Vertebral deformity is the classical hallmark of osteoporosis. Three types of vertebral deformity are usually described: crush, wedge and biconcave deformities. However, there are few data concerning ...the descriptive epidemiology of the individual deformity types, and differences in their underlying pathogenesis and clinical impact remain uncertain. The aim of this study was to compare the epidemiological characteristics of the three types of vertebral deformity and to explore the relationships of the number and type of deformity with back pain and height loss. Age-stratified random samples of men and women aged 50 years and over were recruited from population registers in 30 European centers (EVOS study). Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. The presence, type and number of vertebral deformities was determined using the McCloskey-Kanis algorithm. A total of13562 men and women were studied; mean age in men was 64.4 years (SD 8.5), and in women 63.8 years (SD 8.5 years). There was evidence of variation in the occurrence of wedge, crush and biconcave deformity by age, sex and vertebral level. Wedge deformities were the most frequent deformity and tended to cluster at the mid-thoracic and thoraco-lumbar regions of the spine in both men and women. Similar predilection for these sites was observed for crush and to a lesser extent biconcave deformities though this was much less marked than for wedge deformities. In both sexes the frequency of biconcave deformities was higher in the lumbar than the thoracic spine and unlike the other deformity types it did not decline in frequency at lower lumbar vertebral levels. The prevalence of all three types of vertebral deformity increased with age and was more marked in women. There were no important differences in the effect of age on the different deformity types. All types of deformity were associated with height loss, which was greatest for individuals with crush deformity. Back pain was also associated with all types of deformity.Overall, these results do not suggest important differences in pathophysiology between the three deformity types. Biomechanical factors appear to be important in determining their distribution within the spine. All deformity types are linked with adverse outcomes, though crush deformities showed greater height loss than the other deformity types.PUBLICATION ABSTRACT
The presence of a prevalent vertebral deformity increases the risk of a future vertebral fracture. The aim of this study was to determine whether certain characteristics of the prevalent deformity, ...including its shape and location in the spine, influenced this effect. The 3100 men and 3500 women who took part in this analysis were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects had lateral thoracic and lumbar spine x-rays at baseline, and again after a mean interval of 3.8 years. Prevalent morphometric vertebral deformities on the baseline film were identified by the McCloskey–Kanis method. Incident fractures were defined as vertebrae that also satisfied the McCloskey–Kanis criterion for prevalent deformities on the follow-up film, and in addition had at least one height (anterior, mid, or posterior) which had reduced by at least 20% between films. Poisson regression was used to assess the association between various characteristics of the prevalent deformity and the risk of an incident vertebral fracture, with generalised estimating equations used to allow for the fact that each subject contributed several vertebrae to the analysis. The risk of an incident fracture increased with the number of prevalent deformities: relative risk (RR) for one prevalent deformity 3.2 (95% confidence interval (CI); 2.1, 4.8); 9.8 (95% CI;6.1, 15.8) for 2; and 23.3 (95% CI;15.3, 35.4) for 3 or more. Relative risks differed significantly according to the shape of the prevalent deformity, ranging from 5.9 (95% CI; 4.1, 8.6) if the anterior and mid heights were reduced to 1.6 (95% CI;0.8, 3.2) if the posterior and mid heights were reduced. Risks varied also according to the severity of the deformity. There were fivefold differences in relative risk of incident fracture depending on the location of the prevalent deformity within the spine. Compared to vertebrae in subjects with no deformities at baseline, the relative risk of an incident fracture within three vertebrae of a prevalent deformity was greater (7.7 (95% CI;5.6, 10.5)) than the risk in more distant vertebrae (4.0 (95% CI;2.6, 6.0)). In summary, the risk of a subsequent vertebral fracture in individuals with preexisting deformities is importantly influenced by the characteristics of these deformities.
The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription ...factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML.
Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global ...experiments have been conducted that identify their cell type and cell stage-specific activity within one developmental pathway and in a chromatin context. Here, we describe a high-throughput method that identifies thousands of differentially active cis-elements able to stimulate a minimal promoter at five stages of hematopoietic progenitor development from embryonic stem (ES) cells, which can be adapted to any ES cell derived cell type. We show that blood cell-specific gene expression is controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work provides an important resource for studies of hematopoietic specification and highlights the mechanisms of how and where extrinsic signals program a cell type-specific chromatin landscape driving hematopoietic differentiation.
Abstract Objective To compare the effectiveness of self-collected and health care worker (HCW)–collected nasal swabs for detection of influenza viruses and determine the patients' preference for type ...of collection. Patients and Methods We enrolled adult patients presenting with influenzalike illness to the Emergency Department at Mayo Clinic, Rochester, Minnesota, from January 28, 2011, through April 30, 2011. Patients self-collected a midturbinate nasal flocked swab from their right nostril following written instructions. A second swab was then collected by an HCW from the left nostril. Swabs were tested for influenza A and B viruses by real-time reverse transcription–polymerase chain reaction, and percent concordance between collection methods was determined. Results Of the 72 paired specimens analyzed, 25 were positive for influenza A or B RNA by at least one of the collection methods (34.7% positivity rate). When the 14 patients who had prior health care training were excluded, the qualitative agreement between collection methods was 94.8% (55 of 58). Two of the 58 specimens (3.4%) from patients without health care training were positive only by HCW collection, and 1 of 58 (1.7%) was positive only by patient self-collection. A total of 53.4% of patients (31 of 58) preferred the self-collection method over the HCW collection, and 25.9% (15 of 58) had no preference. Conclusion Self-collected midturbinate nasal swabs provide a reliable alternative to HCW collection for influenza A and B virus real-time reverse transcription–polymerase chain reaction.
