Pediatric glaucoma: current perspectives

Giorgio Marchini, Marco Toscani, Francesca Chemello Eye Clinic, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy Abstract: "Childhood glaucoma" is a heterogeneous group of severe pediatric conditions often associated with significant visual loss and characterized by elevated intraocular pressure (IOP) and optic-disk cupping. Successful IOP control is crucial but challenging and most often achieved surgically, with medical therapy playing a supportive role. There are many classifications of childhood glaucoma, but they can simply be divided into primary, in which a developmental abnormality of the anterior chamber angle only exists, and secondary, in which aqueous outflow is reduced due to independent mechanisms that secondarily impair the function of the filtration angle. The worldwide prevalence of childhood blindness ranges from 0.03% in high-income countries to 0.12% in undeveloped countries. The majority of cases do not have an identified genetic mutation and, where the mutation is known, the genes often account for only a small proportion of cases. Several pathogenetic mechanisms are known to contribute to the development of childhood glaucoma. Whatever the cause, it results in a reduced aqueous outflow at the level of the trabecular meshwork. Age of onset and magnitude of the elevated IOP largely determine the clinical manifestation the high variability of clinical manifestations. Glaucoma from any cause in a neonate and infant is characterized by the classic triad of epiphora, photophobia, and blepharospasm, and could be associated with eye enlargement (buphthalmos) and Haab striae. The eye examination, usually performed under general anesthesia, includes: tonometry, anterior-segment examination, gonioscopy, corneal diameter and axial length measurement, dilated fundoscopy with optic-nerve-head evaluation. Medical therapy, considering the high frequency of side effects, is generally used as temporizing IOP-lowering treatment before surgery or as adjuvant treatment postoperatively in case of partially successful procedures for refractory glaucomas. Surgery is the nodal point of the management of refractory childhood glaucoma, so it is crucial to opt for a forward-looking strategy to reach the target IOP and minimize the visual loss. Keywords: childhood glaucoma, congenital glaucoma, glaucoma surgical therapy, childhood visual los

Ectopic mineralization in heart valves: New insights from in vivo and in vitro procalcific models and promising perspectives on noncalcifiable bioengineered valves

Ectopic calcification of native and bioprosthetic heart valves represents a major public health problem causing severe morbidity and mortality worldwide. Valve procalcific degeneration is known to be caused mainly by calcium salt precipitation onto membranes of suffering non-scavenged cells and dead-cellderived products acting as major hydroxyapatite nucleators. Although etiopathogenesis of calcification in native valves is still far from being exhaustively elucidated, it is well known that bioprosthesis mineralization may be primed by glutaraldehyde-mediated toxicity for xenografts, cryopreservation-related damage for allografts and graft immune rejection for both. Instead, mechanical valves, which are free from calcification, are extremely thrombogenic, requiring chronic anticoagulation therapies for transplanted patients. Since surgical substitution of failed valves is still the leading therapeutic option, progressive improvements in tissue engineering techniques are crucial to attain readily available valve implants with good biocompatibility, proper functionality and long-term durability in order to meet the considerable clinical demand for valve substitutes. Bioengineered valves obtained from acellular non-valvular scaffolds or decellularized native valves are proving to be a compelling alternative to mechanical and bioprosthetic valve implants, as they appear to permit repopulation by the host\u2019s own cells with associated tissue remodelling, growth and repair, besides showing less propensity to calcification and adequate hemodynamic performances. In this review, insights into valve calcification onset as revealed by in vivo and in vitro procalcific models are updated as well as advances in the field of valve bioengineering

Biochar impact on the estimation of the colorimetric-based enzymatic assays of soil

This study was carried out in order to assess the influence of biochar applications on the estimation of colorimetric-based enzymatic assays and to verify the effectiveness of the most common methods. Since most methods used to determine enzymatic activities in the soil are based on colorimetry, biochar may absorb substrates and/ or coloured products thereby distorting the analytical result. Biochar was added to two soils, with different textures and cation exchangeable capacities, at a rate of 2% (w/w), and seven enzyme activities were determined following standard methods. The biochar amendment lowered the spectrophotometer reading of the activity of FDAase and dehydrogenase in the sandy soil. In the three enzymatic activities based on p-nitrophenol production (β-glucosidase, phosphatase and arylsulphatase), the addition of biochar did not change the enzyme assays. The biochar led to an overestimation in terms of the protease and urease activities in the sandy soil. In the clay loamy soil, biochar did not change the response of any of the enzyme activities tested. A biochar dose of up to 2% only guarantees the effectiveness of the most common spectrophotometric methods for not excessively sandy soils

Cholesterol dependent macropinocytosis and endosomal escape control the transfection efficiency of lipoplexes in CHO Living Cells

Here we investigate the cellular uptake mechanism and final intracellular fate of two cationic liposome formulations characterized by similar physicochemical properties but very different lipid composition and efficiency for intracellular delivery of DNA. The first formulation is made of cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic helper dioleoylphosphocholine (DOPC), while the second one is made of the cationic 3 beta-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic lipid dioleoylphosphatidylethanolamine (DOPE). Combining pharmacological and imaging approaches we show that both DOTAP-DOPC/DNA and DC-Chol-DOPE/DNA lipoplexes are taken up in Chinese hamster ovary (CHO) living cells mainly through fluid-phase macropinocytosis. Our results also indicate that lipoplex macropinocytosis is a cholesterol-sensitive uptake mechanism. On the other side, both clathrin-mediated and caveolae-mediated endocytosis play a minor role, if any, in the cell uptake. Colocalization of fluorescently tagged lipoplexes and Lysosensor, a primary lysosome marker, reveals that poorly efficient DOTAP-DOPC/DNA lipoplexes are largely degraded in the lysosomes, while efficient DC-Chol-DOPE/DNA systems can efficiently escape from endosomal compartments

