Hydraulic fracturing volume is associated with induced earthquake productivity in the Duvernay play.

A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (104 to 105 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index-modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.

Tension band plating is less effective in achieving equalization of leg length.

PURPOSE: Little data is available on the efficiency of different implants for epiphysiodesis. The purpose of this study is to compare the efficacy between plates and staples in decreasing leg-length discrepancy. METHODS: A retrospective review of 19 children who underwent temporary epiphysiodesis of the legs was conducted, with a minimum of two years of follow-up. The bone length and length ratio to the short side were measured at six months, one year and two years postoperatively. The change in discrepancy was compared between staples and plates by an independent t-test, and the shortest time to a significant decrease in discrepancy was determined using a paired t-test. RESULTS: Ten patients underwent 13 staple procedures in nine femurs and four tibias for a 2.8-cm discrepancy at age 11.8 years, and nine patients underwent 14 plate procedures in seven femurs and seven tibias for a 3.1-cm discrepancy at age 12.4 years. Patients were followed up to skeletal maturity, except two. The use of staples decreased the discrepancy in the bone ratio from +4.8% to +1.2% in two years, and the use of plates decreased this ratio from +5.1% to +3.3% in two years. The change in the length ratio was significantly greater after stapling. Six months were required after stapling before the first significant decrease in discrepancy; it took two years after plating. CONCLUSIONS: This study showed a significantly lower efficacy for decreasing leg-length discrepancy by tension band plating. Orthopaedic surgeons should be aware of the limitations of using plates for suppressing bone growth. LEVEL OF EVIDENCE: III.

Translational control of PML contributes to TNFα-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs.

The tumor suppressor protein promyelocytic leukemia (PML) is a key regulator of inflammatory responses and tumorigenesis and functions through the assembly of subnuclear structures known as PML nuclear bodies (NBs). The inflammation-related cytokine tumor necrosis factor-α (TNFα) is known to induce PML protein accumulation and PML NB formation that mediate TNFα-induced cell death in cancer cells and inhibition of migration and capillary tube formation in endothelial cells (ECs). In this study, we uncover a novel mechanism of PML gene regulation in which the p38 MAPK and its downstream kinase MAP kinase-activated protein kinase 1 (MNK1) mediate TNFα-induced PML protein accumulation and PML NB formation. The mechanism includes the presence of an internal ribosome entry site (IRES) found within the well-conserved 100 nucleotides upstream of the PML initiation codon. The activity of the PML IRES is induced by TNFα in a manner that involves MNK1 activation. It is proposed that the p38-MNK1-PML network regulates TNFα-induced apoptosis in breast cancer cells and TNFα-mediated inhibition of migration and capillary tube formation in ECs.

Experimental study of fat grafting under negative pressure for wounds with exposed bone.

BACKGROUND: The combination of fat grafting and negative pressure (VAC) therapy represents a synergistic interaction of all essential components for wound healing. The aim of this experimental study was to determine whether it could promote healing of wounds with exposed bone. METHODS: Full-thickness wounds with denuded bone in Sprague-Dawley rats were treated with either polyurethane foam dressing, fat grafting alone, polyurethane foam dressing with VAC, or polyurethane foam dressing with VAC combined with a single, or two administrations of fat graft. Wound healing kinetics, tissue growth, cell proliferation (Ki-67) and angiogenesis (platelet endothelial cell adhesion molecule 1 and α-smooth muscle actin) were investigated. Messenger RNA levels related to angiogenesis (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF)), profibrosis (platelet-derived growth factor A and transforming growth factor ß), adipocyte expression (fatty acid-binding protein (FABP) 4 and peroxisome proliferator activated receptor γ), and extracellular matrix remodelling (collagen I) were measured in wound tissues. RESULTS: Wounds treated by VAC combined with fat grafting were characterized by cell proliferation, neoangiogenesis and maturation of functional blood vessels; they showed accelerated granulation tissue growth over the denuded bone compared with VAC- or foam dressing-treated wounds. Fat grafting alone over denuded bone resulted in complete necrosis. Expression of angiogenesis markers (VEGF and b-FGF) and adipocyte expression factors (FABP-4) was upregulated in wounds treated with VAC combined with fat grafting. CONCLUSION: Fat grafting with VAC therapy may represent a simple but effective clinical solution for a number of complex tissue defects, and warrants testing in clinical models. SURGICAL RELEVANCE: The combination of fat grafting and vacuum therapy represents a synergistic interaction of regenerative cells, hospitable wound matrix and stimulating micromechanical forces. It could accelerate complex wound healing through cell proliferation, neoangiogenesis and maturation of functional blood vessels. The efficacy of a multimodal wound healing approach is established in this experimental model; it could easily be translated into clinical trials of treatment for difficult wounds.

Synthesis and characterization of Pt nanoparticles with different morphologies in mesoporous silica SBA-15 for methanol oxidation reaction.

Mesoporous SBA-15 silica materials functionalized with and without carboxylic acid groups were used to effectively control the morphology of Pt crystals, and the materials thus obtained were applied to methanol oxidation reactions. The Pt particles aggregated to form long spheroids inside the channels in pure SBA-15. When carboxylic acid groups were utilized, the SBA-15(-COOH) material facilitated the formation of higher Pt surface area, smaller Pt nanoparticles and nearly spherical shape due to the strong interaction between Pt(4+) ions and carboxylic acid on SBA-15. The Pt(4+) ions on the SBA-15(-COOH) material can be directly transformed to reduced Pt particles during calcination. The methanol oxidation activity on a Pt surface is strongly dependent on the shape of Pt particles. The near-spherical Pt nanoparticles on the SBA-15(-COOH) exhibited higher catalytic activity during methanol oxidation than Pt catalysts on unmodified SBA-15. The near-spherical Pt particles on the SBA-15(-COOH) contained large numbers of terrace sites on their surfaces, which led to high efficiency during methanol oxidation.

Deacetylation of the tumor suppressor protein PML regulates hydrogen peroxide-induced cell death.

The promyelocytic leukemia protein (PML) is a tumor suppressor that is expressed at a low level in various cancers. Although post-translational modifications including SUMOylation, phosphorylation, and ubiquitination have been found to regulate the stability or activity of PML, little is known about the role of its acetylation in the control of cell survival. Here we demonstrate that acetylation of lysine 487 (K487) and SUMO1 conjugation of K490 at PML protein are mutually exclusive. We found that hydrogen peroxide (H2O2) promotes PML deacetylation and identified SIRT1 and SIRT5 as PML deacetylases. Both SIRT1 and SIRT5 are required for H2O2-mediated deacetylation of PML and accumulation of nuclear PML protein in HeLa cells. Knockdown of SIRT1 reduces the number of H2O2-induced PML-nuclear bodies (NBs) and increases the survival of HeLa cells. Ectopic expression of wild-type PML but not the K487R mutant rescues H2O2-induced cell death in SIRT1 knockdown cells. Furthermore, ectopic expression of wild-type SIRT5 but not a catalytic defective mutant can also restore H2O2-induced cell death in SIRT1 knockdown cells. Taken together, our findings reveal a novel regulatory mechanism in which SIRT1/SIRT5-mediated PML deacetylation plays a role in the regulation of cancer cell survival.

Transition into driven equilibrium of the balanced steady-state free precession as an ultrafast multisection T2-weighted imaging of the brain.

