Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation.

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.

Dual photoresponsive & water-triggered nitric oxide releasing materials based on rhodium-based metal-organic polyhedra.

The exogenous administration of nitric oxide (NO) is considered a potential therapeutic treatment against a great variety of diseases due to its significant role in multiple physiological functions. Due to the gaseous nature, short lifetime and dose- and tissue-dependent activity of this molecule, the development of new administration procedures is required to control the NO delivery in terms of dosage, timing, and location. In this work, we propose a new molecular material based on robust metal-organic polyhedra (MOPs) for controlled NO release. We select dirhodium paddlewheel complex-based cuboctahedral MOPs (RhMOP), in which NO can chemically coordinate to the open-metal sites at the axial sites of dirhodium paddlewheel moieties. We further prepare amorphous coordination polymer particles (CPPs) by connecting RhMOP with bis(imidazole) linkers at the external axial sites. Both molecular MOPs and polymeric CPPs show relevant NO payloads and the release of NO can be triggered by two different stimuli: light and humidity. We show that imidazole ligands coordinating to the external axial sites of the paddlewheel moieties tune the light-triggered NO release property. We further demonstrate that the size and the extrinsic pores of CPPs are important for enhanced NO release.

Extraocular Rectus Muscle Stretching as a Weakening Procedure.

INTRODUCTION: Anterior segment ischemia may occur when three or more rectus muscles are operated in the same eye. Our purpose was to investigate the efficacy of rectus muscle stretching as a vessel-sparing weakening technique, in comparison with a retrospectively collected series of patients. METHODS: Non-operated patients with an indication of medial rectus muscle weakening surgery (deviation up to 20 PD, prism diopters) who could cooperate with topical or sub-Tenon's anesthesia. Clinical workup included routine complete ophthalmological evaluation. One double-needle 6/0 Mersilene suture was used on each side of the muscle at 4 mm distance of the insertion and pulled/stretched to insert in the sclera 3-5 mm posterior to the muscle locking passes. Main outcome measure was distance deviation at 2 months after surgery (alternate prism and cover test). RESULTS: Seven patients with esotropia of 12-20 PD, recruited in a 20-month period, were included. Preoperative median deviation was 20 PD, whereas postoperative median deviation was 4 PD (range 0-8 PD). On a visual pain scale (1-10) median pain score was 3 (range 2-5). Remarkable postoperative complications did not occur. Significant differences with a retrospectively collected series of patients' data, treated with standard medial rectus recession, were not observed. CONCLUSIONS: Preliminary data indicate that stretching of a rectus muscle has some weakening effect, that could be useful to correct small-angle strabismus, and may be suggested as a vessel-sparing technique when two rectus muscles have previously been operated in the same eye. TRIAL REGISTRATION: ClinicalTrials.gov NCT05778565.

Short-Peptide Supramolecular Hydrogels for In Situ Growth of Metal-Organic Framework-Peptide Biocomposites.

The development of bio-MOFs or MOF biocomposites through the combination of MOFs with biopolymers offers the possibility of expanding the potential applications of MOFs, making use of more environmentally benign processes and reagents and giving rise to a new generation of greener and more bio-oriented composite materials. Now, with the increasing use of MOFs for biotechnological applications, the development of new protocols and materials to obtain novel bio-MOFs compatible with biomedical or biotechnological uses is needed. Herein, and as a proof of concept, we have explored the possibility of using short-peptide supramolecular hydrogels as media to promote the growth of MOF particles, giving rise to a new family of bio-MOFs. Short-peptide supramolecular hydrogels are very versatile materials that have shown excellent in vitro and in vivo biomedical applications such as tissue engineering and drug delivery vehicles, among others. These peptides self-assemble by noncovalent interactions, and, as such, these hydrogels are easily reversible, being more biocompatible and biodegradable. These peptides can self-assemble by a multitude of stimuli, such as changes in pH, temperature, solvent, adding salts, enzymatic activity, and so forth. In this work, we have taken advantage of this ability to promote peptide self-assembly with some of the components required to form MOF particles, giving rise to more homogeneous and well-integrated composite materials. Hydrogel formation has been triggered using Zn2+ salts, required to form ZIF-8, and formic acid, required to form MOF-808. Two different protocols for the in situ MOF growth have been developed. Finally, the MOF-808 composite hydrogel has been tested for the decontamination of water polluted with phosphate ions as well as for the catalytic degradation of toxic organophosphate methyl paraoxon in an unbuffered solution.

A mesoporous Zr-based metal-organic framework driven by the assembly of an octatopic linker.

Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.

Oxime@Zirconium-Metal-Organic Framework Hybrid Material as a Potential Antidote for Organophosphate Poisoning.

A novel material with dual activity toward organophosphate (OP) poisoning, based on Zr-MOF-808 and neutral oxime RS69N, has been prepared. The hybrid material has a significant drug payload (5.2 ± 0.9 oxime to MOF-808 molar ratio) and shows a sustained oxime release in simulated physiological media, leading to the successful reactivation of OP-inhibited acetylcholinesterase. At the same time, the hybrid system presents an efficient and moderately fast removal rate of a toxic organophosphorus model compound (diisopropylfluorophosphate) from simulated physiological media (t1/2 = 183 min; 95% removal rate after 24 h).

Bifocal use in hyperopic anisometropic amblyopia treated with atropine: a proof-of-concept randomized trial.

OBJECTIVES: To investigate the effect of bifocal wearing in the amblyopic eye when atropine is used in the sound eye for the treatment of hyperopic anisometropic amblyopia. METHODS: Children 4-8 years old were randomly assigned to bifocal + atropine (n = 16) or only atropine (control, n = 19) groups of treatment in a proof-of-concept study. Measurements included visual acuity (logMAR), prism and cover test, stereoacuity (Randot preschool or Randot circles), contrast sensitivity (MARS test), accommodation (Grand Seiko WAM5500 and dynamic retinoscopy), retinoscopic and subjective refraction, before starting treatment and at 6 months, except accommodation, which was remeasured at 9-11 months. Main outcome measure was change in logMAR lines of visual acuity, and secondary outcome measures were change in stereoacuity and contrast sensitivity in the amblyopic eye, at 6 months. RESULTS: Improvement in visual acuity of the amblyopic eye was significantly better (p = 0.04) in the atropine plus bifocal (3.3 ± 0.9 logMAR lines) than in the atropine only group (2.6 ± 0.8 logMAR lines), whereas change in stereoacuity and contrast sensitivity was not significantly different between the two groups. Differences in accommodative gain, which was impaired in the amblyopic compared to the sound eye, before treatment, decreased after treatment, in the atropine group (0.62 ± 0.16 vs 0.79 ± 0.2, p = 0.3), and atropine + bifocal group (0.69 ± 0.15 vs 0.82 ± 0.2, p = 0.4). CONCLUSIONS: Use of bifocal lens add in the amblyopic eye of children with hyperopic anisometropic amblyopia, treated by atropine penalization, is beneficial in the follow-up period of 6 months.

Nanosized Calcium Phosphates as Novel Macronutrient Nano-Fertilizers.

The need for qualitatively and quantitatively enhanced food production, necessary for feeding a progressively increasing World population, requires the adoption of new and sustainable agricultural protocols. Among them, limiting the waste of fertilizers in the environment has become a global target. Nanotechnology can offer the possibility of designing and preparing novel materials alternative to conventional fertilizers, which are more readily absorbed by plant roots and, therefore, enhance nutrient use efficiency. In this context, during the last decade, great attention has been paid to calcium phosphate nanoparticles (CaP), particularly nanocrystalline apatite and amorphous calcium phosphate, as potential macronutrient nano-fertilizers with superior nutrient-use efficiency to their conventional counterparts. Their inherent content in macronutrients, like phosphorus, and gradual solubility in water have been exploited for their use as slow P-nano-fertilizers. Likewise, their large (specific) surfaces, due to their nanometric size, have been functionalized with additional macronutrient-containing species, like urea or nitrate, to generate N-nano-fertilizers with more advantageous nitrogen-releasing profiles. In this regard, several studies report encouraging results on the superior nutrient use efficiency showed by CaP nano-fertilizers in several crops than their conventional counterparts. Based on this, the advances of this topic are reviewed here and critically discussed, with special emphasis on the preparation and characterization approaches employed to synthesize/functionalize the engineered nanoparticles, as well as on their fertilization properties in different crops and in different (soil, foliar, fertigation and hydroponic) conditions. In addition, the remaining challenges in progress toward the real application of CaP as nano-fertilizers, involving several fields (i.e., agronomic or material science sectors), are identified and discussed.

Zirconium Metal-Organic Polyhedra with Dual Behavior for Organophosphate Poisoning Treatment.

Organophosphate nerve agents and pesticides are extremely toxic compounds because they result in acetylcholinesterase (AChE) inhibition and concomitant nerve system damage. Herein, we report the synthesis, structural characterization, and proof-of-concept utility of zirconium metal-organic polyhedra (Zr-MOPs) for organophosphate poisoning treatment. The results show the formation of robust tetrahedral cages [((n-butylCpZr)3(OH)3O)4L6]Cl6 (Zr-MOP-1; L = benzene-1,4-dicarboxylate, n-butylCp = n-butylcyclopentadienyl, Zr-MOP-10, and L = 4,4'-biphenyldicarboxylate) decorated with lipophilic alkyl residues and possessing accessible cavities of ∼9.8 and ∼10.7 Šinner diameters, respectively. These systems are able to both capture the organophosphate model compound diisopropylfluorophosphate (DIFP) and host and release the AChE reactivator drug pralidoxime (2-PAM). The resulting 2-PAM@Zr-MOP-1(0) host-guest assemblies feature a sustained delivery of 2-PAM under simulated biological conditions, with a concomitant reactivation of DIFP-inhibited AChE. Finally, 2-PAM@Zr-MOP systems have been incorporated into biocompatible phosphatidylcholine liposomes with the resulting assemblies being non-neurotoxic, as proven using neuroblastoma cell viability assays.

Elevation Matrix Data in the Evaluation of Keratoconus and Normal Corneas.

INTRODUCTION: To determine whether elevation matrix data of the anterior corneal surface could be useful for the diagnosis of keratoconus. METHODS: In a cross-sectional study, subjects aged 10-40 years with keratoconus (n = 74) or age-matched controls (n = 36) underwent complete ophthalmological examination, including Scheimpflug corneal topography (Pentacam HR). Exclusion criteria comprised previous ocular surgery, other eye disease, or significant corneal scarring. A raw data matrix of distance measurements to the most anterior corneal point was used to compare each subject with the mean normal cornea. A central 6-mm zone (6.1 × 6.1 mm) and two inferior eccentric matrices (0.4 × 6.1 and 1.1 × 1.1 mm) were used. Outcome measures were sensitivity, specificity, positive and negative predictive value, likelihood ratio, accuracy, and odds ratio. RESULTS: Sensitivity of central matrix for the diagnosis of keratoconus was low (6.7%) whereas specificity reached 94.4%. Sensitivity and specificity were respectively 93.2% and 94% for the 6.1 × 0.4 mm eccentric matrix and 97.2% and 97.2% for the 1.1 × 1.1 mm eccentric matrix. Positive predictive and negative predictive values were 71.4% and 33%, respectively, for the central matrix; 97.1% and 87.1%; 98.6% and 94.5%, for the two eccentric matrices, respectively. The likelihood ratio of a positive test was 1.1, 16.7, and 35, respectively. Sensitivity and specificity of the eccentric matrices were significantly better in the diagnosis of subclinical keratoconus (but not definite keratoconus) than other Pentacam indices. CONCLUSIONS: Using eccentric elevation matrix data analysis of the cornea is useful in the detection of keratoconus versus normal corneas.

Physiological and Molecular Investigation of Urea Uptake Dynamics in Cucumis sativus L. Plants Fertilized With Urea-Doped Amorphous Calcium Phosphate Nanoparticles.

At present, the quest for innovative and sustainable fertilization approaches aiming to improve agricultural productivity represents one of the major challenges for research. In this context, nanoparticle-based fertilizers can indeed offer an interesting alternative with respect to traditional bulk fertilizers. Several pieces of evidence have already addressed the effectiveness of amorphous calcium phosphate-based nanoparticles as carriers for macronutrients, such as nitrogen (N), demonstrating increase in crop productivity and improvement in quality. Nevertheless, despite N being a fundamental nutrient for crop growth and productivity, very little research has been carried out to understand the physiological and molecular mechanisms underpinning N-based fertilizers supplied to plants via nanocarriers. For these reasons, this study aimed to investigate the responses of Cucumis sativus L. to amorphous calcium phosphate nanoparticles doped with urea (U-ACP). Urea uptake dynamics at root level have been investigated by monitoring both the urea acquisition rates and the modulation of urea transporter CsDUR3, whereas growth parameters, the accumulation of N in both root and shoots, and the general ionomic profile of both tissues have been determined to assess the potentiality of U-ACP as innovative fertilizers. The slow release of urea from nanoparticles and/or their chemical composition contributed to the upregulation of the urea uptake system for a longer period (up to 24 h after treatment) as compared to plants treated with bulk urea. This prolonged activation was mirrored by a higher accumulation of N in nanoparticle-treated plants (approximately threefold increase in the shoot of NP-treated plants compared to controls), even when the concentration of urea conveyed through nanoparticles was halved. In addition, besides impacting N nutrition, U-ACP also enhanced Ca and P concentration in cucumber tissues, thus having possible effects on plant growth and yield, and on the nutritional value of agricultural products.

Urea-functionalized amorphous calcium phosphate nanofertilizers: optimizing the synthetic strategy towards environmental sustainability and manufacturing costs.

Nanosized fertilizers are the new frontier of nanotechnology towards a sustainable agriculture. Here, an efficient N-nanofertilizer is obtained by post-synthetic modification (PSM) of nitrate-doped amorphous calcium phosphate (ACP) nanoparticles (NPs) with urea. The unwasteful PSM protocol leads to N-payloads as large as 8.1 w/w%, is well replicated by using inexpensive technical-grade reagents for cost-effective up-scaling and moderately favours urea release slowdown. Using the PSM approach, the N amount is ca. 3 times larger than that obtained in an equivalent one-pot synthesis where urea and nitrate are jointly added during the NPs preparation. In vivo tests on cucumber plants in hydroponic conditions show that N-doped ACP NPs, with half absolute N-content than in conventional urea treatment, promote the formation of an equivalent amount of root and shoot biomass, without nitrogen depletion. The high nitrogen use efficiency (up to 69%) and a cost-effective preparation method support the sustainable real usage of N-doped ACP as a nanofertilizer.

On the amorphous layer in bone mineral and biomimetic apatite: A combined small- and wide-angle X-ray scattering analysis.

The occurrence of an amorphous calcium phosphate layer covering the crystalline apatite core has been suggested to be an intrinsic feature of both bone mineral and synthetic biomimetic analogs. However, an exahustive quantitative picture of the amorphous-crystalline relationship in these materials is still missing. Here, we present a multiple scale modelling that combines small-angle X-ray scattering (SAXS) and synchrotron wide-angle X-ray total scattering (WAXTS) analyses to investigate the amorphous-crystalline spatial interplay in bone sample and biomimetic carbonated nano-apatites. SAXS analysis indicates the presence of a single morphology consisting of tiny nanoplates (NPLs) and provides a measure of their thickness (falling in the 3-5 nm range). WAXTS analysis was performed by developing atomistic models of apatite NPLs incorporating lattice strain, mostly attributed to the carbonate content, and calculating the X-ray patterns using the Debye Scattering Equation. Upon model optimization, the size and strain parameters of the crystalline platelets were derived and the amorphous component, co-existing with the crystalline one, separated and quantified (in the 23-33 wt% range). Notably, the thickness of the apatite core was found to exhibit nearly null (bone) or minor (< 0.5 nm, biomimetic samples) deviations from that of the entire NPLs, suggesting that the amorphous material remains predominantly distributed along the lateral sides of the NPLs, in a core-crown-like arrangement. The lattice strain analysis indicates a significant stiffness along the c axis, which is comparable in bone and synthetic samples, and larger deformations in the other directions. STATEMENT OF SIGNIFICANCE: Current models of bone mineral and biomimetic nanoapatites suggest the occurrence of an amorphous layer covering the apatitic crystalline nanoplates in a core-shell arrangement. By combining X-ray scattering techniques in the small and wide angle regions, we propose a joint atomic-to-nanometre scale modelling to investigate the amorphous-crystalline interplay within the nanoplates. Estimates are extracted for the thickness of the entire nanoplates and the crystalline core, together with the quantification of the amorphous fraction and apatite lattice strain. Based on the thickness matching, the location of the amorphous material mostly along the edges of the nanoplates is inferred, with a vanishing or very thin layer in the thickness direction, suggesting a core-crown-like arrangement, with possible implications on the mineral surface reactivity.

Towards a more sustainable viticulture: foliar application of N-doped calcium phosphate nanoparticles on Tempranillo grapes.

BACKGROUND: The use of nanomaterials for the efficient delivery of active species in viticulture is still an unexplored opportunity. Nitrogen, an essential nutrient for grapevine development and wine quality, is commonly provided in the form of urea. However, the application of conventional fertilisers contributes to nitrate leaching and denitrification, thus polluting groundwater and causing a serious environmental impact. Nanotechnology is offering smart solutions towards more sustainable and efficient agriculture. In the present work, we assessed the efficiency of nontoxic amorphous calcium phosphate (ACP) nanoparticles as nanocarriers of urea (U-ACP) through field experiments on Tempranillo grapevines. Four treatments were foliarly applied: U-ACP nanofertiliser (0.4 kg N ha-1 ), commercial urea solutions at 3 and 6 kg N ha-1 (U3 and U6) and a control treatment (water). RESULTS: The grapes harvested from plants treated with U-ACP and U6 provided similar levels of yeast assimilable nitrogen, despite the very large reduction of nitrogen dosage. The concentration of amino acids was greater in U-ACP-treated plants than those of the control and U3 treatments and, barring a few exceptions, the values were comparable with those observed in grapes obtained following U6 treatment. Nanofertilisers provided a high arginine concentration in the musts but low proline concentrations in comparison to the U6 treatment. CONCLUSIONS: The results of this work show the potential benefits of nanotechnology over conventional practices for nitrogen fertilisation. Significantly, the application of U-ACP allowed a considerable reduction of nitrogen dosage to maintain the quality of the harvest, thereby mitigating the environmental impact. © 2020 Society of Chemical Industry.

Mixed-Metal Cerium/Zirconium MOFs with Improved Nerve Agent Detoxification Properties.

A series of Ce/Zr mixed-metal-organic frameworks with different topology/connectivity, namely, Ce/Zr-UiO-66 (U01, U02, and U03) (fcu (12-c)), Ce/Zr-DUT-67-PZDC (D01 and D02) (reo (8-c)), and Ce/Zr-MOF-808 (M01, M02, and M03) (spn (6-c)) were evaluated toward the detoxification of toxic nerve agent model diisopropylfluorophosphate (DIFP) at room temperature in unbuffered aqueous solution. Noteworthily, the catalytic rate for P-F bond cleavage increased with increasing Ce/Zr molar ratio. A further increase in catalytic activity can be achieved by Mg(OMe)2 doping of the mixed-metal MOFs as exemplified with M01@Mg(OMe)2 and M02@Mg(OMe)2 systems. The results show that Mg(OMe)2 incorporation into the mesoporous cavities of M01 and M02 give rise to P-F hydrolytic degradation half-lives of nearly 5 and 2 min with 100% degradation of DIFP after 55 and 65 min for M01@Mg(OMe)2 1:2 and M02@Mg(OMe)2 1:4, respectively.

Porous materials as carriers of gasotransmitters towards gas biology and therapeutic applications.

The discovery of NO, CO, and H2S as gasotransmitters and their beneficial role in multiple physiological functions opened an era of research devoted to exogenously delivering them as therapeutic agents. However, the gaseous nature of these molecules demands new forms of administration that enable one to control the location, dosage and timing of their delivery. Porous materials are among the most suitable scaffolds to store, deliver and release gasotransmitters due to their high surface area, tunable composition and reactivity. This review highlights the strategies employed to load and release gasotransmitters from different kinds of porous materials, including zeolites, mesoporous silica, metal-organic frameworks and protein assemblies.

The role of nanoparticle structure and morphology in the dissolution kinetics and nutrient release of nitrate-doped calcium phosphate nanofertilizers.

Bio-inspired synthetic calcium phosphate (CaP) nanoparticles (NPs), mimicking the mineral component of bone and teeth, are emergent materials for sustainable applications in agriculture. These sparingly soluble salts show self-inhibiting dissolution processes in undersaturated aqueous media, the control at the molecular and nanoscale levels of which is not fully elucidated. Understanding the mechanisms of particle dissolution is highly relevant to the efficient delivery of macronutrients to the plants and crucial for developing a valuable synthesis-by-design approach. It has also implications in bone (de)mineralization processes. Herein, we shed light on the role of size, morphology and crystallinity in the dissolution behaviour of CaP NPs and on their nitrate doping for potential use as (P,N)-nanofertilizers. Spherical fully amorphous NPs and apatite-amorphous nanoplatelets (NPLs) in a core-crown arrangement are studied by combining forefront Small-Angle and Wide-Angle X-ray Total Scattering (SAXS and WAXTS) analyses. Ca2+ ion release rates differ for spherical NPs and NPLs demonstrating that morphology plays an active role in directing the dissolution kinetics. Amorphous NPs manifest a rapid loss of nitrates governed by surface-chemistry. NPLs show much slower release, paralleling that of Ca2+ ions, that supports both detectable nitrate incorporation in the apatite structure and dissolution from the core basal faces.

Reducing Nitrogen Dosage in Triticum durum Plants with Urea-Doped Nanofertilizers.

