Search

Chronic otitis externa (OE) in dogs frequently requires anaesthetised ear flushing.To evaluate hypochlorous acid as an ear flushing and antimicrobial agent in dogs with chronic OE.Twenty dogs with chronic OE caused by the same organisms bilaterally.One ear was flushed under anaesthesia with hypochlorous acid, the other with saline solution. Subsequently, the ear flushed with hypochlorous acid was cleaned with the same solution twice daily for 2 weeks, the other ear with a commercial ear cleaner. An ear medication containing miconazole, polymyxin B and prednisolone was used once daily in both ears. Clinical scores were determined before the flush. Ear cytological results were obtained, a hearing test was conducted before and after the ear flush, and a culture was taken directly after flushing. Ears were evaluated after 2 weeks of therapy.Yeast was present in the ears of 11, cocci in one and a mixed infection in eight dogs. Five ears were negative on culture after flushing with hypochlorous acid, one after the saline flush. Clinical and cytological scores decreased significantly with both solutions after 2 weeks of treatment. There was no difference between treatments in any of the scores at any time point between treatments and in the results of the hearing test before and after the flushing procedure. Adverse effects were not seen.Hypochlorous acid is a suitable cleaning solution for canine OE.L'otite externe (OE) chronique chez le chien nécessite fréquemment un rinçage des oreilles sous anesthésie.Évaluer l'acide hypochloreux en tant qu'agent antimicrobien et de rinçage des oreilles chez les chiens atteints d'OE chronique.Vingt chiens atteints d'OE chronique causée par les mêmes organismes bilatéralement. MATÉRIELS ET MÉTHODES: Une oreille a été rincée sous anesthésie avec de l'acide hypochloreux, l'autre avec une solution saline. Par la suite, l'oreille rincée à l'acide hypochloreux a été nettoyée avec la même solution deux fois par jour pendant deux semaines, l'autre oreille avec un nettoyant pour oreilles commercial. Un médicament pour les oreilles contenant du miconazole, de la polymyxine B et de la prednisolone a été utilisé une fois par jour dans les deux oreilles. Les scores cliniques ont été déterminés avant le rinçage. Les résultats cytologiques de l'oreille ont été obtenus, un test auditif a été effectué avant et après le rinçage de l'oreille et une culture a été prise directement après le rinçage. Les oreilles ont été évaluées après deux semaines de traitement. RÉSULTATS: Des levures étaient présentes dans les oreilles de 11 chiens, des cocci chez un et une infection mixte chez huit chiens. Cinq oreilles étaient négatives à la culture après rinçage à l'acide hypochloreux, une après le rinçage salin. Les scores cliniques et cytologiques ont diminué significativement avec les deux solutions après deux semaines de traitement. Il n'y avait aucune différence entre les traitements dans aucun des scores à aucun moment entre les traitements et dans les résultats du test auditif avant et après la procédure de rinçage. Aucun effet indésirable n'a été observé.L'acide hypochloreux est une solution de nettoyage appropriée pour l'OE canine.INTRODUCCIÓN: La otitis externa crónica (OE) en perros requiere con frecuencia un enjuague de oídos bajo anestesia.Evaluar el ácido hipocloroso como agente antimicrobiano y enjuague de oídos en perros con OE crónica.Veinte perros con OE crónica causada por los mismos organismos de forma bilateral. MATERIALES Y MÉTODOS: Se enjuagó un oído bajo anestesia con ácido hipocloroso, el otro con solución salina. Posteriormente, el oído enjuagado con ácido hipocloroso se limpió con la misma solución dos veces al día durante dos semanas, el otro oído con un limpiador de oídos comercial. Se utilizó un medicamento para los oídos que contenía miconazol, polimixina B y prednisolona una vez al día en ambos oídos. Las puntuaciones clínicas se determinaron antes del lavado. Se obtuvieron resultados citológicos del oído, se realizó una prueba de audición antes y después del lavado del oído y se tomó un cultivo directamente después del lavado. Las orejas se evaluaron después de dos semanas de terapia.se observaron levaduras en los oídos de 11 perros, cocos en uno y una infección mixta en ocho perros. Cinco oídos dieron negativo en el cultivo después del lavado con ácido hipocloroso, uno después del lavado con solución salina. Las puntuaciones clínicas y citológicas disminuyeron significativamente con ambas soluciones después de dos semanas de tratamiento. No hubo diferencia entre tratamientos en ninguna de las puntuaciones en ningún momento entre tratamientos y en los resultados de la prueba de audición antes y después del procedimiento de lavado. No se observaron efectos adversos. CONCLUSIÓN Y RELEVANCIA CLÍNICA: El ácido hipocloroso es una solución limpiadora adecuada para la OE canino.Bei einer chronischen Otitis externa (OE) benötigen Hunde häufig eine Ohrspülung in Narkose.Die Evaluierung hypochloriger Säure als Ohrreiniger und antimikrobiellem Wirkstoff bei Hunden mit chronischer OE.Zwanzig Hunde mit chronischer OE, die bilateral von denselben Organismen verursacht wurden.Ein Ohr wurde unter Narkose mit hypochloriger Säure, das andere mit Kochsalzlösung gespült. In der Folge wurde das Ohr, welches mit hypochloriger Säure gespült worden war, mit derselben Lösung zweimal täglich zwei Wochen lang gereinigt, das andere Ohr wurde mit einem kommerziellen Ohrreiniger gereinigt. Eine Ohrmedikation bestehend aus Mikonazol, Polymyxin B und Prednisolon wurde einmal täglich in beiden Ohren angewendet. Die klinischen Werte wurden vor der Spülung erhoben. Es wurde eine Ohrzytologie gemacht, ein Hörtest vor und nach der Spülung erhoben, sowie eine Kultur angelegt, die direkt nach der Spülung gewonnen wurde. Die Ohren wurden nach einer zweiwöchigen Therapie evaluiert.Hefepilze traten in 11 Ohren, Kokken in einem und eine gemischte Infektion bei acht Hunden auf. Fünf Ohren hatten eine Negativkultur nach der Spülung mit hypochloriger Säure, eines war negativ nach der Spülung mit Kochsalzlösung. Klinische und zytologische Werte nahmen bei beiden Lösungen nach einer zwei-wöchigen Behandlung signifikant ab. Es bestand zu keinem Zeitpunkt ein Unterschied zwischen den Behandlungen und den Ergebnissen der Hörtests vor und nach der Spülung. Es wurden keine Nebenwirkungen gesehen. SCHLUSSFOLGERUNG UND KLINISCHE BEDEUTUNG: hypochlorige Säure ist eine passende Reinigungslösung für die canine OE.背景: 犬の慢性外耳炎(OE)には麻酔下での耳洗浄が必要となることが多い。 目的: 本研究の目的は、慢性外耳炎を有する犬において、次亜塩素酸を耳洗浄剤および抗菌剤として評価することであった。 対象動物: 同一菌による両側性慢性OEを持つ犬20頭。 材料と方法: 片耳は麻酔下で次亜塩素酸によって、もう片方は生理食塩水で洗浄した。その後、次亜塩素酸で洗浄した耳は同液で1日2回、2週間洗浄し、もう片方の耳は市販のイヤークリーナーで洗浄した。ミコナゾール、ポリミキシンB、プレドニゾロン含有点耳薬を1日1回両耳に使用した。洗浄前に臨床的スコアを決定した。耳の細胞診の結果、耳洗浄の前後に聴力検査を実施し、耳洗浄後に培養検査を直接行った。耳は2週間の治療後に評価した。 結果: 11頭の耳に酵母、1頭に球菌、8頭に混合感染を認めた。次亜塩素酸による洗浄後5耳、生理食塩水による洗浄後1耳は培養陰性であった。治療開始2週間後、いずれの溶液でも臨床的および細胞学的スコアは有意に減少した。治療間のどの時点でも、また洗浄処置前後の聴力検査の結果でも、いずれのスコアにも治療間の差はなかった。また、有害事象も認めなかった。 結論と臨床的関連性: 次亜塩素酸は犬の OE に適した洗浄液である。.背景: 犬的慢性外耳炎 (OE) 经常需要麻醉后耳道冲洗。 目的: 评价次氯酸作为慢性OE犬的耳道灌洗液和抗菌剂的使用效果。 动物: 20只患有双侧相同微生物引起的慢性OE犬。 材料和方法:麻醉后一侧耳道用次氯酸冲洗，另一侧用生理盐水冲洗。随后，用次氯酸冲洗的耳道仍用相同溶液清洗，每日两次，持续两周，另一侧耳道用市售耳清洁剂清洁。双耳使用含有咪康唑、多粘菌素 B 和泼尼松龙的耳药，每日一次。在冲洗前确定临床评分。记录耳细胞学结果，在耳冲洗前后进行听力测试，冲洗后直接采集分泌物培养。治疗两周后评价耳道。.Otite externa (OE) crônica em cães frequentemente requer lavagem ótica sob anestesia.Avaliar o ácido hipocloroso como um limpador de orelhas e agente antimicrobiano em cães com OE crônica.Vinte cães com OE crônica causada pelos mesmos microrganismos bilateralmente. MATERIAIS E MÉTODOS: Uma orelha foi lavada sob anestesia com ácido hipocloroso e a outra com solução salina. Subsequentemente, a orelha lavada com ácido hipocloroso foi lavada com a mesma solução duas vezes ao dia por duas semanas, a outra orelha foi lavada com um limpador comercial. Uma fórmula otológica contendo miconazol, polimixina B e prednisolona foi utilizada uma vez ao dia em ambas as orelhas. Escores clínicos foram mensurados antes da lavagem. Citologias otológicas foram coletadas, teste de audição foi realizado antes e depois da lavagem, cultura e antibiograma foi coletada logo após a lavagem. As orelhas foram avaliadas após duas semanas de tratamento.Leveduras estavam presentes nas orelhas de 11, cocos em um e infecção mista em oito cães. Cinco cães foram negativos na cultura após a lavagem com ácido hipocloroso e um após a lavagem com salina. Os escores clínicos e citológicos reduziram bastante com ambas as soluções, após duas semanas de tratamento. Não houve diferença entre os tratamentos em nenhum escore e qualquer tempo entre tratamentos e nos resultados dos testes de audição antes e depois da lavagem. Não foram observados efeitos colaterais. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: O ácido hipocloroso é uma solução de limpeza adequada para OE canina.

