Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.     

Changes in socioeconomic differentials in old age life expectancy in four Nordic countries: the impact of educational expansion and education-specific mortality

Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to find out to what extent the change in national LEs is attributable to education-specific mortality and the shifting educational composition. We used national register data comprising total 65 + populations in Denmark, Finland, Norway and Sweden to create period life tables stratified by five-year age groups (65–90 +), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63–90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10–37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00698-y.     

Differential spectrofluorometry in the human vitreous: blood-retina barrier permeability to fluorescein and fluorescein glucuronide

A method is described for the separate quantitation of fluorescein and fluorescein glucuronide in the vitreous by differential spectrofluorometry. An ocular fluorometer was equppied with monochromatic laser excitation at two rapidly interchangeable wavelengths. The data analysis accounts for absorption of light in the cornea, lens, and extrinsic ocular fluorophores. Examination of seven patients with insulin-dependent diabetes and different degrees of diabetic retinopathy demonstrated that both fluorescein and fluorescein glucuronide enter the eye through the blood-retina barrier. The mean ratio between the permeabilities of fluorescein glucuronide and fluorescein was 0.9 (range, 0.3–1.9). Thus, differences in the molecular size and lipid solubility of the two substances appear to be of little or no importance for their inward penetration of the barrier. No association was found between the relative permeability and the degree of retinopathy.This study was supported by Danish Medical Research Council grant 12-8301 Offprint requests to: M. Larsen     

Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels

Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile.