Expeditious Strategy Research Articles

Revisiting the Role of Balloon Atrial Septostomy Prior to the Arterial Switch Operation.

Patients with dextro-transposition of the great arteries (d-TGA) frequently undergo balloon atrial septostomy (BAS) prior to the arterial switch operation (ASO) to promote atrial-level mixing. Balloon atrial septostomy has inherent risks as an invasive procedure and may not always be necessary. This study revisits the routine utilization of BAS prior to ASO. Single-center, retrospective review of d-TGA patients undergoing the ASO from July 2018 to March 2023. Preoperative patient characteristics, pulse oximetry oxygen saturations (SpO2), cerebral/renal near-infrared spectroscopy (NIRS) readings along with prostaglandin status at the time of the ASO were analyzed with descriptive and univariate statistics. Thirty patients underwent the ASO. Of these, 7 (23%) were female, 25 (83%) were white, and median weight at ASO was 3.2 kg (range 0.8-4.2). Twenty-two (73%) patients underwent BAS. There were no demographic differences between BAS and no-BAS patients. Of those who underwent BAS, there was a significant increase in SpO2 (median 83% [range 54-92] to median 87% [range 72-95], P = .007); however, there was no change in NIRS from pre-to-post BAS. Six (27%) patients in the BAS group were prostaglandin-free at ASO. Balloon atrial septostomy patients underwent the ASO later compared with no-BAS patients (median 8 [range 3-32] vs 4 [range 2-10] days old, P = .016) and had a longer hospital length of stay (median 13 [range 7-43] vs 10 [range 8-131] days, P = .108). While BAS is an accepted preoperative procedure in d-TGA patients to improve oxygen saturations, it is also an additional invasive procedure, does not guarantee prostaglandin-free status at the time of ASO, and may increase the interval to ASO. Birth to direct early ASO, with prostaglandin support, should be revisited as an alternative, potentially more expeditious strategy.

A Metal‐Free KOtBu‐Mediated Protocol towards the Synthesis of Quinolines, Indenoquinolines and Acridines

AbstractAn expeditious strategy has been developed for the synthesis of diverse quinolines, indenoquinolines and acridines using KOtBu‐mediated reaction conditions. The designed process utilizes 2‐aminoaryl carbaldehydes/2‐aminoaryl ketones and methyl/methylene group containing ketones as readily available feedstock. The chemical transformation was affected at room temperature within a short duration of time to obtain diverse N‐heterocycles yields up to 92 %. The established process also exhibits considerable functional group tolerance with an operational simplicity.

Expedient Synthesis of Superarmed Glycosyl Donors via Oxidative Thioglycosidation of Glycals.

Superarmed glycosyl donors have higher reactivity compared to their perbenzylated armed counterparts. Generally, the 2-O- benzoyl-3,4,6-tri-O-benzyl protecting group pattern gives rise to increased reactivity due to an O-2/O-5 cooperative effect. Despite having a high reactivity profile and applicability in many expeditious strategies for glycan synthesis, regioselective introduction of the superarming protecting group pattern is tedious for most sugar series. Reported herein is a streamlined synthetic route to yield superarmed glycosyl donors of the d-gluco and d-galacto series equipped with an ethylthio, phenylthio, p-tolylthio, benzoxazol-2-ylthio, O-allyl, or O-pentenyl anomeric leaving group. This streamlined approach was made possible due to the refinement of the oxidative thioglycosylation reaction of the respective glucal and galactal precursors. The applicability of this approach to the direct formation of disaccharides is also showcased.

El diseño utilitario

Given the limitations of the expediency/conservation dichotomy for understanding the lithic assemblages from the first millennium in Antofagasta de la Sierra (Catamarca, Argentina), the utilitarian design proposal constitutes progress toward understanding the specific technology of agropastoral societies. The term raised the issue that the lack of conservation-related elements poses for describing the material product of an expeditious strategy. The proposal subsequently supported efforts to estimate the work that the formative societies of Northwestern Argentina invested in lithic production. This research revisits its contributions, applying them to the knapped stone assemblage of Structure 4 (E4) at the Las Escondidas site (Quebrada de Miriguaca, Antofagasta de la Sierra) – a site occupied at the beginning of the first millennium, that shows different activities, including artisan production. Reconstructing some aspects of the technological behavior involved in the production, use and disposal of the instrument set at E4 gave rise to several reflections on the scope and applicability of the utilitarian design concept in relation to work investment.

Irritability in Huntington's Disease.

Huntington’s disease (HD) is a heritable and fatal neurodegenerative disease characterized by a triad of motor, cognitive and neuropsychiatric symptoms. A common and particularly detrimental neuropsychiatric alteration in HD gene carriers is irritability, which frequently manifests as abrupt and unpredictable outbursts of anger. This symptom increases the burden of HD in multiple ways, such as jeopardizing employment and straining familial or caregiver support. Although irritability in HD is diagnosed by the administration of standardized rating scales and clinical expertise, measurement of severity and progression is complicated by several factors. Currently, individuals with HD who present with irritability may be managed with a variety of psychotropic medications, primarily antidepressants and antipsychotics. While these therapies offer relief to individuals suffering from irritability in HD, they are often not sufficient. Here, we review irritability in the context of HD and emphasize the need for treatments that are better tailored to mitigate this troublesome symptom. An expeditious strategy in pursuit of this goal involves evaluating the efficacy of approved medications that are used to treat similar neuropsychiatric symptoms.

Household flooring associated with reduced infant diarrhoeal illness in Zimbabwe in households with and without WASH interventions.

Diarrhoeal illness is a leading cause of childhood morbidity and mortality and has long-term negative impacts on child development. Although flooring, water and sanitation have been identified as important routes of transmission of diarrhoeal pathogens, research examining variability in the association between flooring and diarrhoeal illness by water and sanitation is limited. We utilised cross-sectional data collected for the evaluation of Zimbabwe's Prevention of Mother-to-Child HIV transmission programme in 2014 and 2017-18. Mothers of infants 9-18months of age self-reported the household's source of drinking water and type of sanitation facility, as well as infant diarrhoeal illness in the four weeks prior to the survey. Household flooring was assessed using interviewer observation, and households in which the main material of flooring was dirt/earthen were classified as having unimproved flooring, and those with solid flooring (e.g. cement) were classified as having improved flooring. Mothers of infants living in households with improved flooring were less likely to report diarrhoeal illness in the last four weeks (PDa =-4.8%, 95% CI: -8.6, -1.0). The association between flooring and diarrhoeal illness did not vary by the presence of improved/unimproved water (pRERI =0.91) or sanitation (pRERI =0.76). Our findings support the hypothesis that household flooring is an important pathway for the transmission of diarrhoeal pathogens, even in settings where other aspects of sanitation are sub-optimal. Improvements to household flooring do not require behaviour change and may be an effective and expeditious strategy for reducing childhood diarrhoeal illness irrespective of household access to improved water and sanitation.

Divergent Access to Imidazopyrazinones and Imidazodiazepinones by Regioswitchable Post‐Ugi Heteroannulation

A metal‐free expeditious strategy for the divergent synthesis of structurally diverse bicyclic imidazo[1,5‐a]pyrazine and imidazo[1,5‐a][1,4]diazepine scaffolds is disclosed by combining an Ugi four‐component reaction of easily available building blocks and an exo/endo selectivity‐switchable post‐Ugi intramolecular heterocyclization. Using PPh3, the intramolecular umpolung aza‐Michael addition is mediated to selectively generate imidazopyrazinones through a 6‐exo‐dig cyclization, while without PPh3 fused imidazodiazepinones are obtained through a thermal 7‐endo‐dig cyclization in moderate yields.

Tecnología lítica de cazadores y pastores andinos: cambios y continuidades en la explotación de recursos líticos durante el Holoceno en el NO de San Juan

En este trabajo se analizan y comparan aspectos de la organización tecnológica de grupos cazadores-recolectores, transicionales y pastores que ocuparon los ambientes de altura del NO de San Juan. En una escala meso espacial y a partir del estudio de la base regional de recursos líticos se realizan análisis de procedencia, secuencias reductivas, variabilidad artefactual y clases técnicas de un registro correspondiente a tres segmentos temporales del Holoceno. El análisis lítico correspondiente a cazadores-recolectores indica la implementación de estrategias expeditivas y conservadas, caracterizadas por predominio de rocas locales, de actividades de formatización de artefactos y de instrumentos con baja y alta inversión de trabajo. El registro de grupos con economías diversificadas indica el desarrollo fundamentalmente de estrategias expeditivas, caracterizadas por el predominio de rocas locales, de actividades para la obtención de soportes y de artefactos con baja inversión de trabajo. Además, se incrementan rocas de procedencia indeterminada, hay mayor variabilidad artefactual, disminuyen las tareas de formatización y las piezas con alta inversión de trabajo. Se detectó la continuidad de la caza como actividad económica y de sistemas de producción lítica secuenciales y regionales que involucran el desarrollo de tareas diversas en tres sectores altitudinales.

