Efficacy of an Esophageal Spacer for Spine Radiosurgery: First Experience.

This is the first study to investigate the use of an esophageal hydrogel spacer in spine stereotactic radiosurgery. The tolerability and the dose reduction to the esophagus are predicted to reduce the incidence of high-grade toxicities, which in turn can permit dose escalation to optimize tumor control.

Increased dipeptidyl peptidase-4 accelerates chronic stress-related thrombosis in a mouse carotid artery model.

OBJECTIVE: Exposure to chronic psychosocial stress is a risk factor for metabolic cardiovascular disorders. Given that dipeptidyl peptidase-4 (DPP-4) has an important role in human pathobiology, we investigated the role of DPP-4 in stress-related thrombosis in mice, focusing on oxidative stress and the von Willebrand factor (vWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). METHODS AND RESULTS: Male mice randomly assigned to nonstress and 2-week immobilized-stress groups underwent iron chloride3 (FeCl3)-induced carotid artery thrombosis surgery for morphological and biochemical studies at specific times. On day 14 post-stress/surgery, stress had enhanced the lengths and weights of arterial thrombi, with alterations of plasma DPP-4, plasminogen activation inhibitor-1 and ADAMTS13. The stressed mice had increased levels of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, gp91phox, p22phox, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsins S and K mRNAs and/or proteins, and reduced levels of endothelial nitric oxide synthase, catalase and superoxide dismutase-1 mRNAs and/or proteins. Stress also accelerated arterial endothelial cell damage. The DPP-4 inhibitor anagliptin ameliorated the stress-induced targeted molecular and morphological changes and thrombosis. In vitro, DPP-4 inhibition also mitigated the alterations in the targeted ADAMTS13 and other oxidative and inflammatory molecules in human umbilical vein endothelial cells in response to H2O2. CONCLUSION: DPP-4 inhibition appeared to improve the FeCl3-induced thrombosis in mice that received stress, possibly via the improvement of ADAMTS13 and oxidative stress, suggesting that DPP-4 could become a novel therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disorders.

Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum.

OBJECTIVE: The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS's role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery. METHODS: Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery. RESULTS: In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0-122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18-24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy. CONCLUSIONS: High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

Dipeptidyl peptidase-4 inhibition prevents vascular aging in mice under chronic stress: Modulation of oxidative stress and inflammation.

BACKGROUND AND AIMS: Chronic psychosocial stress is a risk factor for cardiovascular disease. In view of the important role of dipeptidyl peptidase-4 (DPP-4) in human pathophysiology, we studied the role of DPP-4 in stress-related vascular aging in mice, focusing on oxidative stress and the inflammatory response. METHODS AND RESULTS: Male mice were randomly divided into a non-stress group and an immobilization stress group treated for 2 weeks. Chronic stress accelerates aortic senescence and increases plasma DPP-4 levels. Stress increased the levels of gp91phox, p22phox, p47phox, p67phox, p53, p27, p21, p16INK4A, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsin S (Cat S), and Cat K mRNAs and/or protein in the aorta of the stressed mice and decreased their levels of endothelial nitric oxide synthase and SirTuin1 (SirT1). DPP-4 inhibitors can improve stress-induced targeting molecules and morphological changes. In vitro, the inhibition of DPP-4 also alleviated the changes in the oxidative and inflammatory molecules in response to hydrogen peroxide in human umbilical vein endothelial cells. CONCLUSIONS: DPP-4 inhibition can improve vascular aging in stressed mice, possibly by improving oxidative stress production and vascular inflammation. Our results suggest that DPP-4 may become a new therapeutic target for chronic stress-related vascular aging in metabolic cardiovascular diseases.

Estimating the need for palliative radiotherapy for non-small cell lung cancer: A criterion-based benchmarking approach.

BACKGROUND AND PURPOSE: Estimates of appropriate treatment rates are required for monitoring and improving access to cancer care. Optimal utilization rates for palliative radiotherapy (PRT) for patients with non-small cell lung cancer (NSCLC) remain undefined. We aim to estimate the appropriate PRT rate for the general NSCLC population. MATERIALS AND METHODS: Ontario's population-based cancer registry identified patients with NSCLC who died of their disease between 2006 and 2010. Multivariate analysis identified factors affecting PRT use, enabling us to define a benchmark population with unimpeded access to PRT. Proportion of cases treated in the last 2 years of life (PRT2y) was standardized to overall population characteristics. Benchmarks were compared to province-wide PRT2y rates. RESULTS: Availability of RT at the diagnosing hospital was the dominant determinant of increased PRT utilization. Patients diagnosed at hospitals with on site RT were therefore designated the benchmark population. The standardized benchmark for PRT2y was 56%, compared to the province-wide rate of 49%. The gap between actual and optimal rates varied across patient ages, treatment indications, and geographic regions. CONCLUSIONS: Approximately 56% of patients who die of NSCLC in Ontario need PRT, but many are never treated.

