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1.
Gait Posture ; 112: 53-58, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38744021

RESUMEN

BACKGROUND: To evaluate whether the knee adduction moment (KAM) could be reduced by a short instruction in the Draw-in (DI) maneuver in healthy adults, and whether knee joint function would improve with a longer DI gait intervention in patients with knee osteoarthritis (OA). METHOD: In Study 1, healthy adults received 10 minutes supervised instruction in DI gait in and then practiced the gait independently for 10 minutes. Three-dimensional motion analysis measurement was performed in each phase. In Study 2, patients with OA performed a 20-minute DI gait intervention daily for 6 weeks. At baseline and after 6 weeks, knee pain, the Knee injury and Osteoarthritis Outcome Score, the MOS 8 item Short-Form Health Survey, thoracic kyphosis angle, knee joint range of motion, knee extension muscle strength, hip abduction muscle strength, and activity level were evaluated. RESULTS: In Study 1, the DI gait to decrease KAM could be learning following only 10 minutes of instruction and 10 minutes of self-practice in healthy adults. In Study 2, knee pain was reduced by 19 % and the thoracic kyphosis angle was reduced by 2.6° after 6 weeks. No significant changes in other parameters were detected, and the implementation rate was 86 ±â€¯14 %. SIGNIFICANCE: In healthy adults, DI gait instruction for 10 minutes of instruction and 10 minutes of self-practice reduced the KAM. In patients with knee OA, 20 minutes of DI gait per day for 6 weeks may reduce knee pain and thoracic kyphosis.

2.
QJM ; 117(3): 187-194, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37878823

RESUMEN

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.


Asunto(s)
Infarto del Miocardio , Humanos , Biomarcadores , Estudios Prospectivos , Infarto del Miocardio/diagnóstico , Troponina I , Valor Predictivo de las Pruebas , Servicio de Urgencia en Hospital , Algoritmos , Troponina T
3.
Sci Rep ; 12(1): 22182, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36564489

RESUMEN

Chromosome damage combined with defective recombinase activity has been widely considered to render cells inviable, owing to deficient double-strand break repair. However, temperature-sensitive recAts polA cells grow well upon induction of DNA damage and supplementation with catalase at restrictive temperatures. These treatments reduce intracellular reactive oxygen species (ROS) levels, which suggests that recAts polA cells are susceptible to ROS, but not chronic chromosome damage. Therefore, we investigated whether polA cells can tolerate a complete lack of recombinase function. We introduced a ΔrecA allele in polA cells in the presence or absence of the hslO-encoding redox molecular chaperon Hsp33 expression plasmid. Induction of the hslO gene with IPTG resulted in increased cell viability in ΔrecA polA cells with the hslO expression plasmid. ΔrecA polA cells in the absence of the hslO expression plasmid showed rich medium sensitivity with increasing ROS levels. Adding catalase to the culture medium considerably rescued growth arrest and decreased ROS. These results suggest that hslO expression manages oxidative stress to an acceptable level in cells with oxidative damage and rescues cell growth. Overall, ROS may regulate several processes, from damage response to cell division, via ROS-sensitive cell metabolism.


Asunto(s)
Daño del ADN , Estrés Oxidativo , Catalasa/genética , Catalasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Recombinasas/metabolismo
4.
Res Vet Sci ; 152: 300-306, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36084371

RESUMEN

The objective of this study was to investigate the age difference in the response to endotoxin in calves related to the plasma endotoxin activity and mRNA expression of cytokines. Fifteen calves were divided into three groups: control (191 ± 21 days), weaning (162.4 ± 17.5 days), and calf (22.4 ± 8.2 days). The weaning and calf groups received 2.5 µg/kg of ultrapure O111:B4 LPS in 10 mL of each autologous serum, whereas the control calves received a similar volume of saline. Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h. Liver samples were collected by ultrasound-guided liver biopsy at 0, 2, 4, and 24 h. Plasma endotoxin activity was measured by the limulus amebocyte lysate kinetic turbidimetric assay. The mRNA expression level of GAPDH, TLR-4, NF-κB2, TNF-α, IL-6, and STAT3 in leukocytes and the liver was measured by real-time PCR. Following LPS challenge, the maximal plasma endotoxin activity, and leukocytic expression of TLR4, NF-κB2, TNF-α, and STAT3 were reached at 0.5, 4, 2-4, 2-4, and 4 h, respectively, in weaning and calf groups. The endotoxin activity in calf remained high until 2 h. Furthermore, the expression of leukocytic STAT3 mRNA in calf was not significantly different from the pre-value. In contrast, STAT3 mRNA in weaning markedly increased at 2 and 4 h. Therefore, this study provides new information to the literature of immune and inflammatory responses in calves.


Asunto(s)
Lipopolisacáridos , Factor de Necrosis Tumoral alfa , Bovinos , Animales , Lipopolisacáridos/farmacología , ARN Mensajero/genética , ARN Mensajero/análisis , Subunidad p52 de NF-kappa B , Endotoxinas , Leucocitos
5.
Phys Rev E ; 105(2-2): 025203, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35291161

RESUMEN

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

6.
Sci Rep ; 10(1): 18596, 2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33122696

RESUMEN

Topological magnetic structure possesses topological stability characteristics that make it robust against disturbances which are a big advantage for data processing or storage devices of spintronics; nonetheless, such characteristics have been rarely clarified. This paper focused on the formation of chiral soliton lattice (CSL), a one-dimensional topological magnetic structure, and provides a discussion of its topological stability and influence of thermal fluctuation. Herein, CSL responses against change of temperature and applied magnetic field were investigated via small-angle resonant soft X-ray scattering in chromium niobium sulfide ([Formula: see text]). CSL transformation relative to the applied magnetic field demonstrated a clear agreement with the theoretical prediction of the sine-Gordon model. Further, there were apparent differences in the process of chiral soliton creation and annihilation, discussed from the viewpoint of competing between thermal fluctuation and the topological metastability.

7.
Br J Surg ; 107(13): 1811-1817, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32638367

RESUMEN

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.


ANTECEDENTES: La quimioterapia intraperitoneal con paclitaxel se considera una terapia experimental para el tratamiento de la carcinomatosis peritoneal. Este estudio tuvo como objetivo determinar la dosis recomendada y evaluar la eficacia clínica y la seguridad de la combinación de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal en pacientes con cáncer de páncreas y metástasis peritoneales. MÉTODOS: Se evaluaron las frecuencias de las toxicidades limitantes de la dosis, y la dosis recomendada se determinó en la fase I. El objetivo principal de la fase II fue la tasa de supervivencia global a 1 año. Los objetivos secundarios fueron los efectos antitumorales, los efectos de alivio de los síntomas, la seguridad y la supervivencia global. RESULTADOS: Las dosis recomendadas de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal fueron de 800, 75 y 20 mg/m2 , respectivamente. De los 46 pacientes incluidos en la fase II del estudio, la mediana de tiempo hasta el fracaso del tratamiento fue de 6,0 meses (rango, 0-22,6). Las tasas de respuesta y de control de la enfermedad fueron del 45% y 95%, respectivamente. La ascitis desapareció en el 40% de los pacientes, y la citología se negativizó en el 39% de los pacientes. La mediana del tiempo de supervivencia fue de 14,5 meses y la tasa de supervivencia global a 1 año del 60,9%. La cirugía de rescate se realizó en ocho (17%) pacientes, y los que se sometieron a cirugía sobrevivieron significativamente más tiempo que los que no fueron tratados quirúrgicamente (mediana de supervivencia no alcanzada versus 12,4 meses). Las toxicidades hematológicas de grado 3/4 ocurrieron en el 76% de los pacientes, mientras que los eventos adversos no hematológicos se presentaron en el 15% de los pacientes. CONCLUSIÓN: Agregar paclitaxel intraperitoneal tuvo eficacia clínica con una tolerabilidad aceptable. (UMIN000018878).


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/secundario , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Anciano , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/mortalidad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intraperitoneales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/mortalidad , Neoplasias Peritoneales/mortalidad , Análisis de Supervivencia , Resultado del Tratamiento
8.
Pharmazie ; 75(6): 279-283, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32539926

RESUMEN

Vancomycin is associated with nephrotoxicity; however, the influence of the number of combined nephrotoxic agents on the incidence of vancomycin nephrotoxicity has not been clarified. We investigated patient backgrounds in 148 inpatients who received vancomycin treatment. The patients were divided into nephrotoxicity (n=35) and non-nephrotoxicity (n=113) groups. A comparison of the patient backgrounds in the two groups revealed significant differences in weight, changes in serum creatinine before vancomycin administration, blood urea nitrogen to serum creatinine ratio, length of vancomycin therapy, vancomycin trough concentration, and number of combined nephrotoxic agents. Multiple logistic regression analysis using these six factors as autonomous variables showed that the highest vancomycin trough concentration (odds ratio, 1.080; 95% confidence interval, 1.030-1.140; p = 0.003) and the number of combined nephrotoxic agents (odds ratio, 1.590; 95% confidence interval, 1.120-2.260; p = 0.010) were significantly related to nephrotoxicity.