For many cancer resections, a hospital volume-outcome relationship exists. The data regarding gastric cancer resection—especially in the western hemisphere—are ambiguous. This study analyzes the impact of gastric cancer surgery caseload per hospital on postoperative mortality and failure to rescue in Germany. All patients diagnosed with gastric cancer from 2009 to 2017 who underwent gastric resection were identified from nation-wide administrative data. Hospitals were grouped into five equal caseload quintiles (I–V in ascending caseload order). Postoperative deaths and failure to rescue were determined. Forty-six thousand one hundred eighty-seven patients were identified. There was a significant shift from partial resections in low-volume hospitals to more extended resections in high-volume centers. The overall in-house mortality rate was 6.2%. The crude in-hospital mortality rate ranged from 7.9% in quintile I to 4.4% in quintile V, with a significant trend between volume categories (p

Readily accessible tetraorganoborate salts undergo selective coupling reactions under blue light irradiation in the presence of catalytic amounts of transition‐metal‐free acridinium photocatalysts to furnish unsymmetrical biaryls, heterobiaryls and arylated olefins. This represents an interesting conceptual approach to forge C−C bonds between aryl, heteroaryl and alkenyl groups under smooth photochemical conditions. Computational studies were conducted to investigate the mechanism of the transformation., Shining light on organoborates: A photocatalyzed oxidative cross‐coupling reaction of functionalized organoborates is described, providing a diverse range of biaryl and olefin products. The mechanism of this C−C bond formation was investigated through quantum chemical calculations, revealing an unusual boracyclic intermediate.

Multisomes are multicompartmental structures formed by a lipid-stabilized network of aqueous droplets, which are contained by an outer oil phase. These biomimetic structures are emerging as a versatile platform for soft matter and synthetic biology applications. While several methods for producing multisomes have been described, including microfluidic techniques, approaches for generating biocompatible, monodisperse multisomes in a reproducible manner remain challenging to implement due to low throughput and complex device fabrication. Here, we report on a robust method for the dynamically controlled generation of multisomes with controllable sizes and high monodispersity from lipid-based double emulsions. The described microfluidic approach entails the use of three different phases forming a water/oil/water (W/O/W) double emulsion stabilized by lipid layers. We employ a gradient of glycerol concentration between the inner core and outer phase to drive the directed osmosis, allowing the swelling of lamellar lipid layers resulting in the formation of small aqueous daughter droplets at the interface of the inner aqueous core. By adding increasing concentrations of glycerol to the outer aqueous phase and subsequently varying the osmotic gradient, we show that key structural parameters, including the size of the internal droplets, can be specifically controlled. Finally, we show that this approach can be used to generate multisomes encapsulating small-molecule cargo, with potential applications in synthetic biology, drug delivery, and as carriers for active materials in the food and cosmetics industries.

Thiete dioxide units have been employed as a template for further functionalization through C−H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized that owe their stability to electrostatic interactions in the solid state. Similar starting materials were further engaged in the formation of cyclic trimeric structures, opening the pathway to unprecedented macrocyclic ring systems., C−H activation: Thiete dioxide units have been employed as a template for further functionalization through C−H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized. Similar starting materials were further engaged in the formation of novel cyclic trimeric structures (see scheme).

The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Förster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA–liposome hybrid carriers. Interestingly, the incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered-release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics., The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (Agreement No. 337969). K.N.B., P.S.C., and T.P.J.K. are grateful for financial support from the Biotechnology and Biological Sciences Research Council (BBSRC), the Newman Foundation, the Wellcome Trust, and the Cambridge Centre for Misfolding Diseases. D.M. is supported by the Winton Programme for the Physics of Sustainability, as well as the Engineering and Physical Sciences Research Council (EPSRC). P.T. gratefully acknowledges funding by the Bavarian Ministry of Science and the Arts through the ONE MUNICH Project “Munich Multiscale Biofabrication” and by the LMU-Cambridge strategic partnership. S.H.A. acknowledges funding by the Gobierno de Aragón-FSE (Research Group E47_20R).

[2+2+2] Cycloaddition reactions belong to the not even large class of reactions, which can be catalyzed or mediated by a significant number of different transition metals. Cobalt complexes belong to the catalysts that paved the way for the extensive use and profound mechanistic knowledge on this particular transformation. Beside the established role, cyclopentadienyl (Cp) cobalt complexes inherit in synthetic applications of the cyclotrimerization reaction, modification of the precatalysts opened up novel reactivities and versatility for such catalytic initiators. At the same time the development of in situ generated cobalt catalysts allowed the conversion of novel substrates as well as novel reaction modes to be realized. In this personal account recent developments will be presented and the possibilities of catalysts containing cobalt atoms in different oxidation states be discussed.

The molecular origins of Alzheimer's disease are associated with the aggregation of the amyloid-β peptide (Aβ). This process is controlled by a complex cellular homeostasis system, which involves a variety of components, including proteins, metabolites, and lipids. It has been shown in particular that certain components of lipid membranes can speed up Aβ aggregation. This observation prompts the question of whether there are protective cellular mechanisms to counterbalance this effect. Here, to address this issue, we investigate the role of the composition of lipid membranes in modulating the aggregation process of Aβ. By adopting a chemical kinetics approach, we first identify a panel of lipids that affect the aggregation of the 42-residue form of Aβ (Aβ42), ranging from enhancement to inhibition. We then show that these effects tend to average out in mixtures of these lipids, as such mixtures buffer extreme aggregation behaviors as the number of components increases. These results indicate that a degree of quality control on protein aggregation can be achieved through a mechanism by which an increase in the molecular complexity of lipid membranes balances opposite effects and creates resilience to aggregation.

Microcapsules are a key class of microscale materials with applications in areas ranging from personal care to biomedicine, and with increasing potential to act as extracellular matrix (ECM) models of hollow organs, tissues, or biomolecular condensates. Such capsules are conventionally generated from non‐ECM materials including synthetic polymers. Here, robust microcapsules with controllable shell thickness from physically‐ and enzymatically‐crosslinked gelatin are fabricated, and a core–shell architecture is achieved by exploiting a liquid–liquid phase‐separated aqueous system in a one‐step microfluidic process. Microfluidic mechanical testing reveals that the mechanical robustness of thicker‐shell capsules could be controlled through modulation of the shell thickness. Furthermore, the microcapsules demonstrate environmentally‐responsive deformation, including buckling driven by osmosis and external mechanical forces. A sequential release of cargo species is obtained through the degradation of the capsules. Stability measurements show the capsules are stable at 37 °C for more than 2 weeks. Finally, through gel–sol transition, microgels function as precursors for the formation of all‐aqueous liquid–liquid phase‐separated systems that are two‐phase or multiphase. These smart capsules that can undergo phase transition are promising models of hollow biostructures, microscale drug carriers, and building blocks or compartments for active soft materials and robots.

For many cancer resections, a hospital volume-outcome relationship exists. The data regarding gastric cancer resection-especially in the western hemisphere-are ambiguous. This study analyzes the impact of gastric cancer surgery caseload per hospital on postoperative mortality and failure to rescue in Germany.All patients diagnosed with gastric cancer from 2009 to 2017 who underwent gastric resection were identified from nation-wide administrative data. Hospitals were grouped into five equal caseload quintiles (I-V in ascending caseload order). Postoperative deaths and failure to rescue were determined.Forty-six thousand one hundred eighty-seven patients were identified. There was a significant shift from partial resections in low-volume hospitals to more extended resections in high-volume centers. The overall in-house mortality rate was 6.2%. The crude in-hospital mortality rate ranged from 7.9% in quintile I to 4.4% in quintile V, with a significant trend between volume categories (p 0.001). In the multivariable logistic regression analysis, quintile V hospitals (average of 29 interventions/year) had a risk-adjusted odds ratio of 0.50 (95% CI 0.39-0.65), compared to the baseline in-house mortality rate in quintile I (on average 1.5 interventions/year) (p 0.001). In an analysis only evaluating hospitals with more than 30 resections per year mortality dropped below 4%. The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue (FtR) decreased significantly with increasing caseload.Patients who had gastric cancer surgery in hospitals with higher volume had better outcomes and a reduced failure to rescue rates for severe complications.

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near-infrared (NIR) dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of NIR dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the enhanced permeability and retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs reveals enhanced OT signals at 24 h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant NIR dyes.

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near infrared dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of near infrared dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the Enhanced Permeability and Retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs revealed enhanced OT signals at 24h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant near infrared dyes.

Compartmentalization and selective transport of molecular species are key aspects of chemical transformations inside the cell. In an artificial setting, the immobilization of a wide range of enzymes onto surfaces is commonly used for controlling their functionality but such approaches can restrict their efficacy and expose them to degrading environmental conditions, thus reducing their activity. Here, we employ an approach based on droplet microfluidics to generate enzyme-containing microparticles that feature an inorganic silica shell that forms a semipermeable barrier. We show that this porous shell permits selective diffusion of the substrate and product while protecting the enzymes from degradation by proteinases and maintaining their functionality over multiple reaction cycles. We illustrate the power of this approach by synthesizing microparticles that can be employed to detect glucose levels through simultaneous encapsulation of two distinct enzymes that form a controlled reaction cascade. These results demonstrate a robust, accessible, and modular approach for the formation of microparticles containing active but protected enzymes for molecular sensing applications and potential novel diagnostic platforms.

Conventional methods carrying out C(sp2)−C(sp2) bond formations are typically mediated by transition‐metal‐based catalysts. Herein, we conceptualize a complementary avenue to access such bonds by exploiting the potential of electrochemistry in combination with organoboron chemistry. We demonstrate a transition metal catalyst‐free electrocoupling between (hetero)aryls and alkenes through readily available alkenyl‐tri(hetero)aryl borate salts (ATBs) in a stereoconvergent fashion. This unprecedented transformation was investigated theoretically and experimentally and led to a library of functionalized alkenes. The concept was then carried further and applied to the synthesis of the natural product pinosylvin and the derivatization of the steroidal dehydroepiandrosterone (DHEA) scaffold., Electro‐Olefination: The electrocoupling between (hetero)aryls and alkenes by alkenyl‐triaryl borates (ATBs) is demonstrated. ATBs are synthesized by a triple ligand exchange reaction on potassium alkenyltrifluroborates with organometallic species and directly oxidized in an electrochemical two‐pot coupling towards functionalized alkenes in a stereoconvergent fashion.

By combining efficient methodologies for the preparation of substituted azetines and thietes with a highly regio- and diastereoselective [3 + 2]-cycloaddition, a straightforward pathway for the synthesis of fused isoxazoline azetidines and thietanes has been designed. With minimal steps and starting from commercial sources, a new library of elaborated architectures was synthesized opening up a new class of molecules with large potential in pharmacology. Finally, a retro [2 + 2]-cycloaddition leading to substituted isoxazoles is described.

Combining a facile preparation of organoboronates with their remarkable stability and functional group tolerance allows for the straightforward synthesis of four- and five-membered carbo- and hetero­cycles. While most strategies rely on the ex situ preparation of boronic acids as isolated intermediates, we demonstrate that in situ transmetalation of sensitive organometallics with boron alkoxides can lead to great stabilization of such species at room temperature. A considerable extension of the library of unsaturated strained structures is achieved through these sequences, expanding the potential applicability of such unusual building blocks.

Spurred on by the recent emerging interest from the chemical community for unsaturated four-membered heterocycles, an unprecedented approach to nitrogen-containing four-membered rings has been designed. 3,4-Disubstituted 2-azetines were synthesized from commercially available substrates, allowing for a straightforward access to a new library of chiral functionalized azetidines and amino alcohols. This original approach was applied to efficiently prepare functionalized azobenzenes, an emerging class of molecules with a large potential in photopharmacology.

