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1.
Circulation ; 149(8): 585-600, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-37994553

RESUMO

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.


Assuntos
Síndrome Coronariana Aguda , Aspirina/análogos & derivados , Nitratos , Intervenção Coronária Percutânea , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Intervenção Coronária Percutânea/efeitos adversos , Quimioterapia Combinada , Aspirina/efeitos adversos , Hemorragia/etiologia , Stents , Trombose/epidemiologia , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento
2.
Proc Natl Acad Sci U S A ; 118(46)2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34750262

RESUMO

DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints. However, its three-dimensional (3D) structure remains elusive with challenges in observing native structures of specimens at tens-of-nanometers resolution. Here, using cryogenic coherent X-ray diffraction imaging, we succeeded in obtaining nanoscale 3D structures of metaphase chromosomes that exhibited a random distribution of electron density without characteristics of high-order folding structures. Scaling analysis of the chromosomes, compared with a model structure having the same density profile as the experimental results, has discovered the fractal nature of density distributions. Quantitative 3D density maps, corroborated by molecular dynamics simulations, reveal that internal structures of chromosomes conform to diffusion-limited aggregation behavior, which indicates that 3D chromatin packing occurs via stochastic processes.


Assuntos
Cromatina/genética , Cromossomos/genética , Linhagem Celular Tumoral , DNA/genética , Células HCT116 , Humanos , Metáfase/genética , Difração de Raios X/métodos , Raios X
3.
Artigo em Inglês | MEDLINE | ID: mdl-38627197

RESUMO

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

4.
PLoS Pathog ; 17(5): e1009228, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33979382

RESUMO

Virus infection, such as hepatitis B virus (HBV), occasionally causes endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is counteractive machinery to ER stress, and the failure of UPR to cope with ER stress results in cell death. Mechanisms that regulate the balance between ER stress and UPR are poorly understood. Type 1 and type 2 interferons have been implicated in hepatic flares during chronic HBV infection. Here, we examined the interplay between ER stress, UPR, and IFNs using transgenic mice that express hepatitis B surface antigen (HBsAg) (HBs-Tg mice) and humanized-liver chimeric mice infected with HBV. IFNα causes severe and moderate liver injury in HBs-Tg mice and HBV infected chimeric mice, respectively. The degree of liver injury is directly correlated with HBsAg levels in the liver, and reduction of HBsAg in the transgenic mice alleviates IFNα mediated liver injury. Analyses of total gene expression and UPR biomarkers' protein expression in the liver revealed that UPR is induced in HBs-Tg mice and HBV infected chimeric mice, indicating that HBsAg accumulation causes ER stress. Notably, IFNα administration transiently suppressed UPR biomarkers before liver injury without affecting intrahepatic HBsAg levels. Furthermore, UPR upregulation by glucose-regulated protein 78 (GRP78) suppression or low dose tunicamycin alleviated IFNα mediated liver injury. These results suggest that IFNα induces ER stress-associated cell death by reducing UPR. IFNγ uses the same mechanism to exert cytotoxicity to HBsAg accumulating hepatocytes. Collectively, our data reveal a previously unknown mechanism of IFN-mediated cell death. This study also identifies UPR as a potential target for regulating ER stress-associated cell death.


Assuntos
Morte Celular , Antígenos de Superfície da Hepatite B/metabolismo , Hepatite B Crônica/complicações , Hepatócitos/patologia , Interferon-alfa/farmacologia , Falência Hepática Aguda/patologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/virologia , Humanos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/metabolismo , Camundongos , Camundongos Transgênicos
5.
Opt Express ; 31(16): 26135-26144, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710481

RESUMO

We demonstrate a propagation-based phase-contrast imaging method for full-field X-ray microscopy based on advanced Kirkpatrick-Baez (AKB) mirrors to achieve high-contrast observations of weak phase objects and correct field curvature aberrations. Through a demonstration performed at SPring-8, the phase contrast of weak phase objects such as polystyrene spheres and chemically fixed cells was successfully observed with high sensitivity (∼0.03 rad). Furthermore, the field of view of the AKB mirrors was expanded to the full area of the obtained images (25 × 30 µm) by correcting the field curvature aberration using reconstructed complex wavefields.

