KCTD1 and Scalp-Ear-Nipple ('Finlay-Marks') syndrome may be associated with myopia and Thin basement membrane nephropathy through an effect on the collagen IV α3 and α4 chains.

INTRODUCTION: Scalp-Ear-Nipple syndrome is caused by pathogenic KCTD1 variants and characterised by a scalp defect, prominent ears, and rudimentary breasts. We describe here further clinical associations in the eye and kidney. METHODS: Fifteen affected members from two unrelated families with p.(Ala30Glu) or p.(Pro31Leu) in KCTD1 were examined for ocular and renal abnormalities. The relevant proteins were studied in the eye and kidney, and the mutation consequences determined from mouse knockout models. RESULTS: Five males and 10 females with a median age of 40 years (range 1-70) with pathogenic variants p.(Ala30Glu) (n = 12) or p.(Pro31Leu) (n = 3) in KCTD1 were studied. Of the 6 who underwent detailed ophthalmic examination, 5 (83%) had low myopic astigmatism, the mean spherical equivalent of 10 eyes was 2.38D, and one (17%) had hypermetropic astigmatism. One female had a divergent strabismus.Five individuals had renal cysts (5/15, 33%), with renal biopsy in one demonstrating a thinned glomerular basement membrane identical to that seen in Thin basement membrane nephropathy (AD Alport syndrome).In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV α3 and α4 chains localised to the cornea and near the retinal amacrine cells. In the kidney, all these proteins except TFAP2 were expressed in the podocytes and distal tubules. TFAP2B and COL4A4 knockout mice also had kidney cysts, and COL4A3 and COL4A4 knockout mice had myopia. CONCLUSION: Individuals with a pathogenic KCTD1 variant may have low myopic astigmatism and represent a further rare genetic cause for a thinned glomerular basement membrane.

The modern UK veterinary profession: photo-elicitation interviewing reveals that small animal and surgical images dominate.

More than 80 per cent of vets are employed in clinical practice but other veterinary roles are vital for society. However, even clinical practice does not seem to fulfil some modern graduates, and an increasing number of veterinarians are leaving the profession to pursue other careers. Research suggests that less than 50 per cent of veterinarians would choose to undertake their career path again, so the profession faces a 'workforce crisis'. Through semi-structured photo-elicitation interviewing, this study has explored the image that students embarking on veterinary education have of the profession. The students' dominant image of the profession, and their perception of the public image, was small animal practice. A large proportion (n=16, 80 per cent) of participants saw themselves working in clinical practice, with many (n=8, 40 per cent) aspiring to focus on surgery. The image of the veterinary profession has changed since the 1970s when the James Herriot mixed practice model was well known to the public. The dominant small animal and surgical image emerging demonstrates a need for members of the profession to work together to educate public and entrant perception, emphasising the diversity of veterinary careers and their value to society, to allow aspiring veterinary entrants to develop a range of career goals.

A survey of current procedural practices of Australian and New Zealand nephrologists.

The aim of this study was to describe the range and extent of current procedural practices of Nephrologists and trainees in Australia and New Zealand with a specific focus on renal biopsy. A web-based survey was constructed based on a 2009 pilot survey conducted by the authors. The survey was distributed by email. A total of 118 responses were received from 60 centers, including six pediatric centers; Nephrologists or trainees performed the following procedures: urine microscopy 36.4%; diagnostic ultrasound 10.2%; renal biopsy 93.2%; simple vascath insertion 64.4%; cuffed vascath insertion 22%; peritoneal catheter insertion 16.9%; fistula ultrasound 20.3%; and fistulography 5%. Trainees performed most renal biopsies (67.8% of respondents) and real-time ultrasound was the commonest technique (97%). The majority of respondents believe that renal biopsy is an essential skill for trainees (78.8%); 10-25 biopsies are required for trainee proficiency (59.3%); an online training module would assist in teaching renal biopsies (67.8%). Cuffed catheter insertion and fistulography were more often performed in nonmetropolitan than in metropolitan centers. Procedures are part of Australian and New Zealand Nephrology, including specialized procedures in a minority of centers. Vascular access procedures are more common in nonmetropolitan centers. Renal biopsy is an important skill, considered essential for trainees by most.

