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The mutual coupling of spin and lattice degrees of freedom is ubiquitous in magnetic materials and potentially creates exotic magnetic states in response to the external magnetic field. Particularly, geometrically frustrated magnets serve as a fertile playground for realizing magnetic superstructure phases. Here, we observe an unconventional two-step magnetostructural transition prior to a half-magnetization plateau in a breathing pyrochlore chromium spinel by means of state-of-the-art magnetization and magnetostriction measurements in ultrahigh magnetic fields available up to 600 T. Considering a microscopic magnetoelastic theory, the intermediate-field phase can be assigned to a magnetic superstructure with a three-dimensional periodic array of 3-up-1-down and canted 2-up-2-down spin molecules. We attribute the emergence of the magnetic superstructure to a unique combination of the strong spin-lattice coupling and large breathing anisotropy.
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This study assessed the dispersion stability of industrial carbide/oxide powders that have mosaic surfaces comprised of multiple surface ligands. A large number (â¼50) of probe liquids were used with an aim to effectively explain the data within the Hansen solubility parameter (HSP) framework. The proposed log-fit method, complemented by multi-HSP analysis featuring harmonic-mean-mixing HSPs, significantly improved the fit to experimental results for various mosaic-surface powders composed of complex surface ligands. X-ray photoelectron spectroscopy and thermal desorption spectroscopy analyses were employed synergistically to decipher the surface ligands of these mosaic-surface powders, which facilitated credible identification and quantification of the surface ligands. These results are in good agreement with the surface ligands and their coverage as determined by the multi-HSP analysis. Consequently, when it comes to characterizing powder surfaces, dispersion stability measurements paired with multi-HSP analysis are superior to conventional XPS and TDS analyses in terms of both topmost surface sensitivity and practicality.
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BACKGROUND: Endoscopic submucosal dissection (ESD) is a potentially efficient therapeutic intervention for superficial esophageal cancer. Additional treatment such as chemoradiotherapy (CRT) or esophagectomy is recommended in cases of muscularis mucosa invasion with positive resection margins or lymphovascular invasion or submucosal layer invasion, which are considered noncurative ESD, due to an increased risk of lymph node metastasis. However, the adequacy of additional CRT after near-circumferential or full-circumferential noncurative ESD has not been fully discussed. In this study, we retrospectively evaluated the efficacy and toxicity of additional CRT for superficial esophageal squamous cell carcinoma (SCC) after near-circumferential or full-circumferential noncurative ESD, which was defined as a mucosal defect measuring ≥ 3/4 of the esophageal circumference. METHODS: We retrospectively evaluated 24 patients who received additional CRT for superficial esophageal SCC after near-circumferential or full-circumferential noncurative ESD between 2012 and 2018. Elective nodal irradiation (ENI) was performed in all patients and boost irradiation (BI) was performed after ENI in 4 patients with positive resection margins. The prescription doses of ENI and BI were 41.4 Gy in 23 fractions and 9 Gy in 5 fractions, respectively. Concurrent chemotherapy (a combination of cisplatin or nedaplatin and 5-fluorouracil) was administered to all patients. RESULTS: The 3-year and 5-year overall survival rates were 92% and 78%, respectively, while the 3-year and 5-year progression-free survival rates were 83% and 70%, respectively. Grade 2 esophageal stenosis occurred in 8 (33%) patients. There was no case of Grade 3 or worse esophageal stenosis. Among them, 4 (17%) patients developed stenosis before additional CRT, which persisted after the completion of additional CRT. The remaining 4 (17%) patients developed de novo stenosis within 5 months following the completion of additional CRT. One patient (4%) still requires regular bougie dilation. Grade 3 and Grade 4 acute toxicity, including anemia, neutropenia, thrombocytopenia, and esophagitis occurred in 1 (4%) and 0 (0%), 6 (25%) and 1 (4%), 1 (4%) and 0 (0%), and 1 (4%) and 0 (0%) patients, respectively. One (4%) patient who underwent salvage CRT for the out-of-field lymph node recurrence died with acute myeloid leukemia. CONCLUSIONS: Additional CRT is a viable treatment option even in patients who have undergone near-circumferential or full-circumferential noncurative ESD. Esophageal stenosis after additional CRT following near-circumferential or full-circumferential noncurative ESD is manageable and acceptable.
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Quimiorradioterapia , Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fluoruracila , Humanos , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Masculino , Feminino , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Idoso , Pessoa de Meia-Idade , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Based on the results of a clinical trial in Japan, transcatheter aortic valve replacement (TAVR) for hemodialysis (HD) patients gained approval; however, mid-term TAVR outcomes and transcatheter aortic valve (TAV) durability in HD patients remain unexplored.MethodsâandâResults: We analyzed background, procedural, in-hospital outcome, and follow-up data for 101 HD patients and 494 non-HD patients who underwent TAVR using balloon-expandable valves (SAPIEN XT or SAPIEN 3) retrieved from Osaka University Hospital TAVR database. Periprocedural mortality and TAVR-related complications were comparable between HD and non-HD patients. However, Kaplan-Meier analysis revealed that HD patients had significantly lower survival rates (log-rank test, P<0.001). In addition, HD patients had significantly higher rates of severe structural valve deterioration (SVD) than non-HD patients (Gray test, P=0.038). CONCLUSIONS: TAVR in HD patients had comparable periprocedural mortality but inferior mid-term survival and TAV durability than in non-HD patients. Indications for TAVR in younger HD patients should be carefully determined, considering the possibility of a TAV-in-TAV procedure when early SVD occurs.
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BACKGROUND: Coronary angioscopy (CAS) has 2 unique abilities: direct visualization of thrombi and plaque color. However, in the recent drug-eluting stent (DES) era, serial CAS findings after DES implantation have not been fully elucidated. We investigated the impact of CAS findings after implantation of a polymer-free biolimus A9-coated stent (PF-BCS) or durable polymer everolimus-eluting stent (DP-EES).MethodsâandâResults: We investigated serial CAS and optical coherence tomography (OCT) findings at 1 and 12 months in 99 patients who underwent PF-BCS or DP-EES implantation. We evaluated factors correlated with angioscopic thrombi and yellow plaque, and the clinical impact of both thrombi and yellow plaque at 12 months (BTY). The BTY group included 17 (22%) patients. The incidence and grade of thrombi and yellow plaque decreased from 1 to 12 months. Although no patients had newly appearing thrombi at 12 months, 2 DP-EES patients had newly appearing yellow plaque at 12 months. Multivariable analysis revealed HbA1c, minimum stent area, and adequate strut coverage were significant factors correlated with 12-month angioscopic thrombi, and DP-EESs were significantly correlated with 12-month yellow plaque. However, BTY was not correlated with clinical events. CONCLUSIONS: The management of diabetes, stent area, and adequate stent coverage are important for intrastent thrombogenicity and polymer-free stents are useful for stabilizing plaque vulnerability.
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PURPOSE: Curcumin ingestion can mitigate muscle damage, soreness, and inflammation following a laboratory-based eccentric exercise. Similar effects were observed in recent field-based studies wherein responses were evaluated after a soccer match. However, various potential confounding factors, such as matching opponent skill levels and daily training conditions, may have influenced the outcomes. In the present study, we investigated whether curcumin intake ameliorates changes in muscle damage markers following a soccer match while controlling for the potential confounding factors. METHODS: Fifteen collegiate athletes were tested in a randomized, double-blind, cross-over manner. They were recruited from the same college soccer team and thus followed the same daily training regimen and competition levels. Furthermore, athletes positioning during matches were counterbalanced. They consumed either 180 mg/day of curcumin or a placebo starting 1 h before the match and continuing for 2 days after a match (two 45-min plays and a 15-min half-time). Muscle soreness, jump performance (including countermovement jump and rebound jump index), and inflammatory and muscle damage markers (high-sensitive C-reactive protein, serum creatine kinase activity, and urinary N-terminal fragment of titin concentration) were evaluated before and after the match. The washout period between matches was set at 1 week. RESULTS: After the match, all markers showed similarity between the placebo and curcumin conditions (all P > 0.208). CONCLUSION: These findings indicate that ingesting 180 mg/day of curcumin may not expedite recovery from muscle damage elicited by soccer matches in collegiate soccer players.
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Desempenho Atlético , Estudos Cross-Over , Curcumina , Suplementos Nutricionais , Músculo Esquelético , Mialgia , Futebol , Humanos , Curcumina/farmacologia , Curcumina/administração & dosagem , Futebol/fisiologia , Masculino , Método Duplo-Cego , Adulto Jovem , Desempenho Atlético/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Músculo Esquelético/lesões , Adulto , Exercício Físico/fisiologiaRESUMO
A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.
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Síndrome da Imunodeficiência Adquirida , Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Adulto Jovem , Adulto , Úlcera/etiologia , Herpesvirus Humano 4 , Remissão Espontânea , Síndrome da Imunodeficiência Adquirida/complicações , Recidiva Local de Neoplasia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: Little is known about intravascular imaging predictors of cardiac events after drug-eluting stent (DES) implantation in hemodialysis (HD) patients. We aimed to reveal the association between calcified nodules (CN) and target lesion failure (TLF) in HD patients after DES implantation. METHODS: We enrolled 114 HD patients who underwent DES implantation between October 2016 and October 2020. The patients were divided into a CN group (39%, 44 patients) and a non-CN group (61%, 70 patients). The primary endpoint was the incidence of TLF, including cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization. RESULTS: HD duration was longer, and the calcium burden was higher in the CN group than in the non-CN group. Over a median follow-up of 607 days [interquartile range: 349-965 days], the cumulative incidence curve showed that the CN group had a significantly higher incidence of TLF than the non-CN group (31.8% vs. 11.4% within 3 years, p = 0.008).ãOn Fine-Gray sub-distribution hazard model analysis, the CN group was associated with an increased rate of TLF (hazard ratio [HR]: 2.86; 95% confidence interval [CI]: 1.21-6.75, p = 0.016). An in-stent CN was observed in 73% of the lesions with target lesion revascularization in the CN group, whereas no in-stent CN was observed in the non-CN group (p = 0.026). CONCLUSIONS: CN was an independent predictor of TLF in patients undergoing HD. In-stent CN was an important cause of TLF after DES implantation in CN lesions in HD patients; therefore, a different strategy should be considered for treating the lesions.
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Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/terapia , Sirolimo , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Diálise RenalRESUMO
To integrate surface and interfacial properties and phenomena into the Hansen solubility parameter (HSP) framework, we propose an equation for estimating both surface tension/energy for liquids and solids as well as interfacial tension/energy. The contact angles of probe liquids on various polymers estimated using the proposed equation based on bulk HSPs (derived from bulk properties such as solubility or swelling, and not on surface properties) are compared with those measured using the sessile drop method. It is found that their correlations are sufficient for predicting wettability in practical use. All the respective tension and energy correlations are reasonably good, confirming the predictive power of the proposed equation for all values of liquid surface tension, solid surface energy, and interfacial tension. The unification of surface and interfacial properties and phenomena with HSPs (derived from bulk properties) enables us to estimate the surface properties from bulk properties and vice versa. The huge database of HSPs is now applicable to not only bulk phenomena but also surface and interfacial phenomena. Furthermore, complex processes or systems composed of multiple constituents and phases can be understood and designed using the modified HSP framework.
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Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain-of-function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.
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Trombocitemia Essencial , Trombocitose , Humanos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Calreticulina/genética , Mutação , Janus Quinase 2/genética , Janus Quinase 2/metabolismoRESUMO
We demonstrated the infectivity and host adaptation of a viola isolate of Plantago asiatica mosaic virus (PlAMV-Vi) in an asymptomatic host, Nicotiana benthamiana, through long-term serial passages. Serial passaging of a green fluorescent protein-tagged full-length cDNA clone of PlAMV-Vi (PlAMV-ViGFP) in N. benthamiana plants resulted in the appearance of a new virus line inducing leaf-crinkle symptoms, the Leaf Crinkle (LC) line. Virus titers were higher for both in the LC and the 14th passage line(s) of PlAMV-ViGFP compared with the original line. The LC line was found to have seven unique nucleotide mutations that may have contributed to its higher virulence and multiplication rate in N. benthamiana.
