Transient Down-Regulation of Sound-Induced c-Fos Protein Expression in the Inferior Colliculus after Ablation of the Auditory Cortex

We tested whether lesions of the excitatory glutamatergic projection from the auditory cortex (AC) to the inferior colliculus (IC) induce plastic changes in neurons of this nucleus. Changes in neuronal activation in the IC deprived unilaterally of the cortico-collicular projection were assessed by quantitative c-Fos immunocytochemistry. Densitometry and stereology measures of sound-induced c-Fos immunoreactivity in the IC showed diminished labeling at 1, 15, 90, and 180 days after lesions to the AC suggesting protein down-regulation, at least up to 15 days post-lesion. Between 15 and 90 days after the lesion, c-Fos labeling recovers, approaching control values at 180 days. Thus, glutamatergic excitation from the cortex maintains sound-induced activity in neurons of the IC. Subdivisions of this nucleus receiving a higher density of cortical innervation such as the dorsal cortex showed greater changes in c-Fos immunoreactivity, suggesting that the anatomical strength of the projection correlates with effect strength. Therefore, after damage of the corticofugal projection, neurons of the IC down-regulate and further recover sound-induced c-Fos protein expression. This may be part of cellular mechanisms aimed at balancing or adapting neuronal responses to altered synaptic inputs

Acoustic Bragg Peak Localization in Proton Therapy Treatment: Simulation Studies

[EN] A full chain simulation of the acoustic hadron therapy monitoring for brain tumors is presented in this work. For the study, a proton beam of 100 MeV was considered. In the first stage, Geant4 was used to simulate the energy deposition and to study the behavior of the Bragg peak. The energy deposition in the medium produced local heating that can be considered instantaneous with respect to the hydrodynamic time scale producing a sound pressure wave. The resulting thermoacoustic signal was subsequently obtained by solving the thermoacoustic equation. The acoustic propagation was simulated by the Finite Element Method (FEM) in the brain and the skull, where a set of piezoelectric sensors were placed. Lastly, the final received signals in the sensors were processed in order to reconstruct the position of the thermal source and, thus, to determine the feasibility and accuracy of acoustic beam monitoring in hadron therapy.Otero, J.; Felis, I.; Ardid Ramírez, M.; Herrero Debón, A.; Merchán, JA. (2019). Acoustic Bragg Peak Localization in Proton Therapy Treatment: Simulation Studies. MDPI. 1-7. https://doi.org/10.3390/ecsa-6-06533S1

Bragg Peak Localization with Piezoelectric Sensors for Proton Therapy Treatment

[EN] A full chain simulation of the acoustic hadrontherapy monitoring for brain tumours is presented in this work. For the study, a proton beam of 100 MeV is considered. In the first stage, Geant4 is used to simulate the energy deposition and to study the behaviour of the Bragg peak. The energy deposition in the medium produces local heating that can be considered instantaneous with respect to the hydrodynamic time scale producing a sound pressure wave. The resulting thermoacoustic signal has been subsequently obtained by solving the thermoacoustic equation. The acoustic propagation has been simulated by FEM methods in the brain and the skull, where a set of piezoelectric sensors are placed. Last, the final received signals in the sensors have been processed in order to reconstruct the position of the thermal source and, thus, to determine the feasibility and accuracy of acoustic beam monitoring in hadrontherapy.This research received was funded by the Spanish Agencia Estatal de Investigacion, grant numbers FPA2015-65150-C3-2-P (MINECO/FEDER) and PGC2018-096663-B-C43 (MCIU/FEDER).Otero-Vega, JE.; Felis-Enguix, I.; Herrero Debón, A.; Merchán, JA.; Ardid Ramírez, M. (2020). Bragg Peak Localization with Piezoelectric Sensors for Proton Therapy Treatment. Sensors. 20(10):1-12. https://doi.org/10.3390/s20102987S1122010A population-based assessment of proton beam therapy utilization in California. (2020). The American Journal of Managed Care, 26(2), e28-e35. doi:10.37765/ajmc.2020.42398Dutz, A., Agolli, L., Bütof, R., Valentini, C., Baumann, M., Lühr, A., … Krause, M. (2020). Neurocognitive function and quality of life after proton beam therapy for brain tumour patients. Radiotherapy and Oncology, 143, 108-116. doi:10.1016/j.radonc.2019.12.024Lesueur, P., Calugaru, V., Nauraye, C., Stefan, D., Cao, K., Emery, E., … Thariat, J. (2019). Proton therapy for treatment of intracranial benign tumors in adults: A systematic review. Cancer Treatment Reviews, 72, 56-64. doi:10.1016/j.ctrv.2018.11.004Amaldi, U., Bonomi, R., Braccini, S., Crescenti, M., Degiovanni, A., Garlasché, M., … Zennaro, R. (2010). Accelerators for hadrontherapy: From Lawrence cyclotrons to linacs. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 620(2-3), 563-577. doi:10.1016/j.nima.2010.03.130Weber, D. C., Abrunhosa-Branquinho, A., Bolsi, A., Kacperek, A., Dendale, R., Geismar, D., … Grau, C. (2017). Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire. Radiotherapy and Oncology, 124(2), 185-189. doi:10.1016/j.radonc.2017.07.012MIZUMOTO, M., OSHIRO, Y., YAMAMOTO, T., KOHZUKI, H., & SAKURAI, H. (2017). Proton Beam Therapy for Pediatric Brain Tumor. Neurologia medico-chirurgica, 57(7), 343-355. doi:10.2176/nmc.ra.2017-0003Sulak, L., Armstrong, T., Baranger, H., Bregman, M., Levi, M., Mael, D., … Learned, J. (1979). Experimental studies of the acoustic signature of proton beams traversing fluid media. Nuclear Instruments and Methods, 161(2), 203-217. doi:10.1016/0029-554x(79)90386-0Aso, T., Kimura, A., Tanaka, S., Yoshida, H., Kanematsu, N., Sasaki, T., & Akagi, T. (2005). Verification of the dose distributions with GEANT4 simulation for proton therapy. IEEE Transactions on Nuclear Science, 52(4), 896-901. doi:10.1109/tns.2005.852697Jones, K. C., Witztum, A., Sehgal, C. M., & Avery, S. (2014). Proton beam characterization by proton-induced acoustic emission: simulation studies. Physics in Medicine and Biology, 59(21), 6549-6563. doi:10.1088/0031-9155/59/21/6549Jones, K. C., Seghal, C. M., & Avery, S. (2016). How proton pulse characteristics influence protoacoustic determination of proton-beam range: simulation studies. Physics in Medicine and Biology, 61(6), 2213-2242. doi:10.1088/0031-9155/61/6/2213Donnelly, B. R., & Medige, J. (1997). Shear Properties of Human Brain Tissue. Journal of Biomechanical Engineering, 119(4), 423-432. doi:10.1115/1.2798289Gu, L., Chafi, M. S., Ganpule, S., & Chandra, N. (2012). The influence of heterogeneous meninges on the brain mechanics under primary blast loading. Composites Part B: Engineering, 43(8), 3160-3166. doi:10.1016/j.compositesb.2012.04.014Peterson, J., & Dechow, P. C. (2003). Material properties of the human cranial vault and zygoma. The Anatomical Record, 274A(1), 785-797. doi:10.1002/ar.a.10096Fellah, Z. E. A., Chapelon, J. Y., Berger, S., Lauriks, W., & Depollier, C. (2004). Ultrasonic wave propagation in human cancellous bone: Application of Biot theory. The Journal of the Acoustical Society of America, 116(1), 61-73. doi:10.1121/1.1755239Raffaele, L. (2016). Advances in hadrontherapy dosimetry. Physica Medica, 32, 187. doi:10.1016/j.ejmp.2016.07.323Dosanjh, M., Amaldi, U., Mayer, R., & Poetter, R. (2018). ENLIGHT: European network for Light ion hadron therapy. Radiotherapy and Oncology, 128(1), 76-82. doi:10.1016/j.radonc.2018.03.014Ahmad, M., Xiang, L., Yousefi, S., & Xing, L. (2015). Theoretical detection threshold of the proton-acoustic range verification technique. Medical Physics, 42(10), 5735-5744. doi:10.1118/1.4929939Smith, A., Gillin, M., Bues, M., Zhu, X. R., Suzuki, K., Mohan, R., … Matsuda, K. (2009). The M. D. Anderson proton therapy system. Medical Physics, 36(9Part1), 4068-4083. doi:10.1118/1.3187229Yock, T. I., & Tarbell, N. J. (2004). Technology Insight: proton beam radiotherapy for treatment in pediatric brain tumors. Nature Clinical Practice Oncology, 1(2), 97-103. doi:10.1038/ncponc0090Riva, M., Vallicelli, E. A., Baschirotto, A., & De Matteis, M. (2018). Acoustic Analog Front End for Proton Range Detection in Hadron Therapy. IEEE Transactions on Biomedical Circuits and Systems, 12(4), 954-962. doi:10.1109/tbcas.2018.2828703Acoustics Module User’s Guidehttps://doc.comsol.com/5.4/doc/com.comsol.help.aco/AcousticsModuleUsersGuide.pdfArdid, M., Felis, I., Martínez-Mora, J. A., & Otero, J. (2017). Optimization of Dimensions of Cylindrical Piezoceramics as Radio-Clean Low Frequency Acoustic Sensors. Journal of Sensors, 2017, 1-8. doi:10.1155/2017/8179672Otero, Felis, Ardid, & Herrero. (2019). Acoustic Localization of Bragg Peak Proton Beams for Hadrontherapy Monitoring. Sensors, 19(9), 1971. doi:10.3390/s19091971Levenberg, K. (1944). A method for the solution of certain non-linear problems in least squares. Quarterly of Applied Mathematics, 2(2), 164-168. doi:10.1090/qam/10666Geant4 A Simulation Toolkithttp://geant4-userdoc.web.cern.ch/geant4-userdoc/UsersGuides/ForApplicationDeveloper/BackupVersions/V10.5-2.0/fo/BookForApplicationDevelopers.pdfBarber, T. W., Brockway, J. A., & Higgins, L. S. (1970). THE DENSITY OF TISSUES IN AND ABOUT THE HEAD. Acta Neurologica Scandinavica, 46(1), 85-92. doi:10.1111/j.1600-0404.1970.tb05606.xAdrián-Martínez, S., Bou-Cabo, M., Felis, I., Llorens, C. D., Martínez-Mora, J. A., Saldaña, M., & Ardid, M. (2015). Acoustic Signal Detection Through the Cross-Correlation Method in Experiments with Different Signal to Noise Ratio and Reverberation Conditions. Lecture Notes in Computer Science, 66-79. doi:10.1007/978-3-662-46338-3_