Is surgery more effective than non-surgical treatment for spinal stenosis, and which non-surgical treatment is more effective? A systematic review.

BACKGROUND: Spinal stenosis can be treated both conservatively and with decompression surgery. OBJECTIVES: To explore the effectiveness of surgery vs conservative treatment, and conservative interventions for spinal stenosis. DATA SOURCES: Medline, CINAHL, AMED, PEDro and Cochrane databases, as well as the reference lists of retrieved studies. STUDY SELECTION: The search included non-English studies, and all conservative interventions were included. STUDY APPRAISAL: The PEDro scale was used to assess quality, and levels of evidence were used to synthesise studies where possible. RESULTS: Thirty-one studies met the inclusion criteria, and 18 were high-quality studies. Decompression surgery was more effective than conservative care in four out of five studies, but only one of these was of high quality. In six high-quality studies, there was strong evidence that steroid epidural injections were not effective; in four out of five studies (two of which were of high quality), there was moderate evidence that calcitonin was not effective. There was no evidence for the effectiveness of all other conservative interventions. LIMITATIONS: Further research is needed to determine if decompression surgery is more effective than conservative care, and which conservative care is most effective. CONCLUSION AND IMPLICATIONS: At present, there is no evidence that favours the effect of any conservative management for spinal stenosis. There is an urgent need to see if any conservative treatment can change pain and functional outcomes in spinal stenosis.

A mixed methods study to evaluate the clinical and cost-effectiveness of a self-managed exercise programme versus usual physiotherapy for chronic rotator cuff disorders: protocol for the SELF study.

BACKGROUND: Shoulder pain is the third most common reason for consultation with a physiotherapist and up to 26% of the general population might be expected to experience an episode at any one time. Disorders of the shoulder muscles and tendons (rotator cuff) are thought to be the commonest cause of this pain. The long-term outcome is frequently poor despite treatment. This means that many patients are exposed to more invasive treatment, e.g. surgery, and/or long-term pain and disability.Patients with this disorder typically receive a course of physiotherapy which might include a range of treatments. Specifically the value of exercise against gravity or resistance (loaded exercise) in the treatment of tendon disorders is promising but appears to be under-used. Loaded exercise in other areas of the body has been favourably evaluated but further investigation is needed to evaluate the impact of these exercises in the shoulder and particularly the role of home based or supervised exercise versus usual treatment requiring clinic attendance. METHODS/DESIGN: A single-centre pragmatic unblinded parallel group randomised controlled trial will evaluate the effectiveness of a self-managed loaded exercise programme versus usual clinic based physiotherapy. A total of 210 study participants with a primary complaint of shoulder pain suggestive of a rotator cuff disorder will be recruited from NHS physiotherapy waiting lists and allocated to receive a programme of self-managed exercise or usual physiotherapy using a process of block randomisation with sealed opaque envelopes. Baseline assessment for shoulder pain, function and quality of life will be undertaken with the Shoulder Pain & Disability Index, the Patient Specific Functional Scale and the SF-36. Follow-up evaluations will be completed at 3, 6 and 12 months by postal questionnaire. Both interventions will be delivered by NHS Physiotherapist's.An economic analysis will be conducted from an NHS and Personal Social Services perspective to evaluate cost-effectiveness and a qualitative investigation will be undertaken to develop greater understanding of the experience of undertaking or prescribing exercise as a self-managed therapy. TRIAL REGISTRATION NUMBER: ISRCTN84709751.

Risk factors for the onset of non-specific neck pain: a systematic review.

OBJECTIVE: Neck pain is a common musculoskeletal disorder, but little is known about which individuals develop neck pain. This systematic review investigated factors that constitute a risk for the onset of non-specific neck pain. DESIGN AND SETTING: A range of electronic databases and reference sections of relevant articles were searched to identify appropriate articles. Studies investigating risk factors for the onset of non-specific neck pain in asymptomatic populations were included. All studies were prospective with at least 1 year follow-up. MAIN RESULTS: 14 independent cohort studies met the inclusion criteria for the review. Thirteen studies were assessed as high quality. Female gender, older age, high job demands, low social/work support, being an ex-smoker, a history of low back disorders and a history of neck disorders were linked to the development of non-specific neck pain. CONCLUSIONS: Various clinical and sociodemographic risk factors were identified that have implications for occupational health and health policy. However, there was a lack of good-quality research investigating the predictive nature of many other variables.

Exploration of patients' perspectives of quality within an extended scope physiotherapists' spinal screening service.

Patient views about Extended Scope Physiotherapy services have rarely been sought. This study aimed to establish the dimensions of quality that were important to patients referred to such a service. This was a qualitative study using face-to-face semistructured interviews and was conducted at one tertiary teaching hospital in the United Kingdom. Thirty-four consecutive patients referred to a spinal extended physiotherapy practitioner service were invited to participate. Thirteen provided informed consent, and 12 were interviewed. Semistructured interviews were recorded and transcribed, and a framework qualitative data analysis was performed. Data analysis revealed five key themes that were important to the participants in the quality of the service: provision of information, professional skills, interpersonal skills, outcome, and patient care pathway. This study has produced key themes within the structure, process, and outcome of a spinal extended physiotherapy practitioner service that are determinants of quality by patients about to use this service. This preliminary work will be used to develop a questionnaire for patients using this service.

The comparative efficacy of percutaneous and surgical coronary revascularization in 2009: a review.

Medical, percutaneous, and surgical therapies for coronary atherosclerotic disease are developing rapidly, with many recent breakthroughs in metabolic control, improvements in catheter and stent engineering, and advances in surgical technique. Treatment guidelines are still in their infancy and do not take into account several of these recent innovations. Consequently, determining the most appropriate treatment for many patients remains challenging. In this review, we examine the most recent revascularization guidelines, discuss important new data and trials comparing contemporary stent technology and coronary artery bypass surgery, and conclude with updated revascularization recommendations.

Constitutive activation of c-Jun N-terminal kinase correlates with histologic grade and EGFR expression in diffuse gliomas.

The c-Jun NH2-terminal kinase (JNK), which belongs to mitogen-activated protein kinase family, plays a major role in apoptosis in various cell types. JNK activation, however, also contributes to proliferation, survival, and tumorigenesis in some tumors, including gliomas. In this study, we used an immunohistochemical approach to examine the activation status of JNK of 226 gliomas in a high-density tissue microarray comprising all WHO codified WHO diffuse glioma subtypes and grades. The results were correlated with grade and EGFR expression status. Constitutively activated JNK (pJNK) was detected in 90.5%, 62.9% and 17.5% of WHO grade IV, III and II gliomas, respectively (p < 0.001). pJNK expression was not detected in the astrocytes or oligodendrocytes of any of 10 normal cerebral and cerebellar brain tissue samples. Among the 76 diffuse gliomas that exhibited EGFR expression, 63 (82.9%) were positive for pJNK. In contrast, only 50% (36/72) of the gliomas that were negative for EGFR were positive for pJNK (p < 0.0001). Overexpression of EGFR vIII in U87 cells or EGF treatment of U87-EGFR stable cells led to marked increase in JNK activation compared to parental U87 cells. Our data thus provide strong support for the hypothesis that JNK activation plays a role in the tumorigenesis and/or progression of diffuse gliomas, and suggests that EGFR is involved in constitutive JNK activation in diffuse gliomas. The ability to inhibit JNK activation might confer increased sensitivity to therapeutic modalities targeting this pathway.

Evidence-informed management of chronic low back pain with the McKenzie method.

The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Heart transplantation in a patient with endomyocardial fibrosis due to hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES), a systemic disease that commonly involves the heart leading to progressive endomyocardial fibrosis, frequently manifests as restrictive cardiomyopathy. In this report, we describe the first case of a patient with endomyocardial fibrosis due to HES who underwent orthotopic heart transplantation at our institution. A literature review and discussion are included.