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Nicotiana , Potexvirus , Virulência , Potexvirus/genética , Doenças das PlantasRESUMO
OBJECTIVE: Elizabethkingia anophelis causes meningitis, bloodstream infections, and respiratory infections in immunocompromised individuals. We examined two E. anophelis strains isolated from the first life-threatening cases caused by this species in Japan to determine the phylogenetic origin and genomic features of them. METHODS: We performed whole genome-based analysis to clarify the genetic relationship for the two strains (EK0004 and EK0079) and Elizabethkingia sp. strains isolated from worldwide and to characterize the genomic features such as the prevalence of virulence- and antimicrobial resistance (AMR)-related genes. PATIENTS: A 29-year-old man with hepatosplenic T-cell lymphoma and a 52-year-old man with systemic lupus erythematosus developed fatal bacteremia and meningitis due to E. anophelis, respectively. RESULTS: Two strains, EK0004 and EK0079, were genetically different but most closely related to the strains isolated from the largest outbreak in Wisconsin, USA from 2015 to 2016, and the strain isolated from cerebrospinal fluid of a patient in Florida, USA in 1982, respectively. The two strains contained AMR-related genes such as those encoding for an extended-spectrum ß-lactamase and multiple metallo-ß-lactamases and several virulence-related genes such as capsular polysaccharide synthesis gene clusters. CONCLUSIONS: Although further functional analyses are required to understand the virulence of these clones, these finding suggests that enough caution of E. anophelis infection in immunocompromised patients is required since the number of infections by this species is increasing outside Japan.
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Infecções por Flavobacteriaceae , Genoma Bacteriano , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Genoma Bacteriano/genética , Filogenia , Japão , Infecções por Flavobacteriaceae/epidemiologia , Infecções por Flavobacteriaceae/genética , GenômicaRESUMO
A tyrosine kinase inhibitor (TKI) was used to treat the patient, a 35-year-old woman who was diagnosed with chronic myeloid leukemia at the age of 22 years. Since a four-year deep molecular response (DMR) was obtained, spontaneous pregnancy was planned under TKI withdrawal. Even though her disease had advanced to MR2.0 at the time of pregnancy confirmation, 2 months from TKI cessation, interferon α therapy was initiated in light of the patient's history. Later, the patient reached MR3.0, gave birth to a healthy baby, and maintained MR3.0-4.0. TKI was resumed after about 6 months of breastfeeding. Treatment-free remission (TFR) is required for natural conception despite the teratogenicity and miscarriage risks associated with BCR::ABL1 TKIs. When planning a pregnancy, it is also necessary to take the patients' backgrounds, disease states, and medical history into account.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Gravidez , Feminino , Adulto Jovem , Adulto , Interferon-alfa/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: The use of hybrid operating rooms (HOR) for transcatheter aortic valve implantation (TAVI) has increased, so radiation exposure during procedures that use X-ray fluoroscopy is a fundamental problem not only for patients but also for surgeons and interventional cardiologists, increasing the risk of cataracts among operators. We investigated the efficacy of leaded glasses and protective sheets for ocular radiation protection.MethodsâandâResults: Between January 2020 and February 2021 we enrolled 54 TAVI procedures using the transfemoral approach. The subjects were divided into a curtain protection group (Group C, n=20), glass protection group (Group G, n=17), and sheet protection group (Group S, n=17). The cumulative dose (CD) of the operators showed a decreasing trend in Group S compared with the other two groups. The CD normalized by dose area product (CD/DAP) of the operators was significantly reduced in Group S compared with Group C. However, Group G showed no significant difference compared with Group C. Regarding the distribution of CD/DAP, Group S had a significantly lower distribution than that in groups C and G. CONCLUSIONS: Protective sheets provide more stable radiation protection than conventional curtains or leaded glasses.
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Estenose da Valva Aórtica , Exposição à Radiação , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Estenose da Valva Aórtica/cirurgia , Doses de Radiação , Fatores de Risco , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Fluoroscopia/efeitos adversos , Valva Aórtica/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: A polymer-free biolimus A9-coated stent (PF-BCS) may achieve better arterial healing than a durable polymer drug-eluting stent owing to its polymer-free feature.MethodsâandâResults: This multicenter, prospective, observational study enrolled 105 patients (132 lesions) who underwent PF-BCS (51 patients, 71 lesions) or durable polymer everolimus-eluting stent (DP-EES, 54 patients, 61 lesions) implantation. Serial coronary angioscopy (CAS) and optical coherence tomography (OCT) examinations were performed at 1 and 12 months, and the serial vessel responses were compared between PF-BCS and DP-EES. The primary outcome measure was the incidence of subclinical intrastent thrombus on CAS. The secondary outcome measures were: adequate strut coverage (≥40 µm) on OCT and maximum yellow color grade on CAS. The incidence of thrombus was high at 1 month (100% vs. 93%, P=0.091), but decreased at 12 months (18% vs. 25%, P=0.56), without a significant difference between PF-BCS and DP-EES. The adequate strut coverage rate was significantly higher (84±14% vs. 69±22%, P<0.001) and yellow color was significantly less intense (P=0.012) at 12 months in PF-BCS than in DP-EES; however, they were not significantly different at 1 month (adequate strut coverage: 47±21% vs. 50±17%, P=0.40; yellow color: P=0.99). CONCLUSIONS: Although the thrombogenicity of PF-BCS was similar to that of DP-EES, the adequate coverage and plaque stabilization rates of PF-BCS were superior to those of DP-EES at 12 months.
