Prediction of vertebral fractures under axial compression and anterior flexion

Vertebral fractures affect at least 12-20% of men and women over the age of 50, and the risk of fracture increases exponentially with age. Despite their high prevalence, the failure mechanisms leading to these fractures are not well understood. For example, clinical observations of fractured vertebra often note that one or both vertebral endplates have collapsed, but the precise involvement of the endplates in the initiation and progression of failure has not yet been defined. The mechanisms of failure may also relate to spatial variations in the density and microstructure of the porous trabecular bone within the vertebra as well as to the health of the adjacent intervertebral discs (IVDs) which transfer loads directly to the vertebral endplates. Delineating the contributions of these factors would shed light on the etiology of vertebral fractures and would aid in development of clinically feasible, patient-specific finite element (FE) models of the vertebra. These models are built from a patient's quantitative computed tomography (QCT) scan and have shown tremendous promise for accurate, patient-specific estimates of bone strength and fracture risk. Further validation studies are required to assess the impact of the choices of material properties and boundary conditions, as a prerequisite for broad implementation of these FE models in clinical care. The overall goal of this work was to define the failure processes involved in vertebral fractures and to evaluate the accuracy of patient-specific FE models in simulating these processes. Mechanical testing of human spine segments, in conjunction with micro-computed tomography, enabled the assessment of deformation at the vertebral endplate and deformation throughout the entire bone, as the vertebra was loaded to failure under both axial compression and anterior flexion. These data were compared against predictions of vertebral deformation obtained from QCT-based FE models. The impact of the choice of boundary conditions was specifically examined by comparing the accuracy of the FE predictions between models that simulated applied loads based on measured distributions of pressure within IVDs and models that used highly idealized boundary conditions. The results of these studies demonstrated that sudden and non-recoverable endplate deflection is a defining feature of biomechanical failure of the vertebra, for both compression and flexion loading. The locations of endplate collapse as vertebral failure progressed were associated with the porosity of the endplate and the microstructure of the underlying trabecular bone. FE analyses incorporating the experimentally observed endplate deflections as boundary conditions provided more accurate predictions of displacements throughout the rest of the vertebra when compared to FE models with highly idealized boundary conditions. Under anterior flexion, the use of boundary conditions informed by measurements of IVD pressure mitigated, but did not eliminate, the inaccuracy of the idealized boundary conditions. No further improvement in accuracy was found when using boundary conditions based on pressure measurements corresponding only to IVDs whose level of degeneration matched that observed in the IVDs adjacent to the vertebra being modeled. Overall, the accuracy of the FE predictions of vertebral deformation was only moderate, particularly near the locations of endplate collapse. The outcomes of this work indicate that the vertebral endplate is principally involved in vertebral fractures and that current methods for QCT-based FE models do not adequately capture this failure mechanism. These outcomes provide a biomechanical rationale for clinical diagnoses of vertebral fracture based on endplate collapse. These outcomes also emphasize that future studies of patient-specific FE models should incorporate physiologically relevant loading conditions and also material properties that more accurately represent the vertebral endplate in order to obtain higher fidelity predictions of vertebral failure

Physicians' Expectations of Benefit from Tube Feeding

Tube feeding is increasingly common, despite evidence for limited medical benefits. We interviewed treating physicians to describe their expectation of benefit for patients receiving a new feeding tube, and to determine whether expected benefits vary by patient characteristics

Spine and Pain Clinics Serving North Carolina Patients With Back and Neck Pain: What Do They Do, and Are They Multidisciplinary?

Cross-sectional survey

Exercise prescription for chronic back or neck pain: Who prescribes it? who gets it? What is prescribed?

While current practice guidelines promote exercise for chronic back and neck pain, little is known about exercise prescription in routine care. The objective of this study was to describe exercise prescription in routine clinical practice for individuals with chronic back or neck pain

The Rising Prevalence of Chronic Low Back Pain

National or state-level estimates on trends in the prevalence of chronic low back pain (LBP) are lacking. The objective of this study was to determine whether the prevalence of chronic LBP, and the demographic, health-related, and care-seeking characteristics of individuals with the condition have changed over the past 14 years

Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6. However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6. Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time. After only four weeks of culture, for all iPSC lines studied, such tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiological sarcomere length (2.2 µm) and density of mitochondria (30%), the presence of transverse tubules, oxidative metabolism, a positive force-frequency relationship and functional calcium handling. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, supporting the utility of this tissue model for studies of cardiac development and disease.The authors acknowledge funding support from the National Institutes of Health of the USA (NIBIB and NCATS grant EB17103 (G.V.-N.); NIBIB, NCATS, NIAMS, NIDCR and NIEHS grant EB025765 (G.V.-N.); NHLBI grants HL076485 (G.V.-N.) and HL138486 (M.Y.); Columbia University MD/PhD program (S.P.M., T.C.); University of Minho MD/PhD program (D.T.); Japan Society for the Promotion of Science fellowship (K.M.); and Columbia University Stem Cell Initiative (D.S., L.S., M.Y.). We thank S. Duncan and B. Conklin for providing human iPSCs, M.B. Bouchard for assistance with image and video analysis, and L. Cohen-Gould for transmission electron microscopy services.info:eu-repo/semantics/publishedVersio

Zebrafish brd2a and brd2b are paralogous members of the bromodomain-ET (BET) family of transcriptional coregulators that show structural and expression divergence

<p>Abstract</p> <p>Background</p> <p>Brd2 belongs to the bromodomain-extraterminal domain (BET) family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME) in humans. The <it>brd2 </it>ortholog in <it>Drosophila </it>is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of <it>Brd2 </it>developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of <it>brd2 </it>cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates.</p> <p>Results</p> <p>We identify cDNAs representing two paralogous <it>brd2 </it>loci in zebrafish, <it>brd2a </it>on chromosome 19 and <it>brd2b </it>on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of <it>brd2 </it>after gene duplication in fishes. <it>brd2 </it>paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA <it>in situ </it>hybridizations in oocytes and embryos implicate <it>brd2a </it>and <it>brd2b </it>as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of <it>brd2 </it>developmental expression in zebrafish are consistent with its proposed role in <it>Homeobox </it>gene regulation.</p> <p>Conclusion</p> <p>Expression profiles of zebrafish <it>brd2 </it>paralogs support a role in vertebrate developmental patterning and morphogenesis. Our study uncovers both maternal and zygotic contributions of <it>brd2</it>, the analysis of which may provide insight into the earliest events in vertebrate development, and the etiology of some forms of epilepsy, for which zebrafish is an important model. Knockdowns of <it>brd2 </it>paralogs in zebrafish may now test proposed function and interaction with homeotic loci in vertebrates, and help reveal the extent to which functional novelty or partitioning has occurred after gene duplication.</p

Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another

Dangerous human-made interference with climate: a GISS modelE study

We investigate the issue of "dangerous human-made interference with climate" using simulations with GISS modelE driven by measured or estimated forcings for 1880–2003 and extended to 2100 for IPCC greenhouse gas scenarios as well as the "alternative" scenario of Hansen and Sato (2004). Identification of "dangerous" effects is partly subjective, but we find evidence that added global warming of more than 1°C above the level in 2000 has effects that may be highly disruptive. The alternative scenario, with peak added forcing ~1.5 W/m2 in 2100, keeps further global warming under 1°C if climate sensitivity is ~3°C or less for doubled CO2. The alternative scenario keeps mean regional seasonal warming within 2σ (standard deviations) of 20th century variability, but other scenarios yield regional changes of 5–10σ, i.e. mean conditions outside the range of local experience. We conclude that a CO2 level exceeding about 450 ppm is "dangerous", but reduction of non-CO2 forcings can provide modest relief on the CO2 constraint. We discuss three specific sub-global topics: Arctic climate change, tropical storm intensification, and ice sheet stability. We suggest that Arctic climate change has been driven as much by pollutants (O3, its precursor CH4, and soot) as by CO2, offering hope that dual efforts to reduce pollutants and slow CO2 growth could minimize Arctic change. Simulated recent ocean warming in the region of Atlantic hurricane formation is comparable to observations, suggesting that greenhouse gases (GHGs) may have contributed to a trend toward greater hurricane intensities. Increasing GHGs cause significant warming in our model in submarine regions of ice shelves and shallow methane hydrates, raising concern about the potential for accelerating sea level rise and future positive feedback from methane release. Growth of non-CO2 forcings has slowed in recent years, but CO2 emissions are now surging well above the alternative scenario. Prompt actions to slow CO2 emissions and decrease non-CO2 forcings are required to achieve the low forcing of the alternative scenario