Effectiveness of intranasal lysine-aspirin in patients with aspirin-sensitive, and aspirin tolerant nasal polyposis: controlled trials

Therapeutic options for patients with aspirin-sensitive, and aspirin tolerant nasal polyps include corticosteroids (topical and systemic), surgery to relieve nasal obstruction, or a combination of the two. Medical therapy i.e. corticosteroids aims to reduce the underlying inflammation and alleviates all nasal symptoms. The aim of surgery is to provide an adequate nasal airway for breathing. Intranasal lysine-aspirin has been used as an option in these patients, and trials have shown its beneficial effects. However, their design and interpretation have been open to scientific criticism. Therefore, we planned to study the effectiveness of intranasal lysine-aspirin in the two groups of polyp patients by conducting trials in a randomised, double blind, and placebo controlled manner. Diagnosis of aspirin-sensitivity or tolerance was confirmed by intranasal lysine-aspirin challenge prior to enrolment in the appropriate trials. Nasal biopsy and polyp tissue were collected from the patients for laboratory-based experiments. Analysis of their results was aimed at improving our understanding of aspirin-sensitivity, and to generate a hypothesis on its pathogenesis. Intranasal lysine-aspirin did not reduce polyp growth, or improve nasal symptoms in aspirin-sensitive or aspirin tolerant patients when compared to placebo. However, intranasal lysine-aspirin (16 mgs) did not have any deleterious effects in both groups. Immunohistochemistry revealed a significant increase in expression of CysLTj receptor on inflammatory cells in nasal biopsies from aspirin-sensitive compared to tolerant patients. This expression reduced following treatment with intranasal lysine-aspirin, which suggested a possible mechanism of desensitization. We also found significantly higher levels of iNOS activity in polyp tissue from aspirin-sensitive compared to tolerant patients. Enhanced expression of CysLTi receptor provides further evidence of the central role played by leukotrienes in aspirin-sensitivity. Also, we suggest that high iNOS activity in polyp tissue is secondary to increased leukotriene production, and that the latter is most likely to be confined to the respiratory mucosa of patients with aspirin-sensitive asthma and/or polyposis

Annual hospital volume of high dose interleukin-2 and inpatient mortality in melanoma and renal cell carcinoma patients

Background Immunotherapy using high dose interleukin-2 (HD IL2) in patients with renal cell carcinoma (RCC) and melanoma is associated with severe toxicities. The association between annual hospital volume of HD IL2 and inpatient mortality is not well studied. In this study we aim to quantify the impact of annual hospital volume of HD IL2 on inpatient mortality using National Inpatient Sample (NIS) data. Methods We did a cross-sectional study using NIS, one of the largest inpatient datasets in United States, from 2003 to 2011. Patients with melanoma and RCC receiving HD IL2 were identified by ICD9 procedure code 00.15. The primary outcome was inpatient mortality. Using Joinpoint regression, which detects change in trend of inpatient mortality with change in annual volume, the hospitals were classified in three volume categories (low: 1-40, medium: 41-120, high: >120). Multivariate logistic regression was used to identify predictors of inpatient mortality controlling for confounders. Results From 2003 to 2011, 29,532 patients with RCC or melanoma who received HD IL2 were identified, and 124 died during the hospitalization (0.4%). The hospitals with low, medium and high annual volume had significant difference in inpatient mortality (0.83%, 0.29%and 0.13% respectively, p = 0.0003). On multivariate analysis, low volume hospitals were associated with significantly higher odds of inpatient mortality (OR 6.1, 95%CI 1.6-23.2, p = 0.003) as compared to high volume hospitals. Additionally, the hospitals with annual volume of 1-20 had even higher rates (1.31% vs. 0.13%, p<0.0001) and multivariate odds (OR 8.9, 95%CI 2.4-33.2, p = 0.0006) of inpatientmortality as compared to high volume hospitals.Conclusions Lower annual hospital volume of HD IL2 is associated with worse outcomes. Annual hospital volume of 1-40 and 1-20 treatments per year is associated with 6 and 9 times higher odds of inpatient mortality respectively as compared to high volume hospitals. Our findings provide preliminary evidence for a volume-outcome relationship for RCC and melanoma patients undergoing HD IL2 treatment. They support future volume-outcome analyses in relation to other anti-cancer therapies that require special training and expertise

Future Boundary Conditions in De Sitter Space

We consider asymptotically future de Sitter spacetimes endowed with an eternal observatory. In the conventional descriptions, the conformal metric at the future boundary I^+ is deformed by the flux of gravitational radiation. We however impose an unconventional future "Dirichlet" boundary condition requiring that the conformal metric is flat everywhere except at the conformal point where the observatory arrives at I^+. This boundary condition violates conventional causality, but we argue the causality violations cannot be detected by any experiment in the observatory. We show that the bulk-to-bulk two-point functions obeying this future boundary condition are not realizable as operator correlation functions in any de Sitter invariant vacuum, but they do agree with those obtained by double analytic continuation from anti-de Sitter space.Comment: 16 page

Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice

<div><p>Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.</p></div

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Complete pathological response in a patient with multiple liver metastases from colon cancer treated with Folfox-6 chemotherapy plus bevacizumab: a case report

The complete pathological response after primary chemotherapy could represent an important prognostic factor in patients affected by colorectal liver metastases

New experimental 23^{23}Na(α,pα,p)26^{26}Mg Reaction Rate for Massive Star and Type-Ia Supernova models

