Luminescent Supramolecular Metallogels: Drug Loading and Eu(III) as Structural Probe.

Supramolecular metallogels combine the rheological properties of gels with the color, magnetism, and other properties of metal ions. Lanthanide ions such as Eu(III) can be valuable components of metallogels due to their fascinating luminescence. In this work, we combine Eu(III) and iminodiacetic acid (IDA) into luminescent hydrogels. We investigate the tailoring of the rheological properties of these gels by changes in their metal:ligand ratio. Further, we use the highly sensitive Eu(III) luminescence to obtain information about the chemical structure of the materials. In special, we take advantage of computational calculations to employ an indirect method for structural elucidation, in which the simulated luminescent properties of candidate structures are matched to the experimental data. With this strategy, we can propose molecular structures for different EuIDA gels. We also explore the usage of these gels for the loading of bioactive molecules such as OXA, observing that its aldose reductase activity remains present in the gel. We envision that the findings from this work could inspire the development of luminescent hydrogels with tunable rheology for applications such as 3D printing and imaging-guided drug delivery platforms. Finally, Eu(III) emission-based structural elucidation could be a powerful tool in the characterization of advanced materials.

Reliability and Agreement in the Cerebellar Tonsil Tip Localization: Two Methods Using the McRae Line Concept in MRI.

BACKGROUND: The cerebellar tonsil tip position (TP) is a common parameter used for the radiologic diagnosis of Chiari malformation type 1 (CM1). However, these paramedian structures are usually not properly visualized in the midsagittal section. Such mismatch may be a source of bias in TP measurements based on the McRae line (ML) traced between median craniometric points. This study aims to evaluate the intraoperator and interoperator reliability and agreement of 2 protocols to trace the ML in magnetic resonance imaging (MRI) for the cerebellar tonsil tip localization, adding a 3-dimensional multiplanar reconstruction (MPR) approach to the midsagittal plane. METHODS: Sixty-two T1-weighted head MRIs were obtained for 32 CM1 patients and 30 controls. Two operators independently applied 2 TP measurement protocols, one considering only the visualization of the sagittal plane and the other using MPR. The intraclass correlation coefficient was used to assess intraoperator and interoperator reliability, and the Bland-Altman graphical method was used to evaluate the agreement between the measurement protocols. RESULTS: The sagittal method significantly underestimated ML and tonsillar herniation when compared with the MPR method. The MPR method provided better reliability of the ML measurement when compared to the sagittal method, but this did not influence the reliability of the TP. Analysis of the Bland-Altman plot showed that the limits of agreement were close to acceptable for the ML, but not for measures of TP. CONCLUSIONS: The standardization of the LM tracing by the MPR method improves the acquisition of data regarding the position of the tonsils.

Investigating Type B Basilar Invagination Through Cephalic Indices.

OBJECTIVE: We sought to compare the diagnostic accuracy of cephalic indices for type B basilar invagination (BI). METHODS: This retrospective study examined head and neck magnetic resonance imaging sequences of 31 Group B BI cases and 96 controls. Two examiners blinded to diagnostic data evaluated the cephalic indices of each magnetic resonance imaging sequence, described as width/length (WLI) and height/width (HWI). The distance of the odontoid process apex to Chamberlain line and clivus canal angle were measured. The interexaminer and intraexaminer reproducibility of the cephalic indices was calculated using intraclass correlation coefficient. The diagnostic accuracy was discerned by the receiver operating characteristic (ROC) curve. All analyses were scrutinized with a 95% confidence interval. RESULTS: Cephalic indices showed interexaminer and intraexaminer reproducibility ≥94%. The areas under the ROC curve were 0.639 (WLI) and 0.874 (HWI) (95% confidence interval: P < 0.05). The HWI showed a sensitivity of 74.7% and a specificity of 85.5% for the cutoff criterion ≤58. The WLI presented a sensitivity of 53.3% and a specificity of 66.7% for the cutoff criterion ≥86. CONCLUSIONS: The HWI showed the largest area under the ROC curve in comparison with the WLI, with robust sensitivity and specificity values, indicating that the proportions between cranial height and width can help clinicians in investigating type B BI.

Foramen Magnum Angle: A New Parameter for Basilar Invagination of Type B.

OBJECTIVE: To describe the foramen magnum angle (FMA) as a new parameter for basilar invagination (BI) type B. METHODS: The FMA was performed on sagittal slice of magnetic resonance imaging (MRI) as a line from the hard palate to the opisthion (angle vertex), and another line from the opisthion to the basion. The MRIs from 31 participants with BI type B and 96 controls were used. Intraclass correlation coefficient, descriptive data, and receiver operating characteristic (ROC) curve were used for statistical analysis at the 95% confidence interval. RESULTS: The interobserver agreement of the FMA was 0.952. Patients with BI type B had a FMA significantly greater (25.9° ± 9.3°) than control participants (11.6° ± 4.9°) (P < 0.001). The area under the ROC curve showed a diagnostic value of 0.947. The FMA showed sensitivity 0.900 and specificity 0.854 for the cutoff criterion 17° (P < 0.001). CONCLUSIONS: The FMA had an optimal diagnostic value that provided complementary evidence to investigate BI type B.

