Nuclear Physics meets Medicine and Biology: Boron Neutron Capture Therapy

BNCT is a tumour treatment based on thermal-neutron irradiation of tissues enriched with 10B, which according to the 10B(n, )7Li reaction produces particles with high Linear Energy Transfer and short range. Since this treatment can deliver a therapeutic tumour dose sparing normal tissues, BNCT represents an alternative for diffuse tumours and metastases, which show poor response to surgery and photontherapy. In 2001 and 2003, in Pavia BNCT was applied to an isolated liver, which was infused with boron, explanted, irradiated and re-implanted. A new project was then initiated for lung tumours, developing a protocol for Boron concentration measurements and performing organ-dose Monte Carlo calculations; in parallel, radiobiology studies are ongoing to characterize the BNCT effects down to cellular level. After a brief introduction, herein we will present the main activities ongoing in Pavia including the radiobiological ones, which are under investigation not only experimentally but also theoretically, basing on a Monte Carlo code recently extended to simulate cell killing

Dietary Tryptophan Induces Opposite Health-Related Responses in the Senegalese Sole (Solea senegalensis) Reared at Low or High Stocking Densities With Implications in Disease Resistance

High rearing densities are typical conditions of both inland and onshore intensive aquaculture units. Despite obvious drawbacks, this strategy is nonetheless used to increase production profits. Such conditions inflict stress on fish, reducing their ability to cope with disease, bringing producers to adopt therapeutic strategies. In an attempt to overcome deleterious effects of chronic stress, Senegalese sole, Solea senegalensis, held at low (LD) or high density (HD) were fed tryptophan-supplemented diets with final tryptophan content at two (TRP2) or four times (TRP4) the requirement level, as well as a control and non-supplemented diet (CTRL) for 38 days. Fish were sampled at the end of the feeding trial for evaluation of their immune status, and mortalities were recorded following intra-peritoneal infection with Photobacterium damselae subsp. piscicida. Blood was collected for analysis of the hematological profile and innate immune parameters in plasma. Pituitary and hypothalamus were sampled for the assessment of neuro-endocrine-related gene expression. During the feeding trial, fish fed TRP4 and held at LD conditions presented higher mortalities, whereas fish kept at HD seemed to benefit from this dietary treatment, as disease resistance increased over that of CTRL-fed fish. In accordance, cortisol level tended to be higher in fish fed both supplemented diets at LD compared to fish fed CTRL, but was lower in fish fed TRP4 than in those fed TRP2 under HD condition. Together with lower mRNA levels of proopiomelanocortin observed with both supplementation levels, these results suggest that higher levels of tryptophan might counteract stress-induced cortisol production, thereby rendering fish better prepared to cope with disease. Data regarding sole immune status showed no clear effects of tryptophan on leucocyte numbers, but TRP4-fed fish displayed inhibited alternative complement activity (ACH50) when held at LD, as opposed to their HD counterparts whose ACH50 was higher than that of CTRLfed fish. In conclusion, while dietary tryptophan supplementation might have harmful effects in control fish, it might prove to be a promising strategy to overcome chronic stress-induced disease susceptibility in farmed Senegalese sole

Neutron Autoradiography Combined With UV-C Sensitization: Toward the Intracellular Localization of Boron

Our group has reported the imprint formation of biological material on polycarbonate nuclear track detectors by UV-C exposure, which is used as an approach to simultaneously visualize cell imprints and nuclear tracks coming from the boron neutron capture reaction. Considering that the cell nucleus has a higher UV-C absorption than the cytoplasm and that hematoxylin preferentially stains the nucleus, we proposed to enhance the contrast between these two main cell structures by hematoxylin staining before UV-C sensitization. In this study, several experiments were performed in order to optimize UV-C exposure parameters and chemical etching conditions for cell imprint formation using the SK-BR-3 breast cancer cell line. The proposed method improves significantly the resolution of the cell imprints. It allows clear differentiation of the nucleus from the rest of the cell, together with nuclear tracks pits. Moreover, it reduces considerably the UV-C exposure time, an important experimental issue. The proposed methodology can be applied to study the boron distribution independently from the chosen cell line and/or boron compounds.Fil: Gadan, Mario Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Lloyd, Rodrigo. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María S.. Comisión Nacional de Energía Atómica; ArgentinaFil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Prime-boost vaccination with chimeric antigens adjuvanted in Montanide™ ISA50 V2 confers protection against experimental Lepeophtheirus salmonis infestation in Atlantic salmon (Salmo salar L.)

