Academic literature on the topic '5-FBVM'

Abstract Fig mosaic virus (FMV) and Fig badnavirus-1 (FBV-1) are two of the most important fig infecting viruses. The incidence and distribution of FBV-1 and FMV were determined by testing in PCR 138 asymptomatic and symptomatic samples. These samples were collected from 60 fig gardens and agricultural fields in three provinces of Iran. The fig infecting viruses FBV-1 and FMV, respectively, were detected in 92 (66.6%) and 34 (24.6%) samples collected from all the surveyed fields. Overall, 24 out of 138 (17.3%) samples showed mixed infections. The sequence analysis of a genomic fragment of 922 nt, comprising the entire ORF-2 and part of the 5’ termini of the ORF-3 of 10 selected FBV-1 Iranian isolates from different provinces, and of the type member from GenBank (Acc. No: JF411989), showed a variation ranging from 1 to 3% at nucleotide level and 1% at the amino acid level. The phylogenetic analysis grouped the FBV-1 isolates into two groups, with the Iranian isolates clustered in two distinct subgroups of group I, according to their geographical origin. In our research, the prevalence and sequence analysis of FBV-1 as the only identified DNA virus infecting fig trees, was studied for the first time in Iran.

Obesity and sedentary lifestyle are associated with increased oxidative stress, inflammation and vessel dysfunction. Previous research has shown that an encapsulated fruit/berry/vegetable juice powder (FBV) supplement or controlled exercise training improve the markers of redox biology, low-grade inflammation and circulation. The aim of the present study was to assess the effects of 8 weeks of supplementation with FBV or placebo, and a single bout of controlled walking on the markers of oxidation, inflammation and skin capillary microcirculation in forty-two obese pre-menopausal women (41 (sd 5) years, non-smokers and BMI 34·5 (sd 3·8) kg/m2) using a randomised, double-blind, placebo-controlled design. All assessments were made before and after 8 weeks of capsule supplementation, and pre- and post-30 min of controlled treadmill walking at 70 % of VO2max. Venous blood was collected for the determination of carbonyl proteins (CP), oxidised LDL (ox-LDL), total oxidation status (TOS) of lipids, malondialdehyde, TNF-α and IL-6. Capillary blood flow, O2 saturation of Hb (SO2Hb) and the relative concentration of Hb (rHb) were assessed at a 2 mm skin depth. Following 8 weeks of supplementation, compared with placebo, the FBV group had a significant (P< 0·05) reduction in CP, ox-LDL, TOS and TNF-α, and a significant increase in blood flow, SO2Hb and rHb. Independent of supplementation, moderate exercise significantly increased blood flow and rHb, with a trend towards increased SO2Hb. Compared with placebo, 8 weeks of supplementation with FBV decreased the markers of systemic oxidation and inflammation. Both FBV supplementation and a single walking bout improved the markers of the microcirculation in these obese women.

Robach, Paul, Daniel Biou, Jean-Pierre Herry, Denis Deberne, Murielle Letournel, Jenny Vaysse, and Jean-Paul Richalet. Recovery processes after repeated supramaximal exercise at the altitude of 4,350 m. J. Appl. Physiol. 82(6): 1897–1904, 1997.—We tested the hypothesis that prolonged exposure to high altitude would impair the restoration of muscle power during repeated sprints. Seven subjects performed two 20-s Wingate tests (WT1 and WT2) separated by 5 min of recovery, at sea level (N) and after 5–6 days at 4,350 m (H). Mean power output (MPO) and O2 deficit were measured during WT. O2 uptake (V˙o 2) and ventilation (V˙e) were measured continuously. Blood velocity in the femoral artery (FBV) was recorded by Doppler ultrasound during recovery. Arterialized blood pH and concentrations of bicarbonate ([[Formula: see text]]), venous plasma lactate ([La−]), norepinephrine ([NE]), and epinephrine ([Epi]) were measured before and after WT1 and WT2. MPO decreased between WT1 and WT2 by 6.9% in N ( P < 0.05) and by 10.7% in H ( P < 0.01). H did not further decrease MPO. O2 deficit decreased between WT1 and WT2 in H only ( P < 0.01). PeakV˙o 2 after WT was reduced by 30–40% in H ( P < 0.01), but excess postexercise O2 consumption was not significantly lowered in H. During recovery in H compared with N, V˙e, exercise-induced acidosis, and [NE] were higher, [Epi] tended to be higher, [La−] was not altered, and [[Formula: see text]] and FBV were lower. The similar [La−] accumulation was associated with a higher exercise-induced acidosis and a larger increase in [NE] in H. We concluded from this study that prolonged exposure to high altitude did not significantly impair the restoration of muscle power during repeated sprints, despite a limitation of aerobic processes during early recovery.

613 Background: REG demonstrated efficacy in pre-treated mCRC pts. Lack of predictive biomarkers, potential toxicities and cost/effectiveness concerns highlight the unmet need for better patient selection. Methods: RAS mutant mCRC pts with biopsiable metastases were enrolled in this phase II trial. Tissue biopsies (6-12 cores) were obtained at baseline (BL), after 2 months if stable disease (SD) and at disease progression (PD). Dynamic contrast enhanced (DCE) MRI was acquired pre and at day 15 post-treatment. Median values of volume transfer constant (Ktrans) and enhancing fraction (EF) [K-trans*EF/100] were generated. Circulating tumour (ct)DNA was collected monthly until PD and tested for clonal RAS mutations by digital droplet PCR. PDOs derived from responders and non-responders pts were implanted orthotopically in the liver of mice and treated with REG for 5 days. Changes in tumour and fractional blood volume (fBV) were monitored by oxygen-enhanced MRI. Results: mCRC pts (n = 27) with paired MRI scans were analysed; a single target lesion per pt was chosen (25 liver and 2 pelvic metastases). Median K-trans*EF/100 product decrease was 58.2%. In the 23 analysable pts (4 received < 1 cycle of treatment due to toxicities), > 70% drop in K-trans*EF/100 (8/23) was associated with higher disease control rate (6/6 vs. 0/6, p = 0.048) measured by RECIST 1.1 at 2 months, improved progression free survival (PFS) [HR = 0.24 (0.07-0.86), p = 0.03], and 4-month PFS (58.3% VS 21.2%). Sequential tissue biopsies analysis confirmed reduction in CD31 in pts with K-trans*EF/100 drop. RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS [HR = 0.25 (0.08 - 0.83), p = 0.02] independently of K-trans*EF/100 drop. PDOs xeno-transplants treated with REG compared to controls had significant lower tumour fBV (4.5 VS 10.6, p = 0.03) and lower microvascular density measured by CD31 staining (4.3 VS 8.9, p = 0.02). Conclusions: Combining DCE MRI and ctDNA predicts depth and duration of anti-angiogenic response to REG monotherapy and may improve pt selection with potential health/economic implications. Clinical trial information: 201400357951.

AbstractHER2-positive breast tumors are found in 25–30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm3 and 1309 ± 120 mm3, respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene.

Abstract Radio-resistance mechanisms limit the benefit of radiation therapy (RT) for melanoma brain metastases. A key pathway for radiation-induced DNA double-strand break repair is non-homologous end joining, which is critically mediated by DNA-dependent protein kinase (DNA-PKcs). Here we evaluated radio-sensitizing effects of M3814, a selective oral inhibitor of DNA-PKcs, in patient-derived xenografts (PDXs) of melanoma brain metastases. In a clonogenic survival assay, M3841 augmented RT-induced killing of M12 cells at concentrations of ≥300 nM, and a minimum of 16 h exposure with ~300 nM M3814 was required for effective sensitization. M3814 inhibited RT-induced (5 Gy) auto-phosphorylation of serine-2056 of DNA-PKcs in primary cultures of M12, M15 and M27 PDX lines. Interestingly, inhibition of RT-induced DNA-PKcs by M3814 coincided with increased KAP1 phosphorylation, a DNA damage signaling regulated via ATM. Persistent γH2AX foci were observed in 28% M12 cells at 24 hours after co-treatment with M3814 and RT as compared to 12% cells following RT alone. In vivo pharmacokinetic analysis after single oral dose of 20 mg/kg M3814, showed reasonably short half-life (~2.44 hours) and poor brain distribution in wild-type FBV mice (Kpuu, 0.027). Consistent with an efflux liability, brain distribution of M3814 in triple knockout mice for BCRP/MDR1A/B was ~11 fold higher (Kpuu, 0.215). Compared to normal brain, much higher M3814 concentrations were detected in intracranially implanted M12 tumors (~23 fold and ~20 fold) 2 and 6 hours after a single oral dose of 50mg/kg respectively. The relative exclusion of M3814 from normal brain as compared to brain metastases suggests that this drug may have a favorable toxicity profile when combined with radiation for treatment of melanoma brain metastases, and this hypothesis is being tested in ongoing efficacy studies.