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Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Trombose , Implantes Absorvíveis , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Stents Farmacológicos/efeitos adversos , Everolimo , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Polímeros , Estudos Prospectivos , Desenho de Prótese , Sirolimo/análogos & derivados , Resultado do TratamentoRESUMO
BACKGROUND: Patients undergoing maintenance hemodialysis (HD) with severe aortic stenosis are at a high risk for bioprosthetic valve dysfunction after transcatheter aortic valve implantation (TAVI). Currently, preoperative factors that predict the occurrence of valve dysfunction after TAVI on HD patients remain to be elucidated. The aim of this study is to analyze the association between preoperative clinical factors and valve stenosis after TAVI on HD patients. METHODS: Twenty-four of HD patients who underwent TAVI at our institution between April 2012 and January 2016 were analyzed. The mean aortic transvalvular pressure gradient (MPG) and effective orifice area index (EOAi) were assessed by serial echocardiography. Associations between preoperative clinical factors and time-series changes in MPG were examined using mixed-effects linear regression model for repeated measures. RESULTS: Three patients developed severe structural valve deterioration with calcific valve stenosis requiring reoperation. A multivariate linear mixed-effects model showed that lower serum magnesium (sMg) levels were associated with the increase of MPG after TAVI (beta-coefficient = 0.019, p = 0.03). No correlation was observed with serum calcium, phosphorus, or intact parathyroid hormone. Time-series changes of MPG and EOAi had significant difference between lower and higher sMg group. All 3 of the patients who underwent reoperation showed lower preoperative sMgs. CONCLUSION: Among bone-mineral metabolism markers, preoperative hypomagnesemia was associated with the increase of MPG after TAVI, suggesting that hypomagnesemia could predict post-TAVI valve dysfunction in HD patients. Further studies with larger sample sizes are warranted.
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Substituição da Valva Aórtica Transcateter , Constrição Patológica , Humanos , Magnésio , Período Pós-Operatório , Diálise Renal/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
OBJECTIVES: Adult T-cell leukemia/lymphoma (ATL) is an intractable T-cell malignancy caused by long-term infection with human T-cell leukemia virus type-1 (HTLV-1). While ATL pathogenesis has been associated with HTLV-1-derived oncogenic proteins, including Tax and HBZ, the contribution of genomic aberrations remains poorly defined. METHODS: To elucidate the genomic basis of ATL, whole exome sequencing was performed on cells from 47 patients with aggressive ATL. RESULTS: We discovered the novel mutation RLTPR Q575E in four patients (8.5%) with a median variant allele frequency of 0.52 (range 0.11-0.68). Despite being reported in cutaneous T-cell lymphoma, three ATL patients carrying RLTPR Q575E lacked skin involvement. Patients carrying RLTPR Q575E also harbored CARD11 (75%), PLCG1 (25%), PRKCB (25%), or IKBKB (25%) mutations related to TCR/NF-κB signaling. Jurkat cells transfected with RLTPR Q575E cDNA displayed increased NF-κB activity and significantly increased IL-2 mRNA levels under stimulation. RLTPR Q575E increased the interaction between RLTPR and CARD11, while RLTPR directly interacted with Tax. CONCLUSIONS: We identified, and functionally validated, a novel gain-of-function mutation in patients with aggressive ATL. During TCR activation by Tax or gain-of-function mutations, RLTPR Q575E selectively upregulates NF-κB signaling and may exert oncogenic effects on ATL pathogenesis.
