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1.
Antiviral Res ; 188: 105036, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33577807

RESUMO

Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. We designed two sets of probes that were labeled with either 6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX) to identify PA/I38 (wild type strain) or PA/I38T, respectively. The established cycling probe real-time PCR system showed a dynamic linear range of 101 to 106 copies with high sensitivity in plasmid DNA controls. This real-time PCR system discriminated between PA/I38T and wild type viruses well. During the 2018/19 season, 377 influenza A-positive clinical samples were collected in Japan before antiviral treatment. Using our cycling probe real-time PCR system, we detected no (0/129, 0.0%) influenza A (H1N1)pdm09 viruses with PA/I38T substitutions and four A (H3N2) (4/229, 1.7%) with PA/I38T substitution prior to treatment. In addition, we found PA/I38T variant in siblings who did not received baloxavir treatment during an infection caused by A (H3N2) that afflicted the entire family. Although human-to-human transmission of PA/I38T variant may have occurred in a closed environment, the prevalence of this variant in influenza A viruses was still limited. Our cycling probe-PCR system is thus useful for antiviral surveillance of influenza A viruses possessing PA/I38T.


Assuntos
Antivirais/farmacologia , Dibenzotiepinas/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Morfolinas/farmacologia , Piridonas/farmacologia , RNA Polimerase Dependente de RNA/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Triazinas/farmacologia , Proteínas Virais/genética , Substituição de Aminoácidos , Animais , Linhagem Celular , Humanos , Vírus da Influenza A/enzimologia , Vírus da Influenza A/isolamento & purificação , Testes de Sensibilidade Microbiana , RNA Viral/biossíntese , Replicação Viral/efeitos dos fármacos
2.
Antiviral Res ; 183: 104951, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32987032

RESUMO

We conducted a prospective, multicenter, non-randomized observational study to assess the duration of fever and symptoms of influenza A/H1N1pdm09 and A/H3N2 infected children < 19 years old treated with either baloxavir or oseltamivir. Additionally, these symptoms were investigated in association with pre- and post-baloxavir treatment-emergent polymerase acidic unit (PA) variants as compared to non-substituted viruses. Following receipt of informed consent, baloxavir was administered to 102 influenza A patients, and oseltamivir to 52 patients during the 2018-2019 influenza season in Japan. The average age was higher in the baloxavir treatment group compared to the oseltamivir treatment group (10.6 ± 2.7 versus 6.9 ± 2.9 years old, p < 0.01). The duration of fever and symptoms in baloxavir-treated A/H1N1pdm09 and A/H3N2-infected children did not differ from those in oseltamivir-treated groups (median 22.0, 11.8, 23.0, and 21.0 h, and median 114.5, 121.0, 123.0, and 122.0 h, respectively). One (1.2%) of 83 A/H3N2 patients possessed a PA/I38T substituted virus prior to treatment. The frequency of PA variants in post-treatment samples obtained 2-11 days after beginning of baloxavir was 12.5% (4/32) for A/H1N1pdm09 and 14.1% (9/64) for A/H3N2 when the total number of cases was used as the denominator, however, were 57.1% (4/7) and 33.3% (9/27) when PCR-positive cases at the time of second sampling was used as the denominator. The most frequent PA substitution was I38T (9), with E23K (1), I38K (1), I38M (1), and PA/I38S (1) also observed. The duration of fever and overall symptoms did not differ significantly following baloxavir treatment in individuals with PA variant viruses, non-substituted virus, or in those that were PCR negative at the second sampling (median 20, 24 and 11 h, and median 121, 115 and 121 h, respectively). Rebound of viral RNA load was observed in 13.5% (2/13) of PA variants but it was not associated with recurrence of fever and symptoms. Hence, prolonged fever or symptoms were not observed in children treated with baloxavir following emergence of PA variants, however, further studies are needed to evaluate the clinical impact of PA variants.