Abstract Introduction: Targeted drugs are needed for HR-MDS/AML, particularly in elderly patients and Venetoclax, approved for some CLL, gives promising results in elderly AML. Assays to predict response to treatment may enable us to deliver personalized treatment. We sought to determine the most informative assay to predict response; viability assays can directly measure the effects of reagents on growth. Progenitor assays can potentially determine if the reagents can target diseased primitive cells. PET scanning can be used to follow response to treatment. Methods: Peripheral blood (PB) or bone marrow (BM) from 7 MDS/AML patients were incubated in a) no treatment, b) ABT-199 (1 µM) (Abbvie), c) GDC-0973 (1 µM) (Genentech) or d) ABT-199+GDC-0973 (1 µM of each) and assessed for viability using the MTT assay (n=2); cell death followed using the Incucyte® Zoom System (Essen Bioscience) (n=2) or methocult progenitor assays (Stem Cell Technologies) (n=4). Having shown that RAS:BCL-2 co-localization correlated with prognosis in MDS/AML patients (Leuk Res 37:312-9, 2013), immunofluorescence was undertaken. A micro PET device dedicated to mice was used to measure BM blast proliferation. After injection of 18F-FLT(a thymidine analogue) in mice untreated (n=7) or ABT-199 (75mg/kg)+GDC-0973(10mg/kg) treated (n=5) normal FVB/N, HR-MDS mice treated with vehicle (n=4), 2-month old HR-MDS before (n=5) and 3-month old before (n=4) and after ABT-199 (75mg/kg)+GDC-0973(10mg/kg) treatment (n=8), PET imaging was performed (Inveon Siemens Medical Systems), analyzed for signal and quantified. Results: Patient details and results are summarized on Table 1. Using the MTT assay 2 PB patient samples were found to be sensitive to ABT-199 treatment (Figure 1A, AS, p=0.00042 and YA, 0.00002) and more sensitive to the combination compared to untreated (AS, p=0.00007 and YA, 0.000003). With the incucyte the BM of one patient (AE) was found to be resistant to both ABT-199 and GDC-0973, but sensitive to the combination (Figure 1B). PB and BM from patient JA were assayed for apoptosis with the incucyte and were found to be sensitive to ABT-199 with increased apoptosis, resistant to GDC-0973 with decreased apoptosis and sensitive to the combination. Four bone marrow samples were tested in the 4 conditions using the progenitor assay (Figure 1C). Three patients were sensitive to GDC-0973, inhibiting any colony formation and the fourth had reduced colony numbers. In this assay patient JA appeared to be sensitive to GDC-0973 treatment whereas the incucyte assay scored this sample to be resistant to apoptosis; thus the cytotoxic effects of GDC-0973 may not be via apoptopsis. As the progenitor assay is likely to score the primitive disease population, this assay may prove more informative than the others without prior selection. One patient (DH) was clearly resistant to ABT-199, whereas the other three (JA, CB and FL) had reduced colony growth. All patients were sensitive to the combination treatment and inhibited colony growth. The RAS:BCL-2 co-localization in the PB revealed no complex in either the Mito or PM upon treatment with ABT-199 alone and some localization in the Mito with GDC-0973. With both ABT-199 and GDC-0973, there were hardly any cells confirming the cytotoxic effects of the combination. As we have previously shown that PM co-localization of the complex is associated with drug resistance (Blood 130:2613, 2017Suppl), we used the combination on our HR-MDS mouse model, where the complex co-localizes in the PM and followed the mice by PET scanning (Figure 1D). Weak signal was visualized in the femurs of untreated and ABT-199+GDC-0973 treated FVB/N mice (FBR 1.17+/-0.34 and 1.02+/-0.08 respectively). Mild PET signal was seen in the femurs of 2 month-old HR-MDS mice, (FBR 1.79+/-0.98). Intense PET signal was seen in the femurs and proximal humerus of HR-MDS mice treated with vehicle (3 month-old, FBR=2.35+/-1.32). Low PET signals were seen in the femurs of 5/8 HR-MDS mice treated with ABT-199+GDC-0973 (FBR=1.93+/-0.84). FBRs of the 3 groups of HR-MDS mice were significantly higher than those of FBV/N groups. Conclusion: Combined Venetoclax (ABT-199) and GDC-0973 targets MDS/AML progenitors and can potentially overcome drug resistance with the disruption of the RAS:BCL-2 complex. Bone marrow disease progression in HR-MDS mice can be monitored with 18F-FLT-PET imaging; PET data shows that the combination slows down disease progression. Disclosures Padua: Abbvie: Research Funding; Genentech: Research Funding. Giraudier:Novartis: Research Funding. Konopleva:Stemline Therapeutics: Research Funding. Andreeff:Oncoceutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; United Therapeutics: Patents & Royalties: GD2 inhibition in breast cancer ; Reata: Equity Ownership; Celgene: Consultancy; Jazz Pharma: Consultancy; Oncolyze: Equity Ownership; Amgen: Consultancy, Research Funding; Eutropics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Patents & Royalties: MDM2 inhibitor activity patent, Research Funding; SentiBio: Equity Ownership; Astra Zeneca: Research Funding.

