A Comparison of a Direct Electron Detector and a High-Speed Video Camera for a Scanning Precession Electron Diffraction Phase and Orientation Mapping.

A scanning precession electron diffraction system has been integrated with a direct electron detector to allow the collection of improved quality diffraction patterns. This has been used on a two-phase α­ß titanium alloy (Timetal® 575) for phase and orientation mapping using an existing pattern-matching algorithm and has been compared to the commonly used detector system, which consisted of a high-speed video-camera imaging the small phosphor focusing screen. Noise is appreciably lower with the direct electron detector, and this is especially noticeable further from the diffraction pattern center where the real electron scattering is reduced and both diffraction spots and inelastic scattering between spots are weaker. The results for orientation mapping are a significant improvement in phase and orientation indexing reliability, especially of fine nanoscale laths of α-Ti, where the weak diffracted signal is rather lost in the noise for the optically coupled camera. This was done at a dose of ~19 e−/Å2, and there is clearly a prospect for reducing the current further while still producing indexable patterns. This opens the way for precession diffraction phase and orientation mapping of radiation-sensitive crystalline materials.

Experiencia inicial en Buenos Aires con la cirugía transoral robótica (TORS) / Initial experience with transoral robotic surgery (TORS) in Buenos Aires

Antecedentes: la cirugía robótica es una alternativa a la cirugía abierta, microcirugía láser CO2, o quimiorradioterapia en vía aerodigestiva superior. El robot permite trasladar la técnica quirúrgica abierta a un abordaje mínimamente invasivo, con acceso por boca, para patología benigna y maligna. Actualmente se emplean diferentes terapéuticas con similares resultados oncológicos. Objetivo: introducir una herramienta quirúrgica para abordaje bucal. Comunicar la experiencia inicial con el uso del robot. Evaluar la preservación de respiración y deglución. Analizar variables que determinaron una disminución en la hospitalización. Material y métodos: 13 mujeres y 11 hombres. Edad entre 16 y 82 años, media de 55,08. Total 24 pacientes con enfermedad inflamatoria crónica (8), tumores benignos (4) y malignos (12). Variables consideradas en cirugía robótica: tiempo y lugar de internación, complicaciones, estado respiratorio y deglutorio, uso de técnicas reconstructivas. Se realizó videoendoscopia de deglución para objetivar la seguridad del método. Resultados: tiempo medio de internación: 1,92 días. El 83,3% internado 1 día. El 79,9% en internación general. Unidad cerrada: 20,1%. Ninguna traqueostomía. Cicatrización del lecho por segunda. Sin complicaciones. Edema de lengua: 2 pacientes. Conclusiones: la cirugía robótica favorece la exéresis con baja morbilidady máxima preservación de tejidos sanos. Disminuye: edema posoperatorio, uso colgajos para reparar el lecho, traqueotomía temporaria, tiempo de internación. La videoendoscopia de deglución demuestra utilidad para determinar la deglución segura. Limitante del presente trabajo es el tamaño de la muestra. Es importante incrementar el número de pacientes para valorizar supervivencia y calidad de vida.

Background: robotic surgery is an alternative to open surgery, CO2 laser microsurgery, or chemoradiation for the upper aero-digestive tract. This system allows surgeons to use the open surgical technique in a minimally invasive approach through the mouth to treat benign and malignant disorders. Different treatments are currently used with similar oncologic outcomes. Objective: the aim of this study was to introduce a surgical tool through transoral approach, report the initial experience with the use of the robotic system, evaluate respiratory and digestive functional preservation and analyze the variables associated with shorter hospital length of stay. Material and methods: A total of 24 patients (13 women and 11 men, mean age 55.08 years [16-82]) were included. Eight patients had chronic inflammatory disease, four had benign tumors and 12 had cancer. The variables considered in robotic surgery were hospital length of stay, place of postoperative care, complications, respiratory and swallowing function and use of reconstructive techniques. Flexible endoscopic evaluation of swallowing was performed to document safe function. Results: mean length of stay was 1.92 days; 83.3% stayed for one day; 79.9% were admitted to the general ward and 20.1% stayed in intensive or intermediate care units. None of the patients required tracheostomy. Healing of the surgical bed occurred by secondary intention. There were no complications. Tongue edema occurred in two patients. Conclusions: robotic surgery favors tumor removal with low morbidity and maximum preservation of healthy tissues while reducing postoperative edema, use of flaps for reconstruction, temporary tracheostomy and hospital length of stay. Flexible endoscopic evaluation of swallowing is useful to determine safe swallowing function. The main limitation of our study is the sample size. It is important to increase the number of patients to evaluate survival and quality of life.

A Facile Synthesis of Blue Luminescent [7]Helicenocarbazoles Based on Gold-Catalyzed Rearrangement-Iodonium Migration and Suzuki-Miyaura Benzannulation Reactions.

New azahelicenes having interesting photophysical properties have been prepared in a four-step sequence. These [7]helicenocarbazoles are efficient blue luminophores, demonstrating the utility of gold catalysis in the preparation of advanced materials.

Photoinduced Gold-Catalyzed Domino C(sp) Arylation/Oxyarylation of TMS-Terminated Alkynols with Arenediazonium Salts.

A selective and convenient synthesis of tri- and tetrasubstituted α,ß-unsaturated ketones, as well as 2,3-diarylbenzofurans has been developed with the aid of light and taking advantage of a cooperative gold/photoredox-catalyzed 2-fold arylation reaction of TMS-terminated alkynols. The reaction of 3-(trimethylsilyl)prop-2-yn-1-ols was competent to generate diarylated α,ß-unsaturated ketones; whereas the photoredox sequence involving 2-[(trimethylsilyl)ethynyl]phenol exclusively afforded 2,3-diarylbenzofurans. The reaction of terminal alkynes proceeded in poor yields while the use of bulkier silyl groups, such as TIPS, resulted unproductive. Apparently, the C(sp) arylation reaction is the first event on the domino bis-arylative sequence. These results could be explained through the intermediation of arylgold(III) species and several single electron transfer processes.

Abordaje combinado endoscópico y externo/endobucal para el tratamiento de grandes litos salivales. Nuestra experiencia / Combined sialendoscopic and external/intraoral approach for the treatment of large salivary stones. Our experience / Abordagem combinada endoscópica e externa/endo-bucal para o tratamento de grandes cálculos salivares. Nossa experiência

Introducción: el tratamiento tradicional de los grandes litos de las glándulas salivales (parótida y submaxilar) implica la exéresis de la glándula. La sialoendoscopía preserva órganos ya que permite diagnosticar y tratar las patologías obstructivas salivales secundarias a alteraciones en sus conductos. La sialoendoscopía intervencionista tiene una tasa de éxito de alrededor del 80% y falla en el 20% restante, debido al gran tamaño de los litos o a largas estenosis. Los abordajes combinados endoscópicos y externos constituyen una alternativa terapéutica. Objetivos: Analizar los beneficios del tratamiento conservador de la glándula parótida y submaxilar con grandes litos. Lugar de aplicación: Hospital de la Policía Federal Argentina Churruca-Visca y Hospital Italiano de Buenos Aires. Argentina...

Introduction: traditional treatment of large stones of the salivary glands (parotid and submandibular) involves the removal of the gland with subsequent morbidity associated with the procedure. The sialendoscopy has meant a breakthrough in organ preservation because it allows using a minimally invasive procedure, diagnose and treat obstructive salivary diseases secondary to alterations in their ducts. However sialendoscopy procedure has a success rate of about 80%. In the remaining 20%, the procedure fails due to the large size of the stones or long stenosis. Combined endoscopic and external approaches constitute a therapeutic alternative in such situations. Objective: Analyze the benefits of conservative treatment of parotid and submandibular gland in large stones. Place of setting: Hospital de la Policía Federal Argentina Churruca-Visca and Hospital Italiano de Buenos Aires. Argentina...

Introdução: o tratamento tradicional dos grandes cálculos das glândulas salivares (parótida e submandibular) implica a exérese da glândula. A sialoendoscopia preserva os órgãos pois permite diagnosticar e tratar as patologias obstrutivas salivares secundárias a alterações em seus condutos. A taxa de sucesso da sialoendoscopia intervencionista é aproximadamente 80%, e a falha em 20% remanescente é devido ao grande tamanho dos cálculos ou a estenoses longas. As abordagens combinadas endoscópicas e externas oferecem uma alternativa terapêutica. Objetivos: Analisar os benefícios do tratamento conservador da glândula parótida e submandibular com cálculos grandes. Local de aplicação: Hospital de la Policía Federal Argentina Churruca-Visca y Hospital Italiano de Buenos Aires. Argentina...

Biocatalytic trifluoromethylation of unprotected phenols.

Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals. Despite tremendous progress within the area of fluorination chemistry, methods for the direct introduction of fluoroalkyl-groups into organic molecules without prefunctionalization are still highly desired. Here we present a concept for the introduction of the trifluoromethyl group into unprotected phenols by employing a biocatalyst (laccase), tBuOOH, and either the Langlois' reagent or Baran's zinc sulfinate. The method relies on the recombination of two radical species, namely, the phenol radical cation generated directly by the laccase and the CF3-radical. Various functional groups such as ketone, ester, aldehyde, ether and nitrile are tolerated. This laccase-catalysed trifluoromethylation proceeds under mild conditions and allows accessing trifluoromethyl-substituted phenols that were not available by classical methods.

