Peripheral Organ Equivalent Dose Estimation Procedure in Proton Therapy.

The aim of this work is to present a reproducible methodology for the evaluation of total equivalent doses in organs during proton therapy facilities. The methodology is based on measuring the dose equivalent in representative locations inside an anthropomorphic phantom where photon and neutron dosimeters were inserted. The Monte Carlo simulation was needed for obtaining neutron energy distribution inside the phantom.

Modified Geometry of Ru Asymmetric Eye Plaques to Improve Dosimetric Calculations in Ophthalmic Brachytherapy.

Ru/Rh asymmetric plaques for ophthalmic brachytherapy have special geometric designs with a cutout intended to prevent irradiation of critical ocular structures proximal to the tumor. In this work, we present new geometric models for PENELOPE+PenEasy Monte Carlo simulations of these applicators, differing from the vendor-reported geometry, that better match their real geometry to assess their dosimetric impact. Simulation results were benchmarked to experimental dosimetric data from radiochromic film measurements, data provided by the manufacturer in the calibration certificates, and other experimental results published in the literature, obtaining, in all cases, better agreement with the modified geometries.

Clinical Outcomes after Surgical Resection Combined with Brachytherapy for Uveal Melanomas.

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy.

Chronic restraint stress induces anxiety-like behavior and remodeling of dendritic spines in the central nucleus of the amygdala.

Previous studies have shown that the anxiogenic effects of chronic stress do not correlate with dendritic remodeling in the central nucleus of the amygdala (CeA). We analyzed the effect of chronic restraint stress (CRS; 20 min/day for 14 days), relative to control (CTRL) conditions on anxiety-like behavior in the elevated plus maze (EPM) and the open field tests, and dendritic morphology, dendritic spine density and spine type numbers in pyramidal neurons of the CeA. Reversal of CRS-induced effects was explored in animals allowed a 14-day stress-free recovery after treatments.

Chronic restraint stress induces serotonin transporter expression in the rat adrenal glands.

Chronic restraint stress (CRS) magnifies restraint-induced corticosterone secretion through a mechanism involving increased adrenocortical 5-HT content and turnover. We analysed the impact of CRS on serotonin transporter (SERT) expression and distribution in rat adrenal glands. Male Wistar rats were submitted to CRS (20 min/day) or undisturbed control conditions for 14 days.

Effect of chronic corticosterone treatment on expression and distribution of serotonin 5-HT7 receptors in rat adrenal glands.

Sensitized stress-induced corticosterone (CORT) secretion in chronically stressed rats involves 5-HT7 receptor activation. The effect of 14-day chronic CORT and vehicle (VEH) administration on 5-HT7 receptor expression in adrenal glands, adrenal 5-HT content, and adrenocorticotropic hormone and CORT secretion was analysed. On day 15, VEH- and CORT-treated animals were perfused or decapitated without stress exposure (0 min) or after 10 and 30 min of restraint for collection of trunk blood and tissues.

Intensity-modulated radiation therapy and volumetric modulated arc therapy versus conventional conformal techniques at high energy: Dose assessment and impact on second primary cancer in the out-of-field region.

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

Monte Carlo verification of radiotherapy treatments with CloudMC.

Background: A new implementation has been made on CloudMC, a cloud-based platform presented in a previous work, in order to provide services for radiotherapy treatment verification by means of Monte Carlo in a fast, easy and economical way. A description of the architecture of the application and the new developments implemented is presented together with the results of the tests carried out to validate its performance.

Methods: CloudMC has been developed over Microsoft Azure cloud.

Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide.

A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μL) of vehicle, CAP (0.

Uncomplicated and Cancer-Free Control Probability (UCFCP): A new integral approach to treatment plan optimization in photon radiation therapy.

Purpose: Biological treatment plan evaluation does not currently consider second cancer induction from peripheral doses associated to photon radiotherapy. The aim is to propose a methodology to characterize the therapeutic window by means of an integral radiobiological approach, which considers not only Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) but also Secondary Cancer Probability (SCP).

Methods: Uncomplicated and Cancer-Free Control Probability (UCFCP) function has been proposed assuming a statistically uncorrelated response for tumour and normal tissues.

Correction: Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study.

[This corrects the article DOI: 10.1371/journal.pone.

Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study.

Objectives: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients.

Methods: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments.

GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?

The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction.

Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders.

A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of stress-related disorders, and the brain serotonin (5-HT) system plays a major role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5-HT system so it is possible that alterations of endocrine 5-HT mechanisms may underlie HPA axis overdrive in stress-related diseases. Available evidence suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system activation, and pharmacological blockade of 5-HT7 receptors produces a fast-acting antidepressant-like action and shortens the onset of antidepressant-like effects of various classes of antidepressants.

Neutron contamination in radiotherapy: estimation of second cancers based on measurements in 1377 patients.

