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Introduction: Despite recent advances in applied instruments and surgical techniques, the incidence of iatrogenic durotomies caused by traditional techniques remains significant. The ultrasonic bone scalpel (UBS) has been shown to improve speed and reduce complications in laminectomies in the cervical and thoracic spine when compared to traditional methods utilizing high-speed burr, punch forceps, or rongeurs. Thus, in this study, we aim to evaluate whether the use of the UBS in the lumbar spine would result in equivalent safety, efficacy, and patient-reported outcomes (PROs) improvement when compared to traditional methods of laminectomy. Methods: Data from a prospectively collected, single-institution registry was queried between January 1, 2019 and September 1, 2021 for patients with a primary diagnosis of lumbar stenosis who received a laminectomy (with or without fusion) using traditional methods or UBS method. Outcomes included 3-month and 12-month values for all PROs Measurement Information System (PROMIS) subdomains, Numerical Rating Scale (NRS) pain score, Oswestry Disability Index (ODI) percentage, Patient Health Questionnaire 9 (PHQ-9) score, operative complications, reoperations, and readmissions. Covariates selected for matching included age, operation type, and number of levels. A variety of statistical tests were utilized. Results: As per our findings, 2:1 propensity matching resulted in 64 "traditional group" patients and 32 "UBS group" patients. Post-match analysis found no differences between the traditional and UBS groups for demographic and baseline measures except for race and ethnicity. For the matched sample, no differences were noted in PROs, reoperations, or readmissions. There was a significant difference in rates of durotomies between the traditional and UBS groups (12.5% vs. 0.0%, p=0.049). Conclusions: Results showed the high-frequency oscillation technology implemented by the UBS helps to decrease the rate of injury to the dura, thus reducing the overall incidence of iatrogenic durotomies. We believe these data provide valuable information to surgeons and patients about the safety and efficacy of the UBS in performing lumbar laminectomies.
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Hearing loss (HL) is one of the most common sensory defects, of which X-linked nonsyndromic hearing loss (NSHL) accounts for only 1-2%. While a COL4A6 variant has been reported in a single Hungarian family with NSHL associated with inner ear malformation, causative role of COL4A6 variants and their phenotypic consequences in NSHL remain elusive. Here we report two families in which we identified a male member with X-linked HL. Each has inherited a rare hemizygous COL4A6 variant from their respective mothers, NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951 + 1 G > C. An in vitro minigene splicing assay revealed that c.951 + 1 G > T leads to skipping of exon 15, strongly suggesting a pathogenic role for this variant in the HL phenotype. The p.Gly1091Ala variant is classified as a variant of unknown significance based on the variant interpretation guidelines. This report provides evidence for variants in the COL4A6 gene resulting in X-linked NSHL. It highlights the importance of in-depth genetic studies in all family members in addition to the proband, especially in multiplex families, to determine the precise etiology of HL.
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Colágeno Tipo IV/genética , Pérdida Auditiva Sensorineural/genética , Femenino , Pérdida Auditiva Sensorineural/patología , Hemicigoto , Humanos , Masculino , Mutación Missense , LinajeRESUMEN
BACKGROUND: Mutations involving the closely linked GJB2 and GJB6 at the DFNB1 locus are a common genetic cause of profound congenital hearing loss in many populations. In some deaf GJB2 heterozygotes, a 309 kb deletion involving the GJB6 has been found to be the cause for hearing loss when inherited in trans to a GJB2 mutation. METHODS: We screened 2,376 probands from a National DNA Repository of deaf individuals. RESULTS: Fifty-two of 318 heterozygous probands with pathogenic GJB2 sequence variants had a GJB6 deletion. Additionally, eight probands had an isolated heterozygous GJB6 deletion that did not explain their hearing loss. In two deaf subjects, including one proband, a homozygous GJB6 deletion was the cause for their hearing loss, a rare occurrence not reported to date. CONCLUSION: This study represents the largest US cohort of deaf individuals harboring GJB2 and GJB6 variants, including unique subsets of families with deaf parents. Testing additional members to clarify the phase of GJB2/GJB6 variants in multiplex families was crucial in interpreting clinical significance of the variants in the proband. It highlights the importance of determining the phase of GJB2/GJB6 variants when interpreting molecular test results especially in multiplex families with assortative mating.