Vinylation of Unprotected Phenols Using a Biocatalytic System.

Readily available substituted phenols were coupled with pyruvate in buffer solution under atmospheric conditions to afford the corresponding para-vinylphenol derivatives while releasing only one molecule of CO2 and water as the by-products. This transformation was achieved by designing a biocatalytic system that combines three biocatalytic steps, namely the C-C coupling of phenol and pyruvate in the presence of ammonia, which leads to the corresponding tyrosine derivative, followed by deamination and decarboxylation. The biocatalytic transformation proceeded with high regioselectivity and afforded exclusively the desired para products. This method thus represents an environmentally friendly approach for the direct vinylation of readily available 2-, 3-, or 2,3-disubstituted phenols on preparative scale (0.5 mmol) that provides vinylphenols in high yields (65-83 %).

Cirugía transoral robótica en otorrinolaringología / Transoral robotic surgery in otolaryngology

La cirugía robótica constituye uno de los avances más novedosos de la medicina de las últimas décadas y el que ha sido más beneficioso para los pacientes. Su aporte fue fundamental para diferentes procedimientos quirúrgicos, al agilizar la cirugía y aumentar su precisión. Actualmente, su utilización en las diferentes especialidades médicas, como la cirugía de cabeza y cuello, permite realizar abordajes mínimamente invasivos, evitando las grandes incisiones externas y reduciendo de esta manera la morbilidad y el tiempo de internación. (AU)

Robotic surgery is one of the advances of medicine in recent decade that has been more novel and beneficial to patients. Its contribution was very important to different surgical procedures, decreasing surgical time and increasing its accuracy. Currently, its use in different medical specialties, such as head and neck surgery, allows minimally invasive approaches, avoiding large external incisions, thereby reducing morbidity and length of stay. (AU)

Chemoenzymatic asymmetric synthesis of 1,4-benzoxazine derivatives: application in the synthesis of a levofloxacin precursor.

A versatile and general route has been developed for the asymmetric synthesis of a wide family of 3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazines bearing different pattern substitutions in the aromatic ring. Whereas hydrolases were not suitable for resolution of these racemic cyclic nitrogenated amines, alternative chemoenzymatic strategies were designed through independent pathways leading to both amine antipodes. On one hand, bioreduction of 1-(2-nitrophenoxy)propan-2-ones allowed the recovery of the enantiopure (S)-alcohols in high yields using the alcohol dehydrogenase from Rhodococcus ruber (ADH-A), whereas evo-1.1.200 ADH led to their counterpart (R)-enantiomers also with complete selectivity and quantitative conversion. Alternatively, lipase-catalyzed acetylation of these racemic alcohols, and the complementary hydrolysis of the acetate analogues, gave access to the corresponding optically enriched products with high stereodiscrimination. Particularly attractive was the design of a chemoenzymatic strategy in six steps for the production of (S)-(-)-7,8-difluoro-3-methyl-3,4-dihydro-2H-benzo-[b][1,4]oxazine, which is a key precursor of the antimicrobial agent Levofloxacin.

A synthetic biology approach for the transformation of l-α-amino acids to the corresponding enantiopure (R)- or (S)-α-hydroxy acids.

Combinatorial assembly and variation of promoters on a single expression plasmid allowed the balance of the catalytic steps of a three enzyme (l-AAD, HIC, FDH) cascade in E. coli. The designer cell catalyst quantitatively transformed l-amino acids to the corresponding optically pure (R)- and (S)-α-hydroxy acids at up to 200 mM substrate concentration.

Evaluación endoscópica de la deglución. Resultados en pacientes con tumores benignos y malignos de laringe y hipofaringe, tratados con cirugía transoral con láser de CO2 / Functional endoscopic evaluation of swallowing. Results inpatients with benign and malignant tumors of the larynx and hypopharynx treated with transoral CO2 laser surgery / A avaliação endoscópica da deglutição. Os resultados em pacientes com tumores benignos e malignos da laringe e hipofaringe tratados com cirurgia transoral laser de CO2

La utilización del LASER de CO2 en laringología comenzó en la década del ‘80, permitiendo la exéresis de tumores por vía transoral. Su indicación se basa en los excelentes resultados oncológicos. La función deglutoria postquirúrgica es un factor importante en la calidad de vida de los pacientes con cáncer del tracto aerodigestivo superior. Los resultados de la deglución son relevantes para elegir la modalidad terapéutica, la cual debe ser no sólo efectiva en controlar el cáncer sino también en preservar la función del órgano. El grado y el tipo de alteración deglutoria deben ser determinados en forma precisa, para establecer el tratamiento postoperatorio adecuado. Esto es posible mediante estudios como la videodeglución y la evaluación endoscópica de la deglución (FEESST)...