BACKGROUND AND PURPOSE: Current T2-weighted imaging takes >3 minutes to perform, for which the ultrafast transition into driven equilibrium (TIDE) technique may be potentially helpful. This study qualitatively and quantitatively evaluates the imaging of transition into driven equilibrium of the balanced steady-state free precession (TIDE) compared with TSE and turbo gradient spin-echo on T2-weighted MR images. MATERIALS AND METHODS: Thirty healthy volunteers were examined with T2-weighted images by using TIDE, TSE, and turbo gradient spin-echo sequences. Imaging was evaluated qualitatively by 2 independent observers on the basis of a 4-point rating scale regarding contrast characteristics and artifacts behavior. Image SNR and contrast-to-noise ratio were quantitatively assessed. RESULTS: TIDE provided T2-weighted contrast similar to that in TSE and turbo gradient spin-echo with only one-eighth of the scan time. TIDE showed gray-white matter differentiation and iron-load sensitivity inferior that of TSE and turbo gradient spin-echo, but with improved motion artifacts reduction on qualitative scores. Nonmotion ghosting artifacts were uniquely found in TIDE images. The overall SNRs of TSE were 1.9-2.0 times those of turbo gradient spin-echo and 1.7-2.2 times of those of TIDE for brain tissue (P < .0001). TIDE had a higher contrast-to-noise ratio than TSE (P = .169) and turbo gradient spin-echo (P < .0001) regarding non-iron-containing gray matter versus white matter. TIDE had a lower contrast-to-noise ratio than turbo gradient spin-echo and TSE (P < .0001) between iron-containing gray matter and white matter. CONCLUSIONS: TIDE provides T2-weighted images with reduced scan times and reduced motion artifacts compared with TSE and turbo gradient spin-echo with the trade-off of reduced SNR and poorer gray-white matter differentiation.

Three-dimensional bone CT reconstruction anatomy of the vidian canal.

OBJECTIVES: To examine the anatomical features of the anterior opening of the vidian canal using three-dimensional (3D) computed tomography (CT) images of the bone. METHODS: We reviewed 62 patients who had undergone bilateral vidian neurectomies. One hundred and twenty-four vidian canals and their surrounding anatomies were analyzed. 3D images were reconstructed using algorithms and compared with conventional two-dimensional (2D) CT images. RESULTS: A bony prominence that overlaid the vidian canal along the sphenoid sinus floor was found in 60 (48.39 %) canals. Pneumatization of the pterygoid process was observed in 45 sides (36.29%). No significant discrepancy was found in detecting these variances between the 2D and the 3D images. The presence of a surgically favorable gap between the palatine and the sphenoid bone was seen in 25 sides (20.16%) without significant association with pterygoid process pneumatization or vidian canal protrusion. This gap was not identified on the 2D CT scans. CONCLUSION: 3D CT reconstruction images of bone provide superior delineation of the gap between the palatine and the sphenoid bone, which is a critical variation for vidian neurectomy. This useful method may contribute to better prediction and guidance of the surgical approach to the vidian canal and pterygopalatine fossa.

Isoforms of the neuronal glutamate transporter gene, SLC1A1/EAAC1, negatively modulate glutamate uptake: relevance to obsessive-compulsive disorder.

The SLC1A1 gene, which encodes the neuronal glutamate transporter, EAAC1, has consistently been implicated in obsessive-compulsive disorder (OCD) in genetic studies. Moreover, neuroimaging, biochemical and clinical studies support a role for glutamatergic dysfunction in OCD. Although SLC1A1 is an excellent candidate gene for OCD, little is known about its regulation at the genomic level. Here, we report the identification and characterization of three alternative SLC1A1/EAAC1 mRNAs: a transcript derived from an internal promoter, termed P2 to distinguish it from the transcript generated by the primary promoter (P1), and two alternatively spliced mRNAs: ex2skip, which is missing exon 2, and ex11skip, which is missing exon 11. All isoforms inhibit glutamate uptake from the full-length EAAC1 transporter. Ex2skip and ex11skip also display partial colocalization and interact with the full-length EAAC1 protein. The three isoforms are evolutionarily conserved between human and mouse, and are expressed in brain, kidney and lymphocytes under nonpathological conditions, suggesting that the isoforms are physiological regulators of EAAC1. Moreover, under specific conditions, all SLC1A1 transcripts were differentially expressed in lymphocytes derived from subjects with OCD compared with controls. These initial results reveal the complexity of SLC1A1 regulation and the potential clinical utility of profiling glutamatergic gene expression in OCD and other psychiatric disorders.