A case of synchronous breast and bilateral lung cancers: literature review and considerations for radiation treatment planning.

Limited literature is available regarding treatment strategies for three concurrent potentially curable malignancies, and only one case of primary breast cancer with bilateral primary lung cancers has been reported. There is no literature available on approaches to radiation treatment planning and delivery in this challenging scenario. We report a case of a 66-year-old female who underwent partial mastectomy and sentinel node biopsy for left-sided breast cancer, pT1cN1(mic). Metastatic work-up revealed bilateral primary lung cancers, biopsy-proven, each Stage cT1N0. Distinguishing synchronous primary tumours from metastatic disease can be challenging. The histological examination suggested three distinct primaries and each was potentially curable. Devising a treatment strategy required balancing the incremental benefits with the toxicity of combining each of the treatments. Stereotactic ablative radiotherapy was the treatment of choice for the patient's lung primaries, as she was deemed a high-risk surgical candidate. Tangential whole breast radiotherapy with regional nodal irradiation was deemed appropriate for her breast cancer. Treatment for all three sites was planned concurrently, taking into account any potential overlap of dose in the composite plan. Each lung lesion was treated with 48 Gy in 4 fractions with stereotactic ablative radiotherapy using volumetric modulated arc therapy technique. The breast and supraclavicular regions were treated with 50 Gy in 25 daily fractions using a field-in-field technique. Optimal clinical outcomes for patients with multiple primary cancers require optimal definitive management. In this unique case of triple primaries, curative-intent radiotherapy to both lungs, the left breast and regional nodes was planned to be given concurrently and treatment was successfully delivered without significant toxicity.

Increased Plasma Dipeptidyl Peptidase-4 Activities in Patients with Coronary Artery Disease.

Dipeptidyl peptidase-4 (DPP4) is one of the most potent mammalian serine proteases participated in the pathogenesis of subclinical atherosclerosis. Here we investigated whether the plasma soluble form of DPP4 is associated with the prevalence of coronary artery disease (CAD) with and without diabetes mellitus (DM). A cross-sectional study was conducted of 496 aged 26-81 years with (n = 362) and without (n = 134) CAD. Plasma DPP4 activity, high sensitive C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein levels were measured. The coronary atherosclerotic plaques were evaluated by coronary angiography. The CAD patients with (n = 84) and without (n = 278) DM had significantly higher DPP4 levels (11.8 ± 3.1 vs. 6.9 ± 3.5 ng/mL, P<0.01) than the nonCAD subjects. The acute coronary syndrome patients (n = 299) had elevated DPP4 levels than those with stable angina patients (n = 83). CAD patients even without DM had increased plasma DPP4 activities as compared with nonCAD subjects (10.9 ± 4.9 vs. 6.4 ± 3.1, ng/L, P< 0.01). A linear regression analysis revealed that overall, the DPP4 levels were positively associated with LCL-C and hs-CRP levels as well as syntax scores. A multiple logistic regression analysis demonstrated that plasma DPP4 activity was independent predictor of CAD (odds ratio, 1.56; 95% CI, 1.19-1.73; P<0.01). Our study shows that increased DPP4 activity levels are associated with the presence of CAD and that the plasma DPP4 level serves as a novel biomarker for CAD even without DM.

Thermal Conductivity of Diamond Packed Electrospun PAN-Based Carbon Fibers Incorporated with Multi Wall Carbon Nanotubes.

Multi wall carbon nanotubes (MWCNTs) and diamond are renowned as superlative material due to their relatively high thermal conductivity and hardness while comparing with any bulk materials. In this research, polyacrylonitrile (PAN) solution incorporated with MWCNTs at an alteration of mass fractions (0 wt%, 0.6 wt%, 1 wt%, 2 wt%) were fabricated via electrospinning under optimized parameters. Dried composite nanofibers were stabilized and carbonized, after which water base polytrafluorethylene (PTFE) mixed with nano diamond powder solution was spin coated on them. Scanning electron microscopy, Raman spectroscopy, X-ray scattering and Laserflash thermal conductivity were used to characterize the composite nanofiber sheets. The result shows that the thermal conductivity increased to 4.825 W/m K from 2.061 W/mK. The improvement of thermal conductivities is suggesting the incorporation of MWCNTs.

Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents.

A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4]triazolo [4,3-a]azepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6- dihydro-4H-benzo[f][1,2,4] triazolo[4,3-a]azepine (7g) was the most promising compound, with median effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure-activity relationship was discussed.

Eosinophilic angiocentric fibrosis of the sinonasal tract.