The CO2 laser have been used for treatment of laryngeal cancers since 1980, with excellent oncological results. The swallowing plays an important roll in superior aerodigestive cáncer patient. Swallowing results are relevant to choose the therapeutic modality, which must be effective in controlling not only cancer but also in preserving organ function. The degree and type of swallowing impairment must be determined precisely, to establish the appropriate postoperative treatment. This is possible through studies like videodeglucion and endoscopic evaluation of swallowing (FEESST)...

O uso do laser de CO2 laringologia começou nos anos 80, permitindo a excisão tumor transoral. A indicação baseia-se nos excelentes resultados oncológicos. Função de deglutição pós-cirúrgico é uma importante qualidade de vida de pacientes com câncer do fator trato aerodigestivo superior. Engolindo resultados são relevantes para escolher a modalidade terapêutica, que deve ser eficaz no controle não só do câncer, mas também em preservar a função do órgão. O grau e tipo de comprometimento da deglutição deve ser determinada com precisão, para estabelecer o tratamento pós-operatório adequado. Isso é possível através de estudos como videodeglucion e avaliação endoscópica da deglutição (FEESST)...

Stereoselective synthesis of γ-hydroxynorvaline through combination of organo- and biocatalysis.

An efficient route for the synthesis of all four diastereomers of PMP-protected α-amino-γ-butyrolacton to access γ-hydroxynorvaline was established. The asymmetric key steps comprise an organocatalytic Mannich reaction and an enzymatic ketone reduction. Three reaction steps could be integrated in a one-pot process, using 2-PrOH both as solvent and as reducing agent. The sequential construction of stereogenic centres gave access to each of the four stereoisomers in high yield and with excellent stereocontrol.

Biocontrolled formal inversion or retention of L-α-amino acids to enantiopure (R)- or (S)-hydroxyacids.

Natural L-α-amino acids and L-norleucine were transformed to the corresponding α-hydroxy acids by formal biocatalytic inversion or retention of absolute configuration. The one-pot transformation was achieved by a concurrent oxidation reduction cascade in aqueous media. A representative panel of enantiopure (R)- and (S)-2-hydroxy acids possessing aliphatic, aromatic and heteroaromatic moieties were isolated in high yield (67-85 %) and enantiopure form (>99 % ee) without requiring chromatographic purification.

One-pot synthesis of enantiopure 3,4-dihydroisocoumarins through dynamic reductive kinetic resolution processes.

A straightforward chemoenzymatic synthesis of enantiopure 4-alkyl-3-methyl-3,4-dihydroisocoumarins through a ketoreductase-catalyzed one-pot dynamic reductive kinetic resolution is reported. E. coli/ADH-A cells have shown outstanding diastereo- and enantioselectivity toward the bioreduction of a series of racemic ketones, with the use of anion exchange resins or triethylamine being compatible in the same aqueous reaction medium. The so-obtained enantiopure alcohols were subsequently cyclized in acid media affording the corresponding lactones in good to excellent conversions (72-96%) and excellent selectivities (dr ≥99:1 and ee >99%).

Analysis of beer volatiles by polymeric imidazolium-solid phase microextraction coatings: Synthesis and characterization of polymeric imidazolium ionic liquids.

Two polymeric ionic liquids, 3-(but-3″-en-1″-yl)-1-[2'-hydroxycyclohexyl]-1H-imidazol-3-ium bis(trifluoromethanesulfonyl)imide (IL-1) and 1-(2'-hydroxycyclohexyl)-3-(4″-vinylbenzyl)-1H-imidazol-3-ium bis(trifluoromethylsulfonyl)imide (IL-2), have been synthesized by a free radical polymerization reaction and used as coatings for solid-phase microextraction (SPME). These new fibers exhibit good film stability, high thermal stability (270-290°C) and long lifetimes, and are used for the extraction of volatile compounds in lemon beer using gas chromatography separation and flame ionization detection. The scanning electron micrographs of the fiber surface revealed a polymeric ionic liquid (PIL) film, which is distributed homogeneously on the fiber. The developed PIL fiber showed good linearity between 50 and 2000µg/L with regression coefficients in the range of 0.996-0.999. The relative standard deviations (RSD) obtained in the peak area were found to vary between 1% and 12%, which assured that adequate repeatability was achieved. The spiked recoveries for three beer samples ranged from 78.4% to 123.6%. Experimental design has been employed in the optimization of extraction factors and robustness assessment. The polymeric IL-1 butenyl fiber showed a greater efficiency compared to the PDMS-DVB (65µm) and CAR-PDMS (75µm) for the extraction of all of the analytes studied.