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Alelos , Substituição de Aminoácidos , Mutação com Ganho de Função , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas dos Microfilamentos/genética , Adulto , Idoso , Feminino , Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Vetores Genéticos/genética , Genótipo , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/metabolismo , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Mutação , NF-kappa B/metabolismo , Retroviridae/genética , Transdução de Sinais , Sequenciamento do ExomaRESUMO
OBJECTIVES: The purpose of this study was to assess the radiological change patterns in skull base meningiomas after conventionally fractionated stereotactic radiotherapy (CFSRT) to determine a simple and valid method to assess the tumor response. MATERIALS AND METHODS: Forty-one patients with a benign skull base meningioma treated by CFSRT from March 2007 to August 2015 were retrospectively evaluated. We measured tumor volume (TV), long-axis diameter (LD), and short-axis diameter (SD) on both pre-treatment images and follow-up images of 1, 3, and 5 years after CFSRT, respectively. The paired t test was used to detect differences in the LD and SD change rates. Spearman's correlation coefficients were calculated to evaluate relationships between the TV and the diameters changes. RESULTS: The number of available follow-up MRIs that was performed at 1, 3, and 5 years after the CFSRT was 41 (100%), 34 (83%), and 23 (56%), respectively. The change rates of SD were significantly higher than those of LD at every time point and more strongly correlated with the change rates of tumor volume at 3 and 5 years after CFSRT. CONCLUSIONS: SD may be useful as a simple indicator of the tumor response for skull base meningioma after CFSRT. KEY POINTS: ⢠The change rate in short-axis diameter is a useful and simple indicator of the response of skull base meningioma to conventionally fractionated stereotactic radiotherapy. ⢠Conventionally fractionated stereotactic radiotherapy for skull base meningioma achieved excellent 5-year local control.
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Neoplasias Meníngeas , Meningioma , Radiocirurgia , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia , Meningioma/diagnóstico por imagem , Meningioma/radioterapia , Estudos Retrospectivos , Base do Crânio , Resultado do TratamentoRESUMO
BACKGROUND: Sleep problems in preschool children can stunt their health and growth. However, the factors that cause sleep problems in children are not well understood. The aim of this study was to determine the relationship between parents' health literacy (HL) and children's sleep problems. The study was conducted at two kindergartens, two nursery schools, and a center for early childhood education in Chitose-city, Hokkaido, Japan. METHOD: This study used a multicenter cross-sectional design. The sample comprised 354 preschoolers (aged 3-6 years) and their parents. In families with two or more children attending the same facility, only the oldest child was asked to participate in the study. Exclusion criteria included participants whose completed questionnaires had missing values. Children's sleep problems were assessed using the Japanese version of the Children's Sleep Habits Questionnaire (CSHQ-J). Parents' HL was assessed using the 14-item Health Literacy Scale (HLS-14). The parents were classified into two groups (high HL group and low HL group). Multiple regression modelling was used to determine the association between HLS-14 and CSHQ-J scores. RESULTS: Of the 354 parents, 255 (72%) were in the high HL group and 99 (28%) in the low HL group. The mean CSHQ-J score was significantly lower in the high HL group than in the low HL group (45.3 ± 6.0 points vs. 46.8 ± 5.9 points, p = 0.043). In multiple regression analyses, parents' HL was independently associated with their CSHQ-J score after adjusting for all confounding factors (adjusted R2 = 0.22, ß = - 0.11; p = 0.043). CONCLUSIONS: Parents' HL appears to affect their children's sleep problems. This finding suggests that parents' HL may be a target for intervention to improve children's sleep problems.
Assuntos
Letramento em Saúde , Transtornos do Sono-Vigília , Criança , Pré-Escolar , Estudos Transversais , Humanos , Japão/epidemiologia , Pais , Sono , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: According to a World Health Organization report, in 2016, 41 million young children globally were overweight or obese. The connection between parents' social capital and their children's health has been studied, but associations between parental social capital and children's weight are largely unexamined. Hence, we assessed the relationship between preschool children's weight and parents' social capital. METHODS: We used BMI assessment data for 357 children (46.5% girls; mean age 5.3 years) in Japan. We examined parents' structural and cognitive social capital using a self-report questionnaire. RESULTS: Multiple logistic regression analysis revealed associations between parents' social capital and children's BMI. Seventy-two (20.2%) of the children had poor BMI (body mass index; overweight or thin). Interpersonal trust was significantly associated with normal BMI in children after adjustment for all confounding factors (OR 2.68; 95% CI, 1.33-5.44; P = .006) and was independently associated with other social capital factors, including norm of reciprocity (OR 3.38; 95% CI, 1.68-6.79; P < .001) and trust in organization (OR 1.24; 95% CI, 1.09-1.42; P = .001). CONCLUSION: Social capital factors were independently associated with each other. Japanese parents' high social capital was an independent predictor of normal BMI among preschool children.