BackgroundCerebral Palsy (CP) is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a) reflect the heterogeneity of the condition and b) can be used to evaluate new translational therapies. To address these key knowledge gaps, we characterized a chronic placental insufficiency (PI) model, using bilateral uterine artery ligation (BUAL) of dams. This injury model results in intrauterine growth restriction (IUGR) in pups, and animals recapitulate the human phenotype both in terms of neurobehavioural and anatomical deficits.MethodsEffects of BUAL were studied using luxol fast blue (LFB)/hematoxylin & eosin (H&E) staining, immunohistochemistry, quantitative Magnetic Resonance Imaging (MRI), and Catwalk neurobehavioural tests.ResultsNeuroanatomical analysis revealed regional ventricular enlargement and corpus callosum thinning in IUGR animals, which was correlated with the extent of growth restriction. Olig2 staining revealed reductions in oligodendrocyte density in white and grey matter structures, including the corpus callosum, optic chiasm, and nucleus accumbens. The caudate nucleus, along with other brain structures such as the optic chiasm, internal capsule, septofimbrial and lateral septal nuclei, exhibited reduced size in animals with IUGR. The size of the pretectal nucleus was reduced only in moderately injured animals. MAG/NF200 staining demonstrated reduced myelination and axonal counts in the corpus callosum of IUGR animals. NeuN staining revealed changes in neuronal density in the hippocampus and in the thickness of hippocampal CA2 and CA3 regions. Diffusion weighted imaging (DWI) revealed regional white and grey matter changes at 3 weeks of age. Furthermore, neurobehavioural testing demonstrated neuromotor impairments in animals with IUGR in paw intensities, swing speed, relative print positions, and phase dispersions.ConclusionsWe have characterized a rodent model of IUGR and have demonstrated that the neuroanatomical and neurobehavioural deficits mirror the severity of the IUGR injury. This model has the potential to be applied to examine the pathobiology of and potential therapeutic strategies for IUGR-related brain injury. Thus, this work has potential translational relevance for the study of CP.

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Both mammalian target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are often over-activated in prostate cancer cells and are associated with cancer progression. In the current study, we evaluated the potential anti-prostate cancer activity of INK-128, an ATP-competitive mTORC1/2 dual inhibitor, both in vitro and in vivo. Our results showed that INK-128 exerted potent anti-proliferative activity in established (PC-3 and LNCaP lines) and primary (patient-derived) human prostate cancer cells by inducing cell apoptosis. The latter was evidenced by increase of annexin V percentage, formation of cytoplasmic histone-associated DNA fragments, and cleavage of caspase-3. INK-128-induced prostate cancer cell apoptosis and cytotoxicity were alleviated upon pretreatment of cells with the pan-caspase inhibitor z-VAD-FMK or the specific caspase-3 inhibitor z-DVED-FMK. At the molecular level, INK-18 blocked mTORC1/2 activation in PC-3 cells and LNCaP cells and downregulated mTOR-regulated genes including cyclin D1, hypoxia-inducible factor 1α (HIF-1α), and HIF-2α. ERK-MAPK activation and androgen receptor expression were, however, not affected by INK-128 treatment. In vivo, oral administration of INK-128 significantly inhibited growth of PC-3 xenografts in nude mice. The preclinical results of this study suggest that INK-128 could be further investigated as a promising anti-prostate cancer agent.

The aim of the present meta-analysis was to compare the benefits of Bacillus Calmetter-Guerin (BCG) and mitomycin C in the treatment of patients with superficial bladder cancer. The present meta-analysis analyzed the benefits of BCG and mitomycin C in the treatment of patients with superficial bladder cancer by comparing progression-free survival (PFS) rates in patients treated with either of the drugs following transurethral resection. The Medline, Cochrane and EMBASE databases were searched between January 1966 and August 31, 2014 for studies that investigated the efficacy of the intravesical instillation of chemotherapy in patients with non-muscle invasive bladder cancer who had been treated with transurethral resection. Search terms included: ‘Urinary bladder neoplasms’, ‘superficial bladder cancer’ and ‘non-muscle invasive bladder cancer’; ‘bacillus Calmette-Guerin’ or ‘BCG’; ‘mitomycin C’; and ‘intravesical administration’. Sensitivity and data quality analyses were performed. A total of 6 randomized controlled studies were included with 1,289 patients. Complete 5-year PFS data for patients who received intravesical resection and were treated with mitomycin C or BCG was provided for 3 of the 6 studies, which were therefore included in the meta-analysis. The overall analysis revealed a significant benefit of BCG compared with mitomycin C in terms of 5-year PFS rate (odds ratio, 0.53; 95% confidence interval, 0.38–0.75; P<0.001), indicating that BCG was superior to mitomycin C therapy in patients with non-muscle invasive bladder cancer following transurethral resection.

Renal cell carcinoma (RCC) is one of the most lethal urological tumours, accounting for 2%-3% of malignancies in the United States. 1There are many kinds of histologic subtypes, among which clear cell RCC (ccRCC) constitutes 70% of RCC. 2 While nephrectomy is curative method for ccRCC, approximately 30% of patients will relapse during the course of disease. 3

We report a facile approach to fabricate an Ag-embedded fullerene (C 60 ) catalyst by the chemical reduction of the AgNO 3 complex encapsulated fullerene microcrystal, which showed an enhanced catalytic reduction of 4-nitrophenol because of the strong absorption and propagation of H 2 along the fullerene surface. With the aid of visible-light radiation, photodegradation of orange G dye is achieved through the formation of an electron donor−acceptor dyad between plasmon Ag nanostructures and fullerene molecules, which effectively offsets the "electron−hole" recombination. Neither Ag nanoparticle nor fullerene crystal used in isolation could perform this chemical conversion, implying that the metal−fullerene hybrid structure is imperative for performing the catalytic reaction. The obtained Ag-embedded fullerene crystal is characterized by scanning electron microscopy (SEM), associated energy-dispersive X-ray spectroscopy (EDX) imaging, and X-ray photoelectron spectroscopy (XPS) and demonstrates that the present hybrid materials would add a supplemental member to a family of photocatalysts toward the organic synthesis and wastewater remediation.

Purpose: Prosthetic iris devices have recently been used to improve cosmesis and reduce glare in aniridia. There is currently no consensus on which prosthetic iris device or which surgical approach is preferred for managing large iris defects.Methods: A novel surgical approach with Gore-Tex polytetrafluoroethylene sutures was used to achieve scleral fixation of an intraocular lens and artificial iris complex in a 19-year-old Caucasian female patient with aniridia, nystagmus, cataracts, and ectopia lentis.Results: Six weeks postoperatively, the intraocular lens-artificial iris complex remained well centered, and the vision in the left eye improved from 20/400 to 20/70. Two years after prosthetic iris device implantation, there have been no complications.Conclusion: This case demonstrates a promising proof-of-concept for long-term management of complicated aniridia cases using an intraocular lens and artificial iris complex prosthetic iris devices. Gore-Tex sutures may be preferable to conventional polypropylene sutures because of their improved durability.

BACKGROUND AND OBJECTIVE: To describe a method for averaging ocular coherence tomography angiography (OCTA) images using a commercially available photo editing software: Adobe Photoshop CC 2017. PATIENTS AND METHODS: This single-center study assessed the feasibility of using Adobe Photoshop as an OCTA image averaging tool. Three 3.0 mm × 3.0 mm OCTA images from each eye were obtained using commercially available OCTA devices. Captured OCTA images were exported in high-resolution TIFF format, imported as an image stack, aligned using an automated function, and averaged by creating a Smart Object using Photoshop CC 2017 software. In conjunction with qualitative assessment, the main outcome of the study was image grader preferences with respect to clarity of the foveal avascular zone (FAZ), blood vessel delineation, and the ability to identify abnormal vasculature. RESULTS: After removing OCTA scans with significant image distortion, 25 sets of images were included in the analysis. Adobe Photoshop CC 2017 successfully aligned and averaged all images of the superficial and deep retinal plexuses that contained a minimum 40% overlap. Three independent retinal specialists found the averaged images to be slightly or definitely preferable to the original 87%, 89%, and 69% of the time with respect to clarity of the FAZ, clarity of blood vessel delineation, and the ability to identify abnormal vasculature, respectively. CONCLUSIONS: Adobe Photoshop CC 2017 is an excellent tool for image averaging, producing high-quality resulting OCTA images. As an easily accessible software, Photoshop has the potential for use in a diversity of pathological conditions. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:802–807.]