explore the implications of adopting a more superficial "course" level of outcome (CLO), when reviewed against a reference set of external LO requirements. MATERIALS AND METHODS: A purposive sample of five courses within the undergraduate dental programme was selected. The mapping of both SLOs and CLOs was reviewed in relation to their total number and the mapping connections to the reference outcomes. RESULTS: There was a mean reduction of 79% in outcomes when comparing SLOs to CLOs. The number of mapping connections between CLOs and the reference set reduced in three courses and increased in two, when compared to SLOs. DISCUSSION: From a purely numerical perspective, changing the detail of learning outcomes has led to a change in mapping connections. As the delivered curriculum has remained unchanged, this demonstrates a potential impact of differing interpretations of learning outcomes. Further review of learning outcomes in relation to the domains categorised within the reference outcome document suggested more mapping links were obtained in clinically focused courses than academic or theoretical courses. CONCLUSION: A demonstrable impact in mapping connections was observed when the detail within the learning outcomes was changed. This has implications for programme leaders in structuring LOs for a curriculum.

Using learning outcomes in dental education.

Explicitly-stated learning outcomes are an expected, integral part of contemporary under- and postgraduate learning programmes in dentistry. Writing learning outcomes, however, can be challenging and undertaken with a risk of not understanding what is meant by them and what well-constructed outcomes are meant to do. Written badly, learning outcomes will not help capture the goals of educational interventions or, perhaps worse, they end up as nothing more than a complex, frustrating hoop-jumping exercise in both their conception and utilisation. Underlying misconceptions of the purpose of learning outcomes or how to develop them are likely contributors to this situation. We would argue that if one understands the background, construct and intended purpose of learning outcomes we are more likely to write them so that they can actually be applied and therefore used effectively.

Developing assessment: involving the sessional clinical teacher.

Assessment development is a fundamental element of curriculum management and a requirement for providers of education to consistently demonstrate attainment of educational standards. Development of authentic, valid and reliable assessment is, however, both challenging and resource intensive. In the UK, dental education standards are regulated by the General Dental Council (GDC). The 'safe beginner' is the threshold determined by the GDC for the passing student - but how do we apply this? This article describes an approach the School of Dental Sciences at Newcastle University has adopted to address the challenges associated with developing assessments. Sessional clinical teachers contribute a significant proportion of the clinical supervision within the BDS programme and also have a good appreciation of both the standard and concept of the 'safe beginner'. By implementing a process of active timetable management, we have identified time where this group could contribute to assessment development. We believe that aspects, which could be enhanced by their involvement, include writing, validation, standard-setting and utilisation of assessment. To achieve this, we recognise a requirement for investment in careful manpower planning and training, but consider that it is realistic and beneficial to include sessional clinical teachers in this essential part of learning and teaching.

Continuing professional development and application of knowledge from research findings: a qualitative study of general dental practitioners.

OBJECTIVES: To explore general dental practitioners' opinions about continuing professional development (CPD) and potential barriers to translating research findings into clinical dental practice. DESIGN: Qualitative focus group and interviews. SUBJECTS, SETTING AND METHODS: Four semi-structured interviews and a single focus group were conducted with 11 general dental practitioners in North East England. OUTCOME MEASURE: Transcripts were analysed using the constant comparative method to identify emergent themes. RESULTS: The key theme for practitioners was a need to interact with colleagues in order to make informed decisions on a range of clinical issues. For some forms of continuing professional development the value for money and subsequent impact upon clinical practice was limited. There were significant practice pressures that constrained the ability of practitioners to participate in certain educational activities. The relevance of some research findings and the formats used for their dissemination were often identified as barriers to their implementation in general dental practice. CONCLUSIONS: There are a number of potential barriers that exist in general dental practice to the uptake and implementation of translational research. CPD plays a pivotal role in this process and if new methods of CPD are to be developed consideration should be given to include elements of structured content and peer review that engages practitioners in a way that promotes implementation of contemporary research findings.