The picture of the Bianchi I model via gauge fixing in Loop Quantum Gravity

The implications of the SU(2) gauge fixing associated with the choice of invariant triads in Loop Quantum Cosmology are discussed for a Bianchi I model. In particular, via the analysis of Dirac brackets, it is outlined how the holonomy-flux algebra coincides with the one of Loop Quantum Gravity if paths are parallel to fiducial vectors only. This way the quantization procedure for the Bianchi I model is performed by applying the techniques developed in Loop Quantum Gravity but restricting the admissible paths. Furthermore, the local character retained by the reduced variables provides a relic diffeomorphisms constraint, whose imposition implies homogeneity on a quantum level. The resulting picture for the fundamental spatial manifold is that of a cubical knot with attached SU(2) irreducible representations. The discretization of geometric operators is outlined and a new perspective for the super-Hamiltonian regularization in Loop Quantum Cosmology is proposed.Comment: 6 page

The non-indigenous Paranthura japonica Richardson, 1909 in the Mediterranean Sea: travelling with shellfish?

An anthurid isopod new to the Mediterranean Sea has recently been observed in samples from three localities of the Italian coast: the Lagoon of Venice (North Adriatic Sea), La Spezia (Ligurian Sea) and Olbia (Sardinia, Tyrrhenian Sea). The specimens collected showed strong affinity to a species originally described from the NW Pacific Ocean: Paranthura japonica Richardson, 1909. The comparison with specimens collected from the Bay of Arcachon (Atlantic coast of France), where P. japonica had been recently reported as non-indigenous, confirmed the identity of the species. This paper reports the most relevant morphological details of the Italian specimens, data on the current distribution of the species and a discussion on the pathways responsible for its introduction. The available data suggest that the presence of this Pacific isopod in several regions of coastal Europe might be due to a series of aquaculture-mediated introduction events that occurred during the last decades of the 1900s. Since then, established populations of P. japonica, probably misidentified, remained unnoticed for a long time

Short-term use of dexamethasone/netilmicin fixed combination in controlling ocular inflammation after uncomplicated cataract surgery

Purpose: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery. Patients and Methods: Open-label, randomized, active-controlled, clinical study con-ducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as “efficacy rate”, whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as “percentage of responders”. Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl. Results: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The “efficacy rate” was 100% in both groups, whereas the “percentage of responders” was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was <0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net. Conclusion: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery

Biomimetic Electrospun Self-Assembling Peptide Scaffolds for Neural Stem Cell Transplantation in Neural Tissue Engineering

Spinal cord regeneration using stem cell transplantation is a promising strategy for regenerative therapy. Stem cells transplanted onto scaffolds that can mimic natural extracellular matrix (ECM) have the potential to significantly improve outcomes. In this study, we strived to develop a cell carrier by culturing neural stem cells (NSCs) onto electrospun 2D and 3D constructs made up of specific crosslinked functionalized self-assembling peptides (SAPs) featuring enhanced biomimetic and biomechanical properties. Morphology, architecture, and secondary structures of electrospun scaffolds in the solid-state and electrospinning solution were studied step by step. Morphological studies showed the benefit of mixed peptides and surfactants as additives to form thinner, uniform, and defect-free fibers. It has been observed that β-sheet conformation as evidence of self-assembling has been predominant throughout the process except for the electrospinning solution. In vitro NSCs seeded on electrospun SAP scaffolds in 2D and 3D conditions displayed desirable proliferation, viability, and differentiation in comparison to the gold standard. In vivo biocompatibility assay confirmed the permissibility of implanted fibrous channels by foreign body reaction. The results of this study demonstrated that fibrous 2D/3D electrospun SAP scaffolds, when shaped as micro-channels, can be suitable to support NSC transplantation for regeneration following spinal cord injury

Low and variable pH decreases recruitment efficiency in populations of a temperate coral naturally present at a CO2 vent

Atmospheric carbon dioxide enrichment alters seawater carbonate chemistry, thus threatening calcifying organisms such as corals. Coral populations at carbon dioxide vents are natural acidification experiments that mimic organism responses to seawater pH values projected for 2100. Even if demographic traits are paramount information to assess ecological relationships and habitat suitability, population dynamics studies on corals thriving under acidified conditions are lacking. Here, we investigate the demography and reproduction of popu- lations of the solitary, symbiotic, temperate coral Balanophyllia europaea naturally living along a pH gradient at a Mediterranean CO2 vent. Gametogenesis and larval production were unaffected while recruitment efficiency collapsed at low and variable pH, contributing to coral abundance decline and suggesting that life stages between larval release and early polyp growth are hindered by acidification. Exploring these processes is crucial to assess coral fate in the forthcoming acidified oceans, to preserve coral ecosystems and the socioeconomic ser- vices they provide