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1.
Behav Sci (Basel) ; 13(11)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37998670

RESUMEN

Tourism to Indian heritage destinations has been on the rise due to the increasing demand for heritage tourism. Increasing customer satisfaction and promoting Indian culture require tourism businesses to understand factors influencing tourists' experiences and behavior towards these destinations. Therefore, this study analyzes four popular heritage tourist destinations in India by using online reviews collected from Google Travel. Data are refined, processed, and visualized using the R programming language and UCINET 6.0. Furthermore, we explore the fundamental framework and interconnections among these characteristics through the utilization of exploratory factor analysis and linear regression analysis with the assistance of the SPSS software package. Based on customer reviews obtained from Google Reviews, an analysis was conducted on 6618 reviews of four heritage tourism destinations in India. From the top 60 words, four clusters of words were created, including "Physical characteristic", "Cultural and historical link", "atmosphere", and "area". Through explanatory factor analysis and linear regression analysis, we found that Physical characteristic, Cultural and historical link, atmosphere, and area all play a significant role in customer satisfaction. This study provides heritage destination managers and Indian government with insights into which attributes impact customer satisfaction the most and offers valuable marketing insights. As a result of this study, we are able to gain a greater understanding of the Indian heritage tourism market, and in doing so, we provide businesses with implications on how to enhance customer service.

2.
EClinicalMedicine ; 41: 101169, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34723164

RESUMEN

BACKGROUND: Nafamostat, a serine protease inhibitor, has been used for the treatment of disseminated intravascular coagulation and pancreatitis. In vitro studies and clinical reports suggest its beneficial effect in the treatment of COVID-19 pneumonia. METHODS: This phase 2 open-label, randomised, multicentre, controlled trial evaluated nafamostat (4.8 mg/kg/day) plus standard-of-care (SOC) in hospitalised patients with COVID-19 pneumonia (i.e., those requiring nasal high-flow oxygen therapy and/or non-invasive mechanical ventilation). The primary outcome was the time to clinical improvement. Key secondary outcomes included the time to recovery, rates of recovery and National Early Warning Score (NEWS). The trial is registered with ClinicalTrials.gov Identifier: NCT04623021. FINDINGS: A total of 104 patients, mean age 58.6 years were enrolled in 13 clinical centres in Russia between 25/9/2020 and 14/11/2020 and randomised to nafamostat plus SOC (n=53) or SOC alone (n=51). There was no significant difference in time to clinical improvement (primary endpoint) between the nafamostat and SOC groups (median 11 [interquartile range (IQR) 9 to 14) vs 11 [IQR 9 to 14] days; Rate Ratio [RR; the ratio for clinical improvement], 1.00; 95% CI, 0.65 to 1.57; p=0.953). In 36 patients with baseline NEWS ≥7, nafamostat was superior to SOC alone in median time to clinical improvement (11 vs 14 days; RR, 2.89; 95% CI, 1.17 to 7.14; p=0.012). Patients receiving nafamostat in this subgroup had a significantly higher recovery rate compared with SOC alone (61.1% (11/18) vs 11.1 % (2/18) by Day 11, p=0.002). The 28-day mortality was 1.9% (1/52) for nafamostat and 8.0% (4/50) for SOC (95% CI, -17.0 to 3.4; p=0.155). No case of COVID-19 related serious adverse events leading to death was recorded in the patients receiving nafamostat. INTERPRETATION: Our study found no significant difference in time to clinical improvement between the nafamostat and SOC groups, but a shorter median time to clinical improvement in a small group of high-risk COVID-19 patients requiring oxygen treatment. To assess the efficacy further, a larger Phase 3 clinical trial is warranted. FUNDING: Korea Research Institute of Bioscience and Biotechnology [2020M3A9H5108928] and Chong Kun Dang (CKD) Pharm (Seoul, Korea).

