Search

Introduction: Wildland fires degrade air quality and adversely affect human health. A growing body of epidemiology literature reports increased rates of emergency departments, hospital admissions and premature deaths from wildfire smoke exposure., Objective: Our research aimed to characterize excess mortality and morbidity events, and the economic value of these impacts, from wildland fire smoke exposure in the U.S. over a multi-year period; to date no other burden assessment has done this., Methods: We first completed a systematic review of the epidemiologic literature and then performed photochemical air quality modeling for the years 2008 to 2012 in the continental U.S. Finally, we estimated the morbidity, mortality, and economic burden of wildland fires., Results: Our models suggest that areas including northern California, Oregon and Idaho in the West, and Florida, Louisiana and Georgia in the East were most affected by wildland fire events in the form of additional premature deaths and respiratory hospital admissions. We estimated the economic value of these cases due to short term exposures as being between $11 and $20B (2010$) per year, with a net present value of $63B (95% confidence intervals $6-$170); we estimate the value of long-term exposures as being between $76 and $130B (2010$) per year, with a net present value of $450B (95% confidence intervals $42-$1200)., Conclusion: The public health burden of wildland fires-in terms of the number and economic value of deaths and illnesses-is considerable., (Published by Elsevier B.V.)

We report an optimized method for RNA extraction from human articular cartilage that does not require the use of specialized equipment or column purification. To maximize RNA yield while minimizing degradation and contamination, chondrocytes are isolated from the extracellular matrix and the traditional TRIzol protocol is modified to include two RNA-DNA-protein phase separations. We compared RNA extracted using this modified method with the traditional TRIzol method by spectrophotometry, Bioanalyzer, and real-time polymerase chain reaction (PCR). With the modified method, RNA recovery is increased by nearly 1μg per 100mg of cartilage, and RNA integrity number (RIN) is improved from 2.0 to 7.5., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Vascularized composite allotransplantation as a viable reconstructive option is gaining recognition and new cases are being reported with increasing frequency including hand, face and laryngeal transplantation. However, only one successful complete lower limb transplantation has been reported to date, in which a functioning limb from one ischiopagus twin with a lethal cardiac anomaly was transplanted to the other. Six years later, the patient is mobilizing well and engaging in sporting activities with her peers in a mainstream school. Clinical evaluation of motor and sensory modalities demonstrated a good functional result. Quality of life was assessed using the short form-36 health survey and lower extremity functional scale disclosing a high level of social and physical capacity. Functional magnetic resonance imaging was performed and showed cortical integration of the limb; the implications of cortical plasticity and vascularized composite allotransplantation for the correction of congenital limb anomalies are presented., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Obliterative bronchiolitis (OB) is thought to be a form of chronic allograft rejection. However, immunosuppressive therapy is not effective once fibrosis has developed. We hypothesize that disordered tissue remodeling is a mechanism for the pathogenesis of OB. We examined allograft airway fibrosis in an intrapulmonary tracheal transplant model of OB. Allograft airways were completely obliterated at day 21 by fibrotic tissue; however, tissue remodeling continued thereafter, as demonstrated by the change of collagen deposition density, shift from type I to type III collagen, shift from fibroblasts to myofibroblasts and shift of expression profiles and activities of matrix metalloproteinases (MMPs). We then used a broad-spectrum MMP inhibitor, SC080, to attempt to manipulate tissue remodeling. Administration of the MMP inhibitor from day 0 to day 28 reduced airway obliteration, without inhibiting T-cell activation. MMP inhibition from day 14 to day 28 showed similar effects on airway obliteration. MMP inhibition from day 21 to day 35 did not reverse the airway obliteration, but significantly reduced the collagen deposition, type III collagen and myofibroblasts in the lumen. We conclude that tissue remodeling plays a critical role in the development and maintenance of fibrosis after transplantation.

Background: Radiographs are ordered routinely for children with ankle trauma. We assessed the predictive value of a clinical examination to identify a predefined group of low-risk injuries, management of which would not be affected by absence of a radiograph. We aimed to show that no more than 1% of children with low-risk examinations (signs restricted to the distal fibula) would have high-risk fractures (all fractures except avulsion, buckle, and non-displaced Salter-Harris I and II fractures of the distal fibula), and to compare the potential reduction in radiography in children with low-risk examinations with that obtained by application of the Ottawa ankle rules (OAR)., Methods: Standard clinical examinations and subsequent radiographs were prospectively and independently evaluated in two tertiary-care paediatric emergency departments in North America. Eligible participants were healthy children aged 3-16 years with acute ankle injuries. Sample size, negative and positive predictive values, sensitivity, and specificity were calculated. McNemar's test was used to compare differences in the potential reduction in radiographs between the low-risk examination and the OAR., Findings: 607 children were enrolled; 581 (95.7%) received follow-up. None of the 381 children with low-risk examinations had a high-risk fracture (negative predictive value 100% [95% CI 99.2-100]; sensitivity 100% [93.3-100]). Radiographs could be omitted in 62.8% of children with low-risk examinations, compared with only 12.0% reduction obtained by application of the OAR (p<0.0001)., Interpretation: A low-risk clinical examination in children with ankle injuries identifies 100% of high-risk diagnoses and may result in greater reduction of radiographic referrals than the OAR.

Aggressive fibromatosis is a monoclonal proliferation of spindle (fibroblast-like) cells. A subset of lesions contain somatic truncating adenomatous polyposis coli (APC) gene mutations, and all of the lesions contain an elevated beta-catenin protein level. A major function of APC is to regulate beta-catenin protein level. Beta-catenin has a dual function in the cell: it is a member of the adherens junction, and it binds transcription factors in the tcf-lef family, transactivating transcription. Cell cultures from aggressive fibromatoses containing an APC mutation were studied. Transient transfection of the full-length APC gene caused decreased proliferation and beta-catenin protein level in these cultures. To determine whether beta-catenin protein level was responsible for the change in proliferation rate, stable transfections of deltaN89beta-catenin (a stabilized form that is not degraded by APC, but retains all other functions) were achieved in half of the cultures derived from each tumor, whereas the other half were transfected with an empty vector. Transfection of the full-length APC gene in cultures that were stably transfected with deltaN89beta-catenin did not result in a change in proliferation. The type I promotor of p56lck contains an HMG consensus region, to which members of the tcf-lef family can bind. p56lck was expressed in cultures not transfected with the full-length APC gene and in cultures transfected with the full-length APC gene and deltaN89beta-catenin, but not in cultures transfected with only the full-length APC gene. These data show that APC truncating mutations give aggressive fibromatosis cells a proliferative advantage through beta-catenin and suggest that beta-catenin acts to transactivate transcription.

Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.