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1.
Artículo en Inglés | MEDLINE | ID: mdl-38514967

RESUMEN

OBJECTIVE: Anchoring the fetal membrane to the uterine wall via a novel suture delivery system could reduce the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery. This study assesses the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the suturing device both ex vivo and in vivo. In the ex vivo studies, 12-French trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For in vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at ~79-90 days gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were successfully anchored to the uterine myometrium using this device in all five trials performed ex vivo. The in vivo trials also revealed successful membrane anchoring compared with controls both at the time of device deployment and five-to-eight weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium via suturing device both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human subjects. This article is protected by copyright. All rights reserved.

2.
Public Health ; 232: 188-194, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38796916

RESUMEN

OBJECTIVES: Long working hour is a known risk factor for metabolic diseases. We explored the association between working hours and metabolic dysfunction-associated steatotic liver disease (MASLD). STUDY DESIGN: Data on working hours among 22,818 workers (11,999 females) from the Korea National Health and Nutrition Examination Survey (2013-2021) were used for this study. METHODS: MASLD was defined as a combination of hepatic steatosis combined with one or more of cardiometabolic risk factors (overweight/obesity, prediabetes/diabetes, raised blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol). Hepatic steatosis was assessed using the hepatic steatosis index. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The overall prevalence of MASLD was 30.4% in men and 18.1% in women. Among male workers, 20.2% worked ≥55 h/week, whereas among female workers, 10.1% worked ≥55 h/week. Compared with working 35-40 h/week, working ≥55 h/week was positively associated with overweight/obesity (OR: 1.21; 95% CI: 1.05-1.40), pre-diabetes mellitus (pre-DM)/DM (OR: 1.20; 95% CI: 1.04-1.38), raised blood pressure (OR: 1.17; 95% CI: 1.02-1.35), and presence of any cardiometabolic risk factors (OR: 1.56; 95% CI: 1.21-2.02). The adjusted OR (95% CI) of the association between working hours and MASLD was 1.27 (1.09-1.47) for ≥55 h/week compared with working 35-40 h/week in male workers. In female workers, long working hours were not clearly associated with cardiometabolic risk factors and MASLD. CONCLUSION: Long working hours are positively associated with MASLD among Korean male workers. Policy interventions are needed to mitigate the adverse metabolic effects of prolonged working hours.


Asunto(s)
Encuestas Nutricionales , Humanos , República de Corea/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Factores de Riesgo , Prevalencia , Enfermedades Metabólicas/epidemiología , Hígado Graso/epidemiología , Tolerancia al Trabajo Programado , Obesidad/epidemiología
3.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36769186

RESUMEN

H2 permeation in peroxide-crosslinked EPDM blended with carbon black (CB) and silica fillers was studied at pressures ranging from 1.2 MPa to 90 MPa via the volumetric analysis technique. H2 uptake in the CB-filled EPDM revealed dual-sorption behaviors via Henry's law and the Langmuir model, which were attributed to H2 absorption by the polymer chains and H2 adsorption at the filler interfaces, respectively. Additionally, single-sorption mechanisms were observed for neat EPDM and silica-blended EPDM according to Henry's law, indicating H2 absorption by the polymer chain. The linear decreases in the diffusivity with filler content for the silica-blended EPDMs were attributed to increases in the diffusion paths caused by the filler. Exponential decreases in the diffusivity with increasing filler content and in the permeation with the physical/mechanical properties for CB-filled EPDMs were caused by decreases in the fractional free volume due to increased densities for the EPDM composites. Moreover, good filler-dependent correlations between permeability and density, hardness, and tensile strength were demonstrated for EPDMs used as sealing materials for O-rings. From the resulting equation, we predicted the permeation value without further measurements. Thus, we can select EPDM candidates satisfying the permeation guidelines used in hydrogen infrastructure for the future hydrogen economy.


