Hybrid Procedure for a Traumatic Aortic Rupture Consisting of Endovascular Repair and Minimally Invasive Arch Vessel Transposition without Sternotomy

Emergency surgical repair for acute traumatic aortic ruptures has been associated with a high peri-procedural mortality rate. Endovascular stent-grafting, as a less invasive procedure, has shown encouraging results. This report describes a patient with a short landing zone, who was treated by transposing the supra-aortic branch without sternotomy, followed by covered stent-grafting with an extended proximal bare portion to enhance fixation.     

Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma

Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d^−/− mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d^−/− mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d^−/− mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model.     

Genomic characterization of a cell-culture-adapted Korean human G9P[8] rotavirus, CAU05-202

The human rotavirus G9 strain is the fifth most common rotavirus worldwide. A human rotavirus G9P[8] strain CAU05-202 was isolated from a young child with diarrhea using a cell culture system, and its major gene sequences were determined. Phylogenetic analysis of the VP7 gene revealed that CAU05-202 clustered into genetic lineage III-d and was most closely related to G9 rotaviruses from Turkey (strain GUH13) and Sri Lanka (strain 05SLC056 and 05SLC057). VP4 and NSP4 gene analysis showed that CAU05-202 belongs to the P[8]-3 lineage and genotype B, respectively. In addition, CAU05-202 has a long RNA electropherotype, supported by VP6 gene analysis, which is clearly associated with subgroup II specificity. Analysis of the G9 rotavirus strain CAU05-202 provides information concerning the genetic relationships among global rotavirus G9 strains, suggesting that closely related G9 strains are persistent and widespread in Asian countries.     

Unitary bioresorbable cage/core bone graft substitutes for spinal arthrodesis coextruded from polycaprolactone biocomposites

A unitary bioresorbable cage/core bone graft substitute consisting of a stiff cage and a softer core with interconnected porosity is offered for spinal arthrodesis. Polycaprolactone, PCL, was used as the matrix and hydroxyapatite, HA, and β-tricalcium phosphate, TCP, were used in the formulation of the cage layer to impart modulus increase and osteoconductivity while the core consisted solely of PCL. The crystallinity, biodegradation rate (under accelerated conditions) and mechanical properties, i.e., the uniaxial compression, relaxation modulus upon step compression and cyclic compressive fatigue properties, of the co-extruded cage/core bone graft substitutes could be manipulated by changes in the concentration of HA/TCP in the cage layer. The cyclic fatigue behavior of the cage/core bone graft substitutes were also compared to the behavior of bovine vertebral cancellous bone characterized under similar testing conditions. The biocompatibility of the cage/core bone graft substitutes were assessed via in vitro culturing of human bone marrow derived stromal cells, BMSCs. The cell proliferation rates, time dependencies of the alkaline phosphates (ALP) activity and the expressions of bone markers, i.e., Runx2, ALP, collagen type I, osteopontin and osteocalcin, and the collected μ-CT images demonstrated the differentiation of BMSCs via osteogenic lineage and formation of mineralized bone tissue to indicate the biocompatibility of the cage/core bone graft substitutes.     

Effects of single-sided inferior turbinectomy on nasal function and airflow characteristics

Knowledge of airflow characteristics in the nasal cavity is essential to understanding the physiologic and pathologic aspects of nasal breathing. Airflows inside post-surgery models were investigated both experimentally and numerically to simulate the inferior turbinectomy. The left cavities of all three models are normal and right cavity is modified by (1) excision of the head of the inferior turbinate, (2) resection of the lower fifth of the inferior turbinate, and (3) resection of almost the entire inferior turbinate. Thin-slice CT (computed tomography) data (0.6mm deep) and meticulous refinement of the model surface by over a decade-long collaboration between engineers and an experienced ENT doctor resulted in the creation of sophisticated nasal cavity models. After numerical experiments and validation by comparison with the PIV results, the CFD code using the Reynolds stress turbulent model and variable temperature boundary condition on the mucosal wall was chosen as the proper numerical framework. Both global quantities (pressure drop, flow rate ratio, total wall heat transfer) and local changes (velocity, temperature, humidity, pressure gradient, and wall shear stress) were numerically investigated. The turbinectomy obviously altered the main stream direction. The flow rate in the upper airway near the olfactory slit decreased in models (1) and (3). This may weaken the olfactory function of the nose. Fluid and thermal properties that are believed to be related with physiology and prognosis are dependent on turbinate resection volume, position, and manner. Widening of the inferior airway does not always result in decreased flow resistance or wall heat transfer. The gains and losses of inferior turbinectomy were considered by analysis of the post-surgery model results. Nasal resistance was increased in model (1) due to sudden airway expansion. Nasal resistance increased and the wall heat transfer decreased in model (3) due to sudden airway expansion and excessive reduction of the mucosal wall surface area. Local shear stress and pressure gradient levels were increased in models (1) and (3).     

