The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Purpose of research was to determine changes in optical quality for monthly disposable soft contact lenses (SCL) wearers with new and monthly worn SCL. Retinal straylight was assessed in SCL wearers using a C-Quant straylight meter. The study included 33 participants (age 22 ± 1.4 years) who wore monthly disposable silicone hydrogel contact lenses. Measurements were taken with month-old SCL that had been worn for no more than 4 hours. Participants then replaced the old lenses with new ones. After a 15-minute adaptation period, straylight measurements were taken with the new SCL. A questionnaire was administered to all participants, inquiring about vision complaints and the type of contact lens material used. The decimal logarithm of the stray-light parameter, log(s), was notably higher with month-old SCL (log(s) = 0.97±0.17) than with brand-new SCL (log(s) = 0.86±0.15), p < 0.001. The average increase in retinal straylight after a month of SCL use was log(s) = 0.11 ± 0.08. The questionnaire revealed that 35% of participants observed a reduction in visual quality after wearing the contact lenses for a month. Results showed that monthly disposable soft contact lenses could reduce visual quality when scheduled replacement time has been reached.

Voltage-gated Ca²⁺ (Ca_v) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Ca_v channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Ca_v channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

The Avian retina is far less known than that of mammals such as mouse and macaque, and detailed study is overdue. The chicken (Gallus gallus) has potential as a model, in part because research can build on developmental studies of the eye and nervous system. One can expect differences between bird and mammal retinas simply because whereas most mammals have three types of visual photoreceptor birds normally have six. Spectral pathways and colour vision are of particular interest, because filtering by oil droplets narrows cone spectral sensitivities and birds are probably tetrachromatic. The number of receptor inputs is reflected in the retinal circuitry. The chicken probably has four types of horizontal cell, there are at least 11 types of bipolar cell, often with bi- or tri-stratified axon terminals, and there is a high density of ganglion cells, which make complex connections in the inner plexiform layer. In addition, there is likely to be retinal specialisation, for example chicken photoreceptors and ganglion cells have separate peaks of cell density in the central and dorsal retina, which probably serve different types of behaviour.

Vertebrate color vision is evolutionarily ancient. Jawless fish evolved four main spectral types of cone photoreceptor, almost certainly complemented by retinal circuits to process chromatic opponent signals. Subsequent evolution of photoreceptors and visual pigments are now documented for many vertebrate lineages and species, giving insight into evolutionary variation and ecological adaptation of color vision. We look at organization of the photoreceptor mosaic and the functions different types of cone in teleost fish, primates, and birds and reptiles. By comparison less is known about the underlying neural processing. Here we outline the diversity of vertebrate color vision and summarize our understanding of how spectral information picked up by animal photoreceptor arrays is adapted to natural signals. We then turn to the question of how spectral information is processed in the retina. Here, the quite well known and comparatively ‘simple’ system of mammals such as mice and primates reveals some evolutionarily conserved features such as the mammalian Blue^ON system which compares short and long wavelength receptors signals. We then survey our current understanding of the more complex circuits of fish, amphibians, birds and reptiles. Together, these clades make up more than 90% of vertebrate species, yet we know disturbingly little about their neural circuits for colour vision beyond the photoreceptors. Here, long-standing work on goldfish, freshwater turtles and other species is being complemented by new insights gained from the experimentally amendable retina of zebrafish. From this body of work, one thing is clear: The retinal basis of colour vision in non-mammalian vertebrates is substantially richer compared to mammals: Diverse and complex spectral tunings are established at the level of the cone output via horizontal cell feedforward circuits. From here, zebrafish use cone-selective wiring in bipolar cells to set-up color opponent synaptic layers in the inner retina, which in turn lead a large diversity of color-opponent channels for transmission to the brain. However, while we are starting to build an understanding of the richness of spectral properties in some of these species’ retinal neurons, little is known about inner retinal connectivity and cell-type identify. To gain an understanding of their actual circuits, and thus to build a more generalised understanding of the vertebrate retinal basis of color vision, it will be paramount to expand ongoing efforts in deciphering the retinal circuits of non-mammalian models.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Inherited retinal diseases (IRDs) are extremely heterogeneous with at least 350 causative genes, complicating the process of genetic diagnosis. We analyzed samples of 252 index cases with IRDs using the Blueprint Genetics panel for “Retinal Dystrophy” that includes 351 genes. The cause of disease could be identified in 55% of cases. A clear difference was obtained between newly-recruited cases (74% solved) and cases that were previously analyzed by panels or whole exome sequencing (26% solved). As for the mode of inheritance, 75% of solved cases were autosomal recessive (AR), 10% were X-linked, 8% were autosomal dominant, and 7% were mitochondrial. Interestingly, in 12% of solved cases, structural variants (SVs) were identified as the cause of disease. The most commonly identified genes were ABCA4, EYS and USH2A, and the most common mutations were MAK-c.1297_1298ins353 and FAM161A- c.1355_1356del. In line with our previous IRD carrier analysis, we identified heterozygous AR mutations that are not the cause of disease in 36% of cases. The studied IRD panel was found to be efficient in gene identification. Some variants were mis-interpreted by the pipeline and therefore multiple analysis tools are recommended to obtain more accurate annotation of potential disease-causing variant.

This systematic examines research into patients diagnosed with retinal vascular occlusive diseases (RVODs) secondary to coronavirus disease 2019 (COVID-19) infection or vaccination. RVODs include central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, and branch retinal artery occlusion. Previous studies have posited a possible link between RVODs and COVID-19. RVODs are of two types: retinal vein occlusion and retinal artery occlusion. These disorders develop when retinal blood vessels become clogged by thrombi or fat deposition. The retina is an important component of the visual apparatus. Its photoreceptors are stimulated by the light hitting the eye and record its pattern. The retina then relays this visual information to the brain. When retinal blood vessels become clogged, the damage can range from slightly reduced vision to complete blindness. COVID-19 causes endothelial dysfunction and increased levels of von Willebrand factor antigens in the blood. Elevation of von Willebrand factor activates the coagulation process and platelet aggregation. The treatment methods and visual prognosis in COVID-19-related RVODs do not differ from conventional RVODs. However, ophthalmologists need to be aware of the possible relationship and should consider RVODs when they encounter patients with vision loss following COVID-19 infection or vaccination.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related or modulated by the oxidative burden of the retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment and in some instances also mediated by autophagy. The fate of these vesicles is diverse, and could end up in the circulation and be used as markers, or target neighbour cells modulating gene and protein expression and eventually also angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles’ cargo or free circulating, on the regulation of retinal angiogenesis is also discussed.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intra-tissue, inter-cellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

A better study of the postnatal retinal development is not only essential for the in-depth understanding of the nature of the vision system but also may provide insights for treatment developments of eye conditions, such as retinopathy of premature (ROP). To date, quantitative analysis of postnatal retinal development is primarily limited to endpoint histological examination. This study is to validate in vivo optical coherence tomography (OCT) for longitudinal monitoring of postnatal retinal development in developing mouse eyes. Three-dimensional (3D) frame registration and super averaging were adopted to investigate the fine structure of the retina. Interestingly, a hyporeflective layer (HRL) between the nerve fiber layer (NFL) and inner plexiform layer (IPL) was observed in developing eyes and gradually disappeared with aging. To interpret the observed retinal layer kinetics, a model based on eyeball expansion, cell apoptosis, and retinal structural modification was proposed.