The $^{23}$Na($\alpha,p$)$^{26}$Mg reaction has been identified as having a significant impact on the nucleosynthesis of several nuclei between Ne and Ti in type-Ia supernovae, and of $^{23}$Na and $^{26}$Al in massive stars. The reaction has been subjected to renewed experimental interest recently, motivated by high uncertainties in early experimental data and in the statistical Hauser-Feshbach models used in reaction rate compilations. Early experiments were affected by target deterioration issues and unquantifiable uncertainties. Three new independent measurements instead are utilizing inverse kinematics and Rutherford scattering monitoring to resolve this. In this work we present directly measured angular distributions of the emitted protons to eliminate a discrepancy in the assumptions made in the recent reaction rate measurements, which results in cross sections differing by a factor of 3. We derive a new combined experimental reaction rate for the $^{23}$Na($\alpha,p$)$^{26}$Mg reaction with a total uncertainty of 30% at relevant temperatures. Using our new $^{23}$Na($\alpha,p$)$^{26}$Mg rate, the $^{26}$Al and $^{23}$Na production uncertainty is reduced to within 8%. In comparison, using the factor of 10 uncertainty previously recommended by the rate compilation STARLIB, $^{26}$Al and $^{23}$Na production was changing by more than a factor of 2. In type-Ia supernova conditions, the impact on production of $^{23}$Na is constrained to within 15%

Effect of Microwave Frying on Acrylamide Generation, Mass Transfer, Color, and Texture in French Fries

[EN] The objective of this work was to evaluate the effect of microwave power on acrylamide generation, as well as moisture and oil fluxes and quality attributes of microwave-fried potatoes. Concretely, 25 g of potato strips, in 250 mL of fresh oil (at room temperature), were subjected to three different microwave powers (315, 430, and 600 W) in a conventional microwave oven. Microwave frying resulted in an acrylamide reduction ranged from 37 to 83% compared to deep-oil frying. Microwave-fried French fries presented lower moisture and higher fat content than deep-oil fried potatoes. Concretely, microwave-fried potatoes presented values of moisture and texture more similar to potato chips than French fries, nonetheless with lower fat levels (less than 20 g/100 g wb) and acrylamide content (lower than 100 ¿g/kg wb) at the reference time. This study presents an alternative way of frying to address the production of healthier potato chips.The authors would like to thank the Universitat Politecnica de Valencia for the PhD scholarship given to Mariola Sansano Tomas.Sansano, M.; De Los Reyes Cánovas, R.; Andrés Grau, AM.; Heredia Gutiérrez, AB. (2018). Effect of Microwave Frying on Acrylamide Generation, Mass Transfer, Color, and Texture in French Fries. Food and Bioprocess Technology. 11(10):1934-1939. doi:10.1007/s11947-018-2144-zS193419391110AACC. (1995). Approved methods of the American association of cereal chemists (9th ed.). St. Paul: The Association.Adedeji, A. A., Ngadi, M. O., & Raghavan, G. S. V. (2009). Kinetics of mass transfer in microwave precooked and deep-fat fried chicken nuggets. Journal of Food Engineering, 91(1), 146–153.Ahrné, L., Andersson, C.-G., Floberg, P., Rosén, J., & Lingnert, H. (2007). Effect of crust temperature and water content on acrylamide formation during baking of white bread: steam and falling temperature baking. LWT-Food Science and Technology, 40(10), 1708–1715.Amrein, T. M., Limacher, A., Conde-Petit, B., Amadò, R., & Escher, F. (2006). Influence of thermal processing conditions on acrylamide generation and Browning in a potato model system. Journal of Agricultural and Food Chemistry, 54(16), 5910–5916.Andrés, A., Arguelles, Á., Castelló, M. L., & Heredia, A. (2013). Mass transfer and volume changes in French fries during air frying. Food and Bioprocess Technology, 6(8), 1917–1924.Barutcu, I., Sahin, S., & Sumnu, G. (2009). Acrylamide formation in different batter formulations during microwave frying. LWT - Food Science and Technology, 42(1), 17–22.Belgin Erdoǧdu, S., Palazoǧlu, T. K., Gökmen, V., Şenyuva, H. Z., & Ekiz, H. İ. (2007). Reduction of acrylamide formation in French fries by microwave pre-cooking of potato strips. 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Dielectric spectroscopy of osmotic solutions and osmotically dehydrated tomato products. Journal of Food Engineering, 80(4), 1218–1225. 2.Granda, C., & Moreira, R. G. (2005). Kinetics of acrylamide formation during traditional and vacuum frying of potato chips. Journal of Food Process Engineering, 28(5), 478–493.Lizhi, H., Toyoda, K., & Ihara, I. (2008). Dielectric properties of edible oils and fatty acids as a function of frequency, temperature, moisture and composition. Journal of Food Engineering, 88(2), 151–158.Oztop, M. H., Sahin, S., & Sumnu, G. (2007). Optimization of microwave frying of potato slices by using Taguchi technique. Journal of Food Engineering, 79(1), 83–91.Parikh, A., & Takhar, P. S. (2016). Comparison of microwave and conventional frying on quality attributes and fat content of potatoes. Journal of Food Science, 81(11), E2743–E2755.Pedreschi, F., & Moyano, P. (2005). Oil uptake and texture development in fried potato slices. 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Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation