Positron range effects of 66Ga in small-animal PET imaging.

PURPOSE: Gallium-66 is a non-conventional positron emitter that stands out not only for its high potential to label peptides, proteins and antibodies, but also because it can provide spatio-temporal information of relatively slow physiological processes in the body due to its conveniently long half-life of 9.5 h. However, 66Ga emits the most energetic positrons for PET imaging. The lack of information of the positron range effect on spatial resolution for this positron emitter is an issue, particularly in preclinical imaging. METHODS: The line spread function (LSF) in tissue-equivalent materials with densities between 0.2 and 1.93 g/cm3 was obtained with 66Ga and 18F. A complementary study with the NEMA NU 4-2008 image quality phantom is also included. RESULTS: High-energy positrons moving in lower density materials produce far-reaching activity distributions. The LSFs were characterized with Lorentzian-Gaussian fits, with spatial resolution (FWHM) in the 2.14-3.2 mm range, and long tails extending a few tens of mm depending on the material type and density. A narrowing of the LSF was observed for lung-equivalent materials, indicating the lack of enough material for the positron annihilation to take place. The NEMA NU 4-2008 image quality phantom produced blurred images, notoriously observed in the hot and cold cylinders used for evaluation of recovery coefficients (RC) and spill-over ratios (SOR), producing very low RC and very large SOR. CONCLUSIONS: Quantitative PET imaging with the non-conventional 66Ga is hampered due to the large range of its high-energy positrons affecting both spatial resolution and activity concentration quantification.

Correction: In situ crosslinking of electrospun gelatin for improved fiber morphology retention and tunable degradation.

Correction for 'In situ crosslinking of electrospun gelatin for improved fiber morphology retention and tunable degradation' by A. P. Kishan et al., J. Mater. Chem. B, 2015, DOI: .

In situ crosslinking of electrospun gelatin for improved fiber morphology retention and tunable degradation.

Electrospinning is a popular technique to fabricate tissue engineering scaffolds due to the exceptional tunability of the fiber morphology, which can be used to control the scaffold mechanical properties, degradation rate, and cell behavior. Recent work has focused on electrospinning natural polymers such as gelatin to improve the regeneration potential of these grafts. Gelatin scaffolds must be crosslinked to avoid rapid dissolution upon implantation with current crosslinking strategies requiring additional post-processing steps. Despite the strong dependence of scaffold properties on fiber morphology, there has been minimal emphasis on retaining the original fiber morphology of electrospun gelatin scaffolds after implantation. This work describes a method for in situ crosslinking of gelatin to produce electrospun fibers with improved fiber morphology retention after implantation. A double barrel syringe with an attached mixing head and a diisocyanate crosslinker were utilized to generate electrospun scaffolds that crosslink during the electrospinning process. These in situ crosslinked fiber meshes retained morphology after 1 week incubation in water at 37 °C; whereas, uncrosslinked meshes lost the fibrous morphology within 24 hours. Degree of crosslinking was quantified and relationships between the crosslinker ratio and enzymatic degradation rate were evaluated. The degradation rate decreased with increased crosslinker ratio, resulting in a highly tunable system. Additionally, tensile testing under simulated physiological conditions indicated that increased crosslinker ratios resulted in increases in initial modulus and tensile strength. Overall, this in situ crosslinking technique provides a method to crosslink gelatin during electrospinning and can be used to tune the degradation rate of resulting scaffolds while enabling improved fiber morphology retention after implantation.

Determination of the in vivo degradation mechanism of PEGDA hydrogels.

Poly(ethylene glycol) (PEG) hydrogels are one of the most extensively utilized biomaterials systems due to their established biocompatibility and highly tunable properties. It is widely acknowledged that traditional acrylate-derivatized PEG (PEGDA) hydrogels are susceptible to slow degradation in vivo and are therefore unsuitable for long-term implantable applications. However, there is speculation whether the observed degradation is due to hydrolysis of endgroup acrylate esters or oxidation of the ether backbone, both of which are possible in the foreign body response to implanted devices. PEG diacrylamide (PEGDAA) is a polyether-based hydrogel system with similar properties to PEGDA but with amide linkages in place of the acrylate esters. This provides a hydrolytically-stable control that can be used to isolate the relative contributions of hydrolysis and oxidation to the in vivo degradation of PEGDA. Here we show that PEGDAA hydrogels remained stable over 12 weeks of subcutaneous implantation in a rat model while PEGDA hydrogels underwent significant degradation as indicated by both increased swelling ratio and decreased modulus. As PEGDA and PEGDAA have similar susceptibility to oxidation, these results demonstrate for the first time that the primary in vivo degradation mechanism of PEGDA is hydrolysis of the endgroup acrylate esters. Additionally, the maintenance of PEGDAA hydrogel properties in vivo indicates their suitability for long-term implants. These studies serve to elucidate key information about a widely used biomaterial system to allow for better implantable device design and to provide a biostable replacement option for PEGDA in applications that require long-term stability.

Comparison of central corneal thickness measured with anterior segment optical coherence tomography versus ultrasonic pachymetry.

PURPOSE: To compare central corneal thickness measured with anterior segment optical coherence tomography (AS-OCT) and ultrasonic pachymetry (UP). METHOD: A prospective, observational and cross-sectional study was performed. The central corneal thickness was measured in 112 eyes of 112 consecutive patients with AS-OCT and UP. All examinations were performed by the same examiner. The measurements obtained between the 2 instruments were compared to assess the level of agreement. RESULTS: The average corneal thickness value obtained by AS-OCT was 531.47 ± 26.23 µm, while that measured by UP was 532.51 ± 26.04 µm. The intraclass correlation coefficient was 0.957 (P <.001). The Student's t-test did not show a statistically significant difference (1.04 ± 7.70 µm, P =.158). Finally, the Bland-Altman analysis showed a high level of agreement between 2 methods of measurement. CONCLUSIONS: In the context of normal corneas, there was good agreement between the measurement of central corneal thickness with AS-OCT and UP, although there was a slight overestimation of the measurement using UP (1.04 µm).

Magnetic properties of a pair of V4 interacting clusters in a Fe matrix.

The magnetic properties of a pair V4 atomic clusters embedded in bulk Fe are determined by using a realistic spd-band Hubbard-like model. The spin density distribution is calculated self-consistenly in the unrestricted Hartree-Fock approximation. The local magnetic moments mu(i) are obtained at various atoms i of the cluster and of the surrounding Fe matrix. We consider two different geometrical arrangements for V clusters, collinear (C) and non-collinear (NC). In all the cases studied the magnetic coupling in the interface cluster-matrix is antiferromagnetic, and the ferromagnetic order of the matrix is not broken by the presence of the V atoms, although the local magnetic moments of Fe atoms at the interface cluster-matrix, are reduced respect to Fe bulk magnetization (2.22 microB) about 8%-20%. We compare the results with those of just one V4 atomic cluster embedded in bulk Fe.

[Mutations in the BRCA1 gene in young Spanish women with breast cancer]. / Mutaciones en el gen BRCA1 en mujeres españolas jóvenes con cáncer de mama.

BACKGROUND: Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years. PATIENTS AND METHODS: We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing. RESULTS: Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial history of breast cancer. Five additional rare variants and polymorphisms were also detected. CONCLUSIONS: The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of establishing DNA-based screening tests for hereditary breast cancer.

[Family prevalence of idiopathic scoliosis]. / Prevalencia familiar de la escoliosis idiopática.

OBJECTIVE: Review of the literature shows that, for the moment, the cause of idiopathic scoliosis remains unknown. It has been attributed to a wide variety of conditions, including genetics. The aim of this paper was to determine the frequency of antecedents and family prevalence of idiopathic scoliosis in first and second degree relatives. PATIENTS AND METHODS: During 1994-1995, the families, including first and second degree relatives, of 100 schoolchildren with idiopathic scoliosis were surveyed for scoliosis. The screening was done initially by clinical examination, the test of Adams and subsequently the diagnosis was confirmed by roentgenography. RESULTS: Our study showed the following results. Twenty-five percent of patients investigated had one or more affected individuals in their family. Prevalence of idiopathic scoliosis in first degree relatives was 5.16% and in second degree relatives 4.31%. It was more frequent in females than in males (p < 0.05). This prevalence is larger than that in the general population (1-2%). CONCLUSIONS: Our conclusion is that the mechanism of inheritance is most likely multifactorial. In view of the predominance of females, an X-linked inheritance is suggested.

Axillary shoulder with exaggerated rotation: the Hill-Sachs defect.

One of the most common fractures of the humeral head resulting from an anterior dislocation is the Hill-Sachs defect. Other special radiographic positions to demonstrate this injury may prove difficult for the patient to assume and maintain. An axillary shoulder projection with exaggerated external rotation is easy to position and clearly demonstrates the Hill-Sachs defect.

Vacuum blotting: a simple method for transferring DNA from sequencing gels to nylon membranes.

We describe a vacuum blotting procedure for transferring DNA fragments from conventional polyacrylamide sequencing gels to nylon membranes. The method employs a combination of vacuum-assisted diffusion (effected by a standard gel drier) and an osmotic gradient (effected by over- and underlying filters presoaked in ammonium acetate). Fragments up to 310 nucleotides in length transfer at 40-60% efficiency within 90 min. When combined with indirect end-labelling, the method allows genomic sequencing of a single-copy gene of Saccharomyces cerevisiae employing as little as 5 micrograms DNA per lane.

Protective effects of O2 radical scavengers and adenosine in PMA-induced lung injury.

We have previously shown that phorbol myristate acetate (PMA) produces acute lung injury in blood-perfused lungs but not in plasma-dextran-perfused lungs. This is compatible with the concept that its major mechanism of injury is the stimulation of O2 radicals by neutrophils, which in turn increase permeability by damaging the endothelial cells. In this study we measured vascular permeability and resistance before and 1 h after PMA in five groups of blood-perfused dog lungs: PMA alone in one group and pretreatment with catalase, superoxide dismutase, deferoxamine, and adenosine each in four other groups. By the use of two indexes of permeability, the filtration coefficient and the isogravimetric capillary pressure, we found that, compared with PMA alone, catalase, deferoxamine, and adenosine provided significant protection, whereas the results with superoxide dismutase were variable. These four drugs also significantly attenuated the marked increased resistance seen with PMA alone. Although the effects seen with the first three can be explained by their scavenging of O2 radicals, adenosine appears to provide protection through a separate mechanism.

Attenuation of permeability lung injury after phorbol myristate acetate by verapamil and OKY-046.

Phorbol myristate acetate (PMA), which produces an experimental model of acute lung injury similar to the adult respiratory distress syndrome, was studied in isolated dog lung lobes perfused at constant pressure in Zone 3 conditions. The effect of 25 to 50 micrograms PMA on pulmonary vascular permeability and resistance was observed in 4 groups of lungs: Group 1, perfused with a plasma/dextran solution; Group 2, perfused with blood; Group 3, blood-perfused and pretreated with verapamil (a calcium channel blocker); and Group 4, blood-perfused and pretreated with OKY-046 (a thromboxane synthetase inhibitor). Permeability changes were assessed by determining capillary filtration coefficient (Kf), isogravimetric capillary pressure (Pci), and in blood-perfused lungs, the protein reflection coefficient (sigma d). An increase in Kf, a decrease in Pci, and a decrease in sigma d, all indicative of an increase in vascular permeability, occurred 1 h after PMA in blood-perfused but not in plasma/dextran-perfused lungs. An increase in pulmonary vascular resistance occurred in both blood- and plasma/dextran-perfused lungs. Verapamil (2 X 10(-5) M) and OKY-046 (7 X 10(-4) M) pretreatment in blood-perfused lungs essentially blocked the PMA-induced change in permeability and significantly attenuated the increased vascular resistance. Total leukocyte and platelet counts fell in all blood-perfused lungs, whether pretreated or not. We conclude that cellular components of blood (platelets and/or leukocytes) are required to produce the permeability injury but not the pulmonary vasoconstriction and that the injury can be attenuated by either a calcium channel blocker or a specific thromboxane synthetase inhibitor. The left ventricular volume change caused by increasing right ventricular volume was measured at normal and elevated pericardial pressures.