3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines ( 3c60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase

Site response analyses for complex geological and morphological conditions: relevant case-histories from 3rd level seismic microzonation in Central Italy

The paper presents the results of 5 case studies on complex site e ects selected within the project for the level 3 seismic microzonation of several municipalities of Central Italy dam- aged by the 2016 seismic sequence. The case studies are characterized by di erent geo- logical and morphological con gurations: Monte San Martino is located along a hill slope, Montedinove and Arquata del Tronto villages are located at ridge top whereas Capitignano and Norcia lie in correspondence of sediment- lled valleys. Peculiarities of the sites are constituted by the presence of weathered/jointed rock mass, fault zone, shear wave veloc- ity inversion, complex surface and buried morphologies. These factors make the de ni- tion of the subsoil model and the evaluation of the local response particularly complex and di cult to ascertain. For each site, after the discussion of the subsoil model, the results of site response numerical analyses are presented in terms of ampli cation factors and acceleration response spectra in selected points. The physical phenomena governing the site response have also been investigated at each site by comparing 1D and 2D numerical analyses. Implications are deduced for seismic microzonation studies in similar geological and morphological conditions.Published5741–57775T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa

An iconic case of pigmentary glaucoma: brief review of the literature

Pigment dispersion syndrome and pigmentary glaucoma are two conditions characterized by pigment dispersion originating from the posterior part of the iris and its accumulation on the trabecular meshwork, corneal endothelium, and anterior surface of the lens. The pigment on the trabecular meshwork can cause chronic inflammation with a secondary reduction of its function and an increase in intraocular pressure. The case presented represents a typical example of pigmentary glaucoma in a myopic patient in which all the signs, symptoms, and complications typical of these pathologies were present. We report and describe an 8-year-long follow-up period with clinical and instrumental examinations

The Choroidal Vascularity Index Versus Optical Coherence Tomography Angiography in the Evaluation of the Choroid with a Focus on Age-Related Macular Degeneration

The choroid is the most vascularized structure of the eye and it is fundamental for the trophism of the outer retina. Its proper functioning and homeostasis represent key points in maintaining normal retinal physiology. Choroidal alterations may be implicated in the development and progression of numerous pathologies; therefore, in-depth studies using imaging techniques can be of crucial relevance to understanding the pathophysiology of retinal-choroidal diseases. The advent of spectral-domain optical coherence tomography (SDOCT) has enabled the non-invasive study of the choroid in vivo and the most recent development, optical coherence tomography angiography (OCTA), allows for the high-resolution visualization of the choriocapillaris and the choroid in regard to vascularization. The choroidal vascularity index (CVI) is a new parameter calculated on SDOCT scans and is defined as the ratio of the luminal area to the total choroidal area. In this review, a study of the choroid using OCTA and CVI will be evaluated in depth and the pros and cons of these two methods will be analyzed, with a particular focus on age-related macular degeneration

Near-infrared reflectance imaging in retinal diseases affecting young patients

Near-infrared reflectance (NIR) is a noninvasive, contactless, and rapid in vivo imaging technique for visualizing subretinal alterations in the photoreceptor layer, retinal pigment epithelium, and choroid. The present report describes the application of this imaging method in retinal and choroidal pathologies affecting young patients where scarce cooperation, poor fixation, and intense glare sensation can result in a challenging clinical examination. A literature search of the MEDLINE database was performed using the terms "near-infrared reflectance"and "spectral-domain optical coherence tomography."Articles were selected if they described the diagnostic use of NIR in children or young adults. Of 700 publications, 42 manuscripts published between 2005 and 2020 were inherent to children or young adults and were considered in this narrative literature review. The first disease category is the phakomatoses where NIR is essential in visualizing choroidal alterations recognized as cardinal biomarkers in neurofibromatosis type 1, microvascular retinal alterations, and retinal astrocytic hamartomas. Another diagnostic application is the accurate visualization of crystals of various nature, including the glistening crystals that characterize Bietti crystalline dystrophy. Acute macular neuropathy and paracentral acute middle maculopathy represent a further disease category with young adulthood onset where NIR is not only diagnostic but also essential to monitor disease progression. A further interesting clinical application is to facilitate the detection of laser-induced maculopathy where funduscopic examination can be normal or subnormal. In conclusion, NIR imaging has a noninterchangeable role in diagnosing certain retinal diseases, especially in children and young adults where there is scarce collaboration and a lack of evident clinical findings. Moreover, this technique can reveal unique retinal and choroidal biomarkers highly specific to rare conditions

Short-term effects of dark chocolate on retinal and choriocapillaris perfusion in young, healthy subjects using optical coherence tomography angiography

(1) Aim: Contrasting results have been published on the effect of dark chocolate on visual function. The aim of this study was to evaluate retinal and choriocapillaris perfusion, using optical coherence tomography angiography (OCT-A), and visual function in healthy subjects following dark chocolate ingestion. (2) Methods: This prospective randomized study was carried out on 18 healthy young subjects at the St. Andrea Hospital, Sapienza, University of Rome. Visual acuity assessment and a complete ophthalmologic examination were carried out at baseline. In session one, each subject was randomized to eat either a 100 g dark chocolate bar or a 100 g white chocolate bar. In session two, the opposite chocolate was given to each participant. OCT-A and best corrected visual acuity (BCVA) were performed before the chocolate was eaten and repeated 1, 2, and 3 h after that. Retinal vessel density and choriocapillaris flow area were assessed. (3) Results: 18 patients with a mean (SD) age of 26.3 (1.5) years were included. No significant differences between dark or white chocolate were found when evaluating foveal density (%), whole density (%), choriocapillaris flow area, and BCVA. (4) Conclusions: Dark chocolate did not result in significant changes in retinal perfusion and choriocapillaris flow area. However, given the results of other studies showing the positive effects of flavonoids on visual function, further studies are warranted using pure chocolate without other components such as caffeine that can potentially affect results. Furthermore, we cannot rule out the possible benefits of higher doses of flavonoids in dietary supplementation over a more extended period and in a larger patient population

Volume rendering of angiographic optical coherence tomography angiography in fovea plana and normal foveal pit

This paper aims to study adaptative vascular arrangements in idiopathic fovea plana with volume-rendered optical coherence tomography angiography (OCTA). A retrospective review of two cases of idiopathic fovea plana (mean age: 26.5 years) and two age-matched controls imaged with OCTA was conducted using spectral-domain OCTA (RTVue XR Avanti, Optovue, Inc., Fremont, CA) equipped with the AngioVue software. Both en face OCTA slabs and OCTA b scans were processed through Fiji software (http://fiji.sc; software version 2.0.0-rc-68/1.52e), and then extracted as image sequences for volume rendering reconstructions using the ImageVis3D volume rendering system (3.1.0 release). Eyes with idiopathic fovea plana demonstrated a regular superficial vascular plexus connecting to a single vascular monolayer representing the deeper vascular plexuses. At this location, several vertical short path connections were demonstrated, in contraposition with normal eyes where short path connections were infrequently observed. Advances in three-dimensional OCTA reconstruction increase the understanding of vascular connections and arrangement in retinal plexuses and possible anatomical variations that cannot be detected with conventional two-dimensional b scans