Expression of Cannabinoid Receptors in the Trigeminal Ganglion of the Horse.

Cannabinoid receptors are expressed in human and animal trigeminal sensory neurons; however, the expression in the equine trigeminal ganglion is unknown. Ten trigeminal ganglia from five horses were collected post-mortem from an abattoir. The expression of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and the cannabinoid-related receptors like transient receptor potential vanilloid type 1 (TRPV1), peroxisome proliferator-activated receptor gamma (PPARÉ£), and G protein-related receptor 55 (GPR55) in the trigeminal ganglia (TG) of the horse were studied, using immunofluorescence on cryosections and formalin-fixed paraffin-embedded (FFPE) sections. Neurons and glial cells were identified using fluorescent Nissl staining NeuroTrace® and an antibody directed against the glial marker glial fibrillary acidic protein (GFAP), respectively. Macrophages were identified by means of an antibody directed against the macrophages/microglia marker ionized calcium-binding adapter molecule 1 (IBA1). The protein expression of CB1R, CB2R, TRPV1, and PPARÉ£ was found in the majority of TG neurons in both cryosections and FFPE sections. The expression of GPR55 immunoreactivity was mainly detectable in FFPE sections, with expression in the majority of sensory neurons. Some receptors were also observed in glial cells (CB2R, TRPV1, PPARγ, and GPR55) and inflammatory cells (PPARγ and GPR55). These results support further investigation of such receptors in disorders of equine trigeminal neuronal excitability.

Is regional ankle block needed in conjunction with general anaesthesia for first ray surgery? A randomised controlled trial of ultrasound guided ankle block versus "blind" local infiltration.

BACKGROUND: Regional anaesthesia is commonly utilised for foot and ankle surgery. Debate remains at to the level of regional anaesthesia that is required. The objective of this study was to evaluate whether surgeon-delivered "blind" local anaesthetic infiltration around the first ray (metatarsal block without ultrasound guidance) was as effective as an ultrasound guided ankle block in providing post-operative analgesia after osseous first ray surgery performed under general anaesthetic. METHODS: 50 patients were recruited to a single surgeon and anaesthetist double-blinded randomised controlled trial at a single-centre. 20mls of 0.5% levobupivacaine was used to perform either an ankle or metatarsal nerve block. RESULTS: Forty-eight patients completed the study: 25 in the ankle block treatment arm and 23 in the metatarsal block arm. The demographics were comparable between groups. There was no statistical difference in visual analogue pain scores at two (21.3 vs 15.2), six (23.6 vs 20.8) and 24 (42.2 vs 50.4) hours following the procedure between the two groups (metatarsal block vs ankle block). Metatarsal block groups had a faster return of normal sensation (2.3 vs 2.8h) but there was no difference in time to safe mobilisation (2.6 vs 2.8h). CONCLUSION: This study demonstrates the efficacy and safety of surgeon delivered "blind" metatarsal block is comparable to an ultrasound guided ankle block for first ray surgery performed under general anaesthetic. LEVEL OF EVIDENCE: 1.

Does functional outcome depend on the quality of the fracture fixation? Mid to long term outcomes of ankle fractures at two university teaching hospitals.

BACKGROUND: The aim of our study was to assess the adequacy of reduction and internal fixation of ankle fractures and the long-term functional outcomes of patients treated in two university teaching hospitals by general orthopaedic surgeons. METHOD: We performed a retrospective study involving two large trauma units in the UK, reviewing all operatively treated unstable ankle fractures performed in one centre between 1st October 2006 and 31st December 2007 and another centre between 1st January 2009 and 31st December 2009. All patients were contacted by postal follow up at a minimum of 6-years using the Olerud-Molander Ankle Score (OMAS). RESULTS: 261 patients underwent operative treatment for ankle fractures during the study period at the two hospitals. 107 patients responded to the questionnaire. Analysis of patients' functional outcome by fracture type reveals that the outcome scores decrease as the complexity of the ankle fracture increases. A significant finding within subgroup analysis found that trimalleolar fractures (B3) have worse outcomes than bimalleolar fractures (B2 and C); which in turn have worse outcomes than isolated lateral malleolar fractures (B1). Analyzing the outcome of patients based on the severity of malreduction revealed that Pettrone's value was inversely proportional to the OMAS. CONCLUSION: We have found a significant reduction in patient reported function in patients whose fractures were malreduced at time of surgery.

Self-harm prevalence and ideation in a community sample of cis, trans and other youth.

Background: Trans youth have been reported to have high rates of self-harm, depression and bullying, and find it difficult to seek support. However, much of this research comes from gender identity clinics; non-clinical samples and those who reject gender binaries remain under-researched. Aims: This study investigated the experiences of a community school-based sample of Trans, identifying youth, Other, and cis-gendered adolescents in relation to their experiences of low mood, bullying, associated support, self-harm ideation and peer-related self-harm. Methods: An online survey was completed by 8440 13-17 year olds (3625 male, 4361 female, 227 Other, and 55 Trans). Results: Trans and Other students had significantly higher rates of self-harm ideation and peer self-harm, in comparison to cis-gendered students. These Trans and Other students reported significantly higher rates of bullying and self-reported depression and significantly less support from teachers and staff at school, in fact these students did not know where to go to access help. Discussion: This community sample confirms findings of high rates of self-harm ideation, self-reported depression and bullying for Trans youth as previously reported in clinic-based samples. However, by accessing a community sample, the salience of the category "Other" was established for young people today. While Other and Trans identified students both struggled to find support, those who identified as Trans were more likely to have been bullied, and have experienced self-reported depression and thoughts of self-harm. Thus, those who identify as transgender represent a high-risk group that needs targeted support within schools and by statutory and nonstatutory community services. Unpacking the category of Other would be beneficial for future research, as well as exploring resilience within this group and intersecting identities such as sexuality, Autism, or experiences such as earlier abuse.

Use of a poll-mounted accelerometer for quantification and characterisation of equine trigeminal-mediated headshaking.

BACKGROUND: Equine trigeminal-mediated (TGM) headshaking (HS) is a neuropathic facial pain syndrome characterised by varying intensity and frequencies of head movements and signs of nasal irritation. An accurate method for quantification and/or characterisation of HS severity is lacking. OBJECTIVES: To develop and validate an objective measure of TGMHS. STUDY DESIGN: Prospective case control study. METHODS: Horses presenting for investigation of HS were recruited alongside those presenting for forelimb lameness (LAME) and pre-purchase examination as well as healthy controls (CONTROL). Head movement data were collected for 5 min whilst trotting on the lunge using a tri-axial accelerometer, with a range of ±16 g and sampling rate of 800 Hz, attached to the bridle headpiece. Recordings were exported for processing. Peak detection was performed using minimum and maximum thresholds of -1 g and +1 g (corrected for gravity) and a minimum peak width of 10 samples. RESULTS: Fifty-six horses were included in the study; 18 TGMHS, 10 non-TGMHS, 12 LAME and 16 CONTROL. Characteristics and frequency of vertical (Z axis) head movements of TGMHS horses differed significantly from other horses. TGMHS horses had peaks with greater mean and maximum positive g-force (P < 0.005) and lower mean and minimum negative g-force (P < 0.001), greater frequency of peaks/min (P < 0.001) and over 12 times greater percentage of peaks >+2 g compared with other horses (P < 0.001). Receiver operator curve characteristics of percentage of peaks >+2 g (CI 0.72-0.95), percentage of peaks <-2 g (CI 0.66-0.92) and percentage of peaks <-2 g and >+2 g (CI 0.72-0.96) showed excellent discrimination of TGMHS horses from LAME, CONTROL and non-TGMHS horses. MAIN LIMITATIONS: Referral population of horses, small sample size and control horses were not evaluated for orthopaedic disease. CONCLUSIONS: Accelerometer data from trotting exercise on the lunge provides an objective measure of HS and can differentiate between TGMHS, non-TGMHS, normal head movements and those associated with forelimb lameness. Accelerometer use may aid HS diagnosis and monitoring of management strategies.