Assuntos
Antivirais/uso terapêutico , Dibenzotiepinas/uso terapêutico , Febre/virologia , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Influenza Humana/tratamento farmacológico , Morfolinas/uso terapêutico , Oseltamivir/uso terapêutico , Piridonas/uso terapêutico , RNA Polimerase Dependente de RNA/genética , Triazinas/uso terapêutico , Proteínas Virais/genética , Adolescente , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Variação Genética , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/enzimologia , Influenza Humana/virologia , Masculino , Estudos Prospectivos , Estações do Ano
3.
Kyobu Geka ; 73(9): 683-685, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-32879272

RESUMO

A 67-year-old woman was admitted with exertional dyspnea. She had undergone mitral valve replacement with Björk-Shiley prosthetic valve (convexo-concave type) 36 years previously for stenosis and regurgitation in another institute. An echocardiography showed a severe degree of aortic stenosis, and the implanted mitral valve function is normal. We performed aortic valve replacement with a bioprosthetic valve and no prophylactic reoperation for the implanted mitral valve. The postoperative courses were uneventful. The patient was discharged from the hospital in good clinical condition. Postoperative echocardiography showed the prosthetic valves were normal. The close follow-up should be needed to prevent fatal valve dysfunction.


Assuntos
Valva Aórtica , Próteses Valvulares Cardíacas , Idoso , Feminino , Humanos , Valva Mitral , Falha de Prótese , Reoperação
4.
Kyobu Geka ; 73(8): 610-613, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32879291

RESUMO

Right-sided aortic arch (RAA) is a rare congenital disorder. A 87-year-old man with chest pain was diagnosed with a right-sided aortic arch and Kommerell's diverticulum by computed tomography (CT). The diverticulum had a maximum diameter of 57 mm, and surgical intervention was chosen because of the possibility of rupture and dissection. We performed thoracic endovascular aortic repair( TEVAR) with a commercially available device, consisting of bypass grafting of the supra-aortic branches. The postoperative courses were uneventful. The patient was discharged from the hospital in good clinical condition. Postoperative CT showed complete exclusion of the diverticulum without endoleak and device migration. Debranching TEVAR for Kommerell's diverticulum was safe and effective.


Assuntos
Divertículo , Procedimentos Endovasculares , Idoso de 80 Anos ou mais , Aorta Torácica , Humanos , Masculino , Artéria Subclávia , Tomografia Computadorizada por Raios X
5.
Kyobu Geka ; 73(6): 445-448, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32475970

RESUMO

An aberrant right subclavian artery (ARSCA) is a relatively rare congenital anomaly of the aortic arch branches. A 63-year-old man suffered from dysphagia, and was referred to our hospital. Computed tomography (CT) revealed an aortic aneurysm (Kommerell's diverticulum) and ARSCA which routed behind the esophagus. We performed total arch replacement with the open stent-grafting technique via median sternotomy. ARSCA was anastomosed to 1 branch of the arch graft at the right side of the trachea, which released esophageal compression. Postoperatively dysphagia disappeared and CT scan indicated successful reconstruction of the distal arch and ARSCA. The open stent-grafting technique is considered to be effective for aortic disease with ARSCA.


Assuntos
Anormalidades Cardiovasculares/cirurgia , Transtornos de Deglutição , Artéria Subclávia/anormalidades , Aorta Torácica , Anormalidades Cardiovasculares/complicações , Transtornos de Deglutição/etiologia , Divertículo , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Artéria Subclávia/cirurgia
6.
Faraday Discuss ; 220(0): 249-268, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31513206

RESUMO

The reactions of the diruthenium tetrahydrido complex, Cp*Ru(µ-H)4RuCp* (1) (Cp* = η5-C5Me5), with pyridines were investigated in relation to the dehydrogenative coupling of 4-substituted pyridines. Complex 1 reacted with γ-picoline to yield the bis(µ-pyridyl) complex, {Cp*Ru(µ-H)(µ-4-MeC5H3)}2 (2a), with the elimination of dihydrogen. Complex 2a immediately reacted with the liberated dihydrogen to yield µ-η2-dihydrobipyridine (dhbpy) complex 4avia C-C bond formation between the two pyridyl groups, in which one of the pyridine rings underwent partial hydrogenation. The X-ray structure of 4a shows that the dhbpy moiety adopts a µ-η2 coordination mode at the Ru2 site. Complex 4a was reversibly converted to 5avia the elimination of dihydrogen in which the dhbpy moiety adopts a µ-η2:η2 mode. Although 5a was coordinatively saturated, 5a readily reacted with tBuNC to yield 6a. This was owing to the ability of the dhbpy ligand changing its coordination mode between the µ-η2:η2 and µ-η2 modes. This also causes the dehydrogenation from the dhbpy ligand to yield µ-η2:η2-bipyridine complex 7a at 140 °C. However, 7a was not shown to be an intermediate of the catalysis. The reaction of 1 with 1,10-phenanthroline afforded µ-η2-phenanthroline complex 8 containing two hydrides, which can be a model compound for the bipyridine elimination from the Ru2 site. Dynamic NMR studies suggested that 8 was isomerised to an unsaturated µ-N-heterocyclic carbene (NHC) complex. The unsaturated nature of the µ-NHC complex is likely responsible for the uptake of the third pyridine molecule to turn over the catalytic cycle.

7.
Science ; 365(6454): 699-704, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31371562

RESUMO

Genetically encoded voltage indicators (GEVIs) enable monitoring of neuronal activity at high spatial and temporal resolution. However, the utility of existing GEVIs has been limited by the brightness and photostability of fluorescent proteins and rhodopsins. We engineered a GEVI, called Voltron, that uses bright and photostable synthetic dyes instead of protein-based fluorophores, thereby extending the number of neurons imaged simultaneously in vivo by a factor of 10 and enabling imaging for significantly longer durations relative to existing GEVIs. We used Voltron for in vivo voltage imaging in mice, zebrafish, and fruit flies. In the mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously over a 15-minute period of continuous imaging. In larval zebrafish, Voltron enabled the precise correlation of spike timing with behavior.


Assuntos
Monitorização Fisiológica/métodos , Neuroimagem/métodos , Neurônios/fisiologia , Imagens com Corantes Sensíveis à Voltagem/métodos , Animais , Comportamento Animal , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Engenharia Genética , Larva , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Mesencéfalo/citologia , Mesencéfalo/fisiologia , Camundongos , Optogenética , Domínios Proteicos , Rodopsinas Microbianas/química , Rodopsinas Microbianas/genética , Natação , Peixe-Zebra
8.
Vaccine X ; 1: 100011, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-31384733

RESUMO

Background: We estimated influenza vaccine effectiveness (VE) in 2015-2016 season against medically attended, laboratory-confirmed influenza, when quadrivalent inactivated vaccine (IIV4) was first introduced in Japan, using test-negative case-control design. Influenza A(H1N1)pdm09 cocirculated with B/Yamagata and B/Victoria during the study period in Japan. Method: We based our case definition on two laboratory tests, real-time reverse transcription polymerase chain reaction (RT PCR), and virus isolation and compared VEs based on these tests. In addition, VE was evaluated by rapid diagnostic test (RDT). Nasopharyngeal swabs were collected from outpatients who visited clinics with influenza-like illness (ILIs) in Hokkaido, Niigata, Gunma and Nagasaki prefectures. Results: Among 713 children and adults enrolled in this study, 578 were influenza positive by RT PCR including, 392 influenza A and 186 influenza B, while 135 were tested negative controls. The adjusted VE by RT PCR for all ages against any influenza was low protection of 36.0% (95% confidence interval [CI], 3.1% to 58.6%), for influenza A was 30.0% (95% CI: -10.0% to 55.5%), and influenza B was moderate 50.2% (95% CI: 13.3% to 71.4%). Adjusted VE for virus isolation for A(H1N1)pdm09 was 37.1% (95% CI: 1.7% to 59.7%), Yamagata lineage 51.3% (95% CI: 6.4% to 74.7%) and Victoria lineage 21.3% (95% CI: -50.0% to 58.9%). VE was highest and protective in 0-5 years old group against any influenza and influenza A and B/Yamagata, but the protective effect was not observed for other age groups and B/Victoria. RDT demonstrated concordant results with RT PCR and virus isolation. Sequencing of hemagglutinin gene showed that all A(H1N1)pdm09 belong to clade 6B including 31 strains (88.6%), which belong to clade 6B.1 possessing S162N mutations that may alter antigenicity and affect VE for A(H1N1)pdm09. Conclusions: IIV4 influenza vaccine during 2015-2016 was effective against A(H1N1)pdm09 and the two lineages of type B. Younger children was more protected than older children and adults by vaccination.