Eosinophilic angiocentric fibrosis (EAF) is an exceedingly rare and potentially disfiguring and obstructing benign lesion involving the upper airways. We report two cases of EAF originating from the nasal cavity in a 31-year-old female and a 58-year-old male exhibiting nasal obstructive symptoms, with imaging features and histopathology characteristic of EAF. Surgical excision was performed on one patient with a disfiguring nasal mass at a tertiary referral rhinology practice within a university centre. Summarized are the relevant clinical issues to increase awareness of this disease. The slow progression and rarity of the disease has previously resulted in diagnostic difficulty. We review the limited current literature surrounding the clinical features and treatment options for this progressive and potentially morbid condition. These cases reinforce that, while rare, inflammatory and fibrosing lesions in general should still be considered as part of the differential diagnosis in patients presenting with obstructive lesions in the sinonasal tract.

[Solidification/Stabilization of Chromite Ore Processing Residue (COPR) Using Zero-Valent Iron and Lime-Activated Ground Granulated Blast Furnace Slag].

The solidification/stabilization (S/S) of chromite ore processing residue (COPR) was performed using zero-valent iron (ZVI) and lime-activated ground granulated blast furnace slag (GGBFS). The degree of Cr immobilization was evaluated using the leaching procedure, mineral composition analysis and morphology analysis. Semi-dynamic leaching tests were implemented to investigate the potential for reusing the final treatment product as a readily available construction material. The results showed that after reduction, all of the S/S treated COPR samples met the pollution control limit of bricks and building block products (Chinese standard HJ/T 301-2007) produced with COPR for total Cr (0.3 mg x L(-1)), the compressive strength of all the S/S samples could meet the compressive strength standard (15 MPa) for producing clay bricks, and Cr existed as the specie that bound to Fe/Mn oxides in the S/S samples. At the same time, all of the S/S treated specimens tested were suitable for utilization at certain levels.

Pressures to "measure up" in surgery: managing your image and managing your patient.

OBJECTIVE: To identify pressures created by surgical culture and social setting and explore mechanisms for how they might impact operative decision-making. BACKGROUND: Surgeons apply judgments within a powerful social context and are constantly socialized and influenced by communicative exchanges. In this study, the authors characterized the nature of the surgical social context, focusing on the interactions between external social influences and the cognitive ability of the surgeon to respond to uncertain, unexpected, or critical moments in operations. METHODS: The authors reviewed the sociological and psychosocial literatures to examine concepts in identity construction, socialization process, and image management literatures and synthesized a conceptual framework allowing for the examination of how social factors and image management might impact surgical performance. RESULTS: The surgeon's professional identity is constructed and negotiated on the basis of the context of surgical culture. Trainees are socialized to display confidence and certainty as part of the "hidden curriculum" and several sociocultural mechanisms regulating "appropriate" surgical behavior exist in this system. In the image management literature, individuals put on a "front" or social performance that is socially acceptable. Several mechanisms for how image management might impact surgical judgment and decision-making were identified through an exploration of the cognitive psychology literature. CONCLUSIONS: Sociopsychological literatures can be linked with decision-making and cognitive capacity theory. When cognitive resources reach their limit during critical and uncertain moments of an operation, the consumption of resources by the pressures of reputation and ego might interfere with the thought processes needed to execute the task at hand. Recognizing the effects of external social pressures may help the surgeon better self-regulate, respond mindfully to these pressures, and prevent surgical error.

Differential recruitment of mechanisms for myogenic responses according to luminal pressure and arterial types.

Mechanosensitive nonselective cation channels (NSC(ms)), protein kinase C (PKC), and Rho kinase (ROCK) are suggested as underlying mechanisms for the myogenic contractile response (MR) to luminal pressure (P(lum)). Here we compared relative contributions from these mechanisms using pharmacological inhibitors in rabbit middle cerebral (RbCA), rat middle cerebral (RtCA), rat femoral (RtFA), and rat mesenteric (RtMA) small arteries. Inner diameters of pressurized arteries under various P(lum) were video-analyzed. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 10 microM) was used as a blocker of NSC(ms). In general, RbCA and RtCA showed higher P(lum) sensitivity of MR than RtFA and RtMA. Ten micromolars of DIDS commonly decreased MRs more effectively at low P(lum) (40-60 mmHg) in all tested arteries except RtCA. In RbCA, PKC inhibitors (100 nM of Go6976 or Go6983) decreased the MR at relatively high P(lum) (80-100 mmHg) whereas ROCK inhibitor (Y-27632, 1 microM) showed a P(lum)-independent inhibition. In RtMA and RtCA, PKC inhibitors (Go6976 and Go6983) had no significant effect whereas Y-27632 generally inhibited the MR. In RtFA, neither PKC inhibitor nor Y-27632 alone affected MRs. Interestingly, in the presence of 10 microM DIDS, Go6983 and Y-27632 decreased the MR of RtFA. In RtMA, it was notable that the MR decreased spontaneously on repeated protocol of P(lum) increase, and the 'run-down' could be effective reversed by maxi-K(+) channel blocker (tetraethylammonium or iberiotoxin). In summary, our study shows the variability of MRs according to the arterial types in terms of their pressure sensitivity and underlying mechanisms that are recruited according to P(lum).