Expression of smooth muscle actin in osteoblasts in human bone.

It is well known that certain connective tissue cells (viz., dermal fibroblasts) can express the gene for a muscle actin--alpha-smooth muscle actin--and can contract. This process contributes to skin wound closure and is responsible for Dupuytren's contracture. The objective of this study was to determine if human osteoblasts can also express the gene for alpha-smooth muscle actin. Immunohistochemistry using a monoclonal antibody for alpha-smooth muscle actin was performed on human cancellous bone samples obtained from 20 individuals at the time of total joint arthroplasty. The percentages of resting and active osteoblasts on the bone surfaces containing this muscle actin isoform were evaluated. Explants of human bone were also studied for the expression of alpha-smooth muscle actin in the tissue and in the outgrowing cells with time in culture. Western blot analysis was performed to quantify the alpha-smooth muscle actin content of the outgrowing cells relative to smooth muscle cell controls. Nine +/- 2% (mean +/- SEM; n = 20) of the cells classified as inactive osteoblasts and 69 +/- 3% (n = 19) of the cells identified as active osteoblasts on the bone surface contained alpha-smooth muscle actin. This difference was highly statistically significant (Student's t test, p < 0.0001). Similar profiles of alpha-smooth muscle actin-expressing cells were found in explants cultured for up to 12 weeks. Cells forming a layer on the surface of the explants and growing out from them in monolayer also contained alpha-smooth muscle actin by immunohistochemistry and Western blot analysis. Human osteoblasts can express the gene for alpha-smooth muscle actin. This expression should be considered a phenotypic characteristic of this cell type, conferred by its progenitor cells: bone marrow stromal-derived stem cells, and perhaps pericytes and smooth muscle cells.     

Promoting Responsible Electronic Documentation: Validity Evidence for a Checklist to Assess Progress Notes in the Electronic Health Record

Construct: We aimed to develop an instrument to measure the quality of inpatient electronic health record– (EHR–) generated progress notes without requiring raters to review the detailed chart or know the patient. Background: Notes written in EHRs have generated criticism for being unnecessarily long and redundant, perpetuating inaccuracy and obscuring providers' clinical reasoning. Available assessment tools either focus on outpatient progress notes or require chart review by raters to develop familiarity with the patient. Approach: We used medical literature, local expert review, and attending focus groups to develop and refine an instrument to evaluate inpatient progress notes. We measured interrater reliability and scored the selected-response elements of the checklist for a sample of 100 progress notes written by PGY-1 trainees on the general medicine service. Results: We developed an instrument with 18 selected-response items and four open-ended items to measure the quality of inpatient progress notes written in the EHR. The mean Cohen's kappa coefficient demonstrated good agreement at .67. The mean note score was 66.9% of maximum possible points (SD = 10.6, range = 34.4%–93.3%). Conclusions: We present validity evidence in the domains of content, internal structure, and response process for a new checklist for rating inpatient progress notes. The scored checklist can be completed in approximately 7 minutes by a rater who is not familiar with the patient and can be done without extensive chart review. We further demonstrate that trainee notes show substantial room for improvement.     

A Systematic Review of Randomized Controlled Trials of Interventions to Improve the Health of Persons During Imprisonment and in the Year After Release