Asunto(s)
Antibacterianos/efectos adversos , Enfermedades Renales/inducido químicamente , Vancomicina/efectos adversos , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vancomicina/administración & dosificación , Vancomicina/farmacocinética
9.
Phys Rev Lett ; 120(7): 077201, 2018 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-29542973

RESUMEN

Fedotovite K_{2}Cu_{3}O(SO_{4})_{3} is a candidate of new quantum spin systems, in which the edge-shared tetrahedral (EST) spin clusters consisting of Cu^{2+} are connected by weak intercluster couplings forming a one-dimensional array. Comprehensive experimental studies by magnetic susceptibility, magnetization, heat capacity, and inelastic neutron scattering measurements reveal the presence of an effective S=1 Haldane state below T≅4 K. Rigorous theoretical studies provide an insight into the magnetic state of K_{2}Cu_{3}O(SO_{4})_{3}: an EST cluster makes a triplet in the ground state and a one-dimensional chain of the EST induces a cluster-based Haldane state. We predict that the cluster-based Haldane state emerges whenever the number of tetrahedra in the EST is even.

10.
Dig Dis Sci ; 63(6): 1605-1612, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29564670

RESUMEN

BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Esofagoscopía , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esofagectomía/efectos adversos , Esofagectomía/mortalidad , Esofagoscopía/efectos adversos , Esofagoscopía/mortalidad , Femenino , Hospitales Universitarios , Humanos , Japón , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
11.
Orthod Craniofac Res ; 21(2): 84-89, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29493884

RESUMEN

OBJECTIVES: To investigate the effect of release of experimentally introduced nasal obstruction on maxillofacial morphology and percutaneous arterial oxygen saturation (SpO2 ) in rats. MATERIALS AND METHODS: Six-week-old male Wistar rats (n = 36) were divided into a control group (n = 6) and a nasal obstruction group (n = 30). In the nasal obstruction group, the right nostril was occluded with silicon, which was subsequently removed after a given experimental period (days 7, 21, 35, 49 and 63). These animals were then divided into groups D7, D21, D35, D49 and D63 (each n = 6), according to the day at which the obstruction was released. The SpO2 was measured in rats with nasal obstruction at five experimental points. The maxillofacial morphology in rats on the first day and 63 days after the start of the experiment was evaluated by microcomputed tomography. RESULTS: The SpO2 was still lower at 2 weeks after the improvement of the nasal obstruction in the D49 group than in the control group. In addition, the height of the nasal maxillary complex of the D35, D49 and D63 groups was significantly decreased compared with the control group. CONCLUSIONS: The results of this study suggest that long-term unilateral nasal obstruction in growing rats may affect the growth of the nasomaxillary complex and reduce the SpO2 permanently. Therefore, early improvement of nasal obstruction in rats during the growth period may improve the SpO2 and cranial development and promote normal growth and development.


Asunto(s)
Huesos Faciales/patología , Maxilar/patología , Obstrucción Nasal/patología , Animales , Huesos Faciales/diagnóstico por imagen , Masculino , Maxilar/diagnóstico por imagen , Obstrucción Nasal/diagnóstico por imagen , Oxígeno/sangre , Ratas Wistar , Factores de Tiempo , Microtomografía por Rayos X
12.
J Viral Hepat ; 25(5): 535-542, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29274188

RESUMEN

It is unclear whether multiple nonstructural (NS) 5A resistance-associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor-naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor-naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.


Asunto(s)
Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Fluorenos/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Mutación Missense , Sofosbuvir/uso terapéutico , Proteínas no Estructurales Virales/genética , Adulto , Anciano , Anciano de 80 o más Años , Farmacorresistencia Viral , Femenino , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ADN , Respuesta Virológica Sostenida , Resultado del Tratamiento , Proteínas no Estructurales Virales/antagonistas & inhibidores
13.
Science ; 357(6358): 1381-1385, 2017 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-28963251

RESUMEN

Charge ordering (CO) is a phenomenon in which electrons in solids crystallize into a periodic pattern of charge-rich and charge-poor sites owing to strong electron correlations. This usually results in long-range order. In geometrically frustrated systems, however, a glassy electronic state without long-range CO has been observed. We found that a charge-ordered organic material with an isosceles triangular lattice shows charge dynamics associated with crystallization and vitrification of electrons, which can be understood in the context of an energy landscape arising from the degeneracy of various CO patterns. The dynamics suggest that the same nucleation and growth processes that characterize conventional glass-forming liquids guide the crystallization of electrons. These similarities may provide insight into our understanding of the liquid-glass transition.