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Conexina 30/genética , Eliminación de Gen , Pruebas Genéticas/métodos , Pérdida Auditiva/genética , Conexina 26/genética , Femenino , Frecuencia de los Genes , Pruebas Genéticas/normas , Pérdida Auditiva/diagnóstico , Heterocigoto , Humanos , Masculino , Reacción en Cadena de la Polimerasa Multiplex/métodos , Reacción en Cadena de la Polimerasa Multiplex/normas , Linaje , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ADN/normasRESUMEN
The rate of reaction between N, N'-dicyclohexylbarbituric acid 1 and ethyl 2-isocyanatoacetate 2 is invariant with temperature. Positive orders in each reactant and dissociation of triethylammonium salts of 1 and product 3 at elevated temperature indicate that reaction occurs via a catalytic mechanism where changes to the positions of equilibria negate changes in the rate of the turnover-limiting step. A model for the consumption of 1 in a flow reactor accurately predicted the outcome of a laboratory-scale multivariate study.
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Barbitúricos/síntesis química , Preparaciones Farmacéuticas/síntesis química , Temperatura , Barbitúricos/química , Estructura Molecular , Preparaciones Farmacéuticas/químicaRESUMEN
Biederman's contemporary theory of basic visual object recognition (Recognition-by-Components) is based on structural descriptions of objects and presumes 36 visual primitives (geons) people can discriminate, but there has been no empirical test of the actual use of these 36 geons to visually distinguish objects. In this study, we tested for the actual use of these geons in basic visual discrimination by comparing object discrimination performance patterns (when distinguishing varied stimuli) of an acquired prosopagnosia patient (LB) and healthy control participants. LB's prosopagnosia left her heavily reliant on structural descriptions or categorical object differences in visual discrimination tasks versus the control participants' additional ability to use face recognition or coordinate systems (Coordinate Relations Hypothesis). Thus, when LB performed comparably to control participants with a given stimulus, her restricted reliance on basic or categorical discriminations meant that the stimuli must be distinguishable on the basis of a geon feature. By varying stimuli in eight separate experiments and presenting all 36 geons, we discerned that LB coded only 12 (vs. 36) distinct visual primitives (geons), apparently reflective of human visual systems generally.
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Reconocimiento Visual de Modelos/fisiología , Prosopagnosia/fisiopatología , Percepción Visual/fisiología , Adulto , Femenino , Humanos , MasculinoRESUMEN
An electrochemical cell coupled with a recycle loop through a transmission FTIR cell is employed in studies of two free radical organic reactions, the oxidation of allylic alcohols and the trifluoromethylation of heteroarenes. Rapid mixing through the recycle loop allows continuous monitoring of reaction progress. Electrochemical generation of free radicals allows their controlled mediation into the reaction mixture for more efficient reaction. Kinetic profiles provide mechanistic insight into reactions under electrochemical control.
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Electrochemical reactions are shown to be effective for the C-H functionalization of a number of heterocyclic substrates that are recalcitrant to conventional peroxide radical initiation conditions. Monitoring reaction progress under electrochemical conditions provides mechanistic insight into the C-H functionalization of a series of heterocycles of interest in medicinal chemistry.
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Carbono/química , Compuestos Heterocíclicos/química , Hidrógeno/químicaRESUMEN
N-N-linked dimeric indole alkaloids represent an unexplored class of natural products for which chemical synthesis has no practical solution. To meet this challenge, an electrochemical oxidative dimerization method was developed, which was applied as the pivotal step of the first total synthesis of dixiamycin B. This method is also general for N-N dimerization of substituted carbazoles and ß-carbolines, providing entry into seldom explored chemical space.
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Electroquímica/métodos , Sesquiterpenos/síntesis química , Oxidación-Reducción , Sesquiterpenos/químicaRESUMEN
We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern. We demonstrate the potential of this building-block approach by synthesizing oligomers with different numbers and spacing of carbohydrates and also show the feasibility of heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides.
