Background
Despite the risk of recurrent laryngeal nerve (RLN) palsy during esophagectomy, no established method of monitoring RLN injury is currently available.
Methods
This study included 187 ...patients who underwent esophagectomy between 2011 and 2018. Among these, intraoperative nerve monitoring (IONM) was done in 142 patients (IONM group), while the remaining 45 patients underwent conventional surgery without IONM (control group). We investigated the incidence of postoperative complications with regard to the use of IONM.
Results
The overall incidence of postoperative RLN palsy was 28% (52/187). The IONM group showed a significantly lower incidence of postoperative RLN palsy as compared to that in the control group (
p
= 0.004). The overall incidence of postoperative pneumonia was 22% (41/187) in those with Clavien–Dindo (CD) classification beyond grade 2. There were no significant differences between the incidence of any grade of postoperative pneumonia and the use of IONM (
p
= 0.195 and 0.333; CD > 2 and > 3, respectively). Multivariate analysis demonstrated that tumors in the upper third odds ratio (OR) 3.12; 95% confidence interval (CI) 1.04–9.29 and lack of IONM use (OR 2.51; 95% CI 1.17–5.38) were independent factors causing postoperative RLN palsy after esophagectomy.
Conclusion
IONM helps to reduce the risk of postoperative RLN palsy after esophageal cancer surgery.
Messenger RNA (mRNA) therapeutics have recently demonstrated high clinical potential with the accelerated approval of SARS-CoV-2 vaccines. To fulfill the promise of unprecedented mRNA-based ...treatments, the development of safe and efficient carriers is still necessary to achieve effective delivery of mRNA. Herein, we prepared mRNA-loaded nanocarriers for enhanced in vivo delivery using biocompatible block copolymers having functional amino acid moieties for tunable interaction with mRNA. The block copolymers were based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) modified with glycine (Gly), leucine (Leu) or tyrosine (Tyr) via ester bonds to generate block catiomers. Moreover, the amino acids can be gradually detached from the block copolymers after ester bond hydrolyzation, avoiding cytotoxic effects. When mixed with mRNA, the block catiomers formed narrowly distributed polymeric micelles with high stability and enhanced delivery efficiency. Particularly, the micelles based on tyrosine-modified PEG-PG (PEG-PGTyr), which formed a polyion complex (PIC) and π-π stacking with mRNA, displayed excellent stability against polyanions and promoted mRNA integrity in serum. PEG-PGTyr-based micelles also increased the cellular uptake and the endosomal escape, promoting high protein expression both in vitro and in vivo. Furthermore, the PEG-PGTyr-based micelles significantly extended the half-life of the loaded mRNA after intravenous injection. Our results highlight the potential of PEG-PGTyr-based micelles as safe and effective carriers for mRNA, expediting the rational design of polymeric materials for enhanced mRNA delivery.
As a result of the Great East Japan Earthquake and associated tsunami in March 2011, the Fukushima Daiichi Nuclear Power Plant (FDNPP) released a large amount of radioactive material into the ...environment, resulting in contamination of many marine organisms. In this study, 15 marine algal species and a seagrass species were collected from the sublittoral zone of the Iwaki Coast of Fukushima Prefecture from May 2012 to June 2015 and analyzed for variations in 110mAg, 134Cs, and 137Cs over time. The results indicated that (1) 110mAg, 134Cs, and 137Cs were present in all marine plants collected in May 2012, (2) the concentration of 110mAg in the seagrass Phyllospadix iwatensis decreased significantly over time while the ecological half-life of 110mAg in P. iwatensis was longer at locations closer to the FDNPP, and (3) the 110mAg/137Cs radioactivity ratio of P. iwatensis was remarkably high until 2015, indicating that detectable 110mAg was present in the coastal environment 4 years after the accident. The concentration of 110mAg in P. iwatensis was higher than those in other marine algae, demonstrating a species-specific mechanism of accumulation.
