Laser-driven production with advanced targets of Copper-64 for medical applications

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations

CD22 expression in b-cell acute lymphoblastic leukemia: Biological significance and implications for inotuzumab therapy in adults

CD22 is a surface molecule expressed early during the ontogeny of B cells in the bone marrow and spleen, and can be found on B cells isolated from the different lymphoid compartments in humans. CD22 is expressed by most blasts from the majority (60–90%) of B-cell acute lymphoblastic leukemia (B-ALL). Current therapies in adults with newly diagnosed B-ALL are associated with complete remission (CR) rates of 50–90%. However, 30–60% of these patients relapse, and only 25–40% achieve disease-free survival of three years or more. Chemotherapy regimens for patients with refractory/relapsed B-ALL are associated with CR rates ranging from 31% to 44%. Novel immune-targeted therapies, such as blinatumomab and inotuzumab (a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic agent calicheamicin), provide potential means of circumventing chemo-refractory B-ALL cells through novel mechanisms of action. Eighty percent of inotuzumab-treated B-ALL patients may achieve a CR state. This review is focused on the biological and clinical activities of CD22 antibodies in BALL, and provides evidence about the potential role played by qualitative and quantitative analysis of the CD22 molecule on individual B-ALL blasts in predicting the depletion of leukemic cells, and, ultimately, leading to better clinical response rates

Retroperitoneal pararenal isolated neurofibroma: report of a case and review of literature

The neurofibroma is a tumour of neural origin. This kind of neoplasm, though, is generally skin located. Rare cases in deep organs or in the peritoneal cavity are also reported in the literature. There are two types of neurofibromas, localized and diffuse; the latter is associated with von Recklinghausen disease and always occurs together with skin neurofibromas. Here we report the case of a 47-year-old man affected by retroperitoneal neurofibroma, but not associated with von Recklinghausen disease. A computed tomography (CT) scan described a retroperitoneal pararenal lesion with no clear involvement of adjacent viscera. We describe the diagnostic modality, treatment planning and the timing of treatment of this neoplasm, reviewing also the literature

BubR1 promotes Bub3-dependent APC/C inhibition during Spindle Assembly Checkpoint signaling.

The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif ("loop") of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets. Here, we asked whether the BubR1 loop directs Bub3 to different phospho-targets. The BubR1 loop is essential for SAC function and cannot be removed or replaced with the Bub1 loop. BubR1 loop mutants bind Bub3 and are normally incorporated in MCC in vitro but have reduced ability to inhibit the MCC target anaphase-promoting complex (APC/C), suggesting that BubR1:Bub3 recognition and inhibition of APC/C requires phosphorylation. Thus, small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade

Combination of ozone and activated carbon for Pharmaceuticals and Personal Care Products (PPCPs) removal in drinking water: influence of compounds characteristics and organic matter competition

The presence of Pharmaceuticals and Personal Care Products (PPCPs) in drinking water is raising concern for potential negative effects on human health. Ozonation and adsorption on activated carbon (AC) are the most promising processes for PPCPs removal among those usually present in drinking water treatment plants (DWTPs). To evaluate the performance of these processes, both individually and in combination, adsorption isotherms were determined on real matrices collected in a DWTP before and after ozonation, focusing on 10 PPCPs identified as the most critical for the analysed DWTP. AC showed higher PPCPs removals than ozonation, but the combination of the two processes was beneficial. However, the effect of ozone on adsorption depends on PPCPs reactivity with ozone. A competitive effect of organic matter on PPCPs adsorption was observed. Finally, the removal of absorbance at 254 nm is a good proxy variable for PPCPs removal

Fate of Pharmaceuticals and Personal Care Products (PPCPs) from discharge to drinking water: a modelling and monitoring integrated framework

Pharmaceuticals and Personal Care Products (PPCPs) presence in drinking water is gaining growing concern for potential negative effects on human health. This study combined modelling of river transport with monitoring campaigns performed over one year at a drinking water treatment plant (DWTP) located at the closure section of Po river basin, to evaluate the types of released PPCPs, their concentrations and fate in both the river and the DWTP. Over the 114 monitored PPCPs, maximum 23 compounds have been detected at the DWTP inlet with concentrations from 10 to 1800 ng/L, varying among PPCPs and in time. The transport in Po river of iopamidol, with the highest concentration at the DWTP inlet, was simulated combining hydrological and quality data and models. Finally, DWTP monitoring showed that ozonation and adsorption onto activated carbon have the main impact in reducing a wide variety of PPCPs, with performances influenced by their characteristics

2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping oflarge granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermaldeposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits74339440

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

En este trabajo se presentan los resultados obtenidos utilizando técnicas de procesamiento de imágenes Aster para asistir al mapeo litológico y mineralógico de grandes cuerpos graníticos y de la alteración hidrotermal asociada al batolito Cerro Áspero, Sierra de Comechingones, Argentina. Este batolito fue construido por el emplazamiento sucesivo de varios plutones subcirculares, epizonales, que intruyeron en el Devónico Superior, a secuencias metamórficas de alto a mediano grado retrabajadas por fajas de deformación. Cada uno de estos plutones desarrolló unidades internas, externas, cuspidales y enjambres de diques. Las unidades internas están compuestas de monzogranitos porfídicos con biotita y las unidades externas, cuspidales y los enjambres de dique están dominados por leucogranitos cuyas composiciones varían desde monzogranítica hasta granitos alcali-feldespáticos, ricos en cuarzo. Las principales mineralizaciones asociadas son depósitos magmáticoshidrotermales de W-Mo y depósitos de fluorita epitermal, post-batolíticos, de edad cretácica. Para identificar la composición litológica y las variaciones en los plutones que lo componen se realizó clasificación supervisada, análisis de componentes principales y cálculos de emisividad. Esta metodología permitió un mejor y más detallado mapeo en el área de estudio, así como precisar los contactos entre los plutones que componen el batolito. La clasificación obtenida con el método SAM (spectral angle mapper) permitió la determinación de diferentes alteraciones hidrotermales (argílica y sílicificación). La alteración argílica está asociada principalmente con depósitos de fluorita epitermal.The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping of large granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermal deposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits.Fil: Radice, Stefania. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maffini, María Natalia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Campanella, Osvaldo Hector. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Ducart, Diego F.. Universidade Estadual do Campinas. Instituto de Geociencias; BrasilFil: Coniglio, Jorge Enrique. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin