Integrated study of factors affecting fetal weight in singleton pregnancies. Nomogram and development of basic and advanced fetal growth customized models

We have performed a multivariate analysis to explore the influence on birth and ultrasound fetal weight estimation of traditional factors as biochemical data and maternal characteristics in combination with non- traditionally explored predictors as paternal height, Pregnancy-associated plasma protein A (PAPP-A), single umbilical artery or Free-beta Human Chorionic Gonadotropin (fß- HCG). The study was performed for a Spanish population (region of Aragon) in singleton pregnancies at term (37-42 weeks). Also, we have created a nomogram and in order to predict the occurrence of SGA (small for gestational age) and LGA (large for gestational age) cases we provide a multivariate predictive model of fetal weight that have been compared with other models in the prediction of ultrasound and birth weights. After study we have created a software application for automated calculation of percentile fetal weight, adjusting the variables when they were significant

Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies

Background On the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved chimeric antigen receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and costimulation of T cells will facilitate clinical development of CD137 agonists in the clinic. Methods We used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored on treatment with agonist anti-CD137 monoclonal antibodies (mAbs). Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 mAb (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISA and Luminex. Flow cytometry was used to monitor CD137 surface expression. Results CD137 costimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 costimulation inside subcutaneously implanted Matrigel plugs. The CD137 signaling domain-containing CAR T cells readily released sCD137 and acquired CD137 surface expression on antigen recognition. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137. Conclusion sCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic costimulatory activity elicited by agonist CD137-targeted agents

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)

Outdoor airborne allergens: Characterization, behavior and monitoring in Europe

Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and asthma. Outdoor aeroallergens are found predominantly in pollen grains and fungal spores, which are allergen carriers. Aeroallergens from pollen and fungi have seasonal emission patterns that correlate with plant pollination and fungal sporulation and are strongly associated with atmospheric weather conditions. They are released when allergen carriers come in contact with the respiratory system, e.g. the nasal mucosa. In addition, due to the rupture of allergen carriers, airborne allergen molecules may be released directly into the air in the form of micronic and submicronic particles (cytoplasmic debris, cell wall fragments, droplets etc.) or adhered onto other airborne particulate matter. Therefore, aeroallergen detection strategies must consider, in addition to the allergen carriers, the allergen molecules themselves. This review article aims to present the current knowledge on inhalant allergens in the outdoor environment, their structure, localization, and factors affecting their production, transformation, release or degradation. In addition, methods for collecting and quantifying aeroallergens are listed and thoroughly discussed. Finally, the knowledge gaps, challenges and implications associated with aeroallergen analysis are describe

Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation

BACKGROUND: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion. PRINCIPAL FINDINGS: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. CONCLUSIONS: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation

Wireless transmission of biosignals for hyperbaric chamber applications

[EN] This paper presents a wireless system to send biosignals outside a hyperbaric chamber avoiding wires going through the chamber walls. Hyperbaric chambers are becoming more and more common due to new indications of hyperbaric oxygen treatments. Metallic walls physically isolate patients inside the chamber, where getting a patient's vital signs turns into a painstaking task. The paper proposes using a ZigBee-based network to wirelessly transmit the patient's biosignals to the outside of the chamber. In particular, a wearable battery supported device has been designed, implemented and tested. Although the implementation has been conducted to transmit the electrocardiography signal, the device can be easily adapted to consider other biosignals.The authors would like to thanks the University of Balearic Islands (UIB), the Miguel Hernandez University (UMH), MEDIBAROX unit of the Perpetuo Socorro Hospital and the "Catedra de Medicina Hiperbarica" (UMH) for their support allowing the use of its facilities for this work. The authors would also like to thank Borja Mas Boned for his help designing the LabVIEW application. This research has been carried out with funding and promotion of "Catedra de Medicina Hiperbarica" of the Miguel Hernandez University. http://nbio.umh.es/es/2010/12/01/catedra-de-medicina-hiperbarica-medibarox/.Perez-Vidal, C.; Gracia Calandin, LI.; Carmona, C.; Alorda, B.; Salinas, A. (2017). Wireless transmission of biosignals for hyperbaric chamber applications. PLoS ONE. 12(3):1-19. https://doi.org/10.1371/journal.pone.0172768S119123Sureda, A., Batle, J. M., Martorell, M., Capó, X., Tejada, S., Tur, J. A., & Pons, A. (2016). Antioxidant Response of Chronic Wounds to Hyperbaric Oxygen Therapy. PLOS ONE, 11(9), e0163371. doi:10.1371/journal.pone.0163371Branco, B. H. M., Fukuda, D. H., Andreato, L. V., Santos, J. F. da S., Esteves, J. V. D. C., & Franchini, E. (2016). The Effects of Hyperbaric Oxygen Therapy on Post-Training Recovery in Jiu-Jitsu Athletes. PLOS ONE, 11(3), e0150517. doi:10.1371/journal.pone.0150517Xu, Y., Ji, R., Wei, R., Yin, B., He, F., & Luo, B. (2016). The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis. PLOS ONE, 11(2), e0148324. doi:10.1371/journal.pone.0148324Lin, B.-S., Lin, B.-S., Chou, N.-K., Chong, F.-C., & Chen, S.-J. (2006). RTWPMS: A Real-Time Wireless Physiological Monitoring System. IEEE Transactions on Information Technology in Biomedicine, 10(4), 647-656. doi:10.1109/titb.2006.874194Hu, S., Wei, H., Chen, Y., & Tan, J. (2012). A Real-Time Cardiac Arrhythmia Classification System with Wearable Sensor Networks. Sensors, 12(9), 12844-12869. doi:10.3390/s120912844Burns, A., Greene, B. R., McGrath, M. J., O’Shea, T. J., Kuris, B., Ayer, S. M., … Cionca, V. (2010). SHIMMER™ – A Wireless Sensor Platform for Noninvasive Biomedical Research. IEEE Sensors Journal, 10(9), 1527-1534. doi:10.1109/jsen.2010.2045498Gil, Y., Wu, W., & Lee, J. (2012). A Synchronous Multi-Body Sensor Platform in a Wireless Body Sensor Network: Design and Implementation. Sensors, 12(8), 10381-10394. doi:10.3390/s120810381Chin-Teng Lin, Kuan-Cheng Chang, Chun-Ling Lin, Chia-Cheng Chiang, Shao-Wei Lu, Shih-Sheng Chang, … Li-Wei Ko. (2010). An Intelligent Telecardiology System Using a Wearable and Wireless ECG to Detect Atrial Fibrillation. IEEE Transactions on Information Technology in Biomedicine, 14(3), 726-733. doi:10.1109/titb.2010.2047401W. Y. Chung, Y. D. Lee, and S. J. Jung, 'A Wireless Sensor Network Compatible Wearable U-Healthcare Monitoring System Using Integrated Ecg, Accelerometer and Spo2', Conf Proc IEEE Eng Med Biol Soc, 2008 (2008), 1529–32.ZigBee Alliance; http://www.zigbee.org/Mahmood, A., Javaid, N., & Razzaq, S. (2015). A review of wireless communications for smart grid. Renewable and Sustainable Energy Reviews, 41, 248-260. doi:10.1016/j.rser.2014.08.036J.S. Lee, Y.W. Su, and C.C. Shen, "A comparative study of wireless protocols: Bluetooth, UWB, ZigBee, and Wi-Fi, 33rd Annual Conference of the IEEE Industrial Electronics Society (IECON), 2007, pp. 46–51.P.P. Parikh, M.G. Kanabar, and T.S. Sidhu, "Opportunities and challenges of wireless communication technologies for smart grid applications, IEEE PES General Meeting, 2010, pp. 1–7.Fadlullah, Z. M., Fouda, M. M., Kato, N., Takeuchi, A., Iwasaki, N., & Nozaki, Y. (2011). Toward intelligent machine-to-machine communications in smart grid. IEEE Communications Magazine, 49(4), 60-65. doi:10.1109/mcom.2011.5741147A.C. Olteanu, G.D. Oprina, N. Tapus, and S. Zeisberg, "Enabling mobile devices for home automation using ZigBee, 19th IEEE International Conference on Control Systems and Computer Science, 2013, pp. 189–195.Shang, Y. (2014). Vulnerability of networks: Fractional percolation on random graphs. Physical Review E, 89(1). doi:10.1103/physreve.89.012813R. Barea-Navarro. Biomedical Instrumentation. Chapter 3. University of Alcala

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

BACKGROUND: Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. METHODS: We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. RESULTS: Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-alpha, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-alpha and MMP-9 baseline levels were significantly increased in non-responders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-alpha and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. CONCLUSION: Baseline levels of TNF-alpha and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators