Charge, Aspect Ratio, and Plant Species Affect Uptake Efficiency and Translocation of Polymeric Agrochemical Nanocarriers.

An incomplete understanding of how agrochemical nanocarrier properties affect their uptake and translocation in plants limits their application for promoting sustainable agriculture. Herein, we investigated how the nanocarrier aspect ratio and charge affect uptake and translocation in monocot wheat (Triticum aestivum) and dicot tomato (Solanum lycopersicum) after foliar application. Leaf uptake and distribution to plant organs were quantified for polymer nanocarriers with the same diameter (∼10 nm) but different aspect ratios (low (L), medium (M), and high (H), 10-300 nm long) and charges (-50 to +15 mV). In tomato, anionic nanocarrier translocation (20.7 ± 6.7 wt %) was higher than for cationic nanocarriers (13.3 ± 4.1 wt %). In wheat, only anionic nanocarriers were transported (8.7 ± 3.8 wt %). Both low and high aspect ratio polymers translocated in tomato, but the longest nanocarrier did not translocate in wheat, suggesting a phloem transport size cutoff. Differences in translocation correlated with leaf uptake and interactions with mesophyll cells. The positive charge decreases nanocarrier penetration through the leaf epidermis and promotes uptake into mesophyll cells, decreasing apoplastic transport and phloem loading. These results suggest design parameters to provide agrochemical nanocarriers with rapid and complete leaf uptake and an ability to target agrochemicals to specific plant organs, with the potential to lower agrochemical use and the associated environmental impacts.

Temperature-Responsive Bottlebrush Polymers Deliver a Stress-Regulating Agent In Vivo for Prolonged Plant Heat Stress Mitigation.

Anticipated increases in the frequency and intensity of extreme temperatures will damage crops. Methods that efficiently deliver stress-regulating agents to crops can mitigate these effects. Here, we describe high aspect ratio polymer bottlebrushes for temperature-controlled agent delivery in plants. The foliar-applied bottlebrush polymers had near complete uptake into the leaf and resided in both the apoplastic regions of the leaf mesophyll and in cells surrounding the vasculature. Elevated temperature enhanced the in vivo release of spermidine (a stress-regulating agent) from the bottlebrushes, promoting tomato plant (Solanum lycopersicum) photosynthesis under heat and light stress. The bottlebrushes continued to provide protection against heat stress for at least 15 days after foliar application, whereas free spermidine did not. About 30% of the ∼80 nm short and ∼300 nm long bottlebrushes entered the phloem and moved to other plant organs, enabling heat-activated release of plant protection agents in phloem. These results indicate the ability of the polymer bottlebrushes to release encapsulated stress relief agents when triggered by heat to provide long-term protection to plants and the potential to manage plant phloem pathogens. Overall, this temperature-responsive delivery platform provides a new tool for protecting plants against climate-induced damage and yield loss.

Visible-Light-Mediated Controlled Radical Branching Polymerization in Water.

Hyperbranched polymethacrylates were synthesized by green-light-induced atom transfer radical polymerization (ATRP) under biologically relevant conditions in the open air. Sodium 2-bromoacrylate (SBA) was prepared in situ from commercially available 2-bromoacrylic acid and used as a water-soluble inibramer to induce branching during the copolymerization of methacrylate monomers. As a result, well-defined branched polymethacrylates were obtained in less than 30 min with predetermined molecular weights (36 000

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

Ketamine as an Analgesic Adjunct for Opioid-Induced Hyperalgesia in a Patient With a Sickle Cell Pain Episode.

Background: Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been proposed as a safe and effective nonopioid analgesic when given in lower doses than those historically used for general anesthesia. Case reports have demonstrated efficacy using low-dose ketamine for pain management and opioid weaning in patients with chronic noncancer pain, but reports of successful use in patients with sickle cell pain are limited. Case Report: A 35-year-old African American male with sickle cell disease presented to the emergency department with severe generalized body aches and left flank pain. Several days later, his pain became localized to the bilateral lower extremities. Escalating opioid doses provided no improvement. Workup was negative for infection, deep venous thrombosis, ischemia, and infarct. On hospital day 29, the Acute Pain Management Service was consulted and initiated a low-dose ketamine infusion for analgesia and to facilitate opioid weaning. Five days later, the patient was discharged pain-free. Conclusion: Ketamine is a potent nonopioid analgesic, and this report adds to the body of literature supporting the use of low-dose ketamine in patients with sickle cell disease to treat poorly controlled pain and opioid-induced hyperalgesia.

Thermally Degradable Poly(n-butyl acrylate) Model Networks Prepared by PhotoATRP and Radical Trap-Assisted Atom Transfer Radical Coupling.

Model poly(n-butyl acrylate) (PBA) networks were prepared by photoinduced atom transfer radical polymerization (photoATRP), followed by curing of polymer stars via atom transfer radical coupling (ATRC) with a nitrosobenzene radical trap. The resulting nitroxyl radical installed thermally labile alkoxyamine functional groups at the junctions of the network. The alkoxyamine crosslinks of the network were degraded back to star-like products upon exposure to temperatures above 135 °C. Characterization of the degraded products via gel permeation chromatography (GPC) confirmed the inversion of polymer topology after thermal treatment.

Injectable bottlebrush hydrogels with tissue-mimetic mechanical properties.

Injectable hydrogels are desired in many biomedical applications due to their minimally invasive deployment to the body and their ability to introduce drugs. However, current injectables suffer from mechanical mismatch with tissue, fragility, water expulsion, and high viscosity. To address these issues, we design brush-like macromolecules that concurrently provide softness, firmness, strength, fluidity, and swellability. The synthesized linear-bottlebrush-linear (LBL) copolymers facilitate improved injectability as the compact conformation of bottlebrush blocks results in low solution viscosity, while the thermoresponsive linear blocks permit prompt gelation at 37°C. The resulting hydrogels mimic the deformation response of supersoft tissues such as adipose and brain while withstanding deformations of 700% and precluding water expulsion upon gelation. Given their low cytotoxicity and mild inflammation in vivo, the developed materials will have vital implications for reconstructive surgery, tissue engineering, and drug delivery applications.

Reflection on the Matyjaszewski Lab Webinar Series and the Rise of Webinars in Polymer Chemistry.

Webinar series are helping our community of polymer scientists to stay engaged and connected, despite the cancellation of in-person meetings and the periodic closure of laboratories to contain the spread of the coronavirus pandemic. The sustainable and inclusive character of these virtual events make them valuable learning and networking opportunities. As organizers of the Matyjaszewski Lab Webinar Series, we share herein our experience, highlighting the benefits of virtual meetings and providing a short guide for webinar organizers. Researchers, particularly young scientists, are encouraged to organize such virtual events to broaden their skills and strengthen their professional network.

Interfacial dilatational rheology as a bridge to connect amphiphilic heterografted bottlebrush copolymer architecture to emulsifying efficiency.

HYPOTHESIS: Molecular architecture and composition of amphiphilic bottlebrush copolymers will dictate the dominant interfacial relaxation modes and the corresponding dilatational rheology for adsorbed layers at oil/water interfaces in a way that will correlate with the emulsifying efficiency of different bottlebrush copolymers. EXPERIMENTS: Amphiphilic, xylene-soluble poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PBA) heterografted bottlebrush copolymers with controlled differences in backbone length, hydrophilicity and arm length were synthesized by atom transfer radical polymerization. Dilatational rheology of adsorbed layers at the xylene/water interface was probed via pendant drop tensiometry by measuring the interfacial stress response to either large-amplitude strain cycling or small-amplitude strain oscillation. The rheological response was recorded as a function of interfacial pressure for adsorbed layers under different compression states. Emulsifying efficiency was determined as the lowest copolymer concentration that yielded water-in-xylene emulsions with at least one-month stability against coalescence. FINDINGS: The more hydrophilic copolymers with longer PEO arms exhibited non-hysteretic stress-strain response curves in large-amplitude strain cycling and a tendency for the modulus to increase with increasing interfacial pressure. These were more efficient emulsifiers than less hydrophilic copolymers that exhibited hysteretic interfacial rheology. Mere existence of significant moduli did not correlate with high emulsifying efficiency, while an increase in modulus with increasing interfacial pressure did so.

A Thermodynamic Roadmap for the Grafting-through Polymerization of PDMS11MA.

Grafting-through atom transfer radical polymerization (ATRP) was used to polymerize a sterically hindered poly(dimethylsiloxane) methacrylate (PDMS11MA, Mn = 1000) macromonomer to high conversion as a function of temperature, solvent, initial monomer concentration, and pressure. Higher polymerization yields were obtained when polymerizations were conducted at (i) lower temperature (T), (ii) in a poor solvent for the side chain, (iii) higher initial monomer concentration ([M]0), and (iv) higher pressure by mitigating the contribution of the equilibrium monomer concentration ([M]eq). The enthalpy of polymerization (ΔHp) and entropy of polymerization (ΔSp) were more negative in poor solvents. Polymerizations at ambient pressure required higher [M]0, use of a poor solvent, and lower temperatures to reach higher conversion with good control, whereas high pressure ATRP (HP-ATRP) displayed better control under dilute conditions. Grafting-through polymerization at high P and higher [M]0 was less controlled, plausibly due to limited solubility and mobility of the copper catalyst in the highly viscous medium.

Poor Solvents Improve Yield of Grafting-Through Radical Polymerization of OEO19MA.

Radical polymerization of poly(ethylene glycol) methyl ether methacrylate (OEO19MA, Mn ∼ 950) at an initial monomer concentration of 150 mM was investigated as a function of solvent composition. Conventional and controlled radical polymerizations in anisole at 60 °C converged at approximately the same equilibrium monomer concentration ([M]eq) of ∼38 mM, suggesting that livingness or diminished termination did not affect the thermodynamic parameters of polymerization. Conventional radical polymerizations (RPs) in anisole, dimethylformamide (DMF), toluene, and 1×PBS buffered water were taken to approximately 98% thermal initiator decomposition to determine [M]eq at reaction completion within a broad temperature range. The enthalpy (ΔHp) and entropy (ΔSp°) of polymerization were solvent-dependent. Polymerizations in 1×PBS were the most thermodynamically favorable, followed by those in DMF, toluene, and anisole. -ΔHp and -ΔSp increased with the square of the difference in the Hansen solubility parameters of poly(ethylene glycol) and the solvent. It is proposed that poor solvents favor polymer-polymer interactions over polymer-solvent interactions, which improves the thermodynamic polymerizability.

Fabrication of Porous Nanonetwork-Structured Carbons from Well-Defined Cylindrical Molecular Bottlebrushes.

Atom transfer radical polymerization was utilized to prepare well-defined cylindrical molecular bottlebrushes which were employed as building blocks and transformed into porous nanonetwork-structured carbons (PNSCs) via hypercross-linking chemistry and shape-regulated carbonization. The as-prepared PNSCs exhibited a unique nanomorphology-tunable characteristic by simply varying carbonization conditions. Because of their three-dimensional network nanomorphologies with well-developed hierarchical porous structures and conductive carbon framework, the PNSCs demonstrated excellent electrochemical performance in lithium-sulfur batteries.

Non-Tacky Fluorinated and Elastomeric STEM Networks.

Soft, elastomeric, non-tacky polymer networks are synthesized by reversible deactivation radical polymerization (RDRP). First, the pristine, structurally tailored and engineered macromolecular (STEM) networks are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and incorporated an atom transfer radical polymerization (ATRP) inimer into the network. Subsequently, poly(n-butyl acrylate) (PBA) and/or poly(octafluoropentyl acrylate) (POFPA) side chains are grafted from the network by photo-induced ATRP. These low glass transition temperature side chains produced soft materials (E = 104-178 kPa). However, only the POFPA-containing networks are also non-tacky. The fluorine content and material properties are investigated by dynamic mechanical analysis, elemental analysis, spectroscopy, and contact angle measurements.

Molecular Bottlebrushes as Novel Materials.

Molecular bottlebrushes are building blocks for the design of unique polymeric materials whose physical properties are fundamentally governed by their densely grafted structures. Recent developments in the area of reversible deactivation radical polymerization enabled facile and effective control over multiple molecular parameters. Owing to large molecular size, anisotropic conformation, and reduced chain entanglement, molecular bottlebrushes have empowered various applications that are challenging to achieve with linear polymers. In this Review, we focus on determining correlations between brushlike architectures and materials properties.

Eplerenone for chronic central serous chorioretinopathy-a randomized controlled prospective study.

PURPOSE: To evaluate the efficacy and safety of eplerenone for chronic nonresolving central serous chorioretinopathy (CSC). METHODS: Prospective, double-blind, randomized placebo-controlled study. Nineteen eyes of 17 patients with persistent subretinal fluid (SRF) due to CSC were enrolled and randomized to receive eplerenone 50 mg/day or placebo for 3 months, followed by a 3-month follow-up. The main outcome measure was change in SRF from baseline to 3 months of treatment. Secondary outcomes included change in SRF at any time-point, complete resolution of SRF, improvement in choroidal thickness and change in best-corrected visual acuity (BCVA). RESULTS: Thirteen eyes were treated with eplerenone and six with placebo. Both groups showed reduction in SRF throughout the treatment period, with a significant reduction at months 1, 3 and 5 only in the treatment group. Twenty-three per cent in the treatment group and 30.8% per cent in the placebo group experienced complete resolution of SRF. A significant improvement in BCVA was noted in the placebo group at 4 months, as well as a significant difference in BCVA between groups at 3 months in favour of the placebo group (p = 0.005). There was no significant difference in choroidal thickness in either group throughout the study period. No adverse events related to eplerenone were noted in the treatment group. CONCLUSION: In this study, eplerenone was not found to be superior to placebo in eyes with chronic CSC.

