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1.
JACC Cardiovasc Interv ; 17(9): 1119-1130, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38749592

RESUMEN

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).


Asunto(s)
Aspirina , Enfermedad de la Arteria Coronaria , Esquema de Medicación , Stents Liberadores de Fármacos , Terapia Antiplaquetaria Doble , Everolimus , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Diseño de Prótesis , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Masculino , Factores de Tiempo , Femenino , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Factores de Riesgo , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Everolimus/administración & dosificación , Everolimus/efectos adversos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Trombosis Coronaria/etiología , Trombosis Coronaria/prevención & control , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Aleaciones de Cromo , Medición de Riesgo , Quimioterapia Combinada
2.
Artículo en Inglés | MEDLINE | ID: mdl-38285607

RESUMEN

BACKGROUND AND AIMS: High bleeding risk (HBR) and acute coronary syndrome (ACS) subtypes are critical in determining bleeding and cardiovascular event risk after percutaneous coronary intervention (PCI). METHODS: In 4476 ACS patients enrolled in the STOPDAPT-3, where the no-aspirin and dual antiplatelet therapy (DAPT) strategies after PCI were randomly compared, the pre-specified subgroup analyses were conducted based on HBR/non-HBR and ST-segment elevation myocardial infarction (STEMI)/non-ST-segment elevation ACS (NSTE-ACS). The co-primary bleeding endpoint was BARC type 3 or 5, and the co-primary cardiovascular endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke at 1 month. RESULTS: Irrespective of the subgroups, the effect of no-aspirin compared with DAPT was not significant for the bleeding endpoint (HBR [N = 1803]: 7.27% and 7.91%, HR 0.91, 95%CI 0.65-1.28; non-HBR [N = 2673]: 3.40% and 3.65%, HR 0.93, 95%CI 0.62-1.39; Pinteraction = 0.94; STEMI [N = 2553]: 6.58% and 6.56%, HR 1.00, 95% CI 0.74-1.35; NSTE-ACS [N = 1923]: 2.94% and 3.64%, HR 0.80, 95%CI 0.49-1.32; Pinteraction = 0.45), and for the cardiovascular endpoint (HBR: 7.87% and 5.75%, HR 1.39, 95%CI 0.97-1.99; non-HBR: 2.56% and 2.67%, HR 0.96, 95%CI 0.60-1.53; Pinteraction = 0.22; STEMI: 6.07% and 5.46%, HR 1.11, 95%CI 0.81-1.54; NSTE-ACS: 3.03% and 1.71%, HR 1.78, 95%CI 0.97-3.27; Pinteraction = 0.18). CONCLUSIONS: In patients with ACS undergoing PCI, the no-aspirin strategy compared to the DAPT strategy failed to reduce major bleeding events irrespective of HBR and ACS subtypes. The numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events was observed in patients with HBR and in patients with NSTE-ACS.

3.
Circulation ; 149(8): 585-600, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-37994553

RESUMEN

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.


Asunto(s)
Síndrome Coronario Agudo , Aspirina/análogos & derivados , Nitratos , Intervención Coronaria Percutánea , Trombosis , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Síndrome Coronario Agudo/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Quimioterapia Combinada , Aspirina/efectos adversos , Hemorragia/etiología , Stents , Trombosis/epidemiología , Trombosis/etiología , Trombosis/prevención & control , Resultado del Tratamiento
4.
Biosci Biotechnol Biochem ; 88(1): 16-25, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-37777845

RESUMEN

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality.


Asunto(s)
Metabolismo Energético , Obesidad , Animales , Ratones , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/genética , Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Ratones Noqueados
5.
Beilstein J Org Chem ; 19: 133-138, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36793535

RESUMEN

A new antibacterial 3-monoacyl-sn-glycerol, nostochopcerol (1), was isolated from a cultured algal mass of the edible cyanobacterium Nostochopsis lobatus MAC0804NAN. The structure of compound 1 was established by the analysis of NMR and MS data while its chirality was established by comparison of optical rotation values with synthetically prepared authentics. Compound 1 inhibited the growth of Bacillus subtilis and Staphylococcus aureus at MIC of 50 µg/mL and 100 µg/mL, respectively.

