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1.
J Org Chem ; 89(14): 9937-9948, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38985331

RESUMEN

Baloxavir marboxil (1; BXM) is a potent drug used for treating influenza infections. The current synthetic route to BXM (1) is based on optical resolution; however, this method results in the loss of nearly 50% of the material. This study aimed to describe an efficient and simpler method for the synthesis of BXM. We achieved a stereoselective synthesis of BXM (1). The tricyclic triazinanone core possessing a chiral center was prepared via diastereoselective cyclization utilizing the readily available amino acid l-serine. The carboxyl moiety derived from l-serine was removed via photoredox decarboxylation under mild conditions to furnish the chiral tricyclic triazinanone core ((R)-14). The synthetic route demonstrated herein provides an efficient and atomically economical method for preparing this potent anti-influenza agent.


Asunto(s)
Dibenzotiepinas , Serina , Estereoisomerismo , Ciclización , Serina/química , Estructura Molecular , Dibenzotiepinas/química , Dibenzotiepinas/síntesis química , Triazinas/química , Triazinas/síntesis química , Oxidación-Reducción , Descarboxilación , Morfolinas/química , Morfolinas/síntesis química , Piridonas/química , Piridonas/síntesis química , Procesos Fotoquímicos , Antivirales/síntesis química , Antivirales/química
2.
Int J Colorectal Dis ; 39(1): 32, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38431759

RESUMEN

PURPOSE: The long-term prognosis of stapled and hand-sewn ileal pouch-anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch-anal anastomosis. METHODS: This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch-anal anastomosis were compared. RESULTS: The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch-anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch-anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch-anal anastomosis than in hand-sewn ileal pouch-anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch-anal anastomosis on overall survival. CONCLUSION: Stapled ileal pouch-anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch-anal anastomosis is recommended for better prognosis in these patients.


Asunto(s)
Adenoma , Poliposis Adenomatosa del Colon , Reservorios Cólicos , Proctocolectomía Restauradora , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Proctocolectomía Restauradora/efectos adversos , Poliposis Adenomatosa del Colon/cirugía , Pronóstico , Neoplasias del Recto/cirugía , Reservorios Cólicos/efectos adversos , Resultado del Tratamiento
3.
J Asthma ; 56(11): 1147-1158, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30822174

RESUMEN

Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/µL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/µL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1 second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as ¥357,958/patient-year, and asthma exacerbations as ¥26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.


Asunto(s)
Antiasmáticos/uso terapéutico , Asma/economía , Asma/epidemiología , Costo de Enfermedad , Eosinofilia Pulmonar/epidemiología , Adolescente , Adulto , Distribución por Edad , Análisis de Varianza , Asma/sangre , Asma/tratamiento farmacológico , Estudios de Cohortes , Bases de Datos Factuales , Manejo de la Enfermedad , Progresión de la Enfermedad , Eosinófilos/inmunología , Femenino , Costos de la Atención en Salud , Hospitales Universitarios , Humanos , Japón/epidemiología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Eosinofilia Pulmonar/sangre , Eosinofilia Pulmonar/tratamiento farmacológico , Pruebas de Función Respiratoria , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Adulto Joven
4.
Int J Clin Oncol ; 22(2): 269-273, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27832386

RESUMEN

BACKGROUND: Lung cancer is the leading cause of cancer death and is closely linked to tobacco smoking. Genetic polymorphisms in genes that encode enzymes involved in metabolizing tobacco carcinogens could affect an individual's risk for lung cancer. While polymorphism of UDP-glucuronosyltransferase1A1 (UGT1A1) is involved in detoxification of benzo(a)pyrene-7,8-dihydrodiol(-), a major tobacco carcinogen, the association between UGT1A1 genotype and lung cancer has not been examined. METHODS: We retrieved the clinical data of 5,285 patients who underwent systemic chemotherapy at Kyoto University Hospital. A total of 765 patients (194 lung cancer patients and 671 patients with other malignancies) with UGT1A1 genotyping data were included in this analysis. We used logistic regression with recessive, dominant, and additive models to identify differences in genotype frequencies between lung cancer and other malignancies. RESULTS: In the recessive model, UGT1A1*28*28 genotype was significantly associated with lung cancer compared to other malignancies (odds ratio 5.3, P = 0.0083). Among lung cancer patients with a smoking history, squamous cell carcinoma was significantly predominant in patients with UGT1A1*28*28 compared to those with other UGT1A1 genotypes (P = 0.024). CONCLUSION: This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Glucuronosiltransferasa/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Adenocarcinoma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/epidemiología , Femenino , Genotipo , Humanos , Japón/epidemiología , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Prospectivos , Carcinoma Pulmonar de Células Pequeñas/epidemiología , Fumar , Adulto Joven
5.
Mol Pain ; 122016.
Artículo en Inglés | MEDLINE | ID: mdl-27030720

RESUMEN

BACKGROUND: Chronic pain associated with inflammation is an important clinical problem, and the underlying mechanisms remain poorly understood. 4-Nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog (NIPSNAP) 1, an interacting protein with neuropeptide nocistatin, is implicated in the inhibition of tactile pain allodynia. Although nocistatin inhibits some inflammatory pain responses, whether NIPSNAP1 affects inflammatory pain appears to be unclear. Here, we examined the nociceptive behavioral response of NIPSNAP1-deficient mice and the expression of NIPSNAP1 following peripheral inflammation to determine the contribution of NIPSNAP1 to inflammatory pain. RESULTS: Nociceptive behavioral response increased in phase II of the formalin test, particularly during the later stage (26-50 min) in NIPSNAP1-deficient mice, although the response during phase I (0-15 min) was not significantly different between the deficient and wild-type mice. Moreover, phosphorylation of extracellular signal-related kinase was enhanced in the spinal dorsal horn of the deficient mice. The prolonged inflammatory pain induced by carrageenan and complete Freund's adjuvant was exacerbated in NIPSNAP1-deficient mice. NIPSNAP1 mRNA was expressed in small- and medium-sized neurons of the dorsal root ganglion and motor neurons of the spinal cord. In the formalin test, NIPSNAP1 mRNA was slightly increased in dorsal root ganglion but not in the spinal cord. In contrast, NIPSNAP1 mRNA levels in dorsal root ganglion were significantly decreased during 24-48 h after carrageenan injection. Prostaglandin E2, a major mediator of inflammation, stimulated NIPSNAP1 mRNA expression via the cAMP-protein kinase A signaling pathway in isolated dorsal root ganglion cells. CONCLUSIONS: These results suggest that changes in NIPSNAP1 expression may contribute to the pathogenesis of inflammatory pain.


Asunto(s)
Inflamación/complicaciones , Inflamación/metabolismo , Neuropéptidos/metabolismo , Péptidos Opioides/metabolismo , Dolor/complicaciones , Dolor/metabolismo , Proteínas/metabolismo , Animales , Inhibidores de la Ciclooxigenasa/farmacología , Dinoprostona/farmacología , Formaldehído , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Inflamación/genética , Péptidos y Proteínas de Señalización Intercelular , Proteínas de la Membrana , Ratones , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
6.
World J Surg Oncol ; 14: 68, 2016 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-26957123

RESUMEN

BACKGROUND: Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST. CASE PRESENTATION: A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery. CONCLUSIONS: Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.


Asunto(s)
Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/terapia , Mesilato de Imatinib/uso terapéutico , Laparoscopía , Terapia Neoadyuvante , Tratamientos Conservadores del Órgano , Neoplasias del Recto/terapia , Canal Anal , Antineoplásicos/uso terapéutico , Terapia Combinada , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/patología
7.
Int J Cancer ; 134(1): 218-23, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23775066

RESUMEN

NK012 is a micelle-forming macromolecular prodrug of 7-ethyl-10-hydroxy camptothecin (SN-38), an active metabolite of irinotecan. It is accumulated and retained in tumor tissues and gradually releases SN-38 in an enzyme-independent manner. NK012 was previously demonstrated to have stronger antitumor activity than irinotecan in a broad range of human solid-tumor xenograft models. In our study, we used an orthotopic multiple myeloma (MM) model created by injecting CD138-positive U266B1, a myeloma cell line that produces human IgE lambda light chain (monoclonal protein, M protein), into immunodeficient NOD/Shi-scid, IL-2Rγc (null) mice. This model shows typical bone marrow infiltration by the human myeloma cells. We evaluated the antimyeloma activity of intravenously administered NK012 in this model and showed that it suppressed the M protein concentration in the plasma and proliferation of myeloma cells in the bone marrow in a dose-dependent manner. NK012 suppressed the progression of hind-leg paralysis and prolonged the survival time of the mice compared to the untreated control group. In combination with bortezomib (BTZ), NK012 increased the median survival time compared to that with BTZ alone. In conclusion, these results suggest that NK012 is a potential candidate for use-alone and in combination-in the treatment of MM in humans.


Asunto(s)
Antineoplásicos/farmacología , Camptotecina/análogos & derivados , Mieloma Múltiple/tratamiento farmacológico , Profármacos/farmacología , Animales , Camptotecina/farmacología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Humanos , Irinotecán , Ratones , Ratones Endogámicos NOD , Ratones SCID , Micelas , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Opt Express ; 22 Suppl 1: A28-34, 2014 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-24921997

RESUMEN

A prototype concentrator photovoltaic (CPV) module with high solar concentration, an added low-cost solar cell, and an adjoining multi-junction solar cell is fabricated and experimentally demonstrated. In the present CPV module, the low cost solar cell captures diffuse solar radiation penetrating the concentrator lens and the multi-junction cell captures concentrated direct solar radiation. On-sun test results show that the electricity generated by a Fresnel lens-based CPV module with an additional crystalline silicon solar cell is greater than that for a conventional CPV module by a factor of 1.44 when the mean ratio of diffuse normal irradiation to global normal irradiation at the module aperture is 0.4. Several fundamental optical characteristics are presented for the present module.

9.
J Med Internet Res ; 16(2): e61, 2014 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-24565806

RESUMEN

BACKGROUND: Decrease of dual-task (DT) ability is known to be one of the risk factors for falls. We developed a new game concept, Dual-Task Tai Chi (DTTC), using Microsoft's motion-capture device Kinect, and demonstrated that the DTTC test can quantitatively evaluate various functions that are known risk factors for falling in elderly adults. Moreover, DT training has been attracting attention as a way to improve balance and DT ability. However, only a few studies have reported that it improves cognitive performance. OBJECTIVE: The purpose of this study was to demonstrate whether or not a 12-week program of DTTC training would effectively improve cognitive functions. METHODS: This study examined cognitive functions in community-dwelling older adults before and after 12 weeks of DTTC training (training group [TG]) or standardized training (control group [CG]). Primary end points were based on the difference in cognitive functions between the TG and the CG. Cognitive functions were evaluated using the trail-making test (part A and part B) and verbal fluency test. RESULTS: A total of 41 elderly individuals (TG: n=26, CG: n=15) participated in this study and their cognitive functions were assessed before and after DTTC training. Significant differences were observed between the two groups with significant group × time interactions for the executive cognitive function measure, the delta-trail-making test (part B-part A; F1,36=4.94, P=.03; TG: pre mean 48.8 [SD 43.9], post mean 42.2 [SD 29.0]; CG: pre mean 49.5 [SD 51.8], post mean 64.9 [SD 54.7]). CONCLUSIONS: The results suggest that DTTC training is effective for improving executive cognitive functions. TRIAL REGISTRATION: Japan Medical Association Clinical Trial Registration Number: JMA-IIA00092; https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=2682 (Archived by WebCite at http://www.webcitation.org/6NRtOkZFh).


