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Constraint Analysis and Bladder Wall Low-Dose-Constraint Reduction in Five-Fraction Urethra-Sparing Prostate SBRT

International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2021年第3期10卷 132-148页

作者： Alejandro Prado Inés Flores Ángel Montero Miguel Ángel de la Casa Leyre Alonso Jaime Martí Pedro Fernández-Letón carmen rubio Medical Physics and Radiation Protection Department Hospital Universitario HM Sanchinarro HM Hospitales Madrid Spain Medical Physics and Radiation Protection Department Hospital General de la Defensa Gómez Ulla Madrid Spain Radiation Oncology Department Hospital Universitario HM Sanchinarro HM Hospitales Madrid Spain

Aim: To compare and analyze dose constraints and target coverage results and to reduce Bladder Wall (Bwall) V18.12 for prostate Stereotactic-Body Radiation Therapy (SBRT) when Seminal Vesicles (SSVV) are included or not. Several indicators based on intersection volumes are obtained to predict constraint fulfillment. Background: Due to prostate’s low alpha-beta ratio and the possibility of increasing the therapeutic ratio several moderate and extreme hypofractionation schemes have been proposed. The scheme selected was a fivefraction urethra-sparing prostate SBRT. Materials and Methods: 150 patients divided into two groups according to the inclusion of SSVV in PTV or not were analyzed. Histograms, average values, standard deviations and degrees of fulfillment were obtained for each constraint or goal and group. A possible reduction of the Bwall V18.12 was addressed by re-optimizing fifty randomly chosen patients. Predictors of constraint fulfilling were obtained by using the intersections of Bwall and Rectum Wall (Rwall) with the PTV. Results: Significant differences in Rwall V32.62 and V29 were obtained when evaluating the influence of SSVV inclusion. A reduction of 12% in the Bwall V18.12 constraint was achieved without compromising coverage and OARs doses. No dependence on the inclusion of SSVV was found. Conclusions: Statistically significant differences have been found in Rwall intermediate-dose constraint when SSVV was included. A reduction of 12% in the Bwall V18.12 constraint has been achieved without compromising the PTV coverage and the rest of OARs constraints. Constraint fulfillment predictors could be useful to evaluate the feasibility of prostate SBRT prior to the planning process for every single patient.

关键词： Prostate SBRT Urethra Sparing Bladder Wall Rectum Wall Seminal Vesicles

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废胶粉对热拌沥青混合料疲劳性能的影响

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中外公路 2017年第2期37卷 241-245页

作者：勾俊芳韩森杨晓飞牛帅 Fernando MORENO-NAVARRO Maria carmen rubio-GMEZ Ana JIMNEZ DEL BARCO-CARRIN 长安大学陕西西安710064 天津市市政工程设计研究院

以废旧轮胎磨成的胶粉颗粒作为改性剂生产橡胶沥青是废物利用的有效措施。该文研究内容包括:沥青混合料疲劳开裂性能的改善措施;橡胶沥青混合料、普通沥青混合料及SBS改性沥青混合料的性能对比。通过借助UGR-FACT与拍照设备,观察裂缝在... 详细信息

以废旧轮胎磨成的胶粉颗粒作为改性剂生产橡胶沥青是废物利用的有效措施。该文研究内容包括:沥青混合料疲劳开裂性能的改善措施;橡胶沥青混合料、普通沥青混合料及SBS改性沥青混合料的性能对比。通过借助UGR-FACT与拍照设备,观察裂缝在每一时刻的传播,研究了4种由相同矿物级配、不同沥青构成的沥青混合料的疲劳性能。结果表明:传统沥青路面一旦出现裂缝,路面损害将迅速发展。而掺入废胶粉延缓了路面表面开裂,因此,橡胶沥青混合料的疲劳开裂寿命远超传统沥青混合料。此外,采用干法工艺在混合料中添加胶粉,比其他添加方式产生的裂缝更窄、更少。

关键词：废胶粉疲劳开裂沥青混合料试验测试

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The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle

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Journal of Genetics and Genomics 2015年第5期42卷 249-260页

作者： carmen Díez-Fernández José Gallego Johannes H?berle Javier Cervera Vicente rubio Institute for Biomedicine of Valencia of the Spanish Research Council Medical School of the Catholic University of Valencia University Children's Hospital Zurich and Children's Research Center Centre for Biomedical Networking Research on Rare Diseases of the Carlos Ⅲ Health Institute

Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.

