MicroRNAs regulate synaptic plasticity underlying drug addiction.

Chronic use of drugs of abuse results in neurochemical, morphological and behavioral plasticity that underlies the emergence of compulsive drug seeking and vulnerability to relapse during periods of attempted abstinence. Identifying and reversing addiction-relevant plasticity is seen as a potential point of pharmacotherapeutic intervention in drug-addicted individuals. Despite considerable advances in our understanding of the actions of drugs of abuse in the brain, this information has thus far yielded few novel treatment options addicted individuals. MicroRNAs are small noncoding RNAs that can each regulate the translation of hundreds to thousands of messenger RNAs. The highly pleiotropic nature of miRNAs has focused attention on their contribution to addiction-relevant structural and functional plasticity in the brain and their potential utility as targets for medications development. In this review, we discuss the roles of miRNAs in synaptic plasticity underlying the development of addiction and then briefly discuss the possibility of using circulating miRNA as biomarkers for addiction.

Serum N-Terminal Type III Procollagen Propeptide: An Indicator of Growth Hormone Excess and Response to Treatment in Feline Hypersomatotropism.

BACKGROUND: N-terminal type III procollagen propeptide (PIIINP) is a biomarker of soft tissue proliferation. Hypersomatotropism (HS) is associated with soft tissue proliferation. HYPOTHESIS: Serum PIIINP is increased in cats with HS and decreases with effective treatment, and may be an additional tool in the diagnosis and treatment of feline HS. ANIMALS: Cats with uncomplicated diabetes mellitus (DM; n = 30) and with HS-induced DM (HSDM; n = 30). Pre- and posttreatment samples were available from 5 cats undergoing radiotherapy (RT) and 16 cats undergoing hypophysectomy (HPX). METHODS: Retrospective and prospective cross-sectional study. Analytical performance of a serum PIIINP ELISA was assessed and validated for use in cats. PIIINP and insulin-like growth factor 1 (IGF-1) radioimmunoassays (RIA) were performed pre- and post-treatment in cats with DM and HSDM. PIIINP and IGF-1 were compared between cats treated by RT and HPX. RESULTS: Serum PIIINP concentrations were significantly higher (P < .001) in HSDM cats (median, 19.6 ng/mL; range, 1.7-27.9) compared to DM cats (median, 5.0 ng/mL; range, 2.1-10.4). A cut-off of 10.5 ng/mL allowed differentiation between DM and HSDM cats with 87% sensitivity and 100% specificity (area under the curve [AUC], 0.91; 95% confidence interval [CI], 0.82-1). After RT, PIIINP increased significantly (P = .043) with no significant change in IGF-1 concentrations. After HPX, serum PIIINP (P = .034) and IGF-1 concentrations (P < .001) decreased significantly. CONCLUSION AND CLINICAL IMPORTANCE: PIIINP concentrations are increased in cats with untreated HSDM compared to those with DM, demonstrating the effect of excess GH on soft tissue. PIIINP concentrations decreased after HPX in most HSDM cats.

Risk factors for early post-operative neurological deterioration in dogs undergoing a cervical dorsal laminectomy or hemilaminectomy: 100 cases (2002-2014).

Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25-64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post-operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures.

Expectations of General Practitioners for Patients Undergoing Elective Total Knee Arthroplasty.

Most patients undergoing total knee arthroplasty (TKA) in Ireland are referred to orthopaedic services by their general practitioners (GPs). We aimed to evaluate Irish GPs' expectations for their patients' perioperative experience and post-operative return to function. A questionnaire was mailed to 350 GPs in all provinces. This included questions relating to GPs' expectations for their patients and their knowledge and sources of information on TKA. 111 completed questionnaires were returned (response rate 31.7%). Overall expectations for functional and psychological outcomes were high, especially regarding pain relief (108 (97.3%)) expected relief from most or all pre-operative pain), mobility (108 (97.3%)) expected patients to walk medium or long distances) and psychological wellbeing (95 (85.5%) considered this somewhat or very important). Only 22 (20.2%) reported receiving any relevant information or training within the previous year. Overall expectations for functional outcomes were high, however greater communication between surgeons and GPs may improve GP information,

Clinical reasoning in canine spinal disease: what combination of clinical information is useful?

Spinal disease in dogs is commonly encountered in veterinary practice. Numerous diseases may cause similar clinical signs and presenting histories. The study objective was to use statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination that could suggest the most likely diagnoses with statistical significance. A retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals before June 2012 for the investigation of spinal disease was performed. Details regarding signalment, history, physical and neurological examinations, neuroanatomical localisation and imaging data were obtained. Univariate analyses of variables (breed, age, weight, onset, deterioration, pain, asymmetry, neuroanatomical localisation) were performed, and variables were retained in a multivariate logistic regression model if P<0.05. Leading diagnoses were intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate logistic regression characterised IM and acute non-compressive nucleus pulposus extrusions as the only peracute onset, non-progressive, non-painful and asymmetrical T3-L3 myelopathies. IVDE was most commonly characterised as acute onset, often deteriorating, painful and largely symmetrical T3-L3 myelopathy. This study suggests that most spinal diseases cause distinctive combinations of presenting clinical parameters (signalment, onset, deterioration, pain, asymmetry, neuroanatomical localisation). Taking particular account of these parameters may aid decision making in a clinical setting.