IntroductionSea lice are crustacean ectoparasites affecting Atlantic salmon production worldwide and impediments to industry growth. Chemical treatment has been the method of choice to control infestation with increasing resistance. Vaccination is an environmentally friendly alternative for sea lice control; however, obtaining high levels of lice reduction through active immunization has proven difficult. This study aimed to explore the efficacy of two sea lice vaccine prototypes under laboratory-controlled conditions.MethodsTherein, fish were vaccinated with two chimeric antigens, TT-P0 or P0-my32, using oil-adjuvanted vaccine formulations and a prime-boost vaccination protocol. Fish were experimentally challenged with copepodids at 2, 5, and 11 months post-prime vaccination.Results and discussionTT-P0 vaccinated fish had a significantly lower lice number at all three challenges, 88, 90, and 20%, respectively, compared to controls. The P0-my32 vaccine gave high protection at early time points post-vaccination, with 91 and 75.4% reduction at 3 and 6 months, respectively, fading off at 12 months (4.2% reduction vs. control). The TT-P0 group had a significantly lower lice number than controls at the 11-month challenge. A higher degree of protection coincided with higher circulating antibody levels against homologous antigens. This proof of concept study encourage the use of vaccination as a tool to reduce the lice burden in salmon, and preclinical and clinical testing at a large scale is needed to document the level of protection attained under field conditions

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

AimIn this work we present a methodology to produce an “imprint” of cells cultivated on a polycarbonate detector by exposure of the detector to UV C radiation.BackgroundThe distribution and concentration of 10B atoms in tissue samples coming from BNCT (Boron Neutron Capture Therapy) protocols can be determined through the quantification and analysis of the tracks forming its autoradiography image on a nuclear track detector. The location of boron atoms in the cell structure could be known more accurately by the simultaneous observation of the nuclear tracks and the sample image on the detector.Materials and MethodsA UV C irradiator was constructed. The irradiance was measured along the lamp direction and at different distances. Melanoma cells were cultured on polycarbonate foils, incubated with borophenylalanine, irradiated with thermal neutrons and exposed to UV C radiation. The samples were chemically attacked with a KOH solution.ResultsA uniform irradiation field was established to expose the detector foils to UV C light. Cells could be seeded on the polycarbonate surface. Both imprints from cells and nuclear tracks were obtained after chemical etching.ConclusionsIt is possible to yield cellular imprints in polycarbonate. The nuclear tracks were mostly present inside the cells, indicating a preferential boron uptake

New photochromes inherently chiral and redox actif based on (ter/tetra)arylenes

Le photochromisme est le processus par lequel une espèce chimique subit une transformation réversible photo-induite entre deux états ayant des spectres d'absorption différents. Cette isomérisation peut être réversible thermiquement et/ou photochimiquement. Les applications potentielles du photochromisme sont nombreuses dans différents domaines car, outre la couleur, le changement structural entre les deux états permet aussi de contrôler une myriade d'autres propriétés et fonctions. Parmi différentes familles de photochromes organiques connues, les diaryléthènes ont été au centre de très nombreuses études en raison de leurs bonnes propriétés photochromiques. Dans ce travail de thèse, nous nous sommes fixés comme premier objectif le développement de nouveaux diaryléthènes dotés d'une chiralité intrinsèque afin de pouvoir photo-moduler non seulement les propriétés optiques mais aussi la chiralité du système. A cette fin, nous avons porté l'effort synthétique sur les tétraarylènes connus pour leurs bonnes caractéristiques photochromiques et la possibilité de réaliser deux réactions de photo-cyclisations différentes au sein d'une seule molécule. Le choix d'utiliser un dihétéroaryle connu, 3,3'-dibenzothiophène, comme block central nous a permis de synthétiser les premiers membres d'une nouvelle famille de diaryléthène doté d'une chiralité axiale intrinsèque et stable.Les différentes études spectroscopiques ont montré que ces nouveaux tétraarylènes possèdent de bonnes propriétés photochromiques, notamment le rendement quantique de cyclisation et le taux de conversion, qui sont en grande partie imputables à leurs structures hélicoïdales avec uniquement le photo-réactif antiparallèle conformère. De plus, une importante et réversible modulation de leurs propriétés chiroptiques sont observées lors des réactions photochromiques (Chapitre 2).Exploitant la structure unique de ces tétraarylènes où les réactions photochromiques (cyclisation et cycloréversion) n'impliquent que trois aryles adjacents, nous avons ensuite voulu introduire une autre propriété et potentiellement un autre mode d'adressage du commutateur en remplaçant un des deux aryles terminaux par un groupe à base de triphénylamine (TPA) qui est à la fois fluorescent et rédox actif. Comme espéré, l'incorporation d'un tel motif ajoute la fluorescence comme une nouvelle propriété photo-commutable tout en conservant la plupart des caractéristiques photochromes des tétraarylènes précédents ainsi que la modulation des propriétés chiroptiques. De plus, une étude électrochimique couplée avec la spectro-élécrochimie et l'oxydo-réduction chimique a permis de mettre en évidence une ouverture oxydante et catalytique de la forme fermée, ajoutant ainsi un nouveau moyen de contrôle sur la commutation.Photochromism is the process by which a chemical species undergoes a reversible photo-induced transformation between two states with different absorption spectra. This isomerization can be thermally and/or photochemically reversible. There is plenty of potential applications of photochromism in various fields because, besides color, the structural change between the two states also allows control over a lot of other properties and functions. The focus has been on diaryléthènes, one of the different families of organic photochromes, due to their good photochromic properties. In this thesis work, our first objective was to develop new diarylethenes with intrinsic chirality able to photo-modulate not only the optical properties but also the chirality. To this end, we focused synthetic efforts on tetraarylenes known for their good photochromic characteristics and the possibility of performing two different photo-cyclization reactions within a single molecule. The choice to use a known diheteroaryl, 3,3'-dibenzothiophene, as the central block allowed us to synthesize the first members of a new family of diarylethene with intrinsic and stable axial chirality. Various spectroscopic studies have shown that these new tetraarylenes possess good photochromic properties, particularly cyclization quantum yield and conversion rate, which are come from their helical structures with only the antiparallel photo-reactive conformer. Furthermore, significant and reversible modulation of their chiroptical properties is observed during photochromic reactions (Chapter 2). Taking avantages of the unique structure of these tetraarylenes where photochromic reactions (cyclization and cycloreversion) involve only three adjacent aryls, we then aimed to introduce another property and potentially add another mode of switch addressing. For that one of the two terminal aryls was replaced by a triphenylamine (TPA)-based group that is both fluorescent and redox-active. As expected, the incorporation of such a motif adds fluorescence as a new photo-switchable property retain most of the photochromic characteristics of the previous tetraarylenes as well as modulation of chiroptical properties. Additionally, an electrochemical study coupled with spectro-electrochemistry and chemical redox has highlighted an oxidative and catalytic opening of the closed form, thus adding a new means of control over switching