HISTORIAL: La sacudida de cabeza (HS) en equinos mediada por el nervio trigémino (TGM), es un síndrome de dolor facial neuropático caracterizado por movimientos de cabeza de intensidad y frecuencia variables y por síntomas de irritación nasal. No existe un método preciso para cuantificar y/o caracterizar la gravedad de HS. OBJETIVOS: Desarrollar y validar una medida objetiva de TGMHS. DISEÑO DEL ESTUDIO: Estudio prospectivo de casos y controles. MÉTODOS: Caballos presentados para la investigación de HS fueron reclutados junto a aquellos presentados para cojera de mano (LAME) y examen de pre­compra como controles saludables (CONTROL). Datos de los movimiento de la cabeza fueron recolectados durante cinco minutos mientras trotaban a la cuerda usando un acelerómetro tri­axial, con un rango de ±16 g y frecuencia de muestreo de 800 Hz, ajustado a la testera de la cabezada. Las grabaciones se exportaron para ser procesadas. Detección de picos fue realizada usando umbrales mínimos y máximos de −1g y + 1g (corregidos para gravedad) y un muestreo mínimo de 10 picos de ancho. RESULTADOS: Cincuenta y seis caballos fueron incluidos en el estudio; 18 TGMHS, 10 no­TGMHS, 12 LAME y 16 CONTROL. Las características y la frecuencia de los movimientos de cabeza verticales (eje Z) de caballos TGMHS, difirieron significativamente de otros caballos. Los caballos TGMHS presentaron picos con una fuerza­g positiva con mayor promedio y máxima (P < 0.005) y una fuerza­g negativa con menor promedio y mínima (P < 0.001), con mayor frecuencia de picos/min (P < 0.001), y un porcentaje mas de doce veces mayor de picos >+2 g en comparación a los otros caballos (P < 0.001). Las características de las curvas del operador del receptor de los picos promedio >+2 g (CI 0.72­0.95), del porcentaje de picos <−2 g (CI 0.66­0.92), y del porcentaje de picos <−2 g y > +2 g (CI 0.72­0.96) mostraron una excelente discriminación de caballos TGMHS con respecto a caballos LAME, CONTROL y no­TGMHS. LIMITACIONES PRINCIPALES: Población de caballos derivados, numero de muestra pequeño, y los caballos control no fueron evaluados por enfermedades ortopédicas. CONCLUSIONES: Los datos de acelerómetros por trote a la cuerda, dan una medida objetiva de HS y permiten diferenciar entre TGMHS, no­TGMHS, movimientos normales de cabeza y aquellos asociados a cojera de mano. El uso de acelerómetros puede ayudar en el diagnostico de HS y monitorear las estrategias de manejo.

History, Rest and Exercise Score (HRE-S) for assessment of disease severity in horses with trigeminal-mediated headshaking.

BACKGROUND: In horses with trigeminal-mediated headshaking (TMHS), clinical signs are likely to be expression of neuropathic facial pain. Currently, subjective assessment of disease severity is used as measure of compromise of animal's welfare. OBJECTIVES: To develop and validate a precise scoring system for TMHS: History, Rest and Exercise Score (HRE-S). The HRE-S consists of three subscores: history score (H-S), resting score (R-S) and exercise score (E-S). STUDY DESIGN: Retrospective observational study. METHODS: Seven masked observers with different experience used HRE-S to score 40 video recordings taken during rest and lungeing including five duplicates. Video recordings were taken from nine horses with TMHS and three controls. Inter- and intraobserver reliability and practicability of HRE-S were assessed. For every video recording severity of clinical signs was graded by every observer using an intuitive global-type-scale and interobserver reliability was calculated. Convergent validity was evaluated comparing HRE-S to groups created by an existing score (grade 0-3). Discriminant validity was analysed comparing HRE-S to groups created by intuitive global-type-scale. RESULTS: Reliability for HRE-S was excellent, irrespective of observers experience: Spearman's Rho = 0.946, p < 0.001 (intraobserver reliability) and intraclass correlation coefficient = 0.98, p < 0.001 (interobserver reliability). Interobserver reliability for intuitive global-type-scale was fair to substantial: Fleiss' κappa = 0.48 (R-S) -0.63 (E-S). Groups created by intuitive global-type-scale had significantly different R-S and E-S (p < 0.05), demonstrating discriminant validity. Convergent validity was proven as horses with grade 3/3 had significantly higher average E-S and total scores compared with an existing score than those with grade 0/3 or 1/3 (p < 0.001). MAIN LIMITATIONS: Retrospective nature, video recordings, sample size. CONCLUSIONS: HRE-S is a valid and reliable score evaluating disease severity in TMHS, independent of observers' experience.

Epidemiology and Diagnosis of Post-Thrombotic Syndrome: Qualitative Synthesis with a Systematic Review.

Background: Post-thrombotic syndrome (PTS) is a common and debilitating sequela of lower limb deep vein thrombosis (DVT). There is significant heterogeneity in reported PTS incidence due to lack of standardised diagnostic criteria. This review aimed to develop diagnostic criteria for PTS and subsequently refine the reported incidence and severity. Methods: PRISMA principles were followed; however, the review was not registered. The Cochrane CENTRAL database, MEDLINE, Embase, the NHS NICE Healthcare Databases Advanced Search interface, and trial registers including isrctn.com and clinicaltrials.gov were searched for studies addressing areas of interest (PTS definition, epidemiology, assessment). An experienced Clinical Librarian undertook the systematic searches, and two independent reviewers agreed on the relevance of the papers. Conflicts were resolved through panel review. Evidence quality was assessed using a modified Coleman scoring system and weighted according to their relevance to the aforementioned areas of interest. Results: A total of 339 abstracts were retrieved. A total of 33 full-text papers were included in this review. Following qualitative analysis, four criteria were proposed to define PTS: (1) a proven thrombotic event on radiological assessment; (2) a minimum 24-month follow-up period after an index DVT; (3) assessment with a validated score; and (4) evidence of progression of venous insufficiency from baseline. Four papers conformed to our PTS definition criteria, and the incidence of mild to moderate PTS ranged from 7 to 36%. On reviewing the studies which utilised the recommended Villalta scale, PTS incidence narrowed further to 23-36%. Incidence and severity reached a plateau at 24 months. Conclusions: Four diagnostic criteria were developed from qualitative synthesis. When these criteria were applied to the literature, the range of reported PTS incidence narrowed. These four criteria may standardise PTS diagnosis in future studies, facilitating the pooling of data for meta-analysis and synthesis of higher levels of evidence.

