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1.
Circ Res ; 130(5): 711-724, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35086342

RESUMEN

BACKGROUND: Oxidative stress in cardiac disease promotes proarrhythmic disturbances in Ca2+ homeostasis, impairing luminal Ca2+ regulation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the RyR2 (ryanodine receptor), and increasing channel activity. However, exact mechanisms underlying redox-mediated increase of RyR2 function in cardiac disease remain elusive. We tested whether the oxidoreductase family of proteins that dynamically regulate the oxidative environment within the SR are involved in this process. METHODS: A rat model of hypertrophy induced by thoracic aortic banding (TAB) was used for ex vivo whole heart optical mapping and for Ca2+ and reactive oxygen species imaging in isolated ventricular myocytes (VMs). RESULTS: The SR-targeted reactive oxygen species biosensor ERroGFP showed increased intra-SR oxidation in TAB VMs that was associated with increased expression of Ero1α (endoplasmic reticulum oxidoreductase 1 alpha). Pharmacological (EN460) or genetic Ero1α inhibition normalized SR redox state, increased Ca2+ transient amplitude and SR Ca2+ content, and reduced proarrhythmic spontaneous Ca2+ waves in TAB VMs under ß-adrenergic stimulation (isoproterenol). Ero1α overexpression in Sham VMs had opposite effects. Ero1α inhibition attenuated Ca2+-dependent ventricular tachyarrhythmias in TAB hearts challenged with isoproterenol. Experiments in TAB VMs and human embryonic kidney 293 cells expressing human RyR2 revealed that an Ero1α-mediated increase in SR Ca2+-channel activity involves dissociation of intraluminal protein ERp44 (endoplasmic reticulum protein 44) from the RyR2 complex. Site-directed mutagenesis and molecular dynamics simulations demonstrated a novel redox-sensitive association of ERp44 with RyR2 mediated by intraluminal cysteine 4806. ERp44-RyR2 association in TAB VMs was restored by Ero1α inhibition, but not by reducing agent dithiothreitol, as hypo-oxidation precludes formation of covalent bond between RyR2 and ERp44. CONCLUSIONS: A novel axis of intraluminal interaction between RyR2, ERp44, and Ero1α has been identified. Ero1α inhibition exhibits promising therapeutic potential by stabilizing RyR2-ERp44 complex, thereby reducing spontaneous Ca2+ release and Ca2+-dependent tachyarrhythmias in hypertrophic hearts, without causing hypo-oxidative stress in the SR.


Asunto(s)
Cardiopatías , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Glicoproteínas de Membrana/metabolismo , Canal Liberador de Calcio Receptor de Rianodina , Animales , Arritmias Cardíacas/metabolismo , Calcio/metabolismo , Señalización del Calcio , Cardiopatías/metabolismo , Isoproterenol/farmacología , Miocitos Cardíacos/metabolismo , Oxidorreductasas/metabolismo , Oxidorreductasas/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo
2.
Alzheimer Dis Assoc Disord ; 38(2): 201-204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38563235

RESUMEN

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , República de Corea/epidemiología , Masculino , Femenino , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/patología , Disfunción Cognitiva/epidemiología , Anciano , Edad de Inicio , Sistema Glinfático/patología , Sistema Glinfático/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Factores de Riesgo
3.
Blood ; 137(9): 1208-1218, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33181835

RESUMEN

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Cardiomiopatías/etiología , Interleucina-18/sangre , Taquicardia Ventricular/etiología , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/fisiopatología , Animales , Arritmias Cardíacas/sangre , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Cardiomiopatías/sangre , Cardiomiopatías/fisiopatología , Humanos , Interleucina-18/análisis , Masculino , Ratones , Taquicardia Ventricular/sangre , Taquicardia Ventricular/fisiopatología , Adulto Joven
4.
Nano Lett ; 21(23): 10114-10121, 2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34817186

RESUMEN

A magnetic model with an unprecedentedly large number of parameters was determined from first-principles calculations for transition-metal phosphorus trisulfides (TMPS3's), reproducing the measured magnetic ground states of bulk TMPS3's. Our Monte Carlo simulations for the critical temperature, magnetic susceptibility, and specific heat of bulk and few-layer TMPS3's agree well with available experimental data and show that the antiferromagnetic order of TMPS3's persists down to monolayers. Remarkably, the orbital polarization, neglected in recent first-principles studies, dramatically enhances the magnetic anisotropy of FePS3 by almost 2 orders of magnitude. A recent Raman study [Kim, K., Nat. Commun. 2019, 10, 345] claimed that magnetic ordering is absent in monolayer NiPS3 but simultaneously reported a strong two-magnon continuum; we show that the criterion used to judge magnetic ordering therein is invalid for monolayer NiPS3, providing an understanding of the two seemingly contradictory experimental results. The rich predictions on the magnetic susceptibility and specific heat of few-layer TMPS3's await experimental verifications.

5.
Biophys J ; 119(3): 690-704, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32668235

RESUMEN

Cardiac small conductance Ca2+-activated K+ (SK) channels are activated solely by Ca2+, but the SK current (ISK) is inwardly rectified. However, the impact of inward rectification in shaping action potentials (APs) in ventricular cardiomyocytes under ß-adrenergic stimulation or in disease states remains undefined. Two processes underlie this inward rectification: an intrinsic rectification caused by an electrostatic energy barrier from positively charged amino acids at the inner pore and a voltage-dependent Ca2+/Mg2+ block. Thus, Ca2+ has a biphasic effect on ISK, activating at low [Ca2+] yet inhibiting ISK at high [Ca2+]. We examined the effect of ISK rectification on APs in rat cardiomyocytes by simultaneously recording whole-cell apamin-sensitive currents and Ca2+ transients during an AP waveform and developed a computer model of SK channels with rectification features. The typical profile of ISK during AP clamp included an initial peak (mean 1.6 pA/pF) followed by decay to the point that submembrane [Ca2+] reached ∼10 µM. During the rest of the AP stimulus, ISK either plateaued or gradually increased as the cell repolarized and submembrane [Ca2+] decreased further. We used a six-state gating model combined with intrinsic and Ca2+/Mg2+-dependent rectification to simulate ISK and investigated the relative contributions of each type of rectification to AP shape. This SK channel model replicates key features of ISK recording during AP clamp showing that intrinsic rectification limits ISK at high Vm during the early and plateau phase of APs. Furthermore, the initial rise of Ca2+ transients activates, but higher [Ca2+] blocks SK channels, yielding a transient outward-like ISK trajectory. During the decay phase of Ca2+, the Ca2+-dependent block is released, causing ISK to rise again and contribute to repolarization. Therefore, ISK is an important repolarizing current, and the rectification characteristics of an SK channel determine its impact on early, plateau, and repolarization phases of APs.


Asunto(s)
Miocitos Cardíacos , Canales de Potasio de Pequeña Conductancia Activados por el Calcio , Potenciales de Acción , Animales , Apamina , Ventrículos Cardíacos , Ratas
6.
J Physiol ; 598(14): 2847-2873, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-30771223

RESUMEN

KEY POINTS: Small-conductance Ca2+ -activated K+ (SK) channels expressed in ventricular myocytes are dormant in health, yet become functional in cardiac disease. SK channels are voltage independent and their gating is controlled by intracellular [Ca2+ ] in a biphasic manner. Submicromolar [Ca2+ ] activates the channel via constitutively-bound calmodulin, whereas higher [Ca2+ ] exerts inhibitory effect during depolarization. Using a rat model of cardiac hypertrophy induced by thoracic aortic banding, we found that functional upregulation of SK2 channels in hypertrophic rat ventricular cardiomyocytes is driven by protein kinase A (PKA) phosphorylation. Using site-directed mutagenesis, we identified serine-465 as the site conferring PKA-dependent effects on SK2 channel function. PKA phosphorylation attenuates ISK rectification by reducing the Ca2+ /voltage-dependent inhibition of SK channels without changing their sensitivity to activating submicromolar [Ca2+ ]i . This mechanism underlies the functional recruitment of SK channels not only in cardiac disease, but also in normal physiology, contributing to repolarization under conditions of enhanced adrenergic drive. ABSTRACT: Small-conductance Ca2+ -activated K+ (SK) channels expressed in ventricular myocytes (VMs) are dormant in health, yet become functional in cardiac disease. We aimed to test the hypothesis that post-translational modification of SK channels under conditions accompanied by enhanced adrenergic drive plays a central role in disease-related activation of the channels. We investigated this phenomenon using a rat model of hypertrophy induced by thoracic aortic banding (TAB). Western blot analysis using anti-pan-serine/threonine antibodies demonstrated enhanced phosphorylation of immunoprecipitated SK2 channels in VMs from TAB rats vs. Shams, which was reversible by incubation of the VMs with PKA inhibitor H89 (1 µmol L-1 ). Patch clamped VMs under basal conditions from TABs but not Shams exhibited outward current sensitive to the specific SK inhibitor apamin (100 nmol L-1 ), which was eliminated by inhibition of PKA (1 µmol L-1 ). Beta-adrenergic stimulation (isoproterenol, 100 nmol L-1 ) evoked ISK in VMs from Shams, resulting in shortening of action potentials in VMs and ex vivo optically mapped Sham hearts. Using adenoviral gene transfer, wild-type and mutant SK2 channels were overexpressed in adult rat VMs, revealing serine-465 as the site that elicits PKA-dependent phosphorylation effects on SK2 channel function. Concurrent confocal Ca2+ imaging experiments established that PKA phosphorylation lessens rectification of ISK via reduction Ca2+ /voltage-dependent inhibition of the channels at high [Ca2+ ] without affecting their sensitivity to activation by Ca2+ in the submicromolar range. In conclusion, upregulation of SK channels in diseased VMs is mediated by hyperadrenergic drive in cardiac hypertrophy, with functional effects on the channel conferred by PKA-dependent phosphorylation at serine-465.