Abstract Since 2014, the promotion of Fundamental British Values (FBV) has been a requirement across formal schooling in England. The agenda has, however, faced criticism from various stakeholders. Much of this denunciation has been directed at the opaque nature of FBV, but the agenda is problematic for more concerning reasons. It is arguable that, in light of the current threat from ethno-nationalism, frameworks such as FBV that focus on a particular definition and formulation of national values run the risk of being interpreted in a manner that is exclusionary and liable to ‘other’ different ethnic groups in the classroom. The FBV framework furthermore overlooks the fact that the UK isalready subject to numerous international human rights obligations, including many that mandate the provision of holistic and effective human rights education at all levels of formal education. This article therefore draws upon the findings of a pilot study conducted with Year 5 learners in four primary schools in the West Midlands showing that teaching about human rights through the FBV agenda is possible, by linking discussion of values at the national level to broader human rights principles. Such an approach satisfies the government’s desire for children to learn about FBV, whilst highlighting that these values also exist in a global context. This, in turn, is likely to be a more effective way of encouraging learners to be global citizens who will contribute to the building of a broader culture that is respectful of human rights.

Introdução: Na atualidade, os hábitos alimentares da população do Brasil e do mundo, se caracterizam por um excessivo consumo de alimentos ricos em açúcares simples, gorduras saturadas e sal. O Diabetes Melito é uma doença crônica não transmissível que se desencadeia, muitas vezes, como consequência de uma alimentação inadequada. Este distúrbio metabólico, gera quadros de hiperglicemia e a terapia nutricional é fundamental no tratamento. Objetivo: O trabalho teve o objetivo de avaliar a ação hipoglicemiante do kombucha como probiótico, farinha de banana verde (FBV) como prebiótico e a associação destes alimentos como simbiótico em uma dieta de cafeteria com alto teor de açúcares oferecida a ratos wistar. Métodos: Para este experimento foram utilizados 35 ratos wistar machos e sadios, recém desmamados com 21 dias de vida, que foram distribuídos em 5 grupos de 7 animais, sendo eles: Grupo 1: dieta ração comercial (controle), Grupo 2: dieta de cafeteria, Grupo 3: dieta de cafeteria + kombucha, Grupo 4: dieta de cafeteria + FBV, Grupo 5: dieta de cafeteria + FBV + kombucha. O ensaio teve uma duração total de 55 dias, onde os primeiros 10 dias foram para induzir o diabetes nos animais dos grupos 2, 3, 4 e 5, mediante a dieta de cafeteria com alto teor de açúcares simples. Posteriormente, começou o período experimental, que teve uma duração de 45 dias, onde o kombucha e solução salina foram administrados por gavagem, com uma dose referente a 5mL/kg de peso do animal. Durante todo o experimento, os animais receberam água e ração ad libitum. Após a eutanásia dos animais, foram coletadas amostras de sangue para análises de glicemia e amilase pancreática mediante turbidimetria. Resultados: Como resultado, foram obtidos os seguintes valores para a glicemia e amilase pancreática de cada grupo: 65,86±11,60 mg/dL e 23,57±4,20 U/L para o Grupo 1; 104,14±114,92 mg/dL e 25,0±14,85 U/L para o Grupo 2; 49,00±13,18 mg/dL e 35,0±15,72 U/L para o Grupo 3; 73,86±24,78 mg/dL e 128,14±50,03 U/L para o Grupo 4; 72,29±33,87 mg/dL e 274,14±105,27 U/L para o Grupo 5, respectivamente. Conclusão: Observando os resultados da glicemia do grupo 1, onde não houve suplementação funcional, verifica-se que a dieta de cafeteria com alto teor de açúcares simples, foi eficaz na indução do diabetes. Ainda analisando os resultados da glicemia, é possível confirmar, que a suplementação isolada, tanto do probiótico kombucha como do prebiótico FBV, apresentam função hipoglicemiante, porém o efeito do prebiótico, é menos eficaz que o efeito do probiótico. Por outro lado, observou-se que, perante a associação simbiótica destes alimentos, o kombucha parece potencializar o efeito redutor da glicemia da FBV. Enquanto aos resultados da concentração de amilase no sangue dos animais, constatou-se que a suplementação isolada de FBV estimulou, consideravelmente, a secreção do referido hormônio e que o kombucha inibiu essa ação estimulante do prebiótico no grupo 5, onde houve associação de ambos sumplementos.