Severe intellectual disability and autistic features associated with microduplication 2q23.1

We report on two patients with developmental delay, hypotonia, and autistic features associated with duplications of chromosome region 2q23.1-2q23.2 detected by chromosome microarray analysis. The duplications include one OMIM Morbid Map gene, MBD5, as well as seven known RefSeq genes (ACVR2A, ORC4L, EPC2, KIF5C, MIR1978, LYPD6B, and LYPD6). MBD5 lies in the minimum area of overlap of the 2q23.1 microdeletion syndrome. This report provides the first detailed clinical examination of two individuals with a duplication of this region and suggests that brain development and cognitive function may be affected by an increased dosage of the genes involved.     

Involvement of endoplasmic reticulum stress in myofibroblastic differentiation of lung fibroblasts

Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress) and triggers the unfolded protein response (UPR). Recent studies suggest that ER stress is involved in idiopathic pulmonary fibrosis (IPF). The present study was undertaken to determine the role of ER stress on myofibroblastic differentiation of fibroblasts. Fibroblasts in fibroblastic foci of IPF showed immunoreactivity for GRP78. To determine the role of ER stress on α-smooth muscle actin (α-SMA) and collagen type I expression in fibroblasts, mouse and human lung fibroblasts were treated with TGF-β1, and expression of ER stress-related proteins, α-SMA, and collagen type I was analyzed by Western blotting. TGF-β1 significantly increased expression of GRP78, XBP-1, and ATF6α, which was accompanied by increases in α-SMA and collagen type I expression in mouse and human fibroblasts. A chemical chaperone, 4-PBA, suppressed TGF-β1-induced UPR and α-SMA and collagen type I induction. We also showed that TGF-β1-induced UPR was mediated through the reactive oxygen species generation. Our study provides the first evidence implicating the UPR in myofibroblastic differentiation during fibrosis. These findings of the role of ER stress and chemical chaperones in pulmonary fibrosis may improve our understanding of the pathogenesis of IPF.     

alpha-CaMKII controls the growth of human osteosarcoma by regulating cell cycle progression

Osteosarcoma is the most frequent type of primary bone cancer in children and adolescents. These malignant osteoid forming tumors are characterized by their uncontrolled hyperproliferation. Here, we investigate the role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the growth of human osteosarcoma. We show that alpha-CaMKII is expressed in human osteosarcoma cell lines and in primary osteosarcoma tissue derived from patients. The pharmacologic inhibition of CaMKII in MG-63 and 143B human osteosarcoma cells by KN-93 resulted in an 80 and 70% decrease in proliferation, respectively, and induced cell cycle arrest in the G(0)/G(1) phase. The in vivo administration of KN-93 to mice xenografted with human osteosarcoma cells significantly decreased intratibial and subcutaneous tumor growth. Mechanistically, KN-93 and alpha-CaMKII siRNA increased p21((CIP/KIP)) gene expression, protein levels, and decreased the phosphorylation of retinoblastoma protein and E2F transactivation. Furthermore, the inhibition of CaMKII decreased membrane-bound Tiam1 and GTP-bound Rac1, which are known to be involved in p21 expression and tumor growth in a variety of solid malignant neoplasms. Our results suggest that CaMKII plays a critical role in the growth of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat conventional high-grade osteosarcoma in children.