Asunto(s)
Miocitos Cardíacos , Canales de Potasio de Pequeña Conductancia Activados por el Calcio , Animales , Apamina , Cardiomegalia/metabolismo , Miocitos Cardíacos/metabolismo , Fosforilación , Ratas , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo
7.
Opt Lett ; 45(23): 6342-6345, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33258807

RESUMEN

We present a highly efficient double plasma mirror (DPM) that provides ultrahigh-contrast multi-petawatt (PW) laser pulses with a temporal contrast ratio reaching 1017 up to 160 ps and 1012 up to 2 ps before the main pulse. The high reflectivity of 70%, along with the high-contrast enhancement factor of 700,000, was achieved from the DPM installed after the final stage of a 4 PW Ti:sapphire laser. The 4 PW laser was equipped with cross-polarized wave generation and optical parametric chirped-pulse amplification stages for initial high-contrast operation. The DPM operation was undertaken with conditions that did not modify the spatiotemporal profiles of incident multi-PW laser pulses. This highly efficient DPM with the high-contrast enhancement promises the utilization of multiple PMs as a practical rear end for upcoming tens of petawatt lasers to achieve ultrahigh temporal contrast.

8.
Am J Emerg Med ; 38(6): 1141-1145, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31493979

RESUMEN

OBJECTIVE: Patients with ST-segment elevation myocardial infarction (STEMI) are sometimes boarded in the emergency department (ED) after percutaneous coronary intervention (PCI). We evaluated the effects of direct and indirect admission to the CCU on mortality and the effect on length of stay (LOS) in patients with STEMI. METHOD: This was a retrospective observational study of patients with STEMI between Jan 2014 and Nov 2017. The patients were divided into the direct admission (DA) group, who were admitted into the CCU immediately after PCI, and the indirect admission (IA) group, who were admitted after boarding in the ED. The primary endpoint was in-hospital mortality. Secondary endpoints were 3-month mortality, LOS in CCU and hospital, and LOS under intensive care. RESULTS: During the study period, 780 patients were enrolled and analyzed. The in-hospital mortality rate and 3-month mortality rate were 5.9% (46 patients) and 8.5% (66 patients). The DA group and IA group had similar in-hospital and 3-month mortality rates (P = .50, P = .28). The median CCU LOS and hospital LOS was similar for both groups (P = .28, P = .46). However, LOS under in intensive care for the IA group was significantly longer than that of the DA group (DA, 31.9 h; IA, 38.7 h; P < .001). CONCLUSION: This study suggests that direct admission after PCI and indirect admission was not associated with mortality in patients with STEMI. In addition, the stay in ED also appears to be associated with the duration of stay under critical care.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Admisión del Paciente/tendencias , Transferencia de Pacientes/tendencias , Infarto del Miocardio con Elevación del ST/mortalidad , Tiempo de Tratamiento/tendencias , Anciano , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/terapia , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento
9.
Sensors (Basel) ; 20(23)2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33260720

RESUMEN

The Angle-of-Arrival (AOA) has a variety of applications in civilian and military wireless communication fields. Due to the rapid development of the location-based service (LBS) industry, the importance of the AOA estimation technique has increased. Although a large antenna array is necessary to estimate accurate AOA information of many signals, the computational complexity of conventional AOA estimation algorithms, such as Multiple Signal Classification (MUSIC), is dramatically increased. In this paper, we propose a cascade AOA estimation algorithm employing CAPON and Beamspace MUSIC, based on a flexible (on/off) antenna array. First, this approach roughly finds AOA groups, including several signal AOAs using CAPON, by applying some of the antenna elements. Then, it estimates each signal AOA in the estimated AOA groups using Beamspace MUSIC by applying the full size of the antenna array. In addition to extremely low computational complexity, the proposed algorithm also has similar estimation performance to that of MUSIC. In particular, the proposed cascade AOA estimation algorithm is highly efficient when employing a massive antenna array. Representative computer simulation examples are provided to illustrate the AOA estimation performance of the proposed technique.

10.
Korean J Parasitol ; 58(1): 61-65, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32145729

RESUMEN

Majority of the imported malaria cases in Korea is attributed to Plasmodium falciparum and P. vivax infections, whereas P. malariae and P. ovale infections are very rare. Falciparum and ovale malaria are mostly imported from Africa, while most of the vivax malaria cases are imported from Southeast Asia. Here, we report 6 Korean imported ovale malaria cases (4 males and 2 females) who had visited in Africa during 2013-2016. These subjects were diagnosed with P. ovale based on microscopic findings, Plasmodium species-specific nested-PCR, and phylogenetic clade using 18S rRNA gene sequences. We identified 2 P. ovale subtypes, 1 P. ovale curtisi (classic type) and 5 P. ovale wallikeri (variant type). All patients were treated with chloroquine and primaquine, and no relapse or recrudescence was reported for 1 year after treatment. With increase of travelers to the countries where existing Plasmodium species, the risk of Plasmodium infection is also increasing. Molecular monitoring for imported malaria parasites should be rigorously and continuously performed to enable diagnosis and certification of Plasmodium spp.


Asunto(s)
Malaria/diagnóstico , Malaria/parasitología , Plasmodium ovale/genética , Plasmodium ovale/aislamiento & purificación , Pueblo Asiatico , Femenino , Humanos , Masculino , ARN Ribosómico 18S/genética , Sudáfrica , Factores de Tiempo , Viaje
11.
Heart Surg Forum ; 22(5): E317-E318, 2019 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-31596704

RESUMEN

Cardiac myxoma typically is thought to be a slow-growing, benign primary. Atrial myxomas can lead to many complications and can also mimic mitral stenosis, infective endocarditis, and other vascular diseases associated with systemic embolization. A 75-year-old woman with a history of lung cancer (pT1cN1, adenocarcinoma), atrial fibrillation, and a cerebral infarction presented with dysarthria and visual disturbances. In our case, we had to consider some questionable issues with the left atrial mass, and whether the recurrence of cerebral events was due to the thrombotic material in the left atrium or from locally recurrent lung cancer from the stump margin of the previously resected left superior pulmonary vein. We present a case with a rapidly-growing left atrial myxoma with a growth rate of 12.60 mm/month, rather than a thrombus or local recurrence of tumor under a medication of non-VKA oral antagonists.


Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mixoma/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Adenocarcinoma/cirugía , Anciano , Fibrilación Atrial/etiología , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiología , Diagnóstico Diferencial , Progresión de la Enfermedad , Endocarditis/diagnóstico , Femenino , Atrios Cardíacos , Neoplasias Cardíacas/patología , Neoplasias Cardíacas/cirugía , Humanos , Neoplasias Pulmonares/cirugía , Estenosis de la Válvula Mitral/diagnóstico , Mixoma/patología , Mixoma/cirugía
12.
Korean J Parasitol ; 57(3): 283-290, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31284351

RESUMEN

A rapid diagnostic test (RDT) kit was developed to detect non-structural protein 1 (NS1) of yellow fever virus (YFV) using monoclonal antibody. NS1 protein was purified from the cultured YFV and used to immunize mice. Monoclonal antibody to NS1 was selected and conjugated with colloidal gold to produce the YFV NS1 RDT kit. The YFV RDTs were evaluated for sensitivity and specificity using positive and negative samples of monkeys from Brazil and negative human blood samples from Korea. Among monoclonal antibodies, clones 3A11 and 3B7 proved most sensitive, and used for YFV RDT kit. Diagnostic accuracy of YFV RDT was fairly high; Sensitivity was 0.0% and specificity was 100% against Dengue viruses type 2 and 3, Zika, Chikungunya and Mayaro viruses. This YFV RDT kit could be employed as a test of choice for point-of-care diagnosis and large scale surveys of YFV infection under clinical or field conditions in endemic areas and on the globe.


