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PloS One 2024The aim of the present work is to explore the impact of the COVID-19 pandemic on research activities in a vast multidisciplinary academic community to identify the most...
PURPOSE
The aim of the present work is to explore the impact of the COVID-19 pandemic on research activities in a vast multidisciplinary academic community to identify the most critical issues.
METHOD
To this purpose we planned a survey addressed to the entire academic research staff at "Sapienza" University of Rome, which represents the largest Italian academic community. A questionnaire consisting of both open and closed-ended questions was delivered to 4118 individuals in April 2021.
RESULTS
A total of 544 responses were collected. All academic roles were sufficiently represented in the study cohort. The median number of critical issues experienced by academic research staff was three. Among these, the three most frequently reported were related to: "Access to libraries / laboratories / research sites" (21.9%), "Limitation to stay abroad / study / research periods" (17.6%), "Progress of experimental work" (14.7%), with variable prevalence according to academic position and gender. Older subjects reported issues with "Projects' financial reporting" and "Expiration of acquired consumable material more frequently". The most common critical aspects reported in relation to the economic burden were: being "Unable to allocate funds" (31.4%), a "Reduction in clinical and scientific activity" (26.3%) and experiencing "Increased expenses (comprising private costs)" (21.2%) with no differences between genders. Researchers in Applied Sciences and Natural Sciences reported a higher frequency of problems in clinical and scientific activities, whereas increased expenses were reported also by researchers operating in the Humanities field. As a possible solution aimed at improving these issues, most subjects, especially those aged >45 years, indicated "Economic aid" (22.6%), "Reduction in bureaucracy" (19.9%) or "Enhancement of the scientific and clinical activities", whereas those aged ≤45 years felt that an increased duration and better access to PhD programs were to be prioritized.
CONCLUSION
Our findings highlight the most critical issues related to research activities during the COVID-19 pandemic in a large academic community. The information achieved may be useful to identify researchers' needs and to design appropriate policies aimed at preparing research institutions for unexpected catastrophic events and limiting the negative impact on academic research activities.
Topics: Humans; COVID-19; Male; Female; Surveys and Questionnaires; Middle Aged; Adult; Italy; Pandemics; SARS-CoV-2; Universities; Aged; Biomedical Research; Research Personnel
PubMed: 38917126
DOI: 10.1371/journal.pone.0304078 -
Biological Research Jun 2024Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness....
BACKGROUND
Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice.
METHODS
In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining.
RESULTS
Our results indicate that 3-4% H does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression.
CONCLUSIONS
Collectively, our results indicate that H could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.
Topics: Animals; Hydrogen; Oxygen; Retinal Neovascularization; Neuroglia; Mice; Disease Models, Animal; Retinopathy of Prematurity; Mice, Inbred C57BL; Retina; Animals, Newborn; Regeneration; Immunohistochemistry; Retinal Vessels
PubMed: 38915069
DOI: 10.1186/s40659-024-00515-z -
Journal of Neuroinflammation Jun 2024Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive...
Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology.
Topics: Animals; Rats; Retina; Disease Models, Animal; Retinal Diseases; Inflammation; Radiation Injuries, Experimental; Radiation Injuries; Male; Microglia
PubMed: 38915029
DOI: 10.1186/s12974-024-03151-2 -
BMC Geriatrics Jun 2024Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults...
BACKGROUND
Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.
METHODS
We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.
RESULTS
LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.
CONCLUSIONS
The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.
Topics: Humans; Male; Aged; Female; Blinking; Reflex, Pupillary; Depression; Aged, 80 and over; Middle Aged; Adult; Pupil; Darkness; Young Adult; Light
PubMed: 38914987
DOI: 10.1186/s12877-024-05034-w -
BMC Ophthalmology Jun 2024This study aimed to explore differences in vitreous humour metabolites and metabolic pathways between patients with and without diabetic retinopathy (DR) and identify...
BACKGROUND
This study aimed to explore differences in vitreous humour metabolites and metabolic pathways between patients with and without diabetic retinopathy (DR) and identify potential metabolite biomarkers.