关键词： Urea cycle diseases Inborn errors Hyperammonemia Site-directed mutagenesis Restrained molecular dynamics Allosteric regulation Carbamoyl phosphate synthetase 1 Enzyme

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Parabrachial neuron development: Effects of pre- and neonatal undernutrition in the rat

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Open Journal of Molecular and Integrative Physiology 2012年第4期2卷 112-118页

作者： carmen Torrero Mirelta Regalado Lorena rubio Manuel Salas Department of Developmental Neurobiology and Neurophysiology Institute of Neurobiology University of Mexico Queretaro Mexico.

Pre-and neonatal fasting in the rat has been used as an experimental model to obtain information on how the newborn gustatory system can be damaged, in- terfering with the basic sensory and hedonic proc- esses to different tastants. Fasting during the prenatal period and for 24 days postnatally results in signifi- cant reductions of body and brain weight, number of branches, dendritic density, and cross-sectional area of the PBN multipolar neurons in the central lateral and central medial subnucleus particularly at post- natal days 20 and 30. Furthermore, the underfeeding paradigm affected more the middle portions of the dendritic tree than other parts of the neurons possibly disturbing the afferent characteristics of neuronal acti- vity propagation that may partly disrupt the elabora- tion of synaptic plasticity at later ages. These findings may play a role in the development of complex physio- logical phenomena such as food intake, taste discrimi- nation, learning taste aversion, and appetitive beha- vior.

关键词： Parabrachial Neurons Development Brainstem Undernutrition Rats

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Effects of Neonatal Undernutrition on Development of the Dorsolateral Prefrontal Cortex Pyramidal Cells in the Rat

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Journal of Behavioral and Brain Science 2014年第1期4卷 49-57页

作者： carmen Torrero Mirelta Regalado Lorena rubio Manuel Salas Department of Developmental Neurobiology and Neurophysiology Institute of Neurobiology National Autonomous University of Mexico Campus UNAM Juriquilla Queretaro Mexico

The dorsolateral prefrontal cortex (dlPFC) of the rat plays a role in the encoding of neuronal signals involved in conflict-induced behavioral adjustment, working memory, planning and executive abilities, attentional control and other cognitive responses. In altricial species, early perinatal undernutrition interferes with the morphofunctional organization of a number of central nervous system (CNS) structures including the prefrontal cortex. The effects of neonatal undernutrition on dendritic arbor density, perikaryon measurements, and the number of spines (detected by rapid-Golgi) of basilar dendritic segments in layer III pyramidal neurons of the dlPFC were examined in male Wistar rats on postnatal (PDs) 12, 20, and 30. In the underfed (U) subjects the distal portions of the dendritic arbors had a consistent hipoplasia, mainly on PD 30, with reduced cross sectional area, perimeter, and spine densities on the basilar dendrites on all days studied. Thus, the alterations of the dlPFC pyramidal neurons may interfere with the plastic synaptic activity and cognitive performance of rats subjected to the stress of early underfeeding. Characterizing these anatomical alterations may help to understand the disrupted cognitive processes associated with neonatal undernutrition.

关键词： Neonatal Undernutrition Prefrontal Cortex Development Stressed Rats

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Development of the Gusto Facial Reflex in Perinatally Undernourished Rats

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Journal of Behavioral and Brain Science 2012年第3期2卷 308-314页

作者： Manuel Salas carmen Torrero Mirelta Regalado Lorena rubio Departamento de Neurobiología del Desarrollo y Neurofisiología Instituto de Neurobiología Universidad Nacional Autónoma de México Campus UNAM Juriquilla Querétaro México

