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1. The study evaluated the effect of dietary metabolisable energy (ME) content and crude protein (CP) level on the growth performance and behaviour of ducks.2. A total of 720, Cherry Valley ducks were allocated to 36 pens in groups of 20 birds. For the initial period, from 1 to 21 d age, six diets, containing a standard (SME), low (LME) and high (HME) ME of 12.14, 11.93 and 12.35 MJ/kg, and standard (SCP) or high (HCP) CP contents of 210 or 220 g/kg diet, respectively, were mixed. For the period from 22 to 42 d age, the diets contained ME of 12.98 (SME), 12.77 (LME), 13.19 (HME) MJ/kg and the levels of CP were 170 (SCP) or 180 (HCP) g/kg, respectively.3. An ME by CP interaction was seen from 1 to 21 d age in ducks fed HME + HCP diet, which had greater weight gain than those fed LME + SCP (P < 0.05). Compared to LME + SCP, dietary HME decrease feeding but increased walking behaviour compared to LME + SCP and SME + SCP (P < 0.05). High CP in LME and SME diets increased drinking behaviour (P < 0.05), but there was no change in HME diet. Compared to LME, feeding HME reduced ground pecking (P < 0.05). Feeding HME reduced feeding behaviour (P < 0.05) from 22 to 42 d age. During the same period, standing behaviour was reduced in HCP + LME (P < 0.05). Drinking was reduced in LME + SCP compared to SME + HCP and HME + HCP (P < 0.05).4. A diet formulated with HME and HCP is effective for enhancing growth performance of ducks aged 1-21 d and saving time for feeding or ground pecking, which may induce spending more time on other activities.
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Pollos , Patos , Animales , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta/veterinaria , Aumento de PesoRESUMEN
BACKGROUND AND PURPOSE: High-resolution postcontrast 3D T1WI is a widely used sequence for evaluating brain metastasis, despite the long scan time. This study aimed to compare highly accelerated postcontrast 3D T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolution by using wave-controlled aliasing in parallel imaging (wave-T1-SPACE) with the commonly used standard high-resolution postcontrast 3D T1-SPACE for the evaluation of brain metastases. MATERIALS AND METHODS: Among the 387 patients who underwent postcontrast wave-T1-SPACE and standard SPACE, 56 patients with suspected brain metastases were retrospectively included. Two neuroradiologists assessed the number of enhancing lesions according to lesion size, contrast-to-noise ratiolesion/parenchyma, contrast-to-noise ratiowhite matter/gray matter, contrast ratiolesion/parenchyma, and overall image quality for the 2 different sequences. RESULTS: Although there was no significant difference in the evaluation of larger enhancing lesions (>5 mm) between the 2 different sequences (P = .66 for observer 1, P = .26 for observer 2), wave-T1-SPACE showed a significantly lower number of smaller enhancing lesions (<5 mm) than standard SPACE (1.61 [SD, 0.29] versus 2.84 [SD, 0.47] for observer 1; 1.41 [SD, 0.19] versus 2.68 [SD, 0.43] for observer 2). Furthermore, mean contrast-to-noise ratiolesion/parenchyma and overall image quality of wave-T1-SPACE were significantly lower than those in standard SPACE. CONCLUSIONS: Postcontrast wave-T1-SPACE showed comparable diagnostic performance for larger enhancing lesions (>5 mm) and marked scan time reduction compared with standard SPACE. However, postcontrast wave-T1-SPACE showed underestimation of smaller enhancing lesions (<5 mm) and lower image quality than standard SPACE. Therefore, postcontrast wave-T1-SPACE should be interpreted carefully in the evaluation of brain metastasis.
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Neoplasias Encefálicas , Imagen por Resonancia Magnética , Encéfalo , Neoplasias Encefálicas/secundario , Medios de Contraste , Sustancia Gris , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
This study determined the mechanical performance of bioactive restoratives in cariogenic environments and compared the flexural properties of various bioactive materials. The materials evaluated included a conventional resin-based composite (Filtek Z350 [FZ]) and 3 bioactive restoratives, namely an alkasite (Cention N [CN]), a giomer (Beautifil-bulk Restorative [BB]), and an enhanced resin-modified glass ionomer (Activa Bioactive Restorative [AV]). Beam-shaped specimens (12 x 2 x 2 mm) were produced, randomly allocated to 4 groups (n=10), and conditioned in deionized solution, remineralizing solution, demineralizing solution (DE), or pH cycled for 14 days at 37°C. After conditioning/pH cycling, the specimens were subjected to 3-point flexural testing. Flexural data were subjected to statistical analysis using analysis of variance or Tukey's test (α=0.05). Mean flexural modulus and strength ranged from 3.54 ± 0.33 to 7.44 ± 0.28 GPa, and 87.07 ± 8.99 to 123.54 ± 12.37 MPa, respectively. While the flexural modulus of the bioactive restoratives was not affected by cariogenic/acidic conditions, flexural strength usually decreased, with the exception of CN. The strength of BB was significantly reduced by DE and pH cycling, while that of AV was lowered by DE. For all conditioning mediums, AV had a significantly lower modulus than the other materials. Apart from conditioning in DE, where differences in flexural strength was insignificant, FZ and AV were generally significantly stronger than BB and CN. The effect of cariogenic environments on flexural strength was found to be material dependent, and aside from the alkasite material (CN), cariogenic conditions were observed to significantly decrease the strength of bioactive restoratives.
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Resinas Compuestas , Resistencia Flexional , Materiales Dentales , Ensayo de Materiales , DocilidadRESUMEN
Importance: In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research. Objective: To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice. Design, Setting, and Participants: This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020. Exposures: Undergoing treatment with immunotherapy or targeted therapy. Main Outcomes and Measures: Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports. Results: Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies. Conclusions and Relevance: These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma/diagnóstico por imagen , Carcinoma/secundario , Ensayos Clínicos como Asunto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/secundario , Terapia Molecular Dirigida , Nivolumab/uso terapéutico , Variaciones Dependientes del Observador , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias de la Tiroides/patología , Resultado del Tratamiento , Carga TumoralRESUMEN
Background: Despite similar survival rates, breast-conserving therapy (BCT) remains a distant second choice after simple mastectomy for patients with early-stage breast cancer in Singapore. Uptake of reconstruction after mastectomy is also low (18 per cent). The aim of this study was to explore the factors influencing a patient's choice for mastectomy when eligible for BCT, and why patients decline reconstruction after mastectomy. Methods: Patients from the National Cancer Centre Singapore, who were eligible for BCT but chose mastectomy without reconstruction, between December 2014 and December 2015 were included. An interviewer-administered questionnaire focusing on patients' reasons for choosing mastectomy over BCT and not opting for immediate breast reconstruction after mastectomy was used. Tumour characteristics were retrieved from medical records. Spearman's rank correlation coefficient, Mann-Whitney U and Kruskal-Wallis tests were used to analyse the correlation between the patient's self-rated influential factors and variables. Statistical significance was taken as P < 0·050. Results: Ninety-one patients were included (90·1 per cent response rate). The main reasons for choosing mastectomy over BCT were: fear of cancer recurrence (considered very important in 74 per cent), the perception that health outweighs breast retention (49 per cent) and the possibility of second surgery for margins (40 per cent). Key factors for rejecting immediate reconstruction after mastectomy were: patient-perceived 'old age' (very important in 53 per cent), concern about two sites of surgery (42 per cent) and financial cost (29 per cent). Given a second chance, 19·8 per cent of patients would undergo BCT instead of mastectomy. Conclusion: This study has identified the considerations that women in Singapore have when deciding on breast cancer surgery. Some perceptions need to be addressed for women to make a fully informed decision, especially as one-fifth regret their initial choice.
