Bilateral Symmetry of Visual Function Loss in Cone-Rod Dystrophies.

PURPOSE: To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. METHODS: This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. RESULTS: Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. CONCLUSIONS: These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of epsilon-poly-L-lysine capped mesoporous silica-based nanoparticles

[EN] Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into epsilon-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr(-)) permeability barrier for the HKAIs. The observed bactericidal activity against Gr(-) bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr(-) and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria. (C) 2016 Elsevier Inc. All rights reserved.This work was funded by FP7 ITN STARS-Scientific Training in Antimicrobial Research Strategies (Contract No. PITN-GA-2009-238490, J.M.W., A.M.), H2020 MSCA IF (AND-659121, N.V.), grant BIO2013-42619-P from the Ministerio de Economia y Competitividad (A.M.), grant from the Spanish Government (Project MAT2015-64139-C4-1-R,N. M., J.R.M, R.M.M.), and a grant from Generalitat Valenciana (Project PROMETEOII/2014/047, N.M.). and Prometeo II/2014/029, A.M.).Velikova, N.; Mas Font, N.; Miguel-Romero, L.; Polo, L.; Stolte, E.; Zaccaria, E.; Cao, R.... (2017). Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of epsilon-poly-L-lysine capped mesoporous silica-based nanoparticles. Nanomedicine Nanotechnology Biology and Medicine. 13(2):569-581. https://doi.org/10.1016/j.nano.2016.09.011S56958113

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Design of a Resilient, High-Throughput, Persistent Storage System for the ATLAS Phase-II DAQ System

The ATLAS experiment will undergo a major upgrade to take advantage of the new conditions provided by the upgraded High-Luminosity LHC. The Trigger and Data Acquisition system (TDAQ) will record data at unprecedented rates: the detectors will be read out at 1 MHz generating around 5 TB/s of data. The Dataflow system (DF), component of TDAQ, introduces a novel design: readout data are buffered on persistent storage while the event filtering system analyses them to select 10000 events per second for a total recorded throughput of around 60 GB/s. This approach allows for decoupling the detector activity from the event selection process. New challenges then arise for DF: design and implement a distributed, reliable, persistent storage system supporting several TB/s of aggregated throughput while providing tens of PB of capacity. In this paper we first describe some of the challenges that DF is facing: data safety with persistent storage limitations, indexing of data at high-granularity in a highly-distributed system, and high-performance management of storage capacity. Then the ongoing R&D to address each of the them is presented and the performance achieved with a working prototype is shown

NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study

BACKGROUND: Preclinical trials have shown beneficial effects of nerve growth factor (NGF) administration on visual function in animal models of retinitis pigmentosa (RP). The aim of this pilot study was to explore the potential efficacy of short term NGF eye drops treatment in patients affected by RP. METHODS: The trial consisted in 10 days daily administration of murine NGF as eye-drops for a total dose of 1 mg NGF/pt. Eight RP patients at an advanced stage of the disease were included in the trial. To monitor safety and potential adverse effects subjects underwent standard clinical measures and were requested to report any general or topic alterations following NGF assumption. Retinal function was assessed at baseline and after treatment by best-corrected visual acuity measurement (BCVA), macular focal electroretinogram (fERG) recording and Goldmann visual field testing. RESULTS: A transient tolerable local corneal irritation was the only adverse effect reported. fERG and BCVA remained within the limits determined by test-retest analysis of a large cohort of RP patients. Three patients reported a subjective feeling of improved visual performance. This was associated to a temporary enlargement of the visual field in all three patients and to improved fERG in two of the three. CONCLUSIONS: Short-term administration of NGF eye-drops caused neither significant adverse effects nor visual function losses in the tested RP patients. A minority of patients experienced an improvement of visual performance as shown by Goldmann visual field and fERG. This study supports the safety and possible efficacy of NGF eye-drops administration in RP patients. TRIAL REGISTRATION: EudraCT n. 2008-004561-26

Intravitreal dexamethasone implant for acute exudative polymorphous vitelliform maculopathy