Asunto(s)
Polímeros , Hollín , Polímeros/química , Dióxido de Silicio , Hidrógeno , Etilenos
4.
Plant J ; 104(5): 1382-1398, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33048402

RESUMEN

Plants cannot fix nitrogen directly; they must absorb it from the soil through their roots, or in rare cases, form associations with nitrogen-fixing bacteria. The efficiency of nitrogen use in most domesticated crops is low, and more than half of the available nitrogen in the soil can leach into the environment. Understanding the nitrogen signaling pathways is essential for maximizing the efficiency of nitrogen use in crops. In the present study, we characterized the Myeloblastosis (Myb)-like gene NITROGEN RESPONSE DEFICIENCY 1 (NID1). We observed that the growth performance of nid1 knockout (KO) mutant Arabidopsis plants was better than that of wild-type Col-0 plants under very low-nitrate conditions, leading to improved growth performance in the nid1 KO plants. The results of chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that NID1 binds to the promoter of the NITRATE TRANSPORTER (NRT)1.1 gene. Furthermore, nid1 KO plants exhibited similar growth performance to the nid1 KO/chl1-5 (nrt1.1 KO) double mutant and chl1-5 (nrt1.1 KO) plants in response to low-nitrate conditions. We suggest that NID1 plays a crucial role as a transcription factor in optimizing plant growth by modulating the transcript abundance of the nitrate transceptor CHL1, leading to enhanced ABA accumulation in low-nitrate conditions.


Asunto(s)
Proteínas de Transporte de Anión/genética , Arabidopsis/crecimiento & desarrollo , Nitratos/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Proteínas de Transporte de Anión/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Técnicas de Inactivación de Genes , Mutación , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
5.
PLoS Pathog ; 15(2): e1007495, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30753248

RESUMEN

The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. On the cell surface, Ngo quickly recruits CD46-cyt1 to the epithelial cell cortex directly beneath the bacteria and causes its cleavage by metalloproteinases and Presenilin/γSecretease; how these interactions affect the Ngo lifecycle is unknown. Here, we show Ngo induces an autophagic response in the epithelial cell through CD46-cyt1/GOPC, and this response kills early invaders. Throughout infection, the pathogen slowly downregulates CD46-cyt1 and remodeling of lysosomes, another key autophagy component, and these activities ultimately promote intracellular survival. We present a model on the dynamics of Ngo infection and describe how this dual interference with the autophagic pathway allows late invaders to survive within the cell.


Asunto(s)
Gonorrea/metabolismo , Proteína Cofactora de Membrana/fisiología , Neisseria gonorrhoeae/patogenicidad , Autofagia/fisiología , Adhesión Bacteriana , Línea Celular , Cuello del Útero , Regulación hacia Abajo , Células Epiteliales , Femenino , Fimbrias Bacterianas , Gonorrea/fisiopatología , Humanos , Lisosomas , Proteína Cofactora de Membrana/inmunología , Glicoproteínas de Membrana , Proteínas de la Membrana/metabolismo , Neisseria gonorrhoeae/metabolismo , Cultivo Primario de Células , Isoformas de Proteínas
6.
J Comput Neurosci ; 49(2): 175-188, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33825082

RESUMEN

The principle of constraint-induced therapy is widely practiced in rehabilitation. In hemiplegic cerebral palsy (CP) with impaired contralateral corticospinal projection due to unilateral injury, function improves after imposing a temporary constraint on limbs from the less affected hemisphere. This type of partially-reversible impairment in motor control by early brain injury bears a resemblance to the experience-dependent plastic acquisition and modification of neuronal response selectivity in the visual cortex. Previously, such mechanism was modeled within the framework of BCM (Bienenstock-Cooper-Munro) theory, a rate-based synaptic modification theory. Here, we demonstrate a minimally complex yet sufficient neural network model which provides a fundamental explanation for inter-hemispheric competition using a simplified spike-based model of information transmission and plasticity. We emulate the restoration of function in hemiplegic CP by simulating the competition between cells of the ipsilateral and contralateral corticospinal tracts. We use a high-speed hardware neural simulation to provide realistic numbers of spikes and realistic magnitudes of synaptic modification. We demonstrate that the phenomenon of constraint-induced partial reversal of hemiplegia can be modeled by simplified neural descending tracts with 2 layers of spiking neurons and synapses with spike-timing-dependent plasticity (STDP). We further demonstrate that persistent hemiplegia following unilateral cortical inactivation or deprivation is predicted by the STDP-based model but is inconsistent with BCM model. Although our model is a highly simplified and limited representation of the corticospinal system, it offers an explanation of how constraint as an intervention can help the system to escape from a suboptimal solution. This is a display of an emergent phenomenon from the synaptic competition.