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Actitud Frente a la Salud , Neoplasias de la Mama/cirugía , Toma de Decisiones , Mastectomía/psicología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Conducta de Elección , Femenino , Humanos , Mamoplastia/psicología , Mamoplastia/estadística & datos numéricos , Mastectomía/métodos , Mastectomía/estadística & datos numéricos , Mastectomía Segmentaria/psicología , Mastectomía Segmentaria/estadística & datos numéricos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/psicología , Estadificación de Neoplasias , Participación del Paciente , Satisfacción del Paciente , Singapur , Encuestas y CuestionariosRESUMEN
Essentials Mitochondrial hyperpolarization enhances the conversion of platelets to a procoagulant phenotype. Mitochondrial calcium uniporter (MCU) function is essential in procoagulant platelet formation. Mitochondrial calcium uniporter deletion does not impact other aspects of platelet activation. Ablation of MCU results in the emergence of a permeability transition pore-independent pathway. SUMMARY: Background Procoagulant platelets comprise a phenotypically distinct subpopulation of activated platelets with high-level phosphatidylserine externalization. When initiated by co-stimulation with thrombin and a glycoprotein VI (GPVI) agonist, the transition to the procoagulant phenotype is mediated by extracellular calcium entry and mitochondrial permeability transition pore (mPTP) formation. Objectives The intracellular mechanisms coordinating these distinct cytoplasmic and mitochondrial processes remain unclear. The mitochondrial calcium uniporter (MCU) protein is a central component of the transmembrane ion channel that allows the passage of Ca2+ from the cytosol into the mitochondrial matrix. Here we investigate the role of the MCU in the regulation of procoagulant platelet formation. Results Procoagulant platelet formation was directly correlated with pre-stimulatory mitochondrial transmembrane potential, a key determinant of calcium flux from the cytoplasm to the mitochondria. The role of MCU in the regulation of procoagulant platelet formation was investigated using MCU null platelets. Procoagulant platelet formation in MCU null platelets was significantly decreased coincident with decreased mPTP formation. In contrast, neither granule release nor initial integrin activation was altered in response to stimulation. In the genomic absence of MCU, developmental induction of an alternative intracellular pathway partially rescued procoagulant platelet formation. Conclusion These results identify a key role for the mitochondrial calcium uptake channel in the regulation of mPTP-mediated procoagulant platelet formation and suggest a novel pharmacologic target for procoagulant-platelet-related pathologies.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Activación Plaquetaria/efectos de los fármacos , Animales , Antimicina A/farmacología , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/metabolismo , Proteínas Portadoras/metabolismo , Membrana Celular/metabolismo , Citosol/metabolismo , Humanos , Potencial de la Membrana Mitocondrial , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Péptidos/metabolismo , Fenotipo , Fosfatidilserinas/metabolismo , Glicoproteínas de Membrana Plaquetaria/agonistas , Rotenona/farmacología , Transducción de Señal/efectos de los fármacos , Trombina/agonistasRESUMEN
People can hear and pay attention to familiar terms such as their own name better than general terms, referred to as the cocktail party effect. We performed a prospective, randomised, double-blind trial to investigate whether calling the patient's name compared with a general term facilitated a patient's response and recovery from general anaesthesia. We enrolled women having breast cancer surgery with general anaesthesia using propofol and remifentanil. Patients were randomly allocated into two groups depending on whether the patient's name or a general term was called, followed by the verbal command - 'open your eyes!' - during emergence from anaesthesia; this pre-recorded sentence was played to the patient using headphones. Fifty patients were allocated to the name group and 51 to the control group. Our primary outcome was the time from discontinuation of anaesthesia until eye opening. The mean (SD) time was 337 (154) s in the name group and 404 (170) s in the control group (p = 0.041). The time to i-gel® removal was 385 (152) vs. 454 (173) s (p = 0.036), the time until achieving a bispectral index of 60 was 174 (133) vs. 205 (160) s (p = 0.3), and the length of stay in the postanaesthesia care unit was 43.8 (3.4) vs. 47.3 (7.1) min (p = 0.005), respectively. In conclusion, using the patient's name may be an easy and effective method to facilitate recovery from general anaesthesia.
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Periodo de Recuperación de la Anestesia , Anestesia General , Adulto , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Nombres , Estudios ProspectivosRESUMEN
p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.
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Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Anoicis/genética , Carcinogénesis/genética , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis/genética , Supervivencia Celular/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Mutación Missense , Neoplasias/patología , Proteína Oncogénica v-akt/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Transducción de SeñalRESUMEN
This work was conducted to investigate the performance and meat characteristics of commercial Korean native duck (KND). A total of 180 1-d-old ducklings of 2-way crossbreds from A and B lines (from National Institute of Animal Science) were used in this work and divided into 4 groups (3 replicates/group, 15 birds/replicate). The four groups were 4 crossbreds as AA (A line [â]×A line [â]), AB (A line [â]×B line [â]), BB (Pure line B strains) and BA (B strains [â]×A strain [â]). Ducks were fed diets based on corn-soybean meal for 0 to 3 wk (22.4% crude protein [CP], 2,945 kcal/kg metabolizable energy [ME]) and 3 to 8 wk (18.4% CP, 3,047 kcal/kg ME). As a result of this study, average body weight of 4 crossbreds were 625, 1,617, 2,466, and 2,836 g at 2, 4, 6, and 8 weeks, respectively, and significantly increased over the period of time (p<0.05). Body weight of BB group was greater than other crossbreds at the age of 6 weeks (p<0.05). There was a significant difference in weekly body weight gains (p<0.05), which were 573, 991, 850, and 371 g at 2, 4, 6, and 8 weeks old, respectively. Uniformity of 4 crossbreds was 84.9%, 80.5%, and 72.5% at 6, 7, and 8 weeks, respectively, and there was no difference among crossbreds. Body weight gain of BB crossbred was highest among crossbreds (p<0.05). Weekly feed intake significantly increased with weeks as 669, 1,839, 2,812, and 3,381 g at 2, 4, 6, and 8 weeks respectively (p<0.05). Feed intakes of AA and BB crossbreds were higher at 2 to 4 weeks old than others and that of BB crossbred was highest at 4 to 6 weeks old (p<0.05). Weekly feed conversion ratios were 1.17, 1.86, 3.32, and 9.37 at 0 to 2, 2 to 4, 4 to 6, and 6 to 8 weeks old, respectively, and it increased with age (p<0.05). There was no significant difference in feed conversion ratio among crossbreds. Carcass yields of 4 crossbreds were 73.6%, 71.6%, 73.5%, and 71.7%, respectively, so there was no significant difference among crossbreds. There was no difference in wing, neck, breast and leg ratios among crossbreds. However, back ratios of 4 crossbreds were 17.6%, 18.0%, 15.8%, and 17.6%, respectively, and back ratio of BB was the highest among crossbreds. Finally, these results may provide the basic data on the production, carcass quality, fatty acid and amino acid composition of commercial KND with 2-way crossbreeding.
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In a phenomenon called subitizing, we can immediately generate exact counts of small collections (one to three objects), in contrast to larger collections, for which we must either create rough estimates or serially count. A parsimonious explanation for this advantage for small collections is that noisy representations of small collections are more tolerable, due to the larger relative differences between consecutive numbers (e.g., 2 vs. 3 is a 50 % increase, but 10 vs. 11 is only a 10 % increase). In contrast, the advantage could stem from the fact that small-collection enumeration is more precise, relying on a unique mechanism. Here, we present two experiments that conclusively showed that the enumeration of small collections is indeed "superprecise." Participants compared numerosity within either small or large visual collections in conditions in which the relative differences were controlled (e.g., performance for 2 vs. 3 was compared with performance for 20 vs. 30). Small-number comparison was still faster and more accurate, across both "more-fewer" judgments (Exp. 1), and "same-different" judgments (Exp. 2). We then reviewed the remaining potential mechanisms that might underlie this superprecision for small collections, including the greater diagnostic value of visual features that correlate with number and a limited capacity for visually individuating objects.
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Juicio/fisiología , Conceptos Matemáticos , Desempeño Psicomotor/fisiología , Percepción Visual/fisiología , Adulto , Femenino , Humanos , Masculino , Detección de Señal Psicológica/fisiología , Adulto JovenRESUMEN
As materials functionality becomes more dependent on local physical and electronic properties, the importance of optically probing matter with true nanoscale spatial resolution has increased. In this work, we mapped the influence of local trap states within individual nanowires on carrier recombination with deeply subwavelength resolution. This is achieved using multidimensional nanospectroscopic imaging based on a nano-optical device. Placed at the end of a scan probe, the device delivers optimal near-field properties, including highly efficient far-field to near-field coupling, ultralarge field enhancement, nearly background-free imaging, independence from sample requirements, and broadband operation. We performed ~40-nanometer-resolution hyperspectral imaging of indium phosphide nanowires via excitation and collection through the probes, revealing optoelectronic structure along individual nanowires that is not accessible with other methods.