3.
Clin Ther ; 35(10): 1528-35, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24050970

RESUMEN

BACKGROUND: Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs. OBJECTIVE: The aim of this study was to investigate any pharmacokinetic interactions between eperisone hydrochloride and aceclofenac in healthy Korean men. METHODS: This was a randomized, open-label, crossover study. Each participant was randomly assigned to 1 of 6 treatment sequences and received eperisone hydrochloride (3 doses of 50 mg each), aceclofenac (2 doses of 100 mg each), or both as a single dose with a 7-day washout period between each dose. Blood samples were collected ≤ 24 hours after dosing, and plasma eperisone hydrochloride and aceclofenac concentrations were determined using validated LC/MS-MS. Pharmacokinetic analyses were conducted using noncompartmental methods. A safety profile was determined using the measurement of vital signs, ECG, and clinical laboratory tests. RESULTS: A total 24 of men were enrolled, and all completed the study. The geometric mean ratios (90% CIs) of the Cmax and AUC0-∞ values for eperisone were 1.18 (0.828-1.673) and 1.12 (0.836-1.507), respectively. The geometric mean ratios (90% CIs) of the Cmax and AUC0-∞ for aceclofenac were 0.93 (0.847-1.022) and 1.01 (0.979-1.036), respectively. A total of 7 adverse events were reported in 7 men. All adverse events were mild, and no significant differences were found between treatment groups. CONCLUSION: No clinically significant pharmacokinetic differences exist between 150 mg eperisone hydrochloride and 200 mg aceclofenac when administrated as a monotherapy or in combination.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Diclofenaco/análogos & derivados , Relajantes Musculares Centrales/farmacocinética , Propiofenonas/farmacocinética , Administración Oral , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Estudios Cruzados , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada , Voluntarios Sanos , Humanos , Masculino , Relajantes Musculares Centrales/administración & dosificación , Propiofenonas/administración & dosificación , República de Corea , Equivalencia Terapéutica , Adulto Joven
4.
BioDrugs ; 27(2): 149-58, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23359067

RESUMEN

BACKGROUND: HM10460A is a newly developed recombinant human granulocyte colony-stimulating factor with long-lasting characteristics. This factor is expected to be used for chemotherapy-related neutropenic conditions. OBJECTIVE: The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of HM10460A following subcutaneous administration to healthy Korean subjects. METHODS: A randomized, double-blind, placebo-controlled, escalating single-dose study was conducted in 40 healthy Korean subjects. The subjects were allocated to single-dose groups of 5, 15, 45, 135 or 350 µg/kg, or placebo. Serial blood samples for pharmacokinetic/pharmacodynamic analyses were collected up to 22 days, and urine samples for pharmacokinetic analysis were collected up to 3 days after subcutaneous administration of HM10460A. The serum and urine concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: Most of the serum concentrations in the 5 and 15 µg/kg dosing groups were below the lower limit of quantification (LLOQ). The median times to the peak concentration (T(max)) of HM10460A in the 45, 135, and 350 µg/kg dosing groups were 8.0, 14.0, and 24.0 h, respectively. The mean ± standard deviation values of the dose-normalized maximum concentration (C(max)) and dose-normalized area under the concentration-time curve (AUC(last)) for the 45, 135, and 350 µg/kg dosing groups were 14.13 ± 6.37, 66.19 ± 38.71, and 34.65 ± 19.69 µg/L/mg, respectively, and 265.0 ± 124.1, 2144 ± 1232, and 1386 ± 701.2 µg h/L/mg, respectively. The concentrations of HM10460A in the urine were below the LLOQ in all of the subjects. In all of the dosing groups, the area under the effect-time curve (AUEC(last)) of both the absolute neutrophil count (ANC) and the CD34(+) cell count increased as the dose increased. CONCLUSION: HM10460A showed dose-dependent pharmacokinetic characteristics, and the systemic exposure of HM10460A was positively correlated with the ANC and CD34(+) cell counts.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacocinética , Fragmentos Fc de Inmunoglobulinas/farmacología , Neutrófilos/efectos de los fármacos , Adulto , Antígenos CD34/biosíntesis , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Inyecciones Subcutáneas , Recuento de Leucocitos , Masculino , Neutrófilos/citología , Factores de Tiempo , Adulto Joven
5.
J Obstet Gynaecol Res ; 36(3): 474-8, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20598023