Nanotechnology is emerging as a very promising tool towards more efficient and sustainable practices in agriculture. In this work, we propose the use of non-toxic calcium phosphate nanoparticles doped with urea (U-ACP) for the fertilization of Triticum durum plants. U-ACP nanoparticles present very similar morphology, structure, and composition than the amorphous precursor of bone mineral, but contain a considerable amount of nitrogen as adsorbed urea (up to ca. 6 wt % urea). Tests on Triticum durum plants indicated that yields and quality of the crops treated with the nanoparticles at reduced nitrogen dosages (by 40%) were unaltered in comparison to positive control plants, which were given the minimum N dosages to obtain the highest values of yield and quality in fields. In addition, optical microscopy inspections showed that Alizarin Red S stained nanoparticles were able to penetrate through the epidermis of the roots or the stomata of the leaves. We observed that the uptake through the roots occurs much faster than through the leaves (1 h vs. 2 days, respectively). Our results highlight the potential of engineering nanoparticles to provide a considerable efficiency of nitrogen uptake by durum wheat and open the door to design more sustainable practices for the fertilization of wheat in fields.

Botulinum toxin in the treatment of partially accommodative esotropia with high AC/A ratio.

PURPOSE: To study the outcome of botulinum toxin (BTX) treatment (group 1) in partially accommodative esotropia with high accommodative convergence/accommodation (AC/A) ratio, in comparison with bilateral medial rectus muscles recessions and posterior fixation (group 2). METHODS: In a retrospective comparative study, children aged 3-8 years old treated between 2011 and 2016, with partially accommodative esotropia with high AC/A ratio, deviation at distance of 10 prism diopters or more, and at least 1 year of follow-up, were included. Visual acuity, alternate prism and cover test, stereoacuity, biomicroscopy, and cycloplegic retinoscopy were carried out at initial, baseline visit, 6 months and 1 year after BTX injection or surgery. Main outcome variables were deviation at distance and near, improvement in stereoacuity, and percentage of success. We used multiple regression or proportional odds analysis to control for potential confounding variables. RESULTS: Of 95 patients, 84 were eligible, 48 children in group 1 and 36 in group 2. Deviation and stereoacuity were similar in the two groups at 6 months, but significantly better in the BTX group at 1 year (median distance deviation 0 prism diopters vs 5 prism diopters, p<0.01), although differences were not clinically relevant. Percentage of success was also significantly better only at 1 year (93% vs 72%, p = 0.01). Change in distance-near disparity was not significantly different in the two groups in the period of study. CONCLUSIONS: Botulinum toxin could be superior to, or as effective as surgery, at middle term, in the treatment of partially accommodative esotropia with high AC/A ratio.

Engineering Biomimetic Calcium Phosphate Nanoparticles: A Green Synthesis of Slow-Release Multinutrient (NPK) Nanofertilizers.

Biomimetic calcium phosphate nanoparticles (CaP) have been actively used in biomedicine, due to their high biodegradability and biocompatibility. However, much less progress has been made regarding their application in precision agriculture, i.e., for the controlled delivery of active species to plants. Herein, we report a straightforward and green synthetic method to dope CaP with potassium (K) and nitrogen (N, as nitrate and urea). By modulating the synthetic conditions in terms of maturation time (at 37 °C) and doping, we prepared K- and N-doped nanoparticles in the form of either amorphous calcium phosphate (ACP) or nanocrystalline apatite (Ap) and studied the impact of the dopants on the ACP-to-Ap transformation pathways. Importantly, we found out that ACP, isolated at low maturation times, incorporates nitrogen (in the form of nitrate and urea) to a larger extent than Ap (2.6 vs 1.1 wt %, respectively). Multinutrient nanofertilizers (so-called nanoU-NPK) with the following composition (wt %) were obtained: Ca (23.3), P (10.1), K (1.5), NO3 (2.9), and urea (4.8). The nanoU-NPK provides a slow and gradual release of the most important plant macronutrients (NPK), with N in two chemical forms, and different kinetics. The concentration of nutrients supplied by 10 g L-1 of nanoU-NPK to the media after 1 week (in mg L-1) was Ca (27.0), P (6.2), K (41.0), NO3 (134.0), and urea (315.0). Preliminary tests on durum wheat have shown that the application of nanoU-NPK allows reducing the amount of nitrogen supplied to the plants by 40% with respect to a conventional treatment, without affecting the final kernel weight per plant. The application of these slow-release NPK nanofertilizers is a promising strategy toward enhancing the efficiency of the fertilization, complying with the concept of precision agriculture.