A theoretical insight into the photophysics of psoralen

Psoralen photophysics has been studied on quantum chemistry grounds using the multiconfigurational second-order perturbation method CASPT2. Absorption and emission spectra of the system have been rationalized by computing the energies and properties of the low-lying singlet and triplet excited states. The S1 ππ* state has been determined to be responsible of the lowest absorption and fluorescence bands and to initially carry the population in the photophysical processes related to the phototherapeutic properties of psoralen derivatives. The low-lying T1 ππ* state is, on the other hand, protagonist of the phosphorescence, and its prevalent role in the reactivity of psoralen is suggested to be related to the elongation of the pyrone ring C3–C4 bond, where the spin density is distributed on both carbon atoms. Analysis of energy gaps and spin-orbit coupling elements indicates that the efficient photophysical process leading to the population of the lowest triplet state does not take place at the Franck-Condon region but along the S1 relaxation [email protected] [email protected] [email protected]

A theory of nonvertical triplet energy transfer in terms of accurate potential energy surfaces: The transfer reaction from π,π∗ triplet donors to 1,3,5,7-cyclooctatetraene

Triplet energy transfer (TET) from aromatic donors to 1,3,5,7-cyclooctatetraene (COT) is an extreme case of “nonvertical” behavior, where the transfer rate for low-energy donors is considerably faster than that predicted for a thermally activated (Arrhenius) process. To explain the anomalous TET of COT and other molecules, a new theoretical model based on transition state theory for nonadiabatic processes is proposed here, which makes use of the adiabatic potential energy surfaces (PES) of reactants and products, as computed from high-level quantum mechanical methods, and a nonadiabatic transfer rate constant. It is shown that the rate of transfer depends on a geometrical distortion parameter γ = (2g2/κ1)1/2 in which g stands for the norm of the energy gradient in the PES of the acceptor triplet state and κ1 is a combination of vibrational force constants of the ground-state acceptor in the gradient direction. The application of the model to existing experimental data for the triplet energy transfer reaction to COT from a series of π,π∗ triplet donors, provides a detailed interpretation of the parameters that determine the transfer rate constant. In addition, the model shows that the observed decrease of the acceptor electronic excitation energy is due to thermal activation of C�C bond stretchings and C–C bond torsions, which collectively change the ground-state COT bent conformation (D2d) toward a planar triplet state (D8h)[email protected]

Dihydrocapsiate does not increase energy expenditure nor fat oxidation during aerobic exercise in men with overweight/ obesity: a randomized, triple-blinded, placebo-controlled, crossover trial