9.
Nat Methods ; 16(8): 763-770, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308547

RESUMO

Current techniques for monitoring GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in vertebrates, cannot follow transients in intact neural circuits. To develop a GABA sensor, we applied the design principles used to create the fluorescent glutamate receptor iGluSnFR. We used a protein derived from a previously unsequenced Pseudomonas fluorescens strain and performed structure-guided mutagenesis and library screening to obtain intensity-based GABA sensing fluorescence reporter (iGABASnFR) variants. iGABASnFR is genetically encoded, detects GABA release evoked by electric stimulation of afferent fibers in acute brain slices and produces readily detectable fluorescence increases in vivo in mice and zebrafish. We applied iGABASnFR to track mitochondrial GABA content and its modulation by an anticonvulsant, swimming-evoked, GABA-mediated transmission in zebrafish cerebellum, GABA release events during interictal spikes and seizures in awake mice, and found that GABA-mediated tone decreases during isoflurane anesthesia.


Assuntos
Técnicas Biossensoriais/métodos , Encéfalo/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Imagem Molecular/métodos , Neurônios/metabolismo , Ácido gama-Aminobutírico/metabolismo , Anestesia , Animais , Animais Geneticamente Modificados , Feminino , Proteínas de Fluorescência Verde/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Convulsões/metabolismo , Convulsões/patologia , Peixe-Zebra
10.
Elife ; 82019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31159922

RESUMO

Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. To disambiguate orexin-dependent and -independent physiological functions of orexin neurons, we generated a novel Orexin-flippase (Flp) knock-in mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was knock-out in homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, such activation increased the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.


Assuntos
Nível de Alerta , Neurônios/fisiologia , Orexinas/metabolismo , Vigília , Potenciais de Ação , Animais , Comportamento Animal , Camundongos
11.
Cell Rep ; 25(3): 640-650.e2, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332644

RESUMO

Neural network remodeling underpins the ability to remember life experiences, but little is known about the long-term plasticity of neural populations. To study how the brain encodes episodic events, we used time-lapse two-photon microscopy and a fluorescent reporter of neural plasticity based on an enhanced form of the synaptic activity-responsive element (E-SARE) within the Arc promoter to track thousands of CA1 hippocampal pyramidal cells over weeks in mice that repeatedly encountered different environments. Each environment evokes characteristic patterns of ensemble neural plasticity, but with each encounter, the set of activated cells gradually evolves. After repeated exposures, the plasticity patterns evoked by an individual environment progressively stabilize. Compared with young adults, plasticity patterns in aged mice are less specific to individual environments and less stable across repeat experiences. Long-term consolidation of hippocampal plasticity patterns may support long-term memory formation, whereas weaker consolidation in aged subjects might reflect declining memory function.


Assuntos
Envelhecimento , Comportamento Animal/fisiologia , Região CA1 Hipocampal/fisiologia , Memória de Longo Prazo/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia , Animais , Meio Ambiente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Imagem com Lapso de Tempo
13.
Nat Chem Biol ; 14(4): 352-360, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29483642

RESUMO

We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library in just a few hours, evaluating each along multiple performance axes. To demonstrate the power of this approach, we created a genetically encoded fluorescent voltage indicator, simultaneously optimizing its brightness and membrane localization using our microscopy-guided cell-picking strategy. We produced the high-performance opsin-based fluorescent voltage reporter Archon1 and demonstrated its utility by imaging spiking and millivolt-scale subthreshold and synaptic activity in acute mouse brain slices and in larval zebrafish in vivo. We also measured postsynaptic responses downstream of optogenetically controlled neurons in C. elegans.