Classification by McKenzie mechanical syndromes: a survey of McKenzie-trained faculty.

OBJECTIVE: The purpose of this survey was to identify the percentage of patients with spine pain who can be classified by McKenzie-trained faculty as having one of either derangement, dysfunction, or postural syndromes. METHODS: McKenzie Institute International faculty members in 20 countries, who are highly trained and are experienced users of the classification system, recorded details on 15 consecutively discharged patients. RESULTS: Responses were received from 57 therapists in 18 countries (89% of potential sample), and details were collected on 607 patients with spine pain. Eighty-three percent were classified in one of the mechanical syndromes; derangement was the most common syndrome. Therapists recorded a mechanical classification in a mean of 82% (SD, 15.1; range, 44%-100%) of their patients with spine pain. CONCLUSIONS: For this study, the McKenzie mechanical syndromes were commonly diagnosed in a large consecutive group of patients at multiple sites by experienced therapists. This classification system may have valuable clinical use in managing patients with spine pain.

Centralization: its prognostic value in patients with referred symptoms and sciatica.

STUDY DESIGN: Prospective, comparative cohort study. OBJECTIVE: To investigate the prognostic significance of centralization in patients with subacute sciatica and referred symptoms. SUMMARY OF BACKGROUND DATA: Previous studies have shown that centralization occurs commonly in the nonspecific low back population, and its occurrence is associated with a good prognosis. The phenomenon has never been evaluated in a population with sciatica and referred symptoms. METHODS: The sample pool was 104 consecutive patients referred for investigation of possible disc herniation. Of these patients, 60 were recruited into the study and underwent a standardized mechanical evaluation using repeated end-range movements, while symptom response was monitored to expose 2 groups: centralization group (CG) and noncentralization group (NCG). All patients were treated in the same way and were followed for one year. If patients did not have improvement surgery was considered. Outcomes included back and leg pain, disability, Nottingham Health Profile, and surgical outcome. RESULTS: There were 25 patients who were classified in the CG, 35 in the NCG, and other baseline characteristics were similar between groups. At 1, 2, and 3 months, the CG had significantly better outcomes than the NCG. At 2 months, the CG had more improvements in leg pain (P = 0.007), disability (P = <0.001), and Nottingham Health Profile (P = 0.001). After 1 year, disability was less in the CG (P = 0.029). In the CG, 3 patients underwent surgery, in the NCG, 16 (P = 0.01). The odds ratio for surgery in the NCG was 6.2. CONCLUSION: Patients with sciatica and suspected disc herniation who have a centralization response to a mechanical evaluation will have significantly better outcomes. Patients who do not have centralization will be 6 times more likely to undergo surgery.

The centralization phenomenon of spinal symptoms--a systematic review.

The centralization phenomenon was first described 20 years ago. It refers to the abolition of distal pain emanating from the spine in response to therapeutic exercises. Since then a number of papers on the subject have been published. A review of current knowledge is appropriate. Selection criteria were established prior to a computer-aided search for published papers. Two reviewers independently extracted data and checked quality; a third reviewer resolved any disagreements. A narrative review was conducted based on the findings. The review primarily considered prevalence, reliability of assessment, and prognostic significance. These have been most commonly reported, and are important to establish the clinical worth of this symptom response. Fourteen studies were identified. Quality of studies varied; prognostic studies were given a mean score of 3.3 out of 6 by using established quality criteria. The prevalence rate of pure or partial centralization was 70% in 731 sub-acute back patients, and 52% in 325 chronic back patients. It is a symptom response that can be reliably assessed during examination (kappa values 0.51-1.0). Centralization was consistently associated with a range of good outcomes, and failure to centralize with a poor outcome. Centralization appears to identify a substantial sub-group of spinal patients; it is a clinical phenomenon that can be reliably detected, and is associated with a good prognosis. Centralization should be monitored in the examination of spinal patients.