In this study, we explore the impact of quantum effects on synaptic activity and their implications for the deterministic model of neural processes. By simulating synaptic events in a large-scale neural network, we demonstrate how small probabilistic quantum events can accumulate and introduce variability in neural behavior. Our model incorporates Dirac delta functions to simulate sudden changes in synaptic probabilities, creating a non-linear, seesaw effect in the cumulative synaptic activity curve. The results reveal that even minimal quantum effects, when scaled to the vast number of synapses in the human brain, can lead to significant dissociations in neural activity. These findings challenge the traditional deterministic view, suggesting that neural processes—and by extension, decision-making and movements—may inherently incorporate elements of randomness. This probabilistic perspective aligns with theories of free will and underscores the need for further empirical research to validate the role of quantum mechanics in neuroscience. Our study provides a theoretical framework for understanding the complex interplay between quantum effects and neural dynamics, opening new avenues for exploring the nature of consciousness and the fundamental principles governing reality.

Brain disorders pose a significant global healthcare challenge due to their complexity and profound impact on individuals and society. This review explores recent advancements in brain disease research, deepening our understanding and progress towards treatments. Technological innovations, like high-resolution imaging and optogenetics, play a pivotal role in illuminating cellular structures and dissecting neural circuits. Genetic analysis identifies dis-ease-associated genes and mutations, yet translating findings to clinical applications remains challenging. Epigenomics, transcriptomics, and proteomics provide molecular insights, un-covering disrupted pathways in conditions like Alzheimer's disease. Stem cell models elucidate developmental mechanisms, and immunotherapies, including CAR T cells, emerge as prom-ising strategies for brain cancers like glioblastoma. Genome editing tools, exemplified by CRISPR, enable precise modification of disease genes in models, deepening our understanding of pathogenesis. Multifaceted approaches integrating human studies, animal models, and bi-oinformatics propel the field forward. However, complexities persist, as disease specificity for cell types or brain regions remains an enigma, and genetic factors interact with environmental influences, highlighting disease intricacies. Ultimately, interdisciplinary efforts combining bi-ophysical and psychospiritual perspectives are essential to fully understand brain health and unlock transformative treatments for these debilitating disorders. A comprehensive under-standing of brain disorders is vital to improve the quality of life for millions and alleviate the global burden of neurological afflictions. Continued collaborative research will lead to an era of improved brain health worldwide.

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-years old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis, and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Inherited retinal diseases (IRD) comprise a heterogeneous set of clinical and genetic disorders that lead to blindness. Given the emerging opportunities in precision medicine and gene thera-py, it has become increasingly important to determine whether DNA variants with uncertain significance (VUS) are responsible for the patients’ IRD. This research was performed to assess the functional consequence of six VUS identified in patients with IRD. Clinical assessments in-cluded an ophthalmic examination, best corrected visual acuity, and kinetic perimetry. Imaging was acquired with the Optos ultra-widefield camera and spectral-domain optical coherence to-mography (SD-OCT). Genetic testing was performed by Molecular Vision Laboratories. VUS that were predicted to alter splicing were analyzed with a minigene assay which revealed that VUS in the genes OPA1, CNGB1, and CLUAP1 altered spicing mechanisms. Due to the emerging gene and cell therapies, these results expand the genotype-phenotype correlations for patients diag-nosed with an IRD.

The study of the development of the vertebrate retina can be addressed from several perspectives: from purely qualitative to a more quantitative approach that takes into account its spatiotemporal features, its three dimensional structure and also the regulation and properties at the systems level. Here we review the ongoing transition towards a full four-dimensional characterization of the developing vertebrate retina, focusing on the challenges at the experimental, image acquisition, image processing and quantification. Using the developing zebrafish retina, we illustrate how quantitative data extracted from these type of highly dense three-dimensional tissues depends strongly on the image quality, image processing and algorithms used to segment and quantify. Therefore, we propose that the scientific community that focuses on developmental systems could strongly benefit from a more detailed disclosure of the tools and pipelines used to process and analyze images from biological samples.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Examining contemporary developments and cutting-edge approaches in the field, this literature review explores how antenna design for transmission lines is changing. Review findings are compiled from a variety of academic sources, including pertinent technical reports published as recently as 2018, conference papers, journal articles, and reports. A variety of antenna topologies suited for transmission lines are evaluated in this paper, including microstrip, slot, and patch antennas, with a focus on theoretical frameworks and practical implementations. This overview clarifies the complex relationship between antenna design and transmission line characteristics by looking at important factors like impedance matching, bandwidth, and radiation pattern management. Notable developments in materials, fabrication methods, and numerical simulations are also examined and their effects on antenna performance explained. Through a comprehensive analysis of the literature, this review offers valuable insights into the state-of-the-art antenna design practices for transmission lines, facilitating informed decision-making and inspiring future research endeavors in this field.

Takayasu arteritis is an inflammatory vasculitis that mainly impacts the large vessels including the aorta and its branches. Ocular manifestations may include retinal ischemia, optic neuropathy, cataracts, and retinal artery occlusion. We present two cases where central retinal artery occlusion was found in patients with Takayasu arteritis and wish to highlight to consider Takayasu arteritis in young patients with unexplained retinal artery occlusion.

Neuroscience has overwhelmingly and understandably focused on the synaptic modality of signal transmission. There is evidence, however, that from an evolutionary perspective, non-synaptic transmission (NST) preceded synaptic signaling. Moreover, in modern nervous systems, NST coexists and extensively interacts with synaptic transmission modifying neuronal dynamics. In fact, NST remains widespread in complex animals, especially within the interoceptive system where the dearth of insulating barriers such as myelin sheaths and the blood-brain barrier enhances the communication between neural and non-neural tissues mediated by NST. We suggest that this physiological arrangement makes a fundamental contribution to interoception¾the process of sensing visceral states¾which is an essential underpinning of the capacity to feel and the foundation of affective processing.

Introduction: ophthalmological assessment of the retinal circulation and the level of VEGF-A is currently considered a non-invasive and safe diagnostic tool to assess the peripheral microcircu-lation Objective: to study retinal hemodynamics and VEGF-A levels in patients with type 1 diabetes mellitus after pancreas transplantation Settings and Design: A prospective, single-stage, single-center, non-randomized clinical trial Methods: 79 patients (158 eyes) with type 1 diabetes mellitus and end-stage diabetic nephropathy participated in the study. Patients were divided into 3 groups: group 1, potential recipients of pancreas and kidney transplant from the waiting list; group 2, patients after kidney transplanta-tion; and group 3, patients after simultaneous pancreas and kidney transplantation. Ophthalmo-logical examination included measuring the macular hemoperfusion density. The level of VEGF-A was examined in the patients' tear by enzyme immunoassay. Results: retinal hemoperfusion density and VEGF-A concentration were expected to correlate with the severity of diabetic changes in the fundus of patients. A lower index of retinal hemoperfusion density and a high level of VEGF-A were noted in patients with proliferative ret-inopathy and macular oedema. Group 3 showed the lowest frequency of the active phase of the proliferative retinopathy and retinal macular oedema, characterized by a higher retinal hemoperfusion density in the foveal and the parafoveal zone of the macular region, and low VEGF-A concentration in tear. Conclusion: measurement of retinal hemoperfusion density and determination of tear VEGF-A concentration are informative objective methods for diagnosing the severity of diabetic changes of the fundus.