Asunto(s)
Pruebas Diagnósticas de Rutina/métodos , Proteínas no Estructurales Virales/análisis , Fiebre Amarilla/diagnóstico , Virus de la Fiebre Amarilla/aislamiento & purificación , Animales , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/inmunología , Femenino , Haplorrinos , Humanos , Inmunización , Ratones , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Fiebre Amarilla/sangre , Fiebre Amarilla/inmunología , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/genética , Virus de la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/fisiología
13.
J Physiol ; 596(8): 1341-1355, 2018 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-29377142

RESUMEN

KEY POINTS: T-wave alternans (TWA) and T-wave lability (TWL) are precursors of ventricular arrhythmias in long QT syndrome; however, the mechanistic link remains to be clarified. Computer simulations show that action potential duration (APD) prolongation and slowed heart rates promote APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos can exacerbate pre-existing or induce de novo APD dispersion, which combines with enhanced ICa,L to result in premature ventricular complexes (PVCs) originating from the APD gradient region. These PVCs can directly degenerate into re-entrant arrhythmias without the need for an additional tissue substrate or further exacerbate the APD dispersion to cause spontaneous initiation of ventricular arrhythmias. Experiments conducted in transgenic long QT rabbits show that PVC alternans occurs at slow heart rates, preceding spontaneous intuition of ventricular arrhythmias. ABSTRACT: T-wave alternans (TWA) and irregular beat-to-beat T-wave variability or T-wave lability (TWL), the ECG manifestations of action potential duration (APD) alternans and variability, are precursors of ventricular arrhythmias in long QT syndromes. TWA and TWL in patients tend to occur at normal heart rates and are usually potentiated by bradycardia. Whether or how TWA and TWL at normal or slow heart rates are causally linked to arrhythmogenesis remains unknown. In the present study, we used computer simulations and experiments of a transgenic rabbit model of long QT syndrome to investigate the underlying mechanisms. Computer simulations showed that APD prolongation and slowed heart rates caused early afterdepolarization-mediated APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos exacerbated pre-existing APD dispersion and, in addition, APD chaos could also induce APD dispersion de novo via chaos desynchronization. Increased APD dispersion, combined with substantially enhanced ICa,L , resulted in a tissue-scale dynamical instability that gave rise to the spontaneous occurrence of unidirectionally propagating premature ventricular complexes (PVCs) originating from the APD gradient region. These PVCs could directly degenerate into re-entrant arrhythmias without the need for an additional tissue substrate or could block the following sinus beat to result in a longer RR interval, which further exacerbated the APD dispersion giving rise to the spontaneous occurrence of ventricular arrhythmias. Slow heart rate-induced PVC alternans was observed in experiments of transgenic LQT2 rabbits under isoproterenol, which was associated with increased APD dispersion and spontaneous occurrence of ventricular arrhythmias, in agreement with the theoretical predictions.


Asunto(s)
Síndrome de QT Prolongado/fisiopatología , Potenciales de Acción , Animales , Electrocardiografía , Modelos Cardiovasculares , Contracción Miocárdica , Conejos , Disfunción Ventricular/fisiopatología
14.
Phys Rev Lett ; 120(13): 136402, 2018 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-29694193

RESUMEN

Strong charge-spin coupling is found in a layered transition-metal trichalcogenide NiPS_{3}, a van der Waals antiferromagnet, from studies of the electronic structure using several experimental and theoretical tools: spectroscopic ellipsometry, x-ray absorption, photoemission spectroscopy, and density functional calculations. NiPS_{3} displays an anomalous shift in the optical spectral weight at the magnetic ordering temperature, reflecting strong coupling between the electronic and magnetic structures. X-ray absorption, photoemission, and optical spectra support a self-doped ground state in NiPS_{3}. Our work demonstrates that layered transition-metal trichalcogenide magnets are useful candidates for the study of correlated-electron physics in two-dimensional magnetic materials.

15.
Nanotechnology ; 29(33): 335501, 2018 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-29808831

RESUMEN

The physical and operating principle of a stress sensor, based on two crossing carbon fibers functionalized with ZnO nanorod-shaped nanostructures, was recently demonstrated. The functionalization process has been here extended to tows made of one thousand fibers, like those commonly used in industrial processing, to prove the idea that the same working principle can be exploited in the creation of smart sensing carbon fiber composites. A stress-sensing device made of two functionalized tows, fixed with epoxy resin and crossing like in a typical carbon fiber texture, was successfully tested. Piezoelectric properties of single nanorods, as well as those of the test device, were measured and discussed.

16.
Parasitology ; 145(12): 1531-1539, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29580315

RESUMEN

Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.


Asunto(s)
Adenilato Quinasa/inmunología , Antígenos Helmínticos/inmunología , Clonorquiasis/diagnóstico , Clonorchis sinensis/inmunología , Adenilato Quinasa/genética , Animales , Antígenos Helmínticos/genética , Western Blotting , Clonorquiasis/parasitología , Clonorchis sinensis/enzimología , Clonorchis sinensis/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Filogenia , Proteínas Recombinantes , Pruebas Serológicas
17.
Am J Emerg Med ; 36(4): 620-624, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28970026

RESUMEN

INTRODUCTION: Although consultations are essential for delivering safe, high-quality care to patients in emergency departments, they contribute to emergency department patient flow problems and overcrowding which is associated with several adverse outcomes, such as increases in patient mortality and poor quality care. This study aimed to investigate how time flow metrics including emergency department length of stay is influenced by changes to the internal medicine consultation policy. METHOD: This study is a pre- and post-controlled interventional study. We attempted to improve the internal medicine consultation process to be more concise. After the intervention, only attending emergency physicians consult internal medicine chief residents, clinical fellows, or junior staff of each internal medicine subspecialty who were on duty when patients required special care or an admission to internal medicine. RESULTS: Emergency department length of stay of patients admitted to the department of internal medicine prior to and after the intervention decreased from 996.94min to 706.62min. The times from consultation order to admission order and admission order to emergency department departure prior to and after the intervention were decreased from 359.59min to 180.38min and from 481.89min to 362.37min, respectively. The inpatient mortality rates and Inpatient bed occupancy rates prior to and after the intervention were similar. CONCLUSION: The improvements in the internal medicine consultation process affected the flow time metrics. Therefore, more comprehensive and cooperative strategies need to be developed to reduce the time cycle metrics and overcrowding of all patients in the emergency department.


Asunto(s)
Ocupación de Camas/estadística & datos numéricos , Mortalidad Hospitalaria , Tiempo de Internación/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Derivación y Consulta/normas , Adulto , Anciano , Estudios de Cohortes , Servicio de Urgencia en Hospital/organización & administración , Estudios de Evaluación como Asunto , Femenino , Humanos , Medicina Interna/organización & administración , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
18.
J Emerg Med ; 54(4): 427-434, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29478860

RESUMEN

BACKGROUND: Mortality prediction in patients with brain trauma during initial management in the emergency department (ED) is essential for creating the foundation for a better prognosis. OBJECTIVE: This study aimed to create a simple and useful survival predictive model for patients with isolated blunt traumatic brain injury that is easily available in the ED. METHODS: This is a retrospective study based on the trauma registry data of an academic teaching hospital. The inclusion criteria were age ≥ 15 years, blunt and not penetrating mechanism of injury, and Abbreviated Injury Scale (AIS) scores between 1 and 6 for head and 0 for all other body parts. The primary outcome was 30-day survival probability. Internal and external validation was performed. RESULTS: After univariate logistic regression analysis based on the derivation cohort, the final Predictor of Isolated Trauma in Head (PITH) model for survival prediction of isolated traumatic brain injury included Glasgow Coma Scale (GCS), age, and coded AIS of the head. In the validation cohort, the area under the curve of the PITH score was 0.970 (p < 0.0001; 95% confidence interval 0.960-0.978). Sensitivity and specificity were 95% and 81.7% at the cutoff value of 0.9 (probability of survival 90%), respectively. CONCLUSIONS: The PITH model performed better than the GCS; Revised Trauma Score; and mechanism of injury, GCS, age, and arterial pressure. It will be a useful triage method for isolated traumatic brain injury in the early phase of management.


Asunto(s)
Lesiones Traumáticas del Encéfalo/mortalidad , Técnicas de Apoyo para la Decisión , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/epidemiología , Estudios de Cohortes , Traumatismos Craneocerebrales/epidemiología , Traumatismos Craneocerebrales/mortalidad , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros/estadística & datos numéricos , República de Corea/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia
19.
Korean J Parasitol ; 56(3): 305-308, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29996637

RESUMEN

This study was aimed to disclose the prevalence rate of tick-borne pathogens from ticks collected from cattle and wild animals in Tanzania in 2012. Ticks were collected from slaughtered cattle and dead wild animals from November 5 to December 23, 2012 and identified. PCR for detecting Anaplasmataceae, Piroplamidae, Rickettsiaceae, Borrelia spp., and Coxiella spp. were done. Among those tested, Rickettsiaceae, Piroplasmidae, and Anaplasmataceae, were detected in ticks from the 2 regions. Rickettsiaceae represented the major tick-borne pathogens of the 2 regions. Ticks from animals in Maswa were associated with a higher pathogen detection rate compared to that in ticks from Iringa. In addition, a higher pathogen detection rate was observed in ticks infesting cattle than in ticks infesting wild animals. All examined ticks of the genus Amblyomma were infected with diverse pathogens. Ticks of the genera Rhipicephalus and Hyalomma were infected with 1 or 2 pathogens. Collectively, this study provides important information regarding differences in pathogen status among various regions, hosts, and tick species in Tanzania. Results in this study will affect the programs to prevent tick-borne diseases (TBD) of humans and livestock in Tanzania.


Asunto(s)
Anaplasma/patogenicidad , Animales Salvajes/parasitología , Borrelia/patogenicidad , Enfermedades de los Bovinos/etiología , Bovinos/parasitología , Coxiella/patogenicidad , Piroplasmida/patogenicidad , Rickettsiaceae/patogenicidad , Enfermedades por Picaduras de Garrapatas/etiología , Enfermedades por Picaduras de Garrapatas/veterinaria , Garrapatas/microbiología , Garrapatas/parasitología , Anaplasma/aislamiento & purificación , Animales , Borrelia/aislamiento & purificación , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Coxiella/aislamiento & purificación , Piroplasmida/aislamiento & purificación , Prevalencia , Rickettsiaceae/aislamiento & purificación , Tanzanía/epidemiología , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/parasitología , Factores de Tiempo
20.
Am J Emerg Med ; 35(12): 1882-1886, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28637583

RESUMEN

INTRODUCTION: The Revised Trauma Score (RTS) is used worldwide in prehospital practice and in the emergency department (ED) settings to triage trauma patients. The main purpose of this study was to evaluate the value of the RTS plus serum albumin (RTS-A) and to compare it with other existing trauma scores as well as to compare the predictive performance of the Trauma and Injury Severity Score with the RTS-A (TRISS-A) with the original TRISS. METHODS: This was a single center, trauma registry based observational cohort study. Data were collected from consecutive patients with blunt or penetrating injuries who presented to the emergency department of a tertiary referral hospital, between January 2012 and June 2016. 3145 and 2447 patients were assigned to the derivation group and validation group, respectively. Main outcome was in-hospital mortality. RESULTS: Among patients in the derivation group, the median [interquartile range] age was 59 [43-73] years, and 66.7% were male. The area under the receiver operating characteristic curves (AUC) of the RTS-A (0.948; 95% CI: 0.939-0.955) was higher than that of the RTS (0.919; 95% CI: 0.909-0.929). In patients with blunt trauma, the AUC of the TRISS-A (0.960; 95% CI: 0.952-0.967) was significantly higher than that of the original TRISS (0.949; 95% CI: 0.941-0.957). CONCLUSION: The value of the RTS-A predicts the in-hospital mortality of trauma patients better than the RTS, and the TRISS-A is a better mortality predictor compared to the original TRISS in patients with blunt trauma.


Asunto(s)
Cuidados Críticos , Servicio de Urgencia en Hospital , Albúmina Sérica/metabolismo , Heridas y Lesiones/metabolismo , Adulto , Anciano , Cuidados Críticos/métodos , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , República de Corea/epidemiología , Índices de Gravedad del Trauma , Triaje , Heridas y Lesiones/mortalidad
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