Asunto(s)
Función Ejecutiva/fisiología , Ejercicio Físico/psicología , Taichi Chuan , Anciano , Estudios de Casos y Controles , Cognición , Humanos , Características de la Residencia
10.
Int J Health Plann Manage ; 29(3): e207-32, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23785010

RESUMEN

Comparison of financial indices helps to illustrate differences in operations and efficiency among similar hospitals. Outlier data tend to influence statistical indices, and so detection of outliers is desirable. Development of a methodology for financial outlier detection using information systems will help to reduce the time and effort required, eliminate the subjective elements in detection of outlier data, and improve the efficiency and quality of analysis. The purpose of this research was to develop such a methodology. Financial outliers were defined based on a case model. An outlier-detection method using the distances between cases in multi-dimensional space is proposed. Experiments using three diagnosis groups indicated successful detection of cases for which the profitability and income structure differed from other cases. Therefore, the method proposed here can be used to detect outliers.


Asunto(s)
Economía Hospitalaria , Administración Financiera de Hospitales , Modelos Estadísticos , Acampadores DRG/economía , Algoritmos , Benchmarking , Humanos
11.
Telemed J E Health ; 20(3): 235-40, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24404820

RESUMEN

OBJECTIVES: The disease activities of rheumatoid arthritis (RA) tend to fluctuate between visits to doctors, and a self-assessment tool can help patients accommodate to their current status at home. The aim of the present study was to develop a novel modality to assess the disease activity of RA by a smartphone without the need to visit a doctor. SUBJECTS AND METHODS: This study included 65 patients with RA, 63.1 ± 11.9 years of age. The 28-joint disease activity score (DAS28) was measured for all participants at each clinic visit. The patients assessed their status with the modified Health Assessment Questionnaire (mHAQ), a self-assessed tender joint count (sTJC), and a self-assessed swollen joint count (sSJC) in a smartphone application. The patients' trunk acceleration while walking was also measured with a smartphone application. The peak frequency, autocorrelation (AC) peak, and coefficient of variance of the acceleration peak intervals were calculated as the gait parameters. RESULTS: Univariate analyses showed that the DAS28 was associated with mHAQ, sTJC, sSJC, and AC (p<0.05). In a stepwise linear regression analysis, mHAQ (ß = 0.264, p<0.05), sTJC (ß = 0.581, p<0.001), and AC (ß = -0.157, p<0.05) were significantly associated with DAS28 in the final model, and the predictive model explained 67% of the DAS28 variance. CONCLUSIONS: The results suggest that noninvasive self-assessment of a combination of joint symptoms, limitations of daily activities, and walking ability can adequately predict disease activity of RA with a smartphone application.


Asunto(s)
Artritis Reumatoide/fisiopatología , Teléfono Celular , Autoevaluación Diagnóstica , Aplicaciones Móviles , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autocuidado/métodos , Encuestas y Cuestionarios
12.
Artículo en Inglés | MEDLINE | ID: mdl-38447981

RESUMEN

The incidence of gastric tube cancers has increased due to improved survival rates in patients after esophagectomy. However, the optimal surgical approach for gastric tube cancer remains controversial. Here, we report the case of a 70-year-old man with advanced gastric cancer arising from a retrosternally placed gastric conduit, 12 years after thoracic esophagectomy for esophageal cancer. Total resection of the gastric conduit was performed with robotic assistance. Although the working space was limited, secure resection was possible. Continuous en bloc mobilization was achieved with neck dissection, and reconstruction was performed via the same retrosternal route using the ileocolon. The patient was discharged on the 14th postoperative day without any adverse events. Robot-assisted surgery can overcome the technical limitations of laparoscopic mediastinal surgery and has advantages such as improved ergonomics, comfort, and elimination of hand tremors, and therefore may be an option for future minimally invasive surgeries.