Assuntos
Evolução Molecular Direcionada/métodos , Proteínas Luminescentes/química , Engenharia de Proteínas/métodos , Robótica , Peixe-Zebra/embriologia , Animais , Encéfalo/diagnóstico por imagem , Caenorhabditis elegans , Separação Celular , Feminino , Citometria de Fluxo , Fluorescência , Biblioteca Gênica , Genes Reporter , Células HEK293 , Hipocampo/citologia , Humanos , Masculino , Camundongos , Microscopia de Fluorescência , Neurônios/citologia , Optogenética
14.
Neurosci Res ; 129: 32-39, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28774814

RESUMO

The serotonergic system in the vertebrate brain is implicated in various behaviors and diseases. Its involvement in motor control has been studied for over half a century, but efforts to build a unified model of its functions have been hampered due to the complexity of serotonergic neuromodulation. This review summarizes the anatomical structure of the serotonergic system, its afferent and efferent connections to other brain regions, and recent insights into the sensorimotor computations in the serotonergic system, and considers future research directions into the roles of serotonergic system in motor control.


Assuntos
Encéfalo/fisiologia , Movimento , Receptores de Serotonina/fisiologia , Neurônios Serotoninérgicos/fisiologia , Serotonina/fisiologia , Vias Aferentes/fisiologia , Animais , Gânglios da Base/fisiologia , Cerebelo/fisiologia , Núcleo Dorsal da Rafe/fisiologia , Vias Eferentes/fisiologia , Humanos , Medula Espinal/fisiologia
15.
Kyobu Geka ; 70(13): 1115-1119, 2017 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-29249792

RESUMO

Generally, infective endocarditis is found at the left side of the heart. The right side infective endocaritis accounts for only 5~10% of all cases of infective endocarditis. The right side infective endocarditis occurs especially among drug users employing intravenous injection. A typical site of infection is the tricupid valve, and isolated pulmonary valve involvement is rare. It is assumed that its rarity is due to the low pressure gradients within the right heart, the low prevalence of valve disease, and the lower oxygen content of the venous blood. We describe a case of isolated pulmonary valve endocarditis requiring valve replacement. Antibiotic therapy was conducted for 4 weeks before surgery and 2 weeks after surgery. Clinical course was favorable and the patent was discharged home 18 days after surgery.


Assuntos
Endocardite Bacteriana/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Valva Pulmonar/cirurgia , Idoso , Procedimentos Cirúrgicos Cardíacos , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/etiologia , Humanos , Masculino , Streptococcus/isolamento & purificação
16.
Cell ; 167(4): 933-946.e20, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27881303

RESUMO

To execute accurate movements, animals must continuously adapt their behavior to changes in their bodies and environments. Animals can learn changes in the relationship between their locomotor commands and the resulting distance moved, then adjust command strength to achieve a desired travel distance. It is largely unknown which circuits implement this form of motor learning, or how. Using whole-brain neuronal imaging and circuit manipulations in larval zebrafish, we discovered that the serotonergic dorsal raphe nucleus (DRN) mediates short-term locomotor learning. Serotonergic DRN neurons respond phasically to swim-induced visual motion, but little to motion that is not self-generated. During prolonged exposure to a given motosensory gain, persistent DRN activity emerges that stores the learned efficacy of motor commands and adapts future locomotor drive for tens of seconds. The DRN's ability to track the effectiveness of motor intent may constitute a computational building block for the broader functions of the serotonergic system. VIDEO ABSTRACT.


Assuntos
Aprendizagem , Modelos Neurológicos , Natação , Peixe-Zebra/fisiologia , Animais , Mapeamento Encefálico , Larva , Optogenética , Núcleos da Rafe/fisiologia , Neurônios Serotoninérgicos/citologia , Neurônios Serotoninérgicos/fisiologia , Processamento Espacial
17.
Kyobu Geka ; 69(2): 99-105, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-27075149

RESUMO

A 58-year-old man presented with severe aortic regurgitation(AR) with quadricuspid valve. Intraoperatively, the small accessory cusp was separated from non-coronary cusp( NCC). The NCC and small accessory cusp were sutured to obtain 1 competent cusp, aiming at an effective height of 8 mm. His AR was trivial at the postoperative 7th day.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Anuloplastia da Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório
18.
Neurosci Res ; 106: 29-37, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26477716