Consultant and trainee attitudes towards supervision of operative procedures in the UK and Ireland.

The e-logbook is used to monitor progression through training and to assess training within teaching units. We document consultant and trainee opinions with regards to supervision status, and to inform guidelines for trainees and trainers using the e-logbook. A questionnaire was sent to consultants and trainees in the UK and Ireland. Eight theatre scenarios were described and respondents were asked to state what they felt was the appropriate supervision status for the trainee. Significantly more consultants in the UK use the e-logbook than those based in Ireland (58.5%:14.5%). There were differences in consensus response to the scenarios between consultants and trainees, and between Irish and UK based surgeons. We have documented the opinions of consultants and trainees from across the UK and Ireland with regards to supervision status for trainees under certain theatre situations. This information should support formal guidelines for all users of the logbook.

The Irish National Joint Registry: where are we now?

BACKGROUND: Ireland is currently in the process of establishing a National Joint Registry. AIM: We aim to determine which implants and surgical techniques are currently being used by Irish orthopaedic surgeons and to examine the impact that a National Joint Registry may have on arthroplasty practice in Ireland. METHODS: The study consisted of a postal questionnaire sent to all public service consultant orthopaedic surgeons in The Republic of Ireland. RESULTS: We had a response rate of 76.6 %. Of this 76.6, 86.4 % regularly perform total hip arthroplasty (THA) and 84.7 % perform total knee arthroplasty. Of those who perform THA, 86.3 % use different implants in younger patients. Thirteen different femoral implants are used, and seven different knee implants. We conservatively estimate that at least 3,918 total hip arthroplasties and 2,604 total knee arthroplasties are performed in Ireland each year. At present we have no way to precisely monitor the number of arthroplasty procedures being performed, and we have no way of accurately monitoring the short- or long-term outcomes of the many implants used. CONCLUSIONS: The establishment of a National Joint Registry for Ireland would benefit the Irish orthopaedic community, and given the large number of procedures being performed, may also be of benefit to the international orthopaedic community.

Publication rates of presentations at the Irish Orthopaedic Association annual meeting.

BACKGROUND: Presentation of scientific research at national and international meetings is an important forum for the dissemination of knowledge. Subsequent publication of a full-text paper in a peer-reviewed journal is the expected outcome of such presentations. The publication rate from these meetings is highly variable. AIMS: To determine the publication rate of abstracts presented at the Irish Orthopaedic Association's Annual Conference and to determine which factors are associated with progression to full-text publication. METHODS: We reviewed the proceedings from the Irish Orthopaedic Association's National Meeting over a 4 year period. We searched the Pubmed database using author names, institution names, and keywords from each abstract's title, to determine how many presented articles progressed to full-text publication. RESULTS: Sixty-six of 203 were published, 97 % within 5 years of presentation. Laboratory based studies presenting novel or innovative findings were more likely to be published than clinical studies. Clinical studies were more likely to be published if they were prospective and had a longer period of follow-up. Retrospective audits were less likely to be published, even with a large cohort size. Changes in authorship of presented papers were related to a longer delay in time to full-text publication. CONCLUSIONS: Thorough planning of research studies is essential to ensure a timely progression to full-text publication in a peer-reviewed journal. Most studies will be published within 5 years of initial presentation.

Migraine-like episodic pain behavior in a dog: can dogs suffer from migraines?

Migraines and other primary headache disorders commonly affect people. There is evidence to suggest that migraines can occur in dogs. In this review, we present a dog with paroxysmal episodes that have a striking resemblance to human migraine, and we give an overview of migraine in people. The current classification, clinical signs, and diagnosis in people are discussed, as well as the anatomy of head pain, pathophysiology, pharmacology, and treatment options.

Biomarkers for smoking cessation.

One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification.

The effect of inclement weather on ankle fracture management in an Irish trauma unit.

INTRODUCTION: Ireland is unfamiliar with extreme weather conditions. Such conditions occurred in winter 2009-2010 and 2010-2011, with much of the country being affected by snow and ice. We reviewed the effect that these conditions had on the treatment of ankle fractures in our trauma unit. MATERIALS AND METHODS: The study period was from November until February for four consecutive years from 2008-2009 until 2011-2012. We compared two winters with extreme weather with two winters with regular weather conditions. Information from Met Eireann was compared with demographics from patient records to differentiate ice-related injuries from non-ice-related injuries. Ankle fractures were classified using the Lauge-Hansen classification. We compared waiting times in A&E, waiting times for theatre, delays relating to injury severity, and overall length of stay for both groups. RESULTS: We identified 44 ice-related injuries and 67 non-ice-related injuries. Ice-related injuries trended towards more severe fracture configurations using the Lauge-Hansen classification. Patients sustaining ankle injuries during inclement weather were significantly younger than patients sustaining injuries during regular weather conditions. There were no other significant differences between the two groups. DISCUSSION: Ice-related injuries trended towards a greater severity of fracture configuration. We identified no significant increase in the time to treatment or overall length of stay of patients sustaining ankle fractures during these times. Ice-related injuries did not have greater rates of complications. These results are a testament to the trauma staff in this unit who absorbed the increased workload without compromising patient care.

