Idiopathic pulmonary fibrosis (IPF) is a diagnostically challenging disease. Clinicians are faced with the need to exclude alternative diagnoses, limited treatment and management guidelines, and few treatment options. Patients with IPF have significantly increased healthcare usage compared with similar patients without the disease.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
November 2017
The results of the CANTOS trial provide exciting evidence in support of the inflammatory hypothesis of atherosclerosis in humans, and is the first phase III clinical trial to show clinical benefit of a targeted anti-inflammatory therapy. However, the modest overall clinical benefit and safety concerns with increased susceptibility to fatal infections indicate that we need much more work in this critical area.
View Article and Find Full Text PDFA deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation.
View Article and Find Full Text PDFHigh-throughput sequencing using the Illumina HiSeq platform is a pervasive and critical molecular ecology resource, and has provided the data underlying many recent advances. A recent study has suggested that "index switching," where reads are misattributed to the wrong sample, may be higher in new versions of the HiSeq platform. This has the potential to invalidate both published and in-progress work across the field.
View Article and Find Full Text PDFThe production of large quantities of functional vascularized bone tissue ex vivo still represent an unmet clinical challenge. Microcarriers offer a potential solution to scalable manufacture of bone tissue due to their high surface area-to-volume ratio and the capacity to be assembled using a modular approach. Microcarriers made of phosphate bioactive glass doped with titanium dioxide have been previously shown to enhance proliferation of osteoblast progenitors and maturation towards functional osteoblasts.
View Article and Find Full Text PDFThe present study examined the predictive role of increased self-reported mindfulness skills on reduced trauma-related guilt in a sample of veterans over the course of residential treatment for posttraumatic stress disorder (PTSD; N = 128). The residential treatment consisted of seven weeks of intensive cognitive processing therapy (CPT) for PTSD, as well as additional psychoeducational groups, including seven sessions on mindfulness skills. Increased mindfulness skills describing, acting with awareness, and accepting without judgment were significantly associated with reductions in trauma-related guilt over the course of treatment.
View Article and Find Full Text PDFNeuromyelitis optica (NMO) is an inflammatory disorder mediated by antibodies to aquaporin-4 (AQP4) with prominent blood-brain barrier (BBB) breakdown in the acute phase of the disease. Anti-AQP4 antibodies are produced mainly in the periphery, yet they target the astrocyte perivascular end feet behind the BBB. We reasoned that an endothelial cell-targeted autoantibody might promote BBB transit of AQP4 antibodies and facilitate NMO attacks.
View Article and Find Full Text PDFAdaptation to new environments often occurs in the face of gene flow. Under these conditions, gene flow and recombination can impede adaptation by breaking down linkage disequilibrium between locally adapted alleles. Theory predicts that this decay can be halted or slowed if adaptive alleles are tightly linked in regions of low recombination, potentially favouring divergence and adaptive evolution in these regions over others.
View Article and Find Full Text PDFObjectives: Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disorder of the central nervous system (CNS) targeted against aquaporin-4 (AQP4). The origin and trafficking of AQP4-specific B cells in NMOSD remains unknown.
Methods: Peripheral ( = 7) and splenic B cells ( = 1) recovered from seven NMOSD patients were sorted into plasmablasts, naïve, memory, and CD27-IgD- double negative (DN) B cells, and variable heavy chain (VH) transcriptome sequences were generated by deep sequencing.
Swipe and wipe are types of transfer patterns commonly encountered at bloodied scenes. So far, there have been little published data on the reliability of evaluating these patterns. In this study, 36 bloodstain patterns were randomly assigned to 12 analysts in three separate trials, and the analysts were required to evaluate the pattern type and directionality.
View Article and Find Full Text PDFBackground And Aims: The patterning of floral ultraviolet (UV) pigmentation varies both intra- and interspecifically in sunflowers and many other plant species, impacts pollinator attraction, and can be critical to reproductive success and crop yields. However, the genetic basis for variation in UV patterning is largely unknown. This study examines the genetic architecture for proportional and absolute size of the UV bullseye in Helianthus argophyllus , a close relative of the domesticated sunflower.
View Article and Find Full Text PDFHistotripsy is a non-invasive therapeutic technique that uses ultrasound generated from outside the body to create controlled cavitation in targeted tissue, and fractionates it into acellular debris. We have developed a new histotripsy approach, termed microtripsy, to improve targeting accuracy and to avoid collateral tissue damage. This in vivo study evaluates the safety and efficacy of microtripsy for non-invasive thrombolysis in a porcine deep vein thrombosis model.
View Article and Find Full Text PDFProlonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours.
View Article and Find Full Text PDFIntrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF.
View Article and Find Full Text PDFThis study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO) were monitored throughout the procedure and for 1 h post-treatment.
View Article and Find Full Text PDFAtherosclerotic plaque rupture with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke. Although smooth muscle cells (SMCs) produce and respond to collagens in vitro, there is no direct evidence in vivo that SMCs are a crucial source of collagens and that this impacts lesion development or fibrous cap formation. We sought to determine how conditional SMC-specific knockout of collagen type XV (COL15A1) in SMC lineage tracing mice affects advanced lesion formation given that ) we have previously identified a sequence variant associated with age-related atherosclerosis, ) COL15A1 is a matrix organizer enhancing tissue structural integrity, and ) small interfering RNA-mediated knockdown increased migration and decreased proliferation of cultured human SMCs.
View Article and Find Full Text PDFLinking molecular evolution to biological function is a long-standing challenge in evolutionary biology. Some of the best examples of this involve opsins, the genes that encode the molecular basis of light reception. In this issue of Molecular Ecology, three studies examine opsin gene sequence, expression and repertoire to determine how natural selection has shaped the visual system.
View Article and Find Full Text PDFCould improving the design of preclinical murine atherosclerosis studies help increase the success rate of cardiovascular clinical trials? In this , the authors advocate for a change from prevention to intervention study designs and rigorous lesion analyses which they argue will enhance the translational potential of murine atherosclerosis studies.
View Article and Find Full Text PDFThe purpose of this study was to determine whether or not the dual constant-depth film fermenter (dCDFF) is able to produce caries-like enamel lesions and to ascertain further information regarding the performance of this fully functional biological caries model. Conditions were defined by the continuation (CF) or cessation (FF) of a saliva-type growth medium supply during 50-mM sucrose exposures (8 times daily). Hydroxyapatite (n = 3) and bovine enamel (n = 3) substrata were included within each condition and samples extracted after 2, 4, 8, and 16 days.
View Article and Find Full Text PDFMany studies have noted similarities between atherosclerosis and cancer including pronounced cellular plasticity, clonal expansion of cellular subtypes, increased DNA mutations, defective efferocytosis pathways, and an important role for proto-oncogenes in disease development. Although it is clear that these 2 diseases have disparate causes, noting the parallels between atherosclerosis and cancer may help us identify unique, targeted therapeutic strategies.
View Article and Find Full Text PDFUrocortin (UCN1) peptide shares structural and functional homology with corticotropin-releasing factor (CRF). UCN1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN1 in the endometrium, or how it is modulated.
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