Acute exudative polymorphous vitelliform maculopathy is a rare retinal disease characterized by bilateral serous macular detachment and subretinal accumulation of yellowish deposits resembling Best dystrophy lesions. Corticosteroid systemic therapy has been used empirically in the attempt to treat this retinal disorder with mixed results. Thus, the benefit of corticosteroid remains undetermined. To our knowledge, we report the first case of acute exudative polymorphous vitelliform maculopathy (AEPVM) treated in one eye with intravitreal dexamethasone implant (Ozurdex; Allergan, Inc., Irvine, California, USA)

Acute acquired concomitant esotropia and decompensated monofixation syndrome: a sensory-motor status assessment

Purpose: To assess and compare sensory-motor status and clinical features of type I and type II Purpose: To assess and compare sensory-motor status and clinical features of type I and type II acute acquired concomitant esotropia (group A) and decompensated monofixation syndrome (group B). Methods: In a retrospective, comparative study twenty-six patients, with a confirmed postoperative diagnosis of types I and II acute acquired concomitant esotropia and monofixation syndrome, were enrolled. A two-tailed unpaired t-test and a two-tailed chi-square test were performed to compare angle deviation and sensory-motor status under viewing conditions and after prismatic adaptation test and progressive prism test of two groups. Results: All of the patients of group A and 4 patients (33%) of group B complained of diplopia under viewing conditions, at the Worth\u2019s 4 dot and Bagolini striated glasses test. The TNO stereo test showed the total absence of stereopsis in 6 patients in group B and a significantly lower stereoacuity in group A in the remaining six patients (p<0.0001). The Prismatic adaptation test was positive in all of the patients in group B and in 10 patients (71%) in group A (p=0.39). The value of the angle deviation after progressive prism test was significantly higher in group B than group A (p = 0.02). At the end of the progressive prism test all of the patients in group A and only two patients in group B were orthotropic (p=0.01). Conclusions: Bagolini striated glasses and Worth\u2019s 4 dot tests under viewing conditions, and responses under prisms allow for the differentiation of the two forms and lead to an accurate aesthetic and functional prognosis. Keywords: acute acquired concomitant esotropia, decompensated monofixation syndrome, prismatic adaptation test, strabismus, diplopia

ARCUATE NERVE FIBER LAYER CHANGES AFTER INTERNAL LIMITING MEMBRANE PEELING IN IDIOPATHIC EPIRETINAL MEMBRANE

PURPOSE: To analyze the relationship between swelling of the arcuate nerve fiber layer (SANFL) and long-term decrease of retinal nerve fiber layer thickness after internal limiting membrane peeling for idiopathic epiretinal membrane, and to investigate if SANFL is related to a mechanical surgical damage. METHODS: Prospective, interventional consecutive case series of 46 eyes that underwent combined epiretinal membrane/internal limiting membrane peeling for idiopathic epiretinal membrane. Infrared, blue autofluorescence, color fundus imaging and measurement of retinal nerve fiber layer thickness in six peripapillary sectors by spectral-domain optical coherence tomography were performed preoperatively and at 2 weeks, 1, 3, 6, and 12 months after surgery. The presence of SANFL was checked postoperatively on infrared and blue autofluorescence fundus imaging, and the extent of each SANFL was measured on infrared fundus images. RESULTS: Areas of SANFL were identified in 39 eyes (84.8%) at 2-week follow-up. Retinal nerve fiber layer thickness significantly decreased in the temporal sectors at 1, 6, and 12 months (P &lt; 0.0001). The linear extent of SANFL was significantly correlated with the percentage of reduction in retinal nerve fiber layer thickness in the temporal (R = 0.45; P &lt; 0.0001) and infero-temporal (R = 0.23; P = 0.0008) sectors at 12 months of follow-up. Correspondence between sites of surgical grasping and the points of origin of SANFL was demonstrated on blue autofluorescence fundus images superimposed on intraoperative surgical frames. CONCLUSION: Early postoperative SANFL is correlated with late focal retinal nerve fiber layer thinning in the temporal sectors. Intraoperative surgical grasping seems to be a leading factor for the onset of SANFL

Bilateral Symmetry of Visual Function Loss in Cone–Rod Dystrophies

PURPOSE: To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. METHODS: This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. RESULTS: Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. CONCLUSIONS: These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control