Purpose: To compare the efficacy and safety of trabeculectomy with a collagen matrix implant (Ologen®) versus trabeculectomy with mitomycin C (MMC) versus trabeculectomy with both Ologen® and MMC (OLO+MMC). Methods: This non-randomized study included 119 eyes of 101 patients with uncontrolled open-angle glaucoma who underwent trabeculectomy, either alone or combined with phacoemulsification. Data were initially registered following a standard surgical protocol and using an electronic database with structured fields. Patients were divided into three groups: 44 received trabeculectomy with adjunctive MMC (MMC group), 34 with Ologen® (OLO group), and 41 with both Ologen® and MMC (OLO+MMC group). The main outcome measures were the change in intraocular pressure (IOP), change in number of medications needed, complete success rate (defined as IOP≤20 mmHg and at least 20% IOP reduction without hypotensive medications), rate of complications, and rate of postoperative interventions. The follow-up period was 36 months.
 Results: IOP significantly decreased (p=0,01) in all groups across all study visits, decreasing from 19.8 ± 4.6 mmHg to 12.7 ± 4.2 mmHg in the MMC group, from 20.5 ± 4.7 mmHg to 13.9 ± 3.5 mmHg in the OLO group, and from 23.5 ± 6.1 mmHg to 13.1 ± 3.5 mmHg in the OLO+MMC group. After correcting for baseline IOP, only the first two postoperative visits (first week and first month) showed significantly greater IOP reduction in the OLO+MMC group. The number of hypotensive medications was significantly reduced from 3.1±0.6 to 0.56±1.1 in the MMC group, from 2.9±0.4 to 0.83±1.1 in the OLO group, and from 3.0±0.6 to 0.45±0.95 in OLO + MMC group, with no statistically significant differences among the groups (p=0,57). Complete success rates were 63,6% in the MMC group, 67,6% in the OLO group, and 80,5% in the OLO +MMC group, with no statistically significant differences among the groups (p=0,21). Suture release was significantly more frequent in the MMC group (86,1%) than in the OLO group (62,1%) and in the OLO + MMC group (45,9%; p=0,02). Bleb needling, with (33.3%; p=0.005) or without (66.7%; p=0.0001) 5-Fluorouracil injection (5-FU), was significantly more common in the MMC group. The highest complete-success rate (61%) was offered by the OLO+MMC group. Conclusion: The use of Ologen® and Mitomycin C provided similar surgical IOP reduction in glaucoma surgery compared with MMC or Ologen® either alone but significantly reduced the need for postoperative interventions.

Optical coherence tomography (OCT) is a non-invasive imaging technique widely used in ophthalmology for visualizing retinal layers, aiding in early detection and monitoring of retinal diseases. OCT is useful for detecting diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME), which affect millions of people globally. Over the past decade, the area of application of Artificial Intelligence (AI), particularly Deep Learning (DL), has significantly increased. The number of medical applications is also rising, with solutions from other domains being increasingly applied to OCT. The segmentation of biomarkers is an essential problem that can enhance the quality of retinal disease diagnostics. For 3D OCT scans, AI is beneficial since manual segmentation is very labor-intensive. In this paper, we employ the new SAM 2 and MedSAM 2 for the segmentation of OCT volumes for two open-source datasets, comparing their performance with the traditional U-Net. The model achieved an overall Dice score of 0.913 and 0.902 for macular holes (MH) and intraretinal cysts (IRC) on OIMHS and 0.888 and 0.909 for intraretinal fluid (IRF) and pigment epithelial detachment (PED) on the AROI dataset, respectively.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, sensitive assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. Here we offer a conceptual framework to identify progressive stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies based on non-invasive pattern electroretinogram (PERG), to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction.

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen-alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial cell line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases (RDDs). This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium iodate (SI)-induced retinal degeneration. The findings indicated that CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.

This study explores novel techniques to improve the detection accuracy of skarn iron deposits using advanced image processing methodologies. Leveraging the capabilities of Aster image, Band Ratio (BR) images, and Principal Component Analysis (PCA), alongside the power of 3D Convolutional Neural Networks (3D-CNN), the research aims to enhance the precision and efficiency of ore detection in complex geological environments. The proposed method employs a specific 3D-CNN architecture, accepting input as a 7×7×C image patch, where C represents the combined number of selected Aster image bands, Principal Component (PC) bands, and computed BR images. To evaluate the accuracy of the proposed method, five distinct image bands combinations, including the proposed bands combination, were tested and evaluated based on the overall accuracy (OA), average accuracy (AA), and kappa coefficient. The results demonstrated that while the incorporation of BR images alongside Aster bands initially seemed promising, it introduced significant confusion in certain classifications, leading to unexpected mis-classification rates. Surprisingly, utilizing solely Aster bands as input parameters yielded higher accuracy rates (OA= 93.13%, AA = 91.96%, Kappa = 90.91%) compared to scenarios involving the integration with band ratios (OA = 87.02%, AA = 79.15, and Kappa = 82.60%) or the integration of BR images to PC bands (OA= 87.78%, AA = 82.39%, Kappa = 83.81%). However, the amalgamation of Aster bands with selected PC bands showed slight improvements in accuracy (OA= 94.65%, AA = 92.93%, Kappa = 93.45%), although challenges in accurately classifying certain features persisted. Ultimately, the proposed combination of Aster bands, PC bands, and BR images (proposed bands combination) presented the most visually appealing and statistically accurate results (OA = 96.95%, AA= 94.87%, and Kappa = 95.93%), effectively addressing misclassifications observed in the other combinations. These findings underscore the synergistic contributions of each of the Aster bands, PC bands, and BR images, with Aster bands proving pivotal for optimal skarn classification, PC bands enhancing intrusions classification accuracy, and BR images strengthening wall rock classification accuracy. In conclusion, the proposed combination of input image bands emerges as a robust and comprehensive methodology, demonstrating unparalleled accuracy in the remote sensing detection of skarn iron minerals.

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p&lt;0.001, Duncan’s new multiple range test) and their total duration (p&lt;0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p&lt;0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

Image registration has an imperative role in medical imaging. In this work, a grey-wolf optimizer (GWO) based non-rigid demons registration is proposed to support the retinal image registration process. A comparative study of the proposed GWO-based demons registration framework with cuckoo search, firefly algorithm, and particle swarm optimization- based demons registration is conducted. In addition, a comparative analysis of different demons registration methods, such as Wang’s demons, Tang’s demons, and Thirion’s demons which are optimized using the proposed GWO is carried out. The results established the superiority of the GWO-based framework which achieved 0.9977 correlation, and fast processing compared to the use of the other optimization algorithms. Moreover, GWO-based Wang’s demons performed better accuracy compared to the Tang’s demons and Thirion’s demons framework. It also achieved the best less registration error of 8.36×10^-5.

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent “age pigment” lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing simultaneously both types of pigments - melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of oxidative degradation of pigment granules are considered. A mechanism has been proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy its melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.

Visual impairment and blindness are a growing public health problem, as they reduce the quality of life of millions of people. The management and treatment of these diseases represent a scientific and therapeutic challenge, since the different cellular and molecular actors involved in the pathophysiology are still being identified. The visual system components, particularly the retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune cells activated by insults contribute to biological events that culminate with vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma and diabetic retinopathy are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cells degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiologic and molecular features, biochemical hallmarks and possible directions for novel treatments, aiming to assist as a guide for innovative research. The expansion of knowledge of the mechanistic bases of the pathobiology of eye diseases, including information on the complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors will allow the identification of new therapeutic strategies.

Adipor1^tm1Dgen and Mfrp^rd6 mutant mice share similar eye disease characteristics. Previously, studies established a functional relationship of ADIPOR1 and MFRP proteins in maintaining retinal lipidome homeostasis and visual function. However, the independent and/or interactive contribution of both the genes to similar disease phenotypes, including fundus spots, decreased axial length and photoreceptor degeneration has yet to be examined. We performed a gene-interaction study where homozygous Adipor1^tm1Dgen and Mfrp^rd6 mice were bred together and the resulting doubly heterozygous F1 offspring were intercrossed to produce 210 F2 progeny. Four-month-old mice from all nine genotypic combinations obtained in the F2 generation were assessed for white spots by fundus photo documentation, for axial length by caliper measurements, and for photoreceptor degeneration by histology. Two-way factorial ANOVA was performed to study individual as well as gene interaction effects on each phenotype. Here, we report the first observation of reduced axial length in Adipor1^tmlDgen homozygotes. We show that while Adipor1 and Mfrp interact to affect spotting and degeneration, they act independently to control axial length, highlighting the complex functional association between these two genes. Further examination of the molecular basis of this interaction may help in uncovering mechanisms by which these genes perturb ocular homeostasis.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p &lt; 0.0001; and WMH: 0.0004±0.0007; p &lt; 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p &lt; 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Background: Visual acuity (VA) assessments are crucial in ophthalmology but traditionally rely on in-clinic evaluations. The emergence of telemedicine has spurred interest in creating dependable self-administered VA tests for use beyond standard clinical environments. This study evaluates the practicality and validity of a self-administered Near VA card test against traditional Snellen and Rosenbaum Pocket Vision Screener (RPVS) methods for home monitoring and enhancing clinical workflow. Methods: In a cross-sectional study a near VA card (Hadassah Self-Visual Acuity Screener-HSVA) was developed with written and videotaped instructions for self-use. Patients with a minimal best corrected VA (BCVA) of 1.0 LogMAR in at least one eye were recruited from Ophthalmology and Optometry clinics. Outcomes included mean BCVA difference between the self-administered and those obtained by the examiner, and correlations among BCVA values obtained by Snellen, RPVS, HSVA and previous distance BCVA according to the patient electronic medical records. Results: A total of 275 participants (mean age: 42.5±19.4 years, range: 18-89 years, 47% female) were included. Test-retest reliability analysis for the HSVA demonstrated very good correlation and repeatability (n=38 patients.; Rs=1.0, P

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C&gt;T; c.748C&gt;T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C&gt;T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P&lt;0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

This review examines additive manufacturing for refractory tungsten (W) and its alloys. It emphasizes the primary challenges and determining factors involved in additive manufacturing pure W, W alloys, and composites. Our focus in this regard extends to both process and alloying strategies designed to address critical issues such as densification, micro-cracking, and mechanical properties in tungsten-based components produced through additive techniques. Throughout the review, we organize existing knowledge and insights into convenient tables, serving as valuable resources for researchers embarking on a deeper exploration of these topics.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

This paper presents a system for identification of wind features, such as gusts and wind shear. These are of particular interest in the context of energy-efficient navigation of Small Unmanned Aerial Systems (UAS). The proposed system generates real-time wind vector estimates and a novel algorithm to generate wind field predictions. Estimations are based on the integration of an off-the-shelf navigation system and airspeed readings in a so-called direct approach. Wind predictions use atmospheric models to characterize the wind field with different statistical analyses. During the prediction stage, the system is able to incorporate, in a big-data approach, wind measurements from previous flights in order to enhance the approximations. Wind estimates are classified and fitted into a Weibull probability density function. A Genetic Algorithm (GA) is utilized to determine the shaping and scale parameters of the distribution, which are employed to determine the most probable wind speed at a certain position. The system uses this information to characterize a wind shear or a discrete gust and also utilizes a Gaussian Process regression to characterize continuous gusts. The knowledge of the wind features is crucial for computing energy-efficient trajectories with low cost and payload. Therefore, the system provides a solution that does not require any additional sensors. The system architecture presents a modular decentralized approach, in which the main parts of the system are separated in modules and the exchange of information is managed by a communication handler to enhance upgradeability and maintainability. Validation is done providing preliminary results of both simulations and Software-In-The-Loop testing. Telemetry data collected from real flights, performed in the Seville Metropolitan Area in Andalusia (Spain), was used for testing. Results show that wind estimation and predictions can be calculated at 1 Hz and a wind map can be updated at 0.4 Hz. Predictions show a convergence time with a 95% confidence interval of approximately 30 s.

PURPOSE: To investigate the oxylipin profiles in aqueous humor of primary open angle glaucoma (POAG) patients. METHODS: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to the liquid chromatography-mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. RESULTS: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified 5 differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The 5 oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk ratio in the POAG patients. In addition, 15-kPGF2α was positively correlated with visual field defect, and LTB4 was negatively correlated with macular thickness.  CONCLUSIONS: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in arachidonic acid metabolism pathway could play a role in POAG and anti-inflammatory therapies could be potential treatment strategies for POAG.

The state-of-the-art smart city has been calling for an economic but efficient energy management over large-scale network, especially for the electric power system. It is a critical issue to monitor, analyze and control electric loads of all users in system. In this paper, we employ the popular computer vision techniques of AI to design a non-intrusive load monitoring method for smart electric energy management. First of all, we utilize both signal transforms (including wavelet transform and discrete Fourier transform) and Gramian Angular Field (GAF) methods to map one-dimensional current signals onto two-dimensional color feature images. Second, we propose to recognize all electric loads from color feature images using a deep neural network with multi-scale feature extraction and attention mechanism. Third, we design our method as a cloud-based, non-intrusive monitoring of all users, thereby saving energy cost during electric power system control. Experimental results on both public and our private datasets have demonstrated our method achieves superior performances than its peers, and thus supports efficient energy management over large-scale Internet of Things.

Objectives- The aim of the study is to describe and validate an optical-coherence-tomography (OCT) based method to easily calculate specific volumes, overcoming the inability of current OCT software to automate a volumetric analysis for specific entities in retinal pathologies. Methods- After manual drawing with caliper of the specific entity on linear OCT scans and consequent automated measurement of its area, the following formula was used for volumetric calculation: Volume [mm³] = ∑area [mm²] x OCT-scan distance [mm]. Two independent observers calculated the retinal volume (RV) in eyes with normal foveal profile (NFP) and compared it with the automated measurements performed by the OCT software; as well as the volume of the foveal cavity (FC) or foveoschisis (FS) in eyes with lamellar macular hole (LMH). The measurements were re-acquired after six weeks. Intra- and inter-observer variability and variability with automated RV calculations were analysed. Results- The study included 62 eyes: 30 NFP and 32 LMH eyes. High degree of agreement was determined for inter-observer and intra-observer variability between the two observers or singular observer with Spectralis for RV in NFP eyes; as well as between the two observers for FC/FS volume in LMH eyes. Conclusions- We describe and validate, showing excellent inter- and intra-observer agreement, an easy, reliable and widely applicable method to calculate volumes which can be applied to any entity requiring a specific study in the context of retinal pathologies.

Retinopathy is a human eye disease that causes changes in retinal blood vessels that leads to bleed, leak fluid and vision impairment. Symptoms of retinopathy are blurred vision, changes in color perception, red spots, and eye pain. In this paper, a new methodology based on Convolutional Neural Networks (CNN) is developed and proposed to diagnose and give a decision about the presence of retinopathy. The CNN model is trained by different images of eyes that have retinopathy and those which do not have retinopathy. The performance of the proposed model is compared with the related methods of DREAM, KNN, GD-CNN and SVM. Experimental results show that the proposed CNN performs better.

Dynamic neural networks (DNN) are types of artificial neural networks (ANN) that are designed to work with sequential data where context in time is important. In contrast to traditional static neural networks that process data in a fixed order, dynamic neural networks use information about past inputs, which is important if dynamic of a certain process is emphasized. They are widely used in natural language processing, speech recognition and time series prediction. In industrial processes, their use is interesting for the prediction of difficult-to-measure process variables. In an industrial process of isomerization, it is crucial to measure the quality attributes affecting the octane number of gasoline. Process analyzers that are commonly used for this purpose are expensive and subject to failures, therefore, in order to achieve continuous production in case of malfunction, mathematical models for estimating the product quality attributes are imposed as a solution. In this paper, mathematical models were developed using dynamic recurrent neural networks (RNN), i.e., their subtype of a long short-term memory (LSTM) architecture. The results of the developed models were compared with the results of several types of other data-driven models developed for an isomerization process, such as multilayer perceptron (MLP) artificial neural networks, support vector machines (SVM) and dynamic polynomial models. The obtained results are satisfactory, which suggests a good possibility of application.