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The present protocol details the synthesis of zinc bis(alkanesulfinate)s that can be used as general reagents for the formation of radical species. The zinc sulfinates described herein are generated from the corresponding sulfonyl chlorides by treatment with zinc dust. The products may be used crude, or a simple purification procedure may be performed to minimize incorporation of water and zinc chloride. Although the synthesis of the zinc sulfinate salts can generally be completed within 3 h, workup can take up to 24 h and purification can take up to 3 h. Following the steps in this protocol would enable the user to generate a small toolkit of zinc sulfinate reagents over the course of 1 week.
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Alcanosulfonatos/química , Alcanosulfonatos/aislamiento & purificación , Descubrimiento de Drogas/métodos , Mesilatos/química , Mesilatos/aislamiento & purificación , Estructura Molecular , Ácidos Sulfínicos/química , Zinc/químicaRESUMEN
Poly/oligo(amidoamine)s (PAAs) have recently been recognised for their potential as well-defined scaffolds for multiple carbohydrate presentation and as multivalent ligands. Herein, we report two complimentary strategies for the preparation of such sequence-defined carbohydrate-functionalised PAAs that use photochemical thiol-ene coupling (TEC) as an alternative to the established azide-alkyne cycloaddition ("click") reaction. In the first approach, PAAs that contained multiple olefins were synthesised on a solid support from a new building block and subsequent conjugation with unprotected thio-carbohydrates. Alternatively, a pre-functionalised building block was prepared by using TEC and assembled on a solid support to provide a carbohydrate-functionalised PAA. Both methods rely on the use of a continuous flow photoreactor for the TEC reactions. This system is highly efficient, owing to its short path length, and requires no additional radical initiator. Performing the reactions at 254 nm in Teflon AF-2400 tubing provides a highly efficient TEC procedure for carbohydrate conjugation, as demonstrated in the reactions of O-allyl glycosides with thiols. This method allowed the complete functionalisation of all of the reactive sites on the PAA backbone in a single step, thereby obtaining a defined homogeneous sequence. Furthermore, reaction at 366 nm in FEP tubing in the flow reactor enabled the large-scale synthesis of an fluorenylmethyloxycarbonyl (Fmoc)-protected glycosylated building block, which was shown to be suitable for solid-phase synthesis and will also allow heterogeneous sequence control of different carbohydrates along the oligomeric backbone. These developments enable the synthesis of sequence-defined carbohydrate-functionalised PAAs with potential biological applications.
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Alquinos/química , Carbohidratos/síntesis química , Oligonucleótidos/química , Polímeros/química , Compuestos de Sulfhidrilo/química , Secuencia de Carbohidratos , Carbohidratos/química , Glicósidos , Ligandos , Estructura Molecular , Fotoquímica , Técnicas de Síntesis en Fase Sólida , EstereoisomerismoRESUMEN
Continuous synthesis meets continuous purification to produce pure products from crude reaction mixtures. In the nucleophilic aromatic substitution of 2,4-difluoronitrobenzene with morpholine the desired monosubstituted product can be continuously separated from the byproducts in a purity of over 99 % by coupling a flow reactor to a simulated moving bed (SMB) chromatography module.
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Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.
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Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with moderate to high diastereoselectivity.
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Compuestos Alílicos/química , Azidas/química , Estructura Molecular , EstereoisomerismoRESUMEN
An efficient, safe and scalable procedure for the continuous flow thermolysis of azidoacrylates to yield indoles has been developed and was applied to the synthesis of related heterocycles. The scalability of the process was demonstrated in the continuous flow synthesis of a precursor to the DAAO inhibitor 4H-furo[3,2-b]pyrrole-5-carboxylic acid.
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Acrilatos/química , Indoles/química , Azidas/química , D-Aminoácido Oxidasa/antagonistas & inhibidores , D-Aminoácido Oxidasa/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Hidrólisis , Indoles/síntesis química , Prolina/análogos & derivadosRESUMEN
A study of the effects of exopericyclic stereocentres on the stereoselectivity of Johnson-Claisen rearrangements of thioether-containing allylic alcohols shows that selectivity is highly dependent upon allylic substitution patterns.