We systematically reviewed randomized controlled trials of interventions to improve the health of people during imprisonment or in the year after release. We searched 14 biomedical and social science databases in 2014, and identified 95 studies.Most studies involved only men or a majority of men (70/83 studies in which gender was specified); only 16 studies focused on adolescents. Most studies were conducted in the United States (n = 57). The risk of bias for outcomes in almost all studies was unclear or high (n = 91). In 59 studies, interventions led to improved mental health, substance use, infectious diseases, or health service utilization outcomes; in 42 of these studies, outcomes were measured in the community after release.Improving the health of people who experience imprisonment requires knowledge generation and knowledge translation, including implementation of effective interventions.Worldwide, more than 11 million people are imprisoned at any given time, and the prison population continues to grow at a rate faster than that of the general population.1 Substantial evidence reveals that people who have experienced imprisonment have poor health compared with the general population, as indicated by the prevalence of mental illness, infectious diseases, chronic diseases, and mortality.2There are several reasons to focus on improving the health of people who experience imprisonment.3 The burden of disease in this population affects the general population directly through increased health care costs and through the transmission of communicable diseases (e.g., HIV, HCV, and tuberculosis) after people are released from detention. Imprisonment has also been associated with worse health in family members of those who are detained, compared with the general population, including chronic diseases4 and poor mental health5,6 in adult relatives and mortality in male children.7 At the community level, higher rates of incarceration have been associated with adverse health outcomes, such as sexually transmitted infections and teen pregnancies.8 There is also evidence that poor health in persons who are released from detention, particularly those with inadequately treated mental illness and substance use disorders,3 may affect public safety and reincarceration rates,3 and that better access to health care is associated with less recidivism.9,10 Finally, the right to health and health care is enshrined in international human rights documents,11,12 and is a legislated responsibility of governments in many countries.Intervening during imprisonment and at the time of release could improve the health of people who experience imprisonment and public health overall.13 Knowledge translation efforts, such as syntheses of effective interventions, could lead to the implementation and further evaluation of interventions,14 and identify areas where further research is needed. To date, only syntheses with a limited focus have been conducted in this population, for example, reviews of interventions related to HIV15 or for persons with serious mental illness.16 Decision makers, practitioners, and researchers in this field would benefit from a broader understanding of the state of evidence regarding interventions to improve health in people who experience imprisonment.To address this gap, we systematically reviewed randomized controlled trials of interventions to improve health in persons during imprisonment and in the year after release. We chose this population because we view imprisonment as a unique opportunity to deliver and to link with interventions for this population, and to highlight interventions that could be implemented by those responsible for the administration of correctional facilities. We limited this study to randomized controlled trials, recognizing that randomized controlled trials provide the highest quality of evidence compared with other study designs.17     

A robust estimate of the number and characteristics of persons released from prison in Australia

Objective: To estimate the number and characteristics of adults released from prison in Australia. Method: We calculated ratios, stratified by age, sex and Indigenous status, by comparing the number of persons released from prison in New South Wales (NSW), with the number in NSW prisons on 30 June of the corresponding year. These stratified ratios were applied to Australia‐wide prison data to estimate the number and characteristics of persons released annually. Results: We estimated that in 2013, 38,576 persons were released from prison in Australia ? 25.3% more than the daily prison population. Young people, Indigenous people and women were over‐represented among those released. We estimated that 3.69 Indigenous women aged 18–24 were released annually for each equivalent person in prison; and 2.75 non‐Indigenous women aged 18–24 were released annually for each equivalent person in prison. Conclusions: The annual ‘flow’ through Australia's prisons is well in excess of the daily number, but information on those moving through prison systems is not yet publicly available. The characteristics of those released from prison differ meaningfully from those of people in prison. Routine, national reporting of prison separations is critical to informing upscaling and targeting of Throughcare services for this profoundly vulnerable population.     

Aldosterone-stimulated down-regulation of both type I and type II adrenocorticosteroid receptors in mouse brain is mediated via type I receptors

