An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.

The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS) of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11) that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19). In a pooled analysis of both studies (73 cases and 186 controls), the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27). Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.

E-learning and near-peer teaching in electrocardiogram education: a randomised trial.

BACKGROUND: Near-peer teaching and electronic learning (e-learning) are two effective modern teaching styles. Near-peer sessions provide a supportive learning environment that benefits both the students and the tutor. E-learning resources are flexible and easily distributed. Careful construction and regular editing can ensure that students receive all of the essential material. The aim of this study is to compare the efficacy of e-learning and near-peer teaching during the pre-clinical medical curriculum. METHODS: Thirty-nine second-year medical students were consented and randomised into two groups. Each group received teaching on electrocardiogram (ECG) interpretation from a predefined syllabus. Eighteen students completed an e-learning module and 21 students attended a near-peer tutorial. Students were asked to complete a multiple-choice exam, scored out of 50. Each student rated their confidence in ECG interpretation before and after their allocated teaching session. RESULTS: The near-peer group (84%) demonstrated a significantly higher performance than the e-learning group (74.5%) on the final assessment (p = 0.002). Prior to the teaching, the students' mean confidence scores were 3/10 in both the near-peer and e-learning groups (0, poor; 10, excellent). These increased to 6/10 in both cases following the teaching session. DISCUSSION: Both teaching styles were well received by students and improved their confidence in ECG interpretation. Near-peer teaching led to superior scores in our final assessment. Given the congested nature of the modern medical curriculum, direct comparison of the efficacy of these methods may aid course design. The aim of this study is to compare the efficacy of e-learning and near-peer teaching.

Everyone gets involved: fostering a high quality teaching and learning culture in the NHS.

The aim was to create an environment where doctors at all levels felt like an important part of the education team. Two teaching fellows were appointed to deliver teaching, encourage participation, and quality-assure teaching. An innovative electronic logbook named Teaching Log (T-Log) was developed to reliably "record and reward" teaching occurring at all career levels. A mentor scheme for medical students was established. Mentor training was provided for junior doctors. A near-peer teaching programme was developed for final year medical students on important skills required to be a safe junior doctor. Between September 2013 and January 2014, 83 doctors at our institution logged 657 teaching episodes using the electronic T-Log. 23% were F1s, 14% were F2s, 24% CT1-2s. 36% of sessions were delivered to 3rd year medical students and 36% were delivered to 5th year students. 24% were small group seminars, 26% were bedside teaching sessions, 12% were lectures, 5% were simulation sessions and 9% were clinical skills. 20% of sessions were delivered to a single student. 100% of respondents (15) agreed that T-Log was easy to use. 100% agreed that T-Log was useful. 100% agreed that they would continue to use T-Log. A survey found the mean score for usefulness of the mentor scheme to be 9.1 (1=not useful, 10=very useful). Students saw their mentors on average 6.5 times during a 10 week period. Confidence scores for all key areas of the curriculum were increased following implementation of the scheme. 100% of students would recommend this scheme to next year's final year students and 100% of mentor respondents (n=8) would participate in the scheme again. Rewarding those who contribute to teaching provides incentive to further increase the quality of education provided to students. T-Log rewards teaching activity. It also provides useful data at an individual level or at institutional level.

Canine dacryolithiasis: a case description and mineral analysis.

A 4-year-old, female, spayed, Labrador retriever was presented with a painless swelling of the left ventromedial eyelid and epiphora of 3 months duration. Bilateral patency of the nasolacrimal system was confirmed by the appearance of fluorescein dye at both nares. Ultrasonography revealed a well-demarcated fluid-filled structure containing echogenic ill-defined material in close proximity to the nasolacrimal system. A transconjunctival surgical approach confirmed the close anatomical proximity of the cyst and the absence of a communication with the inferior canaliculus. The cyst contained multiple intraluminal calculi (dacryoliths). Following surgical excision of the cyst, the epiphora resolved and no recurrence was noted over a 12-month follow-up period. On histopathology, the cystic structure was lined by stratified squamous epithelium, consistent with lacrimal canaliculus epithelium. Presumed progression of a canalicular diverticulum to a cyst with the formation of intraluminal dacryoliths was suspected. Mineral analysis of the dacryoliths revealed a calcium carbonate composition.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008.

BACKGROUND: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. METHODS: Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. RESULTS: Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. CONCLUSIONS: The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.

Penetrating ocular gunshot injury in a Labrador Retriever.

A 3½-year-old, female (spayed) working black Labrador Retriever was referred to the Unit of Comparative Ophthalmology at the Animal Health Trust after a penetrating lead gunshot injury to the right eye. Clinical examination revealed penetrating injuries to the right cornea, left lateral canthus, and left forelimb. Radiography revealed the presence of multiple metallic foreign bodies in the head and one in the left forelimb. B-mode ocular ultrasonography confirmed the presence of an intraocular metallic foreign body within the posterior tunics of the right eye. Medical treatment of the right eye over a period of 1 month resulted in a comfortable, visual eye. Long-term follow-up over 4½ years revealed a slow deterioration in vision because of progressive lens opacification and the presence of a localized area of chorioretinopathy.