15.
Nat Commun ; 8: 15457, 2017 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-28580933

RESUMEN

Despite remarkable progress in developing multifunctional materials, spin-driven ferroelectrics featuring both spontaneous magnetization and electric polarization are still rare. Among such ferromagnetic ferroelectrics are conical spin spiral magnets with a simultaneous reversal of magnetization and electric polarization that is still little understood. Such materials can feature various multiferroic domains that complicates their study. Here we study the multiferroic domains in ferromagnetic ferroelectric Mn2GeO4 using neutron diffraction, and show that it features a double-Q conical magnetic structure that, apart from trivial 180o commensurate magnetic domains, can be described by ferromagnetic and ferroelectric domains only. We show unconventional magnetoelectric couplings such as the magnetic-field-driven reversal of ferroelectric polarization with no change of spin-helicity, and present a phenomenological theory that successfully explains the magnetoelectric coupling. Our measurements establish Mn2GeO4 as a conceptually simple multiferroic in which the magnetic-field-driven flop of conical spin spirals leads to the simultaneous reversal of magnetization and electric polarization.

16.
Oncogenesis ; 6(5): e334, 2017 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-28504692

RESUMEN

Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear. To address this, we examined whether Mint3 in fibroblasts contributes to tumour growth. Mint3 depletion in mouse embryonic fibroblasts (MEFs) decreased tumour growth of co-injected human breast cancer cells, MDA-MB-231 and epidermoid carcinoma A431 cells in mice. In MEFs, Mint3 also promoted cancer cell proliferation in vitro in a cell-cell contact-dependent manner. Mint3-mediated cancer cell proliferation depended on HIF-1, and further gene expression analysis revealed that the cell adhesion molecule, L1 cell adhesion molecule (L1CAM), was induced by Mint3 and HIF-1 in fibroblasts. Mint3-mediated L1CAM expression in fibroblasts stimulated the ERK signalling pathway via integrin α5ß1 in cancer cells, and promoted cancer cell proliferation in vitro and tumour growth. In cancer-associated fibroblasts (CAFs), knockdown of MT1-MMP, which promotes Mint3-mediated HIF-1 activation, or Mint3 decreased L1CAM expression. As MEFs, CAFs also promoted cancer cell proliferation in vitro, and tumour growth via Mint3 and L1CAM. In human breast cancer specimens, the number of fibroblasts expressing L1CAM, Mint3 and MT1-MMP was higher in cancer regions than in adjacent benign regions. In addition, more phospho-ERK1/2-positive cancer cells existed in the peripheral region surrounded by the stroma than in the central region of solid breast cancer nest. Thus, Mint3 in fibroblasts might be a good target for cancer therapy by regulating cancer cell-stromal cell communication.

17.
Br J Surg ; 104(5): 536-543, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28112814

RESUMEN

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity after distal pancreatectomy. The aim of this study was to investigate whether duct-to-mucosa pancreaticogastrostomy of the pancreatic stump decreased clinical POPF formation compared with handsewn closure after distal pancreatectomy. METHODS: This multicentre RCT was performed between April 2012 and June 2014. Patients undergoing distal pancreatectomy were assigned randomly to either duct-to-mucosa pancreaticogastrostomy or handsewn closure. The primary endpoint was the incidence of clinical POPF. Secondary endpoints were rates of other complications and length of hospital stay. RESULTS: Some 80 patients were randomized, and 73 patients were evaluated in an intention-to-treat analysis: 36 in the pancreaticogastrostomy group and 37 in the handsewn closure group. The duration of operation was significantly longer in the pancreaticogastrostomy group than in the handsewn closure group (mean 268 versus 197 min respectively; P < 0·001). The incidence of clinical POPF did not differ between groups (7 of 36 versus 7 of 37; odds ratio (OR) 1·03, 95 per cent c.i. 0·32 to 3·10; P = 1·000). The rate of intra-abdominal fluid collection was significantly lower in the pancreaticogastrostomy group (6 of 36 versus 21 of 37; OR 0·15, 0·05 to 0·45; P < 0·001). There were no statistically significant differences in the rates of other complications or length of hospital stay. CONCLUSION: Duct-to-mucosa pancreaticogastrostomy did not reduce the incidence of clinical POPF compared with handsewn closure of the pancreatic stump after distal pancreatectomy. Registration number UMIN000007426 (http://www.umin.ac.jp).


