Deep learning for automatic prediction of early activation of treatment naïve non-exudative MNVs in AMD.

BACKGROUND: Around 30% of non-exudative macular neovascularizations(NE-MNVs) exudate within 2 years from diagnosis in patients with age-related macular degeneration(AMD).The aim of the study is to develop a deep learning classifier based on optical coherence tomography(OCT) and OCT angiography(OCTA) to identify NE-MNVs at risk of exudation. METHODS: AMD patients showing OCTA and fluorescein angiography (FA) documented NE-MNV with a 2-years minimum imaging follow-up were retrospectively selected. Patients showing OCT B-scan-documented MNV exudation within the first 2 years formed the EX-GROUP while the others formed QU-GROUP.ResNet-101, Inception-ResNet-v2 and DenseNet-201 were independently trained on OCTA and OCT B-scan images. Combinations of the 6 models were evaluated with major and soft voting techniques. RESULTS: Eighty-nine (89) eyes of 89 patients with a follow-up of 5.7 ± 1.5 years were recruited(35 EX GROUP and 54 QU GROUP). Inception-ResNet-v2 was the best performing among the 3 single convolutional neural networks(CNNs).The major voting model resulting from the association of the 3 different CNNs resulted in improvement of performance both for OCTA and OCT B-scan (both significantly higher than human graders' performance). Soft voting model resulting from the combination of OCTA and OCT B-scan based major voting models showed a testing accuracy of 94.4%. Peripheral arcades and large vessels on OCTA enface imaging were more prevalent in QU GROUP. CONCLUSIONS: Artificial intelligence shows high performances in identifications of NE-MNVs at risk for exudation within the first 2 years of follow up, allowing better customization of follow up timing and avoiding treatment delay. Better results are obtained with the combination of OCTA and OCT B-scan image analysis.

The invention of writing on Rapa Nui (Easter Island). New radiocarbon dates on the Rongorongo script.

Placing the origin of an undeciphered script in time is crucial to understanding the invention of writing in human history. Rapa Nui, also known as Easter Island, developed a script, now engraved on fewer than 30 wooden objects, which is still undeciphered. Its origins are also obscure. Central to this issue is whether the script was invented before European travelers reached the island in the eighteenth century AD. Hence direct radiocarbon dating of the wood plays a fundamental role. Until now, only two tablets were directly dated, placing them in the nineteenth c. AD, which does not solve the question of independent invention. Here we radiocarbon-dated four Rongorongo tablets preserved in Rome, Italy. One specimen yielded a unique and secure mid-fifteenth c. date, while the others fall within the nineteenth c. AD. Our results suggest that the use of the script could be placed to a horizon that predates the arrival of external influence.

Refractive outcome in combined phacovitrectomy: Anterior segment changes and corrective factor for IOL power calculation improvement.

PURPOSE: To analyze differences in refractive outcome Δ (difference between postoperative and expected refractive error) and in anterior segment changes between cataract surgery patients and combined phacovitrectomy patients. We also aimed to provide a corrective formula allowing to minimise the refractive outcome Δ in combined surgery patients. METHODS: Candidates for phacoemulsification and combined phacovitrectomy (respectively PHACO and COMBINED groups) were prospectively enrolled in two specialised centres. Patients underwent best corrected visual acuity (BCVA) assessment, ultra-high speed anterior segment optical coherence tomography (OCT), gonioscopy, retinal OCT, slit lamp examination and biometry at baseline, 6 weeks postoperatively and 3 months postoperatively. RESULTS: No differences in refractive Δ, refractive error and anterior segment parameters were noted between PHACO and COMBINED group (109 and 110 patients respectively) at 6 weeks. At 3 months, COMBINED group showed a spherical equivalent of -0.29 ± 0.10 D versus -0.03 ± 0.15 D in PHACO group (p = 0.023). COMBINED group showed a significantly higher Crystalline Lens Rise (CLR), angle-to-angle (ATA) and anterior chamber width (ACW) and a significantly lower anterior chamber depth (ACD) and refractive Δ with all 4 considered formulas at 3 months. For IOL power lower than 15, a hyperopic shift was observed instead. CONCLUSIONS: Anterior segment OCT suggests anterior displacement of the effective lens position in patients undergoing phacovitrectomy. A corrective formula can be applied to IOL power calculation to minimize undesired refractive error.

Refractive Outcomes With New Generation Formulas for Intraocular Lens Power Calculation in Radial Keratotomy Patients.

PURPOSE: Radial keratotomies (RKs) are responsible for corneal irregularities resulting in biometric errors and lower best-corrected visual acuity (BCVA) due to lower-order and higher-order optical aberrations. The aim of the study was to compare performances of new and old generation formulas in a population of RK patients. METHODS: RK patients who underwent phacoemulsification with intraocular lens (IOL) implantation were retrospectively recruited. Inclusion criteria were availability of preoperative and 6-month postoperative BCVA assessment, topography, and tomography. Documented refraction instability, corneal ectasia, and previous ocular surgery except for RK were exclusion criteria. Mean prediction error (ME), mean absolute prediction error (MAE), and incidence of MAE > 0.25D were calculated for SRK-T, Barrett True K, EVO 2.0, Kane, and PEARL-DGS. RESULTS: Twenty-seven patients with a mean baseline BCVA of 0.32 ± 0.18 logMAR and a mean corneal root mean square (RMS) value of 1.59 ± 0.91 µm were included. EVO 2.0, Kane, and PEARL-DGS showed a significantly lower MAE and lower ME compared with all other formulas ( P < 0.001 and P < 0.001) and a significant lower incidence of MAE >0.25D ( P < 0.001). Significant differences were still detected when using 3-mm mean keratometry for IOL calculation. CONCLUSIONS: PEARL-DGS, Kane, and EVO 2.0 formulas show superior accuracy in IOL power calculation compared with SRK-T and Barrett True K in RK patients, with no significant differences between the 3.

MANAGEMENT OF RETINAL DETACHMENT ASSOCIATED WITH MORNING GLORY SYNDROME USING THE HUMAN AMNIOTIC MEMBRANE.

PURPOSE: This case report describes an innovative procedure for addressing retinal detachment in patients with morning glory syndrome. METHODS: An 18-year-old woman with unilateral morning glory syndrome complicated by macula-off retinal detachment without any visible peripheral retinal breaks underwent three corrective surgeries. In the first surgery, a 25-gauge pars plana vitrectomy with a 3-mm human amniotic membrane patch positioned on the optic disc and gas endotamponade was performed. When the gas reabsorbed, inferior retinal detachment recurred, and a second vitrectomy with silicone oil endotamponade was conducted. At three months, the retina was still attached under the silicone oil, so the oil was removed. At the second follow-up, retinal detachment had recurred, and a third vitrectomy with a larger amniotic patch and silicone oil endotamponade was performed. RESULTS: Three months following the last surgery, the subretinal fluid had totally reabsorbed, and the retina was completely attached. The best-corrected visual acuity was 20/100. CONCLUSION: To the best of our knowledge, the first description of a human amniotic patch associated with vitrectomy in morning glory syndrome complicated with retinal detachment is described. Using human amniotic membranes, positioned onto the optic nerve, and silicone oil endotamponade could be useful for morning glory syndrome complicated by retinal detachment.

Smaller-Incision new-generation implantable miniature telescope: Three-months follow-up study.

PURPOSE: To evaluate three months follow-up of SING IMT implant in patients affected by late-stage AMD. DESIGN: Prospective cohort study. SUBJECTS: In a total of 80 eyes of 40 patients who underwent the enrollment tests, 11 patients' eyes affected by late-stage AMD matched the inclusion criteria and underwent SING IMT implant from February to June 2022. METHODS: Before surgery, each patient underwent the enrollment examination to verify inclusion and exclusion criteria. MAIN OUTCOME MEASURES: BCVA for distance and for near, IOP, ACD and ECD were evaluated at 1 and 3 months follow up. Also quality of life in doing the activities of daily life was evaluated. RESULTS: BCVA for distance and for near improved from baseline to 3 months follow up (23.91 ± 9.418 ETDRS letters and 59.09 ± 11.58 ETDRS letters respectively (p < 0.001). An endothelial cell loss was shown (p < 0.001), with a rate of cell density reduction around 8.3% (baseline vs 3 months). CONCLUSIONS: SING IMT could be a valid surgical device to improve patients' sight and quality of life which have been deteriorated by late-stage macular degeneration. Further studies with more patients and longer follow up are needed to confirm our results.

What Is behind In-Stream Advertising on YouTube? A Remote Neuromarketing Study employing Eye-Tracking and Facial Coding techniques.

Not all elements displayed in a YouTube in-stream video ad are attributable to the ad itself. Some of those are automatically introduced by the platform, such as the countdown timer and the time progress bar. In recent years, some authors started exploring the effects associated with the presence of such non-ad items, providing valuable findings. However, objective evaluation of viewers' visual attention is lacking in this context as well as emotional investigation. In addition, previous research showed how the manipulation of seemingly negligible details can yield dramatically different outcomes in the context of in-stream advertising. To extend knowledge, the authors explored the effects of the non-ad items' presence by employing eye-tracking and facial coding techniques in combination with self-reports in a between-subjects experimental design focusing on the YouTube 15-s, mid-roll, non-skippable in-stream ad format. Results showed that the ad format currently employed by YouTube performs worse than its equivalent without the non-ad items on all the investigated measures and than its equivalent in which the non-ad items' presence was experimentally reduced on facial coding disgust, self-reported disgust, ad irritation, and ad attitude. Managerial insights and challenges concerning the future of in-stream advertising and neuromarketing are highlighted.

A Neuroergonomic Approach Fostered by Wearable EEG for the Multimodal Assessment of Drivers Trainees.

When assessing trainees' progresses during a driving training program, instructors can only rely on the evaluation of a trainee's explicit behavior and their performance, without having any insight about the training effects at a cognitive level. However, being able to drive does not imply knowing how to drive safely in a complex scenario such as the road traffic. Indeed, the latter point involves mental aspects, such as the ability to manage and allocate one's mental effort appropriately, which are difficult to assess objectively. In this scenario, this study investigates the validity of deploying an electroencephalographic neurometric of mental effort, obtained through a wearable electroencephalographic device, to improve the assessment of the trainee. The study engaged 22 young people, without or with limited driving experience. They were asked to drive along five different but similar urban routes, while their brain activity was recorded through electroencephalography. Moreover, driving performance, subjective and reaction times measures were collected for a multimodal analysis. In terms of subjective and performance measures, no driving improvement could be detected either through the driver's subjective measures or through their driving performance. On the other side, through the electroencephalographic neurometric of mental effort, it was possible to catch their improvement in terms of mental performance, with a decrease in experienced mental demand after three repetitions of the driving training tasks. These results were confirmed by the analysis of reaction times, that significantly improved from the third repetition as well. Therefore, being able to measure when a task is less mentally demanding, and so more automatic, allows to deduce the degree of users training, becoming capable of handling additional tasks and reacting to unexpected events.

Time-Dependent Analysis of Human Neurophysiological Activities during an Ecological Olfactory Experience.

It has been demonstrated that odors could affect humans at the psychophysiological level. Significant research has been done on odor perception and physiological mechanisms; however, this research was mainly performed in highly controlled conditions in order to highlight the perceptive phenomena and the correlated physiological responses in the time frame of milliseconds. The present study explored how human physiological activity evolves in response to different odor conditions during an ecological olfactory experience on a broader time scale (from 1 to 90 s). Two odors, vanilla and menthol, together with a control condition (blank) were employed as stimuli. Electroencephalographic (EEG) activity in four frequency bands of interest, theta, alpha, low beta, and high beta, and the electrodermal activity (EDA) of the skin conductance level and response (SCL and SCR) were investigated at five time points taken during: (i) the first ten seconds of exposure (short-term analysis) and (ii) throughout the entire exposure to each odor (90 s, long-term analysis). The results revealed significant interactions between the odor conditions and the time periods in the short-term analysis for the overall frontal activity in the theta (p = 0.03), alpha (p = 0.005), and low beta (p = 0.0067) bands, the frontal midline activity in the alpha (p = 0.015) and low beta (p = 0.02) bands, and the SCR component (p = 0.024). For the long-term effects, instead, only one EEG parameter, frontal alpha asymmetry, was significantly sensitive to the considered dimensions (p = 0.037). In conclusion, the present research determined the physiological response to different odor conditions, also demonstrating the sensitivity of the employed parameters in characterizing the dynamic of such response during the time. As an exploratory study, this work points out the relevance of considering the effects of continuous exposure instead of short stimulation when evaluating the human olfactory experience, providing insights for future studies in the field.

Little reason to call them small noncoding RNAs.

Hundreds of different species of small RNAs can populate a bacterial cell. This small transcriptome contains important information for the adaptation of cellular physiology to environmental changes. Underlying cellular networks involving small RNAs are RNA-RNA and RNA-protein interactions, which are often intertwined. In addition, small RNAs can function as mRNAs. In general, small RNAs are referred to as noncoding because very few are known to contain translated open reading frames. In this article, we intend to highlight that the number of small RNAs that fall within the set of translated RNAs is bound to increase. In addition, we aim to emphasize that the dynamics of the small transcriptome involve different functional codes, not just the genetic code. Therefore, since the role of small RNAs is always code-driven, we believe that there is little reason to continue calling them small noncoding RNAs.

Virtual and Reality: A Neurophysiological Pilot Study of the Sarcophagus of the Spouses.

Art experience is not solely the observation of artistic objects, but great relevance is also placed on the environment in which the art experience takes place, often in museums and galleries. Interestingly, in the last few years, the introduction of some forms of virtual reality (VR) in museum contexts has been increasing. This has solicited enormous research interest in investigating any eventual differences between looking at the same artifact either in a real context (e.g. a museum) and in VR. To address such a target, a neuroaesthetic study was performed in which electroencephalography (EEG) and autonomic signals (heart rate and skin conductance) were recorded during the observation of the Etruscan artifact "Sarcophagus of the Spouses", both in the museum and in a VR reproduction. Results from EEG analysis showed a higher level of the Workload Index during observation in the museum compared to VR (p = 0.04), while the Approach-Withdrawal Index highlighted increased levels during the observation in VR compared to the observation in the museum (p = 0.03). Concerning autonomic indices, the museum elicited a higher Emotional Index response than the VR (p = 0.03). Overall, preliminary results suggest a higher engagement potential of the museum compared to VR, although VR could also favour higher embodiment than the museum.

Correlation between AI-measured lacquer cracks extension and development of myopic choroidal neovascularization.

OBJECTIVES: To investigate the correlation between the AI-measured area of the lacquer cracks (LC) at their first detection and the occurrence of a choroidal neovascularization (CNV) during the follow-up in patients affected by pathologic myopia. Secondary outcome was the detection of a correlation between the time to onset of CNV with both baseline LC area and LC area increase during follow-up. METHODS: Optical coherence tomography (OCT) acquisitions of patients diagnosed with LC were retrospectively analysed. The study population was divided in a CNV group (showing the documented onset of a CNV) and a n-CNV group (no CNV development during follow-up). LC area was measured using MatLab software after the application of a customized method for LC segmentation on infrared (IR) enface images. RESULTS: Forty-five (45) patients with a mean follow-up of 4.9 ± 1.5 years were included. LC area at baseline was 2.82 ± 0.54 mm2 and 1.70 ± 0.49 mm2 in CNV (20 patients) and n-CNV group (25 patients) group respectively (p < 0.001). LC area increase was significantly higher in CNV group (p < 0.001). Time to onset of CNV was linearly correlated with both LC area at baseline (p = 0.006) and LC area increase (p < 0.001). CONCLUSIONS: Myopic CNV development is associated with lager LC areas and higher LC area increase during time. Earlier CNV onset is inversely correlated with LC area and LC area increase.

Perivenular Capillary Rarefaction in Diabetic Retinopathy: Interdevice Characterization and Association to Clinical Staging.

Purpose: Geometric perfusion deficit (GPD) is a newly described OCT angiography (OCTA) parameter identifying the total area of presumed retinal ischemia. The aim of our study is to characterize differences in GPD and other common quantitative OCTA parameters between macular full field, perivenular zones, and periarteriolar zones for each clinical stage of nonproliferative diabetic retinopathy (DR) and to assess the influence of ultrahigh-speed acquisition and averaging on the described differences. Design: Prospective observational study. Participants: Forty-nine patients, including 11 (22.4%) with no sign of DR, 12 (24.5%) with mild DR, 13 (26.5%) with moderate DR, and 13 (26.5%) with severe DR. Patients with diabetic macular edema, proliferative DR, media opacity, head tremor, and overlapping retinal diseases or systemic diseases influencing OCTA were excluded. Methods: OCT angiography was performed 3 times for each patient: 1 using Solix Fullrange single volume (V1) mode, 1 using Solix Fullrange 4 volumes mode with automatically averaged scan (V4), and 1 using AngioVue. Main Outcome Measures: Full macular, periarteriolar, and perivenular perfusion density (PD), vessel length density (VLD), vessel density index, and GPD for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: In patients showing no sign of DR, PD and VLD were significantly lower in the perivenular area in both the DCP and SCP using V1 and V4, whereas GPD was significantly higher in the perivenular zone in the DCP and SCP with all 3 devices. In patients with mild DR, all 3 measurements (PD, VLD, and GPD) were significantly different in the perivenular zone with all 3 devices. In patients with moderate DR, PD and VLD were lower in the DCP and SCP when measured with V1 and V4. Moreover, GPD was higher in the perivenular zone in the DCP with all 3 devices, whereas only V4 detected a difference in the SCP. In severe DR, only V4 detected a lower PD and VLD and a higher GPD in the DCP of the perivenular zone. V4 also detected a higher GPD in the SCP. Conclusions: Geometric perfusion deficit highlights prevalent perivenular location of macular capillary ischemia in all stages of DR. In severe DR patients, only averaging technology allows detection of the same finding. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Multifaceted Interplay between Hfq and the Small RNA GssA in Pseudomonas aeruginosa.

Behind the pathogenic lifestyle of Pseudomonas aeruginosa exists a complex regulatory network of intertwined switches at both the transcriptional and posttranscriptional levels. Major players that mediate translation regulation of several genes involved in host-P. aeruginosa interaction are small RNAs (sRNAs) and the Hfq protein. The canonical role of Hfq in sRNA-driven regulation is to act as a matchmaker between sRNAs and target mRNAs. Besides, the sRNA CrcZ is known to sequester Hfq and abrogate its function of translation repression of target mRNAs. In this study, we describe the novel sRNA GssA in the strain PA14 and its multifaceted interplay with Hfq. We show that GssA is multiresponsive to environmental and physiological signals and acts as an apical repressor of key bacterial functions in the human host such as the production of pyocyanin, utilization of glucose, and secretion of exotoxin A. We suggest that the main role of Hfq is not to directly assist GssA in its regulatory role but to repress GssA expression. In the case of pyocyanin production, we suggest that Hfq interplays with GssA also by converging a positive effect on this pathway. Furthermore, our results indicate that both Hfq and GssA play a positive role in anaerobic growth, possibly by regulating the respiratory chain. On the other hand, we show that GssA can modulate not only Hfq expression at both transcriptional and posttranscriptional levels but also that of CrcZ, thus potentially influencing the pleiotropic role of Hfq. IMPORTANCE The pathogenic lifestyle of the bacterium Pseudomonas aeruginosa, a leading cause of life-threatening infections in the airways of cystic fibrosis patients, is based on the fine regulation of virulence-associated factors. Regulatory small RNAs (sRNAs) and the RNA-binding protein Hfq are recognized key components within the P. aeruginosa regulatory networks involved in host-pathogen interaction. In this study, we characterized in the highly virulent P. aeruginosa strain PA14 the novel sRNA GssA. We found that it can establish a many-sided reciprocal interplay with Hfq which goes beyond the canonical mechanism of direct physical interaction that had previously been characterized for other sRNAs. Given that the Hfq-driven regulatory network of virulence factors is very broad and important for the progression of infection, we consider GssA as a new RNA target that can potentially be used to develop new antibacterial drugs.

NEW ARTIFICIAL INTELLIGENCE ANALYSIS FOR PREDICTION OF LONG-TERM VISUAL IMPROVEMENT AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To predict improvement of best-corrected visual acuity (BCVA) 1 year after pars plana vitrectomy for epiretinal membrane (ERM) using artificial intelligence methods on optical coherence tomography B-scan images. METHODS: Four hundred and eleven (411) patients with Stage II ERM were divided in a group improvement (IM) (≥15 ETDRS letters of VA recovery) and a group no improvement (N-IM) (<15 letters) according to 1-year VA improvement after 25-G pars plana vitrectomy with internal limiting membrane peeling. Primary outcome was the creation of a deep learning classifier (DLC) based on optical coherence tomography B-scan images for prediction. Secondary outcome was assessment of the influence of various clinical and imaging predictors on BCVA improvement. Inception-ResNet-V2 was trained using standard augmentation techniques. Testing was performed on an external data set. For secondary outcome, B-scan acquisitions were analyzed by graders both before and after fibrillary change processing enhancement. RESULTS: The overall performance of the DLC showed a sensitivity of 87.3% and a specificity of 86.2%. Regression analysis showed a difference in preoperative images prevalence of ectopic inner foveal layer, foveal detachment, ellipsoid zone interruption, cotton wool sign, unprocessed fibrillary changes (odds ratio = 2.75 [confidence interval: 2.49-2.96]), and processed fibrillary changes (odds ratio = 5.42 [confidence interval: 4.81-6.08]), whereas preoperative BCVA and central macular thickness did not differ between groups. CONCLUSION: The DLC showed high performances in predicting 1-year visual outcome in ERM surgery patients. Fibrillary changes should also be considered as relevant predictors.

Deep learning to distinguish Best vitelliform macular dystrophy (BVMD) from adult-onset vitelliform macular degeneration (AVMD).

Initial stages of Best vitelliform macular dystrophy (BVMD) and adult vitelliform macular dystrophy (AVMD) harbor similar blue autofluorescence (BAF) and optical coherence tomography (OCT) features. Nevertheless, BVMD is characterized by a worse final stage visual acuity (VA) and an earlier onset of critical VA loss. Currently, differential diagnosis requires an invasive and time-consuming process including genetic testing, electrooculography (EOG), full field electroretinogram (ERG), and visual field testing. The aim of our study was to automatically classify OCT and BAF images from stage II BVMD and AVMD eyes using a deep learning algorithm and to identify an image processing method to facilitate human-based clinical diagnosis based on non-invasive tests like BAF and OCT without the use of machine-learning technology. After the application of a customized image processing method, OCT images were characterized by a dark appearance of the vitelliform deposit in the case of BVMD and a lighter inhomogeneous appearance in the case of AVMD. By contrast, a customized method for processing of BAF images revealed that BVMD and AVMD were characterized respectively by the presence or absence of a hypo-autofluorescent region of retina encircling the central hyperautofluorescent foveal lesion. The human-based evaluation of both BAF and OCT images showed significantly higher correspondence to ground truth reference when performed on processed images. The deep learning classifiers based on BAF and OCT images showed around 90% accuracy of classification with both processed and unprocessed images, which was significantly higher than human performance on both processed and unprocessed images. The ability to differentiate between the two entities without recurring to invasive and expensive tests may offer a valuable clinical tool in the management of the two diseases.

Unsupervised deep learning supports reclassification of Bronze age cypriot writing system.

Ancient undeciphered scripts present problems of different nature, not just tied to linguistic identification. The undeciphered Cypro-Minoan script from second millennium BCE Cyprus, for instance, currently does not have a standardized, definitive inventory of signs, and, in addition, stands divided into three separate subgroups (CM1, CM2, CM3), which have also been alleged to record different languages. However, this state of the art is not consensually accepted by the experts. In this article, we aim to apply a method that can aid to shed light on the tripartite division, to assess if it holds up against a multi-pronged, multi-disciplinary approach. This involves considerations linked to paleography (shapes of individual signs) and epigraphy (writing style tied to the support used), and crucially, deep learning-based strategies. These automatic methods, which are widely adopted in many fields such as computer vision and computational linguistics, allow us to look from an innovative perspective at the specific issues presented by ancient, poorly understood scripts in general, and Cypro-Minoan in particular. The usage of a state-of-the-art convolutional neural model that is unsupervised, and therefore does not use any prior knowledge of the script, is still underrepresented in the study of undeciphered writing systems, and helps to investigate the tripartite division from a fresh standpoint. The conclusions we reached show that: 1. the use of different media skews to a large extent the uniformity of the sign shapes; 2. the application of several neural techniques confirm this, since they highlight graphic proximity among signs inscribed on similar supports; 3. multi-stranded approaches prove to be a successful tool to investigate ancient scripts whose language is still unidentified. More crucially, these aspects, together, point in the same direction, namely the validation of a unitary, single Cypro-Minoan script, rather than the current division into three subgroups.

Subretinal Pigment Epithelium Illumination Combined With Focal Electroretinogram and Visual Acuity for Early Diagnosis and Prognosis of Non-Exudative Age-Related Macular Degeneration: New Insights for Personalized Medicine.

PURPOSE: To evaluate the correlation between functional visual acuity and focal electroretinograms (fERGs) and morphological abnormalities in the retinal pigment epithelium and outer retinal atrophy (RORA) assessed by subretinal illumination (SRI) parameter at optical coherence tomography (OCT) examinations as signs of early disease in early and intermediate non-exudative age-related macular degeneration (ne-AMD). METHODS: One hundred forty-one eyes of 74 patients were retrospectively evaluated. A subgroup of patients (34/74) had a follow-up of at least 1 year. The study included both cross-sectional and longitudinal analyses. All eyes were assessed by OCT to measure the macular outer nuclear layer thickness, extent of ellipsoid zone interruption, absence or presence of drusen/reticular pseudodrusen in the foveal and perifoveal fields, and the SRI area closest to the fovea. Additionally, fERGs were performed. RESULTS: In the cross-sectional analysis, visual acuity and fERG amplitude were correlated (P < 0.01) with the SRI area. The fERG amplitude was correlated (P < 0.01) with the extent of ellipsoid zone interruption and tended to be lower in reticular pseudodrusen compared with drusen. In the longitudinal analysis, fERG amplitudes and outer retinal thickness tended to decrease on average by 15% and 18%, respectively, after 1 year of follow-up. The baseline RORA area, but not fERG amplitude or visual acuity, significantly predicted with 77% accuracy (P < 0.01) morphological deterioration, which was determined by an increase in the RORA area after 1 year. CONCLUSIONS: Functional visual acuity and its morphological correlations can be assessed in early and intermediate ne-AMD eyes. SRI, as a result of RORA, is a potential predictor of ne-AMD progression in a short-term follow-up. TRANSLATIONAL RELEVANCE: SRI assessment, an objective method to measure RORA, is a potential biomarker for non-exudative AMD progression.

The Small RNA ErsA Impacts the Anaerobic Metabolism of Pseudomonas aeruginosa Through Post-Transcriptional Modulation of the Master Regulator Anr.

Pseudomonas aeruginosa is one of the most critical opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. In previous work, we indicated that the small RNA ErsA plays a role in the regulatory network of P. aeruginosa pathogenicity in airways infection. To give further insight into the lifestyle functions that could be either directly or indirectly regulated by ErsA during infection, we reanalyzed the categories of genes whose transcription appeared dysregulated in an ersA knock-out mutant of the P. aeruginosa PAO1 reference strain. This preliminary analysis indicated ErsA as a candidate co-modulator of denitrification and in general, the anaerobiosis response, a characteristic physiologic state of P. aeruginosa during chronic infection of the lung of cystic fibrosis (CF) patients. To explain the pattern of dysregulation of the anaerobic-lifestyle genes in the lack of ErsA, we postulated that ErsA regulation could target the expression of Anr, a well-known transcription factor that modulates a broad regulon of anoxia-responsive genes, and also Dnr, required for the transcription activation of the denitrification machinery. Our results show that ErsA positively regulates Anr expression at the post-transcriptional level while no direct ErsA-mediated regulatory effect on Dnr was observed. However, Dnr is transcriptionally downregulated in the absence of ErsA and this is consistent with the well-characterized regulatory link between Anr and Dnr. Anr regulatory function is critical for P. aeruginosa anaerobic growth, both through denitrification and fermentation of arginine. Interestingly, we found that, differently from the laboratory strain PAO1, ErsA deletion strongly impairs the anaerobic growth by both denitrification and arginine fermentation of the RP73 clinical isolate, a multi-drug resistant P. aeruginosa CF-adapted strain. This suggests that P. aeruginosa adaptation to CF lung might result in a higher dependence on ErsA for the transduction of the multiple signals to the regulatory network of key functions for survivance in such a complex environment. Together, our results suggest that ErsA takes an upper place in the regulatory network of airways infection, transducing host inputs to biofilm-related factors, as underlined in our previous reports, and to functions that allow P. aeruginosa to thrive in low-oxygen conditions.

The DNA repair protein ATM as a target in autism spectrum disorder.

Impairment of the GABAergic system has been reported in epilepsy, autism, attention deficit hyperactivity disorder, and schizophrenia. We recently demonstrated that ataxia telangiectasia mutated (ATM) directly shapes the development of the GABAergic system. Here, we show for the first time to our knowledge how the abnormal expression of ATM affects the pathological condition of autism. We exploited 2 different animal models of autism, the methyl CpG binding protein 2-null (Mecp2y/-) mouse model of Rett syndrome and mice prenatally exposed to valproic acid, and found increased ATM levels. Accordingly, treatment with the specific ATM kinase inhibitor KU55933 (KU) normalized molecular, functional, and behavioral defects in these mouse models, such as (a) delayed GABAergic development, (b) hippocampal hyperexcitability, (c) low cognitive performances, and (d) social impairments. Mechanistically, we demonstrate that KU administration to WT hippocampal neurons leads to (a) higher early growth response 4 activity on Kcc2b promoter, (b) increased expression of Mecp2, and (c) potentiated GABA transmission. These results provide evidence and molecular substrates for the pharmacological development of ATM inhibition in autism spectrum disorders.