Purpose: Second cancer, as a consequence of a curative intent radiotherapy (RT), represents a growing concern nowadays. The unwanted neutron exposure is an important contributor to this risk in patients irradiated with high energy photon beams. The design and development by our group of a neutron digital detector, together with the methodology to estimate, from the detector readings, the neutron equivalent dose in organs, made possible the unprecedented clinical implementation of an online and systematic neutron dosimetry system.

Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: involvement of 5-HT₇ receptors.

Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT₇ receptor antagonist); 2) 5-HT₇ receptor-like immunoreactivity (5-HT₇-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups.

Monte Carlo simulation of COMS ophthalmic applicators loaded with Bebig I25.S16 seeds and comparison with planning system predictions.

Purpose: To simulate the Bebig model I125.S16 source and obtain AAPM Task Group Report 43 brachytherapy dosimetry parameters for comparison to consensus and previously published values. The seed model will then be incorporated into a Monte Carlo model of COMS eye plaques and simulation results will be used for seed-carrier set modeling in a commercial planning system.

Effect of inter-renal aortic coarctation-induced hypertension on function and expression of vascular α(1A)- and α(1D)-adrenoceptors.

We investigated the effect of inter-renal aortic coarctation on the function and expression of vascular α(1A)- and α(1D)-adrenoceptors and plasma angiotensin II (ATII) in rats. Male Wistar rats, either sham operated (SO), or with aortic coarctation for 7 (AC7) and 14 days (AC14) were used for agonist-induced pressor responses in vehicle (physiological saline)- and antagonist-treated anesthetized animals, immunoblot analysis (α(1A)- and α(1D)-adrenoceptor in aorta and caudal arteries), and immunoassay (plasma ATII). The α(1D)-adrenoceptor antagonist, BMY-7378 (BMY) blocked noradrenaline-induced responses in the order SO > AC7 ≫ AC14; in contrast, the α(1A)-adrenoceptor antagonist RS-100329 (RS), produced a marginal shift to the right of the dose-response curve to noradrenaline, along with a strong decrease of the maximum pressor effect in the order SO > AC7 = AC14.

Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT(7) receptors.

Objective: To explore whether pharmacological stimulation of the 5-hydroxytryptamine(7) (5-HT(7) ) receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats.

Background: The serotonin 5-HT(7) receptor was proposed to be involved in migraine pathogenesis and evidence suggests it plays a role in peripheral nociception and hyperalgesia through an action on sensory afferent neurons.

Methods: The potential activating or sensitizing role of 5-HT(7) receptors on trigeminal sensory neurons, as visualized by Fos-like immunoreactivity in the superficial layers of the trigeminal nucleus caudalis in rats, was investigated using the 5-HT(7) receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively.

Increased angiotensin II AT1 receptor mRNA and binding in spleen and lung of AT2 receptor gene disrupted mice.

To clarify the relationship between Angiotensin II AT(1) and AT(2) receptors, we studied AT(1) receptor mRNA and binding expression in tissues from AT(2) receptor gene disrupted (AT(2)(-/-)) female mice, where AT(2) receptors are not expressed in vivo, using in situ hybridization and quantitative autoradiography. Wild type mice expressed AT(1A) receptor mRNA and AT(1) receptor binding in lung parenchyma, the spleen, predominantly in the red pulp, and in liver parenchyma. In wild type mice, lung AT(2) receptors were expressed in lung bronchial epithelium and smooth muscle, and were not present in the lung parenchyma, the spleen or the liver.

Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection: final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903.

Background: The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials.

Methods: We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.

Pharmacological evidence that 5-HT(1B/1D) receptors mediate hypotension in anesthetized rats.

5-Carboxamidotryptamine (5-CT; 0.003-310 microg/kg, i.v.

5-HT7 receptor-mediated dilatation in the middle meningeal artery of anesthetized rats.

Topical administration of 5-carboxamidotryptamine (5-CT; 0.01-1000 microM) to the exposed dura mater encephali of anesthetized rats produced decreases in blood pressure and dilatation in the middle meningeal artery. Pretreatment with the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide hydrochloride monohydrate (GR-127935; 1 mg/kg, i.

Improvement of dyslipidemia in patients switching from stavudine to tenofovir: preliminary results.

In a prospective, multicentre, switch study to identify the most frequently occurring nucleoside reverse transcriptase inhibitor (NRTI)-associated toxicities that cause NRTI withdrawal in virologically suppressed HIV-infected patients, among those who underwent stavudine substitution by tenofovir, 271 had hypertriglyceridemia and 193 had hypercholesterolemia. After 12 weeks of switching from stavudine to tenofovir, triglyceride and cholesterol levels showed significant de-creases, which suggests that such a switch may reverse, at least partly, stavudine-associated dyslipidaemia.