The retinal pigment epithelium (RPE) is an important monolayer of cells present in the outer retina forming a major part of the blood-retina-barrier (BRB). It performs many essential tasks for the maintenance of retinal integrity and function. With increasing knowledge of the retina, it is getting clearer that both common retinal disorders, like age related macular degeneration, and rare genetic disorders originate in the RPE. This calls for a better understanding of the functions of various proteins within the RPE. In this regard, mice enabling an RPE-specific gene deletion are a powerful tool to study the role of a particular protein within the RPE cells in their native environment, simultaneously negating any potential influences of systemic changes. Moreover, since the RPE cells interact closely with the adjacent photoreceptors, these mice also provide an excellent avenue to study the importance of a particular gene function within the RPE to the retina as a whole. In this review, we outline and compare the features of various Cre mice created for this purpose, allowing researchers a well-informed decision on the choice of Cre mouse to use in relation to their research needs.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

The development of fetal organs can be impacted by systemic changes in the mother's circulation, and the placenta is essential for pregnancy homeostasis and feeding. In clinical obstetrics, oxytocin (OXT) is used to induce labor. To further explore the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among newborns whose mothers either received OXT prenatally or underwent natural labor. Our previous study revealed that the oxytocin receptor (OXTR), a vital component of the neural retina that forms the blood-retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that. the formation of the neural retina and vessels within it may be impacted by perinatal OXT injection, which suggests that it may be used as a therapeutic intervention for developing eye illnesses such as retinopathy of prematurity (ROP). We first studied the amounts of OXT in neonatal cord blood. To investigate this subcellular activity, we administered OXT to mature RPE cells. With the aid of network analysis, our results suggest that perinatal administration of OXT may affect the growth of the neural retina and its corresponding retinal vessels, making it a potential therapeutic intervention for developmental eye diseases such as retinopathy of prematurity (ROP).

To date, the development of unmanned technologies using autonomous underwater vehicles (AUV) has become an urgent demand for solving the problem of inspection of industrial sub-sea structures. A key issue here is precise localization of AUVs relative to underwater objects. However, the well-known challenges of recognizing and coordinating underwater objects (impossibility to use GPS, undercurrents, etc.) do not allow high-precision navigation if based solely on a standard suite of AUV navigation tools (sonars, etc.). An alternative is a technology of processing of optical images that, at short distances, can provide higher accuracy of AUV navigation compared to a technology of acoustic measurement processing. In this study, in the context of the problem of subsea production system inspection, we propose a method to recognize underwater objects and provide coordinate reference of AUV to them, based on stereo-image processing. Its distinctive features are the use of a non-standard technique for generating a geometric model of an object from its views (foreshortening) taken from positions of a pre-made overview trajectory, the use of various characteristic geometric elements when recognizing objects, and the original algorithms for comparing visual data of the inspection trajectory with an a priori model of the object.

Vertical Indoor Farming (VIF) with hydroponics offers a promising perspective for sustainable food production. Intelligent control of VIF system components plays a key role in reducing operating costs and increasing crop yields. Modern machine vision (MV) systems use Deep Learning (DL) in combination with camera systems for various tasks in agriculture, such as disease and nutrient deficiency detection, and flower and fruit identification and classification for pollination and harvesting. This study presents the applicability of MV technology with DL modelling to detect the growth stages of chilli plants using YOLOv8 networks. The influence of different bird’s eye and side view datasets and different YOLOv8 architectures was analysed. To generate the image data for training and testing the YOLO models, chilli plants were grown in a hydroponic environment and imaged throughout their life cycle using four camera systems. The growth stages were divided into growing, flowering and fruiting classes. All trained YOLOv8 models showed reliable identification of growth stages with high accuracy. The results indicate that models trained with data from both views show better generalisation. YOLO’s middle architecture achieved the best performance.

The purpose of the study was to determine the “retinal thickness deviation” (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations be-tween RTD and best-corrected visual acuity (BCVA). We conducted a retrospective study, in-cluding consecutive DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline, 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) μm at baseline, 97.0 (99.7) μm at 12 months and 89.9 (75.3) μm at 24 months of follow-up (P < .001). RTD showed a moderate association with BCVA at baseline (R2=0.134, p<0.001) and 12 months (R2=0.197, p<0.001), and a substantial association at 24 months (R2=0.272, p<0.001). The CST showed a moderate association with BCVA at baseline (R2=0.132, p<0.001) and 12 months (R2=0.136, p<0.001), while the association was weak at 24 months (R2=0.065, p=0.009). In conclusion, RTD showed a good association with visual outcome in DME eyes undergoing intravitreal treatment.

Convolutional neural network architectures have become increasingly complex, which has improved the performance slowly on well-known benchmark datasets in the recent years. In this research, we have analyzed the true need for such complexity. We have introduced G-Net light, a lightweight modified GoogleNet with improved filter count per layer to reduce feature overlaps and complexity. Additionally, by limiting the amount of pooling layers in the proposed architecture, we have exploited the skip connections to minimize the spatial information loss. The investigations on the proposed architecture are evaluated on three retinal vessel segmentation publicly available datasets. The proposed G-Net light outperforms other vessel segmentation architectures by reducing the number of trainable parameters..

Dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of similar intensity and duration failed to induce pathology. The repetitive spOHT induced a rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, gasdermin D (GsdmD) and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinograms (PERG) amplitude, and significant loss of RGCs at 7 days post-injury. Inactivation of inflammasome complexes in NLRP1-/- , Casp1-/- and GsdmD-/- knockout animals, significantly suppressed the spOHT induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.

Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate if Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signaling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μM at 72 hours, and that 5 μM CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.

Это исследование сосредоточено на разработке системы искусственного зрения для гибкого дельта-робота-манипулятора и ее интеграции с межмашинной связью для оптимизации взаимодействия устройств в реальном времени. Эта интеграция направлена ​​на увеличение скорости роботизированной системы и улучшение ее общей производительности. Предлагаемое сочетание системы искусственного зрения с межмашинной связью позволяет обнаруживать и распознавать цели с высокой точностью в режиме реального времени в ограниченном пространстве, предназначенном для позиционирования, дальнейшей локализации и выполнения производственных процессов, таких как сборка или сортировка деталей. . В данном исследовании RGB-изображения используются в качестве входных данных для алгоритма MASK-R-CNN, а результаты обрабатываются в соответствии с особенностями прототипа дельта-манипулятора робота. Данные, полученные от MASK-R-CNN, адаптированы для использования в системе управления дельта-роботом с учетом ее уникальных характеристик и требований к позиционированию. Технология M2M позволяет манипулятору робота быстро реагировать на изменения, например, на перемещение объектов или изменение их положения, что имеет решающее значение для задач сортировки и упаковки. Система была протестирована в условиях, близких к реальным, чтобы оценить ее производительность и надежность.

This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. The primary aim is to systematically categorize and analyze the current trends and future directions in medical education research. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. Methods: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies into categories like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. Results: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. Conclusion: Medical education research is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential gaps in research, especially in underrepresented regions, indicating directions for future research efforts.

Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials.

Traditional computer vision techniques aim to extract meaningful information from images but often depend on manual feature engineering, making it difficult to handle complex real-world scenarios. Fractional Calculus (FC), which extends derivatives to non-integer orders, provides a flexible way to model systems with memory effects and long-term dependencies, making it a powerful tool for capturing fractional rates of variation. Recently, Neural Networks (NNs) have demonstrated remarkable capabilities in learning complex patterns directly from raw data, automating computer vision tasks and enhancing performance. Therefore, the use of fractional calculus in neural network-based computer vision is a powerful method to address existing challenges by effectively capturing complex spatial and temporal relationships in images and videos. This paper presents a survey of Fractional Calculus Neural Network-based (FC NN-based) computer vision techniques for denoising, enhancement, object detection, segmentation, restoration, and NN compression. The survey compiles existing FFC NN-based approaches, elucidates underlying concepts, and identifies open questions and research directions. By leveraging FC's properties, FC NN-based approaches offer a novel way to improve the robustness and efficiency of computer vision systems.