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Páncreas/cirugía , Pancreatectomía/métodos , Enfermedades Pancreáticas/cirugía , Fístula Pancreática/epidemiología , Técnicas de Sutura , Adulto , Anciano , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Humanos , Incidencia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Membrana Mucosa , Pancreatectomía/efectos adversos , Fístula Pancreática/etiología , Fístula Pancreática/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos
18.
Clin Microbiol Infect ; 23(6): 407.e1-407.e7, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27998820

RESUMEN

OBJECTIVES: When considering treatment for chronic hepatitis B (CHB), it is important to discriminate between patients with persistent low HBV DNA and patients with active hepatitis, who may proceed to cirrhosis. In this study, we sought to identify mutations in patients expected to have persistent low HBV DNA and ultimately exhibit clearance of hepatitis B surface antigen (HBsAg). METHODS: Serum samples were obtained from 33 CHB genotype C patients, divided based on HBV DNA and alanine aminotransferase (ALT) levels following observation for >2 years: Group A (n=10), transient HBV DNA ≥5.0 log copies/mL and ALT ≥120 IU/L; Group B (n=11), persistent HBV DNA <5.0 and ALT <60; and Group C (n=12), persistent HBV DNA <4.0 and ALT <30. Full-length HBV sequences were compared among groups. Subsequently, 82 patients with CHB were evaluated for the I97L mutation and the additional mutation P79Q. We compared cumulative incidences of persistent low HBV DNA and HBsAg clearance in patients with or without I97L and P79Q by the Kaplan-Meier method. RESULTS: Incidence of Core mutation I97L differed significantly among groups: A, 30% (3/10); B, 36.4% (4/11); C, 83.3% (10/12) (p = 0.021). Cumulative incidences of persistent low HBV DNA and HBsAg clearance were significantly higher in patients with I97L than in those with wild-type I97 (p = 0.003 and p = 0.016, respectively), and even higher in those with P79Q. CONCLUSIONS: In patients with CHB, measurement of I97L and additional mutation P79Q would be useful for predicting persistent low HBV DNA, normal ALT, and HBsAg clearance.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Mutación , Adulto , Alanina Transaminasa/metabolismo , Femenino , Genotipo , Virus de la Hepatitis B/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad
19.
Adv Exp Med Biol ; 929: 45-66, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27771920

RESUMEN

The active components in cloves are eugenol and isoeugenol. Eugenol has recently become a focus of interest because of its potential role in alleviating and preventing chronic diseases such as cancer, inflammatory reactions, and other conditions. The radical-scavenging and anti-inflammatory activities of eugenol have been shown to modulate chronic diseases in vitro and in vivo, but in humans, the therapeutic use of eugenol still remains to be explored. Based on a review of the recent literature, the antioxidant, anti-proliferative, and anti-inflammatory activities of eugenol and its related compounds are discussed in relation to experimentally determined antioxidant activity (stoichiometric factor n and inhibition rate constant) and theoretical parameters [phenolic O-H bond dissociation enthalpy (BDE), ionization potential (IP according to Koopman's theorem), and electrophilicity (ω)], calculated using a density functional theory method. Dimers of eugenol and its related compounds showed large antioxidant activities and high ω values and also exerted efficient anti-inflammatory activities. Eugenol appears to possess multiple antioxidant activities (dimerization, recycling, and chelating effect) in one molecule, thus having the potential to alleviate and prevent chronic diseases.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Descubrimiento de Drogas/métodos , Eugenol/uso terapéutico , Syzygium/química , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Modelos Animales de Enfermedad , Eugenol/química , Eugenol/aislamiento & purificación , Humanos , Estructura Molecular , Fitoterapia , Plantas Medicinales , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad
20.
Sci Rep ; 6: 23611, 2016 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-27021464

RESUMEN

In strongly correlated electron systems, enhanced fluctuations in the proximity of the ordered states of electronic degrees of freedom often induce anomalous electronic properties such as unconventional superconductivity. While spin fluctuations in the energy-momentum space have been studied widely using inelastic neutron scattering, other degrees of freedom, i.e., charge and orbital, have hardly been explored thus far. Here, we use resonant inelastic x-ray scattering to observe charge fluctuations proximate to the charge-order phase in transition metal oxides. In the two-leg ladder of Sr(14-x)Ca(x)Cu24O41, charge fluctuations are enhanced at the propagation vector of the charge order (qCO) when the order is melted by raising temperature or by doping holes. In contrast, charge fluctuations are observed not only at qCO but also at other momenta in a geometrically frustrated triangular bilayer lattice of LuFe2O4. The observed charge fluctuations have a high energy (~1 eV), suggesting that the Coulomb repulsion between electrons plays an important role in the formation of the charge order.

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