Trypanosome mRNAs share a common 5' spliced leader sequence.

A 5'-terminal leader sequence of 35 nucleotides was found to be present on multiple trypanosome RNAs. Based on its representation in cDNA libraries, we estimate that many, if not all, trypanosome mRNAs contain this leader. This same leader was originally identified on mRNAs encoding the molecules responsible for antigenic variation, variant surface glycoproteins. Studies of selected cDNAs containing this leader sequence revealed that leader-containing transcripts can be stage-specific, stage-regulated, or constitutive. They can be abundant or rare, and transcribed from single or multigene families. No linkage between the genomic leader sequences and the structural gene exons was observed. Possible mechanisms by which the leader sequences are added to trypanosome mRNAs are discussed

Multiple parallel skin markers for minimal incision lumbar disc surgery; a technical note

BACKGROUND: Spinal surgery depends on accurate localization to prevent incorrect surgical approaches. The trend towards minimally invasive surgery that minimizes surgical exposure and reduces postoperative pain increasingly requires surgeons to accurately determine the operative level before an incision is made. Preoperative localization with a C-arm image intensifier is popular, but the exposure of both patients and theatre staff to radiation is a disadvantage, as well as being time-consuming. METHODS: We describe a simple surgical tool developed to help localize exact spinal levels in conjunction with a simple AP X-ray film immediately before surgery. Multiple parallel skin markers were made using a circular oven rack comprising multiple 1.5 cm spaced parallel wires attached to a circular outside rim. The longest line was placed on the line of the postero-superior iliac spine (PSIS) over the junction of the L5-S1 region. RESULTS AND CONCLUSIONS: Based on the film taken, the incision can be accurately made at the intended level. The incision wound can be minimized to 3.0 cm even when using conventional disc surgery instruments

Renal epithelial cells retain primary cilia during human acute renal allograft rejection injury

OBJECTIVES: Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. RESULTS: Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary cilium-mediated activation of hedgehog signalling is still possible during the acute phase of renal allograft rejection

Caregiver delivered sensory electrical stimulation for post stroke upper limb spasticity: A single blind crossover randomized feasibility study

We developed a 64 channel sensory electrical stimulator which delivers a dynamic and variable ‘Sensory Barrage’ Stimulation (SBS). Our aim was to assess the feasibility of caregivers delivering the stimulation in the community for a clinical trial comparing single channel Transcutaneous Electrical Nerve Stimulation (TENS) with SBS for post stroke upper limb spasticity. We trained caregivers of 16 participants with post stroke upper limb spasticity to sequentially administer SBS and TENS for 60 min daily for four weeks each, with a washout period of two weeks in between. Outcome measures tested were recruitment and retention rates, compliance with interventions and daily recording of Participant -reported Numerical Rating Scale (NRS). We also collected results of Action Research Arm Test (ARAT), Leeds Arm Spasticity Impact Scale (LASIS) and Modified Ashworth Scale (MAS) for spasticity. Out of 21 potential participants, 16 consented and 15 completed the protocol. Ten participants received TENS for 80% (23/28) of the intended hours. Eleven participants completed NRS for at 80% (45/56) of the study days. All participants attended all visits. The MAS reduced by at least one in five participants after SBS and in three after TENS. Minimal Clinically Important Difference (MCID) of four points increase in ARAT was seen in five participants following TENS, and in four following SBS. A MCID of 18% decrease in NRS was reported by eight participants after TENS and three after SBS. This study demonstrated the feasibility of undertaking a trial of sensory electrical stimulation for post-stroke spasticity with caregivers delivering intervention in community. The study was not powered to detect efficacy of the interventions. Trial registration number: NCT02907775.Date 20-9-2016

The propensity to adopt evidence-based practice among physical therapists

<p>Abstract</p> <p>Background</p> <p>Many authors, as well as the American Physical Therapy Association, advocate that physical therapists adopt practice patterns based on research evidence, known as evidence-based practice (EBP). At the same time, physical therapists should be capable of integrating EBP within the day-to-day practice of physical therapy. The purpose of this study was to determine the extent to which personal characteristics and the characteristics of the social system in the workplace influence the propensity of physical therapists to adopt EBP.</p> <p>Methods</p> <p>The study used a 69 item mailed self-completion questionnaire. The questionnaire had four major sections. The first three sections were each drawn from a different theoretical framework and from different authors' work. The instrument was developed to capture the propensity of physical therapists to adopt EBP, characteristics of the social system in the workplace of physical therapists, personal characteristics of physical therapists, and selected demographic variables of physical therapists. The eligible population consisted of 3,897 physical therapists licensed by the state of Georgia in the United States of America. A random sample of 1320 potential participants was drawn.</p> <p>Results</p> <p>939 questionnaires were returned for a response rate of 73%. 831 of the participants' questionnaires were useable and became the basis for the study. There was a moderate association between desire for learning (<it>r </it>= .36, <it>r</it>²= .13), highest degree held (<it>r </it>= .29, <it>r</it>²= .08), practicality (<it>r </it>= .27, <it>r</it>²= .07) and nonconformity (<it>r </it>= .24, <it>r</it>²= .06) and the propensity to adopt EBP. A negative correlation was found between age, years licensed and percentage of time in direct patient care. The findings demonstrated that the best three variables for predicting the propensity to adopt EBP in physical therapy were: desire for learning, highest degree held, and practicality.</p> <p>Conclusion</p> <p>The study confirms there is no single factor to facilitate research evidence into day-to-day practice. Multiple practice change strategies will be needed to facilitate change in practice.</p

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

The presentation, clinical features, complications, and treatment of congenital dacryocystocele

Purpose To determine the incidence and presenting features of congenital dacryocystocele in the United Kingdom. To report on those cases complicated by dacryocystitis, respiratory compromise, and the treatment undertaken. Methods A prospective observational study of cases of congenital dacryocystocele presenting in the United Kingdom between September 2014 and October 2015. Infants <3 months of age presenting with a cystic swelling in the medial canthal area were included. Cases were identified via the British Ophthalmology Surveillance Unit (BOSU) reporting system. Results A total of 49 cases were reported during the study period. This gives an incidence of 1 in 18 597 live births. There was a 71% response rate to the questionnaire. The average age at presentation was 16.94 days. Dacryocystoceles were unilateral in 91% of cases. Dacryocystitis was a complicating factor in 49% of patients and 17% had respiratory distress. Uncomplicated dacryocystocele responded well to conservative measures in 86%. Surgical intervention was required in 23% of patients. Those cases complicated by dacryocystitis (29%) and nasal obstruction (17%) were more likely to require surgical intervention compared to those with dacryocystocele alone (14%). Digital massage appears to reduce the likelihood of requiring surgical intervention. The mean time to resolution was 19 days. Conclusions Congenital dacryocystocele is a rare presentation in the United Kingdom. Dacryocystitis and respiratory compromise commonly complicate a dacryocystocele. The use of digital massage as an early intervention is advocated and conservative measures may be sufficient in cases of uncomplicated dacryocystocele