Asunto(s)
Modelos Neurológicos , Corteza Visual , Plasticidad Neuronal , Neuronas , Sinapsis
7.
Plant Biotechnol J ; 17(2): 517-530, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30059608

RESUMEN

Jatropha curcas (physic nut), a non-edible oilseed crop, represents one of the most promising alternative energy sources due to its high seed oil content, rapid growth and adaptability to various environments. We report ~339 Mbp draft whole genome sequence of J. curcas var. Chai Nat using both the PacBio and Illumina sequencing platforms. We identified and categorized differentially expressed genes related to biosynthesis of lipid and toxic compound among four stages of seed development. Triacylglycerol (TAG), the major component of seed storage oil, is mainly synthesized by phospholipid:diacylglycerol acyltransferase in Jatropha, and continuous high expression of homologs of oleosin over seed development contributes to accumulation of high level of oil in kernels by preventing the breakdown of TAG. A physical cluster of genes for diterpenoid biosynthetic enzymes, including casbene synthases highly responsible for a toxic compound, phorbol ester, in seed cake, was syntenically highly conserved between Jatropha and castor bean. Transcriptomic analysis of female and male flowers revealed the up-regulation of a dozen family of TFs in female flower. Additionally, we constructed a robust species tree enabling estimation of divergence times among nine Jatropha species and five commercial crops in Malpighiales order. Our results will help researchers and breeders increase energy efficiency of this important oil seed crop by improving yield and oil content, and eliminating toxic compound in seed cake for animal feed.


Asunto(s)
Euphorbiaceae/enzimología , Jatropha/enzimología , Familia de Multigenes , Liasas de Fósforo-Oxígeno/metabolismo , Biocombustibles , Mapeo Cromosómico , Euphorbiaceae/genética , Euphorbiaceae/crecimiento & desarrollo , Perfilación de la Expresión Génica , Jatropha/genética , Jatropha/crecimiento & desarrollo , Lípidos/biosíntesis , Anotación de Secuencia Molecular , Ésteres del Forbol/metabolismo , Liasas de Fósforo-Oxígeno/genética , Filogenia , Fitomejoramiento , Aceites de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Semillas/enzimología , Semillas/genética , Semillas/crecimiento & desarrollo
8.
Lupus ; 28(11): 1294-1301, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31583978

RESUMEN

OBJECTIVES: Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN. METHODS: We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD). RESULTS: The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% (p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063-0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047-0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894-59.089, p = 0.064). CONCLUSION: Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.


Asunto(s)
Inmunosupresores/administración & dosificación , Nefritis Lúpica/fisiopatología , Ácido Micofenólico/administración & dosificación , Proteinuria/epidemiología , Adulto , Femenino , Humanos , Nefritis Lúpica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Proteinuria/etiología , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
9.
Int J Syst Evol Microbiol ; 66(9): 3585-3593, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27298306

RESUMEN

Members of the genus Neisseria have been isolated from or detected in a wide range of animals, from non-human primates and felids to a rodent, the guinea pig. By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific internal transcribed spacer region of the rRNA operon, we isolated four strains of the genus Neisseria from the oral cavity of the wild house mouse, Mus musculus subsp. domesticus. The isolates are highly related and form a separate clade in the genus, as judged by tree analyses using either multi-locus sequence typing of ribosomal genes or core genes. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T=DSM 101846T=CCUG 68283T=LMG 29261T), was studied further. Strain AP2031T/N. musculi grew well in vitro. It was naturally competent, taking up DNA in a DNA uptake sequence and pilT-dependent manner, and was amenable to genetic manipulation. These and other genomic attributes of N. musculi sp. nov. make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions.


Asunto(s)
Ratones/microbiología , Neisseria/clasificación , Filogenia , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Genes Bacterianos , Boca/microbiología , Tipificación de Secuencias Multilocus , Neisseria/genética , Neisseria/aislamiento & purificación , América del Norte , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
10.
Cytopathology ; 27(2): 83-90, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25580773

RESUMEN

OBJECTIVE: The diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology specimens is challenging because of its subtle, minimally atypical findings. Furthermore, as SurePath(™) liquid-based cytology (LBC) is becoming a widely used method in urine cytology, the inevitable cytomorphological alterations resulting from this technique call for new morphological diagnostic criteria in LGPUC. METHODS: Logistic regression analysis was carried out on SurePath slides from surgically proven voided urine specimens. The study was designed to include a test set (n = 141) and a validation set (n = 61), and evaluated significant discriminative parameters between LGPUC and benign papillary urothelial neoplasm (BPUN). RESULTS: Of the seven cytological findings that were found to have statistical significance in univariate analysis, five were found to be independent variables: loss of polarity of papillaroid clusters, irregular contours, absence of columnar cells, hobnail features and hyperchromasia. These independent variables had an area under the curve (AUC) of 0.781. CONCLUSIONS: The distinctive cytological criteria identified above may prove to be helpful in cases in which other conventional criteria for LGPUC are insufficient for diagnosis.


Asunto(s)
Carcinoma Papilar/orina , Citodiagnóstico , Neoplasias/orina , Neoplasias Urológicas/orina , Carcinoma Papilar/patología , Diagnóstico Diferencial , Células Epiteliales/patología , Humanos , Neoplasias/patología , Neoplasias Urológicas/patología
11.
Ann Oncol ; 26(2): 348-54, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25403583

RESUMEN

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation are considered mutually exclusive in nonsmall-cell lung cancer (NSCLC). However, sporadic cases having concomitant EGFR and ALK alterations have been reported. The present study aimed to assess the prevalence of NSCLCs with concomitant EGFR and ALK alterations using mutation detection methods with different sensitivity and to propose an effective diagnostic and therapeutic strategy. PATIENTS AND METHODS: A total of 1458 cases of lung cancer were screened for EGFR and ALK alterations by direct sequencing and flourescence in situ hybridization (FISH), respectively. For the 91 patients identified as having an ALK translocation, peptide nucleic acid (PNA)-clamping real-time PCR, targeted next-generation sequencing (NGS), and mutant-enriched NGS assays were carried out to detect EGFR mutation. RESULTS: EGFR mutations and ALK translocations were observed in 42.4% (612/1445) and 6.3% (91/1445) of NSCLCs by direct sequencing and FISH, respectively. Concomitant EGFR and ALK alterations were detected in four cases, which accounted for 4.4% (4/91) of ALK-translocated NSCLCs. Additional analyses for EGFR using PNA real-time PCR and ultra-deep sequencing by NGS, mutant-enriched NGS increased the detection rate of concomitant EGFR and ALK alterations to 8.8% (8/91), 12.1% (11/91), and 15.4% (14/91) of ALK-translocated NSCLCs, respectively. Of the 14 patients, 3 who were treated with gefitinib showed poor response to gefitinib with stable disease in one and progressive disease in two patients. However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival. CONCLUSIONS: A portion of NSCLC patients have concomitant EGFR and ALK alterations and the frequency of co-alteration detection increases when sensitive detection methods for EGFR mutation are applied. ALK inhibitors appear to be effective for patients with co-alterations.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN/métodos , Genes erbB-1 , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Crizotinib , Femenino , Gefitinib , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Quinazolinas/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Sulfonas/uso terapéutico , Translocación Genética
12.
J Eukaryot Microbiol ; 62(5): 637-49, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25912654

RESUMEN

Apusomonads comprise an understudied and undersampled group of heterotrophic flagellates that is closely related to opisthokonts, the supergroup containing animals and fungi. We cultured representatives of a new clade of apusomonads, Chelonemonas n. gen., which is sister to marine forms of Thecamonas in SSU rRNA gene phylogenies. Scanning electron microscopy shows that members of Chelonemonas have a hexagonal patterning to their submembranous pellicle, which is not known to exist in other apusomonads. We propose that the subfamily Thecamonadinae refer to the marine Thecamonas/Chelonomonas clade. We also report two new strains of Multimonas, one of which is genetically divergent from previously described strains, and here described as a new species, Multimonas koreensis. Both strains of Multimonas have appendages on their dorsal surface that could be extrusomes, and a frilled appearance to the border of their pellicle. Explorations of taxon sampling in SSU rRNA gene phylogenies confirm the new strains' evolutionary affinities, but do not resolve relationships among the five main apusomonad clades. These phylogenies also separate the freshwater species "Thecamonas" oxoniensis from the marine members of the genus Thecamonas. The new strains described here may provide valuable genetic and morphological data for evaluating the relationships and evolution of apusomonads.