High-density lipoproteins (HDL) have been shown to reduce organ injury and mortality in animal models of shock via modulation of the expression of adhesion molecules and pro-inflammatory enzymes. As ...renal inflammation plays an important role in the development of ischemia/reperfusion (I/R) injury of the kidney, the aim of this study was to investigate the ability of HDL to alleviate renal dysfunction and injury in a rat model of renal I/R. HDL (80 mg/kg, intravenous) was administered to male Wistar rats 30 min before bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h. After 6-h reperfusion, HDL significantly reduced (1) renal and tubular dysfunction, (2) tubular and reperfusion-injury, and (3) histologic evidence of renal injury. HDL also improved renal function (after 24-h and 48-h reperfusion) and reduced histologic signs of renal injury (after 48-h reperfusion). Administration of HDL significantly reduced the numbers of polymorphonuclear leukocytes (PMN) infiltrating into renal tissues during reperfusion, which was reflected by an attenuation of the increase in renal myeloperoxidase activity caused by I/R. Furthermore, HDL markedly reduced expression of the adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), and P-selectin during reperfusion. The increase in renal malondialdehyde levels caused by renal I/R was also significantly reduced by HDL, suggesting attenuation of lipid peroxidation subsequent to oxidative stress. These results demonstrate that HDL significantly reduces renal I/R injury and severity of ischemic acute renal failure. It is proposed that the mechanism of protection involves reduction of the expression of adhesion molecules, resulting in reduction of PMN infiltration and oxidative stress.
At Mayo Medical Center (Rochester, MN), surveillance rectal (and other-site) cultures have been routinely collected from liver transplant recipients as part of a selective bowel decontamination ...program. Beginning in 1995, vancomycin-resistant enterococcus (VRE) colonization and infection were identified in Mayo Clinic liver and kidney transplant patients through our surveillance cultures. The purpose of this study is to describe the natural history of VRE colonization in this patient population. Fifty-two patients with VRE colonization (predominantly with a single vanB clone) were identified from September 1995 through December 1997. Five hundred ninety cultures were reviewed for this study (mean, 11.3 cultures/patient). The median time from initial VRE colonization to the last surveillance culture obtained was 306 days (range, 1 to 1,393 days). VRE infection was documented in 6 patients (11.3%). Eighteen patients (35%) met the criteria for clearance of VRE colonization, defined as VRE-negative rectal culture results on at least 3 consecutive occasions greater than 1 week apart. However, VRE was detected on subsequent surveillance cultures from 2 of these patients (11% relapse rate). Of the remaining 34 patients, 16 remained colonized with VRE and 18 did not meet the definition for clearance of VRE colonization because of incomplete follow-up. This study documents that VRE colonization usually persists for months to years in liver and kidney transplant patients. (Liver Transpl 2001;7:27-31.)
Computing in science and engineering is now ubiquitous: digital technologies underpin, accelerate, and enable new, even transformational, research in all domains. Access to an array of integrated and ...well-supported high-end digital services is critical for the advancement of knowledge. Driven by community needs, the Extreme Science and Engineering Discovery Environment (XSEDE) project substantially enhances the productivity of a growing community of scholars, researchers, and engineers (collectively referred to as "scientists"' throughout this article) through access to advanced digital services that support open research. XSEDE's integrated, comprehensive suite of advanced digital services federates with other high-end facilities and with campus-based resources, serving as the foundation for a national e-science infrastructure ecosystem. XSEDE's e-science infrastructure has tremendous potential for enabling new advancements in research and education. XSEDE's vision is a world of digitally enabled scholars, researchers, and engineers participating in multidisciplinary collaborations to tackle society's grand challenges.
Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In ...prosthetic-joint infection, microorganisms are typically present in a biofilm on the surface of the prosthesis. We hypothesized that culturing of samples obtained from the prosthesis would improve the microbiologic diagnosis of prosthetic-joint infection.
We performed a prospective trial comparing culture of samples obtained by sonication of explanted hip and knee prostheses to dislodge adherent bacteria from the prosthesis with conventional culture of periprosthetic tissue for the microbiologic diagnosis of prosthetic-joint infection among patients undergoing hip or knee revision or resection arthroplasty.
We studied 331 patients with total knee prostheses (207 patients) or hip prostheses (124 patients); 252 patients had aseptic failure, and 79 had prosthetic-joint infection. With the use of standardized nonmicrobiologic criteria to define prosthetic-joint infection, the sensitivities of periprosthetic-tissue and sonicate-fluid cultures were 60.8% and 78.5% (P<0.001), respectively, and the specificities were 99.2% and 98.8%, respectively. Fourteen cases of prosthetic-joint infection were detected by sonicate-fluid culture but not by prosthetic-tissue culture. In patients receiving antimicrobial therapy within 14 days before surgery, the sensitivities of periprosthetic tissue and sonicate-fluid culture were 45.0% and 75.0% (P<0.001), respectively.
In this study, culture of samples obtained by sonication of prostheses was more sensitive than conventional periprosthetic-tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection, especially in patients who had received antimicrobial therapy within 14 days before surgery.
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