Background: Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure (EE) and fat oxidation (FATox), yet whether they can modulate those parameters during exercise conditions remains poorly understood. We hypothesized that dihydrocapsiate (DHC) ingestion would increase EE and specifically FATox during an acute bout of aerobic exercise at FATmax intensity (the intensity that elicits maximal fat oxidation during exercise [MFO]) in men with overweight/ obesity. Since FATmax and MFO during aerobic exercise appear to be indicators of metabolic flexibility, whether DHC has an impact on FATox in this type of population is of clinical interest. Methods: A total of 24 sedentary men (age = 40.2 ± 9.2 years-old; body mass index = 31.6 ± 4.5 kg/m2 [n = 11 overweight, n = 13 obese]) participated in this randomized, triple-blinded, placebocontrolled, crossover trial (registered under ClinicalTrials.gov Identifier no. NCT05156697). On the first day, participants underwent a submaximal exercise test on a cycle ergometer to determine their MFO and FATmax intensity during exercise. After 72 hours had elapsed, the participants returned on 2 further days (≥ 72 hours apart) and performed a 60 min steady-state exercise bout (i.e. cycling at their FATmax, constant intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized. Respiratory gas exchange was monitored by indirect calorimetry. Serum marker concentrations (i.e. glucose, triglycerides, non-esterified fatty acids (NEFAs), skin temperature, thermal perception, heart rate, and perceived fatigue) were assessed. Results: There were no significant differences (P > 0.05) between DHC and placebo conditions in the EE and FATox during exercise. Similarly, no significant changes were observed in glucose, triglycerides, or NEFAs serum levels, neither in the skin temperature nor thermal perception across conditions. Heart rate and perceived fatigue did not differ between conditions. Conclusions: DHC supplementation does not affect energy metabolism during exercise in men with overweight/obesity.Spanish Junta de Andalucia via Consejeria de Conocimiento, Investigacion y Universidades, Proyectos I+D+i del Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER 2018) B.CTS.377.UGR18Spanish Government PTA 12264-I FPU16/02828 FPU16/0515

Reversible Functional Changes Evoked by Anodal Epidural Direct Current Electrical Stimulation of the Rat Auditory Cortex

Rat auditory cortex was subjected to 0.1 mA anodal direct current in seven 10-min sessions on alternate days. Based on the well-known auditory cortex control of olivocochlear regulation through corticofugal projections, auditory brainstem responses (ABRs) were recorded as an indirect test of the effectiveness and reversibility of the multisession protocol of epidural stimulation. Increases of 20–30 dB ABR auditory thresholds shown after epidural stimulation reverted back to control levels 10 min after a single session. However, increases in thresholds revert 4 days after multisession stimulation. Less changes in wave amplitudes and threshold shifts were shown in ABR recorded contralaterally to the electrically stimulated side of the brain. To assess tissue effects of epidural electric stimulation on the brain cortex, well characterized functional anatomical markers of glial cells (GFAP/astrocytes and Iba1/microglial cells) and neurons (c-Fos) were analyzed in alternate serial sections by quantitative immunocytochemistry. Restricted astroglial and microglial reactivity was observed within the cytoarchitectural limits of the auditory cortex. However, interstitial GFAP overstaining was also observed in the ventricular surface and around blood vessels, thus supporting a potential global electrolytic stimulation of the brain. These results correlate with extensive changes in the distribution of c-Fos immunoreactive neurons among layers along sensory cortices after multisession stimulation. Quantitative immunocytochemical analysis supported this idea by showing a significant increase in the number of positive neurons in supragranular layers and a decrease in layer 6 with no quantitative changes detected in layer 5. Our data indicate that epidural stimulation of the auditory cortex induces a reversible decrease in hearing sensitivity due to local, restricted epidural stimulation. A global plastic response of the sensory cortices, also reported here, may be related to electrolytic effects of electric currents

Imaging the volcanic structures beneath Gran Canaria Island using new gravity data

From a new gravity data set that covers homogeneously the whole surface of Gran Canaria (Canary Islands, Spain) and marine gravity data in the nearest offshore, we have obtained a Bouguer anomaly gravity map of the island which improves the previous ones. Using these gravity anomalies, we have applied a gravity inversion approach to investigate the structures beneath the surface of Gran Canaria Island and derive a 3D gravity sources model. The geometry of structures with anomalous density values is constrained up to a depth of approximately 20,000 m below the sea level. The interpretation of the density model identified structures related to the different volcanic stages of Gran Canaria. Several deep-rooted high-density structures represent the intrusive bodies emplaced in the early formation of Gran Canaria and the magma plumbing system of the Miocene volcanic edifices. A low-density body in the center of the island may be associated with the syenitic core of the felsic central volcanic edifice (Tejeda Caldera). Shallow low-density structures identified fractures which acted as feeder dikes of monogenetic volcanoes during the rejuvenated stage. Finally, the NW-SE rift, which is the most important volcano-tectonic structure of Gran Canaria, has a characteristic gravimetric signature and represents a long-lived extensional fracture zone that has controlled the volcanic activity at least since the Miocene