Asunto(s)
Eucariontes/clasificación , Eucariontes/aislamiento & purificación , Animales , Evolución Biológica , Eucariontes/citología , Eucariontes/genética , Genes de ARNr , Variación Genética , Procesos Heterotróficos , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 18S , Análisis de Secuencia de ADN
13.
Clin Radiol ; 69(7): 703-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24703719

RESUMEN

AIM: To evaluate the outcomes of angioplasty of the communicating veins when superficial veins of the upper arm were almost totally obliterated in haemodialysis patients. MATERIALS AND METHODS: Twenty-one angioplasties of the communicating veins that were performed for failing haemodialysis fistulas in patients with almost totally obliterated superficial veins of the upper arm from December 2006 to March 2011 were retrospectively reviewed. Fistulas were of the following types: native radiocephalic fistulas (n = 20) and radio-antecubital fistulas (n = 1). All angioplasties were performed using 5-8 mm conventional balloons. Cutting balloon angioplasty was additionally performed in five patients. The primary, secondary, and target lesion patency rate was calculated using Kaplan-Meier analysis. RESULTS: The communicating vein was located in the antecubital fossa. Technical and clinical success rates were 100% and 95.2%, respectively. Follow-up duration was 1-52 months (mean 20 months). The primary patency rates were 76%, 43%, and 29% at 3, 6, and 12 months, respectively, and target lesion patency rates were 81%, 62%, and 43% at 3, 6, and 12 months, respectively. The secondary patency rates were 81%, 76%, and 57% at 3, 6, and 12 months, respectively. There were no major or minor complications. CONCLUSION: Angioplasty of the communicating vein is effective in restoring function in failing haemodialysis fistula in patients with obliterated superficial veins of the upper arm.


Asunto(s)
Angioplastia/métodos , Brazo/irrigación sanguínea , Venas Braquiocefálicas/cirugía , Diálisis Renal , Anastomosis Quirúrgica/métodos , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/cirugía , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Dispositivos de Acceso Vascular , Grado de Desobstrucción Vascular
14.
Nat Cancer ; 5(6): 866-879, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38355777

RESUMEN

We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Ipilimumab , Nivolumab , Piridinas , Receptor ErbB-2 , Humanos , Femenino , Persona de Mediana Edad , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Adulto , Receptor ErbB-2/metabolismo , Benzamidas/uso terapéutico , Benzamidas/administración & dosificación , Anciano , Ipilimumab/uso terapéutico , Ipilimumab/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Supervivencia sin Progresión
15.
Ann Oncol ; 24(3): 756-60, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23117072

RESUMEN

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.


Asunto(s)
Antineoplásicos/farmacocinética , Benzamidas/farmacocinética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/farmacocinética , Polimorfismo de Nucleótido Simple , Pirimidinas/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Adulto , Anciano , Hidrocarburo de Aril Hidroxilasas/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Transporte de Catión Orgánico/genética , Transportador 2 de Cátion Orgánico , Resultado del Tratamiento , Adulto Joven
16.
Clin Radiol ; 68(6): e309-15, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23465323

RESUMEN

AIM: To evaluate the anatomical causes of maturation failure and to assess clinical outcomes after the causative lesions of immature arteriovenous fistula (AVF) have been corrected by endovascular treatment. MATERIALS AND METHODS: The medical records and radiological data from 141 patients who underwent endovascular treatment for immature AVF were retrospectively reviewed. Clinical outcomes, such as the success rates and the patency rates following the procedure, were included. The variables, including patients' age, gender, co-morbidities, fistula age, fistula type, numbers of lesions, degree of stenosis, presence of accessory veins, were analysed as the potential predictors of primary and secondary patency. RESULTS: Technical and clinical success rates were 95.7% (135 of 141 AVFs) and 86.5% (122 of 141 AVFs), respectively. The primary and secondary patency rates were 71.9% and 82.8% at 1 year, 60.1% and 82.0% at 2 years, and 54.5% and 82.0% at 3 years, respectively. By multivariate analysis using Cox proportional hazards model, stenosis of >90% was the only independent predictor for both the primary and secondary patency rates [hazard ratio (HR) 5.026, 95% confidence interval (CI) 2.47-10.24, p < 0.0001 for primary patency and HR 11.076, CI 1.49-82.58, p = 0.019 for secondary patency, respectively]. CONCLUSION: All immature AVFs had significant anatomical causes of failure to mature, which could be safely and effectively salvaged with endovascular treatment. A degree of stenosis >90% was an independent predictor for both the primary and secondary patency after the treatment.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/métodos , Procedimientos Endovasculares , Procedimientos Endovasculares/métodos , Femenino , Oclusión de Injerto Vascular/cirugía , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Diálisis Renal/métodos , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Grado de Desobstrucción Vascular
17.
Gene Ther ; 19(3): 329-37, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21654823