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BACKGROUND AND PURPOSE: The ability of US to differentiate benign thyroid nodules from malignant ones is still a matter of debate. The aim of this study was to assess the diagnostic efficacy of a US-based classification system for solid and PCTNs through a prospectively designed study. MATERIALS AND METHODS: We studied 1289 thyroid nodules in 1036 patients who underwent thyroid US, US-FNA, and thyroid surgery. Each thyroid nodule was prospectively classified into 1 of 5 diagnostic categories following real-time US examination: benign, probably benign, borderline, possibly malignant, and malignant. Solid nodules were classified by using all 5 categories, and PCTNs were classified by all except the borderline category. We calculated the diagnostic efficacy of thyroid US by comparing US diagnoses with histopathologic results of surgically resected thyroid nodules. RESULTS: One thousand fifty-five solid nodules and 234 PCTNs were prospectively classified as benign (n = 435 and 179), probably benign (n = 213 and 25), borderline (n = 94 and 0), possibly malignant (n = 115 and 15), and malignant (n = 198 and 15), respectively. Of these 1289 nodules, 505 were surgically resected and confirmed by pathology (191 benign and 314 malignant nodules); there were 44 resected solid nodules with a borderline category. For solid nodules and PCTNs, the sensitivity, specificity, positive and negative predictive values, and accuracy of US diagnosis were 86.1 and 66.7, 90.0 and 88.9, 94.3 and 75.0, 77.3 and 84.2, and 87.5% and 81.5%, respectively, based on 505 surgical specimens and excluding the 42 solid borderline nodules. CONCLUSIONS: Our US-based classification system can provide helpful guidance for the management of thyroid nodules.
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Quistes/diagnóstico por imagen , Quistes/epidemiología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/epidemiología , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricos , Comorbilidad , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , República de Corea/epidemiologíaRESUMEN
Projects to manage arthropod pests using entomopathogenic nematodes (EPNs) in Brazil, Korea and USA are reviewed to identify conditions and practices that affected the use of EPNs for pest management. A proliferation of covered agriculture in Korea, the growth in demand for high value, pesticide-free produce in Korea and Brazil, and the cost-effectiveness of EPNs created favorable conditions for the widespread adoption of EPN products in Brazilian guava orchards and Korean vegetable greenhouses. In Florida, EPNs imported from South America function successfully as classical biocontrol agents against invasive mole crickets attacking pasture and turf. However, the low value of pasture and the availability of cost-effective chemical insecticides in turf have depressed the demand for EPN products to control mole crickets. In Florida citrus orchards, a recent, dramatic increase in the use of chemical insecticides to control an arthropod vector of a devastating bacterial disease of citrus (huanglongbing) reduced the demand for EPN products to control Diaprepes root weevils. Nevertheless, a rich and diverse EPN fauna in the Florida peninsula provides significant control of subterranean stages of root weevils in some habitats, and is the focus of research to develop cultural practices that exploit the potential for increased pest management through EPN conservation.
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BACKGROUND: Heartburn is commonly associated with the presence of acid in the oesophageal lumen. However, in patients with nonerosive reflux disease (NERD), the mechanism by which acid traverses the mucosa is not clear. We hypothesized that the luminal acid signal traverses the oesophageal epithelium in the form of the highly permeant gas CO(2) , which then is reconverted to H(+) in the submucosa. MATERIALS AND METHODS: Ten patients with heartburn, normal upper endoscopy and increased oesophageal acid exposure (NERD patients) and 10 healthy subjects were enrolled. Perceptual responses to intraoesophageal acid (0·1 N HCl solution) and a high PCO(2) solution were determined using a randomized cross over design. Stimulus-response functions to perfusions were quantified by three parameters: lag time to symptom perception, intensity rating and perfusion sensitivity score. RESULTS: In NERD patients, the difference in lag time to typical symptom perception, intensity rating and perfusion sensitivity score between high PCO(2) and acid perfusions was statistically significant (P = 0·02, 0·01 and 0·02, respectively). However, the difference in the same perfusion parameters between acid and high PCO(2) perfusions was nonsignificant in healthy controls. When NERD and controls were compared, the difference between the different perfusion variables was nonsignificant (adjusted to age). CONCLUSIONS: In NERD subjects, acid perfusion reliably evoked heartburn symptoms of greater intensity than in healthy controls. Nevertheless, a high PCO(2) perfusion failed to produce symptoms in either group.