6.
Jpn J Clin Oncol ; 53(6): 472-479, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36999211

RESUMO

BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Salpingo-Ooforectomia , População do Leste Asiático , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Ovariectomia , Predisposição Genética para Doença
7.
Nature ; 543(7643): 131-135, 2017 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-28219079

RESUMO

Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure. The mechanism of O=O bond formation, however, remains obscure owing to the lack of intermediate-state structures. Here we describe the structural changes in PSII induced by two-flash illumination at room temperature at a resolution of 2.35 Å using time-resolved serial femtosecond crystallography with an XFEL provided by the SPring-8 ångström compact free-electron laser. An isomorphous difference Fourier map between the two-flash and dark-adapted states revealed two areas of apparent changes: around the QB/non-haem iron and the Mn4CaO5 cluster. The changes around the QB/non-haem iron region reflected the electron and proton transfers induced by the two-flash illumination. In the region around the OEC, a water molecule located 3.5 Å from the Mn4CaO5 cluster disappeared from the map upon two-flash illumination. This reduced the distance between another water molecule and the oxygen atom O4, suggesting that proton transfer also occurred. Importantly, the two-flash-minus-dark isomorphous difference Fourier map showed an apparent positive peak around O5, a unique µ4-oxo-bridge located in the quasi-centre of Mn1 and Mn4 (refs 4,5). This suggests the insertion of a new oxygen atom (O6) close to O5, providing an O=O distance of 1.5 Å between these two oxygen atoms. This provides a mechanism for the O=O bond formation consistent with that proposed previously.


Assuntos
Cristalografia/métodos , Elétrons , Lasers , Luz , Oxigênio/química , Oxigênio/efeitos da radiação , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/efeitos da radiação , Biocatálise/efeitos da radiação , Cianobactérias/química , Transporte de Elétrons/efeitos da radiação , Análise de Fourier , Manganês/química , Manganês/metabolismo , Modelos Moleculares , Ferroproteínas não Heme/química , Ferroproteínas não Heme/metabolismo , Ferroproteínas não Heme/efeitos da radiação , Oxigênio/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Prótons , Temperatura , Fatores de Tempo , Água/química , Água/metabolismo
8.
Support Care Cancer ; 31(9): 547, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656213

RESUMO

PURPOSE: Vitamin D plays a crucial role in skeletal metabolism and holds significant importance in the pathophysiology of multiple myeloma (MM). This study aimed to determine the prevalence of vitamin D deficiency among Japanese MM patients and its correlation with clinical outcomes. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed in 68 MM patients at a single institution in Japan, analyzing their association with clinical status, laboratory parameters including procollagen type 1 N-propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), health-related quality of life (HR-QOL) scores, and overall survival. Additionally, patients with suboptimal 25(OH)D levels received cholecalciferol supplementation (1000 IU/day), and changes in laboratory parameters were monitored. RESULTS: The median 25(OH)D level was 22 ng/ml, with 32% and 51% of patients exhibiting vitamin D deficiency (< 20 ng/ml) and insufficiency (20-29 ng/ml), respectively. The 25(OH)D levels were unrelated to sex, age, MM stage, or bone lesions, but the vitamin D-deficient group showed a tendency towards lower HR-QOL scores. Among patients achieving complete remission, vitamin D supplementation increased P1NP, while TRACP-5b remained unchanged. Overall survivals from vitamin D measurement and from MM diagnosis were significantly worse in the vitamin D-deficient group compared to the vitamin D-insufficient/-sufficient group. CONCLUSION: The study identified a considerable number of Japanese MM patients with insufficient serum vitamin D levels, with one-third being deficient. Additionally, vitamin D deficiency predicted poor overall survival in Japanese MM patients. Further investigation is required to determine whether vitamin D supplementation can improve the frailty and survival of vitamin D-deficient MM patients.


Assuntos
Mieloma Múltiplo , Deficiência de Vitamina D , Humanos , Prevalência , Qualidade de Vida , População do Leste Asiático , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Fosfatase Ácida Resistente a Tartarato , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Vitamina D
9.
Heart Vessels ; 38(5): 711-720, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36446927