EEG in bipolar disorders - a literature review

Background : Bipolar disorders are mostly genetically determined brain disorders, but primary brain dysfunctions and damage to the brain may also provoke clinical features suggesting the presence of a bipolar disorder. Aims: To review our current knowledege about standard EEG and qEEG findings in patients with bipolar I and II disorders, and discuss the value of assessing EEG and qEEG in routine clinical assesment of patients with bipolar I and II disorders. Methods: A literature search was conducted (key words: bipolar disorder, manic depression, EEG, electroencephalography) in PsychInfo PsychInfo (149 articles), Medline Ovid (510 articles) and Pubmed (524 articles) and by browsing some key psychiatric journals (Am J Psychiatry, Arch Gen Psychiatry, Biol Psychiatry, Electroencephalography, Cinical Neurophysi, Epilepsy and Behavior , J Affective dis, J Neurol, Neurosurg Psychiatry). EEG abnormality was defined as interictal spike discharge or sharp waves, epilepsy or findings suggesting epileptic disturbance including TIRDA; IRDA and small sharp spike activity. Theta-activity was only counted as abnormal if the activity was described as unilateral focal slowing of physiological rhythms by 1 Hz or more, or was unilateral with loss of reactivity of a physiological rhythm (e.g. loss of reactivity of the alfa-rhythm to eye opening or mental alerting) occuring in an awake adult not using any drugs. Results: Most studies were more than five years old and of limited quality in particular when it came to neuropsychiatric assessments and control of psychiatric comorbidity known to influence EEG patterns.. Abnormal EEG was found in a subgroup of patients with bipolar I and II disorders. Abnormality was associated with negative family history of affective disorders; female gender and higher mean age. The findings regarding qEEG characteristics and bipolar disorder were less consistent. In general terms there was asymmetric activity in frontotemporal brain regions in patients with bipolar disorders. qEEG predicted treatment response in some studies. Interpretation: Currently regular EEG is most useful for identification of abnormal brain dysfunctions in the temporal and frontal brain areas underlying bipolar symptomatology. qEEG offers promising possibilities for predicting treatment response. However, interpretation of qEEG records are still cumbersome and time-consuming limiting its use as a clinical tool. There is a great need for better designed electrophysiological studies of bipolar disorders. Good studies may provide important clinical information for the treatment of bipolar disorders

Nouveaux photochromes de la famille des (ter/tétra)arylènes intrinsèquement chiraux et redox actifs