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Dióxido de Carbono/farmacología , Esófago/efectos de los fármacos , Pirosis/inducido químicamente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios Cruzados , Monitorización del pH Esofágico , Femenino , Determinación de la Acidez Gástrica , Reflujo Gastroesofágico/inducido químicamente , Reflujo Gastroesofágico/fisiopatología , Pirosis/fisiopatología , Humanos , Ácido Clorhídrico/farmacología , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Umbral Sensorial , Adulto JovenRESUMEN
The purpose is to evaluate sensitivity of basal-like breast cancer to treatment with anti-DR5 alone and in combination with chemotherapy. Cytotoxicity of TRA-8 anti-DR5 alone and in combination with doxorubicin or paclitaxel was examined. The role of a DR5-associated molecule (DDX3) in the regulation of apoptosis by recruitment of cIAP1 to the DR5/DDX3 complex was studied. SUM159 and 2LMP orthotopic xenografts were treated with TRA-8 alone and in combination with Abraxane or doxorubicin, and tumor growth inhibition determined. Diffusion-weighted magnetic resonance imaging was used to monitor early tumor response. The majority (12/15) of basal-like cell lines were very sensitive to TRA-8-induced cytotoxicity (IC(50) values of 1.0-49 ng/ml). In contrast, 8/11 luminal or HER2-positive cell lines were resistant (IC(50) > 1,000 ng/ml). Enhanced killing of basal-like cell lines was produced by combination treatment with TRA-8 and doxorubicin. Majority of basal cell lines expressed lower levels of DR5-associated DDX3 and cIAP1 than luminal and HER2-positive cell lines. TRA-8 inhibited growth of basal xenografts and produced 20% complete 2LMP tumor regressions. TRA-8 and chemotherapy produced greater 2LMP growth inhibition than either alone. An increase in apparent diffusion coefficient in 2LMP tumors was measured in a week of therapy with TRA-8 and Abraxane. Basal-like cell lines were more sensitive to TRA-8-mediated cytotoxicity than HER2-over-expressing and luminal cell lines, and chemotherapy enhanced cytotoxicity. High sensitivity of basal cells to TRA-8 correlated with low expression of DR5/DDX3/cIAP1 complex. Treatment with TRA-8 and chemotherapy may be an effective therapy for basal-like breast cancer.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Basocelulares/tratamiento farmacológico , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/antagonistas & inhibidores , Paclitaxel Unido a Albúmina , Albúminas/administración & dosificación , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/toxicidad , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico , Línea Celular Tumoral , ARN Helicasas DEAD-box/metabolismo , Doxorrubicina/administración & dosificación , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Imagen por Resonancia Magnética , Ratones , Ratones Desnudos , Neoplasias Basocelulares/diagnóstico , Paclitaxel/administración & dosificación , Unión Proteica , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismoRESUMEN
BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) levels are increased by light exposure but the role and mechanism of 5-HT in the pigmentation of skin cells are unclear. OBJECTIVES: To clarify the effect of 5-HT on melanogenesis and to determine the 5-HT receptor subtype involved. METHODS: B16F10, SK-MEL-2 and Melan-A cells were cultured in Dulbecco's modified Eagle's medium with low fetal bovine serum. The three cell lines were treated with various concentrations of 5-HT, and 5-HT receptor agonists and antagonists. The involvement of the 5-HT receptor 2A (5-HTR2A) was examined by gene silencing and use of 5-HTR2A antagonists. RESULTS: 5-HT and the 5-HTR2A agonist, DOI, increased melanogenesis in the three cell lines. These increased events were suppressed by 5-HTR2A antagonists or gene silencing of the HTR2A gene. CONCLUSIONS: 5-HTR2A is involved in melanogenesis. These findings highlight the role of 5-HT and suggest new ways of controlling melanogenesis.
