Publications

BACKGROUND: Staphylococcus aureus is a microorganism associated with nosocomial infections, characterized by its high pathogenicity and antibiotic resistance, posing a critical risk in hospital environments. This study aimed to determine its presence, antibiotic susceptibility, and the detection of virulence, adhesion, and regulatory genes on hospital surfaces using phenotypic and molecular methods.

MATERIALS AND METHODS: A total of 200 surface samples were collected from a secondary-level hospital, including clinical wards, ICU, and emergency areas. S. aureus was isolated using phenotypic techniques (mannitol, coagulase, DNase) and genotypic methods (detection of nucA and femB). Antimicrobial susceptibility was evaluated using the Kirby-Bauer method. Polymerase Chain Reaction (PCR) was employed to identify resistance and virulence genes.

RESULTS: S. aureus was detected in 7.5% of the samples analyzed, with higher prevalence in Clinic I and Emergency areas. The most contaminated surfaces included door handles, tables, and keyboards, identified as critical transmission points. Among the isolated strains, 66.6% were resistant to penicillin, while 100% were sensitive to methicillin and vancomycin. Virulence genes (tst, sea) were present in 26.6% and 13.3% of the strains, respectively. Regarding regulatory genes, agrI (73.3%) was the most common, followed by agrIII. For adhesion factors, icaD and icaC were the most frequently detected genes.

CONCLUSION: These findings highlight the pathogenic potential of S. aureus and its ability to persist on inert surfaces, representing a significant risk for infection transmission.

PURPOSE: Corneal confocal microscopy (CCM) is a powerful tool for detecting early signs of neurodegenerative diseases by analyzing the corneal nerve fiber morphology. Current automated analysis tools, such as ACCMetrics, are outdated and lack extensibility. Most deep learning-based models are limited to single tasks and are rarely open source. This paper proposes SuperCCM, a fully automated, modular, open source Python package, for the comprehensive analysis of CCM images.

METHODS: SuperCCM integrates a complete analysis pipeline comprising image segmentation, skeletonization, topological modeling, and quantitative parameter extraction. The system provides five default modules and supports the easy integration of custom algorithms. A finely annotated dataset (SuperCCM-FineSet, 210 images from 34 participants) was developed to train and evaluate the segmentation models using multistage training with coarsely labeled data from the CORN-1 dataset. Model performance was assessed using clDice, and the morphological parameters were compared with manual annotations.

RESULTS: SuperCCM achieved high segmentation accuracy on an independent test set, with the best encoder-decoder combination (VGG-11 + U-Net) reaching a clDice score of 0.879. For morphological quantification, SuperCCM demonstrated strong consistency with manual annotations, yielding higher intraclass correlation coefficients and lower errors across most parameters compared with ACCMetrics.

CONCLUSIONS: SuperCCM offers an extensible, open source, clinically relevant framework for CCM image analysis. Bridging algorithm development and clinical research enable the accurate and automated quantification of corneal nerve parameters and support the integration of novel deep learning models.

TRANSLATIONAL RELEVANCE: SuperCCM promotes reproducible research and supports the development of new diagnostic tools and deep learning models for corneal confocal microscopy imaging.

PURPOSE: RPE65 is a key enzyme in the visual cycle, converting all-trans retinyl esters into 11-cis retinol, a crucial step in regenerating the photopigment necessary for vision. Mutations cause a spectrum of inherited retinal diseases (IRDs), from severe generalized early-onset dystrophies, such as Leber congenital amaurosis, to classical retinitis pigmentosa or mild phenotypes, including congenital stationary night blindness, such as fundus albipunctatus.

METHODS: We analyzed two independent patients with mild RPE65-associated IRDs using multimodal diagnostics, including best-corrected visual acuity; Goldman visual field; dark-adapted testing, including scotopic perimetry; full-field electroretinography; and multimodal retinal imaging. Phenotypes were evaluated based on existing literature and predicted variant impact.

RESULTS: Both patients exhibited overall mild IRDs with only slightly impaired rod function and largely preserved cone function. Identified RPE65 missense variants likely allow partial enzyme function, consistent with comparatively mild and slowly progressive disease. Superior rod scotomas and mid-peripheral morphologic changes were identified despite normal or near-normal full-field function.

CONCLUSIONS: Functional rod changes in the inferior mid-periphery of the retina, which may be followed by metabolic stress and structural retinal changes, seem to be the hallmark of mild RPE65-associated IRDs and may represent early site-specific pathology. These changes may be linked to an increased susceptibility to UV-induced retinal damage associated with RPE65 mutations. Local rod function assessment is critical for proper disease monitoring and guiding therapeutic decisions.

TRANSLATIONAL RELEVANCE: Localized multimodal diagnostics help detect early changes in mild RPE65-associated IRDs, supporting precise monitoring and gene therapy counseling.

PURPOSE: Infantile strabismus syndrome is a common disorder characterized by a chronic misalignment of the eyes that is present in infancy. The disorder is associated with a wide range of abnormalities including severe impairments of binocular vision, impaired depth perception, impaired motion perception, amblyopia, nystagmus, a loss of disparity vergence, asymmetrical smooth pursuit gain, and saccade disconjugacy. The chronic inability to direct both eyes to the same visual target forces the brain to decide which eye to bring to any given object of interest in the visual field. We wondered if different populations of saccade-related neurons in superior colliculus might be activated, depending on which eye is to be brought to the target. We hypothesized, therefore, that the height of the movement field peak might differ for right-eye-to-target versus left-eye-to-target saccades.

METHODS: This study used single-unit, extracellular recording to investigate the bursts of saccade-related neurons in the superior colliculus in a nonhuman primate model of this disorder. Movement fields were plotted separately for saccades that brought the left eye or right eye to the target. Several statistical methods were used to compare the height of the peak between conditions.

RESULTS: A majority of the isolated neurons showed significantly stronger bursts when a particular eye was directed to a visual target, compared to when the fellow eye was brought to the target.

CONCLUSIONS: These results imply that, in monkeys with strabismus, different (but overlapping) populations of burst neurons are active depending on which eye is directed to a visual target.

PURPOSE: Glaucoma is characterized by progressive retinal ganglion cell (RGC) death and optic nerve degeneration. Chemokines are a family of small, secreted proteins that mediate cell-cell communication, an essential process for maintaining microenvironmental homeostasis and regulating pathophysiological changes in multicellular organisms. However, the contribution of retina-derived chemokines to RGC loss in glaucoma remains poorly understood.

METHODS: We reanalyzed a publicly available retinal bulk RNA sequencing dataset from a mouse model of glaucoma to identify differentially expressed chemokines. A mouse model of microbead-induced glaucoma and primary RGCs and astrocytes were used to assess the role of the C-X-C motif chemokine ligand 10 (CXCL10)/C-X-C motif chemokine receptor 3 (CXCR3) axis in disease.

RESULTS: Several chemokines were significantly upregulated during disease progression, including CXCL10, previously implicated in neurodegeneration. In the microbead model, CXCL10 expression increased markedly by day 5 post-injection. At 6 weeks, deletion of CXCR3, the receptor for CXCL10, significantly prevented RGC loss and axonal degeneration without affecting intraocular pressure (IOP). Visual function, assessed by pattern electroretinography and visual acuity, was preserved in CXCR3-deficient mice. Mechanistically, CXCL10/CXCR3 signaling upregulated complement component 3 (C3) in astrocytes and C3a receptor (C3aR) in RGCs, driving toxic astrocyte-RGC crosstalk. Gene therapy using intravitreal injection of adeno-associated virus-mediated dominant-negative CXCL10 or pharmacological blockade of C3aR effectively reduced RGC loss.

CONCLUSIONS: CXCL10/CXCR3 signaling is a key mediator of RGC loss in glaucoma. Targeting this pathway, along with its upregulated C3/C3aR axis, represents a promising IOP-independent therapeutic strategy for glaucoma.

When a manual reaching target is selected from a number of alternatives, decision uncertainty can often result in curvature of movement trajectories toward a nonchosen alternative. This curvature in the two-dimensional object plane is typically attributed to competitive interactions between different movement goals. Several models of action selection assume an explicit link between the momentary position of the hand and the state of the underlying decision process. Under this assumption, tracking the position of the hand can be used to infer the temporal evolution of the decision. However, even without a selection requirement, movements show variable amounts of curvature due to motor noise. We assessed the relative contributions of decision uncertainty and motor noise to the variability in curvature in naturalistic reach-to-grasp actions. Participants had to pick up one of two blocks (the brighter/dimmer block) and we manipulated decision uncertainty by varying the luminance difference between the two blocks. Single target baseline reaches were included to model the variability in curvature without a choice requirement. We assessed to what extent this baseline model can account for the curvature distributions observed under choice conditions, and tested several modifications of the model to capture any effects of decision uncertainty. The best model of the curvature distributions under choice conditions involved a mixture of the baseline component along with a separate choice component. The weight of this choice component and analysis of the likelihood of observed reaches under the choice/baseline components, suggest that the majority of reaches were unaffected by decision uncertainty and were compatible with the natural variability in movement trajectories due to motor noise. Unless the variability induced by factors unrelated to the decision process is adequately accounted for, the role of decision uncertainty may be overstated when it is inferred from reach trajectories.

OBJECTIVE: This narrative review aimed to investigate the potential differences in antenatal care provision, perinatal outcomes, and administration of obstetric neuraxial analgesia between migrant women and their native counterparts in high-income countries.

METHODS: Between March and July 2024, we searched four electronic databases through Ovid and PubMed: Medline, Embase, Global Health, and Maternity and Infant Care. The search terms used included "migrant", "refugee", "asylum seeker", "perinatal", "antenatal", "pregnancy", "neonate", "obstetric anaesthesia", "neuraxial analgesia", and "outcome". We included peer-reviewed articles published in English that presented data on the provision of antenatal and perinatal care, as well as the administration of obstetric neuraxial analgesia to refugee mothers who migrated to high-income countries.

RESULTS: Among the 795 screened records, 41 studies met the inclusion criteria. Of these, ten focused on obstetric neuraxial analgesia administration, while the remaining studies highlighted the differences in antenatal care and perinatal outcomes.

CONCLUSION: Access to antenatal care, utilisation of neuraxial analgesia, and perinatal and neonatal outcomes for migrant women differ from those of their native counterparts, reflecting the significant challenges encountered during the perinatal period.

After removing a virtual reality headset, people can be surprised to find that they are facing a different direction than expected. Here, we investigated if people can maintain spatial representations of one environment while immersed in another. In the first three experiments, stationary participants were asked to point to previously seen targets in one environment, either the real world or a virtual environment, while in the other environment. We varied the amount of misalignment between the two environments (detectable or undetectable), the virtual environment itself (lab or kitchen), and the instructions (general or egocentric priming). Pointing endpoints were based primarily on the locations of objects in the currently seen environment, suggesting a strong reliance on allocentric cues. In the fourth experiment, participants moved in virtual reality while keeping track of an unseen real-world target. We confirmed that the pointing errors were due to a reliance on the currently seen environment. It appears that people hardly ever keep track of object positions in a previously seen environment and instead primarily rely on currently available spatial information to plan their actions.

PURPOSE: The purpose of this study was to assess the inter-reader and inter-visit reliability of en face Bruch's membrane (BrM) calcification measurements in Pseudoxanthoma elasticum (PXE), investigate how the patient's age influences the BrM calcification extent, and evaluate the association between BrM calcification and delayed rod-mediated dark adaptation.

METHODS: This prospective natural history study (PROPXE, ClinicalTrials.gov ID: NCT05662085) included 26 patients (14 women and 12 men; median age = 55 years, interquartile range = 43-59 years) diagnosed with PXE. Participants underwent comprehensive ophthalmic evaluations, including widefield infrared reflectance imaging (up to 83 degrees eccentricity) and dark adaptometry at retinal eccentricities of 8 degrees, 15 degrees, 30 degrees, and 46 degrees along the temporal retina. The primary outcomes were inter-visit and inter-reader reliability of the temporal inner peau d'orange boundary extent, its correlation with age, and its relationship with rod-intercept time (RIT) during dark adaptation.

RESULTS: The temporal inner peau d'orange boundary showed excellent inter-reader and inter-visit reliability (inter-reader intraclass correlation coefficient [ICC] = 0.92 and inter-visit ICC = 0.95) and varied significantly with age (+4.35 deg/decade, P = 0.001). A greater temporal inner peau d'orange boundary extent was strongly associated with delayed rod-mediated dark adaptation at 8 degrees (+1.05 min/deg, P = 0.002) and 15 degrees (+0.91 min/deg, P = 0.001) eccentricities. A threshold effect was observed, with delayed dark adaptation at 8 degrees and 15 degrees eccentricity (from the fovea; i.e. 23 degrees and 30 degrees from the optic nerve head) manifesting once the temporal inner boundary exceeded 27.15 degrees and 32.56 degrees eccentricity (from the optic nerve head), respectively.

CONCLUSIONS: Patients with PXE demonstrate significant rod-mediated dark adaptation deficits correlating with the temporal inner peau d'orange boundary extent. These findings support the use of BrM calcification extent as an objective marker for disease severity, facilitating earlier therapeutic intervention than currently possible in PXE.

The accurate inference of causality between actions and their sensory outcomes requires determining their temporal relationship correctly despite variable delays within and across sensory modalities. Temporal recalibration-the perceptual realignment of actions with delayed sensory feedback-has been demonstrated across various sensorimotor domains. Here, we investigate whether this mechanism extends to saccadic eye movements and sensory events contingent on them. In three experiments, participants made horizontal saccades that triggered high-contrast flashes at varying delays. They then reported whether the flashes occurred during or after the saccade, allowing us to track perceived event timing. Exposure to consistent delays between saccade onset and the flash led to a shift in perceptual reports: flashes presented after saccade offset were more often judged as occurring during the movement. This recalibration effect was robust even when we manipulated relevant visual cues such as the presence of a structured background or the continuity of the saccade target. In a replay condition, we found a significant but much smaller recalibration effect between replayed saccades and flash, demonstrating the importance of action execution for visuomotor temporal recalibration. These findings highlight the visual system's remarkable adaptability to temporal delays between eye movements and their sensory consequences. A similar recalibration mechanism may support perceptual stability in natural vision by dynamically realigning saccades with their resulting visual input, even amid changing visual conditions.