Field effect transistor (FET) based signal-transduction (Bio-FET) is an emerging technique for label-free and real-time basis biosensors for a wide range of targets. Glucose has constantly been of ...interest due to its clinical relevance. Use of glucose oxidase (GOD) and a lectin protein Concanavalin A are two common strategies to generate glucose-dependent electrochemical events. However, these protein-based materials are intolerant of long-term usage and storage due to their inevitable denaturing.
A phenylboronic acid (PBA) modified self-assembled monolayer (SAM) on a gold electrode with an optimized disassociation constant of PBA, that is, 3-fluoro-4-carbamoyl-PBA possessing its pKa of 7.1, was prepared and utilized as an extended gate electrode for Bio-FET.
The prepared electrode showed a glucose-dependent change in the surface potential under physiological conditions, thus providing a remarkably simple rationale for the glyco-sensitive Bio-FET. Importantly, the PBA modified electrode showed tolerance to relatively severe heat and drying treatments; conditions under which protein based materials would surely be denatured.
A PBA modified SAM with optimized disassociation constant (pKa) can exhibit a glucose-dependent change in the surface potential under physiological conditions, providing a remarkably simple but robust method for the glyco-sensing.
This protein-free, totally synthetic glyco-sensing strategy may offer cheap, robust and easily accessible platform that may be useful in developing countries. This article is part of a Special Issue entitled Organic Bioelectronics—Novel Applications in Biomedicine.
•A phenylboronate modified self-assembled monolayer was prepared on a gold electrode.•The electrode showed a glucose-dependent change in the surface potential.•This allowed us to potentiometrically detect glucose without the use of any labels.•The electrode also showed tolerance to heat and the following drying treatments.•This may offer the usage under severe conditions such as developing countries.
Lambert‐Eaton myasthenic syndrome (LEMS) is an autoimmune paraneoplastic syndrome with proximal muscle weakness, that often complicates small cell lung cancer. It is known that neurological symptoms ...do not improve with malignancy treatment alone in many LEMS patients, therefore treatment is often difficult. Since Lambert‐Eaton myasthenic syndrome is a rare disease with a frequency of about 1/100 that of myasthenia gravis, there are only a few case reports on malignancy complications other than small cell lung cancer. We report a LEMS patient in his 40s who was found to have an anterior mediastinal mass. We performed surgical resection and confirmed the diagnosis of primary thymic marginal zone B‐cell lymphoma by pathological diagnosis using immunostaining. Thymectomy and malignant lymphoma treatment with rituximab had no effect on neurological symptoms. The neurological symptoms improved only after we provided comprehensive care with the haematology, neurology, and rehabilitation department.
Lambert‐Eaton myasthenic syndrome (LEMS) is a condition in which antibodies are produced against voltage‐gated calcium channels in presynaptic nerve endings, resulting in an inability to release acetylcholine. It is characterized by fatigue and weakness of the proximal muscles of the extremities and is complicated by ocular symptoms, autonomic symptoms, and cerebellar ataxia. We report the case of a patient in whom comprehensive care with multiple departments successfully improved LEMS symptoms with primary thymic marginal zone B‐cell lymphoma.
A reversible boronate–diol interaction provides a versatile synthetic platform for molecular recognitions whose binding specificity can be molecularly tailored. We found that boronate derivatives ...with relatively strong acidity generally undergo a diphosphate-specific recognition among other phosphates under weakly acidic pH conditions, a feature relevant to DNA sequencing. 11B and 31P NMR studies identified “tetrahedral boronate and divalent diphosphate” as a pair responsible for forming a 1:1 stoichiometric complex, which manifests as a unique pH-dependent stability.
The excretory system produces urine by ultrafiltration via a filtration epithelium. Podocytes are widely found as filtration epithelial cells in eucoelomates. In some animal taxa, including insects ...and crustaceans, nephrocytes serve to separate toxic substances from the body fluid, in addition to podocytes.
Drosophila
nephrocytes have been recently utilized as a model system to study podocyte function and disease. However, functionality and cellular architecture are strikingly different between
Drosophila
nephrocytes and eucoelomate podocytes, and the phylogenetic relationship between these cells remains enigmatic. In this study, using focused-ion beam-scanning electron microscopy (FIB-SEM) tomography, we revealed three-dimensional architecture of decapod nephrocytes with unprecedented accuracy—they filled an enormous gap, which can be called “missing link,” in the evolutionary diversity of podocytes and nephrocytes. Thus, we concluded that nephrocytes are part of the spectrum of filtration epithelial diversity in animal phylogeny.
This study is devoted to the development of novel glucose-responsive polymers that operate under physiological conditions (pH 7.4, 37 °C), aiming for future use in a self-regulated insulin delivery ...system to treat diabetes mellitus. The approach involves the use of a newly synthesized phenylborate derivative {4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid, DDOPBA} possessing an appreciably low pK a (∼7.8) as a glucose-sensing moiety, as well as the adoption of poly(N-isopropylmethacrylamide), PNIPMAAm, as the main chain that exhibits critical solution behavior in the range close to physiological temperature. Glucose- and pH-dependent changes in the critical solution behavior of the resultant copolymers were investigated at varying temperatures, revealing definite glucose sensitivities near the physiological conditions. Furthermore, DDOPBA moieties in the copolymers maintained constant apparent pK a values even when the temperature approaches the critical solution points of the main chain, indicating that spacing of the phenylborate moiety from the polymer backbone is a feasible way to minimize the microenvironment effect caused by a temperature-induced change in the hydration state of the polymer strands.
Phenylboronic acid (PBA) derivatives, which are often termed 'boronolectins,' are regarded as a synthetic mimic of lectins because of their ability to interact with various carbohydrates. This unique ...chemistry has already borne fruit as the molecular bases for glucose sensors and some bio-separation applications. This focus review highlights some of the emerging PBA-based research directions toward more versatile diagnostic and therapeutic targets, which the authors are currently pursuing. The topics reviewed include PBA-mediated targeting to sialic acid (SA) as a methodology relevant to tumor diagnosis and treatment. Other drug delivery systems, including those for siRNA and insulin, in which PBA has a unique role in physicochemical signal transduction, will also be summarized.
RNA interference (RNAi) by small interfering RNAs (siRNAs) is a promising therapeutic approach. Because siRNA has limited intracellular access and is rapidly cleared in vivo, the success of RNAi ...depends on efficient delivery technologies. Particularly, polyion complexation between block catiomers and siRNA is a versatile approach for constructing effective carriers, such as unit polyion complexes (uPIC), core-shell polyion complex (PIC) micelles and vesicular siRNAsomes, by engineering the structure of block catiomers. In this regard, the flexibility of block catiomers could be an important parameter in the formation of PIC nanostructures with siRNA, though its effect remains unknown. Here, we studied the influence of block catiomer flexibility on the assembly of PIC structures with siRNA using a complementary polymeric system, i.e. poly(ethylene glycol)-poly(L-lysine) (PEG-PLL) and PEG-poly(glycidylbutylamine) (PEG-PGBA), which has a relatively more flexible polycation segment than PEG-PLL. Mixing PEG-PGBA with siRNA at molar ratios of primary amines in polymer to phosphates in the siRNA (N/P ratios) higher than 1.5 promoted the multimolecular association of uPICs, whereas PEG-PLL formed uPIC at all N/P ratios higher than 1. Moreover, uPICs from PEG-PGBA were more stable against counter polyanion exchange than uPICs from PEG-PLL, probably due to a favorable complexation process, as suggested by computational studies of siRNA/block catiomer binding. In in vitro experiments, PEG-PGBA uPICs promoted effective intracellular delivery of siRNA and efficient gene knockdown. Our results indicate the significance of polycation flexibility on assembling PIC structures with siRNA, and its potential for developing innovative delivery systems.
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