After decades of studies, the pathogenesis of Autism Spectrum Disorder (ASD) remains unclear and there still lackseffective treatment strategies for core symptoms. Our recent work, combined with others’ research in a diversity ofmodels and clinical trials, suggested a concise, but potentially rational theory that can illustrate the key of the pathogenesis and treatment of ASD from the aspect of damage control.

Ultra-wide field optical coherence tomography (UWF-OCT) has been recently introduced into clinical ophthalmological practice. To date, there is little data on the reference values of retinal thickness (RT) and choroidal thickness (CT) measured with this technique. This study aimed to analyze the variance of RT and CT in healthy eyes with UWF-OCT tests performed with the largest available scan size of 23 x 20 mm. The data were analyzed with reference to the patients' age, gender, and the axial length of the eyeball. The results of UWF-OCT scanning enabled us to picture the shape of the retina and choroid in a large portion of the eyeball. Both anatomical entities become significantly thinner at the periphery. The peripheral CT is greater in the upper and temporal sectors; the RT is higher in the nasal compared to the temporal sectors. Both choroid and retina lose thickness with age, however, CT and RT do not show a statistically significant correlation with the axial length after adjusting for age and gender. Age-related variations in thickness are especially prominent in the choroid. The CT in UWF-OCT testing is significantly greater in females while the RT is greater in males. UWF-OCT testing provides additional information on the anatomical structure of the retina and choroid compared to standard-field OCT

The number of people affected by eye conditions is growing every year, due to the popularity of electronic devices and an aging population. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many eye drops on the market, most of them have important limitations due to quick clearance mechanisms and ocular barriers. One solution with tremendous potential is the contact lens used as medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability, patient compliance, and reduce side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus in order to target successful in vitro and in vivo sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physical and chemical properties caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses bioinspired polymeric materials to improve biocompatibility, a specialized molecule recognition technique called molecular imprinting, or a stimuli-responsive system to improve biocompatibility and support drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices in ophthalmic therapies and projects an outlook onto future opportunities in the field of eye conditions management by means of active principles-eluting contact lens.

The main sources of intrinsic noise in excitable cells at the microcircuit and network levels are the stochastic characteristics of ion channel gating and activation of the synaptic conductance. Studies using in vivo, in vitro, and in silico methods to examine the effects of synaptic background activity were not adequately investigated in non-neuronal excitatory cells, where neurotransmitter-based innervation also occurs. We created a mathematical model to replicate the background synaptic noise dynamics in a non-neuronal cell. We utilized the stochastic Ornstein-Uhlenbeck process to represent excitatory synaptic conductance, which was incorporated into a whole-cell model to produce spontaneous and evoked cellular electrical activities. The single-cell model includes many biophysically detailed ion channels represented by a set of ordinary differential equations in Hodgkin-Huxley and Markov formalisms. This paradigm effectively induced irregular spontaneous depolarizations (SDs) and spontaneous action potential (sAP) resembling in vitro-like electrical activity in the cells. The input resistance decreased by multiple factors, and the spontaneous action potential firing rate elevated. The potential to reach the action potential threshold is altered. Background synaptic activity can alter the input/output characteristics of non-neuronal excitatory cells. Suppressing these baseline activities would facilitate the discovery of new pharmaceutical targets for different clinical diseases.

Natural polluted insulator surfaces are always coated with various kinds of soluble constituents, and those constituents affect flashover performance differentially. Currently this fact is not considered either in laboratory experiments or field pollution degree measurements, causing the existing insulation selection method to be deficient. In this paper a systematical research on insulator flashover voltage gradient correction involving types of soluble pollution constituents was presented. Taking typical type glass insulator as the sample, its flashover tests polluted by typical soluble chemicals NaCl, NaNO₃, KNO₃, NH₄NO₃, MgSO₄, Ca(NO₃)₂ and CaSO₄ were carried out. Then the flashover gradient correction was made combining the flashover performance of each soluble constituent, the ESDD contribution of the seven constituents, as well as the saturation performance of CaSO₄. The correction was well verified with the flashover test results of insulator polluted by three types of soluble mixture. Research results indicate that the flashover gradient correction method proposed by this paper performs well in reducing the calculating error. It is recommended to carry out component measurements and flashover gradient correction to better select outdoor insulation configuration.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

Background and Objectives: To analyze survival in peritoneal and hemodialysis patients using chest radiography and biochemical parameters, determine dialysis etiologies and common mortality causes, reveal prognostic factors, and contribute to clinical practice. Materials and Methods: This retrospective cohort study was based on the analysis of data from 33 peritoneal dialysis and 37 hemodialysis patients who were followed and treated in our hospital between October 2018 and February 2020. Chest X-ray measurements (cardiothoracic index, pulmonary vascular pedicle width, right pulmonary artery diameter, diaphragmatic height) and biochemical parameters (urea, albumin, creatinine, parathormone, ferritin, hemoglobin, arterial blood gas, potassium) were analyzed to assess their impact on survival. Statistical analyses were performed using the Shapiro-Wilk, Wilcoxon signed rank test, Mann-Whitney U test, McNemar test, Kaplan-Meier survival analysis, Cox regression analysis, Spearman correlation test, Phi test, and ROC analysis. Results: The most common etiologies of dialysis were hypertension, type 2 diabetes mellitus, and urogenital disorders. The most common cause of death in peritoneal dialysis patients was peritonitis (38.5%), while in hemodialysis patients, it was cardiovascular diseases (47.4%). In chest X-ray measurements, pulmonary vascular pedicle width (p=0.003) and pulmonary artery diameter increased significantly (p=0.002) in hemodialysis patients, while pulmonary vascular pedicle width (p=0.028) and diaphragmatic height (p=0.004) increased significantly in peritoneal dialysis patients. No significant difference was found between the two groups in terms of biochemical parameters. Kaplan-Meier survival analysis showed that there was no significant difference in survival between peritoneal dialysis and hemodialysis methods (P>0.05). Significant correlations were found between both radiologic status and clinical status and between intact parathormone levels and pulmonary vascular pedicle width (p=0.016, p=0.024). In Cox regression analysis, age, intact parathormone levels, iPTH/PVPW ratio, and clinical status were found to be factors affecting survival (p

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develop genetic tests and genetic therapies for IRDs yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 10 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism by which F. fructus alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia was investigated. The compounds, targets, and related diseases of F. fructus were studied utilizing the traditional Chinese medicine systems pharmacology (TCMSP) database. Information on the target genes was classified using the UniProt database. A network was built using Cytoscape 3.9.1, and functional dyspepsia-related genes were checked using the Cytoscape string application. The efficacy of F. fructus on functional dyspepsia, including gastroparesis and gastrointestinal motility, was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. In a functional dyspepsia mouse model, F. fructus significantly suppressed the symptoms when compared to that in the control group. Our animal studies showed that the mechanism of action of F. fructus is closely related to gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provides a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia can be described by the relationship between seven key compounds of F. fructus, including oleic acid and β-sitosterol, and 12 functional dyspepsia-related genes.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Our aim was to investigate the impact of shiftwork on changes in central retinal arteriolar equivalent (CRAE), a measure of arteriolar width, and central retinal venular equivalent (CRVE), a measure of venular width, over five years. Participants were 117 officers (72.7% men) examined at the first (2011-2014) and second (2015-2019) follow-up examinations of the Buffalo Cardio-Metabolic Occupational Police Stress study. Shiftwork data were obtained from City of Buffalo, NY payroll records. Retinal diameters were measured using a standardized protocol. ANCOVA was used to compare mean change in CRAE and CRVE between the two examinations across shiftwork categories. Among men only, those who worked ≥70% hours on day shift had a larger decrease in mean CRAE (-7.13±2.51) compared to those who worked <70% day (-0.08±0.96); p=0.011. Among patrol officers, those who worked ≥70% day had a larger decrease in CRAE compared with those who worked <70% day; p=0.015. Also, officers who worked ≥70% day had an increase in mean CRVE (µm) (4.56±2.56) compared to those who worked <70% (-2.32±1.32); p=0.027. Over the five-year period, we observed adverse changes in arteriolar and venular diameters among officers who worked ≥70% on day shift. Results should be interpreted with caution due to small sample sizes.