Synthesis of pyrazolo[5,1-a]isoquinolines through copper-catalyzed regioselective bicyclization of N-propargylic sulfonylhydrazones

An expeditious strategy for the synthesis of pyrazolo[5,1-a]isoquinolines through copper(ii)-catalyzed regioselective bicyclization of N-propargylic sulfonylhydrazones has been developed.

An expedited approach for sustained delivery of bone morphogenetic protein-7 to bone defects using gene activated fragments of subcutaneous fat.

Delivery of bone morphogenetic protein-7 (BMP-7) to bone defects can be improved by applying gene transfer methods. However, traditional ex vivo gene therapy approaches are cumbersome and costly, requiring the extraction and culturing of cells. Therefore, we evaluated a novel, expedited ex vivo BMP-7 gene transfer technology based on the use of fragments of subcutaneous fat tissue. We created 5-mm mid-femoral bone defects in the right femora of 23 male, syngeneic Fischer 344 rats. Adipose tissue was harvested from the subcutaneous fat depot of two donor rats. Bone defects were treated with either unmodified fat (control group) or adenovirally BMP-7 transduced fat fragments (treatment group). Healing of bone defects was assessed by radiographs, microcomputed tomography (μCT) and histology at 6 weeks after the implantation of fat tissue fragments. Radiographs, μCT-imaging and histology revealed relevant bone formation in six out of 10 rats treated with BMP-7 activated fat grafts. Two of the defects were bridged. By contrast, femora of the control group receiving unmodified fat did not display signs of osseous healing. BMP-7 gene activated fat treatment led to a significantly higher bone volume (11.18 ± 9.48 mm(3) ) than treatment with unmodified fat grafts (3.19 ± 1.68 mm(3) ) (p = 0.008). Implantation of BMP-7 gene activated fat tissue fragments can elicit regeneration of large bone defects in rats and could become a clinically expeditious strategy for in vivo bone tissue engineering. However, gene expression must be improved in order to reliably induce osseous bridging of critical-size bone defects. Copyright © 2016 John Wiley & Sons, Ltd.

Turmeric Sesquiterpenoids: Expeditious Resolution, Comparative Bioactivity, and a New Bicyclic Turmeronoid.

An expeditious strategy to resolve turmerone, the lipophilic anti-inflammatory principle of turmeric (Curcuma longa), into its individual bisabolane constituents (ar-, α-, and β-turmerones, 2-4, respectively) was developed. The comparative evaluation of these compounds against a series of anti-inflammatory targets (NF-κB, STAT3, Nrf2, HIF-1α) evidenced surprising differences, providing a possible explanation for the contrasting data on the activity of turmeric oil. Differences were also evidenced in the profile of more polar bisabolanes between the Indian and the Javanese samples used to obtain turmerone, and a novel hydroxylated bicyclobisabolane ketol (bicycloturmeronol, 8) was obtained from a Javanese sample of turmeric. Taken together, these data support the view that bisabolane sesquiterpenes represent an important taxonomic marker for turmeric and an interesting class of anti-inflammatory agents, whose strict structure-activity relationships are worth a systematic evaluation.

Cloning, expression and purification flagellar sheath adhesion of Helicobacter pylori in Escherichia coli host as a vaccination target.

PurposeHelicobacter pylori is a widely distributed gram-negative bacterium that infects the human stomach and duodenum. HpaA is a H. pylori–specific lipoprotein that has been shown to be an effective protective antigen against H. pylori infection. HpaA of H. pylori as a vaccine antigen is fully competent for stimulation of immune responses. The aim of this project is cloning, expression, and purification flagellar sheath adhesion of H. pylori in Escherichia coli host by fast protein liquid chromatography (FPLC) as a vaccination target.Materials and MethodsThe hpaA gene was inserted into pET28a (+) as cloning and expression vectors respectively. The recombinant plasmid (pET-hpaA) was subjected to sequencing other than polymerase chain reaction (PCR) and digestion analysis. Protein expression was induced by adding 1 mM isopropyl-β-D-thiogalactoside to cultures of E. coli strain BL21 transformed with pET-hpaA. Protein expression assessed with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Protein purification of flagellar sheath adhesion was by FPLC.ResultsThe restriction endonuclease digestion, PCR amplification analysis showed that the hpaA gene of 730 bp was amplified from H. pylori DNA and sequencing analysis of the pET-hpaA confirmed the cloning accuracy and in frame insertion of hpaA fragment. SDS-PAGE analysis showed the expression of an approximately 29,000 Da protein.ConclusionSequencing results along with SDS-PAGE analysis confirms the expression of recombinant hpaA in the heterologous E. coli BL21. Conclusion A prokaryotic expression system for hpaA gene was successfully constructed. These results indicate that production of a specific recombinant protein is an alternative and potentially more expeditious strategy for development of H. pylori vaccine.

Rapid Synthesis of Unsymmetrical Sulforhodamines Through Nucleophilic Amination of a Monobrominated Sulfoxanthene Dye

AbstractA transition‐metal‐free method for the synthesis of N‐substituted unsymmetrical sulforhodamine fluorophores from an unusual monobrominated sulfoxanthene dye and primary or secondary amines by direct SNAr‐type reactions is presented. The simplicity and effectiveness of this “postamination” procedure were demonstrated through the rapid preparation of a library of multifunctional red‐emitting rhodamine analogues. Some of these analogues are equipped with a reactive handle and retain the two water‐solubilizing sulfonic acid moieties of the starting halogenated derivative; this makes them ideal candidates for biolabeling applications. The potential utility of this expeditious strategy to finely tune the photophysical (Stokes shift) and physicochemical properties (amphiphilic character and water solubility) of the sulforhodamine scaffold was also demonstrated through the appendage of a fluorescent amine to create a fluorescence resonance energy transfer (FRET) pair, a long‐chain amine, and tetraazamacrocycles derived from cyclen.

Comparing the Metabolome of a Caribbean Sponge to 420 FDA Approved Drugs, a Molecular Networking Approach

Historically, isolated natural products have provided an unparalleled starting point for drug discovery efforts. However, the dereplication and isolation of promising compounds remains difficult and time-consuming, especially when working with crude extracts. There is a need to create more expeditious strategies to determine the identity and potential activity of compounds early in the process. Molecular networking is a technique developed at UCSD that permits a visual comparison of different small molecules based upon the similarities of their MS/MS fragmentation patterns. One promising application of this technology is to guide the isolation and identification of compounds within extracts based upon their similarity to known compounds. Here we report the use of molecular networking to compare the most abundant metabolites of a sponge extract with 420 FDA approved compounds with known structures and activities. Unknown molecules showing similarities to known drugs were selected for structural elucidation by NMR and biochemical and in-silico assays.

ChemInform Abstract: Superarmed and Superdisarmed Building Blocks in Expeditious Oligosaccharide Synthesis

AbstractReview: 97 refs.

ChemInform Abstract: Expeditious Oligosaccharide Synthesis via Selective, Semi‐Orthogonal, and Orthogonal Activation

AbstractReview: 179 refs.

Expeditious oligosaccharide synthesis via selective, semi-orthogonal, and orthogonal activation

Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby increasing the total number of synthetic steps while decreasing the efficiency of the synthesis. In contrast, expeditious strategies allow for the rapid chemical synthesis of complex carbohydrates by minimizing extraneous chemical manipulations. Oligosaccharide synthesis by selective activation of one leaving group over another is one such expeditious strategy. Herein, the significant improvements that have recently emerged in the area of the selective activation are discussed. The development of orthogonal strategy further expands the scope of the selective activation methodology. Surveyed in this article, are representative examples wherein these excellent innovations have been applied to the synthesis of various oligosaccharide sequences.

Efficient Preparation of Terminal Conjugated Dienes by Coupling of Dienol Phosphates with Grignard Reagents under Iron Catalysis

An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.

Protective anti-Helicobacter immunity is induced with aluminum hydroxide or complete Freund's adjuvant by systemic immunization.

To determine whether systemic immunization against Helicobacter pylori could be achieved with an adjuvant approved for human use, the efficacy of vaccination with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was evaluated in a murine model of Helicobacter infection. Immunization with antigen and AlOH induced interleukin-5-secreting, antigen-specific T cells, and immunization with antigen and complete Freund's adjuvant induced interferon-gamma-secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune responses conferred protection after challenge with either H. pylori or H. felis, as confirmed by the complete absence of any bacteria, as assessed by both histology and culture of gastric biopsy samples. Protection was antibody independent, as demonstrated with antibody-deficient muMT mice (immunoglobulin-gene knockout mice), and CD4(+) spleen T cells from immunized mice were sufficient to transfer protective immunity to otherwise immunodeficient rag1(-/-) recipients. These results suggest an alternative and potentially more expeditious strategy for development of a human-use H. pylori vaccine.

ChemInform Abstract: A New and Expeditious Strategy for the Synthesis of β‐Amino Acids from Δ2‐Oxazolines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.