Intra-abdominal blockage of a ventriculoperitoneal shunt by a suspected mesenteric pseudocyst in a dog.

BACKGROUND: There are few reports of abdominal complications following ventriculoperitoneal (VP) shunt placement for the treatment of hydrocephalus in dogs. CASE REPORT: A 3-year-old dog underwent successful VP shunting for the treatment of hydrocephalus, but re-presented 10 months later with progressive central vestibular syndrome. Magnetic resonance imaging of the brain suggested VP catheter obstruction. The dog was euthanased and on postmortem examination the abdominal tip of the VP catheter was ensheathed and blocked by fibrous mesentery, possibly a pseudocyst. CONCLUSIONS: Abdominal complications are common in humans, with pseudocysts reported in up to 4.5% of cases. This diagnosis should be considered for dogs re-presenting following VP shunt surgery.

Cervical vertebral stenosis associated with a vertebral arch anomaly in the Basset Hound.

OBJECTIVES: To report the clinical presentation, imaging characteristics, treatment results, and histopathological findings of a previously undescribed vertebral malformation in the Basset Hound. ANIMALS AND METHODS: Retrospective case series study. Eighteen Basset Hounds presented for evaluation of a suspected cervical spinal cord problem. All dogs underwent computed tomography myelography or magnetic resonance imaging of the cervical region. RESULTS: Thirteen male and 5 female Basset Hounds between 6 months and 10.8 years of age (median: 1.4 years) were studied. Clinical signs varied from cervical hyperesthesia to nonambulatory tetraparesis. Imaging demonstrated a well-defined and smooth hypertrophy of the dorsal lamina and spinous process of ≥ 2 adjacent vertebrae. Although this bony abnormality could decrease the ventrodorsal vertebral canal diameter, dorsal midline spinal cord compression was predominantly caused by ligamentum flavum hypertrophy. The articulation between C4 and C5 was most commonly affected. Three dogs were lost to follow-up, 10 dogs underwent dorsal laminectomy, and medical management was initiated in 5 dogs. Surgery resulted in a good outcome with short hospitalization times (median: 4.5 days) in all dogs, whereas medical management produced more variable results. Histopathology confirmed ligamentum flavum hypertrophy and demonstrated the fibrocartilaginous nature of this anomaly. CONCLUSIONS AND CLINICAL IMPORTANCE: Dorsal lamina and spinous process hypertrophy leading to ligamentum flavum hypertrophy should be included in the differential diagnosis of Basset Hounds with cervical hyperesthesia or myelopathy. Prognosis after decompressive surgery is favorable. Although a genetic component is suspected, additional studies are needed to determine the specific etiology of this disorder.

Research in higher surgical training: which rotation?

BACKGROUND: Orthopaedic higher surgical trainees in Ireland are allocated to one of eight training rotations. Each trainee is expected to publish at least one research paper per year during training. AIM: To assess the research productivity of each training rotation over a 10-year period. METHODS: A PubMed search was performed for each orthopaedic unit affiliated to higher surgical training (HST) in order to identify full-text research papers published between 2001 and 2010. The results were analysed to determine which training rotations are most productive in terms of research. RESULTS: We identified 267 papers published from 16 units over the 10-year period. There were substantial differences in the number of papers published from each unit, and substantial differences between the eight set trainee rotations. CONCLUSIONS: It is essential that each trainee makes an honest assessment of their potential for conducting and producing valuable and relevant research, and chooses an HST rotation that is appropriate to their needs. Publication of research articles is easier to achieve on some HST rotations than on others.

The cervical spine of professional front-row rugby players: correlation between degenerative changes and symptoms.

BACKGROUND: Injuries to the cervical spine (C-spine) are among the most serious in rugby and are well documented. Front-row players are particularly at risk due to repetitive high-intensity collisions in the scrum. AIM: This study evaluates degenerative changes of the C-spine and associated symptomatology in front-row rugby players. MATERIALS AND METHODS: C-spine radiographs from 14 professional rugby players and controls were compared. Players averaged 23 years of playing competitive rugby. Two consultant radiologists performed a blind review of radiographs evaluating degeneration of disc spaces and apophyseal joints. Clinical status was assessed using a modified AAOS/NASS/COSS cervical spine outcomes questionnaire. RESULTS: Front-row rugby players exhibited significant radiographic evidence of C-spine degenerative changes compared to the non-rugby playing controls (P < 0.005). Despite these findings the rugby players did not exhibit increased symptoms. CONCLUSION: This highlights the radiologic degenerative changes of the C-spine of front-row rugby players. However, these changes do not manifest themselves clinically or affect activities of daily living.