RESUMO

Preventing phrenic nerve injury (PNI) during balloon-based ablation is essential. The superior vena cava-right atrial (SVC-RA) junction is located just opposite the balloon position during right superior pulmonary vein (RSPV) ablation, and the phrenic nerve runs nearby on the lateral side. We compared the occurrence of PNI between the two balloon-based ablation systems and also the lesions created at the SVC-RA junction, which were expected to represent the effect on extra-PV structures. Cryoballoon ablation (CBA, n = 110) and hot-balloon ablation (HBA, n = 90) were performed in atrial fibrillation patients. High-density maps of the SVC-RA junction were created in 93 patients (CBA = 53, HBA = 40), and the damaged area (< 1.0 mV) was determined as an "SVC lesion". CBA had a higher occurrence of transient PNI (7.3% vs 1.1%, p = 0.035), but all recovered during the 6-month follow-up. An apparent SVC lesion was documented in 43% of the patients (40/93), and all patients with PNI had this lesion. CBA created a frequent (CBA vs HBA = 55% vs 28%, p = 0.008) and wider (0.8[0.4-1.7] cm2 vs 0.5[0.3-0.7] cm2, p = 0.005) SVC lesion than HBA. A multivariate analysis revealed that the use of a CBA system was a predictive factor of the occurrence of SVC lesions. CBA had a higher occurrence of transient PNI but not a permanent form. Every patient with PNI had lesions on the SVC-RA junction, and CBA revealed more substantial ablation effects at the SVC-RA junction than HBA. This may be caused by the different characteristics of the two balloon-based ablation systems and their balloon positions.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Humanos , Veia Cava Superior/cirurgia , Nervo Frênico/lesões , Criocirurgia/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Veias Pulmonares/cirurgia , Biomarcadores , Ablação por Cateter/efeitos adversos , Resultado do Tratamento
10.
Nano Lett ; 22(11): 4603-4607, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35612588

RESUMO

Experimental characterization of the nanostructure of metastable functional materials has attracted significant attention with recent advances in computational materials discovery. However, since metastable glass-ceramics are easily damaged by irradiation, damage-free nanoimaging has not been realized thus far. Herein, we propose novel high-contrast coherent diffractive imaging that quantitatively analyzes the intact internal nanostructure of metastable glass-ceramics using femtosecond X-ray pulses. The immersion of sample particles in a solvent helps enhance the reconstructed image contrast and allows us to distinguish an ∼7% electron density difference between an amorphous form and crystals. Furthermore, morphological operations with a band-pass filter quantitatively elucidate the depth information. The evaluated volume ratio of the amorphous to crystalline phases is ∼2.5:1 for the measured metastable (Li2S)70-(P2S5)30 glass-ceramic particle. Sulfide glass-ceramics are used as electrolytes for all-solid-state batteries, which are indispensable for reducing the carbon footprint. Our results will facilitate structural studies on fragile metastable materials with important scientific and industrial implications.

11.
Int Heart J ; 64(2): 145-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37005310

RESUMO

We retrospectively examined the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo stenosis in large coronary vessels (LV; pre- or postprocedural reference vessel diameter ≥ 2.75 mm) in comparison with placement of drug-eluting stents (DESs).Consecutive de novo stenotic lesions in the LV electively and successfully treated with either PCB (n = 73) or DESs (n = 81) from January 2016 to December 2018 at our center were included. The primary endpoint was the incidence of target lesion failure (TLF), including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. The impact of PCB on TLF was examined using Cox proportional hazards models by including 39 variables. The secondary endpoint, angiographic restenosis, defined as a follow-up percent diameter stenosis > 50, was examined in angiographic follow-up lesions after PCB angioplasty (n = 56) and DES placement (n = 53). This retrospective investigation was conducted in July 2022.The mean PCB size and length were 3.23 ± 0.42 and 18.4 ± 4.3 mm, respectively. The TLF frequency in the PCB group (6.8% during the mean observational interval of 1536 ± 538 days) was not significantly different from that in the DES group (14.6%, 1344 ± 606 days, P = 0.097). PCB was not a significant predictor of TLF in the univariate analysis (hazard ratio: 0.424; 95%CI: 0.15-1.21; P = 0.108). There was no angiographic restenosis after PCB angioplasty.The present observational single-center study showed that PCB for de novo stenosis in the LV had no significant adverse impact on TLF and had favorable angiographic outcomes.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Reestenose Coronária , Stents Farmacológicos , Humanos , Doença da Artéria Coronariana/complicações , Paclitaxel/farmacologia , Stents Farmacológicos/efeitos adversos , Estudos Retrospectivos , Constrição Patológica , Angiografia Coronária/efeitos adversos , Resultado do Tratamento , Angioplastia Coronária com Balão/efeitos adversos , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Stents/efeitos adversos
12.
Rinsho Ketsueki ; 64(3): 203-208, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37019674