METHODS
Clinical data and vitreous fluid samples were collected from 125 patients (40 without diabetes, 85 with DR). The metabolite profiles of the vitreous fluid samples were analysed using ultra-high performance liquid chromatography, Q-Exactive mass spectrometry, and multivariate statistical analysis. A machine learning model based on Least Absolute Shrinkage and Selection Operator Regularized logistic regression was used to build a risk scoring model based on selected metabolite levels. Candidate metabolites were regressed to glycated haemoglobin levels by a logistic regression model.
RESULTS
Twenty differential metabolites were identified between the DR and control groups and were significantly enriched in five Kyoto Encyclopedia of Genes and Genomes pathways (arginine biosynthesis; tricarboxylic acid cycle; alanine, aspartate, and glutamate metabolism; tyrosine metabolism; and D-glutamate metabolism). Ferrous ascorbate significantly contributes to poorer glycaemic control outcomes, offering insights into potential new pathogenic pathways in DR.
CONCLUSIONS
Disorders in the metabolic pathways of arginine biosynthesis, tricarboxylic acid cycle, alanine, aspartate, glutamate metabolism, tyrosine metabolism, and D-glutamate metabolism were associated with DR. Risk scores based on vitreous fluid metabolites can be used for the diagnosis and management of DR. Ferrous ascorbate can provide insights into potential new pathogenic pathways for DR.
Topics: Humans; Diabetic Retinopathy; Vitreous Body; Biomarkers; Male; Metabolomics; Female; Middle Aged; Ascorbic Acid; Aged; Chromatography, High Pressure Liquid
PubMed: 38914965
DOI: 10.1186/s12886-024-03530-6 -
Scientific Reports Jun 2024Hydrogen peroxide is considered deleterious molecule that cause cellular damage integrity and function. Its key redox signaling molecule in oxidative stress and exerts...
Hydrogen peroxide is considered deleterious molecule that cause cellular damage integrity and function. Its key redox signaling molecule in oxidative stress and exerts toxicity on a wide range of organisms. Thus, to understand whether oxidative stress alters visual development, zebrafish embryos were exposed to HO at concentration of 0.02 to 62.5 mM for 7 days. Eye to body length ratio (EBR) and apoptosis in retina at 48 hpf, and optomotor response (OMR) at 7 dpf were all measured. To investigate whether hydrogen peroxide-induced effects were mediated by oxidative stress, embryos were co-incubated with the antioxidant, glutathione (GSH) at 50 μM. Results revealed that concentrations of HO at or above 0.1 mM induced developmental toxicity, leading to increased mortality and hatching delay. Furthermore, exposure to 0.1 mM HO decreased EBR at 48 hpf and impaired OMR visual behavior at 7 dpf. Additionally, exposure increased the area of apoptotic cells in the retina at 48 hpf. The addition of GSH reversed the effects of HO, suggesting the involvement of oxidative stress. HO decreased the expression of eye development-related genes, pax6α and pax6β. The expression of apoptosis-related genes, tp53, casp3 and bax, significantly increased, while bcl2α expression decreased. Antioxidant-related genes sod1, cat and gpx1a showed decreased expression. Expression levels of estrogen receptors (ERs) (esr1, esr2α, and esr2β) and ovarian and brain aromatase genes (cyp19a1a and cyp19a1b, respectively) were also significantly reduced. Interestingly, co-incubation of GSH effectivity reversed the impact of HO on most parameters. Overall, these results demonstrate that HO induces adverse effects on visual development via oxidative stress, which leads to alter apoptosis, diminished antioxidant defenses and reduced estrogen production.
Topics: Animals; Oxidative Stress; Apoptosis; Zebrafish; Hydrogen Peroxide; Antioxidants; Zebrafish Proteins; Glutathione; Retina; Estrogens; Gene Expression Regulation, Developmental; Embryo, Nonmammalian; Vision, Ocular
PubMed: 38914633
DOI: 10.1038/s41598-024-64933-5 -
Translational Vision Science &... Jun 2024To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
PURPOSE
To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
METHODS
This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis.
RESULTS
In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group.
CONCLUSIONS
AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors.
TRANSLATIONAL RELEVANCE
Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data.
