Human Disease/Clinical Medical Sciences in Dentistry: Current state and future directions of undergraduate teaching in the UK and Ireland.

In March 2017, a group of teachers of human disease/clinical medical science (HD/CMSD) representing the majority of schools from around the UK and Republic of Ireland met to discuss the current state of teaching of human disease and also to discuss how the delivery of this theme might evolve to inform improved healthcare. This study outlines how the original teaching in medicine and surgery to dental undergraduate students has developed into the theme of HD/CMSD reflecting changing needs as well as guidance from the regulators, and how different dental schools have developed their approaches to reach their current state. Each school was also asked to share a strengths, weakness, opportunities and threats (SWOT) analysis of their programme and to outline how they thought their HD/CMSD programme may develop. The school representatives who coordinate the delivery and assessment of HD/CMSD in the undergraduate curriculum have extensive insight in this area and are well-placed to shape the HD/CMSD development for the future.

Liquid chromatography/mass spectrometry based detection and semi-quantitative analysis of INSL5 in human and murine tissues.

RATIONALE: Insulin-like peptide 5 (INSL5) is a hormone produced by enteroendocrine L-cells in the colon that has recently been implicated in the control of metabolic homeostasis. However, research into its physiology has been hindered by the reported unreliability of commercially available immunoassays and additional detection assays would benefit this emerging field. METHODS: Peptides from purified murine L-cells and homogenates from both human and mouse colonic tissues were extracted by precipitating larger proteins with acetonitrile. Untargeted liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses, followed by database searching, were used to detect and identify various INSL5 gene derived peptides and characterise their precise sequence. A similar approach was developed to quantify INSL5 levels in primary intestinal culture supernatants after purification and concentration by solid-phase extraction. RESULTS: Mass spectral analysis of purified enteroendocrine cells and tissue homogenates identified the exact sequence of A and B chains of INSL5 endogenously expressed in L-cells. Differences in the endogenously processed peptide and the Swissprot database entry were observed for murine INSL5, whereas the human sequence matched previous predictions from heterologous expression experiments. INSL5 was detected in the supernatant of human and mouse primary colonic cultures and concentrations increased after treatment with a known L-cell stimulus. CONCLUSIONS: The first LC/MS/MS-based method capable of the detection and semi-quantitative analysis of endogenous INSL5 using MS-based techniques has been demonstrated. The methodology will enable the identification of stimulants for INSL5 secretion from murine and human primary colonic epithelial cultures.

Oral hairy leukoplakia in healthy, immunocompetent individuals.

Oral hairy leukoplakia (OHL), while typically associated with HIV infection and immunosuppression, is rarely seen in HIV negative immunocompetent individuals. We report on two cases of OHL in immunocompetent patients.

Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs).

BACKGROUND: Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline. METHODS: An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline. RESULTS: We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains. CONCLUSIONS: The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline. TRIAL REGISTRATION: EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.

The antimicrobial effects of helium and helium-air plasma on Staphylococcus aureus and Clostridium difficile.

UNLABELLED: Healthcare-associated infections (HCAI) affect 5-10% of acute hospital admissions. Environmental decontamination is an important component of all strategies to prevent HCAI as many bacterial causes survive and persist in the environment, which serve as ongoing reservoirs of infection. Current approaches such as cleaning with detergents and the use of chemical disinfectant are suboptimal. We assessed the efficacy of helium and helium-air plasma in killing Staphylococcus aureus and Clostridium difficile on a glass surface and studied the impact on bacterial cells using atomic force microscopy (AFM). Both plasma types exhibited bactericidal effects on Staph. aureus (log3·6 - >log7), with increased activity against methicillin-resistant strains, but had a negligible effect on Cl. difficile spores (<1log). AFM demonstrated cell surface disruption. The addition of air increased the microbicidal activity of the plasma and decreased the exposure time required for an equivalent log reduction. Further evaluation of cold plasma systems is warranted with, for example, different bacteria and on surfaces more reminiscent of the health care environment as this approach has potential as an effective decontaminant. SIGNIFICANCE AND IMPACT OF THE STUDY: Many bacterial causes of healthcare infection can survive in the inanimate environment for lengthy periods and be transmitted to patients. Furthermore, current methods of environmental decontamination such as detergents, chemical disinfectants or gaseous fumigation are suboptimal for a variety of reasons. We assessed the efficacy of helium and helium-air plasma as a decontaminant and demonstrated a significant reduction in bacterial counts of Staphylococcus aureus on a glass surface. Atomic force microscopy morphologically confirmed the impact on bacterial cells. This approach warrants further study as an alternative to current options for hospital hygiene.

