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BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/classificação , Fibrilação Atrial/cirurgia , Teorema de Bayes , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Recidiva , Método Simples-Cego , Taquicardia/etiologia , Resultado do TratamentoRESUMO
Lizards in the genus Anolis comprise hundreds of species that display a wide range of phenotypic variation closely related to their environment. One example is the Guadeloupean anole (Anolis marmoratus ssp.) that display extreme phenotypic variation, primarily in adult male color and pattern, with twelve described subspecies on the archipelago. Here we examine the relationship between phenotypic and genetic divergence among five subspecies on the two main islands and test the role of geographic isolation and the environment in reducing gene flow. We also examined two offshore island populations to assess the impact of complete geographic isolation on gene flow. We analyzed color phenotypes by measuring spectral reflectance and genomic diversity using SNPs. Genetic divergence was correlated with dorsolateral head and body color phenotypes, and slope and geographic distance were nearly equivalent at explaining this divergence. There was minimal genome-wide divergence at neutral loci among phenotypically disparate subspecies on the two main islands and their differentiation is consistent with a model of divergence with gene flow. Our spatial visualization of gene flow showed an impact of environmental features consistent with a hypothesis of ecologically driven divergence. Nonetheless, subspecies on the two main islands remain interconnected by substantial gene flow and their phenotypic variation is likely maintained at selection-gene flow equilibrium by divergent selection at loci associated with their color phenotypes. Greater isolation, such as inhabiting a remote island, may be required for reducing gene flow. Our findings highlight the role of the environment, adaptation, and geographic isolation on gene flow.
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Fluxo Gênico , Lagartos , Fenótipo , Lagartos/genética , Lagartos/classificação , Animais , Masculino , Genética Populacional , Variação Genética , Polimorfismo de Nucleotídeo Único , Meio Ambiente , Ilhas , Pigmentação/genética , Isolamento Reprodutivo , Geografia , Feminino , GuadalupeRESUMO
AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Estenose de Veia Pulmonar , Humanos , Veias Pulmonares/cirurgia , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Método Simples-Cego , Resultado do Tratamento , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/etiologiaRESUMO
AIMS: Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. METHODS AND RESULTS: The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.
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Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Ablação por Cateter/métodos , Resultado do Tratamento , Veias Pulmonares/cirurgia , Feminino , Masculino , Recidiva , Europa (Continente) , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Fecal calprotectin (FC) serves as a non-invasive marker for the assessment of gut inflammation in patients with inflammatory bowel disease (IBD). Laboratory measurements are usually performed with immunologic methods like enzyme-linked immunosorbent assay. Recently, quantitative home tests based on the lateral flow technology with smartphones as read-out devices have been developed. We compared the quantitative and qualitative performance of the quantitative lateral flow home test Preventis SmarTest® Calprotectin Home and the immunological test used in our laboratory (Eurospital Calprest® Turbo). METHODS: Fourty-five routine samples were analyzed in parallel with both tests according to the manufacturer's instructions. The read-out of the home test was performed with two smartphones (Apple iPhone 14 Pro and Samsung Galaxy XCover 5). The qualitative interpretation (positive, negative, borderline) was conducted using the cut-offs provided by the manufacturers. RESULTS: Statistically significant correlations with the laboratory standard method were observed for both smartphones (Spearman's rho 0.703 and 0.715, all p<0.005). The home test showed systematically higher concentrations compared to the routine assay. We found minimal qualitative agreement between the two tests (Cohen's kappas (κ)=0.323 and 0.300; p=0.003 and 0.005) showing a lower rate of positives with the home test. Both used smartphones showed good quantitative and qualitative agreement. CONCLUSIONS: The tests are quantitatively not interchangeable. However, the home test may be applicable for the serial follow-up management of patients with IBD. The higher rate of samples classified as negative with the home test may lead to an underestimation of affected patients.
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AIMS: Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. METHODS AND RESULTS: All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. CONCLUSION: The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.
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Fibrilação Atrial , Ablação por Cateter , Poria , Veias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/epidemiologia , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fluoroscopia , Veias Pulmonares/cirurgia , RecidivaRESUMO
BACKGROUND: Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. METHODS: This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). RESULTS: Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants. CONCLUSIONS: The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.