Photochromism is the process by which a chemical species undergoes a reversible photo-induced transformation between two states with different absorption spectra. This isomerization can be thermally and/or photochemically reversible. There is plenty of potential applications of photochromism in various fields because, besides color, the structural change between the two states also allows control over a lot of other properties and functions. The focus has been on diaryléthènes, one of the different families of organic photochromes, due to their good photochromic properties. In this thesis work, our first objective was to develop new diarylethenes with intrinsic chirality able to photo-modulate not only the optical properties but also the chirality. To this end, we focused synthetic efforts on tetraarylenes known for their good photochromic characteristics and the possibility of performing two different photo-cyclization reactions within a single molecule. The choice to use a known diheteroaryl, 3,3'-dibenzothiophene, as the central block allowed us to synthesize the first members of a new family of diarylethene with intrinsic and stable axial chirality. Various spectroscopic studies have shown that these new tetraarylenes possess good photochromic properties, particularly cyclization quantum yield and conversion rate, which are come from their helical structures with only the antiparallel photo-reactive conformer. Furthermore, significant and reversible modulation of their chiroptical properties is observed during photochromic reactions (Chapter 2). Taking avantages of the unique structure of these tetraarylenes where photochromic reactions (cyclization and cycloreversion) involve only three adjacent aryls, we then aimed to introduce another property and potentially add another mode of switch addressing. For that one of the two terminal aryls was replaced by a triphenylamine (TPA)-based group that is both fluorescent and redox-active. As expected, the incorporation of such a motif adds fluorescence as a new photo-switchable property retain most of the photochromic characteristics of the previous tetraarylenes as well as modulation of chiroptical properties. Additionally, an electrochemical study coupled with spectro-electrochemistry and chemical redox has highlighted an oxidative and catalytic opening of the closed form, thus adding a new means of control over switching.Le photochromisme est le processus par lequel une espèce chimique subit une transformation réversible photo-induite entre deux états ayant des spectres d'absorption différents. Cette isomérisation peut être réversible thermiquement et/ou photochimiquement. Les applications potentielles du photochromisme sont nombreuses dans différents domaines car, outre la couleur, le changement structural entre les deux états permet aussi de contrôler une myriade d'autres propriétés et fonctions. Parmi différentes familles de photochromes organiques connues, les diaryléthènes ont été au centre de très nombreuses études en raison de leurs bonnes propriétés photochromiques. Dans ce travail de thèse, nous nous sommes fixés comme premier objectif le développement de nouveaux diaryléthènes dotés d'une chiralité intrinsèque afin de pouvoir photo-moduler non seulement les propriétés optiques mais aussi la chiralité du système. A cette fin, nous avons porté l'effort synthétique sur les tétraarylènes connus pour leurs bonnes caractéristiques photochromiques et la possibilité de réaliser deux réactions de photo-cyclisations différentes au sein d'une seule molécule. Le choix d'utiliser un dihétéroaryle connu, 3,3'-dibenzothiophène, comme block central nous a permis de synthétiser les premiers membres d'une nouvelle famille de diaryléthène doté d'une chiralité axiale intrinsèque et stable.Les différentes études spectroscopiques ont montré que ces nouveaux tétraarylènes possèdent de bonnes propriétés photochromiques, notamment le rendement quantique de cyclisation et le taux de conversion, qui sont en grande partie imputables à leurs structures hélicoïdales avec uniquement le photo-réactif antiparallèle conformère. De plus, une importante et réversible modulation de leurs propriétés chiroptiques sont observées lors des réactions photochromiques (Chapitre 2).Exploitant la structure unique de ces tétraarylènes où les réactions photochromiques (cyclisation et cycloréversion) n'impliquent que trois aryles adjacents, nous avons ensuite voulu introduire une autre propriété et potentiellement un autre mode d'adressage du commutateur en remplaçant un des deux aryles terminaux par un groupe à base de triphénylamine (TPA) qui est à la fois fluorescent et rédox actif. Comme espéré, l'incorporation d'un tel motif ajoute la fluorescence comme une nouvelle propriété photo-commutable tout en conservant la plupart des caractéristiques photochromes des tétraarylènes précédents ainsi que la modulation des propriétés chiroptiques. De plus, une étude électrochimique couplée avec la spectro-élécrochimie et l'oxydo-réduction chimique a permis de mettre en évidence une ouverture oxydante et catalytique de la forme fermée, ajoutant ainsi un nouveau moyen de contrôle sur la commutation

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Tibetan Buddhism, as an indigenous religion, has a significant and far-reaching influence in the Tibetan areas of China. This study, focusing on Lhasa, explores the integration of Tibetan Buddhist spiritual perceptions within urban spaces. Employing a novel approach that combines street view data and deep learning technology, the research aims to identify and map the spatial distribution of Tibetan Buddhist spiritual sites against the backdrop of the urban landscape. Our analysis reveals a notable concentration of these spiritual places near urban architectural and cultural heritage areas, highlighting the profound connection between residents' cultural life and spiritual practices. Despite challenges posed by modern urbanisation, these spiritual sites demonstrate resilience and adaptability, continuing to serve as cultural and spiritual pillars of the Tibetan Buddhist community. This study contributes to the fields of urban planning, religious studies, and digital humanities by demonstrating the potential of technology in examining the impact of urban development on cultural and religious landscapes. The research underscores the importance of protecting and integrating spaces of spiritual perception in urban development planning. It shows that safeguarding these spaces is crucial not only for cultural heritage preservation but also for achieving sustainable urban development and social harmony. This study opens new avenues for interdisciplinary research, advocating for a deeper understanding of the dynamic relationship between urban development and spiritual spaces from psychological, sociological, and environmental science perspectives. As urban landscapes evolve, the study emphasises the need to maintain a balance between material sustainability and cultural and spiritual richness in urban planning.</p