We report herein versatile, transition metal-free and additive-free (hetero)aryl-aryl coupling reactions promoted by the oxidative electrocoupling of unsymmetrical tetra(hetero)arylborates (TABs) prepared from ligand-exchange reactions on potassium trifluoroarylborates. Exploiting the power of electrochemical oxidations, this method complements the existing organoboron toolbox. We demonstrate the broad scope, scalability, and robustness of this unconventional catalyst-free transformation, leading to functionalized biaryls and ultimately furnishing drug-like small molecules, as well as late stage derivatization of natural compounds. In addition, the observed selectivity of the oxidative coupling reaction is related to the electronic structure of the TABs through quantum-chemical calculations and experimental investigations. ispartof: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY vol:142 issue:9 pages:4341-4348 ispartof: location:United States status: published

The self-assembly of the protein clathrin on biological membranes facilitates essential processes of endocytosis and has provided a source of inspiration for materials design by the highly ordered structural appearance. By mimicking the architecture of the protein building blocks and clathrin self-assemblies to coat liposomes with biomaterials, advanced hybrid carriers can be derived. Here, we present a method for fabricating DNA-coated liposomes by hydrophobically anchoring and subsequently connecting DNA-based triskelion structures on the liposome surface inspired by the assembly of the protein clathrin. Dynamic light scattering, ζ-potential, confocal microscopy, and cryo-electron microscopy measurements independently demonstrate successful DNA coating. Nanomechanical measurements conducted with atomic force microscopy show that the DNA coating enhances the mechanical stability of the liposomes relative to uncoated ones. Furthermore, we provide the possibility to reverse the coating process by triggering the disassembly of the DNA coats through a toehold-mediated displacement reaction. Our results describe a straightforward, versatile, and reversible approach for coating and stabilizing lipid vesicles through the assembly of rationally designed DNA structures. This method has potential for further development toward the ordered arrangement of tailored functionalities on the surface of liposomes and for applications as hybrid nanocarriers., The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (Agreement No. 337969). K.N.B. and T.P.J.K. are grateful for financial support from the Biotechnology and Biological Sciences Research Council (BBSRC), the Newman Foundation, the Wellcome Trust and the Cambridge Centre for Misfolding Diseases. K.V. and L.P. acknowledge funding from the BBSRC (Grant BB/M024830/1). J.G.N. received support from Heptares Therapeutics, the Ministerio de Ciencia, Innovación y Universidades (RTI2018-095629-J-I00), and the Fondo Europeo de Desarrollo Regional (FEDER). D.S. is supported by Winton Programme for the Physics of Sustainability, as well as the Engineering and Physical Sciences Research Council (EPSRC). S.H.A. acknowledges funding by the University of Zaragoza (UZ2018-CIE-04 and JIUZ-2018-CIE-04) and by the Gobierno de Aragón-FSE (Research Group E47_17R).

The self-assembly of the protein clathrin on biological membranes facilitates essential processes of endocytosis in biological systems and has provided a source of inspiration for materials design by the highly ordered structural appearance. By mimicking the architecture of clathrin self-assemblies to coat liposomes with biomaterials, new classes of hybrid carriers can be derived. Here we present a method for fabricating DNA-coated liposomes by hydrophobically anchoring and subsequently growing a DNA network on the liposome surface which structurally mimics clathrin assemblies. Dynamic light scattering (DLS), ζ-potential and cryo-electron microscopy (cryo-EM) measurements independently demonstrate successful DNA coating. Nanomechanical measurements conducted with atomic force microscopy (AFM) show that the DNA coating enhances the mechanical stability of the liposomes relative to uncoated ones. Furthermore, we provide the possibility to reverse the coating process by triggering the disassembly of the DNA coating through a toehold-mediated displacement reaction. Our results describe a straightforward, versatile, and reversible approach for coating and stabilizing lipid vesicles by an interlaced DNA network. This method has potential for further development towards the ordered arrangement of tailored functionalities on the surfaces of liposomes and for applications as hybrid nanocarrier.

Serum testing for allergen-specific immunoglobulin (Ig)E is commonly employed to identify allergens used for allergen-specific immunotherapy in dogs, yet the reliability of results has been a matter of debate.The aim of this study was to evaluate the reproducibility of serum tests for environmental allergen-specific IgE in three European laboratories.Serum was obtained from 33 client-owned dogs diagnosed with atopic dermatitis, divided into three aliquots and sent to the laboratories under different names. Two aliquots were sent simultaneously to one of the laboratories on the first day; the third sample was then sent to the same laboratory on the subsequent day. The laboratory for each patient was chosen according to a predetermined randomization list. The agreement between different samples from the same dog for each of the laboratories was calculated with a Cohen's Kappa test. Spearman's rank coefficients (rThe intra- and interassay agreements for laboratories A, B and C were 0.79 and 0.75, 0.92 and 0.90, and 0.90 and 0.85, respectively. The CVs were 18.92% and 22.95%, 14.43% and 18.79%, and 15.38% and 18.75% (respectively) and the rThe differences in reproducibility between laboratories complicate test interpretation and underline the importance of interpreting results of serum testing for allergen-specific IgE in the context of the patient's clinical history.Le test sérologique pour les immunoglobulines (Ig)E spécifiques d’allergènes est fréquemment employé pour identifier les allergènes à inclure dans la désensibilisation spécifique d’allergène chez le chien, alors que la fiabilité des tests fait encore débat.Le but de cette étude est d’évaluer la reproductibilité des tests sériques pour les IgE spécifiques d’allergènes environnementaux dans trois laboratoires européens. SUJETS/MÉTHODES: Le serum a été obtenu sur 33 chiens de propriétaires atteints de dermatite atopique, répartis en trois groupes, et envoyés aux laboratoires sous différents noms. Deux séries ont été envoyées simultanément à un des laboratoires le premier jour ; la troisième série a été envoyée au même laboratoire le jour suivant. Le laboratoire pour chaque patient a été choisi selon une liste randomisée prédéterminée. La concordance entre les différents échantillons du même chien pour chaque laboratoire a été calculée avec un test Kappa de Cohen. Les coefficients de Spearman (rLes différences de reproductibilité entre les laboratoires complique l’interprétation des tests et souligne l’importance de l’interprétation des résultats des tests sériques pour les IgE spécifiques d’allergènes dans le contexte clinique de chaque animal.INTRODUCCIÓN: las pruebas séricas de inmunoglobulina (Ig) E específicas de alérgenos se emplean comúnmente para identificar los alérgenos utilizados para la inmunoterapia específica de alérgenos en perros, aunque la fiabilidad de los resultados ha sido un tema de debate. OBJETIVO: el objetivo de este estudio fue evaluar la reproducibilidad de las pruebas séricas de IgE ambiental específica de alérgenos en tres laboratorios europeos. ANIMALES/MÉTODOS: el suero se obtuvo de 33 perros de propietarios particulares diagnosticados con dermatitis atópica, se dividió en tres alícuotas y se envió a los laboratorios con diferentes nombres. Se enviaron dos alícuotas simultáneamente a uno de los laboratorios el primer día; la tercera muestra se envió al mismo laboratorio al día siguiente. El laboratorio de cada paciente se eligió de acuerdo con una lista de aleatorización predeterminada. La concordancia entre diferentes muestras del mismo perro para cada uno de los laboratorios se calculó con una prueba Kappa de Cohen. Además, se calcularon los coeficientes de rango de Spearman (rsp) y los coeficientes de variación (CV). RESULTADOS: Las concordancias intra e interensayo para los laboratorios A, B y C fueron 0,79 y 0,75, 0,92 y 0,90 y 0,90 y 0,85, respectivamente. Los CV fueron 18,92% y 22,95%, 14,43% y 18,79%, 15,38% y 18,75% (respectivamente) y el rsp 0,73 y 0,68, 0,95 y 0,92 y 0,82 y 0,74 (respectivamente). CONCLUSIÓN Y RELEVANCIA CLÍNICA: las diferencias de reproducibilidad entre laboratorios complican la interpretación de las pruebas y subrayan la importancia de interpretar los resultados de las pruebas séricas de IgE específica de alérgenos en el contexto de la historia clínica del paciente.Serumtests für Allergen-spezifisches (Ig)E werden häufig verwendet, um Allergene zu identifizieren, die zur Allergen-spezifischen Immuntherapie bei Hunden Verwendung finden, wobei die Verlässlichkeit der Ergebnisse ein Diskussionsthema darstellt. ZIEL: Das Ziel dieser Studie war eine Evaluierung der Reproduzierbarkeit von Serumtests für Umweltallergen-spezifisches IgE in drei europäischen Laboratorien.Serum wurde von 33 Hunden in Privatbesitz, die mit atopischer Dermatitis diagnostiziert worden waren, genommen und in drei aliquote Anteile aufgeteilt und an die Laboratorien unter verschiedenen Namen eingesendet. Zwei Aliquote wurden gleichzeitig am ersten Tag an eines der Laboratorien gesendet; die dritte Probe wurde dann am darauffolgenden Tag an das gleiche Labor geschickt. Das Labor für den jeweiligen Patienten wurde anhand einer vorgefertigten Randomisierungsliste ausgesucht. Die Übereinstimmung der unterschiedlichen Proben desselben Hundes für jedes Labor wurde mittels Cohen´s Kappa Test kalkuliert. Zusätzlich wurden der Spearman´s Rangkorrelationskoeffizient (rDie Intra- und Interassay Übereinstimmungen für die Laboratorien A, B und C lagen bei 0,79 und 0,75 bzw 0,92 und 0,90 bzw 0,90 und 0,85. Die CVs lagen bei 18,92% und 22,95% bzw 14,43% und 18,79% bzw 15,38% und 18,75% und der rDie Unterschiede bei der Reproduzierbarkeit zwischen den Laboratorien machen die Interpretation der Tests kompliziert und unterstreichen die Wichtigkeit, die Serum-Testergebnisse für Allergen-spezifisches IgE im Zusammenhang mit der klinischen Patientenhistorie zu interpretieren.背景: アレルゲン特異的免疫グロブリン (Ig)E血清検査は、犬のアレルゲン特異的免疫療法に使用されるアレルゲンを同定するために一般的に使用されているが、その結果の信頼性については議論の余地がある。 目的: 本研究の目的は、ヨーロッパの3つの研究室における環境アレルゲン特異的IgE血清検査の再現性を評価することであった。 動物/方法: アトピー性皮膚炎と診断されたオーナー所有犬33頭から血清を採取し、3分割し、異なる名前で検査室に送付した。初日に分割した2サンプルを同時に1つの検査室に送り、3つ目のサンプルを翌日に同じ検査室に送った。各患者の検査室は、あらかじめ決められたランダム化リストに従って選択された。各検査室について、同じ犬からの異なるサンプル間の一致度を、コーエンのカッパ検定を用いて計算した。スピアマンの順位係数 (r背景: 敏原特异性免疫球蛋白(Ig)E的血清检测,通常用于鉴定过敏原,借以进行犬过敏原特异性免疫治疗, 然而结果的可靠性一直存有争议。 目的: 本研究的目的是评价3个欧洲实验室的环境过敏原特异性IgE血清检测结果的可重复性。 动物/方法: 33只诊断为特应性皮炎的私家犬, 采集血清, 分为3等份, 并以不同的名称送至实验室。第一天将两等份样本同时送至其中一个实验室; 然后在第二天将第三份样本送至同一实验室。根据预定的随机化列表选择每例病患的实验室。用Cohen’s Kappa检验计算每个实验室同一只犬不同样本间的一致性。另外计算Spearman秩系数(rsp)以及变异系数(CV)。 结果: 实验室A、B和C的批内和批间一致性分别为0.79和0.75、0.92和0.90以及0.90和0.85。CV分别为18.92%和22.95%、14.43%和18.79%、15.38%和18.75%,rsp分别为0.73和0.68、0.95和0.92、0.82和0.74。 结论和临床相关性: 实验室之间的重现性差异使检测判读变得复杂, 划重点--应在病患临床病史背景下,判读过敏原特异性IgE血清检测结果。.O teste sorológico de detecção de imunoglobulina (Ig)E alérgeno-específica é comumente empregado para identificar os alérgenos utilizados ​​para imunoterapia alérgeno-específica em cães, mas a confiabilidade dos resultados tem sido motivo de debate.Avaliar a reprodutibilidade de testes sorológicos para IgE alérgeno-específica para alérgenos ambientais em três laboratórios europeus. ANIMAIS/MÉTODOS: O soro foi obtido de 33 cães de clientes com diagnóstico de dermatite atópica, dividido em três alíquotas e enviado aos laboratórios com diferentes nomes. Duas alíquotas foram enviadas simultaneamente para um dos laboratórios no primeiro dia; a terceira amostra foi então enviada ao mesmo laboratório no dia seguinte. O laboratório de cada paciente foi escolhido de acordo com uma lista de randomização pré-determinada. A concordância entre diferentes amostras do mesmo cão para cada um dos laboratórios foi calculada com um teste Kappa de Cohen. Os coeficientes de Spearman (rAs concordâncias intra e interensaios para os laboratórios A, B e C foram 0,79 e 0,75, 0,92 e 0,90 e 0,90 e 0,85, respectivamente. Os CVs foram de 18,92% e 22,95%, 14,43% e 18,79%, e 15,38% e 18,75% (respectivamente) e o r