Position of the midline septum of the guttural pouches in horses subjected to computed tomography.

Standing computed tomographic (CT) examination of the equine guttural pouch frequently reveals deviation of the midline septum. The significance of deviation is currently unknown. The aims of this retrospective, single-centre study were to determine the prevalence of deviation of the midline septum of the guttural pouch and determine whether there was an association between the presence and degree of deviation of the septum, and guttural pouch disease. Case records were reviewed, identifying 95 horses that had undergone a standing, sedated, head CT and guttural pouch endoscopy. The presence, laterality, subjective degree and angle of deviation of the midline septum on CT was recorded. A total of 69 (72.6%) horses were identified with deviation of the midline septum, with the mean angle of deviation 13.4o and a maximum deviation of 52.6o. No significant association between the presence of deviation of the midline septum (P = .722) or severity of deviation (P = .428) and an endoscopic abnormality within the guttural pouch was found. The laterality of deviation and guttural pouch abnormalities were also not associated (P = .000). Deviation of the midline septum of the guttural pouch is a common finding on CT examination, and does not have clinical significance in this study.

Audit changes practice-a simple education intervention can lead to better outcome in ankle fracture surgery.

BACKGROUND: Unstable ankle fractures are common, and majority requires open reduction and internal fixation (ORIF). There is emerging evidence that the rate of malreduction has remained high despite advances in surgical techniques and implants. Malreduced ankle is a prominent cause of post-traumatic ankle arthritis leading to poor patient reported outcome. The aim of this study was to investigate the quality of anatomical reduction and surgical fixation of ankle fractures and the impact of simple education intervention on the quality of reduction of these fractures. METHODOLOGY: An audit cycle was completed in two phases; retrospective review (phase 1) of 114 cases operated prior to an education intervention using infographic posters and then a prospective (phase 2) review of 96 consecutive cases operated after the education intervention. Data including age, fracture morphology, time to surgery, and the quality of reduction were assessed. The quality of anatomical reduction was evaluated using radiological parameters described by Pettrone. Paediatric, Weber A, pathological and open fractures were excluded. Education interventions included regional teaching and dissemination of infographic posters. Mann- Whitney U test and Chi-squared test were used to compare continuous and categorical data between phase 1 and 2 respectively. P value < 0.05 was considered significant. RESULTS: Phase one cohort showed malreduced fixation in 25% of cases. Inadequate restoration of fibular length was the most common type of malreduction. After implementation of education intervention, malreduction rate reduced to 9.4% in phase 2 (p = 0.015). There were no significant differences between age, gender, and time to surgery between phase one and two. CONCLUSION: This study demonstrates that simple education intervention can lead to better understanding of fixation and decrease the rate of malreduction of these fractures. We recommend that using Pettrone's radiological criteria in correction of corresponding anatomy of ankle fracture is a useful tool to avoid malreduction.

30-day mortality following trauma and orthopaedic surgery during the peak of the COVID-19 pandemic: a multicentre regional analysis of 484 patients.