Asunto(s)
Neoplasias Esofágicas , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Anciano , Procedimientos Quirúrgicos Robotizados/efectos adversos , Esofagectomía/efectos adversos , Resultado del Tratamiento , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/cirugía
13.
Blood ; 117(13): 3575-84, 2011 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-21245486

RESUMEN

Adult T-cell leukemia-lymphoma (ATL) is an aggressive disease, incurable by standard chemotherapy. NK314, a new anticancer agent possessing inhibitory activity specific for topoisomerase IIα (Top2α), inhibited the growth of various ATL cell lines (50% inhibitory concentration: 23-70nM) with more potent activity than that of etoposide. In addition to the induction of DNA double-strand breaks by inhibition of Top2α, NK314 induced degradation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), resulting in impaired DNA double-strand break repair. The contribution of DNA-PK to inhibition of cell growth was affirmed by the following results: NK314 inhibited cell growth of M059J (a DNA-PKcs-deficient cell line) and M059K (a cell line with DNA-PKcs present) with the same potency, whereas etoposide exhibited weak inhibition of cell growth with M059K cells. A DNA-PK specific inhibitor, NU7026, enhanced inhibitory activity of etoposide on M059K as well as on ATL cells. These results suggest that NK314 is a dual inhibitor of Top2α and DNA-PK. Because ATL cells express a high amount of DNA-PKcs, NK314 as a dual molecular targeting anticancer agent is a potential therapeutic tool for treatment of ATL.


Asunto(s)
Proteína Quinasa Activada por ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/antagonistas & inhibidores , Leucemia de Células T/patología , Fenantrenos/farmacología , Adulto , Animales , Antígenos de Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Roturas del ADN de Doble Cadena/efectos de los fármacos , Roturas del ADN de Doble Cadena/efectos de la radiación , Reparación del ADN/efectos de los fármacos , ADN-Topoisomerasas de Tipo II , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Células Jurkat , Leucemia de Células T/tratamiento farmacológico , Ratones , Ratones SCID , Terapia Molecular Dirigida , Fenantrenos/uso terapéutico , Radiación Ionizante , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Stud Health Technol Inform ; 184: 242-6, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23400164

RESUMEN

Virtual reality (VR) simulation is expected to be advantageous to surgical training for invasive operations such as incision and dissection that are unrepeatable in the real world. This study focuses on ablation in order to provide a simulation model for soft tissue rupture progression. To simulate soft tissue handling by two or more manipulators, the model must calculate the stress accumulation at the tip of a rupture. This stress accumulation is affected by the stress condition caused by the manipulators. Herein, the authors propose a method to integrate multiple stresses with two different hypotheses. The proposed model was evaluated through the simulation of primitive board ablation.


Asunto(s)
Tejido Conectivo/fisiología , Tejido Conectivo/cirugía , Modelos Biológicos , Cirugía Asistida por Computador/métodos , Interfaz Usuario-Computador , Simulación por Computador , Humanos , Presión , Estrés Mecánico , Integración de Sistemas
15.
PNAS Nexus ; 2(3): pgad067, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37007707

RESUMEN

Solar cells are a promising optoelectronic device for the simultaneous solution of energy resource and environmental problems. However, their high cost and slow, laborious production process so far severely hinder a sufficient widespread of clean, renewable photovoltaic energy as a major alternative electricity generator. This undesirable situation is mainly attributed to the fact that photovoltaic devices have been manufactured through a series of vacuum and high-temperature processes. Here we realize a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS)/Si heterojunction solar cell fabricated only in ambient and room temperature conditions from a plain Si wafer, with an over 10% energy conversion efficiency. Our production scheme is based on our finding that PEDOT:PSS photovoltaic layers actively operate even on highly doped Si substrates, which substantially mitigates the condition requirements for electrode implementation. Our approach may pave the way for facile, low-cost, high-throughput solar cell fabrication, useful in various fields even including developing countries and educational sites.