RESUMO

The purpose of this study was to investigate characteristics of the semantic processing of sentences' final verbs in stutterers using event-related potential (ERP). ERPs elicited from semantically violating and non-violating verbs in Japanese sentences were compared between 13 adults who stutter (AWS) and 13 adults who do not stutter (AWNS). The stimulus sentences elicited the N400 and the late positive component (LPC) in both groups. The amplitude of the N400, however, was attenuated in AWS. Regarding the LPC, the LPC in the 450-700ms time window (the early LPC) was evident in both groups, but the LPC in the 700-850 time window (the late LPC) was only apparent in AWS. Because AWS judged sentence congruency as accurately as AWNS did, it is assumed that AWS depended more on the LPC for semantic processing, resulting in the enhancement of the late LPC. We speculate that semantic processing of sentences for AWS is more time consuming than that for AWNS.


Assuntos
Potenciais Evocados , Gagueira/psicologia , Comportamento Verbal , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Semântica , Gagueira/fisiopatologia , Adulto Jovem
19.
Gen Thorac Cardiovasc Surg ; 63(6): 335-42, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25836326

RESUMO

OBJECTIVE: The second best arterial graft to the left coronary artery (LCA) system between the radial artery (RA) and the right internal thoracic artery (RITA) has been unknown. Moreover, a composite RA may be inferior to direct aorta-RA bypass grafting. The aim of the present study is to compare clinical outcomes between the RA anastomosed to the aorta and the RITA as a second arterial graft to the LCA. METHODS: A total of 805 patients received off-pump coronary arterial bypass grafting between 2000 and 2013. Of these patients, 232 received the bilateral internal thoracic arteries (BITA) and 152 received left internal thoracic arteries (LITA) + RA anastomosed to the aorta, following the inclusion criteria. Patients (1) received at least two arterial grafts in the LCA, (2) did not have renal insufficiency, and (3) did not receive composite RA grafts. A propensity score-matched analysis was performed, resulting in 118 matched pairs. RESULTS: There was no difference in operative mortality and stroke rate between the matched groups; however, the mean operation time was significantly shorter in the LITA + RA and the incidence of mediastinitis was lower in the LITA + RA (BITA: 2.5 %, LITA + RA: 0 %, p < 0.01). Kaplan-Meier cumulative mortality and freedom from cardiac events were similar. The long-term patency rates of the RITA and the RA were similar at 5 years (RITA: 78 %, RA: 84 %, p = 0.55). CONCLUSIONS: The RA anastomosed to the aorta appears to have good long-term outcomes, similar to the RITA as the second arterial graft. Furthermore, the choice of RA avoids sternal complications and shortens the operation time compared to the use of BITA.


Assuntos
Aorta/cirurgia , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Artéria Torácica Interna/cirurgia , Artéria Radial/transplante , Idoso , Anastomose Cirúrgica/métodos , Implante de Prótese Vascular/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
Neuron ; 84(1): 92-106, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25277455

RESUMO

CREB is a pivotal mediator of activity-regulated gene transcription that underlies memory formation and allocation. The contribution of a key CREB cofactor, CREB-regulated transcription coactivator 1 (CRTC1), has, however, remained elusive. Here we show that several constitutive kinase pathways and an activity-regulated phosphatase, calcineurin, converge to determine the nucleocytoplasmic shuttling of CRTC1. This, in turn, triggered an activity-dependent association of CRTC1 with CREB-dependent regulatory elements found on IEG promoters. Forced expression of nuclear CRTC1 in hippocampal neurons activated CREB-dependent transcription, and was sufficient to enhance contextual fear memory. Surprisingly, during contextual fear conditioning, we found evidence of nuclear recruitment of endogenous CRTC1 only in the basolateral amygdala, and not in the hippocampus. Consistently, CRTC1 knockdown in the amygdala, but not in the hippocampus, significantly attenuated fear memory. Thus, CRTC1 has a wide impact on CREB-dependent memory processes, but fine-tunes CREB output in a region-specific manner.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Medo/fisiologia , Hipocampo/metabolismo , Memória/fisiologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Neurônios/metabolismo , Ratos
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