Calcareous degeneration of the canine cornea.

The purpose of this paper is to describe a specific presentation of canine corneal calcification. Fourteen cases are described. In seven cases the corneal lesions were bilaterally symmetrical. In five cases the corneal lesion was unilateral. Two dogs were uniocular, the contralateral eye had been enucleated between 1 and 3 months previously by the referring veterinary surgeon following corneal ulceration and perforation. Of a total of 21 eyes with corneal calcification, 16 eyes had associated ulceration. The ulceration presented as follows: two eyes had descemetocoeles, four eyes had corneal perforations, eight eyes had stromal ulceration, and two eyes had superficial punctate ulceration. The cause of the corneal mineralization remains undetermined but underlying systemic disease, particularly hyperadrenocorticism (Cushing's Syndrome), is suspected as a possible contributing factor in some of these cases. Histopathology was carried out on three cases following a keratectomy and placement of a conjunctival pedicle flap into the ulcerated lesion.

The importance of propolis in patch testing--a multicentre survey.

BACKGROUND: Propolis is widely used in 'natural' cosmetics, remedies, and over-the-counter products. The incidence of propolis allergy is increasing, and cross-reaction with fragrance mix I (FMII), colophonium, and Myroxylon pereirae can occur. OBJECTIVES: To find out the prevalence and clinical relevance of positive patch tests to propolis and assess cross-reactions with Myroxylon pereirae, colophonium, FMI, and beeswax. METHODS: Two thousand eight hundred and twenty-eight subjects in 10 UK centres were patch tested with propolis and beeswax. Generic data were acquired from British Contact Dermatology Society (BCDS) database and further relevant information was requested by survey of participating centres. RESULTS: The prevalence of propolis allergy was 1.9% (55/2828). Out of these 55 subjects, only 4 (7.2%) were allergic to beeswax, 22 (40%) to Myroxylon pereirae, 15 (27.2%) to colophonium, and 6 (10.9%) to FMI. Additional data for 41 propolis allergic subjects were collected by questionnaire. Hands were the most common sites of involvement, and cosmetics were the most common source of contact. Eight out of 12 subjects reported improvement in eczema following avoidance of propolis. CONCLUSIONS: Propolis is an important allergen of increasing frequency and its inclusion in BCDS baseline series is appropriate. Cross-sensitivity to beeswax is rare.

The European baseline series in 10 European Countries, 2005/2006--results of the European Surveillance System on Contact Allergies (ESSCA).

BACKGROUND: Continual surveillance based on patch test results has proved useful for the identification of contact allergy. OBJECTIVES: To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. PATIENTS/METHODS: Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. RESULTS: Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. CONCLUSIONS: Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.

Expression of cyclooxygenase-2 by equine ocular and adnexal squamous cell carcinomas.

OBJECTIVE: To investigate whether cyclooxygenase-2 (COX-2) is expressed by equine ocular and adnexal squamous cell carcinomas (SCC). METHODS: Forty-three samples of histologically confirmed cases of ocular SCC or carcinoma in situ (CIS) from 34 horses presented to the Animal Health Trust between 1992 and 2004 were subjected to a standard, two-layered, indirect immunohistochemical method using a rabbit polyclonal antihuman COX-2 antibody. Ten formalin-fixed, paraffin-embedded tissue samples taken from recognized predilection sites for SCC, from the grossly normal eyes of 10 horses euthanized for reasons unrelated to this study, were used as negative controls. Samples of equine fetal kidney were used as positive controls. Following immunolabeling, the number of normal and neoplastic epithelial cells exhibiting positive COX-2 expression was recorded along with staining intensity and distribution. RESULTS: Of 43 tumors, 34 were defined as first presentation tumors. When compared with control tissue, in which 0% (0/10) of samples expressed COX-2, significantly more of these samples with SCC (58.6%, 17/29: P = 0.002), CIS (60%, 3/5: P = 0.022) or either tumor type (58.8%, 20/34: P = 0.001) exhibited positive cytoplasmic and perinuclear immunohistochemical staining for COX-2. Of the samples exhibiting positive immunohistochemical staining, only 10% (2/20) showed staining in 2%-10% of neoplastic cells, while 90% (18/20) showed staining in 1% of neoplastic cells. About 70% (14/20) of those positively immunolabeled samples exhibited an intensity of staining greater than or equal to the staining exhibited by the equine fetal kidney positive control. CONCLUSION: Neoplastic tissue from both equine ocular SCC and CIS exhibit COX-2 expression at significantly higher levels than normal control ocular tissue. However, the percentage of cells expressing positive immunohistochemical staining is consistently low. On the basis of this study, it is unlikely that anti-COX-2 therapy would be of benefit in the treatment of equine ocular and adnexal SCC.

Corneal squamous cell carcinoma in a Border Collie.

A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.