Microtubule organization within mitotic spindles revealed by serial block face scanning electron microscopy and image analysis

Serial block face scanning electron microscopy (SBF-SEM) is a powerful method to analyze cells in 3D. Here, working at the resolution limit of the method, we describe a correlative light-SBF-SEM workflow to resolve microtubules of the mitotic spindle in human cells. We present four examples of uses for this workflow that are not practical by light microscopy and/or transmission electron microscopy. First, distinguishing closely associated microtubules within K-fibers; second, resolving bridging fibers in the mitotic spindle; third, visualizing membranes in mitotic cells, relative to the spindle apparatus; and fourth, volumetric analysis of kinetochores. Our workflow also includes new computational tools for exploring the spatial arrangement of microtubules within the mitotic spindle. We use these tools to show that microtubule order in mitotic spindles is sensitive to the level of TACC3 on the spindle

The Agewell trial: a pilot randomised controlled trial of a behaviour change intervention to promote healthy ageing and reduce risk of dementia in later life.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk. We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness, diet and health. METHODS: This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation, provide preliminary evidence regarding efficacy, and explore feasibility and acceptability. Primary outcomes were engagement in physical and cognitive activity. Participants aged over 50 living independently in the community were recruited through a community Agewell Centre. Following baseline assessment participants were randomly allocated to one of three conditions: control (IC) had an interview in which information about activities and health was discussed; goal-setting (GS n = 24) had an interview in which they set behaviour change goals relating to physical, cognitive and social activity, health and nutrition; and goal-setting with mentoring (GM, n = 24) had the goal-setting interview followed by bi-monthly telephone mentoring. Participants and researchers were blinded to group assignment. Participants were reassessed after 12 months. RESULTS: Seventy-five participants were randomised (IC n = 27, GS n = 24, GM n = 24). At 12-month follow-up, the two goal-setting groups, taken together (GS n = 21, GM n = 22), increased their level of physical (effect size 0.37) and cognitive (effect size 0.15) activity relative to controls (IC n = 27). In secondary outcomes, the two goal-setting groups taken together achieved additional benefits compared to control (effect sizes ≥ 0.2) in memory, executive function, cholesterol level, aerobic capacity, flexibility, balance, grip strength, and agility. Adding follow-up mentoring produced further benefits compared to goal-setting alone (effect sizes ≥ 0.2) in physical activity, body composition, global cognition and memory, but not in other domains. Implementation of the recruitment procedure, assessment and intervention was found to be feasible and the approach taken was acceptable to participants, with no adverse effects. CONCLUSIONS: A brief, low-cost goal-setting intervention is feasible and acceptable, and has the potential to achieve increased activity engagement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30080637.This trial was funded by Medical Research Council grant G1001888/1 to LC, JVH, IRJ, JT and CJW. The funding body played no role in the design of the study, in collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We acknowledge the support of Age Cymru Gwynedd a Môn including John Clifford Jones, Maldwyn Roberts, Stephen Williams and Mici Plwm. We would like to thank Sharman Harris and Catrin Searell, Department of Clinical Chemistry, Ysbyty Gwynedd, Bangor, the volunteers at the Nefyn Agewell Centre, and all the members of the Nefyn Agewell Centre, and especially all those who took part in the research project. We are grateful to Professor Carol Brayne, Cambridge University, Professor Martin Knapp, London School of Economics, Professor Mike Martin, Zürich University, and Professor Robin Morris, King’s College London Institute of Psychiatry, who acted as external advisors to the project. Special thanks go to Andrew Brand for statistical advice

Regeneration of the Semitendinosus Tendon Harvested for Anterior Cruciate Ligament Reconstruction. Evaluation Using Ultrasonography

In a prospective study, 40 consecutive patients who underwent anterior cruciate ligament reconstruction with doubled semitendinosus and gracilis tendon autografts were examined pre- and postoperatively by ultrasound to investigate the anatomy of the donor site before and after the harvest of the tendons. The patients underwent ultrasonography at 2 weeks and 1, 2, 3, 6, 12, 18, and 24 months postoperatively. A total of 298 postoperative sonographic evaluations were performed. The semitendinosus tendon was imaged in the sagittal and axial planes: structure and margins were evaluated with the sagittal views; thickness and width were measured with the axial views. In all cases the following sequence of healing was documented: 2 weeks after surgery the semitendinosus tendon site was occupied by an area of increased thickness and decreased echogenicity, suggesting the presence of traumatic edema of the soft tissue surrounding the tenotomy. At 1 month, an irregular hypoechoic structure appeared in a near-anatomic position; at 2 months after surgery, thickness, width, and cross-sectional area of this structure were significantly greater than preoperatively. The amount of regenerated tissue increased up to that seen in the tissue of the 6-month examinations, which also showed a more uniform echostructure. The scans performed at 1 year showed distinct edges and reduction in thickness and width. At 18 and 24 months the echogenicity of the structure occupying the donor site was very similar to that of the normal semitendinosus tendon. However, this structure was clearly identified about 4 cm proximal to the pes anserinus, revealing a more proximal insertion of the regenerated semitendinosus tendon

Best practice in reducing the suicide risk in head and neck cancer patients: a structured review

The treatment of head and neck cancer (HNC) is often radical and the patient’s journey challenging, especially for individuals who are struggling with pre-existing mental health problems and who lack social support. Patients frequently suffer from high levels of emotional distress at some point before, during, or after treatment, and their risk of suicide is markedly elevated. This structured review aimed to identify the extent of the problem, appropriate interventions, and areas for future research. We found that the incidence of suicide among HNC patients was significantly elevated above that of the demographically matched general population. Furthermore, the risk was frequently higher in patients with HNC than in those with cancers in other sites. Despite the clear burden of suicide in patients with HNC, there is an absence of evidence on interventions used to reduce suicidal ideation and the risk of suicide. Recommendations for practice are made, drawing from the wider literature on the prevention of suicide

Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.

Peer reviewedPublisher PD

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Conservative treatment of a comminuted cervical fracture in a racehorse

The 'classical' or 'Hangman' neck fracture involves the odontoid peg (process) of the second cervical vertebra (C2), and is described as an axial, dens or odontoid peg fracture in both the veterinary and human literature. Possible surgical treatment in both foals and adult horses requires a technique that allows decompression, anatomical alignment and stabilisation of the odontoid fracture. A limited number of surgical cases in foals have been reported in literature, but never in an adult horse. A mature Irish Thoroughbred racehorse was diagnosed with a type 2a odontoid peg fracture. Clinical signs included reluctance to move the head and neck, a left hind limb lameness and a neurological status of grade 2. The horse was treated conservatively and raced successfully five months after the diagnosed injury