Predictors of bloodstream infection associated with permanently implantable venous port in solid cancer patients.

BACKGROUND: The purpose of this study is to characterize the risk factors of bloodstream infection (BSI) associated with the use of permanent implantable venous ports (Port-A) in solid cancer patients. METHODS: Solid cancer patients implanted with a Port-A were prospectively observed for the occurrence of Port-A-associated BSI (PABSI), defined as BSI without other identifiable infection foci. A PABSI risk score was developed using the Cox proportional hazards model. RESULTS: A total of 415 patients were registered; 88 PABSI episodes occurred in 58 patients (incidence1.05 per 1000 catheter-days). All but one patient had stage IV cancer. Independent predictors of PABSI occurrence included neutropenia, total parenteral nutrition (TPN), chronic steroid use, invasive procedures, postoperative antibiotics, and preoperative antibiotics. A PABSI risk score with a cut-off value of 0 (sensitivity 88.5%, specificity 64.3%) was defined for stage IV cancer patients as follows: neutropenia, +1.350; TPN, +1.256; chronic steroid use, +1.947; preoperative antibiotics, -0.970; postoperative antibiotics, +0.959; and invasive procedures, +1.098. The median PABSI-free survival was 4.47 months for patients with scores ≥ 0 but not reached for patients with scores <0 (P < 0.0001). CONCLUSION: The PABSI risk score can assist in identifying high-risk solid cancer patients and may assist in designing future preventive strategies.

The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of the tumor-suppressor protein promyelocytic leukemia protein.

The promyelocytic leukemia (PML) protein is a tumor suppressor originally identified in acute promyelocytic leukemia and implicated in tumorigenesis in multiple forms of cancer. Here, we demonstrate that the PML protein undergoes ubiquitination-mediated degradation facilitated by an E3 ligase UHRF1 (ubiquitin-like with PHD and RING finger domains 1), which is commonly upregulated in various human malignancies. Furthermore, UHRF1 negatively regulates PML protein accumulation in primary human umbilical vein endothelial cells (HUVECs), HEK 293 cells and cancer cells. Knockdown of UHRF1 upregulates whereas ectopic overexpression of UHRF1 downregulates protein abundance of endogenous or exogenous PML, doing so through its binding to the N-terminus of PML. Overexpression of wild-type UHRF1 shortens PML protein half-life and promotes PML polyubiquitination, whereas deletion of the RING domain or coexpression of the dominant-negative E2 ubiquitin-conjugating enzyme, E2D2, attenuates this modification to PML. Finally, knockdown of UHRF1 prolongs PML half-life and increases PML protein accumulation, yet inhibits cell migration and in vitro capillary tube formation, whereas co-knockdown of PML compromises this inhibitory effect. These findings suggest that UHRF1 promotes the turnover of PML protein, and thus targeting UHRF1 to restore PML-mediated tumor suppression represents a promising, novel, anticancer strategy.

Susceptibility-weighted imaging, an additional tool to diagnose brain death: initial experience.

We describe findings suggestive of brain death on susceptibility-weighted imaging. We retrospectively reviewed brain magnetic resonance (MR) images of 15 patients who had cardiac arrest and found four cases with evidence of brain death. We then reviewed susceptibility-weighted imaging (SWI) findings on these cases. SWI images in the four cases with brain death showed deoxygenated blood in intracranial arteries. This preliminary result suggests that SWI may be used to diagnose brain death.

Mite allergen decreases DC-SIGN expression and modulates human dendritic cell differentiation and function in allergic asthma.