Age-related macular degeneration (AMD) is a complex, multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily its “dry” type, which is by far the most common (90% of all AMD cases). In recent years, AMD became younger: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review is to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.

The most prevalent Ca2+-buffer proteins (CaBPs: parvalbumin—PV; calbindin—CaB; calretinin—CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. To examine this, we performed immunohistochemistry (IHC) in the mouse retina. We found variability in the expression levels and cell numbers for CaR, with stronger and more numerous labels in the dorso-central area. CaBP+ cells contributed to RGCs with all soma sizes, indicating heterogeneity. We separated 4-9 RGC clusters in each area based on expression levels and soma sizes. Besides the overall high variety in cluster number and size, the peripheral half of the temporal retina showed the greatest cluster number, indicating a better separation of RGC subtypes there. Multiple labels showed that 39% of the RGCs showed positivity for a single CaBP, 30% expressed two CaBPs, 25% showed no CaBP expression and 6% expressed all three proteins. Finally, we observed an inverse relation between CaB and CaR expression levels in CaB/CaR dually- and CaB/CaR/PV triple labeled RGCs, suggesting a mutual complementary function.

Mobile health technologies enable continuous, quantitative assessment of mobility and gait in real-world environments, facilitating early diagnosis of gait disorders, disease progression monitoring, and prediction of adverse events like falls. Traditionally, mobile gait assessment predominantly relied on body-fixed sensors positioned at the feet or lower trunk. Here, we investigate the potential of an algorithm utilizing an ear-worn motion sensor for spatiotemporal segmentation of gait patterns. We collected 3D acceleration profiles from the ear-worn sensor during varied walking speeds in 53 healthy adults. Temporal convolutional networks were trained to detect stepping sequences and predict spatial relations between steps. The resulting algorithm, mEar, accurately detects initial and final ground contacts (F1 score of 99% and 91%, respectively). It enables determination of temporal and spatial gait cycle characteristics (among others stride time and stride length) with good to excellent validity at a precision sufficient to monitor clinically relevant changes in walking speed, stride-to-stride variability, and side asymmetry. This study highlights the ear as a viable site for monitoring gait and proposes its potential integration with in-ear vital sign monitoring. Such integration offers a practical approach to comprehensive health monitoring and telemedical applications, by integrating multiple sensors in a single anatomical location.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

This literature review delves into the realm of fault detection techniques for transmission lines, aiming to provide a comprehensive overview of recent advancements and key trends in the field. Employing a structured approach, the review synthesizes a plethora of research spanning from 2019 to 2024, sourced from diverse databases including IEEE Xplore, ScienceDirect, ResearchGate, Scopus, Litmaps, and Google Scholar. The methodology encompasses a systematic literature search protocol, stringent inclusion and exclusion criteria, meticulous data extraction, and a multi-dimensional analysis framework. The literature review uncovers a spectrum of fault detection methodologies, ranging from traditional signal processing techniques like Discrete Wavelet Transform and phase angle-based methods to cutting-edge deep learning algorithms such as Capsule Networks and Convolutional Neural Networks. Insights gleaned from the review underscore the critical importance of fault detection in maintaining the reliability, safety, and efficiency of power grids, highlighting its role as a frontline defense against widespread outages and equipment damage. Key findings from the review shed light on the efficacy of different fault detection approaches, showcasing their strengths and limitations across diverse system conditions. Furthermore, the review identifies common trends and challenges, including the need for real-world validation, scalability, adaptability to various network configurations, and cybersecurity considerations. This literature provides valuable insights and recommendations for future research endeavors in fault detection for transmission lines. By embracing advancements in both traditional and emerging techniques, researchers can continue to enhance the resilience and dependability of power transmission systems, ensuring their ability to withstand evolving challenges and safeguard critical infrastructure.

Water footprint has been widely used to illustrate the consumption of water in many situations; for instance, in products, processes or regions of interest. In this work, we analyzed – using a sensitivity analysis approach – the effect of some variables in the calculation of the water footprint in the viticulture in Brazilian Serra Gaúcha (the major producing region of Brazilian Wine).The classical Penman-Monteith model for evapotransporation was considered, with uncertainties in some parameters (dead mulch covering fraction in the vineyard, maximum temperatures for some months, altitudes and latitudes of the site). The sensitivity analysis was conducted using the SAFE toolbox under Octave framework. The results indicated that the the portion of the water footprint corresponding to the evapotranspiration is more sensitive to the values of mulch covering fraction and the altitude of the site in comparison with the latitude and the maximum temperatures.

Dehydrolutein accumulates in substantial concentrations in the retina. The aim of this study was to compare antioxidant properties of dehydrolutein with other retinal carotenoids, lutein and zeaxanthin, and their effects on ARPE-19 cells. The time-resolved detection of characteristic singlet oxygen phosphorescence was used to compare the singlet oxygen quenching rate constants of dehydrolutein, lutein, and zeaxanthin. The effects of these carotenoids on photosensitized oxidation were tested in liposomes, where photooxidation was induced by light in the presence of photosensitizers, and monitored by oximetry. To compare the uptake of dehydrolutein, lutein, and zeaxanthin, ARPE-19 cells were incubated with carotenoids for up to 19 days, and carotenoid contents were determined by spectrophotometry in cell extracts. To investigate the effects of carotenoids on phototocytotoxicity, cells were exposed to light in the presence of rose bengal or all-trans-retinal. The results demonstrate that the rate constants for singlet oxygen quenching are 0.77x1010, 0.55x1010, and 1.23x1010 M-1s-1 for dehydrolutein, lutein and zeaxanthin, respectively. Overall, dehydrolutein is similar to lutein or zeaxanthin in protection of lipids against photosensitized oxidation. ARPE-19 cells accumulate substantial amounts of both zeaxanthin and lutein but no detectable amounts of dehydrolutein. Cells pre-incubated with carotenoids are equally susceptible to photosensitized damage as cells without carotenoids. Carotenoids provided to cells together with the extracellular photosensitizers offer partial protection against photodamage. In conclusion, the antioxidant properties of dehydrolutein are similar to lutein and zeaxanthin. The mechanism responsible for its lack of accumulation in ARPE-19 cells deserves further investigation.

In the face of escalating climate concerns and the push for sustainable development, the global shift towards renewable and decentralized energy systems presents new challenges and opportunities. This study investigates integrating decentralized energy production, particularly photovoltaic (PV) systems, into national energy planning, aiming to optimize energy strategies that balance local production and consumption with national objectives. By analyzing the Swiss energy model, the research employs the EnergyScope and REHO models to assess the strategic implications of decentralized versus centralized energy systems. Results show that a decentralized approach can significantly reduce PV installation needs to 35 GW, about 23% of potential capacity, and decrease annual system costs by 10% to CHF 1230 per capita. This strategy emphasizes local consumption, minimizes grid reinforcement demands, and leverages economic advantages while addressing overproduction challenges through effective energy storage and grid management. Conclusions underline the strategic value of combining centralized and decentralized methods for resilient and sustainable energy planning. The study contributes to the discourse on energy policy and infrastructure planning, advocating for a hybrid model that accommodates both local conditions and broader energy objectives, urging further research into climate impacts and technology integration for a comprehensive energy future.