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Sequenciamento de Nucleotídeos em Larga Escala , Farmacogenética , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
BACKGROUND: Computed tomography angiography (CTA) has been widely used for perforator mapping in abdominal-based reconstruction, but it is less widespread in the anterolateral thigh (ALT) flap. However, CTA may be quite useful for ALT planning, as this flap has demonstrated substantial variability in intrapatient bilateral vascular anatomy. This study investigated whether standard use of preoperative CTA resulted in selection of the donor extremity with preferential perforator anatomy, and whether this affected operative time and postoperative outcomes. METHODS: A retrospective review of 105 patients who underwent proposed ALT flap reconstruction was performed. Seventy-nine patients received bilateral lower extremity CTAs, which were evaluated for dominant perforator anatomy (septocutaneous, musculoseptocutaneous, or musculocutaneous). Donor extremity selection was noted, and predicted perforator anatomy was compared with that encountered intraoperatively. RESULTS: Among the 73 patients who received bilateral imaging and ultimately received an ALT, congruent findings between imaging and surgical exploration were observed in 51 (69.8%) patients. Thirty (37.9%) patients had asymmetric perforator anatomy between their bilateral extremities on imaging. Among these, the leg with optimal perforator anatomy was selected in 70% of cases. There were no significant reductions among postoperative complication rates, but selection of the donor site with preferential anatomy was associated with a decrease in operative time (p = 0.049) among patients undergoing extremity reconstruction. CONCLUSION: CTA is a useful tool for optimizing donor site selection for ALT flaps and reducing operative time. We believe that standard use of preoperative CTA in ALTs warrants further consideration.
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Retalho Perfurante , Procedimentos de Cirurgia Plástica , Angiografia por Tomografia Computadorizada , Humanos , Duração da Cirurgia , Retalho Perfurante/irrigação sanguínea , Cuidados Pré-Operatórios/métodos , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Coxa da Perna/irrigação sanguíneaRESUMO
AIMS: Extra-atrial injury can cause complications after catheter ablation for atrial fibrillation (AF). Pulsed field ablation (PFA) has generated preclinical data suggesting that it selectively targets the myocardium. We sought to characterize extra-atrial injuries after pulmonary vein isolation (PVI) between PFA and thermal ablation methods. METHODS AND RESULTS: Cardiac magnetic resonance (CMR) imaging was performed before, acutely (<3 h) and 3 months post-ablation in 41 paroxysmal AF patients undergoing PVI with PFA (N = 18, Farapulse) or thermal methods (N = 23, 16 radiofrequency, 7 cryoballoon). Oesophageal and aortic injuries were assessed by using late gadolinium-enhanced (LGE) imaging. Phrenic nerve injuries were assessed from diaphragmatic motion on intra-procedural fluoroscopy. Baseline CMR showed no abnormality on the oesophagus or aorta. During ablation procedures, no patient showed phrenic palsy. Acutely, thermal methods induced high rates of oesophageal lesions (43%), all observed in patients showing direct contact between the oesophagus and the ablation sites. In contrast, oesophageal lesions were observed in no patient ablated with PFA (0%, P < 0.001 vs. thermal methods), despite similar rates of direct contact between the oesophagus and the ablation sites (P = 0.41). Acute lesions were detected on CMR on the descending aorta in 10/23 (43%) after thermal ablation, and in 6/18 (33%) after PFA (P = 0.52). CMR at 3 months showed a complete resolution of oesophageal and aortic LGE in all patients. No patient showed clinical complications. CONCLUSION: PFA does not induce any signs of oesophageal injury on CMR after PVI. Due to its tissue selectivity, PFA may improve safety for catheter ablation of AF.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Esôfago/diagnóstico por imagem , Esôfago/cirurgia , Átrios do Coração/cirurgia , Humanos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
AIMS: Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. thermal ablation. METHODS AND RESULTS: Cardiac magnetic resonance was performed pre-ablation, acutely (<3 h), and 3 months post-ablation in 41 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 18) or thermal ablation (n = 23, 16 radiofrequency ablations, 7 cryoablations). Late gadolinium enhancement (LGE), T2-weighted, and cine images were analysed. In the acute stage, LGE volume was 60% larger after PFA vs. thermal ablation (P < 0.001), and oedema on T2 imaging was 20% smaller (P = 0.002). Tissue changes were more homogeneous after PFA than after thermal ablation, with no sign of microvascular damage or intramural haemorrhage. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after thermal ablation. The maximum strain on PV antra, the LA expansion index, and LA active emptying fraction declined acutely after both PFA and thermal ablation but recovered at the chronic stage only with PFA. CONCLUSION: Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.
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Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Meios de Contraste , Fibrose , Gadolínio , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Humanos , Imageamento por Ressonância MagnéticaRESUMO
RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably.
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Ciprofloxacina/química , Riboswitch , Bioengenharia , Regulação da Expressão Gênica , Células HeLa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Ligantes , Mutação , Conformação de Ácido Nucleico , Técnica de Seleção de Aptâmeros , Saccharomyces cerevisiae/genéticaRESUMO
Pseudophilautus comprises an endemic diversification predominantly associated with the wet tropical regions of Sri Lanka that provides an opportunity to examine the effects of geography and historical climate change on diversification. Using a time-calibrated multi-gene phylogeny, we analyze the tempo of diversification in the context of past climate and geography to identify historical drivers of current patterns of diversity and distribution. Molecular dating suggests that the diversification was seeded by migration across a land-bridge connection from India during a period of climatic cooling and drying, the Oi-1 glacial maximum around the Eocene-Oligocene boundary. Lineage-through-time plots suggest a gradual and constant rate of diversification, beginning in the Oligocene and extending through the late Miocene and early Pliocene with a slight burst in the Pleistocene. There is no indication of an early-burst phase of diversification characteristic of many adaptive radiations, nor were there bursts of diversification associated with favorable climate shifts such as the intensification of monsoons. However, a late Miocene (8.8 MYA) back-migration to India occurred following the establishment of the monsoon. The back migration did not trigger a diversification in India similar to that manifest in Sri Lanka, likely due to occupation of available habitat, and consequent lack of ecological opportunity, by the earlier radiation of a sister lineage of frogs (Raorchestes) with similar ecology. Phylogenetic area reconstructions show a pattern of sister species distributed across adjacent mountain ranges or from different parts of large montane regions, highlighting the importance of isolation and allopatric speciation. Hence, local species communities are composed of species from disparate clades that, in most cases, have been assembled through migration rather than in situ speciation. Lowland lineages are derived from montane lineages. Thus, the hills of Sri Lanka acted as species pumps as well as refuges throughout the 31 million years of evolution, highlighting the importance of tropical montane regions for both the generation and maintenance of biodiversity.
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Anuros/classificação , Biodiversidade , Geografia , Animais , Filogenia , Sri Lanka , Fatores de TempoRESUMO
Described herein is a synthetic strategy for the total synthesis of (±)-phomoidrideâ D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.
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Anidridos Maleicos/síntese química , Compostos Bicíclicos com Pontes/química , Ciclização , Reação de Cicloadição , Oxirredução , EstereoisomerismoRESUMO
During the past years customized gene network design has become of tremendous interest among various disciplines in life science. The identification of artificial genetic elements sensitive to internal or external stimuli constitutes the foundation for the design and realization of conditional gene expression systems. Typically, strategies involving selection or screening steps are employed alongside approaches focusing on rational design to select for the desired functionality of a given element. Here we present a fluorescence-based in vivo screening approach that combines an initial in vitro selection with subsequent extensive screening steps and a final rational design to identify RNA based regulators in baker's yeast. These artificial RNA regulators, termed synthetic riboswitches, are derived from RNA aptamers. Our method allows for the separation of aptamers featuring the potential to be transformed into a riboswitch from those inherently unable to confer control over gene expression. The system may be applied to virtually all existing aptamer-ligand pairs and as such presents a powerful means to enhance the setup of switchable genetic circuits.
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Aptâmeros de Nucleotídeos/química , Riboswitch , Sequências Repetidas Invertidas , Técnica de Seleção de Aptâmeros , LevedurasRESUMO
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
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Aves/genética , Evolução Molecular , Genoma/genética , Lagartos/genética , Mamíferos/genética , Animais , Galinhas/genética , Sequência Rica em GC/genética , Genômica , Humanos , Dados de Sequência Molecular , Filogenia , Sintenia/genética , Cromossomo X/genéticaRESUMO
A stereocontrolled first total synthesis of muraymycin D1 (1) has been achieved. The synthetic route is highly stereoselective, featuring (1) selective ß-ribosylation of the C2-methylated amino ribose, (2) selective Strecker reaction, and (3) ring-opening reaction of a diastereomeric mixture of a diaminolactone to synthesize muraymycidine (epi-capreomycidine). The acid-cleavable protecting groups for secondary alcohol and uridine ureido nitrogen are applied for simultaneous deprotections with the Boc and tBu groups. Muraymycin D1 (1) and its amide derivatives (2 and 3) exhibited growth inhibitory activity against Mycobacterium tuberculosis (MIC50 = 1.56-6.25 µg/mL) and strong enzyme inhibitory activities against the bacterial phosphotransferases (MurX and WecA) (IC50 = 0.096-0.69 µM).