Total arterial coronary artery bypass grafting in patients with diabetes: an 8-year experience.

OBJECTIVE: Coronary artery bypass grafting using arterial conduits may improve survival and minimise harvest site complications. However, in diabetes, the outcomes of coronary artery bypass grafting performed exclusively using arterial conduits are uncertain. We reviewed our experience with this approach. METHODS: From 1996 to 2008, 400 patients with diabetes (managed with oral hypoglycaemics, insulin or both) underwent primary isolated coronary artery bypass grafting for triple vessel coronary disease. In 246 (61.5%), total arterial revascularisation was achieved using single or bilateral internal thoracic arteries supplemented by one or more radial arteries (arterial group), while in the remaining 154 (38.5%), at least one venous conduit was used (mixed conduits group: mean 1.5 veins per patient). Propensity-score matching was used to adjust for bias. RESULTS: Total arterial revascularisation patients were more likely to be younger (arterial: 63 ± 10 years vs mixed: 67 ± 10 years, P < 0.0001), of elective priority (85% vs 75%, P = 0.018) and less likely to have moderate-severe left ventricular dysfunction (23% vs 36%, P = 0.024). Use of bilateral internal thoracic arteries was similar between groups (16% vs 11%, P = 0.19). There was a comparable in-hospital mortality (1.9% vs 2.0%, P > 0.99) and major morbidities, except the arterial group who experienced less stroke (0.4% vs 3.2% vs P = 0.04) and harvest site infections (0.4% vs 4%, P = 0.016). Mean follow was 7.8 ± 3.7 years. Estimated survival at 12-year survival in the arterial group was 80% ± 3.2% vs 54% ± 5.5% (P < 0.0001). Subsequently, 103 propensity-score-matched patient pairs were created between the two groups. After matching, in-hospital mortality (1% vs 2%, P > 0.99) and major morbidities were similar, as was an estimated 12-year survival (69% ± 6.1% vs 59% ± 6.5%, P > 0.99). CONCLUSIONS: The use of veins to supplement arterial conduits did not deleteriously affect survival. However, the significant number of patients receiving arterial grafts in both groups may have masked any potential difference. Greater numbers and longer follow-up will reveal the potential of this approach.

Post-operative pain after laparoscopic right hemicolectomy for Crohn's disease: a case control study.

AIM: Surgery for Crohn's disease (CD) is characterized by an enhanced inflammatory response. While inflammation can induce hyperalgesia, post-operative pain following surgery for CD has not been characterized. This retrospective study compared a consecutive series of patients undergoing laparoscopic right hemicolectomy for CD and neoplasia performed by a single surgeon. METHOD: Elective resections performed between Jan-2016 and Aug-2017 managed in an enhanced recovery pathway were eligible for inclusion. Patients were excluded if open surgery was performed, an ileostomy was fashioned, no patient-controlled analgesia (PCA) was used or data were incomplete. Results : 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. RESULTS: 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. CONCLUSIONS: CD patients experience increased post-operative pain, require more post-operative analgesia and have an enhanced post-operative inflammatory response. Further studies to elucidate the mechanism of this hyperalgesia and strategies to obviate it are required.

Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

Cocaine-related admissions to an intensive care unit: a five-year study of incidence and outcomes.

Cocaine misuse is increasing and it is evidently considered a relatively safe drug of abuse in Ireland. To address this perception, we reviewed the database of an 18-bed Dublin intensive care unit, covering all admissions from 2003 to 2007. We identified cocaine-related cases, measuring hospital mortality and long-term survival in early 2009. Cocaine-related admissions increased from around one annually in 2003-05 to 10 in 2007. Their median (IQR [range]) age was 25 (21-35 [17-47]) years and 78% were male. The median (IQR [range]) APACHE II score was 16 (11-27 [5-36]) and length of intensive care stay was 5 (3-9 [1-16]) days. Ten patients died during their hospital stay. A further five had died by the time of follow-up, a median of 24 months later. One was untraceable. Cocaine toxicity necessitating intensive care is increasingly common in Dublin. Hospital mortality in this series was 52%. These findings may help to inform public attitudes to cocaine.

Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells.

In this paper we present keratin expression data that lend strong support to a model of corneal epithelial maturation in which the stem cells are located in the limbus, the transitional zone between cornea and conjunctiva. Using a new monoclonal antibody, AE5, which is highly specific for a 64,000-mol-wt corneal keratin, designated RK3, we demonstrate that this keratin is localized in all cell layers of rabbit corneal epithelium, but only in the suprabasal layers of the limbal epithelium. Analysis of cultured corneal keratinocytes showed that they express sequentially three major keratin pairs. Early cultures consisting of a monolayer of "basal" cells express mainly the 50/58K keratins, exponentially growing cells synthesize additional 48/56K keratins, and postconfluent, heavily stratified cultures begin to express the 55/64K corneal keratins. Cell separation experiments showed that basal cells isolated from postconfluent cultures contain predominantly the 50/58K pair, whereas suprabasal cells contain additional 55/64K and 48/56K pairs. Basal cells of the older, postconfluent cultures, however, can become AE5 positive, indicating that suprabasal location is not a prerequisite for the expression of the 64K keratin. Taken together, these results suggest that the acidic 55K and basic 64K keratins represent markers for an advanced stage of corneal epithelial differentiation. The fact that epithelial basal cells of central cornea but not those of the limbus possess the 64K keratin therefore indicates that corneal basal cells are in a more differentiated state than limbal basal cells. These findings, coupled with the known centripetal migration of corneal epithelial cells, strongly suggest that corneal epithelial stem cells are located in the limbus, and that corneal basal cells correspond to "transient amplifying cells" in the scheme of "stem cells----transient amplifying cells----terminally differentiated cells."

Oral manifestations of lupus.

INTRODUCTION: Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. METHODS: We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. RESULTS: A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. CONCLUSION: Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

Dislocation loop formation by swift heavy ion irradiation of metals.

A coupled two-temperature, molecular dynamics methodology is used to simulate the structural evolution of bcc metals (Fe and W) and fcc metals (Cu and Ni) following irradiation by swift heavy ions. Electronic temperature dependent electronic specific heat capacities and electron-phonon coupling strengths are used to capture the full effects of the variation in the electronic density of states. Tungsten is found to be significantly more resistant to damage than iron, due both to the higher melting temperature and the higher thermal conductivity. Very interesting defect structures, quite different from defects formed in cascades, are found to be created by swift heavy ion irradiation in the bcc metals. Isolated vacancies form a halo around elongated interstitial dislocation loops that are oriented along the ion path. Such configurations are formed by rapid recrystallization of the molten cylindrical region that is created by the energetic ion. Vacancies are created at the recrystallization front, resulting in excess atoms at the core which form interstitial dislocation loops on completion of crystallization. These unique defect structures could, potentially, be used to create metal films with superior mechanical properties and interesting nanostructures.

The influence of the electronic specific heat on swift heavy ion irradiation simulations of silicon.

The swift heavy ion (SHI) irradiation of materials is often modelled using the two-temperature model. While the model has been successful in describing SHI damage in metals, it fails to account for the presence of a bandgap in semiconductors and insulators. Here we explore the potential to overcome this limitation by explicitly incorporating the influence of the bandgap in the parameterisation of the electronic specific heat for Si. The specific heat as a function of electronic temperature is calculated using finite temperature density functional theory with three different exchange correlation functionals, each with a characteristic bandgap. These electronic temperature dependent specific heats are employed with two-temperature molecular dynamics to model ion track creation in Si. The results obtained using a specific heat derived from density functional theory showed dramatically reduced defect creation compared to models that used the free electron gas specific heat. As a consequence, the track radii are smaller and in much better agreement with experimental observations. We also observe a correlation between the width of the band gap and the track radius, arising due to the variation in the temperature dependence of the electronic specific heat.