RESUMEN

AIM: To determine the pregnancy termination rate, and perinatal and 1-year infant mortality rates following prenatally-detected congenital heart disease (CHD) and trends over an 11-year period. METHODS: Between 1994 and 2005, 1603 gravidas underwent fetal echocardiography in our institution, in which 378 fetuses were diagnosed with CHD. The study period was divided into the following three groups for time-trend analysis: 1994-1997, 1998-2001, and 2002-2005. Data regarding gestational age at diagnosis and delivery, the presence of extracardiac or chromosomal abnormalities, pregnancy termination rate, and perinatal and 1-year mortalities were collected by review of medical records and telephone interviews. RESULTS: Among 378 fetuses with a prenatally-detected CHD, complete perinatal and infant outcomes were available for 336 fetuses (88.9%). There was a gradual increase in prenatally-detected CHD by fetal echocardiography during the study period (1994-1997, 10.3%; 1998-2001, 17.3%; and 2002-2005, 24.3%). The mean gestational ages at diagnosis and delivery were 27.2 +/- 5.6 and 37.8 +/- 2.9 weeks, respectively. Overall, the pregnancy termination rate in this study population was 20.2% and the perinatal and 1-year infant mortality rates were 6.3% and 9.7%, respectively. Among the fetuses who underwent cardiac surgery, surgical mortality occurred in two (3.8%); both died more than 1 month after surgery. Although the pregnancy termination rates remained unchanged, there was a significant decrease in perinatal and 1-year infant mortality rates over the study period. CONCLUSION: Although the perinatal and 1-year infant mortalities following prenatally-detected CHD have continued to decrease significantly during the past 11 years, pregnancy termination rates have remained unchanged.


Asunto(s)
Aborto Inducido/estadística & datos numéricos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/mortalidad , Ultrasonografía Prenatal , Aborto Inducido/tendencias , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Corea (Geográfico)/epidemiología , Embarazo
6.
J Biol Chem ; 283(51): 35805-14, 2008 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-18842582

RESUMEN

Pre-mRNA splicing entails reversible phosphorylation of spliceosomal proteins. Recent work has revealed essential roles for Ser/Thr phosphatases, such as protein phosphatase-1 (PP1), in splicing, but how these phosphatases are regulated is largely unknown. We show that nuclear inhibitor of PP1 (NIPP1), a major PP1 interactor in the vertebrate nucleus, recruits PP1 to Sap155 (spliceosome-associated protein 155), an essential component of U2 small nuclear ribonucleoprotein particles, and promotes Sap155 dephosphorylation. C-terminally truncated NIPP1 (NIPP1-DeltaC) formed a hyper-active holoenzyme with PP1, rendering PP1 minimally phosphorylated on an inhibitory site. Forced expression of NIPP1-WT and -DeltaC resulted in slight and severe decreases in Sap155 hyperphosphorylation, respectively, and the latter was accompanied with inhibition of splicing. PP1 overexpression produced similar effects, whereas small interfering RNA-mediated NIPP1 knockdown enhanced Sap155 hyperphosphorylation upon okadaic acid treatment. NIPP1 did not inhibit but rather stimulated Sap155 dephosphorylation by PP1 in vitro through facilitating Sap155/PP1 interaction. Further analysis revealed that NIPP1 specifically recognizes hyperphosphorylated Sap155 thorough its Forkhead-associated domain and dissociates from Sap155 after dephosphorylation by associated PP1. Thus NIPP1 works as a molecular sensor for PP1 to recognize phosphorylated Sap155.


Asunto(s)
Endorribonucleasas/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas/metabolismo , Proteína Fosfatasa 1/metabolismo , Precursores del ARN/metabolismo , Empalme del ARN/fisiología , Proteínas de Unión al ARN/metabolismo , Ribonucleoproteína Nuclear Pequeña U2/metabolismo , Endorribonucleasas/genética , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas/genética , Fosforilación/fisiología , Proteína Fosfatasa 1/genética , Estructura Terciaria de Proteína/fisiología , Precursores del ARN/genética , Factores de Empalme de ARN , Proteínas de Unión al ARN/genética , Ribonucleoproteína Nuclear Pequeña U2/genética
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