Is Basilar Invagination Related with Stenosis of the Hypoglossal Nerve Canal?

OBJECTIVE: To analyze the association between basilar invagination (BI) and stenosis in the hypoglossal canal (HC). METHODS: A case-control study with magnetic resonance images (MRIs) of the head from a local database was performed. The study used MRIs of 31 patients with BI (type B) and 36 controls, both groups over 18 years of age and without sex distinction. The internal (ID) and external (ED) diameters of the HC were measured on the coronal plane using the Osirix in its free version 3.9.2 (Mac-Apple platform). We used the Kolmogorov-Smirnov test (with Lilliefors adjustment) to evaluate the normality of the variables, the Levine test to verify the homogeneity of the variances, and Student's t test to verify differences between groups. All analyses were within the 95% confidence interval. RESULTS: Control group presented right and left ED values of 4.7 ± 0.8 mm and 4.6 ± 0.9 mm, respectively, while the right and left ID showed 4.4 ± 0.9 mm and 4.3 ± 0.8 mm, respectively. The group with BI showed right and left ED values of 3.3 ± 0.9 mm and 3.1 ± 0.9 mm, and the right and left ID had values of 2.8 ± 0.7 mm and 2.7 ± 0.7 mm, respectively. Both ED and ID were smaller in the group with BI (P < 0.001). CONCLUSIONS: Patients with BI of type B presented the narrowing of HC when compared with control participants.

Towards an Information Infrastructure for Medical Image Sharing.

Information infrastructures involve the notion of a shared, open infrastructure, constituting a space where people, organizations, and technical components associate to develop an activity. The current infrastructure for medical image sharing, based on PACS/DICOM technologies, does not constitute an information infrastructure since it is limited in its ability to share in a scalable, comprehensive, and secure manner. This paper proposes the DICOMFlow, a decentralized, distributed infrastructure model that aims to foment the formation of an information infrastructure in order to share medical images and teleradiology. As an installed base, it uses the PACS/DICOM infrastructure of radiology departments and the internet e-mail infrastructure. Experiments performed in real and simulated environments have indicated the feasibility of the proposed infrastructure to foment the formation of an information infrastructure for medical image sharing and teleradiology.

Are the Absorption Spectra of Doxorubicin Properly Described by Considering Different Tautomers?

The elucidation of the action of doxorubicin (DOX) has been considered a challenge for cancer therapy. Using theoretical approaches, we investigated the structure and electronic properties of DOX as a function of pH, which we thought likely to be related to the influence of its tautomers. Regarding the relative stabilities among the tautomers, the results obtained from PM6 were the most similar to those obtained from DFT. The theoretical absorption spectrum for each tautomeric species simply showed a single absorption peak located around 400 nm, in contrast to the experimental absorption spectra in the literature that showed four absorption bands. The experimental evidence was properly explained by considering four tautomeric conformers of DOX. The spectroscopic study of the deprotonated tautomers also suggested the presence of four deprotonated tautomers at more basic pH values. The spectrum at pH 10.08 can be explained by the presence of protonated and deprotonated doxorubicin species.

Diagnostic accuracy of classical radiological measurements for basilar invagination of type B at MRI.

OBJECTIVE: To evaluate the diagnostic accuracy of classical measurements for basilar invagination (BI) of type B at MRI. METHODS: This study used head MRIs from 31 participants with BI type B and 96 controls. The radiological criterion for BI was the odontoid process invagination using the obex as reference. It based on the independent prospective reading of two neuroradiologists. Concordance between the two neuroradiologists was analysed through the KAPPA index, and the discrepancy was resolved in a consensus meeting. A third examiner measured in two occasions (double blind) the distance of the odontoid apex to Chamberlain's line (DOCL) and McGregor's line (DOMG), clivus canal angle (CCA), Welcker's basal angle (WBA), and Boogaard's angle (BOA). Intra-examiner reproducibility of the measurements was evaluated with the intraclass correlation coefficient and the diagnostic accuracy by ROC curve. All analyses were at 95% confidence interval. RESULTS: Agreement between the two neuroradiologists was statistically relevant (KAPPA = .91; P = .0001). The intra-examiner reproducibilities were .98 (DOCL), .97 (DOMG), .96 (CCA), .94 (WBA), and .95 (BOA) (P < .05). The areas under the ROC curve were .963 (DOCL), .940 (DOMG), .880 (CCA), .867 (WBA), and .951 (BOA) (P < .05). The cut-off criteria were ≥ 7 mm (DOCL), ≥ 8 mm (DOMG), ≤ 145° (CCA), ≥ 142° (WBA), and ≥ 136° (BOA). The diagnostic accuracies were .904 (DOCL), .870 (DOMG), .844 (CCA), .810 (WBA), and .899 (BOA). CONCLUSION: The DOCL and BOA presented the highest diagnostic accuracy for BI type B. These slides can be retrieved under Electronic Supplementary Material.