No aliasing at edges in normal viewing.

Although spatial aliasing by the extrafoveal retina can occur under natural viewing conditions, it does not commonly disturb our vision. One possible explanation for this is that real scenes do not have sufficient power in the high frequencies to produce aliasing. We examined whether aliasing distorted the appearance of a high contrast edge, which is a common stimulus in the environment. Observers made a two-interval forced-choice discrimination between low-pass filtered and unfiltered edges at 0, 10, 20, and 40 deg eccentricity. This discrimination could be made only when frequency components were removed below both the cone and ganglion cell Nyquist frequencies at each eccentricity. Since supra-Nyquist frequency components could not be detected in edges, they are incapable of producing aliasing.

The spatial grain of motion perception in human peripheral vision.

Motion reversal effects (the apparent reversal of the direction of motion of a high frequency sinusoidal grating) have been attributed to aliasing by the cone mosaic [Coletta et al. (1990). Vision Research, 30, 1631-1648] and postreceptoral layers [Anderson & Hess (1990). Vision Research, 30, 1507-1515] in human observers. We present data and a new model which suggest that at least two sampling arrays of different densities affect direction discrimination out to 30 degrees eccentricity. The first sampling layer matches anatomical estimates of the cone density. The second sampling layer is too dense to be the parasol cells alone; midget ganglion cells certainly contribute to this task. This is further evidence that motion perception is not mediated exclusively by the magnocellular stream.

Sharpness overconstancy in peripheral vision.

Although much has been learned about the spatial sampling and filtering properties of peripheral vision, little attention has been paid to the remarkably clear appearance of the peripheral visual field. To study the apparent sharpness of stimuli presented in the periphery, we presented Gaussian blurred horizontal edges at 8.3, 16.6, 24, 32, and 40 deg eccentricity. Observers adjusted the sharpness of a similar edge, viewed foveally, to match the appearance of the peripheral stimulus. All observers matched blurred peripheral stimuli with sharper foveal stimuli. We have called this effect "sharpness overconstancy". For field sizes of 4 deg, there was greater overconstancy at larger eccentricities. Scaling the field size of the peripheral stimuli by a cortical magnification factor produced sharpness overconstancy which was independent of eccentricity. In both cases, there was a slight sharpness underconstancy for peripherally presented edges blurred only slightly. We consider various explanations of peripheral sharpness overconstancy.

Sharpness overconstancy: the roles of visibility and current context.

In a previous study we found that blurred edges presented in peripheral vision look sharper than when they are looked at directly, a phenomenon we have called peripheral sharpness overconstancy (Galvin et al. (1997). Vision Research, 37, 2035-2039). In the current study we show that when visibility of the stimulus edges is compromised by very brief presentations, we can demonstrate sharpness overconstancy for static, foveal viewing. We also test whether the degree of sharpening is a function of the current visual context, but find no difference between the peripheral sharpness overconstancy (at 24 degrees eccentricity) of edges measured in a blurred context and that measured in a sharp context. We conclude that if the visual system does carry a template for sharp edges which contributes to edge appearance when visibility is poor, then that template is resistant to changes in context.

Historical reflections on hypertension.

Sixty million Americans have hypertension, a major cardiovascular risk factor. Its presence accelerates the atherosclerotic process, producing strokes, heart attacks, heart failure, renal failure, and peripheral vascular disease. This article highlights the historical landmarks in the study of this disease from the first documented measurement of blood pressure in 1733, through the most recent pharmacologic approaches to treatment. In addition, the roles of the kidney and the renin-angiotensin-aldosterone system are examined.

Structural findings regarding the Silencing the Self Scale.

Principal components factor analysis, based on scores of 363 college women, confirmed four subscales of the Silencing the Self Scale; however, 5 items loaded differently in the structure of these subscales. Recommendations for scale revision and studies with other populations are suggested.