Les déficiences en transporteur vésiculaire de l'acétylcholine (VAChT) sont l'un des symptômes précoces de perte neuronale lors de la maladie d'Alzheimer, perte fortement corrélée avec la gravité de la démence associée. Comme le (2R,3R)-5-IBVM est le radioligand de référence du VAChT utilisé en imagerie TEMP, la synthèse par fluoro-de-diazenation a conduit à son analogue fluoré, le 5-FBVM, ainsi qu’à ses énantiomères. Par étude 3D-QSAR, confirmée par évaluation in vitro, chaque énantiomère du 5-FBVM montre une affinité pour le VAChT similaire au 5-IBVM. D'autres travaux ont permis d'améliorer le rendement en 5- FBVM par fluoro-de-triazénation du précurseur triazène, le 5-TVB, en utilisant seulement de l’éthérate de trifluorure de bore qui joue le double rôle d’acide de Lewis et d’agent fluorant, dans le tétrachlorure de carbone, sous irradiation micro-onde. L’optimisation de la fluoro-detriazénation en étudiant différents paramètres expérimentaux compatibles avec un radiomarquage a permis d’obtenir le 5-[18F]FBVM. Ce résultat encourageant devrait conduire à l’obtention du 5-[18F]FBVM
Deficiencies in vesicular acetylcholine transporter (VAChT) are among the earliest neuronal changes preceding clinical symptoms of Alzheimer's disease, and show a strong correlation with the severity of dementia. As (2R,3R)-5-IBVM is the lead and the only SPECT radioligand for VAChT human imaging, we synthesized by fluoro-de-diazoniation its fluoro analog 5-FBVM with corresponding enantiomers, and confirmed by 3D QSAR and in vitro studies that both enantiomers of 5-FBVM are of the same order affinity as 5-IBVM. Furthermore, we greatly improved 5-FBVM yield via fluoro-de-triazenation of the corresponding triazene precursor 5-TBV using boron trifluoride etherate under non-protic acid conditions in tetrachloromethane under optimized microwave irradiation. By testing different reaction parameters in numerous experimental attempts to find fluoro-de-triazenation conditions which can be transposed to radiofluorination, we may accomplished 5-[18F]FBVM. This encouraging result warrants to optimize 5-[18F]FBVM yield via promising methods obtained in cold chemistry

Chapter 5 considers the response of Engagement to the FBV requirement. This is the more infrequent instances of direct engagement with the FBV in schools, including teachers’ incursions into controversial/sensitive issues. The chapter explores some of the practical and affective constraints for teachers, on conducting what Cantle has called ‘dangerous conversations’. Chapter 5 also explores the priorities of teacher-respondents, their interpretation of the FBV policy to fit with their emphasis on developing students’ moral behaviours, especially mutual respect, and the commonalities and differences across the schools in the research, in terms of how ‘useful’ staff understood the FBV requirement to be in relation to their pupil populations.

Chapter 4 starts with a general overview of the teacher-respondents’ reactions to the FBV. It then moves on to describe and analyse the four main school responses to the promotion of FBV identified in the research. These are Representing Britain, Repackaging FBV, Relocating FBV and Engagement with FBV (the latter is discussed in Chapter 5). The first response, Representing Britain, describes the use of symbols and stereotypes traditionally associated with Britain as a mechanism through which to promote FBV. Repackaging describes a ‘business-as-usual’ response where schools absorb the promotion of FBV into their existing practices. Relocating describes the rise in ‘inward-looking’ values/character education. I argue that this emphasis on personal development is preferred over more ‘outward-looking’ citizenship education. Throughout, I identify the characteristics of the ‘good’ citizen inherent in the different responses, focusing both on the desired characteristics of both the ‘good’ school citizen and the future adult citizen.