The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model

There is much interest in utilizing the intrinsic properties of magnetic nanoparticles (MNPs) for the theranostic approaches in medicine. With an aim to develop a potential therapeutics for glioma treatment, efficacy of aqueous dispersible paclitaxel loaded MNPs (Pac-MNPs) were studied in glioblastoma cell line (U-87). The identified potential receptor, glycoprotein non-metastatic melanoma protein B (GPNMB) overexpressed by glioblastoma cells, was actively targeted using GPNMB conjugated Pac-MNPs in U-87 cells. As blood brain barrier (BBB) is the primary impediment in the treatment of glioblastoma, therefore, an attempt was taken to evaluate the biodistribution and brain uptake of Pac-MNPs in rats. The bioavailability of Pac-MNPs illustrated a prolonged blood circulation in vivo, which demonstrated the presence of significant amounts of drug in rat brain tissues as compared to native paclitaxel. Further, the transmission electron microscopy (TEM) study revealed significant accumulation of the Pac-MNPs in the brain tissues. Being an effective contrast enhancement agent for magnetic resonance imaging (MRI) at tissue levels, the MNPs devoid of any surfactant demonstrated enhanced contrast effect in liver and brain imaging. Hence, the significant prevalence of drugs in the rat brain tissues, in vitro targeting potentiality as well as the augmented contrast effect elicit the non-invasive assessment and theranostic applications of MNPs for brain tumor therapy.     

A comparative analysis of topical corticosteroids and non-steroidal anti-inflammatory drugs to control inflammation and macular edema following uneventful phacoemulsification

Purpose:To compare the efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and prednisolone acetate in controlling inflammation and preventing cystoid macular edema (CME) after uneventful phacoemulsification.Methods:All patients who underwent uneventful phacoemulsification from December 2020 to Feb 2021 were included in the study. These were randomly assigned to receive any one anti-inflammatory agent among topical nepafenac (0.1%) [96 eyes], bromfenac (0.07%) [93 eyes], preservative-free ketorolac (0.4%) [94 eyes], nepafenac (0.3%) [96 eyes], or prednisolone acetate (1%) [91 eyes]. The efficacy of the drugs was evaluated by comparing the grade of anterior chamber (AC) cells, conjunctival hyperemia, pain score, visual acuity, intraocular pressure (IOP), and central macular thickness (CMT) at 1 and 6 weeks after surgery.Results:At 1 and 6 weeks, there was no significant difference in pain score, conjunctival hyperemia, AC cells, change in IOP, and visual acuity between the prednisolone and the NSAIDs groups, though nepafenac 0.3% was most effective. At 6 weeks, there was no significant difference in the number of patients developing subclinical CME in the prednisolone versus NSAID group. The mean increase in CMT was significantly lower in nepafenac 0.3% than prednisolone at 1 and 6 weeks (P = 0.003 and 0.004, respectively).Conclusion:NSAIDs used in isolation are comparable to prednisolone in preventing inflammation and pain after uneventful phacoemulsification. However, nepafenac 0.3% is most comparable to prednisolone and more efficacious in reducing the incidence of CME. We recommend that nepafenac 0.3% can be used as a sole anti-inflammatory agent in patients with uneventful phacoemulsification.     

Triad of columnar cell alteration, lobular carcinoma in situ, and tubular carcinoma of the breast

Columnar cell alteration in the breast encompasses a spectrum of pathologic changes ranging from simple columnar cell change to more complex columnar cell hyperplasia with and without atypia to in situ carcinoma, often with a micropapillary architecture. For reasons that remain unclear, the columnar cell lesions are associated with tubular carcinomas and lobular carcinoma in situ. Therefore it is important to be familiar with the spectrum of changes and the associated lesions, especially in breast core biopsies for further management.     

LiF TLD-100 as a Dosimeter in High Energy Proton Beam Therapy—Can It Yield Accurate Results?

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within ±5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within ± 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy.     

Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion

Neurofibromatosis type 1 (NF1), affecting primarily the growth of neural crest-derived tissues, is one of the most common autosomal dominant genetic disorders with an unusually high spontaneous mutation rate. In four cases of sporadic NF1, demonstrated by hemizygosity to have a deletion involving the NF1 gene, we were able to assign the deletion event to the maternally derived chromosome. One of these individuals was determined to be a somatic mosaic for NF1, as a trace of the maternally derived haplotype was detected at the NF1 locus. This indicated a postzygotic, as opposed to gametic, deletion event. It may be that somatic mosaicism is more common in NF1 than has hitherto been appreciated and may responsible in part for the high mutation rate in this disorder. In addition, it is suggested that the mechanism(s) of gene deletion is subject to a parent of origin effect, being more frequent on the maternally derived chromosome. This is in contrast to the other types of mutations which, in sporadic NF1, have been found to occur preferentially on the paternally derived chromosome. Hum Mutat 9:452–457, 1997 © 1997 Wiley-Liss, Inc.     

In situ laser irradiation: the kinetics of the changes in the nonlinear/linear optical parameters of As50Se40Sb10 thin films for photonic applications

The photosensitivity of amorphous chalcogenide thin films brings out light-induced changes in the nonlinear and linear optical parameters upon sub-bandgap and bandgap laser irradiation. The present work reports the in situ laser irradiated changes in the optical properties of As₅₀Se₄₀Sb₁₀ thin films. The thermally evaporated film showed an exponential decrease in optical bandgap and increase in Urbach energy. The decay rate of the bandgap was 6.24 min and growth rate of Urbach energy was 6.67 min respectively. The dynamics of photo-induced changes were observed from the changes in linear refractive index and its dependent parameters such as 3^rd order nonlinear susceptibility, nonlinear refractive index, dispersion and dielectric parameters. The conversion of heteropolar to homopolar bonds induced the photodarkening mechanism that changed the dispersion parameters. The decrease in E_d and E_o reduced the oscillator strength along with the zero-frequency dielectric constant. The optical and electrical conductivity changed significantly with time. The changes were saturated with time which brings stability in the film properties that is useful for various optical applications. However, no structural and compositional changes upon laser irradiation were noticed from the X-ray diffraction and EDX studies respectively. The surface homogeneity was checked from the FESEM picture.

The photosensitivity of amorphous chalcogenide thin films brings out light-induced changes in the nonlinear and linear optical parameters upon sub-bandgap and bandgap laser irradiation.