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Antibacterianos/síntese química , Antibacterianos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Peptídeos/síntese química , Peptídeos/farmacologia , Antibacterianos/química , Técnicas de Química Sintética , Testes de Sensibilidade Microbiana , Peptídeos/química , EstereoisomerismoRESUMO
Over the past five years a number of different synthesis approaches has been reported to obtain so-called 'black' titania. One of the outstanding features of the material is that certain synthesis processes lead to the formation of an intrinsic co-catalytic center and thus enable noble-metal free photocatalytic H2 -generation. In the present work, using TiO2 nanotube layers, we compare three common 'blackening' approaches, namely i)â the original high-pressure hydrogenation (HPT-H2 ), ii)â a classic high temperature reduction in Ar, and iii) an electrochemical (cathodic) reduction. We demonstrate that except for high pressure hydrogenation also cathodic reduction leads to an activation of TiO2 - that is, it exhibits noble-metal-free photocatalytic H2 generation. Moreover, we show that a combination of cathodic reduction/high pressure hydrogenation leads to a synergistic effect, that is, a significant enhancement of the combined co-catalytic activity.
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Here we report that TiO2 nanotube (NT) arrays, converted by a high pressure H2 treatment to anatase-like "black titania", show a high open-circuit photocatalytic hydrogen production rate without the presence of a cocatalyst. Tubes converted to black titania using classic reduction treatments (e.g., atmospheric pressure H2/Ar annealing) do not show this effect. The main difference caused by the high H2 pressure annealing is the resulting room-temperature stable, isolated Ti(3+) defect-structure created in the anatase nanotubes, as evident from electron spin resonance (ESR) investigations. This feature, absent for conventional reduction, seems thus to be responsible for activating intrinsic, cocatalytic centers that enable the observed high open-circuit hydrogen generation.
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The high-pressure hydrogenation of commercially available anatase or anatase/rutile TiO2 powder can create a photocatalyst for H2 evolution that is highly effective and stable without the need for any additional co-catalyst. This activation effect cannot be observed for rutile; however, for anatase/rutile mixtures, a strong synergistic effect can be found (similar to results commonly observed for noble-metal-decorated TiO2). EPR and PL measurements indicated the intrinsic co-catalytic activation of anatase TiO2 to be due to specific defect centers formed during hydrogenation. These active centers can be observed specifically for high-pressure hydrogenation; other common reduction treatments do not result in this effect.
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BACKGROUND: Many complex abdominal hernias are referred to tertiary academic institutions for evaluation and treatment. The purpose of this study was to compare clinical outcomes from complex abdominal hernia repairs and abdominal wall reconstructions at a community hospital vs high volume academic centers participating in Abdominal Core Health Quality Collaborative (ACHQC). METHODS: Patients undergoing elective complex abdominal hernia repair were identified in our community setting and treated between 2016 and 2019. These results were then compared to Academic centers in the ACHQC database. Complex hernia definition was limited to those who have undergone any myofascial advancement procedure for homogeneity. Informed consent was obtained, and study was IRB approved. All data was de-identified. RESULTS: A total of 180 patients underwent complex abdominal hernia repair at our community hospital. The ACHQC database identified 6299 patients meeting criteria at participating academic centers. Demographics were similar between the two groups including hernia grade, size and wound class. Academic centers tended to have patients with previous component separations (25.7% vs 10.6%) and immunosuppressed (7.2% vs 2.8%), while the community hospital patients included more patients with tobacco use (18.9% vs 12.1%) and hypertension (65% vs 54.9%). Operative times were significantly less at the community hospital, patients requiring >240 minutes of time for repair at academic centers (39.6% vs 5%). Postoperatively length of stay was significantly shorter at the community hospital group averaging 3.7 days vs academic centers of 6 days (P < .05). Although overall complications were less in the community hospital group (26.5% vs 19.4%). Readmission within 30 days was nearly twice as frequent in the community hospital group (14.4% vs 7.7%). CONCLUSION: Community hospitals can provide comparable care and surgical expertise as major academic centers in regard to complex hernias in a large majority of cases. There is a need for dedicated care coordination and continuous review of supporting staff and outcomes is necessary to assure quality care. There is still a need to identify which patients would benefit from treatment at an academic center as opposed to a community hospital in order to maximize patient access and outcomes at both types of hospital setting. Further investigation needs to be performed regarding criteria for which patients should be transferred to academic centers for their complex hernia care. Identifying patients who would benefit from treatment at Academic Centers as opposed to Community hospitals should continue to be investigated.