Demonstration of quantum entanglement between a single electron spin confined to an InAs quantum dot and a photon.

The electron spin state of a singly charged semiconductor quantum dot has been shown to form a suitable single qubit for quantum computing architectures with fast gate times. A key challenge in realizing a useful quantum dot quantum computing architecture lies in demonstrating the ability to scale the system to many qubits. In this Letter, we report an all optical experimental demonstration of quantum entanglement between a single electron spin confined to a single charged semiconductor quantum dot and the polarization state of a photon spontaneously emitted from the quantum dot's excited state. We obtain a lower bound on the fidelity of entanglement of 0.59±0.04, which is 84% of the maximum achievable given the timing resolution of available single photon detectors. In future applications, such as measurement-based spin-spin entanglement which does not require sub-nanosecond timing resolution, we estimate that this system would enable near ideal performance. The inferred (usable) entanglement generation rate is 3×10(3) s(-1). This spin-photon entanglement is the first step to a scalable quantum dot quantum computing architecture relying on photon (flying) qubits to mediate entanglement between distant nodes of a quantum dot network.

Ecology of zoonotic infectious diseases in bats: current knowledge and future directions.

Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.

Randomised cross-over study of oral appliances for snoring.

OBJECTIVES: To compare a mandibular advancement splint to a control bite raising appliance in the treatment of snoring with or without mild obstructive sleep apnoea syndrome. DESIGN: A prospective two-treatment randomised cross-over clinical trial. SETTING: Single centre secondary care Dental Hospital. PARTICIPANTS: Fifty-two subjects (36 men, 16 women) diagnosed with non-apnoeic snoring or mild obstructive sleep apnoea syndrome (apnoea/hypopnoea index < or =15 events/h), were recruited from Departments of Respiratory Medicine and ENT surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust. MAIN OUTCOME MEASURES: The Snoring Symptoms Inventory questionnaire (SSI) and the Epworth Sleepiness Score (ESS) were used to evaluate changes in symptoms. Patient reported outcomes (compliance, adverse events, splint preference) were recorded by questionnaire. Subjects attended for five study visits and used a mandibular advancement splint and a bite raising appliance at home each for 4 weeks, with a 3-week washout period between devices. RESULTS AND CONCLUSIONS: Thirty-eight subjects completed the study. Both the mandibular advancement splint and bite raising appliance significantly reduced the SSI compared to the baseline scores: mandibular advancement splint 5.5, P = 0.013; bite raising appliance 3.1, P = 0.005. No statistically significant difference between the two treatment periods was detected (P > 0.05). The reduction in the Epworth Sleepiness Score was: mandibular advancement splint 1.0, P = 0.02; bite raising appliance 0.3, P = 0.4. The change in the Epworth Sleepiness Score was not statistically significantly different between the mandibular advancement splint and bite raising appliance treatment periods (P > 0.05). CONCLUSIONS: In this cohort of patients diagnosed with snoring +/- mild OSA: 1 both the mandibular advancement splint and bite raising appliance designs of splint appeared to reduce the symptoms of snoring; 2 no difference in the magnitude of this effect was detected in favour of one design of splint.

Host immunity to repeated rabies virus infection in big brown bats.