16.
J Org Chem ; 77(3): 1367-77, 2012 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-22196045

RESUMEN

Full details of the total synthesis of pacidamycin D (4) and its 3'-hydroxy analogue 32 are described. The chemically labile Z-oxyacyl enamide moiety is the most challenging chemical structure found in uridylpeptide natural products. Key elements of our approach to the synthesis of 4 include the efficient and stereocontrolled construction of the Z-oxyvinyl halides 6 and 7 and their copper-catalyzed cross-coupling with the tetrapeptide carboxamide 5, a thermally unstable compound containing a number of potentially reactive functional groups. This synthetic route also allowed us to easily prepare 3'-hydroxy analogue 32. The assemblage by cross-coupling of the Z-oxyvinyl halide 6 and the carboxamide 5 at a late stage of the synthesis provided ready access to a range of uridylpeptide antibiotics and their analogues, despite their inherent labile nature with potential epimerization, simply by altering the tetrapeptide moiety.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Técnicas de Química Sintética/métodos , Péptidos/síntesis química , Péptidos/farmacología , Nucleósidos de Pirimidina/síntesis química , Nucleósidos de Pirimidina/farmacología , Antibacterianos/química , Catálisis , Cobre/química , Pruebas de Sensibilidad Microbiana , Péptidos/química , Pseudomonas aeruginosa/efectos de los fármacos , Nucleósidos de Pirimidina/química
17.
Bioorg Med Chem Lett ; 22(14): 4810-5, 2012 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-22677318

RESUMEN

The second-generation synthesis of 3'-hydroxypacidamycin D (2) has been accomplished via an Ugi-four component reaction at a late stage of the synthesis. This approach provided ready access to a range of analogues including diastereomers of the diaminobutylic acid residue and hybrid-type analogues of mureidomycins. Biological evaluations of these analogues indicated that the stereochemistry at the diaminobutylic acid residue has a crucial impact on both the MraY biochemical inhibition and whole-cell antibacterial activity.


Asunto(s)
Antibacterianos/síntesis química , Oligopéptidos/síntesis química , Nucleósidos de Pirimidina/síntesis química , Aldehídos/química , Antibacterianos/farmacología , Hidroxilación , Estructura Molecular , Oligopéptidos/farmacología , Pseudomonas/efectos de los fármacos , Nucleósidos de Pirimidina/farmacología , Relación Estructura-Actividad
18.
Rheumatol Int ; 32(12): 3869-74, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22193221

RESUMEN

A disturbance in gait pattern is a serious problem in patients with rheumatoid arthritis (RA). The aim of the present study was to examine the utility of the smartphone gait analysis application in patients with RA. The smartphone gait analysis application was used to assess 39 patients with RA (age 65.9 ± 10.0 years, disease duration 11.9 ± 9.4 years) and age-matched control individuals (mean age, 69.1 ± 5.8 years). For all RA patients, the following data were obtained: disease activity score (DAS) 28, modified health assessment questionnaire (mHAQ), and assessment of walking ability. Patients walked 20 m at their preferred speed, and trunk acceleration was measured using a Smartphone. After signal processing, we calculated the following gait parameters for each measurement terminal: peak frequency (PF), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. The gait parameters of RA and control groups were compared to examine the comparability of the 2 groups. Criterion-related validity was determined by evaluating the correlation between gait parameters and clinical parameters using Spearman's correlation coefficient. The RA group showed significantly lower scores for the walking speed, AC, and CV than the control group. There were no significant differences in PF. PF (gait cycle) was mildly associated with gait speed (P < 0.05). AC (gait balance) was moderately associated with the DAS, mHAQ, gait ability, and gait speed (P < 0.05). CV (gait variability) was moderately associated with the DAS, gait ability, and gait speed (P < 0.05). This is the first study to examine the use of a smartphone device for gait pattern measurement. The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with RA.