Multifunctional System Polyaniline-Decorated ZIF-8 Nanoparticles as a New Chemo-Photothermal Platform for Cancer Therapy.

Polyaniline-decorated ZIF-8 nanoparticles (nPANI@nZIF-8) were easily synthesized and employed as a multifunctional system for the delivery of the antitumor drug 5-fluorouracil (5-FU). Because of the storage ability of the network ZIF-8, 68% of the total amount of the 5-FU drug was released at pH 5.2. The system exhibits absorption in the near-infrared (NIR) region and can be used in the photothermal therapy owing to the presence of nPANI, which has a strong NIR uptake. This absorption causes local hyperthermia by aiding in the diffusion of the drug molecules contained by the polymer into nPANI@nZIF-8/5-FU achieving a greater release of the 5-FU drug, about 80% activated by an NIR laser (λ = 980 nm). This hyperthermia reached about 70 °C (200 µL, 1 mg mL-1 nPANI@nZIF-8), which was directly proportional to the concentration of the material. Therefore, our work can aid in the construction of new chemo-photothermal platforms that may be employed in cancer therapy.

Relationship between basilar invagination and brachycephaly in Northeastern Brazil.

BACKGROUND: Basilar invagination (BI) is an abnormality characterized by a superior projection at the craniovertebral junction (CVJ). The high prevalence of BI in Northeastern Brazil associated with brachycephaly, which is measured by the cranial index (CI), has been widely reported by several neurosurgeons and radiologists from that region since the 1950s. However, strong evidence for this relationship is still pending. The aim of this study is to investigate whether there is a relationship between BI and CI in a sample with participants from Northeastern Brazil. METHODS: The study used magnetic resonance images (MRIs) from 34 patients with BI and 92 controls. These participants had the CI correlated with radiological measurements used in BI diagnosis: Welcker's basal angle (WBA), clivus-canal angle (CCA), apex distance of the odontoid process to Chamberlain's line (DOCL), and Boogaard's angle (BOA). Craniometry was performed using the software Osirix, version 3.9.2 and statistical analysis by SPSS. We used Pearson's test for correlation analysis and the ROC curve was used for depicting CI accuracy related to BI diagnosis. All tests were calculated at the 95% confidence interval. RESULTS: The BI group showed a moderate correlation between CI and CVJ measurements (P < 0.05). The control group had a weak correlation between CI and DOCL, and no statistical significance was verified for other correlations (P > 0.05). The area under the ROC was 0.659 and a CI greater than 86 had a specificity of approximately 80% for BI (P = 0.002). CONCLUSIONS: The results indicated a greater cephalic projection of the CVJ in patients with high CI in the BI group. Moreover, a CI above 86 has a good diagnosis specificity for BI, showing evidence of a relationship between hyperbrachycephaly and CVJ anomalies in Northeastern Brazil.

'Real-life' report on the management of chronic GvHD in the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.

Highly-sensitive Eu(3+) ratiometric thermometers based on excited state absorption with predictable calibration.

Temperature measurements ranging from a few degrees to a few hundreds of Kelvin are of great interest in the fields of nanomedicine and nanotechnology. Here, we report a new ratiometric luminescent thermometer using thermally excited state absorption of the Eu(3+) ion. The thermometer is based on the simple Eu(3+) energy level structure and can operate between 180 and 323 K with a relative sensitivity ranging from 0.7 to 1.7% K(-1). The thermometric parameter is defined as the ratio between the emission intensities of the (5)D0 → (7)F4 transition when the (5)D0 emitting level is excited through the (7)F2 (physiological range) or (7)F1 (down to 180 K) level. Nano and microcrystals of Y2O3:Eu(3+) were chosen as a proof of concept of the operational principles in which both excitation and detection are within the first biological transparent window. A novel and of paramount importance aspect is that the calibration factor can be calculated from the Eu(3+) emission spectrum avoiding the need for new calibration procedures whenever the thermometer operates in different media.

N-Acetylcysteine and High-Dose Atorvastatin Reduce Oxidative Stress in an Ischemia-Reperfusion Model in the Rat Kidney.

OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties.

Inkjet Printing of Lanthanide-Organic Frameworks for Anti-Counterfeiting Applications.

Photoluminescent lanthanide-organic frameworks (Ln-MOFs) were printed onto plastic and paper foils with a conventional inkjet printer. Ln-MOF inks were used to reproduce color images that can only be observed under UV light irradiation. This approach opens a new window for exploring Ln-MOF materials in technological applications, such as optical devices (e.g., lab-on-a-chip), as proof of authenticity for official documents.

Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males.