Topics: Humans; Aqueous Humor; Female; Proteomics; Male; Aged; Metabolomics; Eye Proteins; Middle Aged; Cataract; Diabetic Retinopathy; Macular Edema; Wet Macular Degeneration; Aged, 80 and over
PubMed: 38913008
DOI: 10.1167/tvst.13.6.17 -
Translational Vision Science &... Jun 2024To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in...
PURPOSE
To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in participants with normal vision.
METHODS
Participants (n = 19; five male and 14 female) were imaged at two time points (average interval of 3.2 years) using an adaptive optics scanning light ophthalmoscope (AOSLO). Foveally centered regions of interest (ROIs) were extracted from AOSLO montages. Cone coordinate matrices were semiautomatically derived for each ROI, and cone mosaic metrics were calculated.
RESULTS
On average, there were no significant changes in cone mosaic metrics between visits. The average ± SD PCD was 187,000 ± 20,000 cones/mm2 and 189,000 ± 21,700 cones/mm2 for visits 1 and 2, respectively (P = 0.52). The average ± SD density at the CDC was 183,000 ± 19,000 cones/mm2 and 184,000 ± 20,800 cones/mm2 for visits 1 and 2, respectively (P = 0.78). The average ± SD 80th percentile isodensity contour area was 15,400 ± 1800 µm2 and 15,600 ± 1910 µm2 for visits 1 and 2, respectively (P = 0.57).
CONCLUSIONS
Foveal cone mosaic density metrics were highly reproducible in the cohort examined here, although further study is required in more diverse populations.
TRANSLATIONAL RELEVANCE
Determination of the normative longitudinal changes in foveal cone topography is key for evaluating longitudinal measures of foveal cone topography in patients with progressive retinal dystrophies.
Topics: Humans; Retinal Cone Photoreceptor Cells; Male; Fovea Centralis; Female; Adult; Reproducibility of Results; Middle Aged; Cell Count; Young Adult; Ophthalmoscopy; Tomography, Optical Coherence; Visual Acuity
PubMed: 38913007
DOI: 10.1167/tvst.13.6.18 -
Journal of Biomedical Optics Jul 2024Retinopathy of prematurity (ROP) poses a significant global threat to childhood vision, necessitating effective screening strategies. This study addresses the impact of...
SIGNIFICANCE
Retinopathy of prematurity (ROP) poses a significant global threat to childhood vision, necessitating effective screening strategies. This study addresses the impact of color channels in fundus imaging on ROP diagnosis, emphasizing the efficacy and safety of utilizing longer wavelengths, such as red or green for enhanced depth information and improved diagnostic capabilities.
AIM
This study aims to assess the spectral effectiveness in color fundus photography for the deep learning classification of ROP.
APPROACH
A convolutional neural network end-to-end classifier was utilized for deep learning classification of normal, stage 1, stage 2, and stage 3 ROP fundus images. The classification performances with individual-color-channel inputs, i.e., red, green, and blue, and multi-color-channel fusion architectures, including early-fusion, intermediate-fusion, and late-fusion, were quantitatively compared.
RESULTS
For individual-color-channel inputs, similar performance was observed for green channel (88.00% accuracy, 76.00% sensitivity, and 92.00% specificity) and red channel (87.25% accuracy, 74.50% sensitivity, and 91.50% specificity), which is substantially outperforming the blue channel (78.25% accuracy, 56.50% sensitivity, and 85.50% specificity). For multi-color-channel fusion options, the early-fusion and intermediate-fusion architecture showed almost the same performance when compared to the green/red channel input, and they outperformed the late-fusion architecture.
CONCLUSIONS
This study reveals that the classification of ROP stages can be effectively achieved using either the green or red image alone. This finding enables the exclusion of blue images, acknowledged for their increased susceptibility to light toxicity.
Topics: Retinopathy of Prematurity; Humans; Deep Learning; Infant, Newborn; Photography; Fundus Oculi; Image Interpretation, Computer-Assisted; Neural Networks, Computer; Color
PubMed: 38912212
DOI: 10.1117/1.JBO.29.7.076001 -
Drug Design, Development and Therapy 2024Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major... (Review)
Review
Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.
Topics: Melatonin; Humans; Diabetic Retinopathy; Macular Degeneration; Animals; Fundus Oculi; Antioxidants
PubMed: 38911030
DOI: 10.2147/DDDT.S471525