Extraocular eye muscles (EOMs) are innervated by axons of three ocular motor nuclei, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the EOMs, pro-vide an overview of vestibular pathway inputs to ocular motor nuclei, and describe congenital disorders that alter the development of ocular motor neurons. Oculomotor neurons originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae which are contra-laterally innervated. Trochlear motor neurons originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons originate variously in the rhombomeres r4-6 and innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow yielding a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. The ocular motor neurons are innervating somites, which receive innervates vestibular nuclei that connects with the brainstem motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders.

Proteins have the ability to adsorb on the surface of materials, such as soft contact lenses (SCLs), and can affect the hydrophobicity, roughness and surface properties of the contact lenses (CLs), which, in turn, can influence the friction between the lenses and the ocular surface. Excessive friction between contact lenses and the ocular surface can lead to discomfort for the wearer and may cause irritation or inflammation of the cornea, better known as corneal ulcers (keratitis). Bovine serum albumin (BSA) is often used as a standard protein in biocompatibility testing of materials, including contact lenses. One standard commercial contact lenses was tested under lubricated conditions to access the coefficient of friction (CoF), being the contact lubricated with a tear like fluid (TLF) solution containing six different concentrations of BSA. In all cases, a good linearity of the results of the friction force was verified, so the first friction law can be applied to determine the value of the coefficient of friction. It was found that friction increases with increasing protein concentration.

Ocular pathologies present significant challenges in achieving effective therapeutic re-sults due to various anatomical and physiological barriers. Natural products, such as flavonoids, alone or in association with allopathic drugs, present many therapeutical actions, including anti-cancer, anti-inflammatory, and antibacterial action. However, their clinical employment is chal-lenging for scientists due to their low water solubility. In this study, we designed a liquid formu-lation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were de-termined by employing the SupraFit software on the Uv-vis titration experiment. A deep physical-chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it con-firmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility of 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), per-mitting the dissolution of the solid complex within 30 min. NMR studies revealed the involve-ment of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecu-lar modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains demonstrating a sig-nificant activity of the formulation to the free components.

We developed a protein to rapidly and accurately diagnose Chagas disease, a life-threatening illness identified by the WHO as a critical worldwide public health risk. Complicating the current health situation are serological test limitations that contribute to most infected persons being unaware of their condition and therefore untreated. To improve diagnostic testing, we developed an immunological mimic of the etiological agent, Trypanosoma cruzi, by combining ten pathogen specific epitopes within the beta-barrel protein structure of Thermal Green Protein. The resulting multi-epitope protein, DxCruziV3, displayed high specificity and sensitivity as the antibody capture reagent in an ELISA platform with an analytical sensitivity that exceeds WHO recommendations. Within an immunochromatographic platform, DxCruziV3 showed excellent performance for the point of application diagnosis in a region endemic for multiple diseases, the municipality of Barcelos in the state of Amazonas, Brazil. In total, 167 individuals were rapidly tested using whole blood from a finger stick. As recommended by the Brazilian Ministry of Health, venous blood samples were laboratory tested by conventional assays for comparison. Test results suggest utilizing DxCruziV3 in different assay platforms can confidently diagnosis chronic infections by T. cruzi. Rapid and more accurate results will benefit everyone but will have the most noticeable impact in resource-limited rural areas where the disease is endemic.

Mosquitoes genus Aedes are the most important arthropod disease vector. Dengue Virus (DENV) and Chikungunya Virus (CHIKV) are the main arboviruses distributed in the world. Based on entomo-virological surveillance, appropriating public health strategies can be addressed to contain cases and control outbreaks. This study aims to show the potential performance of two new molecular methods for detecting DENV serotypes and CHIKV in mosquitoes. Mosquitoes were collected in urban areas and sylvatic areas between July to August 2023, DENV and CHIKV were screened using new multiplex RT-PCR and RT-q PCR. A total of 2150 mosquitoes were trapped including 976 Aedes (959 Ae. egypti, 6 Ae. furcifer and 11 Ae. Vittatus) and 1174 Culex from 39 pools of a maximum of 30 mosquitoes each, tested by molecular screening, 7.7% (3/39) were positive for DENV, DENV-1 was detected in one pool (1/3), and DENV-3 in two pools (2/3). All the pools were negative for CHIKV. The overall minimum infection rate (MIR) of DENV in this study was 3.07 (95% CI: 2.24 —19.86). This study shows the usefulness of our new molecular tools in DENV serotypes and CHIKV surveillance.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Microglia-related retinal inflammation is associated with a variety of retinal diseases. Lycium barbarum Glycopeptide (LBGP) is the main active component of Lycium barbarum polysaccharide (LBP) isolated from Lycium barbarum, which possesses antioxidation, neuroprotection, and immunoregulation. However, whether LBGP has beneficial effects on LPS/IFN-γ (L/I) induced retinal microglial activation and its underlying mechanism remains to be elucidated. In this study, we observed the anti-inflammatory properties of LBGP in microglia activated by LPS and IFN-γ (L/I), examining both primary retinal microglia and BV2 microglial cells. Cells were pretreated with LBGP for 2h before stimulated with LPS/IFN-γ (L/I) for 24h. The dosages of LBGP for cells were evaluated by using the CCK-8 assay. The morphological changes were observed using an optical microscope. The changes in expression of cytokines and inflammatory mediators were measured with Griess assay, ELISA, qPCR, and immunofluorescence. Western blotting was used to assess MAPK, NF-κB signal transducer. LBGP pre-treatment significantly reversed L/I-induced microglia morphological alterations in area, perimeter, Feret's diameter, and roundness. LBGP significantly alleviated the L/I-induced microglial activation in primary and BV2 microglial cells. LBGP switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by downregulating the expression of M1 markers (iNOS, IL-1β, IL-6, COX2, CD16, and CD86) and upregulating the expression of M2 markers (arginase 1 and CD206). Furthermore, LBGP attenuated the activation of NF-κB and MAPK pathways in L/I-activated BV2 cells. In summary, it is suggested that LBGP pretreatment significantly alleviated L/I-induced retinal inflammation by regulating microglial(M1/M2) polarization via NF-κB and MAPK signaling pathways.

Bistable rhodopsins have two stable forms which can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applica-tions such as optogenetics. In this work we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We have performed hybrid QM/MM simulations to study three isomers of the retinal chromo-phore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from a QM/MM molecular dy-namics trajectory and compared to experimental counterparts. The chromophore-protein in-teractions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted including a structural change in the polyene chain of the chromophore as well as changes in the nearby hydrogen bond network.

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited ten affected dogs to the study. The progression of PRA for two of the dogs was followed for two years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.

Intracortical microelectrodes that can be implanted have the ability to capture fast-changing neuron action potentials in the living brain. Despite this potential, many obstacles must still be overcome for reliable, long-term, high-quality recordings and accurate analysis of brain activity. These challenges include improving recording quality, enhancing recording stability, increasing recording capacity, and adding multi-functional features. One potential approach to enhance implantable microelectrodes involves the advancement of materials, refinement of implantation methodologies, and augmentation of the number of sites for recording. However, these challenges are still being actively researched, and advancements in microelectrode technology are underway. The difficulties with implantable microelectrodes are evaluated, and solutions are presented from different perspectives. The latest advancements in microelectrode technology are reviewed and condensed, and future possibilities are explored.