Bats are natural reservoirs for the majority of lyssaviruses globally, and are unique among mammals in having exceptional sociality and longevity. Given these facets, and the recognized status of bats as reservoirs for rabies viruses (RABVs) in the Americas, individual bats may experience repeated exposure to RABV during their lifetime. Nevertheless, little information exists with regard to within-host infection dynamics and the role of immunological memory that may result from abortive RABV infection in bats. In this study, a cohort of big brown bats (Eptesicus fuscus) was infected intramuscularly in the left and right masseter muscles with varying doses [10(-0.1)-10(4.9) median mouse intracerebral lethal doses (MICLD(50))] of an E. fuscus RABV variant isolated from a naturally infected big brown bat. Surviving bats were infected a second time at 175 days post-(primary) infection with a dose (10(3.9)-10(4.9) MICLD(50)) of the same RABV variant. Surviving bats were infected a third time at either 175 or 305 days post-(secondary) infection with a dose (10(4.9) MICLD(50)) of the same RABV variant. When correcting for dose, similar mortality was observed following primary and secondary infection, but reduced mortality was observed following the third and last RABV challenge, despite infection with a high viral dose. Inducible RABV-neutralizing antibody titres post-infection were ephemeral among infected individuals, and dropped below levels of detection in several bats between subsequent infections. These results suggest that long-term repeated infection of bats may confer significant immunological memory and reduced susceptibility to RABV infection.

Effect of rinsing with mouthwashes after brushing with a fluoridated toothpaste on salivary fluoride concentration.

The aim of the study was to determine whether rinsing with a mouthwash after brushing with a fluoridated toothpaste affected oral fluoride (F) retention and clearance compared with an oral hygiene regime without mouthwash. In this supervised, single-blind study, 3 regimes were compared: (A) brushing for 1 min with 1 g of 1,450 microg F/g NaF toothpaste followed by rinsing for 5 s with 10 ml water; (B) as A but followed by rinsing for 30 s with 20 ml of 100 mg F/l NaF mouthwash, and (C) as B but rinsing for 30 s with a non-fluoridated mouthwash. Twenty-three adults applied each treatment once in a randomised order, separated by 1-week washout periods, and used a non-fluoridated toothpaste at home prior to and during the study. Whole saliva samples (2 ml), collected before each treatment commenced and 10, 20, 30, 60, 90 and 120 min afterwards, were subsequently analysed for fluoride by ion-specific electrode. The mean (SD) back-transformed log (area under salivary F clearance curve) values were: A = 2.36 (+3.37, -1.39), B = 2.54 (+2.72, -1.31) and C = 1.19 (+1.10, -0.57) mmol F/l x min, respectively. The values for regimes A and B were statistically significantly greater than that for regime C (p < 0.001; paired t test). These findings suggest that use of a non-F mouthwash after toothbrushing with a F toothpaste may reduce the anticaries protection provided by toothbrushing with a F toothpaste alone. The use of a mouthwash with at least 100 mg F/l should minimise this risk.

Tigecycline therapy significantly reduces the concentrations of inflammatory pulmonary cytokines and chemokines in a murine model of Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.

Is laparoscopically assisted radical vaginal hysterectomy for cervical carcinoma safe? A case control study with follow up.

OBJECTIVE: To compare a new surgical approach, laparoscopically assisted radical vaginal hysterectomy (LARVH) with open radical hysterectomy in women with cervical cancer. Can selected women benefit from the minimally invasive approach without compromising safety (recurrence rate) and morbidity (complications)? DESIGN: Retrospective case control study. SETTING: A tertiary referral unit for gynaecological malignancies. POPULATION: Thirty women undergoing LARVH were included and compared with 30 women undergoing open radical surgery. The control group was matched for age, body mass index and disease stage. METHODS: Retrospective collection of data from patient files and follow up. MAIN OUTCOME MEASURES: Recurrence rate, complication rate, hospital stay, nodal counts, blood loss, operating time. RESULTS: Recurrence rates were equal (6.7%). There was one death, in the LARVH group. Follow up was mean 31 months in the LARVH group and 30.9 months in the open group. Blood loss as measured by mean drop in haemoglobin was greater in the open group (2.03 versus 3.01 g/dl, P = 0.02). Transfusions were given in 40% of women in the open group and 16.7% in the LARVH group. Hospital stay was significantly less in the LARVH group (5.9 versus 7.8 nights, P = 0.003). Mean operating time was longer in the LARVH group (131 versus 187 minutes P = 0.0001). Mean nodal counts did not differ significantly (17.4 in open vs 14.8 in LARVH, P > 0.05). There were seven perioperative complications in the open group and four in the LARVH group. There have been two recurrences in each group (6.67%) at mean follow up of 31 (LARVH) and 30.9 (open) months. CONCLUSIONS: The first 30 LARVH procedures performed in this unit are comparable in terms of safety (recurrence rate and complication rate) and economic factors (shorter hospital stay mitigating longer operating time). Further development of this technique is warranted.