In the rat, the taste system plays a critical role in motivating the animal to consume nutrients and avoid toxic substances. In neonatal rat the orofacial movements can be modified by the application of sucrose and quinine in the mouth, producing ingestion or rejection responses, respectively, but there is no information available on the gusto facial reflexes (GFR) under perinatal fasting. The aim of the present study was to determine how undernutrition can affect the development of orofacial responses to sucrose, quinine, and NaCl during early development. Pregnant dams were undernourished by being given 50% of a balanced diet from G6 to G12, 60% from G13-G18, and 100% from G19-G21. On postpartum days 0 - 9, prenatally underfed (UG) pups continued the undernourishment by remaining for 12 h with a foster dam and 12 h with a nipple-ligated mother. Stimuli were presented as a single droplet of sucrose (S), sodium chloride (NaCl), quinine hydrochloride (Q), and water (W) onto the lips at 1, 3, 5, 7, and 9 days of age, and mouth-opening frequency (MO) and lip-licking frequency (LL) were analyzed. The results show consistent effects associated with age, but not with diet, except in the cases of 0.01 M Q, which provoked in the UG subjects increased MO and the reduction of LL, and 0.1 M Q, which consistently reduced both responses. Moreover, S provoked increases in both MO and LL at 0.1 M while NaCl and water elicited minimal effects on GFR. These data suggest that perinatal undernutrition affects the basic components of the gustatory system necessary to produce GFR in the first postnatal days by possibly interfering with the integration of taste input for food learning and the hedonic aspects of gustatory cues.

关键词： Gusto Facial Reflex Newborn Rats Undernutrition

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Analysis of the Sensory and Hedonic Impacts of Sweet and Bitter Tastes in Perinatally Underfed Rats

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Journal of Behavioral and Brain Science 2014年第9期4卷 423-431页

作者： Lorena rubio-Navarro carmen Torrero Mirelta Regalado Manuel Salas Departamento de Neurobiología del Desarrollo y Neurofisiología Instituto de Neurobiología Universidad Nacional Autónoma de México Campus UNAM Juriquilla Querétaro México

Newborn rats discriminate tastes and generate gustofacial response (GFR) because the neuronal substrate is already operating. The oral application of sucrose or quinine hydrochloride produces a specific GFR. We analyzed the effects of perinatal undernutrition on the GFR development of rats at two cue concentrations. In the undernourished group, pregnant dams received different percentages of a balance diet. After birth, prenatally underfed pups continue the undernourishment by remaining for 12 h with a foster dam, and for 12 h with a nipple-ligated mother. Cues were presented as a single droplet of sucrose, sodium chloride, or quinine at low or high concentrations onto the lips at postnatal days (PDs) 1 and 3, and mouth-opening (MOF) and lip-licking frequencies (LLF) were noted. On PD 1 the undernourished group showed smaller MOF increases in response to low salt and quinine stimuli than the controls but no differences at high concentrations. On PD 3, both low and high concentrations of the sucrose and quinine cues significantly increased the MOF in the underfed compared to the control group. Low but not high salt decreased LLF on PD1 in the underfed compared to the control group. On PD 3 the undernourished pups showed significant increases of LLF with low quinine compared with the control rats, but the reverse was observed with high quinine. These data suggest that perinatal undernutrition affects the development of the sensory and hedonic aspects of taste causing changes in GFR expression.

关键词： Undernutrition Gustofacial Responses Gustatory System Development Rats

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Sweet and Bitter Tastes Evoked Different Neuronal Activation in the Rostral Portion of the Nucleus of the Solitary Tract of Developing Rats

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Journal of Behavioral and Brain Science 2012年第3期2卷 291-298页

The impact of the gustatory stimuli on the rostral portion of the nucleus of the solitary tract (rNST) was investigated in developing rats, by using c-fos immunohistochemical staining. Wistar male rats of 5, 15, and 25 days of age were isolated from the mother for 12 h, then stimulated via the intraoral route with quinine, sucrose, or NaCl, and sacrificed 90 min later. The water-stimulated group showed minimal c-fos-like immunoreactivity (FLI) compared with taste-stimulated groups that exhibited different FLI in the rNST at the different ages. At all ages the quinine-stimulated group induced FLI in the medial subfield, while sucrose induced FLI in the lateral subfield of the rNST. The intensity of FLI was highest at P15, and it declined at P25. These findings provide detailed insight into the anatomical basis of rNST activation that is involved in early food intake and the learning capacity of the newborn.