House dust mites (HDMs) induce allergic asthma in sensitized individuals, although how HDMs activate immature mucosal dendritic cells (DCs) to render the T helper cell type 2 (Th2)-mediated immune response is unclear. In this study, our results showed a significant calcium-dependent lectin binding of Dermatophagoides pteronyssinus (Der p) extracts to DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), the C-type lectin receptors (CLRs) of DCs. Moreover, monocyte-derived DCs (MDDCs) of Der p-sensitized asthmatics (AS) exhibited decreased expression of DC-SIGN, increased endocytosis, and impaired differentiation of DC precursors. The Der p-induced downregulation of DC-SIGN expression in the differentiation of immature MDDCs may be because of the internalization of Der p-DC-SIGN complex. MDDCs of AS produced more interleukin (IL)-6 and less IL-12p70 cytokines when stimulated with lipopolysaccharide (LPS) or Der p than those of nonallergic controls (NC). In the co-culture experiments, MDDCs pretreated with Der p induced GATA-3 expression and IL-4 cytokine productions in naive CD4(+) T cells. These effects of Der p on the differentiation and function of MDDCs could be partially blocked by anti-DC-SIGN antibodies. In conclusion, our results suggest a critical step of allergen sensitization that involves CLRs in the innate immune response of DCs, which may provide a therapeutic or preventive potential for allergic asthma.

Blending of polyethylenimine with a cationic polyurethane greatly enhances both DNA delivery efficacy and reduces the overall cytotoxicity.

Three blending methods were introduced to combine a biodegradable cationic- polyurethane (PUg3) and polyethylenimine (PEI) together with DNA by different mixing sequences. Results of gel electrophoresis assays and particle size measurements show that complexes prepared by method 1 and 3 bear an ability to condense DNA into small nanoparticles. On the contrary, the use of method 2 in making complexes produces significantly large particles because of the weaker interaction with DNA and lack of DNA condensation. Moreover, cell proliferation assays show that no cytotoxicity of the DNA/blended-polymers complexes (exhibited by method 1) was found and due to a result of the outer coating of PUg3, reducing cytotoxic PEI exposure outside the complexes. With a new technique in pharmaceutics, the complexes prepared for DNA delivery by mixing of PEI and PUg3 with DNA in a sequence (method 1) could achieve an even better transfection efficiency (reaching 40% higher) than using PEI alone as well as reduce the cytotoxicity substantially. In conclusion, a new class of complexes (non-viral combo-system) made by a skillful blending sequence (method 1) has been designed and demonstrated to obtain the beneficial properties from two useful and individual polymers for gene delivery. This method can be used in greatly improving the transfection efficiency of polymer-based gene vectors. The blended polymers with DNA also have a better biocompatibility and no cytotoxicity, which are the requirements and critical points for great success in performing gene therapy in vivo.

Extratesticular epidermoid cyst mimicking enlarged testis.

Epidermoid cysts are benign simple epithelial tumors usually appearing as hypoechoic lesions with scattered echogenic reflectors on sonography. Herein, we present a 53-year-old man with an extratesticular epidermoid cyst in the right scrotum which shows confusing sonographic findings, normal-appearing echogenicity of the lesion and atrophied testis, which lead to a diagnostic dilemma. With a variety of sonographic presentations in extratesticular epidermoid cysts, magnetic resonance (MR) imaging could play a complementary role in difficult cases.

CT Angiographic Diagnosis of a Ruptured Intraventricular Arteriovenous Malformation in a Teenager Playing a Video Game.

Intraventricular arteriovenous malformation (AVM) is a rare congenital vascular disorder that is often associated with primary intraventricular hemorrhage (IVH) and a rapid clinical course. Acute imaging diagnosis requires depiction of both the location of hemorrhage and vascular nidus for emergent management. In this report, a 17-year-old teenager developed primary IVH with presentation of consciousness change during a video game. Multidetector-row computed tomographic angiography (CTA) demonstrated an AVM in the right lateral ventricle and its angioarchitectural relationship to the surrounding intracranial structures. Although selective angiography is essential both in planning treatment for cerebral AVMs and in establishing the final diagnosis, CTA can be an important first-line imaging modality to quickly confirm the diagnosis and hence initiate prompt management.