Citations

Abstract A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre‐clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP‐43 inclusions, and recommend standard approaches for the workup of cases and their clinico‐pathologic correlation.

Abstract A complex network of transcription factors contributes to the establishment and maintenance of the osteoblastic phenotype. Although relatively few transcription factors, such as Runx2 and osterix, are essential to the process of osteoblastic differentiation, others serve the purpose of fine-tuning in response to various environmental and hormonal cues. The nuclear receptor (NR) superfamily of transcription factors are involved in numerous aspects of bone biology. In this study, we characterized the expression pattern of the entire NR superfamily in differentiating primary murine calvarial cells in order to identify novel NR regulatory patterns. Dynamic patterns of NR expression were observed throughout the differentiation process. Interestingly, retinoic acid receptor-related orphan receptor β (Rorβ) expression was markedly suppressed at later stages of differentiation. To gain further insight into the function of NRs in bone biology, the NR superfamily was also profiled in mouse bone marrow precursor cells isolated from either young (6-month) or aging, osteoporotic (18–22-month) mice. Of interest, Rorβ was potently overexpressed in the aged cohort. Collectively, these data provided evidence that Rorβ expression is inversely correlated with osteogenic potential, suggesting Rorβ may be an important and unexplored regulator of osteogenesis. To validate this hypothesis, a cell model stably expressing Rorβ in mouse osteoblastic MC3T3-E1 cells was produced (MC3T3-Rorβ). These cells displayed markedly suppressed bone nodule formation as well as reduced osteocalcin and osterix gene expression. Because these genes are Runx2 targets, we reasoned that Rorβ may interfere with Runx2 activity. Consistent with this, transient transfection analysis demonstrated that Rorβ inhibited Runx2-dependent activation of a Runx2-reporter construct. In summary, our data provide a comprehensive profile of NR expression during osteoblast differentiation and identify Rorβ as a novel regulator of osteogenesis and potentially of age-related bone loss through antagonism of Runx2 activity. © 2012 American Society for Bone and Mineral Research.

In the past several decades, the fields of ultrasound and magnetic resonance elastography have shown promising results in noninvasive estimates of mechanical properties of soft tissues. These techniques often rely on measuring shear wave velocity due to an external or internal source of force and relating the velocity to viscoelasticity of the tissue. The mathematical relationship between the measured velocity and material properties of the myocardial wall, arteries, and other organs with non-negligible boundary conditions is often complicated and computationally expensive. A simple relationship between the Lamb–Rayleigh dispersion and the shear wave dispersion is derived for both the velocity and attenuation. The relationship shows that the shear wave velocity is around 20% higher than the Lamb–Rayleigh velocity and that the shear wave attenuation is about 20% lower than the Lamb–Rayleigh attenuation. Results of numerical simulations in the frequency range 0–500 Hz are presented.

AbstractOver the past several years, genome‐wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large‐Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large‐scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene‐gene and gene‐environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized.Genet. Epidemiol. 36 : 22–35, 2012. © 2011 Wiley Periodicals, Inc.

AbstractIt has been well established that a high level of stress is associated with medical problems, mental health difficulties and absenteeism at the workplace. The aim of this single‐arm study design was to examine the potential effectiveness of a 12‐session multidisciplinary stress reduction programme on reducing perceived stress and improving health behaviours and quality of life. One hundred and four women participated in a programme that incorporated group support, skill building and cognitive behavioural and relaxation techniques. A series of Bonferroni corrected t‐tests found that the participants reported having significantly (p < 0.001) lower levels of perceived stress, improved health behaviours (sleep, nutrition, physical activity) improved overall health and improved quality of life at the end of the 12 week programme and at 1‐month follow‐up. Although the effect sizes for improvement were all large, there was no control group, so regression to the mean or selection bias may have impacted the results. Therefore, these results provide initial support for the implementation of gender‐based worksite stress reduction programmes and provide guidance in designing an effective worksite stress reduction programme. Further research using randomized controlled trials is warranted. Copyright © 2011 John Wiley & Sons, Ltd.

ABSTRACT Assays that detect treponema-specific antibodies, which are either automated or can be done as point-of-care tests, have been developed, some of which are FDA approved. These assays have the advantage of being easily performed and demonstrate high sensitivity, both key features of an infectious disease screening test. As a result, many high-volume clinical laboratories have begun to offer a reverse syphilis testing algorithm where a treponema-specific test is used for screening, followed by a nontreponemal test (i.e., rapid plasma reagin [RPR]) to assess disease activity and treatment status. Concerns about physicians being able to understand and apply this new testing algorithm have been expressed (8). In this point-counterpoint, Michael Loeffelholz of the University of Texas Medical Branch at Galveston explains why his laboratory has adopted this reverse algorithmic approach. Matthew Binnicker of the Mayo Clinic, Rochester, MN, explains why the reverse algorithm may not be suitable for all clinical laboratories and every clinical situation.

ABSTRACT We describe the first direct comparison of the reverse and traditional syphilis screening algorithms in a population with a low prevalence of syphilis. Among 1,000 patients tested, the results for 6 patients were falsely reactive by reverse screening, compared to none by traditional testing. However, reverse screening identified 2 patients with possible latent syphilis that were not detected by rapid plasma reagin (RPR).