The concentrations of type I and type II adrenocorticosteroid receptors in brain cytosol obtained from adrenalectomized-ovariectomized female mice were measured with five different assay conditions. Among the five brain regions studied, hippocampus had the highest concentration of type I receptors, whereas cerebral cortex had the highest concentration of type II receptors. The value of properly correcting for dexamethasone cross-binding to type I receptors when type II receptors are being assayed was demonstrated using the type II receptor-selective ligand RU28362. A time-course study revealed a transient up-regulation of both receptor classes in most brain regions after adrenalectomy-ovariectomy, with maximal values achieved 3-5 days postsurgery and a reduction to near-intact levels by 16 days postsurgery. A single sc injection of aldosterone given to adrenalectomized-ovariectomized mice produced a profound down-regulation of type I receptors in hippocampal, cerebral cortex, hypothalamic, brain stem, and cerebellar samples, whereas it down-regulated type II receptors only in hippocampal and cerebral cortical samples. A similar injection of RU28362 failed to down-regulate type I receptors in any brain region, but it did reduce the concentration of type II receptors in all brain regions except cerebellum. The actions of aldosterone appear to be mediated solely through type I receptors, since injections of the type I receptor antagonist RU26752 prevented aldosterone-induced down-regulation of both type I and type II receptors, whereas RU26752 had no effect on the down-regulatory actions of RU28362. The ability of aldosterone to down-regulate type I, but not type II, receptors in hypothalamic, brain stem, and cerebellar samples suggests that type I and type II receptors are concentrated in separate populations of cells in these brain regions, whereas in hippocampus and cerebral cortex there is a sufficient degree of colocalization to permit type II receptor down-regulation via the action of aldosterone-type I receptor complexes. We speculate that this action is mediated at least in part at the genomic level by the suppression of type I and type II receptor mRNA synthesis brought about by the interactions of transformed aldosterone-type I receptor complexes with the DNA regulatory elements upstream from the genes for these receptors.     

2D measurements of cup orientation are less reliable than 3D measurements

Background and purpose — 2D analysis of metal-on-metal (MoM) hip arthroplasty (HA) has been conducted in several large series on conventional radiographs with the use of Ein Bild Roentegen Analyse (EBRA) software, but there have been no comparisons with 3D analysis in the literature. The main aim of this study was to quantify the agreement in measurements of cup version of large-diameter MoM hips obtained by EBRA and by 3D computed tomography (3D-CT). The secondary aim was to quantify the agreement for cup inclination. Lastly, we wanted to determine the inter- and intra-observer reliability of both methods.

Patients and methods — 87 MoM hips in 81 patients were analyzed for cup inclination and version in 2D on conventional radiographs using EBRA software. The results were compared with 3D measurements using CT.

Results — Cup version was underestimated by EBRA when compared to 3D-CT, by 6° on average with the pelvis supine and by 8° on average with the pelvis orientated to the anterior pelvic plane (APP). For inclination, the mean difference was no more than 1°. 53% of hips were within a 10° safe zone of 45° inclination and 20° version when measured by 3D-CT with the pelvis supine (and 54% with the pelvis in the APP). The proportion was only 24% when measured by EBRA. Inter- and intra-observer reliability of cup version is poorer using 2D analysis than when using 3D-CT.

Interpretation — Errors in version in 2D were due to the difficulty in delineating the cup rim, which was obscured by a large-diameter metal head of the same radio-opacity. This can be overcome with 3D analysis. The present study demonstrates that measurements using EBRA have poor agreement and are less reliable than those with 3D-CT when measuring cup version and inclination in MoM hips.     

Hormone therapy for radiorecurrent prostate cancer

Background

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option.

Methods

Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer.

Results

Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence.

Conclusions

Hormone therapy remains an option for men with radiorecurrent prostate cancer.     

Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity

Journal of Neurology - Therapy of autoimmune diseases of the central and peripheral nervous system with intravenous IgG immunoglobulin (IVIg) is well established. Since IVIg is produced from pooled...     

Extraartikuläre Skapula- und Skapulafortsatzfrakturen

Extra-articular scapula fractures are rare injuries, which are often associated in high-energy trauma or in multiple injured cases. In the past extra-articular scapula fractures were treated conservatively and randomized treatment studies had been rare for those cases. However, biomechanical studies of the scapula, newly designed anatomical implants as well as minimal invasive approaches to the scapula have improved the operative treatment in those cases. However, in principle only dislocated and instable extra-articular scapula fractures should be addressed operatively.