RESUMO

During laparoscopic cholecystectomy, an 89-year-old man was discovered to have a prolonged APTT. He was transferred to our hospital for a thorough examination because wound bleeding necessitated a reoperation. Based on coagulation factor VIII activity (FVIII:C) of 3.6% and FVIII inhibitor levels of 48.5 BU/ml, he was diagnosed with acquired hemophilia A (AHA). Due to concerns about his advanced age and postoperative infection, immunosuppressive therapy with prednisolone 0.5 mg/kg/day was initiated. His clinical course was favorable, except hemorrhagic shock caused by intramuscular hemorrhage on the right back, although low FVIII inhibitor levels persisted for more than a month; additionally, lower leg edema and increased urinary protein were also observed. He was diagnosed as with AHA and secondary nephrotic syndrome, possibly because of early gastric cancer. As a result, radical endoscopic submucosal dissection (ESD) was performed while a recombinant coagulation factor VIIa preparation was administered. AHA improved rapidly following ESD, and coagulative remission was achieved. Simultaneously, the nephrotic syndrome improved. Because the control of malignant tumors may improve the status of AHA, the timing of malignant tumor intervention must be considered considering the risk of bleeding and infection associated with immunosuppression.


Assuntos
Hemofilia A , Síndrome Nefrótica , Neoplasias Gástricas , Masculino , Humanos , Idoso de 80 Anos ou mais , Hemofilia A/tratamento farmacológico , Fator VIII/uso terapêutico , Síndrome Nefrótica/complicações , Neoplasias Gástricas/complicações , Prednisolona/uso terapêutico
13.
Rinsho Ketsueki ; 64(1): 60-65, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36775309

RESUMO

An 86-year-old Japanese male patient visited a nearby hospital with painful swelling in his left upper and lower limbs 35 days after the second dose of the BNT162b2 mRNA coronavirus disease-2019 (COVID-19) vaccine. He was referred to our hematological department due to a prolonged activated partial thromboplastin time and was urgently admitted. He was diagnosed with acquired hemophilia A (AHA) based on factor VIII (FVIII) activity of 1.7%, FVIII inhibitor of 152.3 BU/ml, and FVIII-binding antibodies detected by enzyme-linked immunosorbent assay. Immunosuppressive therapy with prednisolone (PSL) at 0.5 mg/kg/day was started owing to the risk of infection due to old age and poor activities of daily living. Hemostasis treatment with bypass hemostatic preparations (rFVIIa preparation, FVIIa/FX) was administered for each bleeding event, such as intramuscular and knee joint bleeding, resulting in good hemostatic effects. Coagulative complete remission was achieved on day 69 with PSL treatment; however, FVIII activity decreased with PSL tapering. AHA relapse with rectus abdominis muscle hematoma was observed after the third vaccination. This is the first Japanese report of AHA after COVID-19 vaccination and the world's first case, in which the presence of anti-FVIII-binding antibodies were observed.


Assuntos
Vacina BNT162 , COVID-19 , Hemofilia A , Hemostáticos , Idoso de 80 Anos ou mais , Humanos , Masculino , Atividades Cotidianas , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Fator VIII/uso terapêutico , Hemofilia A/induzido quimicamente , Hemofilia A/terapia , Hemostáticos/uso terapêutico , Prednisolona/uso terapêutico
14.
Anal Chem ; 94(38): 13136-13144, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36111576

RESUMO

Characterizing interactions between microbial cells and their specific inhibitory drugs is essential for developing effective drugs and understanding the therapeutic mechanism. Functional metal nanoclusters can be effective inhibitory agents against microorganisms according to various characterization methods, but quantitative three-dimensional (3D) spatial structural analysis of intact cells is lacking. Herein, using coherent X-ray diffraction imaging, we performed in situ 3D visualization of unstained Staphylococcus aureus cells treated with peptide-mineralized Au-cluster probes at a resolution of ∼47 nm. Subsequent 3D mass-density mapping and quantitative structural analyses of S. aureus in different degrees of destruction showed that the bacterial cell wall was damaged and cytoplasmic constituents were released from cells, confirming the significant antibacterial effects of the Au-cluster probe. This study provides a promising nondestructive approach for quantitative imaging and paves the way for further research into microbe-inhibitor drug interactions.


Assuntos
Imageamento Tridimensional , Staphylococcus aureus , Antibacterianos/química , Antibacterianos/farmacologia , Imageamento Tridimensional/métodos , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Difração de Raios X
15.
J Exp Bot ; 73(3): 998-1015, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34606587

RESUMO

Oryza coarctata is the only wild rice species with significant salinity tolerance. The present work examines the role of the substantial rhizomatous tissues of O. coarctata in conferring salinity tolerance. Transition to an erect phenotype (shoot emergence) from prostrate growth of rhizome tissues is characterized by marked lignification and suberization of supporting sclerenchymatous tissue, epidermis, and bundle sheath cells in aerial shoot-proximal nodes and internodes in O. coarctata. With salinity, however, aerial shoot-proximal internodal tissues show reductions in lignification and suberization, most probably related to re-direction of carbon flux towards synthesis of the osmporotectant proline. Concurrent with hypolignification and reduced suberization, the aerial rhizomatous biomass of O. coarctata appears to have evolved mechanisms to store Na+ in these specific tissues under salinity. This was confirmed by histochemical staining, quantitative real-time reverse transcription-PCR expression patterns of genes involved in lignification/suberization, Na+ and K+ contents of internodal tissues, as well as non-invasive microelectrode ion flux measurements of NaCl-induced net Na+, K+, and H+ flux profiles of aerial nodes were determined. In O. coarctata, aerial proximal internodes appear to act as 'traffic controllers', sending required amounts of Na+ and K+ into developing leaves for osmotic adjustment and turgor-driven growth, while more deeply positioned internodes assume a Na+ buffering/storage role.


Assuntos
Oryza , Oryza/metabolismo , Folhas de Planta/metabolismo , Rizoma/metabolismo , Salinidade , Tolerância ao Sal , Sódio/metabolismo
16.
Hepatol Res ; 52(11): 937-946, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35921254

RESUMO

AIM: Conventionally, the skeletal muscle area with computed tomography (CT) attenuation ranging from -29 to +150 Hounsfield unit (HU) divided by height squared (the conventional skeletal muscle index [SMI]) was used as an index of skeletal muscle mass. However, it includes fat-infiltrated skeletal muscle, which is known to have poor function. This study aims to determine whether the low-fat SMI, which uses skeletal muscle mass with CT attenuation ranging from +30 to +150 HU, or conventional SMI appropriately reflects the function of skeletal muscle. METHODS: We retrospectively analyzed 120 patients with cirrhosis whose handgrip strength was measured. Among them, 48 patients underwent a physical performance assessment such as liver frailty index (LFI) and short physical performance battery (SPPB), and 80 underwent quality of life (QOL) assessment. The relationships between each SMI and handgrip strength, LFI, SPPB, and QOL were evaluated. RESULTS: Low-fat SMI was significantly correlated with handgrip strength (males, R = 0.393, p = 0.002; females, R = 0.423, p < 0.001) and LFI (males, R = -0.535, p = 0.035; females, R = -0.368, p = 0.039), whereas conventional SMI was not. When using low-fat SMI, patients with low skeletal muscle mass had significantly low handgrip strength, LFI, SPPB, and physical and social-related QOL score than those without. By contrast, no significant differences were found for any items when using conventional SMI. CONCLUSIONS: Low-fat SMI is a good index of skeletal muscle mass that appropriately reflects skeletal muscle function.

17.
Int Heart J ; 63(2): 217-225, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35185090

RESUMO

We conducted a single-center, retrospective, lesion-based study to examine the safety and efficacy of drug-coated balloons (DCBs) for de novo coronary stenosis in patients with acute coronary syndrome (ACS) by comparing them with those of drug-eluting stents (DESs).A total of 309 consecutive lesions in patients with ACS who were successfully treated by emergent procedures using either a DCB (n = 107) or a DES between January 2016 and December 2019 were included in the study. The primary endpoint was the incidence of target lesion failure (TLF), defined as cardiac death without mortality due to ACS, non-fatal myocardial infarction, and any target lesion revascularization, including acute occlusion, after DCB use and definite stent thrombosis after DES placement. A propensity score-matched analysis was used to adjust the 36 baseline variables. Retrospective investigations were conducted in January 2021.Baseline adjustment yielded 91 lesions in each group, with a mean balloon size of 3.02 ± 0.22 mm and a mean length of 20.9 ± 6.2 mm in the DCB group. The frequency of TLF in the DCB group (9.9% during the mean observational interval of 671 ± 508 days) was not significantly different from that in the DES group (13.2% during a period of 626 ± 543 days, P = 0.467). The cumulative TLF-free ratio in the DCB group was not significantly different from that in the DES group (P = 0.475, log-rank test).The present propensity score-matched comparison showed statistically equivalent midterm clinical outcomes after DCB use to those of DES placement for de novo lesions in patients with ACS treated by emergent procedures.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Reestenose Coronária , Stents Farmacológicos , Infarto do Miocárdio , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/complicações , Reestenose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/complicações , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
18.
Rinsho Ketsueki ; 63(1): 55-61, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35135953