Respiratory tract infection with Mycoplasma pneumoniae in interleukin-12 knockout mice results in improved bacterial clearance and reduced pulmonary inflammation.

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 10(7) CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-gamma than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-alpha (P = 0.078). No differences were found for IL-1beta, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.

Smoking cessation as a dental intervention--views of the profession.

OBJECTIVE: To undertake a questionnaire-based survey to determine the attitudes and activities of dental professionals in primary care in the Northern Deanery of the UK in relation to providing smoking cessation advice. METHODS: Questionnaires for dentists, hygienists and dental nurses were sent to hygienists to distribute to other members of the team. The information collected included: smoking status of the professionals and the practice; roles of the dental team in giving smoking cessation advice; levels of training received; and potential barriers to giving this brief intervention. RESULTS: Over 90% of practices were smoke-free environments and significantly more dental nurses (23%) were smokers compared to dentists (10%) and hygienists (7%) (p<0.01). The majority of dentists and hygienists enquired about smoking status of their patients and all three groups believed that hygienists and dentists should offer brief smoking cessation advice. Potential barriers to delivering smoking cessation advice were identified: lack of remuneration; lack of time; and lack of training. CONCLUSION: Dental teams in primary care are aware of the importance of offering smoking cessation advice and, with further training and appropriate remuneration, could guide many of their patients who smoke to successful quit attempts.

Silencing the snorers: no gain without pain?

OBJECTIVE: To compare the estimated effects of conservative surgery to those of a mandibular advancement splint (MAS) in the treatment of habitual snoring. METHOD: Prospective, observational, non-randomized cohort study. RESULTS: Adequate follow-up data were available for 88 participants (23 following coblation, 65 after provision of an MAS). The mean reduction in snoring symptoms inventory (SSI) score for the 23 subjects undergoing coblation was 9.83 (+/-standard deviation 11.43). Reported pain duration was greatest with uvula amputation, but uvula coblation did not always adequately reduce its bulk. Of the 65 MAS patients, 39 (60 per cent) used the device regularly, with a mean fall in SSI of 12 (+/-16.4, p=0.001). Approximately one in four patients in both groups achieved a significant fall in SSI (>15 points), and the measured effect sizes were close to 0.75 for both treatments. CONCLUSIONS: Mandibular advancement splints and coblation have similar efficacies. However, their efficacy does not match that of radical surgery.

The effect of smoking on periodontal treatment response: a review of clinical evidence.

BACKGROUND: Smoking has been identified as a significant risk factor for periodontal diseases and is regarded as being responsible for incomplete or delayed healing in patients following treatment. AIM AND METHOD: The aim of this conventional review was to review, collate and tabulate the relative effectiveness of treatments of chronic periodontitis in smokers, non-smokers and ex-smokers. OBSERVATIONS: The majority of clinical trials show significantly greater reductions in probing depths and bleeding on probing, and significantly greater gain of clinical attachment following non-surgical and surgical treatments in non-smokers compared with smokers. This benefit is also seen at class I and II furcation sites and in patients prescribed systemic or local antimicrobial treatments. CONCLUSIONS: Data from epidemiological, cross-sectional and case-control studies strongly suggest that quitting smoking is beneficial to patients following periodontal treatments. The periodontal status of ex-smokers following treatment suggests that quitting the habit is beneficial although there are only limited data from long-term longitudinal clinical trials to demonstrate unequivocally the periodontal benefit of quitting smoking.