Importance of 3-D image reconstruction of spectral-domain OCT on outcome of grid laser photocoagulation for diffuse diabetic macular edema.

AIM: To present the outcome of modified grid laser photocoagulation (GLP) in diffuse diabetic macular edema (DDME) in eyes without extrafoveal and/or vitreofoveal traction. METHODS: Inclusion criteria for the retrospective study were DDME eyes of patients with type II diabetes mellitus that had ≥4 months of follow-up following GLP. Only one eye per patient was analyzed. Using 3-D spectral-domain optical coherence tomography (3-D SD-OCT), eyes that had either extrafoveal or vitreofoveal traction, or had been previously treated by an intravitreal medication(s) were excluded. Treated DDME eyes were divided into 4 groups: A) "Classic" DDME that involved the central macula; B) edema did not involve the macular center; C) eyes associated with central epiretinal membrane (ERM); D) DDME that was associated with macular capillary dropout ≥2 disc-diameter (DD). RESULTS: GLP outcome in 35 DDME eyes after 4-24 (mean, 13.1±6.9) months was as follows: Group A) 18 eyes with "classic" DDME. Following one or 2 (mean, 1.2) GLP treatments, best-corrected visual acuity (BCVA) improved by 1-2 Snellen lines in 44.4% (8/18) of eyes, and worsened by 1 line in 11.1% (2/18). Central macular thickness (CMT) improved by 7%-49% (mean, 26.6%) in 77.8% (14/18) of eyes. Causes of CMT worsening (n=4) were commonly explainable, predominantly (n=3) associated with emergence of extrafoveal traction, 5-9 months post-GLP. Group B) GLP(s) in DDME that did not involve the macular center (n=6) resulted in improved BCVA by 1-2 lines in 2 eyes. However, the central macula became involved in the edema process after the GLP in 3 (50%) eyes, associated with an emergence of extrafoveal traction in one of these eyes 4 months following the GLP. Group C) GLP failed in all 5 eyes associated with central ERM. Group D) GLP was of partial benefit in 2 of 6 treated eyes with macular capillary dropout ≥2DD. CONCLUSION: Eyes with DDME that involved the macular center were found to achieve favourable outcomes after GLP(s) during mid-term follow-up, unless complicated pre-GLP or post-GLP by vitreoretinal interface abnormalities, often extrafoveal traction or ERM, or by capillary dropout ≥2DD. Prospective studies with larger cohorts are required.

Epiretinal membranes and incomplete posterior vitreous detachment in diabetic macular edema, detected by spectral-domain optical coherence tomography.

PURPOSE. To present the vitreoretinal interface in diabetic macular edema (DME) associated with both epiretinal membrane (ERM) and incomplete posterior vitreous detachment (PVD), as detected by spectral-domain optical coherence tomography (SD-OCT). METHODS. In a retrospective study, findings were analyzed in one eye in consecutive patients. Excluded were eyes that had undergone vitreoretinal intervention or that had complete PVD or complete vitreous attachment. RESULTS. Of 44 eyes with DME and ERM, incomplete PVD was apparent in 23 (52.2%) eyes. A hyperreflective unified ERM/posterior vitreous cortex (PViC) membrane, or EVi membrane, was apparent in various sizes in 20 (87.0%) of the 23 eyes. This unified membrane (n = 20) was associated with vitreopapillary adherence in 19 (82.6%) of 23 eyes. Two major OCT presentations (n = 23) were encountered: incomplete vitreopapillary detachment (n = 11; 25% of 44), with attachment to the macular ERM, and posterior vitreous detachment from the macula, associated with vitreopapillary adhesion (n = 10; 22.7%), in four different manifestations. In the remaining two eyes, there was no association between the ERM and the PViC. CONCLUSIONS. In eyes with DME, ERM, and incomplete PVD, the posterior cortical vitreous and ERM appeared as one united EVi membrane in various lengths in most eyes, typically associated with vitreopapillary adhesion. These findings may have clinical importance in the context of epimacular membrane characteristics and its removal in DME.