RESUMO

Neuropsychiatric symptoms comprise one of the five classic symptoms of autoimmune thrombotic thrombocytopenic purpura (aTTP). Although aTTP is typically transient, it is sometimes complicated by cerebral infarction with residual disability. This report presents the case of an 87-year-old man previously admitted to a different hospital with fever and transient consciousness loss. After receiving platelet transfusion with diagnosis of Evans syndrome, he was transferred to our hospital with worsening consciousness disturbance. He was subsequently diagnosed with aTTP with a PLASMIC score of 6 points, ADAMTS13 activity of less than 0.5%, and its inhibitor of 7.4 BU/ml. Platelet count and consciousness were rapidly improved with plasmapheresis and steroids, but motor aphasia emerged. MRI showed multiple cerebral infarctions, including a large infarction in the left frontal lobe. Thus, unfractionated heparin was administered. When his platelet count dropped once again on the 20th day, rituximab was added. The treatment eventually proved to be successful, and his aTTP remained in remission one year after the onset. Treatment for cerebral infarctions was switched to DOAC, and rehabilitation was continued. However, his ADL has not yet recovered. Advances in aTTP treatment have cured many similar cases. Thus, rituximab is now considered a treatment option for refractory cases. However, ischemic organ damage in acute phase and sequelae are observed. Therefore, early diagnosis and novel therapy are required.


Assuntos
Púrpura Trombocitopênica Trombótica , Proteína ADAMTS13 , Idoso de 80 Anos ou mais , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/etiologia , Heparina , Humanos , Masculino , Troca Plasmática , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico
19.
Rinsho Ketsueki ; 63(10): 1392-1396, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36351645

RESUMO

From a young age, a 63-year-old Japanese man had experienced difficulties with hemostasis during tooth extraction and epistaxis and swelling of bruised areas. He had previously been diagnosed with mild hemophilia (FVIII:C 8.5%) at age of 60 due to swelling of a right hip bruise and was administered FVIII concentrate for the first time. He had frequent bleeding around his shoulder joints and was given FVIII concentrates every time, but his hemostasis was poor. He was referred to our hospital because his FVIII activity decreased to<1% and a low-titer inhibitor (2.0 BU/ml) was detected. Because of a shoulder hematoma and new subcutaneous bleeding on both forearms, recombinant FVIIa was used to perform the hemostatic treatment. Following hemostasis, emicizumab was administered subcutaneously every 2 weeks at a dose of 3.0 mg/kg. Approximately 2 months after starting emicizumab, inhibitors were no longer detected, and FVIII activity increased to 8% after 9 months. We encountered a case of mild hemophilia A with an inhibitor that was first diagnosed in old age. The incidence of inhibitors in non-severe hemophilia A is about 10%, and about 70% of those resolves spontaneously. In this case, suppression of bleeding by emicizumab may have contributed to the spontaneous disappearance of the inhibitor.


Assuntos
Anticorpos Biespecíficos , Hemofilia A , Masculino , Humanos , Pessoa de Meia-Idade , Hemofilia A/tratamento farmacológico , Hemofilia A/diagnóstico , Fator VIII/uso terapêutico , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia
20.
Occup Ther Health Care ; 36(4): 408-421, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34802382

RESUMO

This study investigates whether reflection on occupational experience during assessment and intervention would help clients express their occupational needs in goal setting. Sixty-two participants who were not able to express their occupational needs in the initial assessment process were either allocated to the occupational experience group who undertook occupation-based assessment and intervention, or the physical training group who engaged in physical training only. The ratio of participants who expressed their occupational needs in each group was 67% (30/45) and 12% (2/17) respectively. Reflection on occupational experience during assessment and intervention to help clients express their occupational needs would have significant implications for practice, as it may encourage clients to reflect on their performance more easily.


Assuntos
Terapia Ocupacional , Objetivos , Humanos , Motivação , Estudos Retrospectivos , Cuidados Semi-Intensivos
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