6.
Nat Nanotechnol ; 18(4): 357-364, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36702955

RESUMEN

The success of the lead halide perovskites in diverse optoelectronics has motivated considerable interest in their fundamental photocarrier dynamics. Here we report the discovery of photocarrier-induced persistent structural polarization and local ferroelectricity in lead halide perovskites. Photoconductance studies of thin-film single-crystal CsPbBr3 at 10 K reveal long-lasting persistent photoconductance with an ultralong photocarrier lifetime beyond 106 s. X-ray diffraction studies reveal that photocarrier-induced structural polarization is present up to a critical freezing temperature. Photocapacitance studies at cryogenic temperatures further demonstrate a systematic local phase transition from linear dielectric to paraelectric and relaxor ferroelectric under increasing illumination. Our theoretical investigations highlight the critical role of photocarrier-phonon coupling and large polaron formation in driving the local relaxor ferroelectric phase transition. Our findings show that this photocarrier-induced persistent structural polarization enables the formation of ferroelectric nanodomains at low temperature, which suppress carrier recombination and offer the possibility of exploring intriguing carrier-phonon interplay and the rich polaron photophysics.

7.
Nano Lett ; 21(22): 9594-9600, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34767368

RESUMEN

Through first-principles real-time density-matrix (FPDM) dynamics simulations, we investigated spin relaxation due to electron-phonon and electron-impurity scatterings with spin-orbit coupling (SOC) in two-dimensional Dirac materials silicene and germanene at finite temperatures. We discussed the applicability of conventional descriptions of spin relaxation mechanisms by Elliott-Yafet (EY) and D'yakonov-Perel' (DP) compared to the FPDM method, which is determined by a complex interplay of intrinsic SOC, external fields, and scattering strength. For example, the electric field dependence of the spin lifetime by FPDM is close to the DP mechanism for silicene at room temperature but similar to the EY mechanism for germanene. Because of its stronger SOC strength and buckled structure in contrast to graphene, germanene has a giant spin lifetime anisotropy and spin-valley locking effect under nonzero Ez and low temperatures. More importantly, germanene has a long spin lifetime (∼100 ns at 50 K) and an ultrahigh carrier mobility, making it advantageous for spin-valleytronic applications.

8.
ESC Heart Fail ; 8(6): 4800-4807, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34687170

RESUMEN

AIMS: Clinical scores that consider physical and social factors to predict long-term observations in patients after acute heart failure are limited. This study aimed to develop and validate a prediction model for patients with acute heart failure at the time of discharge. METHODS AND RESULTS: This study was retrospective analysis of the Kitakawachi Clinical Background and Outcome of Heart Failure Registry database. The registry is a prospective, multicentre cohort of patients with acute heart failure between April 2015 and August 2017. The primary outcome to be predicted was the incidence of all-cause mortality during the 3 years of follow-up period. The development cohort derived from April 2015 to July 2016 was used to build the prediction model, and the test cohort from August 2016 to August 2017 was used to evaluate the prediction model. The following potential predictors were selected by the least absolute shrinkage and selection operator method: age, sex, body mass index, activities of daily living at discharge, social background, comorbidities, biomarkers, and echocardiographic findings; a risk scoring system was developed using a logistic model to predict the outcome using a simple integer based on each variable's ß coefficient. Out of 1253 patients registered, 1117 were included in the analysis and divided into the development (n = 679) and test (n = 438) cohorts. The outcomes were 246 (36.2%) in the development cohort and 143 (32.6%) in the test cohort. Eleven variables including physical and social factors were set into the logistic regression model, and the risk scoring system was created. The patients were divided into three groups: low risk (score 0-5), moderate risk (score 6-11), and high risk (score ≥12). The observed and predicted mortality rates were described by the Kaplan-Meier curve divided by risk group and independently increased (P < 0.001). In the test cohort, the C statistic of the prediction model was 0.778 (95% confidence interval: 0.732-0.824), and the mean predicted probabilities in the groups were low, 6.9% (95% confidence interval: 3.8-10%); moderate, 30.1% (95% confidence interval: 25.4%-34.8%); and high, 79.2% (95% confidence interval: 72.6%-85.8%). The predicted probability was well calibrated to the observed outcomes in both cohorts. CONCLUSIONS: The Kitakawachi Clinical Background and Outcome of Heart Failure score was helpful in predicting adverse events in patients with acute heart failure over a long-term period. We should evaluate the physical and social functions of such patients before discharge to prevent adverse outcomes.


Asunto(s)
Actividades Cotidianas , Insuficiencia Cardíaca , Insuficiencia Cardíaca/epidemiología , Humanos , Japón/epidemiología , Pronóstico , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo/métodos
9.
J Phys Chem Lett ; 12(27): 6299-6304, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34227805

RESUMEN

High defect tolerance has been considered a primary reason for the long charge carrier lifetime and high photoluminescence quantum yield in bulk lead halide perovskites (LHPs). On the other hand, surface defects play a critical role in determining charge carrier dynamics and optical properties, especially for LHP nanocrystals and quantum dots. Understanding the nature of surface defects and developing strategy for their effective passivation are thus of strong interest. Focusing on a prototypical LHP, CsPbBr3, our work uses first-principles calculations to reveal that interstitial sites and antisites can have lower formation energies when they form at the surface while simultaneously creating deep trap states within the bandgap. Meanwhile, the formation of halide vacancies is energetically less favorable. On the basis of a new surface defect model, we demonstrate the explicit role of molecular ligands in passivating these defects, which eliminate trap states in favor of shallow states and enhance photoluminescence.

10.
Clin Cardiol ; 44(6): 848-856, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33963771

RESUMEN

BACKGROUND: In Japan, both the prevalence of the elderly and super-elderly and those of acute heart failure (AHF) have been increasing rapidly. METHODS: This registry was a prospective multicenter cohort, which enrolled a total of 1253 patients with AHF. In this study, 1117 patients' follow-up data were available and were categorized into three groups according to age: <75 years old (nonelderly), 75-84 years old (elderly), and ≥ 85 years old (super-elderly). The endpoint was defined as all-cause death and each mode of death after discharge during the 3-years follow-up period. RESULTS: Based on the Kaplan-Meier analysis, a gradually increased risk of all-cause death according to age was found. Among the three groups, the proportion of HF death was of similar trend; however, the proportion of infection death was higher in elderly and super-elderly patients. After adjusting for potentially confounding effects using the Cox and Fine-Gray model, the hazard ratio (HR) of all-cause death increased significantly in elderly and super-elderly patients (HR, 2.60; 95% confidence interval [CI], 1.93-3.54 and HR, 5.04; 95% CI, 3.72-6.92, respectively), when compared with nonelderly patients. The highest sub-distribution HR in detailed mode of death was infection death in elderly and super-elderly patients (HR, 4.25; 95% CI, 1.75-10.33 and HR, 10.10; 95% CI, 3.78-27.03, respectively). CONCLUSIONS: In this population, the risk of all-cause death was found to increase in elderly and super-elderly. Elderly patients and especially super-elderly patients with AHF were at a higher risk for noncardiovascular death, especially infection death.


Asunto(s)
Insuficiencia Cardíaca , Enfermedad Aguda , Anciano , Humanos , Japón/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros
11.
Circ Rep ; 3(4): 217-226, 2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33842727

RESUMEN

Background: This study investigated whether combination therapy (CT) with renin-angiotensin system inhibitors and ß-blockers improved endpoints in acute heart failure (AHF). Methods and Results: AHF patients were recruited to this prospective multicenter cohort study between April 2015 and August 2017. Patients were divided into 3 categories based on ejection fraction (EF), namely heart failure (HF) with reduced EF (HFrEF), HF with midrange EF (HFmrEF), and HF with preserved EF (HFpEF), and a further into 2 groups according to physical status (those who could walk independently outdoors and those who could not). The composite endpoint included all-cause mortality and hospitalization for HF. Data at the 1-year follow-up were available for 1,018 patients. The incidence of the composite endpoint was significantly lower in the CT than non-CT group for HFrEF patients, but not among HFmrEF and HFpEF patients. For patients who could walk independently outdoors, a significantly lower rate of the composite endpoint was recorded only in the HFrEF group. The differences were maintained even after adjustment for comorbidities and prescriptions, with hazard ratios (95% confidence intervals) of 0.39 (0.20-0.76) and 0.48 (0.22-0.99), respectively. Conclusions: In this study, CT was associated with the prevention of adverse outcomes in patients with HFrEF. Moreover, CT prevented adverse events only among patients without a physical disorder, not among those with a physical disorder.

12.
Circ J ; 84(9): 1528-1535, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32713877

RESUMEN

BACKGROUND: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF).Methods and Results:This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge. We divided the patients into 4 groups: (i) patients without LTCI, (ii) patients requiring support level 1 or 2, (iii) patients with care level 1 or 2, and (iv) patients with care levels 3-5. The Kaplan-Meier analysis identified a lower rate of the composite endpoint in group (i) than in the other groups. After adjusting for potentially confounding effects using a Cox proportional regression model, the hazard ratio (HR) of the composite endpoint increased significantly in groups (iii) and (iv) (adjusted HR, 1.62; 95% confidence interval [CI], 1.22-1.98 and adjusted HR, 1.62; 95% CI, 1.23-2.14, respectively) when compared with group (i). However, there was no significant difference between groups (i) and (ii). CONCLUSIONS: The level of LTCI was associated with a higher risk of the composite endpoint after discharge in acute HF patients.


Asunto(s)
Insuficiencia Cardíaca/economía , Insuficiencia Cardíaca/epidemiología , Seguro de Cuidados a Largo Plazo , Sistema de Registros , Enfermedad Aguda/economía , Enfermedad Aguda/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Humanos , Japón/epidemiología , Estimación de Kaplan-Meier , Masculino , Alta del Paciente , Readmisión del Paciente , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento
13.
Nutrients ; 12(6)2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32516922

RESUMEN

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin-ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 (Fgf21) and uncoupling protein 1 (Ucp1) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Microalgas/química , Obesidad/metabolismo , Obesidad/prevención & control , Quinazolinas/administración & dosificación , Quinazolinas/farmacología , Termogénesis/efectos de los fármacos , Aumento de Peso/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Factores de Crecimiento de Fibroblastos/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/etiología , Quinazolinas/aislamiento & purificación , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proteína Desacopladora 1/metabolismo
14.
Chem Sci ; 11(6): 1573-1580, 2020 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34084388

RESUMEN

The packing structures of organic semiconductors in the solid state play critical roles in determining the performances of their optoelectronic devices, such as organic field-effect transistors (OFETs). It is a formidable challenge to rationally design molecular packing in the solid state owing to the difficulty of controlling intermolecular interactions. Here we report a unique materials design strategy based on the ß-methylthionation of acenedithiophenes to generally and selectively control the packing structures of materials to create organic semiconductors rivalling rubrene, a benchmark high-mobility material with a characteristic pitched π-stacking structure in the solid state. Furthermore, the effect of the ß-methylthionation on the packing structure was analyzed by Hirshfeld surface analysis together with theoretical calculations based on symmetry-adapted perturbation theory (SAPT). The results clearly demonstrated that the ß-methylthionation of acenedithiophenes can universally alter the intermolecular interactions by disrupting the favorable edge-to-face manner in the parent acenedithiophenes and simultaneously inducing face-to-face and end-to-face interactions in the ß-methylthionated acenedithiophenes. This "disrupt and induce" strategy to manipulate intermolecular interactions can open a door to rational packing design based on the molecular structure.

15.
Adv Mater ; 31(21): e1901060, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30968488

RESUMEN

Understanding and ultimately controlling the large electromechanical effects in relaxor ferroelectrics requires intimate knowledge of how the local-polar order evolves under applied stimuli. Here, the biaxial-strain-induced evolution of and correlations between polar structures and properties in epitaxial films of the prototypical relaxor ferroelectric 0.68PbMg1/3 Nb2/3 O3 -0.32PbTiO3 are investigated. X-ray diffuse-scattering studies reveal an evolution from a butterfly- to disc-shaped pattern and an increase in the correlation-length from ≈8 to ≈25 nm with increasing compressive strain. Molecular-dynamics simulations reveal the origin of the changes in the diffuse-scattering patterns and that strain induces polarization rotation and the merging of the polar order. As the magnitude of the strain is increased, relaxor behavior is gradually suppressed but is not fully quenched. Analysis of the dynamic evolution of dipole alignment in the simulations reveals that, while, for most unit-cell chemistries and configurations, strain drives a tendency toward more ferroelectric-like order, there are certain unit cells that become more disordered under strain, resulting in stronger competition between ordered and disordered regions and enhanced overall susceptibilities. Ultimately, this implies that deterministic creation of specific local chemical configurations could be an effective way to enhance relaxor performance.

16.
IDCases ; 15: e00498, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30775241

RESUMEN

INTRODUCTION: Kluyvera ascorbata is a gram-negative, catalase-positive, oxidase-negative, aerobic fermentative bacterium with flagella. This organism colonizes in the human body and its pathogenicity is extremely low; few clinical cases of K. ascorbata infection have been reported. PRESENTATION OF CASE: We report on a patient who experienced severe sepsis and acute cholangitis due to K. ascorbata bacteremia and was treated with levofloxacin following antibiotic susceptibility testing. To our knowledge, this is the first case report of third-generation cephalosporins resistant K. ascorbata infection in Japan. DISCUSSION: Although this pathogen produces innate CTX-M type ß-lactamases and is generally resistant to first- and second-generation penicillins and cephalosporins, multi-drug resistant K. ascorbata infection, including ceftriaxone resistant infection has seldom been reported. CONCLUSION: The increase of drug-resistant pathogens is of concern; in such cases, rapid microbial identification and appropriate antibiotic selection are crucial for successful treatment.

17.
J Cardiol ; 73(6): 522-529, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30598389

RESUMEN

BACKGROUND: Although activities of daily living (ADL) are recognized as being pertinent in averting relevant readmission of heart failure (HF) and mortality, little research has been conducted to assess a correlation between a decline in ADL and outcomes in HF patients. METHODS: The Kitakawachi Clinical Background and Outcome of Heart Failure Registry is a prospective, multicenter, community-based cohort of HF patients. We categorized the patients into four types of ADL: independent outdoor walking, independent indoor walking, indoor walking with assistance, and abasia. We defined a decline in ADL (decline ADL) as downgrade of ADL and others (non-decline ADL) as preservation of ADL before discharge compared with admission. RESULTS: Among 1253 registered patients, 923 were eligible, comprising 98 (10.6%) with decline ADL and 825 (89.4%) with non-decline ADL. Decline ADL exhibited a higher risk of hospitalization for HF and mortality compared with non-decline ADL. A multivariate analysis revealed that decline ADL emerged as an independent risk factor of hospitalization for HF [hazard ratio (HR), 1.42; 95% confidence interval (CI): 1.01-1.96; p=0.046] and mortality (HR, 1.95; 95% CI: 1.23-2.99; p<0.01). Although 66.3% of patients with decline ADL were registered for long-term care insurance, few received daycare services (32.7%) or home-visit medical services (8.2%). CONCLUSIONS: Decline in ADL is a predictor of hospitalization for HF and mortality in HF patients.