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Melaninas/biosíntesis , Melanosis/etiología , Receptor de Serotonina 5-HT2A/fisiología , Serotonina/fisiología , Animales , Western Blotting , Movimiento Celular/efectos de los fármacos , Silenciador del Gen , Humanos , Melanocitos/metabolismo , Melanoma/fisiopatología , Melanosis/metabolismo , Ratones , ARN Interferente Pequeño/farmacología , Receptor de Serotonina 5-HT2A/genética , Serotonina/farmacología , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Neoplasias Cutáneas/fisiopatología , Células Tumorales CultivadasRESUMEN
Using first-principles theory and experiments, chemical contributions to surface-enhanced Raman spectroscopy for a well-studied organic molecule, benzene thiol, chemisorbed on planar Au(111) surfaces are explained and quantified. Density functional theory calculations of the static Raman tensor demonstrate a strong mode-dependent modification of benzene thiol Raman spectra by Au substrates. Raman active modes with the largest enhancements result from stronger contributions from Au to their electron-vibron coupling, as quantified through a deformation potential. A straightforward and general analysis is introduced to extract chemical enhancement from experiments for specific vibrational modes; measured values are in excellent agreement with our calculations.
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Oro/química , Fenoles/química , Espectrometría Raman , Compuestos de Sulfhidrilo/química , Adsorción , Modelos Moleculares , Conformación Molecular , Teoría Cuántica , Propiedades de SuperficieRESUMEN
Lipid rafts have been known to be platforms to initiate cellular signal transduction of insulin-like growth factor (IGF) inducing skeletal muscle differentiation and hypertrophy. Here, tripartite motif 72 (TRIM72), with a really interesting new gene (RING)-finger domain, a B-box, two coiled-coil domains, and a SPRY (SPla and RYanodine receptor) domain, was revealed to be predominantly expressed in the sarcolemma lipid rafts of skeletal and cardiac muscles. Adenoviral TRIM72 overexpression prevented but RNAi-mediated TRIM72 silencing enhanced C2C12 myogenesis by modulating the IGF-induced insulin receptor substrate-1 (IRS-1) activation through the molecular association of TRIM72 with IRS-1. Furthermore, myogenic activity was highly enhanced with increased IGF-induced Akt activation in the satellite cells of TRIM72(-/-) mice, compared to those of TRIM72+/+ mice. Because TRIM72 promoter analysis shows that two proximal E-boxes in TRIM72 promoter were essential for MyoD- and Akt-dependent TRIM72 transcription, we can conclude that TRIM72 is a novel antagonist of IRS-1, and is essential as a negative regulator of IGF-induced muscle differentiation.
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Proteínas Portadoras/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Desarrollo de Músculos , Músculo Esquelético/fisiología , Animales , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Diferenciación Celular , Línea Celular , Femenino , Masculino , Microdominios de Membrana/metabolismo , Proteínas de la Membrana , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/metabolismo , Transducción de SeñalRESUMEN
People can rapidly judge the average size of a collection of objects with considerable accuracy. In this study, we tested whether this size-averaging process relies on relatively early object representations or on later object representations that have undergone iterative processing. We asked participants to judge the average size of a set of circles and, in some conditions, presented two additional circles that were either smaller or larger than the average. The additional circles were surrounded by four-dot masks that either lingered longer than the circle array, preventing further processing with object substitution masking (OSM), or disappeared simultaneously with the circle array, allowing the circle representation to reach later visual processing stages. Surprisingly, estimation of average circle size was modulated by both visible circles and circles whose visibility was impaired by OSM. There was also no correlation across participants between the influence of the masked circles and susceptibility to OSM. These findings suggest that relatively early representations of objects can contribute to the size-averaging process despite their reduced visibility.
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Percepción del Tamaño , Agudeza Visual , Percepción Visual , Fijación Ocular , Humanos , Enmascaramiento PerceptualRESUMEN
Granular cell tumour is a rare disorder that is characterised by an oval-shaped tumour that has with eosinophilic granules within the tumour cells. It is extremely rare to find this disease arising from the retroperitoneum. We report here on a case of a 46-year-old man with a retroperitoneal granular cell tumour that mimics pancreatic cancer, and describe the CT and MRI findings.