RESUMEN

The successful development of efficient and safe gene delivery vectors continues to be a major obstacle to gene delivery in stem cells. In this study, we have developed an elastin-like polypeptide (ELP)-mediated adeno-associated virus (AAV) delivery system for transducing fibroblasts and human neural stem cells (hNSCs). AAVs have significant promise as therapeutic vectors because of their safety and potential for use in gene targeting in stem cell research. ELP has been recently employed as a biologically inspired 'smart' biomaterial that exhibits an inverse temperature phase transition, thereby demonstrating promise as a novel drug carrier. The ELP that was investigated in this study was composed of a repetitive penta-peptide with [Val-Pro-Gly-Val-Gly]. A novel AAV variant, AAV r3.45, which was previously engineered by directed evolution to enhance transduction in rat NSCs, was nonspecifically immobilized onto ELPs that were adsorbed beforehand on a tissue culture polystyrene surface (TCPS). The presence of different ELP quantities on the TCPS led to variations in surface morphology, roughness and wettability, which were ultimately key factors in the modulation of cellular transduction. Importantly, with substantially reduced viral quantities compared with bolus delivery, ELP-mediated AAV delivery significantly enhanced delivery efficiency in fibroblasts and hNSCs, which have great potential for use in tissue engineering applications and neurodegenerative disorder treatments, respectively. The enhancement of cellular transduction in stem cells, as well as the feasibility of ELPs for utilization in three-dimensional scaffolds, will contribute to the advancement of gene therapy for stem cell research and tissue regenerative medicine.


Asunto(s)
Dependovirus/genética , Dependovirus/metabolismo , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Células-Madre Neurales/metabolismo , Oligopéptidos/metabolismo , Animales , Línea Celular , Supervivencia Celular , Humanos , Ratones , Oligopéptidos/aislamiento & purificación , Unión Proteica , Propiedades de Superficie , Transducción Genética
18.
Phys Rev Lett ; 108(19): 195504, 2012 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-23003057

RESUMEN

Ion irradiation experiments and atomistic simulations were used to demonstrate that irradiation-induced lattice swelling in a complex oxide, Lu2Ti2O7, is due initially to the formation of cation antisite defects. X-ray diffraction revealed that cation antisite formation correlates directly with lattice swelling and indicates that the volume per antisite pair is approximately 12 Å3. First principles calculations revealed that lattice swelling is best explained by cation antisite defects. Temperature accelerated dynamics simulations indicate that cation Frenkel defects are metastable and decay to form antisite defects.

19.
Diabet Med ; 29(9): e290-6, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22519862

RESUMEN

AIMS: Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea. METHODS: Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. RESULTS: The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. CONCLUSION: There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/epidemiología , Pacientes Internos , Enfermedades del Sistema Nervioso Periférico/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , República de Corea/epidemiología , Estudios Retrospectivos , Adulto Joven
20.
Trop Med Int Health ; 17(12): 1534-43, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23051841

RESUMEN

OBJECTIVES: To investigate the magnitude and characteristics of the economic burden resulting from acute pesticide poisoning (APP) in South Korea. METHODS: The total costs of APP from a societal perspective were estimated by summing the direct medical and non-medical costs together with the indirect costs. Direct medical costs for patients assigned a disease code of pesticide poisoning were extracted from the Korean National Health Insurance Reimbursement Data. Direct non-medical costs were estimated using the average transportation and caregiving costs from the Korea Health Panel Survey. Indirect costs, incurred by pre-mature deaths and work loss, were obtained using 2009 Life Tables for Korea and other relevant literature. RESULTS: In 2009, a total of 11,453 patients were treated for APP and 1311 died, corresponding to an incidence of 23.1 per 100,000 population and a mortality rate of 2.6 per 100,000 population in South Korea. The total costs of APP were estimated at approximately US$ 150 million, 0.3% of the costs of total diseases. Costs due to pre-mature mortality accounted for 90.6% of the total costs, whereas the contribution of direct medical costs was relatively small. CONCLUSION: Costs from APP demonstrate a unique characteristic of a large proportion of the indirect costs originating from pre-mature mortality. This finding suggests policy implications for restrictions on lethal pesticides and safe storage to reduce fatality and cost due to APP.


Asunto(s)
Costo de Enfermedad , Plaguicidas/envenenamiento , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Tablas de Vida , Masculino , Persona de Mediana Edad , Modelos Econométricos , Mortalidad Prematura , Enfermedades Profesionales/economía , Enfermedades Profesionales/epidemiología , Intoxicación/economía , Intoxicación/epidemiología , Intoxicación/mortalidad , República de Corea/epidemiología , Suicidio/economía , Suicidio/estadística & datos numéricos
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