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1.
Phys Rev Lett ; 132(5): 056101, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364152

RESUMO

The slow transition from an out-of-equilibrium glass towards a supercooled liquid is a complex relaxation phenomenon. In this Letter, we study the correlation between mechanical relaxation and equilibration kinetics in a Pd_{20}Pt_{20}Cu_{20}Ni_{20}P_{20} high-entropy metallic glass. The evolution of stress relaxation with aging time was obtained with an unprecedented detail, allowing us to pinpoint new interesting features. The long structural relaxation towards equilibrium contains a wide distribution of activation energies, instead of being just associated to the ß relaxation as commonly accepted. The stress relaxation time can be correlated with the equilibration rate and we observe a decrease of microstructural heterogeneity which contrasts with an increase of dynamic heterogeneity. These results significantly enhance our insight of the interplay between relaxation dynamics and thermodynamics in metallic glasses.

2.
J Phys Condens Matter ; 35(42)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37429290

RESUMO

Linearly polarized soft x-rays provide information about electronic or magnetic anisotropy through absorption into materials or generation of photoelectrons. In order to change the relative angle between linear polarization and sample crystalline axes, either x-ray polarization or the sample needs to be rotated. Due to difficulties of polarization control in the soft x-ray range, a conventional approach was to rotate the sample. However, this method is not compatible, for example, withoperandomeasurements on non-uniform samples where sample size and rotational motion are severely restricted. At BL07LSU of SPring-8, we developed a new method to rotate the linear polarization angle using a segmented cross undulator. We report an application of this linear polarization rotation to resonant photoemission spectroscopy on an magnetic atomic layer Fe2N on Cu(111) to probe the electronic anisotropy of the 3dstates in the vicinity of the Fermi level.

4.
Phys Rev Lett ; 129(17): 175501, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36332263

RESUMO

Lacking the structural information of crystalline solids, the origin of the relaxation dynamics of metallic glasses is unclear. Here, we report the evolution of stress relaxation of high-entropy metallic glasses with distinct ß relaxation behavior. The fraction of liquidlike zones, determined at each temperature by the intensity of stress decay, is shown to be directly related to both the aging process and the spectrum of relaxation modes obtained by mechanical spectroscopy. The results shed light on the intrinsic correlation between the static and dynamic mechanical response in high-entropy and conventional metallic glasses, pointing toward a sluggish diffusion high-entropy effect in the liquid dynamics.

5.
AJNR Am J Neuroradiol ; 43(11): 1639-1645, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36202554

RESUMO

BACKGROUND AND PURPOSE: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated. MATERIALS AND METHODS: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival. RESULTS: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival. CONCLUSIONS: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA.


Assuntos
Adenoma Pleomorfo , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/diagnóstico por imagem , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Prognóstico , Imageamento por Ressonância Magnética , Carcinoma/diagnóstico por imagem
6.
AJNR Am J Neuroradiol ; 43(3): 368-375, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241425

RESUMO

BACKGROUND AND PURPOSE: An accurate assessment of the hemodynamics of an intracranial dural AVF is necessary for treatment planning. We aimed to investigate the utility of 4D-MRA based on superselective pseudocontinuous arterial spin-labeling with CENTRA-keyhole and view-sharing (4D-S-PACK) for the vessel-selective visualization of intracranial dural AVFs. MATERIALS AND METHODS: We retrospectively analyzed the images of 21 patients (12 men and 9 women; mean age, 62.2 [SD,19.2] years) with intracranial dural AVFs, each of whom was imaged with DSA, 4D-S-PACK, and nonselective 4D-MRA based on pseudocontinuous arterial spin-labeling combined with CENTRA-keyhole and view-sharing (4D-PACK). The shunt location, venous drainage patterns, feeding artery identification, and Borden classification were evaluated by 2 observers using both MRA methods on separate occasions. Vessel selectivity was evaluated on 4D-S-PACK. RESULTS: Shunt locations were correctly evaluated in all 21 patients by both observers on both MRA methods. With 4D-S-PACK, observers 1 and 2 detected 76 (80.0%, P < .001) and 73 (76.8%, P < .001) feeding arteries of the 95 feeding arteries identified on DSA but only 39 (41.1%) and 46 (48.4%) feeding arteries with nonselective 4D-PACK, respectively. Both observers correctly identified 10 of the 11 patients with cortical venous reflux confirmed by DSA with both 4D-S-PACK and 4D-PACK (sensitivity = 90.9%, specificity = 90.9% for each method), and they made accurate Borden classifications in 20 of the 21 patients (95.2%) on both MRA methods. Of the 84 vessel territories examined, vessel selectivity was graded 3 or 4 in 73 (91.2%) and 66 (88.0%) territories by observers 1 and 2, respectively. CONCLUSIONS: 4D-S-PACK is useful for the identification of feeding arteries and accurate classifications of intracranial dural AVFs and can be a useful noninvasive clinical tool.


Assuntos
Artérias , Angiografia por Ressonância Magnética , Angiografia Digital/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Marcadores de Spin
9.
World J Surg ; 44(8): 2770-2776, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32318792

RESUMO

BACKGROUND: The role of adjuvant hepatic intra-arterial infusion chemotherapy (HAI) is considered to be a promising option. METHODS: We examined treatment effects of adjuvant HAI using cisplatin in 37 hepatocellular carcinoma (HCC) patients with portal vein infiltration (PVI) who underwent hepatectomy in comparison with those in 85 patients who did not. RESULTS: PVI in 89 patients. Increased levels of aspartate transaminase, tumor markers, size and microvessel tumor infiltration (MVI) or cirrhosis, poorly differentiation, non-adjuvant HAI was associated with lower overall survival (p = 0.09). Poor differentiation, MVI and HAI were independently risk factors associated with tumor-free and overall survivals by the multivariate analysis (p < 0.05). Adjuvant HAI tended to show longer survivals in comparison with no-HAI (p = 0.08) and the multivariate analysis revealed significant efficacy of HAI for better prognosis. CONCLUSION: Adjuvant HAI showed effectiveness on prolonging tumor-free and patient survival in HCC with PVI and is a promising option in the daily clinical practice.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Hepatectomia/mortalidade , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
10.
Sci Rep ; 10(1): 4074, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139763

RESUMO

Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of 131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.


Assuntos
Poluição Ambiental/efeitos adversos , Acidente Nuclear de Fukushima , Inquéritos Epidemiológicos , Radioisótopos do Iodo/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Monitoramento de Radiação , Neoplasias da Glândula Tireoide/epidemiologia , Criança , Humanos , Japão/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Doses de Radiação , Neoplasias da Glândula Tireoide/etiologia
11.
J Hosp Infect ; 102(1): 116-119, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30629999

RESUMO

This paper reports a case of nosocomial transmission of Mycobacterium tuberculosis by brief casual contact. Routine variable number tandem repeat typing in Yamagata Prefecture, Japan found that M. tuberculosis clinical isolates from two patients showed indistinguishable genotypes. The patients had an epidemiological relationship of sharing a waiting room in a hospital on the same day. As comparative genomics detected only two single nucleotide variants between the isolates, it was concluded that recent tuberculosis transmission occurred in the waiting room. These results indicate that the physical separation of infectious tuberculosis patients is an essential control measure for preventing unpredictable nosocomial transmission by casual contact.


Assuntos
Transmissão de Doença Infecciosa , Genômica , Tipagem Molecular , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/transmissão , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Isolamento de Pacientes , Polimorfismo de Nucleotídeo Único
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 6644-6647, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31947365

RESUMO

To regain the locomotive ability in daily living, many prosthetic knee joint units have been developed for transfemoral amputees. Until now, several prosthetic knees have been developed for stair ascent as commercial products. Such microprocessor controlled knees are multifunctional, and they are able to realize many activities of daily living for transfemoral amputees. However, those prosthetic knees are very expensive, so they have not been widely adopted. The purpose of the present study was to develop a control method for transfemoral prosthetic knees that deals with variation of gait parameters within subjects. We made improvement on the control algorithm that we previously developed for level walking and stair ascending. To evaluate the newly proposed algorithm and threshold values, the database of the level walking was used. Although gait detection for the stance phase of stair ascending could not be evaluated because of absence of a database for stair ascent, the precision and recall of the gate detection algorithm for the stance phase and swing phase of level walking were increased.


Assuntos
Amputados , Atividades Cotidianas , Fenômenos Biomecânicos , Fêmur , Humanos , Joelho , Desenho de Prótese , Coxa da Perna , Caminhada
13.
Int J Tuberc Lung Dis ; 22(10): 1239-1242, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30236195

RESUMO

BACKGROUND: Two false-positive tuberculosis (TB) cases in Yamagata Prefecture, Japan, 2016. OBJECTIVE: To report the effectiveness of comparative genomics of Mycobacterium tuberculosis for identification of cross-contamination cases. DESIGN: Case report of laboratory cross-contamination. RESULTS: Beginning with detection of an identical genotype in two M. tuberculosis strains using variable number of tandem repeat typing, we suspected M. tuberculosis cross-contamination of specimens collected in a mycobacteriology laboratory based on epidemiological investigations. This suspicion was confirmed using comparative genomics of the two M. tuberculosis strains and a strain from an epidemiologically unrelated specimen from the same batch as the two strains in the mycobacteriology laboratory. All strains had an identical genomic sequence with no single nucleotide variants. CONCLUSION: Comparative genomics, which offers the highest discrimination power, is a potent tool for identifying laboratory cross-contamination using epidemiological investigations.


Assuntos
Reações Falso-Positivas , Genômica , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Genótipo , Humanos , Japão , Laboratórios Hospitalares , Polimorfismo de Fragmento de Restrição , Manejo de Espécimes , Tuberculose/diagnóstico
14.
Plant Signal Behav ; 13(6): e1477907, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29944442

RESUMO

In Arabidopsis thaliana, the bHLH transcription factor, GLABRA3 (AtGL3), is an important regulator of epidermal cell differentiation and positively controls anthocyanin accumulation. In contrast, we previously showed that Solanum lycopersicum GLABRA3 (SlGL3), the AtGL3 homolog, suppressed anthocyanin accumulation in Arabidopsis. To clarify this functional discrepancy in anthocyanin accumulation, we analyzed the SlGL3 expression pattern in anthocyanin-induced tomato. The SlGL3 expression was significantly reduced in tomato seedlings rich in anthocyanin as a result of inorganic phosphate (Pi) starvation. This was consistent with the previous result obtained in Arabidopsis, wherein the overexpression of SlGL3 was shown to inhibit anthocyanin accumulation. Our study suggests that the function of SlGL3 is different from that of AtGL3, and it might inhibit anthocyanin accumulation in tomato.


Assuntos
Antocianinas/metabolismo , Solanum lycopersicum/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Fosfatos/deficiência , Fosfatos/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/metabolismo
15.
Data Brief ; 18: 1773-1776, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29904678

RESUMO

Intercellular movement of transcription factor proteins is essential for plant development. The R3 type MYB transcription factor protein, CAPRICE (CPC), moves from non-hair cells to root-hair cells where it promotes root hair formation in Arabidopsis root epidermis. In contrast, the CPC homolog of ENHANCER OF TRY AND CPC1 (ETC1) cannot move in root epidermal cells. In this work, we present protein localization data of CPC-ETC1 chimeric proteins. Localization of CPC-ETC1-GFP fusion proteins of chimera1 and chimera2 transgenic plants was observed using confocal laser scanning microscope. Insertion of ETC1-specific amino acids into CPC somewhat prevents normal protein localization of CPC in root epidermal cells. Cell-to-cell movement of chimera1 and chimera2 proteins from non-hair cells to root-hair cells was interfered. Nuclear localization was also inhibited, especially in chimera1.

16.
AJNR Am J Neuroradiol ; 39(7): 1369-1375, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29748204

RESUMO

BACKGROUND AND PURPOSE: Glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging allows the direct measurement and mapping of glycosaminoglycans. In this study, we aimed to evaluate the usefulness of gagCEST imaging in the quantitative assessment of intervertebral disc degeneration in a comparison with Pfirrmann grade and T1-ρ measurements. MATERIALS AND METHODS: Ninety-six lumbar intervertebral discs in 24 volunteers (36.0 ± 8.5 years of age, 21 men and 3 women) were examined with both gagCEST imaging and T1-ρ measurements. The gagCEST imaging was performed at 3T with a saturation pulse with 1.0-second duration and the B1 amplitude of 0.8 µT followed by imaging by a 2D fast spin-echo sequence. The Z-spectra were obtained at 25 frequency offsets from -3 to +3 ppm (step, 0.25 ppm). A point-by-point B0 correction was performed with a B0 map. The gagCEST signal and T1-ρ values were measured in the nucleus pulposus in each intervertebral disc. The Pfirrmann grades were assessed on T2-weighted images. RESULTS: The gagCEST signal at grade I (5.36% ± 2.79%) was significantly higher than those at Pfirrmann grade II (3.15% ± 1.40%, P = .0006), grade III (0.14% ± 1.03%, P < .0001), grade IV (-1.75% ± 2.82%, P < .0001), and grade V (-1.47% ± 0.36%, P < .0001). The gagCEST signal at grade II was significantly higher than those of grade III (P < .0001), grade IV (P < .0001), and grade V (P < .0001). The gagCEST signal was significantly correlated negatively with Pfirrmann grade (P < .0001) and positively correlated with T1-ρ (P < .0001). CONCLUSIONS: GagCEST imaging could be a reliable and quantitative technique for assessing intervertebral disc degeneration.


Assuntos
Glicosaminoglicanos/análise , Processamento de Imagem Assistida por Computador/métodos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Correlação de Dados , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade
17.
Mater Sci Eng C Mater Biol Appl ; 88: 95-103, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29636143

RESUMO

The close match of stiffness between implant material and bone is critically important to avoid stress-shielding effect and ensure a fast healing of injured tissues. Here, we introduce liquid metal dealloying method for synthesis of robust open porous biomaterials possessing low Young's modulus. The remarkable advantage of the liquid metal dealloying method is a large flexibility in selecting chemical composition of a desired porous biomaterial together with unique tunable microstructure. To demonstrate the versatility of the method, a number of open porous TixZr100-x alloys with different chemical compositions and microstructural characteristics was developed by dealloying precursor (TixZr100-x)yCu100-y alloys in liquid magnesium. The effects of the processing conditions and the precursors' chemical composition on the microstructure of the porous TixZr100-x as well as their mechanical behavior were discussed in detail. In particular, the porous TixZr100-x distinguish themselves due to a low and tunable stiffness ranging from 3.2 to 15.1 GPa and a rather high strength reaching up to 480 MPa. This unique combination of mechanical properties of the new open porous TixZr100-x alloys becomes even more interesting in view of preliminary biological tests highlighting their excellent cytocompatibility. Overall, the liquid metal dealloying provides an opportunity for designing a new biomaterials platform with flexible tunable functionality.


Assuntos
Ligas , Materiais Biocompatíveis , Teste de Materiais , Silicatos , Titânio , Zircônio , Ligas/química , Ligas/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Células Cultivadas , Humanos , Porosidade , Silicatos/química , Silicatos/farmacologia , Titânio/química , Titânio/farmacologia , Zircônio/química , Zircônio/farmacologia
18.
Nutr Metab Cardiovasc Dis ; 27(8): 679-687, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28735816

RESUMO

BACKGROUND AND AIMS: To investigate whether the progression from prediabetes to diabetes is lower among those who undertake Ningen Dock (comprehensive health checkups with lifestyle education and doctor's consultation) than those who undertake basic mandatory occupational health checkups. METHODS AND RESULTS: Subjects aged 30-69 years with complete annual data from 2008 to 2012 for either Ningen Dock or basic health checkups were enrolled. Subjects with prediabetes (fasting plasma glucose 100-125 mg/dl or HbA1c 5.7-6.4%) at baseline were selected (14,928 in the comprehensive group and 10,433 in the basic group). The incidence of diabetes (fasting plasma glucose ≥ 126 mg/dl, HbA1c ≥ 6.5% or taking glucose-lowering drugs) and the reduction of risk factors were compared. After 4 years, 3226 cases of diabetes occurred among 25,361 subjects with prediabetes. The incidence of diabetes was lower in the comprehensive group than the basic group (2.9 vs. 3.8 cases/100 person-years, hazard ratio 0.75, 95% confidence interval 0.68-0.81 after adjustment). Moreover, more overweight subjects controlled their body mass index (16.2% vs. 13.2%) and more began a daily exercise habit (11.8% vs. 8.5%) in the comprehensive group than in the basic group. The incidence of diabetes was lower in subjects who could control their weight or start daily exercise at year 1 in the comprehensive group. CONCLUSION: Progression from prediabetes to diabetes was significantly lower in subjects undertaking a comprehensive health checkup with lifestyle education. Lifestyle education at health checkup for people with prediabetes might prevent progression to diabetes by reducing modifiable risk factors.


Assuntos
Diabetes Mellitus/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Obesidade/terapia , Educação de Pacientes como Assunto , Estado Pré-Diabético/terapia , Comportamento de Redução do Risco , Autocuidado , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Dieta Saudável , Progressão da Doença , Exercício Físico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Phys Rev E ; 95(5-1): 052112, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28618546

RESUMO

The intriguing and still open question concerning the composition law of κ-entropy S_{κ}(f)=1/2κ∑_{i}(f_{i}^{1-κ}-f_{i}^{1+κ}) with 0<κ<1 and ∑_{i}f_{i}=1 is here reconsidered and solved. It is shown that, for a statistical system described by the probability distribution f={f_{ij}}, made up of two statistically independent subsystems, described through the probability distributions p={p_{i}} and q={q_{j}}, respectively, with f_{ij}=p_{i}q_{j}, the joint entropy S_{κ}(pq) can be obtained starting from the S_{κ}(p) and S_{κ}(q) entropies, and additionally from the entropic functionals S_{κ}(p/e_{κ}) and S_{κ}(q/e_{κ}),e_{κ} being the κ-Napier number. The composition law of the κ-entropy is given in closed form and emerges as a one-parameter generalization of the ordinary additivity law of Boltzmann-Shannon entropy recovered in the κ→0 limit.

20.
Eur J Clin Microbiol Infect Dis ; 36(10): 1839-1845, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28477235

RESUMO

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.


Assuntos
Antibacterianos/farmacologia , Parede Celular/metabolismo , Daptomicina/farmacologia , Regulação Bacteriana da Expressão Gênica , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Idoso , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Mutação de Sentido Incorreto , Fenótipo
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