Chiral triazolium salts and ionic liquids: from the molecular design vectors to their physical properties through specific supramolecular interactions.

An exhaustive experimental study based on X-ray diffraction analysis, NMR, FTIR-ATR (attenuated total reflection), and Raman spectroscopy as well as theoretical calculations is reported in order to understand how the non-covalent intermolecular contacts are fundamental to explain structure-property relationships and allowing us to correlate a basic macroscopic property (i.e., the melting point, T(m)) with the structural variables of a family of enantiopure 1,4-dialkyl-1,2,4-triazolium salts. The effect of different structural vectors such as the ring size, the spatial disposition of the substituent, the substitution on the oxygen atom, the nature of the anion, or the N4 alkylation of the triazole on the intermolecular interactions of these chiral salts of a well-defined 3D structure is reported. The non-covalent intermolecular contacts mainly implicating the triazolium H3 proton are fundamental to explain structure-property relationships and, therefore, the physical properties of these new chiral salts, rather than simple anion-cation interactions. Overall, our findings highlight the importance of the specific supramolecular interactions for the understanding of the physical properties of triazolium salts and ionic liquids.

Stereoselective synthesis of 2,3-disubstituted indoline diastereoisomers by chemoenzymatic processes.

Racemic indolines including a variety of structural motifs such as C-2 and C-3 substitutions (alkyl or aryl), cis/trans relative stereochemistry and functionalization of the aromatic ring (fluoro, methyl or methoxy groups) have been efficiently prepared through Fischer indolization and subsequent diastereoselective reduction of the unprotected indoles. Combination of Candida antarctica lipase type A and allyl 3-methoxyphenyl carbonate has been identified as the best tandem for their kinetic resolutions, observing excellent stereodiscriminations for most of the tested indolines.

Asymmetric chemoenzymatic synthesis of ramatroban using lipases and oxidoreductases.

A chemoenzymatic asymmetric route for the preparation of enantiopure (R)-ramatroban has been developed for the first time. The action of lipases and oxidoreductases has been independently studied, and both were found as excellent biocatalysts for the production of adequate chiral intermediates under very mild reaction conditions. CAL-B efficiently catalyzed the resolution of (±)-2,3,4,9-tetrahydro-1H-carbazol-3-ol that was acylated with high stereocontrol. On the other hand, ADH-A mediated bioreduction of 4,9-dihydro-1H-carbazol-3(2H)-one provided an alternative access to the same enantiopure alcohol previously obtained through lipase-catalyzed resolution, a useful synthetic building block in the synthesis of ramatroban. Inversion of the absolute configuration of (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol has been identified as a key point in the synthetic route, optimizing this process to avoid racemization of the azide intermediate, finally yielding (R)-ramatroban in enantiopure form by the formation of the corresponding amine and the convenient functionalization of both exocyclic and indole nitrogen atoms.

Highly stereoselective chemoenzymatic synthesis of the 3H-isobenzofuran skeleton. Access to enantiopure 3-methylphthalides.

A straightforward synthesis of (S)-3-methylphthalides has been developed, with the key asymmetric step being the bioreduction of 2-acetylbenzonitriles. Enzymatic processes have been found to be highly dependent on the pH value, with acidic conditions being required to avoid undesired side reactions. Baker's yeast was found to be the best biocatalyst acting in a highly stereoselective fashion. The simple treatment of the reaction crudes with aqueous HCl has provided access to enantiopure (S)-3-methylphthalides in moderate to excellent yields.

Polymeric imidazolium ionic liquids as valuable stationary phases in gas chromatography: chemical synthesis and full characterization.

Seven new functionalized polymerizable ionic liquids were chemically prepared, and later applied for the preparation of polymeric stationary phases in gas chromatography. These coated GC columns, which exhibited good thermal stabilities (240-300°C) and very high efficiencies (3120-4200 plates/m), have been characterized using the Abraham solvation parameter model. The chromatographic behavior of these polymeric IL columns has been deeply studied observing excellent selectivities in the separation of many organic substances such as alkanes, ketones, alcohols, amines or esters in mixtures of polar and non polar solvents or fragrances. Remarkably, the challenging separation of xylene isomers has been possible using a bis(trifluoromethylsulfonyl)amide based imidazolium IL coated column as a gas chromatography stationary phase.