Asunto(s)
Artritis Reumatoide/fisiopatología , Teléfono Celular , Marcha/fisiología , Trastornos del Movimiento/diagnóstico , Caminata/fisiología , Anciano , Artritis Reumatoide/complicaciones , Fenómenos Biomecánicos/fisiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/complicaciones , Trastornos del Movimiento/fisiopatología
19.
Telemed J E Health ; 18(4): 292-6, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22400972

RESUMEN

Smartphones are very common devices in daily life that have a built-in tri-axial accelerometer. Similar to previously developed accelerometers, smartphones can be used to assess gait patterns. However, few gait analyses have been performed using smartphones, and their reliability and validity have not been evaluated yet. The purpose of this study was to evaluate the reliability and validity of a smartphone accelerometer. Thirty healthy young adults participated in this study. They walked 20 m at their preferred speeds, and their trunk accelerations were measured using a smartphone and a tri-axial accelerometer that was secured over the L3 spinous process. We developed a gait analysis application and installed it in the smartphone to measure the acceleration. After signal processing, we calculated the gait parameters of each measurement terminal: peak frequency (PF), root mean square (RMS), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. Remarkable consistency was observed in the test-retest reliability of all the gait parameter results obtained by the smartphone (p<0.001). All the gait parameter results obtained by the smartphone showed statistically significant and considerable correlations with the same parameter results obtained by the tri-axial accelerometer (PF r=0.99, RMS r=0.89, AC r=0.85, CV r=0.82; p<0.01). Our study indicates that the smartphone with gait analysis application used in this study has the capacity to quantify gait parameters with a degree of accuracy that is comparable to that of the tri-axial accelerometer.


Asunto(s)
Aceleración , Marcha , Telemedicina/instrumentación , Adolescente , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Japón , Masculino , Reproducibilidad de los Resultados , Procesamiento de Señales Asistido por Computador , Telemedicina/métodos , Adulto Joven
20.
Biopsychosoc Med ; 15(1): 6, 2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33736660

RESUMEN

PURPOSE: To assess the validity and reliability of the Japanese version of the Daily Record of Severity of Problems (J-DRSP, 24 items) for evaluating symptoms of premenstrual syndrome (PMS), and to develop a short form version of the J-DRSP. METHODS: Using the "DRSP-JAPAN" smartphone app, we collected daily J-DRSP records from cycle day - 6 (CD - 6) to CD 10, with CD 1 representing the menstruation onset date. Factorial validity (exploratory factor analysis: EFA, confirmatory factor analysis: CFA) and criterion validity were examined, and test-retest reliability (intraclass correlation: ICC) evaluated. The short-form version of the J-DRSP was developed using classical test theory. RESULTS: In total, 304 women participated and 243 recorded symptoms on at least 4 days spanning the week of the luteal phase (CD - 6 to CD 0) and 4 days spanning the week of the follicular phase (CD 4 to CD 10), with CD 0 set as the day before menstruation started. The EFA revealed a two-factor structure. Kaiser-Meyer-Olkin was 0.992, and Bartlett's test of sphericity chi-square was 3653.89 (P < 0.001). However, the model fitness of CFA was found to be suboptimal (comparative fit index (CFI): 0.83, root mean square error of approximation (RMSEA): 0.12). Total scores for J-DRSP and the sum scores for each subscale were higher on CD 0 than on CD 10 (p < 0.001), suggesting validity for some criteria. ICC values for the total J-DRSP score from CD 0 to CD - 1, and between CD 9 to CD 10, were 0.60 (95% CI: 0.48-0.72) and 0.76 (95% CI: 0.69-0.82), respectively. Having eliminated some original items after considering factor loading for each item, we developed an 8-item Short-Form J-DRSP (J-DRSP (SF)) comprising 2 factors (S-Psychological and S-Physical, 4 items for each). CFA showed a better model fit (CFI: 0.99, RMSEA: 0.048), and ICC values in the luteal and follicular phases were 0.61 (95%CI: 0.51-0.68) and 0.70 (95%CI: 0.62-0.77), respectively. CONCLUSION: The J-DRSP has moderate to good reliability and a certain level of validity. The 8-item J-DRSP (SF) has a two-factor structure and can be used effectively among Japanese women to assess their PMS symptoms.

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