Pseudophakic cystoid macular edema associated with extrafoveal vitreoretinal traction.

PURPOSE: To describe an association between extrafoveal vitreoretinal traction and intractable chronic pseudophakic cystoid macular edema (CME) by the use of optical coherence tomography (OCT). METHODS: In a retrospective case series study, charts and OCT findings of patients who had postoperative recalcitrant pseudophakic CME for at least 6 months and vitreoretinal traction membranes were analyzed. Excluded were eyes that either had another vitreoretinopathy that could affect the analysis or had undergone an intravitreal intervention. RESULTS: Three eyes (three patients) with macular edema following uneventful cataract surgery were detected to be associated with multifocal extrafoveal vitreoretinal traction sites in each. Retinal edema that was underlying each of the traction sites in all eyes was in continuum in at least one site per eye with the central macular edema, thus manifesting as diffuse macular edema. CONCLUSION: Chronic pseudophakic macular edema may be related to extrafoveal vitreoretinal traction.

Extrafoveal traction in retinal vein occlusion using spectral domain optical coherence tomography.

BACKGROUND: To present extrafoveal vitreous traction membranes, and their prevalence and association with diffuse macular oedema in eyes with retinal vein occlusion (RVO), using 3-D spectral-domain optical coherence tomography (SD-OCT). METHODS: In a retrospective institutional observational study, charts and qualified SD-OCT findings of consecutive patients with either central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) associated with macular oedema were analyzed. Exclusion criteria covered eyes that had: 1) another retinopathy that could affect the data analysis, 2) vitreoretinal adherence without signs of retinal traction, 3) undergone vitreoretinal surgery, or 4) been treated by intravitreal administration of medication(s). An age-matched control group (n = 72) afforded the normal central subfield thickness. RESULTS: Twenty-six eyes (of 26 patients) with either CRVO (n = 12) or BRVO (n = 14) were analyzed. Four eyes were excluded because they had a lack of macular oedema (n = 2), had an earlier pars plana vitrectomy (n = 1), or had previous treatment by intravitreal bevacizumab (n = 1). Of the 22 remaining eyes, both the SD-OCT B-mode video clip and the 3-D image reconstruction enabled a detection of extrafoveal traction membranes, either unifocally or multifocally, in nine eyes: four (of 11; 36.4 %) in CRVO, and five eyes (of 11; 45.5%) in BRVO. The retinal oedema in these nine eyes, which underlined at least one of the traction sites per eye, and the accompanied subretinal fluid in four of these nine eyes, were in continuum in each eye with the diffuse macular oedema and serous macular detachment respectively. During follow-up, a spontaneous release of a traction membrane coupled with resolution of the macular oedema occurred in one eye with BRVO. Of the four eyes that were excluded, two eyes had extrafoveal vitreous traction membranes. CONCLUSIONS: The SD-OCT B-mode video clip and its 3-D image reconstruction enabled relatively frequent detection of extrafoveal vitreous traction membranes in RVO and their association with diffuse macula oedema and macular detachment. A larger cohort is required to validate these findings and to compare the efficacy of early release of such traction membranes, either surgically or possibly by pharmacologic vitreolysis, with the current therapeutic modalities.

Optical coherence tomography as an adjunctive tool for diagnosing papilledema in young patients.

PURPOSE: The authors examined the peripapillary (3.4-mm diameter) retinal nerve fiber layer thickness (RNFL thickness) as depicted by optical coherence tomography (OCT) in young patients with pseudopapilledema or papilledema. METHODS: In 17 consecutive patients (6 to 20 years old) with bilateral newly diagnosed papilledema or pseudopapilledema, the eye with the thicker mean global RNFL per patient was analyzed. Excluded were patients in whom cerebrospinal fluid opening pressure was between 190 and 250 mm H(2)O ("gray zone"). RNFL thickness was compared in eyes with papilledema and pseudopapilledema using the Mann-Whitney U test. RESULTS: Papilledema was clinically diagnosed in 9 patients and pseudopapilledema in 6 patients; 2 patients were excluded. Median RNFL thickness in the eyes with papilledema was greater than that of both eyes with pseudopapilledema and controls at all 12 clock hours. In all 9 patients with papilledema, RNFL was thickened contiguously for 8 to 12 clock hours above the upper 95% confidence interval limit of normal. CONCLUSION: The peripapillary RNFL thickness as depicted by OCT was found to be a reliable adjunctive tool in the differentiation of newly diagnosed papilledema and pseudopapilledema in young patients. Larger cohorts are required to confirm these observations and conclusion.