Asunto(s)
Actividades Cotidianas , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Caminata
18.
Nat Mater ; 17(8): 657-658, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29941921
19.
Nature ; 546(7658): 391-395, 2017 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-28617453

RESUMEN

Despite more than 50 years of investigation, it is still unclear how the underlying structure of relaxor ferroelectrics gives rise to their defining properties, such as ultrahigh piezoelectric coefficients, high permittivity over a broad temperature range, diffuse phase transitions, strong frequency dependence in dielectric response, and phonon anomalies. The model of polar nanoregions inside a non-polar matrix has been widely used to describe the structure of relaxor ferroelectrics. However, the lack of precise knowledge about the shapes, growth and dipole patterns of polar nanoregions has led to the characterization of relaxors as "hopeless messes", and no predictive model for relaxor behaviour is currently available. Here we use molecular dynamics simulations of the prototypical Pb(Mg1/3,Nb2/3)O3-PbTiO3 relaxor material to examine its structure and the spatial and temporal polarization correlations. Our simulations show that the unusual properties of relaxors stem from the presence of a multi-domain state with extremely small domain sizes (2-10 nanometres), and no non-polar matrix, owing to the local dynamics. We find that polar structures in the multi-domain state in relaxors are analogous to those of the slush state of water. The multi-domain structure of relaxors that is revealed by our molecular dynamics simulations is consistent with recent experimental diffuse scattering results and indicates that relaxors have a high density of low-angle domain walls. This insight explains the recently discovered classes of relaxors that cannot be described by the polar nanoregion model, and provides guidance for the design and synthesis of new relaxor materials.

20.
J Photochem Photobiol B ; 172: 102-108, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28544967

RESUMEN

A UV-absorbing compound was purified and identified as a novel glycosylated mycosporine-like amino acid (MAA), 13-O-ß-galactosyl-porphyra-334 (ß-Gal-P334) from the edible cyanobacterium Nostoc sphaericum, known as "ge xian mi" in China and "cushuro" in Peru. Occurrence of the hexosylated derivative of shinorine (hexosyl-shinorine) was also supported by LC-MS/MS analysis. ß-Gal-P334 accounted for about 86.5% of total MAA in N. sphaericum, followed by hexosyl-shinorine (13.2%) and porphyra-334 (0.2%). ß-Gal-P334 had an absorption maximum at 334nm and molecular absorption coefficient was 46,700 at 334nm. Protection activity of ß-Gal-P334 from UVB and UVA+8-methoxypsoralen induced cell damage on human keratinocytes (HaCaT) was assayed in comparison with other MAA (porphyra-334, shinorine, palythine and mycosporine-glycine). The UVB protection activity was highest in mycosporine-glycine, followed by palythine, ß-Gal-P334, porphyra-334 and shinorine in order. ß-Gal-P334 had highest protection activity from UVA+8-methoxypsoralen induced cell damage followed by porphyra-334, shinorine, mycosporine-glycine and palythine. We also found an antioxidant (radical-scavenging) activity of ß-Gal-P334 by colorimetric and ESR methods. From these findings, ß-Gal-P334 was suggested to play important roles in stress tolerant mechanisms such as UV and oxidative stress in N. sphaericum as a major MAA. We also consider that the newly identified MAA, ß-Gal-P334 has a potential for use as an ingredient of cosmetics and toiletries.


Asunto(s)
Ciclohexanonas/química , Glicina/análogos & derivados , Nostoc/química , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Rayos Ultravioleta , Aminoácidos/química , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Cromatografía Líquida de Alta Presión , Ciclohexanonas/aislamiento & purificación , Ciclohexanonas/farmacología , Ciclohexilaminas/química , Glicina/química , Glicina/aislamiento & purificación , Glicina/farmacología , Glicosilación , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Conformación Molecular , Nostoc/metabolismo , Estrés Oxidativo/efectos de la radiación , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Espectrometría de Masas en Tándem
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