AIMS: Now that we are in the deceleration phase of the COVID-19 pandemic, the focus has shifted to how to safely reinstate elective operating. Regional and speciality specific data is important to guide this decision-making process. This study aimed to review 30-day mortality for all patients undergoing orthopaedic surgery during the peak of the pandemic within our region. METHODS: This multicentre study reviewed data on all patients undergoing trauma and orthopaedic surgery in a region from 18 March 2020 to 27 April 2020. Information was collated from regional databases. Patients were COVID-19-positive if they had positive laboratory testing and/or imaging consistent with the infection. 30-day mortality was assessed for all patients. Secondly, 30-day mortality in fracture neck of femur patients was compared to the same time period in 2019. RESULTS: Overall, 496 operations were carried out in 484 patients. The overall 30-day mortality was 1.9%. Seven out of nine deceased patients underwent surgery for a fractured neck of femur. In all, 27 patients contracted COVID-19 in the peri-operative period; of these, four patients died within 30 days (14.8%). In addition, 21 of the 27 patients in this group had a fractured neck of femur, 22 were over the age of 70 years (81.5%). Patients with American Society of Anesthesiologists (ASA) grade > 3 and/or age > 75 years were at significantly higher risk of death if they contracted COVID-19 within the study period. CONCLUSION: Overall 30-day postoperative mortality in trauma and orthopaedic surgery patients remains low at 1.9%. There was no 30-day mortality in patients ASA 1 or 2. Patients with significant comorbidities, increasing age, and ASA 3 or above remain at the highest risk. For patients with COVID-19 infection, postoperative 30-day mortality was 14.8%. The reintroduction of elective services should consider individual patient risk profile (including for ASA grade). Effective postoperative strategies should also be employed to try and reduce postoperative exposure to the virus.Cite this article: Bone Joint Open 2020;1-7:392-397.

Trigeminal-mediated headshaking in horses: prevalence, impact, and management strategies.

Trigeminal-mediated headshaking is a little-understood neuropathic facial pain condition of the horse. The condition may affect around 1% of the equine population to a degree of severity sufficient to require veterinary attention. As a pain condition, this represents a significant welfare issue. Horses are usually more severely affected at exercise which can leave them unable to perform, or even dangerous to ride and handle. With little known about the condition and variable response to treatments, severely affected horses are often euthanized. This review article considers the literature on trigeminal-mediated headshaking, focusing on what is known, and indeed not known, about the prevalence of the condition and its impact. The current published management options are considered, along with their challenges and limitations.

Genome Assembly and Annotation of the Trichoplusia ni Tni-FNL Insect Cell Line Enabled by Long-Read Technologies.

BACKGROUND: Trichoplusiani derived cell lines are commonly used to enable recombinant protein expression via baculovirus infection to generate materials approved for clinical use and in clinical trials. In order to develop systems biology and genome engineering tools to improve protein expression in this host, we performed de novo genome assembly of the Trichoplusiani-derived cell line Tni-FNL. METHODS: By integration of PacBio single-molecule sequencing, Bionano optical mapping, and 10X Genomics linked-reads data, we have produced a draft genome assembly of Tni-FNL. RESULTS: Our assembly contains 280 scaffolds, with a N50 scaffold size of 2.3 Mb and a total length of 359 Mb. Annotation of the Tni-FNL genome resulted in 14,101 predicted genes and 93.2% of the predicted proteome contained recognizable protein domains. Ortholog searches within the superorder Holometabola provided further evidence of high accuracy and completeness of the Tni-FNL genome assembly. CONCLUSIONS: This first draft Tni-FNL genome assembly was enabled by complementary long-read technologies and represents a high-quality, well-annotated genome that provides novel insight into the complexity of this insect cell line and can serve as a reference for future large-scale genome engineering work in this and other similar recombinant protein production hosts.

Trigeminal Nerve Root Demyelination Not Seen in Six Horses Diagnosed with Trigeminal-Mediated Headshaking.

Trigeminal-mediated headshaking is an idiopathic neuropathic facial pain syndrome in horses. There are clinical similarities to trigeminal neuralgia, a neuropathic facial pain syndrome in man, which is usually caused by demyelination of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. Our hypothesis was that the neuropathological substrate of headshaking in horses is similar to that of trigeminal neuralgia in man. Trigeminal nerves, nerve roots, ganglia, infraorbital, and caudal nasal nerves from horse abattoir specimens and from horses euthanized due to trigeminal-mediated headshaking were removed, fixed, and processed for histological assessment by a veterinary pathologist and a neuropathologist with particular experience of trigeminal neuralgia histology. No histological differences were detected between samples from horses with headshaking and those from normal horses. These results suggest that trigeminal-mediated headshaking may have a different pathological substrate from trigeminal neuralgia in man.

Primary intraocular primitive neuroectodermal tumor (retinoblastoma) causing unilateral blindness in a gelding.

A 14-year-old gray gelding was presented for investigation of a visible, pale-colored ocular mass in the right eye. An intraocular mass was identified clinically and ultrasonographically as originating from the superior nasal quadrant of the ciliary body and retina. The mass occupied the majority of the vitreous chamber and some of the superior anterior chamber of the eye. The affected eye was blind. Following exenteration, a primary intraocular primitive neuroectodermal tumor (i.e. a retinoblastoma/medulloepithelioma), a rarely described intraocular mass in adult horses, was identified by pathologic examination. The gelding returned to normal use following a short recovery period.