关键词： c-fos Rostral Portion of the Nucleus of the Solitary Tract Gustatory Development Rats

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Maternal Response of Perinatally Underfed Wistar Virgin Females Exposed to Newborn Rats

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Journal of Behavioral and Brain Science 2019年第3期9卷 78-89页

作者： Manuel Salas Mirelta Regalado carmen Torrero Minerva Ortiz-Valladares Lorena rubio Department of Developmental Neurobiology and Neurophysiology Institute of Neurobiology National Autonomous University of Mexico Campus UNAM Juriquilla Queretaro Mexico

Nutrition plays a major role in the survival of the progeny, and its perinatal deficiencies delay physical development and interfere with social and cognitive performance later in life. The effects of early undernutrition on maternal social performance of sensitized adult virgin rats were evaluated. Several maternal and non-maternal responses were measured in virgin female Wistar rats randomly divided into two groups, control and early undernourished, during 19 days of chronic daily exposure to fresh foster pups in home-cage conditions. Underfed females (F0) received different percentages of a balanced diet during gestation. After birth, pups were underfed (F1) by alternating every 12 h between litters two lactating dams, one with ligated nipples. Weaning was at 25 days of age followed by an ad lib diet until postpartum day 90, when sensitized virgins were maternally tested daily for seven successive sessions. Significantly (p < 0.05) low body weight scores in UG F1 virgins of five different ages were observed. The UG F1 females expressed significantly (p < 0.05) lower frequency values in sniffing, licking, retrieving, crouching, and handling shavings, with clear prolonged sniffing, retrieving and handling shaving latencies towards the foster pups compared with CG F1 sensitized females. Self-grooming was not affected, whereas exploration was significantly reduced. Current findings suggest that perinatal undernutrition interfered the organization of a core neuronal circuitry underlying the mother-litter interactions involved in social and cognitive performance of sensitized adult virgins. Furthermore, the behavioral maternal alterations in F1 virgins may possibly generate a risky negative social environment to induce cognitive and/or brain disorders in later generations.

关键词： Early Undernutrition Maternal Sensitization Cognitive Development Rats

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Olfactory Discrimination in Adult Male Rats Undernourished during the Pre- and Neonatal Period

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Journal of Behavioral and Brain Science 2012年第3期2卷 283-290页

作者： Mitzi G. Carreon carmen Torrero Mirelta Regalado Lorena rubio Manuel Salas Developmental Neurobiology and Neurophysiology Department Neurobiology Institute University of Mexico Campus UNAM Juriquilla Queretaro Mexico

In the neonatal rat, the olfactory system is a fundamental channel to locate and recognize the mother, to survive and develop early social behavior, and to distinguish related or unrelated members of a litter. Perinatal undernutrition in rats alters the neuronal organization and functioning of the olfactory system and its ascending relays, possibly affecting odor discrimination. In this study we compared the frequency and time spent visiting the source of urine obtained from unrelated female subjects and amyl acetate odors vs water in adult perinatally underfed rats. Each test initiated with one daily presentation during three consecutive aliquots of deionized water (10 μl) placed on a filter paper for 2 min, separated by 1-min intervals for habituation. The water presentations were followed by three exposures to an odor, all at the same dilution (either 1:1 or 1:80) for dishabituation. Control (C) and undernourished (U) subjects display similar, significant habituation/dishabituation responses, except that the U subjects showed greater increases in the frequency and duration of visits to undiluted and diluted urine and amyl acetate cues compared to the controls. These findings are similar to previous studies showing that adult rats investigate novel odors longer than the familiar ones. Thus, perinatal undernutrition appears to interfere with the foundation of the olfactory development causing long-term olfactory discrimination deficits as revealed by the increased frequency and duration of visits to the source of odors that may be relevant for social behavior.

关键词： Olfactory Discrimination Main Olfactory System Perinatal Undernutrition

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